Mds-foundation.org

Spring 2001 • Volume 6, Issue 1
THE MDS NEWS
The Newsletter of The Myelodysplastic Syndromes Foundation
From the Guest
years, whereas those with lower risk can expect tosurvive for several years, even without treatment.
Editor’s Desk
Once the prognostic grouping is determined, thetreatment plan is developed. Relatively low intensity Elihu H. Estey, MD
treatments are recommended for patients with MD Anderson Cancer Center, Houston, Texas
low risk. Higher intensity treatments, such aschemotherapy, are not usually recommended for Treatment of Myelodysplastic Syndromes
these patients as the risks associated with the Selection of the treatment plan for a patient with treatments themselves may be greater than those myelodysplastic syndromes (MDS) depends upon associated with the disease. Furthermore, adverse the prognosis for the disease course. Currently, the effects of the high-intensity treatments may preclude best approach for assessing prognosis is to utilize the patient from benefiting from new treatments the International Prognostic Scoring System (IPSS).
which are under development. Patients in the high The IPSS incorporates the results from three types risk groups, however, are candidates for both low- of analyses — the levels of blood counts, the percent of immature cells (“blasts”) in the bone marrow, and While it is important to note that no therapy for the karyotype (chromosome pattern) of the bone MDS has been shown to prolong survival, it is equally marrow cells — to distinguish four prognostic risk important to comment that new approaches may be groups; the four groups are Low, Intermediate-1, successful in this regard. After all, effective treatments Intermediate-2, and High. Patients having lower risk have only recently been developed for diseases like (Low and Intermediate-1 groups) generally do not tuberculosis, hypertension, and HIV infection. Of have excess blasts in the bone marrow but rather course, determination of the effectiveness of potential have blood counts which are mildly to moderately treatments must be first proven through formal clinical abnormal. Higher risk patients, meaning those in the trials before the treatment program can be broadly Intermediate-2 or High Risk groups, have severely available. Participation in clinical trials of new MDS abnormal blood counts, excess blasts in the marrow, therapies will bring all patients closer to improved and/or chromosomal abnormalities. The higher risk patients are more likely to experience MDStransformation into acute myeloid leukemia (AML) Clinical trials and experience have also shown and to have shorter survival, often less than 1-2 that some therapies may no longer be appropriate.
Included on this list are androgens (male hormonessuch as danazol) and amifostine (Ethyol®), except for Contents
certain uses undergoing evaluation in clinical trials.
In addition, “colony-stimulating factors” (such as G-CSF, also known as filgrastim or Neupogen®, and GM-CSF, also known as sargramostim or Leukine®) are no longer recommended as solo treatments; while G-CSF and GM-CSF effectively increase the number of normal white blood cells, these treatments do not prevent infection or prolong life expectancy. Recommendations for other treatments vary. Some treatments, such as transfusions of red cells and/or platelets, remain an important part of the manage- ment of MDS. Management also includes monitoring for iron overload that often accompanies frequent red cell transfusions as well as administration of deferoxamine (Desferal®) which counteracts iron overload, thus lessening the risk of future heart and liver problems and diabetes. Other treatments are less broadly used, such as the combination of G-CSF and erythropoietin, because only certain patients are likely to respond, as has been shown in this case immunosuppressive drug ATG has been shown to occasionally raise blood counts in MDS and is now New low- and high-intensity treatments are under being combined with other immunosuppressive investigation and are providing encouraging results, agents, such as cyclosporine and fludarabine, with patience as a key part of the treatment program.
When used to treat MDS, 3-4 months may be High-Intensity Therapies Being Evaluated for
required before response to the various low-intensity Treatment of MDS
approaches can be observed. Response to high- 1. Chemotherapy – While chemotherapy is a standard intensity approaches may be observed within procedure, new drugs and combinations of new drugs with both older drugs are being evaluated Low-Intensity Therapies Being Evaluated for
for treatment of MDS. Some of the new combi- Treatment of MDS
nation drugs are troxacitabine, Mylotarg®, and a 1. Inhibitors of Ras – Ras is a protein that participates drug (“genasense”) that opposes the action of in signaling abnormal cells to continue to divide Bcl2, a protein that prevents the killing of cancer which, in turns, leads to an excess of blast cells.
Drugs known as farnesyl transferase inhibitors block 2. Bone marrow transplantation – New methods of the functioning of Ras and, therefore, slow the transplantation are being investigated, with the accumulation of blast cells. In a study of R115777, goal of reducing the intensity of the chemotherapy a farnesyl transferase inhibitor, for treatment of treatment which is administered prior to the acute myeloid leukemia, some patients did respond transplant. If successful, older patients will have to the treatment, although the exact response rate less risk associated with the procedure. New is unknown and at least some of the patients might methods to specifically reduce complications of have responded to standard therapies.
transplant are also being investigated.
2. Inhibitors of angiogenesis – Angiogenesis is the For further information about treatments for MDS or term applied to the formation of new blood vessels.
about MDS in general, go to www.mds-foundation.org Because the bone marrow of MDS patients often or www.conference-cast.com/webtie/sots/leukemia2/ has an abnormally high number of blood vessels, transcripts.htm, a website established by the National therapies that inhibit angiogenesis are of interest.
Cancer Institute to disseminate information shared at a “State of the Science” meeting on MDS held in bevacizumab. The former has been reported to Desferal® is a trademark of Novartis Pharmaceutical Corporation.
although, once again, the benefit over standard Ethyol® is a trademark of Alza Pharmaceuticals.
therapies has not yet been established.
Leukine® is a trademark of Immunex Corporation.
3. Thalidomide – This drug, which was removed from Myelotarg® is a trademark of Wyeth-AyerstNeupogen® is a trademark of Amgen Inc.
the marketplace in the 1950s after it produced fetalmalformations, has been shown to have remarkableactivity for treatment of myeloma (cancer of a type Thank You to
of white blood cell). Thalidomide has also beenreported to increase blood counts in MDS patients, Our Pharmaceutical
although these reports as yet require confirmation.
4. Decitabine – Through inappropriate methylation, Partners
genes that normally suppress cancer becomeinactivated in MDS. Demethylation of these genes, We would like to thank our pharmaceutical therefore, slows the development of cancer. An partners for their support of the Foundation and inducer of demethylation, 5-azacytidine, was shown its work. They have contributed in the form of to improve blood counts and quality of life for patients unrestricted educational grants, which support with MDS. Decitabine is similar to 5-azacytidine not only this newsletter but also the development but, being a more potent inducer of demethylation, of the MDS home page on the World Wide Web, decitabine may be even more effective.
the Centers of Excellence program, continuing 5. ATG + cyclosporine or fludarabine – Inappropriate medical education programs, the Patient Registry, activity of the immune system may result in low and the dissemination of patient information.
blood counts, a characteristic of MDS. The About the Foundation
MDS Board of Directors
John M. Bennett, MD
The Myelodysplastic Syndromes Foundation was established by an international group of physicians and researchers to provide an ongoing exchange of information relating to MDS.
Until the Foundation was set up, no formal working group had been devoted to MDS. During the past decade we have Jeanne E. Anderson, MD
conducted five international symposia — in Austria, England, the United States, Spain, and the Czech Republic. The Sixth International Symposium will be held in Stockholm, Sweden, One major role of the Foundation is our internationalinformation network. This network provides patients with Pierre Fenaux, MD, PhD
Professor of Hematology
referrals to Centers of Excellence, contact names for available programs, sharing of new research and treatment options, and extension of educational support to both physicians and patients. Ultimately, we hope to provide Peter L. Greenberg, MD
funding and oversight for international studies in MDS.
In response to the needs expressed by patients, families, and physicians, we are establishing patient advocacy groups, research funding, and physician education.
The MDS Foundation is a publicly supported organization, Terry Hamblin, MD, FRCP, FRC Path
Treasurer
exempt from federal income tax under section 501(C)(3) Our Web Site
Kathy Heptinstall, BSN, RN
Operating Director
The MDS Foundation has established its own Web
page for healthcare professionals, patients, and other
interested people. The Professional Forum and the
Professor G.J. Mufti
Patient Forum are integral parts of our Web site.
Head of Haematological MedicineHealthcare NHS Trust The Web site has recently been updated to better
serve the needs of our patients, their families, and
the physicians who treat them.
Charlotte M. Niemeyer, MD
We welcome your suggestions.
Professor of PediatricsUniversity Children’s Hospital Please visit us at http://www.mds-foundation.org
Hussain I. Saba, MD, PhD
Professor of Medicine
University of South Florida
Tampa, Florida, USA
Franz Schmalzl, MD
Professor, Department of Internal Medicine
University Hospital of Innsbruck
Innsbruck, Austria
Jody Simon, MS, RPh
Tampa, Florida, USA
Ortho Biotech, Inc., has supplied the MDS Robert J. Weinberg, Esq.
Foundation with an unrestricted educational grant. Pepper Hamilton LLPPhiladelphia, Pennsylvania, USA Patient Services
Patient Advocacy
The MDS Foundation is pleased to share with our Committee
patients and their families that flight services areavailable within the continental United States to Established by the
AirLifeLine is a nationwide organization of over
MDS Foundation
1,100 pilots who are caring, committed andcompassionate individuals donating their time, The MDS Foundation has been working todevelop a strategy for setting up patient groups aircraft and fuel to provide free transportation for
nationwide. Until recently, we did not have the Generally, the criteria for patient travel with us are: wished. Thanks to the generosity of families • The patient must be ambulatory or be mobile and friends of patients lost to this disease, enough to board and exit the aircraft. The patient the Foundation was able to establish a Patient must be able to sit in a seat and wear a seatbelt.
Patient may bring along a family member or a support person to assist them. In the case of a forming nationwide patient advocacy groups, developing new information for patients andplanning fund raising programs to support these • The patient should be medically stable and able to activities. Committee members include Jennifer fly in an unpressurized aircraft. Our pilots are not Rand, Jody Simon, Joe and Charlotte Pagano, medically trained and their planes are not medically and Foundation representatives: Kathy Heptinstall, equipped. Oxygen is allowed with the pilot’s consent.
John Bennett, Betty Anne Nixon, Laura Ciesielski, • The patient must demonstrate financial need and be unable to afford other means of commercial Any member of the Foundation, patients, friends transportation. We do waive this requirement for and family members are invited to join with us to financial need if the patient has a time critical move these projects forward. Please contact situation such as an organ transplant.
Betty Anne Nixon at the Foundation office: • The patient’s flight should be less than approxi- mately 1,000 from his or her home to the medical Your help is needed!!
destination. The average mission is between250–500 miles. However, we can coordinateflights up to 1,000 miles one way.
It is the mission of Angel Flight to ensure that no
financially needy patient is denied access to distant,
Marrow Donor
specialized treatment for lack of means of airtransportation.
For those patients diagnosed with a fatal blood disorder,bone marrow transplantation (BMT) is often the only AirLifeLine
chance of survival. Related donors provide suitable Angel Flight
matches only 33 percent of the time. This leavesnearly 70 percent of patients without a match.
Corporate Angel Network
The need is especially critical in racial and ethnic National Patient Travel Center
Registering as a donor is simple. A blood sample isall you need to enter your tissue type into the NationalMarrow Donor Program (NMDP) computerized registry.
If you are in good health and between the ages of 18and 55, you can contact NMDP at 1-800-MARROW-2.
They will send additional information, including the The MDS Foundation is supported by an unrestricted educational grant from Amgen, Thousand Oaks, California. 6th International
Saturday, June 16, 2001
Symposium on
Myelodysplastic
■ Mini Symposium – Sideroblastic Anemia Syndromes
■ The Role of Mitochondria in Iron Transport and June 14-17, 2001
Sunday, June 17, 2001
Stockholm, Sweden
SCIENTIFIC TOPICS
ORGANIZING COMMITTEE
Eva Hellström-Lindberg, PresidentÄke Öst, Vice President SCIENTIFIC PROGRAM
Thursday, June 14, 2001
■ Classification of Myelodysplastic Syndrome: For further information please contact:
Friday, June 15, 2001
Symposium Secretariat
Scientific Secretariat
Suzanne Fleishman Memorial Lecture
Hosted by The Myelodysplastic Syndromes Additional information available from the Congress
■ Complimentary and Alternative Therapies website: http://www.congrex.com\mds2001.
A Living Endowment
condolence card to the family, making them awareof the gift. The Lees have made a commitment tocontinue to donate to the Foundation, not only on One Family’s Pledge
occasions of loss, but even as remembrances for The family of MDS patient, Eugene Lee, is one of birthdays and anniversaries. The Foundation sends many thousands of families living with the reality of a handwritten acknowledgement card to the family, MDS. They have come up with an extraordinary way making them aware of these gifts in the Lees name.
to contribute to the MDS Foundation and support A fund has been initiated established in Eugene’s our mission of working as a resource for patients, name for this purpose, and the funds will be used families, and healthcare professionals.
Eugene and Meta Lee recently learned of friends The MDS Foundation is very grateful for the heartfelt who had experienced the unfortunate loss of their support of Eugene and Meta Lee. Our work as a non-profitorganization depends on public funding. If you would like mother. The Lees made a decision to honor their to contribute in this way, or if you have a unique idea of friends and their mother by making a donation to your own, please write to us at PO Box 353, 36 Front Street, the MDS Foundation. The Foundation sent a personal Crosswicks, NJ 08515, or call us at 1-800-MDS-0839. Selected
(4.5+, 6+ and 3+ respectively). Clearly, patients withlow cytokine and apoptosis levels appear to benefit Abstracts in MDS
from the treatment with Thalidomide. This constitutes abiologically recognizable subgroup of good-riskpatients who are likely to respond to manipulations of Adapted from abstracts presented at
cytokine pathways. The precise mechanism of the American Society of Hematology,
Thalidomide activity in MDS remains obscure and is December 2000, San Francisco, California
most likely a result of its anti-angiogenic, anti-cytokineand immunomodulatory effects.
Biologic Determinants of Clinical Response to
Thalidomide in Myelodysplasia
Thalidomide as a Single Agent or in Combi-
S. Mundle, F. Zorat,* V. Shetty, K. Allampallam,
nation With Topotecan, Pentoxifylline and/or
S. Alvi,* L. Lisak,* L. Little,* L. Dean,* R. Nascimben,*
Enbrel in Myelodysplastic Syndromes (MDS)
M. Ekbal,* M. duRandt,* E. Broderick,* P. Venugopal,
A. Raza, L. Lisak,* L. Little,* M. Ekbal,* M. du Rant,*
A. Raza
E. Ali,* F. Nascimben,* M. Tareen,* P. Venugopal
Rush Cancer Institute, Rush-Presbyterian-St. Luke’s
Rush Cancer Institute, Rush-Presbyterian-
Medical Center (RPSLMC), Chicago, IL
St. Luke’s Medical Center, Chicago, IL
Based on the earlier observations of increased levels of Recent biologic insights have led to the development tumor necrosis factor a (TNFα) and excessive of novel therapeutic venues for the treatment of MDS apoptosis in the bone marrow (BM) of patients with designed to suppress pro-inflammatory cytokines myelodysplastic syndromes (MDS), a suppressor of and/or angiogenesis, as well as modulation of the TNFα; Thalidomide, was used in the therapy of MDS at immune system. Thalidomide has activity in all three our center on a protocol approved by the IRB of areas. In our first trial, 83 MDS patients received RPSLMC. Thalidomide was administered at an initial thalidomide starting at 100 mg PO and increasing as total daily oral dose of 100 mg PO increased to 400 mg tolerated to 400 mg PO for 12 weeks; 32 went off study as tolerated. Thirty-one patients [refractory anemia due to side effects (26) or disease progression (6) (RA)-18, RA with ringed sideroblasts (RARS)-6, RA with while 51 are evaluable for response. The median age excess blasts (RAEB)-6 and chronic myelomonocytic of these 51 patients was 68 years, there were 36 leukemia (CMML)-1] completed 12 weeks of therapy.
males / 15 females, 48 had primary and 3 had Significant hematological responses were noted in 16 secondary MDS, 44 had normo- or hypercellular and patients (11/18 RA and 5/6 RARS). In order to 7 had a hypocellular marrow. Initial FAB showed 28 determine the biologic correlates of these responses, RA, 9 RARS, 12 RAEB, 1 RAEB-t, and 1 CMMoL. IPSS patients’ sera were assessed by ELISA for the levels of scoring showed that 17 had low risk, 26 had int-1, 4 TNFα, transforming growth factor ß (TGFß), basic had int-2 and 4 had high risk disease. Abnormal fibroblast growth factor (bFGF) and vascular cytogenetics were present in 35 while 16 had normal endothelial growth factor (VEGF). Additionally, plastic karyotypes. There were no complete responders, embedded bone marrow biopsy sections were partial responses were seen in 21/51 (41%) patients, examined for the extent of apoptosis by in situ end 8 patients who were transfusion dependent became labeling (ISEL) and for the presence of TNFα, and TGFß completely independent of transfusions. The median by immunohistochemistry using a subjective rating duration of response has not been reached yet, the scale of 1+ to 8+. In the sera of both responders [R] longest treated patients having completed 1 year of and non-responders [NR] the VEGF levels correlated therapy. Responses were noted in all three lineages, positively with TGFß and TNFα levels. Interestingly, a but were most effective in the erythroid series. Low significant correlation was seen with bFGF (r=0.679, risk patients with no excess blasts and higher pre- p=0.04) only in NR. Also, while VEGF correlated therapy platelets were more likely to respond. In half negatively with hemoglobin (Hgb) levels in this the RAEB cases, the blasts remained unaffected even group (r= –0.8, p=0.03), demonstrated a positive though hematopoiesis improved significantly. Several correlation with Hgb in R group (r=0.609, p=0.058).
cases responded 1-10 weeks after stopping therapy.
Surprisingly, in the R group, BM biopsies showed Currently, low risk MDS are treated with either a significantly lower median levels of apoptosis, TGFß combination of thalidomide with Enbrel, or PCD and TNFα, (1+, p=0.19; 1+, p=0.012, and 2+, p=0.04 (pentoxifylline, Cipro, dexamethasone), while topotecan respectively), as compared to those in the NR group is administered initially to reduce the blast count in high-risk patients followed by thalidomide. Initial months with 6 patients maintaining their responses for results on these combination therapies appear to be over 12 months. Headaches and nausea were the superior to thalidomide alone. Mechanism of response most common reported side effects but they were not remains unclear, although post-therapy levels of pro- severe enough to interrupt therapy in any patients. Liver inflammatory cytokines, apoptosis and angiogenesis function tests did not rise significantly above baseline.
were decreased. Delayed responses appear to At the time of analysis, 12 patients remain alive and indicate immune-modulation as the likely mechanism free from progression. Ten patients transformed to in at least a subset of patients. In conclusion, AML. Of the remaining 7 patients, 1 died from intra- thalidomide appears to be a promising addition to MDS cranial hemorrhage, 1 from perforated bowel, 2 from therapeutic armament and deserves further study.
other causes, and 3 were lost to follow-up. Inconclusion, danazol may be effective in MDS patients Danazol for the Treatment of Thrombocytopenia
in Myelodysplastic Syndrome
Geoffrey W. Chan,* Gina DiVenuti,*
Low Dose Interleukin-11 is Well-Tolerated and
Kenneth B. Miller
Induces Platelet Responses in Myelodysplasia
and Other Bone Marrow Failure States
Department of Hematology/Oncology, Tufts–
New England Medical Center, Boston, MA, USA
R. Kurzrock, J. Cortes, D. Thomas, S. Pilat,*
M. Talpaz
Therapy for thrombocytopenia in myelodysplastic syn-drome remains limited. Danazol, an attenuated University of Texas M.D. Anderson Cancer Center,
androgen with immunomodulatory properties, is Houston, TX, USA
effective in some patients with ITP. We report on 29 Interleukin-11 (IL-11) is a thrombopoietic cytokine that MDS patients, 9 RA, 11 RAEB, 5 RAEB-t, 4 CMML, attenuates post-chemotherapy thrombocytopenia.
who were treated with danazol 200 mg po tid. Median The dose used post-chemotherapy is ≅ 50 µg/kg/day age was 68.5 years (range 44 to 93 years) with 18 s.c. Very little is known about the activity of IL-11 in males and 11 females. Cytogenetic studies revealed 4 bone marrow failure states. Our preliminary experience patients with 5q-, 4 with monosomy 7, 3 with three or with IL-11 at doses of 50 µg/kg/day suggested that more chromosomal abnormalities, 10 with other bone marrow failure patients developed significant abnormalities, and 8 with normal karyotypes. Median peripheral and pulmonary edema after the prolonged platelet count prior to therapy was 41,000 per mm3 dosing necessary for treating these conditions. We (range 10,000 to 97,000 per mm3). Seven patients therefore initiated a study of low-dose IL-11 (10 µg/kg/d).
required platelet transfusions prior to initiating therapy.
Response criteria included doubling of platelets and After six weeks, 22 out of 29 patients (76%) rise to >50 x 109/L or tripling of platelets and rise to responded with elevations in platelet counts ranging >20×109/L. Sixteen patients are evaluable for response.
from 1,000 to 181,000 per mm3. Nine responders had Their median age was 58 years (range, 5 to 84 years).
started with platelet counts less than 30,000 per mm3 Six patients had diploid cytogenetics; the others had a and another seven responders had started with variety of chromosomal abnormalities. Six of 16 patients platelet counts between 30,000 and 50,000 per mm3.
(38%) showed a platelet response to IL-11 and two Ten patients (34%) increased their platelet counts by had a multi-lineage response (to IL-11 alone [N=1]; more than 50%, 14 of 22 responders increased their to IL-11 + G-CSF and EPO [N = 1]). Responders platelet counts above 50,000 per mm3, and 5 included 5 of 11 patients with myelodysplasia (MDS) responders who were platelet transfusion dependent and 1 of 4 patients with aplastic anemia (AA).
no longer required platelets. After three months, 18 out Response duration was 12, 13, 14+, 22+, 25 and 30 of 26 patients (72%) had an elevation in platelet weeks. Side-effects of IL-11 were mild (peripheral counts. Thirteen patients (50%) had increased their edema, N=7; conjunctival injection, N=7 or myalgia platelet counts by more than 50%. Responses were [N=1]) (all grade 1). Seven patients had no side- seen in all FAB subtypes at six weeks (9/9 RA, 9/11 effects. Our pilot study suggests that administration of RAEB, 1/5 RAEBT, 4/4 CMML) and at twelve weeks low dose IL-11 (10 µg/kg/day) can raise platelet counts, (7/9 RA, 6/ 10 RAEB, 3/3 RAEB-t, 3/4 CMML). There without significant toxicity, in selected thrombocytopenic was no correlation between the pretreatment platelet count and response to danazol. No appreciableincreases in the hematocrit or white blood cell countswere observed. Mean duration of treatment was 9.4 High Dose (HD) Chemotherapy in High Risk
Comparison of Interphase Fish and
(HR) Myelodysplastic Syndrome (MDS): Covariate
Metaphase Cytogenetics to Study
Adjusted Comparison of Five Regimens
Myelodysplasia: An Eastern Cooperative
Miloslav Beran,1 Yu Shen,*2 Hagop Kantarjian,1
Oncology Group (ECOG) Study
Simona Despa,*2 Elihu Estey1
G. Dewald,* G. Hicks,* R. Higgins,* C. Griffin,*
1Leukemia, The University of Texas MD Anderson
A. Cherry*, J. Rowe, M. Tallman, J. Bennett,
Cancer Center, Houston, TX; 2Biomathematics,
K. Miller
The University of Texas MD Anderson Cancer
Mayo Clinic, Rochester, MN, USA
Center, Houston, TX
This investigation compared standard metaphase To further define the role of high dose combination chromosome studies with interphase studies using chemotherapy in patients with diagnosis (Dx) of HR chromosome specific DNA probes with fluorescence MDS (RAEB, RAEBt) we have analyzed (a) association in situ hybridization (FISH) to detect neoplastic clones between covariates and CR status, (b) relationship in bone marrow from patients with myelodysplastic between diagnosis and CR status (c) significance of syndromes (MDS). FISH was used with chromosome treatment effect for time to relapse and death (d) specific DNA probes to detect abnormalities of covariate-adjusted activity of five consecutive chromosomes 5, 7, 8, 11, 13 and 20. For each patient, treatment regimens. In the cohort of 394 patients, 229 the percentage of neoplastic nuclei in 200 (58%) achieved CR. The CR rates by regimens are consecutive cells for each probe was established.
Chromosome studies were done on ≤ 25 metaphasesfor the same specimens. FISH was done on 34 fixed p value
————— ———— ———— ———— ———— ———— ————
cell pellets from cytogenetic studies and 8 bone marrow aspirate smears from morphology studies.
NO CR (%) 19 (28) 30 (39) 61 (52) 30 (41) 25 (42) Patients included 5 with high risk MDS (E3996) and 37 —————————————————————————————————
with low risk MDS (E1996). Excluding -Y as a marker * I=idarubicin; F=fludarabine; A=intermediate or high dose cytosine of clonality, an abnormal clone was identified in arabiaosidc; T=topotecan; C=cyclophosphamide.
metaphases from 14/42 (33.3%) patients and 28 In multivariate analysis, disease duration (AHD), (66.7%) were normal. By comparison, interphase FISH performance status (PS), protected environment (PE) studies on these same specimens detected an and days to response but not IPSS were significant abnormal clone in 11/41 (26.8%), only normal nuclei in predictors of CR (two-sided p<0.05). With covariate 30 (73.2%) and failed in 1 (2.4%). Among patients with an abnormal clone by cytogenetics 1 had RA, 3 RARS, comparable CR rates. Dx was not associated with CR 8 RAEB and 2 RAEB-T. Among patients with normal status in IA, CAT, FA and FAI; within TA group RAEB cytogenetics 4 had RA, 13 RARS, 7 RAEB, 2 RAEB-T was more likely to achieve CR than RAEBt (p=0.01).
and 1 CMML. Abnormalities were detected in Overall logrank test documented significant treatment metaphases of 3 patients that were not evident by effect in terms of overall survival (p<0.01), and time to FISH in interphase cells either because the FISH relapse (p=0.01). The trend for time to relapse was strategy was not designed to detect the abnormality or the same as for time to death among five treatment probe hybridization failed. Each of the 28 patients with groups. Multivariate analysis for time to death only normal metaphases also had only normal revealed treatment, cytogenetics, age, prior interphase cells. FISH detected ≥1 abnormalities of chemotherapy, PE, PS, hemoglobin and platelets chromosome 5,7,8, 11,13 and 20 in 2,3,4, 0,0 and 4 independent risk factors. Survival for IA patients was patients, respectively. FISH failed for all probes in 1/34 comparable to TA, both being superior to FAI, FA and fixed cell pellets, for chromosome 11 in 1/8 smears, CAT. IA was more effective in sustaining remission and for chromosome 20 in 3/8 smears. Results of this than FA or FAI but not different from TA. In summary, study dispel the argument that patients with MDS no difference between anthracycline or non- often have chromosome abnormalities that are missed anthracycline-containing regimens were observed.
by chromosome studies due to sampling errors. The Effective in inducing CR, particularly in e.g. – 5 / – 7 results indicate that approximately 70% of patients karyotype, HD therapy is not associated with with low risk MDS do not have abnormalities that are improvement in CR duration and survival.
detectable by either chromosome studies or FISH. Theresults suggest that the sensitivity of interphase FISHstudies for MDS is nearly as good as cytogenetic studies. FISH may be useful in clinical practice to morphologic findings of marrow dysplasia still carries study bone marrow specimens when chromosome a risk of leukemia transformation or death from studies are not successful or when only smears are cytopenias. The cytogenetic abnormalities in this group are generally typical of MDS, with del(20)qbeing the most frequently encountered. Del(20)q wasseen alone in 19% of our patients; in a recent series of Clonal Cytogenetic Anomalies Suggestive of
A Myelodysplastic Syndrome in Patients With
640 MDS patients, this anomaly was seen alone in only Morphologically Normal Bone Marrow
2% of cases with the refractory anemia FAB subtype.
Aspirates
Continued follow-up will more clearly define theprognosis in this heterogeneous cohort.
David P. Steensma, Gordon W. Dewald,* Janice M.
Hodnefield,* Ayalew Tefferi, Curtis A. Hanson
Mayo Clinic, Rochester, MN, USA
Addition of Thalidomide (T) to Chemotherapy
Did Not Increase Remission Rate in Poor
Clonal cytogenetic abnormalities are found in the Prognosis AML/MDS
bone marrow cells of 40 to 60% of patients with Elihu Estey, Maher Albitar, Jorge Cortes, Francis
Giles, Deborah Thomas, Charles Koller, Miloslav
occasionally observed patients with morphologically Beran, Hagop Kantarjian
normal bone marrow aspirates, but with clonalabnormalities on conventional cytogenetic analysis M.D. Anderson Cancer Center, Houston, TX, USA
suggestive of MDS. Between October 1994 and April Marrow microvascular density (MVD) appears 2000, 58 such patients were seen at our institution (36 increased in AML (Blood 95:309, 2000) and high men, 22 women; age range, 19–88 years; median levels of cellular vascular epithelial growth factor age, 71). The indications for marrow aspiration in this (VEGF) seem independently associated with worse group were cytopenias alone (32 patients), staging or treatment outcome (Blood 95:2637,2000). Therefore follow-up of a lymphoproliferative or plasma cell we randomly assigned adults with newly-diagnosed disorder (21 patients), or another miscellaneous AML, RAEB-t, or RAEB to receive liposomal reason (5 patients). 27 of the 58 patients had daunorubicin (LD, 100 mg/m2 daily days 1–3) and ara- previously been treated with an alkylating agent (14 C (A, 1 g/m daily days 1–4) with or without the “anti- cyclophosphamide, 7 melphalan, 4 chlorambucil, 1 angiogenesis” agent T (400 mg daily × 1 week, then BCNU, 1 nitrogen mustard) starting a median of 68 600 mg daily) for remission induction. In remission, months earlier. 51 patients were anemic, 30 had patients received 6 mos of LDA, +/– T as originally erythrocyte macrocytosis, 30 were leukopenic, and 40 assigned. Eligibility required an abnormal karyotype were thrombocytopenic; 26 were pancytopenic. The other than t(15;17), t(8;21), or inv (16). A Bayesian marrow was hypocellular in 21 cases, normocellular design stipulated that accrual into either arm would in 14, and hypercellular in 23. As of August 2000, with stop should the probability become <0.02 that the a median follow-up of 7 months, 18 of the 58 patients early CR (ECR, Blood 95:72,2000) rate was not at least were dead. Of these 18 patients, 1 died of acute 20% higher than the 46% rate seen in patients with the myelogenous leukemia (AML), 4 of complications described cytogenetics given other regimens related to cytopenias, 6 of a previously diagnosed 1991–99. With this stopping rule, the probability of lymphoproliferative disorder, and 7 of unrelated early termination should the true ECR rate with an arm causes. The cytogenetic findings were as follows: be >0.66 (0.46 + 0.2) was 0.07. 74 patients were among those with 1 or 2 clonal cytogenetic anomalies, the most common abnormality was del(20)q [11patients], followed by: del(7)q or monosomy 7 [6 LDA (38 patients) LDA+T (36 pis)
patients], trisomy 8 [4 patients], del(5)q [3 patients], Median Age
del(13)q [3 patients], and t(1;7)(q10;p10) [2 —————————————— —————— ——————
patients]. 21 patients had other unique clonal cytogenetic anomalies, and 11 patients had a complex karyotype (3 or more anomalies). There were no significant differences between the karyotypes ofpatients treated with alkylating agents and untreated patients. We conclude that a clonal cytogenetic anomaly suggestive of MDS in the absence of These ECR rates led to termination of both arms. In transfusion-independence following ATG or particular, the probability that the ECR rate with cyclosporine (p < 0.05). HLA DR15 frequency in LDA + T is ≥20% higher than historical is <0.01; the responders was 57% compared with 31% for non- probability that it is ≥10% higher is .05. Early death responders (p=0.03). The high frequency of HLA (weeks 1–7) rates were 24% LDA, 19% LDA + T; DR15 in MDS, comparable to that seen in AA, relapse rates also appear similar. The median daily suggests a link between HLA DR2/15 and immune- dose of T was only 57% of that scheduled, principally mechanisms of marrow failure in MDS and AA.
because of fatigue. Achievement of ECR was Furthermore, DR15 typing could help predict MDS unrelated to daily administered T dose (p=0.91) or patients most likely to improve marrow function after pre-Rx values of MVD (p=0.69, assessed in 18 patients, 10 ECRs) or plasma VEGF (p = 0 .33assessed in 40, 19 ECRs); the latter observations also Validation of the WHO Proposals for a New
applied considering only the LDA + T group. Addition Classification of Myelodysplastic Syndromes:
of T to LDA seems unlikely to improve average Analysis of 1640 Patients
remission rate in poor prognosis AML/MDS.
U. Germing,* N. Gattermatm, C. Strupp,*
M. Aivado,* C. Aul*
HLA DR15 (DR2) is Over-Represented in
Dept. of Hematology, Heinrich-Heine-University,
Myelodysplastic Syndrome (MDS) and is
Düsseldorf; Dept. of Hematology, St. Johannes
Associated With a Response to
Hospital, Duisburg, Germany
Immunosuppression
A working group of the World Health Organisation Yogen Saunthararajah, Ryotaro Nakamura,
proposed a new classification of MDS.
Jamie Robyn, Fausto Loberiza, Kevin E. Brown,
Myeloproliferative CMML and RAEB-T were removed Neal S. Young, A. John Barrett
and RAEB was split into two groups, with medullary Hematology Branch, National Heart, Lung, and
blast counts below and above 10%. A group of Blood Institute, National Institute of Health,
patients with less than 5% medullary blasts but Bethesda, MD, USA
multilineage dysplasia was defined. MDS patients with In vitro and clinical data suggests that immune- 5q- were considered a separate group. The present mediated marrow suppression, well defined in study validates this classification with respect to aplastic anemia (AA), is also a feature of some prognosis and cytogenetic features in a large series of patients with MDS. However autoimmune mechanisms patients (n=1640) with a long-term follow up.
in MDS, and the characteristics of patients likely torespond to immunosuppression remain incompletely defined. Since HLA-DR2 and its commonest defined p < 0.00005
allele HLA DR15 are known to be overexpressed in AA, we studied serologically-defined HLA DR frequencies in 1752 AA and 707 MDS (RA, RAEB, and RARS) patients undergoing stem cell transplants reported to the International Bone Marrow Transplant Registry (IBMTR) and molecularly-defined HLA DR frequencies in patients with AA (n=100) or MDS (n=82) treated with immunosuppressive regimens at NIH. Compared with 14.2% (n=3978) in healthy North American controls, the frequencies of HLA DR-2 in MDS and AA patients were 26.5% (χ2=62, p ≤ 0.0001) and 38% (χ2=400, p < 0.0001), respectively. In the NIHCaucasian patients, molecular typing revealed that Figure 1. PSA=pure sideroblastic anemia; PRA=pure refractoryanemia; RCMD=refractory cytopenia with multilineage dysplasia; HLA-DR 15 frequency (constituting >80% of the RSCMD=refractory sideroblastic anemia with multilineage dysplasia. serologically defined HLA DR2 allele) was increasedin both AA (58%, χ2= 92, p<0.0001) and MDS (41% We confirmed a significant difference in survival and χ2=30, p<0.0001) compared with Caucasian controls frequency of AML evolution between RAEB I and (14.4%, n=4980). In multivariate analysis of NIH MDS RAEB II, and a striking difference between pure patients, HLA DR15 was significantly associated with refractory anemia and multilineage dysplasia (with or without ring sideroblasts). Karyotype anomalies weremore frequent in patients with multilineage dysplasia.
The good prognosis of 5q- patients was restricted tothose with medullary blast below 5%. The WHO the Foundation
classification defines morphological subgroups thatclearly differ with respect to prognosis.
The MDS Foundation relies entirely on gifts andmembership fees to further its work. We would Myelodysplastic Syndromes, from FAB to
like to acknowledge the generosity of the WHO: Comparison of Classifications on 431
following individuals and organizations that Unselected Patients from a Single Institution
have recently provided gifts to the Foundation: T. Noesslinger,* R. Reisner,* H. Gruener,*
H. Tuechler,* E. Pittermann,* M. Pfeilstoecker*
Mrs. Naomi J. Sapp
(Intr. by Renate Heinz)
Dansville, NY
3rd Med. Dept. for Haematology and Ludwig
Mrs. Hertisene C. Griffin
Boltzmann Institute for Hematology and Leukemia
Hamlet, NC
Research, both Hanusch Hospital Vienna,
Vienna, Austria
H. Joachim Deeg, MD
Seattle, WA
In 1976 the FAB group established for the first timediagnostic criteria for myelodysplastic syndromes Mr. Norman Greer
(MDS). In 1982 the same group introduced the FAB- Long Beach, NY
classification (RA, RARS, RAEB, RAEB-t, CMML). In Mr. Aaron Rabinowitz
1999 a revised classification (WHO) was published: RA, Melbourne, FL
RARS, Refractory Cytopenia with multilineagedysplasia (RC+Dys), RAEB, 5q- syndrome and MDS Mr. George C. Allen
unclassifiable; CMML and RAEB-t should be excluded.
Koloa, HI and Ellsworth, ME
Between 1976 and 1999 431 patients (median survival The Foundation extends its sincerest thanks to 30 months) were diagnosed at our institution as primary MDS according to FAB-classification: 142RA (med. surv. 66 mo), 47 RARS (73 mo), 92 RAEB(15 mo), 51 RAEB-t (9 mo), 99 CMML (24 mo). 281patients (median survival 43 months) were classifiableaccording to WHO: 43 RA (66 mo), 4 RARS (65 mo),91 RC+Dys (86 mo, in FAB: 65 RA, 26 RARS), 92 MDS Patient Registry
RAEB (15 mo), 1 5q-syndrome, 50 MDS unclassifiable(67 mo, in FAB: 33 RA, 17 RARS). We compared bothclassifications using morphological and clinical data, Pharmacia & Upjohn generously provided an as well as cytogenetics. In addition we studied the unrestricted grant to help support the Myelodysplastic homogeneity of the above mentioned subgroups by Syndromes Foundation’s Patient Registry. The evaluating prognostic scoring systems, especially the Foundation gratefully acknowledges this support and IPSS, taking into account cytogenetic data. The first looks forward to building the Patient Registry with our expected phenomenon was a significant patient shift Centers of Excellence. The Patient Registry will help into the lower risk groups according to the IPSS (FAB further research into the treatment of MDS.
58% vs. WHO 76% of the patients in low- andintermediate-1 risk group).
Our data stress the necessity of incorporatingcytogenetic results in classification parameters.
Consequences for future clinical trials and also forfuture prognostic systems will be discussed.
MDS Centers of Excellence
Would you like your treatment center to become part of the referral system for MDS patients and be designated as a Center
of Excellence? To be recognized as a Center of Excellence, an institution must have the following:
■ An established university (or equivalent) program ■ Documentation of peer-reviewed publications in the field ■ Recognized morphologic expertise in MDS ■ The ability and intention to register patients in the MDS ■ Available cytogenetics and/or molecular genetics ■ Ongoing research, including Institutional Review Please contact the Foundation for further information and an application form for your center. The following centers have qualified as MDS Centers of Excellence:
UNITED STATES
Seattle Cancer Care Alliance
OUTSIDE THE UNITED STATES
Patras University Hospital
University of Washington
Cedars-Sinai Medical Center
A.C. Camargo Hospital –
Cancer Center
Peter MacCallum Cancer Institute
Southwest Regional Cancer Center
University of Melbourne
City of Hope National Medical Center
Academic Hospital
Free University Amsterdam
Stanford University
St. Johannes Hospital
Stanford University Medical Center
Dana-Farber Cancer Institute
Heinrich-Heine University
Centre Hospitalier
Service des maladies de Sang
Tufts University School of Medicine
Duke University
Universitaire of Lille
South Hampton University
New England Medical Center
Duke University Medical Center
The Royal Bournemouth Hospital
D’ Hematologie Hôpital Cochin
University of Arizona
Indiana University
University Paris V Service
Tokyo Medical College
Arizona Cancer Center
Indiana University Medical Center
Heinrich-Heine University Düsseldorf
University of Aarhus
University of Chicago
Johns Hopkins Oncology Center
University Hospital
The University Hospital
University of Chicago Medical Center
Johns Hopkins Institutions
Hôpital Saint Louis
University of Athens
University of Nebraska
Mayo Clinic
University Paris VII
Laikon Hospital
University of Nebraska Medical Center
MCP Hahnemann University
Hospital Universitario de Salmanca
University of Cape Town
University – New York Presbyterian Hospital
Groote Schuus Hospital
Weill Medical College of Cornell
Medical College of Wisconsin
Hospital Universitario La Fe
Physicians and Clinics
University of Dundee Medical School
University Of Pennsylvania
Bone Marrow Transplant Program
Dundee Teaching Hospital
University of Pennsylvania
Cancer Center
Johann Wolfgang Goethe University
Memorial Sloan-Kettering
University of Innsbruck
Cancer Center
University of Rochester
Community Hospital
Karolinska Institute
University of Rochester Medical Center
Huddinge University Hospital
Prim. Univ. Prof. Dr. Franz Schmalzl New York Medical College
University of Nijmegen
Zalmen A. Arlin Cancer Center
University of South Florida
University Hospital St. Radboud
King Chulalongkorn
H. Lee Moffitt Cancer Center
Memorial Hospital
and Research Institute
New York Presbyterian Hospital
University of Tasmania
Columbia College of Physicians
Royal Hobart Hospital
and Surgeons
King’s Healthcare NHS Trust
University of Texas
King’s College Hospital
Health Sciences Center
University Tor Vergata
New York University
Ospedale S. Eugenio
School of Medicine
Kyoto University Hospital
University of Texas
North Shore University Hospital
MD Anderson Cancer Center
Medizinische Hochschule Hannover
University of Vienna
Hannover Medical School
Oregon Health Science University
Washington University School of Medicine
Oregon Cancer Center
Barnard Cancer Center
Odense University Hospital
Rush Presbyterian –
William Beaumont Hospital,
St. Luke’s Medical Center
Cancer Center
Rush Cancer Institute
In Memorium
A memorial fund has been established in the name of
Mr. Jerry Dashe
Donations have been made in Mr. Dashe’s memory by: A memorial fund has been established in the name of
Mr. Frank T. Akins
Donations have been made in Mr. Akins’ memory by: A memorial fund has been established in the name of
Barry Mizes and Ellen Bern, Saint Louis, MO Mrs. Eva Diossy
Donations have been made in Mrs. Diossy’s memory by: A memorial fund has been established in the name of
Mrs. Frances N. Artuso
Donations have been made in Mrs. Artuso’s memory by: William & Linda IversenPalatine, IL A memorial fund has been established in the name of
Mrs. Jean Hackney
Donations have been made in Mrs. Hackney’s memory by: A memorial fund has been established in the name of
Mrs. Irene Kulnis
Donations have been made in Mrs. Kulnis’ memory by: A memorial fund has been established in the name of
Mr. Eduardo Perez Casalduc
Donations have been made in Mr. Casalduc’s memory by: A memorial fund has been established in the name of
A memorial fund has been established in the name of
Mr. Kenneth Dale Cash
Mr. Henry Lauro
Donations have been made in Mr. Cash’s memory by: Donations have been made in Mr. Lauro’s memory by: Robert & Jo-Ann Freund, Oakland, NJ A memorial fund has been established in the name of
Mrs. Marianne Lottes
Donations have been made in Mrs. Lottes’s memory by: A memorial fund has been established in the name of
Mrs. Peggy S. Cope
A memorial fund has been established in the name of
Donations have been made in Mrs. Cope’s memory by: Mr. David Miquelon
Donations have been made in Mr. Miquelon’s memory by: Donna Peterson Byron Family, Collins, OK A memorial fund has been established in the name of
Mrs. Anna M. Pagano
Donations have been made in Mrs. Pagano’s memory by: Charles & Patricia Gallagher, Fairfield, NJ A memorial fund has been established in the name of
Mr. Eduardo Perez
Donations have been made in Mr. Perez’s memory by: A memorial fund has been established in the name of
Mr. Leo Pompliano
Donations have been made in Mr. Pompliano’s memory by: International Clinical
risk hematologic malignancies. Contact: M. Laughlin, MD.
Phone: 216-844-8609.
Trials: An Update
NCI-G98-1431. Case Western Reserve University/Ireland
Cancer Center. Phase II study of unrelated umbilical
cord blood transplantation for severe aplastic anemia,
The following trials are current as of the date of this inborn errors in metabolism, or inherited hematologic newsletter. We will update the list in The MDS News each stem cell disorders. Contact: M. Laughlin, MD. Phone: quarter. If you are a treating physician who would benefit from any such study, you may want to contact the NCI-G98-1444. Memorial Sloan-Kettering Cancer Center.
appropriate institution. If you are an MDS patient, you may Phase II study of decitabine for MDS. Contact: S. Nimer, wish to discuss a trial with your primary treating physician to see if you qualify as a candidate.
NCI-G99-1523. Phase II study of unrelated umbilical cord
Clinical trials study new interventions (drugs or blood transplantation in patients with malignant or procedures) to evaluate their safety and effectiveness in nonmalignant hematological disease. Contact: E. Sievers, humans. Trials follow a careful set of steps, allowing for the systematic gathering of information to answer ques- NCI-G99-1542. Phase I pilot study of RAS peptide cancer
tions and confirm hypotheses that were formed earlier, in vaccine and sargramostim (GM-CSF) in patients with MDS.
either laboratory experiments or preliminary trials.
Contact: S.D. Nimer, MD. Phone: 212-639-7871.
A clinical trial falls into one of four phases: NCI-G99-1543. Phase II study of allogeneic bone marrow
Phase I. This is the first time a drug is used in humans.
transplantation in patients with hematologic malignancies.
The trial is designed to determine dosage, route of Contact: P.V. O’Donnell, MD. Phone: 410-614-0205.
administration (oral, intravenous, or by injection), andschedule of administration (how many times a day or NCI-G99-1544. Phase III study of sargramostim (GM-
week). In this phase researchers also begin to determine CSF) following T-cell depleted allogeneic bone marrow the drug’s safety. The phase I trial is normally conducted transplantation in patients with MDS. Contact: P.V.
O’Donnell, MD. Phone: 410-614-0205.
in healthy adults and enrolls only a small number ofpeople.
NCI-G99-1573. Cancer Institute of New Jersey. Phase I
Phase II. Patients with the disease receive the drug at study of 12-O-tetradecanoylphorbol-13-acetate (TPA) in dose levels determined in the earlier phase. The phase II patients with relapsed or refractory hematologic malig- trial begins to determine the effectiveness of the drug and nancies or bone marrow disorders. Contact: R. Strair, MD.
Phone: 908-235-6777.
provides more information about its safety.
Phase III. The drug is tested alone or against an NCI-G99-1603. UCLA-Jonsson Comprehensive Cancer
approved standard drug. The typical phase III trial enrolls Center. Phase I pilot study of nonmyeloablative chemo- a large number of patients. If it is a comparison trial, therapy followed by unrelated peripheral blood stem cell patients may be randomly assigned to receive either the transplantation in patients with advanced hematologicmalignancies. Contact: C. Emmanouilides, MD. Phone: new drug or the standard intervention.
Phase IV. In phase IV the drug, already approved by theFDA and available to the public, undergoes continued NCI-G99-1617. Duke University. Phase II study of
evaluation. The phase IV designation is rare.
allogeneic mixed chimerism peripheral blood stem celltransplantation utilizing in vivo and in vitro monoclonal Some trials — screening studies evaluating supportive antibody CD52 (campath-1H) in patients with high risks care or prevention — are not conducted in phases. In hematologic malignancies or diseases. Contact: D.A.
these trials a group following a certain disease combating strategy, such as a detection method, is compared to acontrol group.
NCI-G99-1618. University of Chicago. Phase II study of
allogeneic peripheral blood stem cell transplantation
following non-myeloblative chemotherapy in patients with
U.S. Trials
hematologic malignancies. Contact: T. Zimmerman, MD.
Phone: 773-702-4145.
NATIONAL CANCER INSTITUTE TRIALS*
NCI-G99-1660. Robert H. Lurie Comprehensive Cancer
NCI-G97-1354. Ireland Cancer Center at Case Western
Center. Phase I study of unmanipulated bone marrow Reserve University. Phase II study of allogeneic peripheral augmented with CD34+ enriched peripheral blood stem blood progenitor cell transplantation using histocompatible cells in patients with hematologic malignancies sibling-matched donor cells after high-dose busulfan/ undergoing allogeneic transplantation. Contact: Richard cyclophosphamide for hematologic malignancy. Contact: H. Lazarus, MD. Phone: 216-844-3629.
NCI-G99-1661. Memorial Sloan-Kettering Cancer Center.
NCI-G98-1406. Roswell Park Cancer Center. Phase II study
Phase I study of sodium salicylate in patients with of cord blood transplantation for hematologic malignancies.
advanced MDS or refractory or relapsed acute Contact: R. Wells, MD. Phone: 513-636-4266.
myelogenous leukemia. Contact: Stephen D. Nimer, MD.
NCI-G98-1429. Ireland Cancer Center at Case Western
Reserve University. Phase II pilot study of unrelated NCI-G99-1658. Robert H. Lurie Comprehensive Cancer
umbilical cord blood transplantation in patients with high- Center, Northwestern University. Phase III randomized study of captopril in patients undergoing autologous bone antibody M195 and etoposide followed by autologous marrow or stem cell transplantation. Contact: Leo I.
peripheral blood stem cell transplantation in patients with advanced MDS or refractory leukemia. Contact: Peter NCI-G00-1686. Robert H. Lurie Comprehensive Cancer
Center, Northwestern University. Phase II study of high NCI-G00-1816. Johns Hopkins Oncology Center. Phase I
dose busulfan and cyclophosphamide followed by study of nonmyeloablative cyclophosphamide plus allogeneic bone marrow transplantation in patients with haploidentical allogeneic bone marrow transplantation in AML or MDS. Contact: Martin Stuart Tallman, MD. Phone: patients with hematologic malignancies. Contact: Paul V.
O’Donnell, MD. Phone: 410-614-0205.
NCI-G00-1688. Robert H. Lurie Comprehensive Cancer
NCI-G00-1868. Ireland Cancer Center. Phase II study of
Center, Northwestern University Phase II pilot study of nonmyeloablative conditioning using fludarabine, cyclo- busulfan and etoposide with autologous bone marrow phosphamide, and anti-thymocyte globulin, followed by transplantation and filgrastim (G-CSF) in patients with allogeneic peripheral blood stem cell transplantation in acute myelogenous leukemia or MDS. Contact: Martin patients with high risk hematologic malignancies or severe Stuart Tallman, MD. Phone: 312-695-6180. anaplastic anemia. Contact: Mary J. Laughlin, MD. Phone: NCI-G00-1691. Robert H. Lurie Comprehensive Cancer
Center, Northwestern University. Phase I pilot study of T- NCI-G00-1891. Herbert Irving Comprehensive Cancer
cell depleted partially matched related donor hematopoietic Center. Phase II study of allogeneic peripheral blood stem stem cell transplantation using intense pre- and post- cell transplantation in patients with hematologic malignancy.
transplantation immunosuppression and megadose Contact: David G. Savage, MD. Phone: 212-305-9783.
CD34 “Veto” cells in patients with high risk hematologic NCI-G00-1897. Herbert Irving Comprehensive Cancer
malignancies. Contact: Richard K. Burt, MD. Phone: 312- Center. Phase II Study of fludarabine and melphalan followed by allogeneic or syngeneic bone marrow or NCI-G00-1732. Ireland Cancer Center. Phase I study of
peripheral blood stem cell transplantation in patients with fludarabine, carboplatin, and topotecan in patients with hematologic malignancies or genetic disorders (summary relapsed or refractory acute leukemia or advanced MDS.
last modified 01/2001). Contact: David G. Savage, MD.
Contact: Brenda Cooper, MD. Phone: 216-844-3213.
NCI-G00-1742. University of Texas – MD Anderson Cancer
NCI-G00-1898. Memorial Sloan-Kettering Cancer Center.
Center. Phase I study of psoralen (S-59) treated allogeneic Phase III randomized study of caspofungin acetate versus cellular immunotherapy plus mega T-cell depleted HLA amphotericin B liposomal in patients with persistent fever nonidentical blood progenitor cell transplantation in and neutropenia following treatment for cancer. Contact: patients with hematologic malignancies or bone marrow Kent Sepkowitz, MD. Phone: 212-639-2441.
failure. Contact: James Gajewski, MD. Phone: 713-792-2933.
NCI-G00-1899. Herbert Irving Comprehensive Cancer
NCI-G00-1755. H. Lee Moffitt Cancer Center and Research
Center. Phase II study of allogeneic umbilical cord and Institute. Phase II study of allogeneic bone marrow placental blood transplantation in patients with chronic transplantation using closely matched related and unrelated myeloid leukemia, acute leukemia, lymphoma, myeloma, donors in patients with malignant or nonmalignant myelodysplasia, aplastic anemia, Fanconi’s Anemia, hematologic disorders. Contact: Steven C. Goldstein, MD.
histiocytosis, hereditary immunodeficiency, or storage disorder. Contact: David G. Savage, MD. Phone: 212-305-9783.
NCI-G00-1759. H. Lee Moffitt Cancer Center and
Research Institute. Phase II study of allogeneic bone
NCI-G00-1900. Fred Hutchinson Cancer Research
marrow transplantation in patients with hematologic Center. Phase II study of gemtuzumab ozogamicin, malignancies. Contact: Steven C. Goldstein, MD. Phone: fludarabine, and total body irradiation followed by allogeneic peripheral blood stem cell or bone marrowtransplantation with cyclosporine and mycophenolate NCI-G00-1762. Fred Hutchinson Cancer Research Center.
mofetil in patients with advanced acute myeloid leukemia Phase I pilot study of fludarabine and low dose total body or myelodysplastic syndrome. Contact: Eric Sievers, MD.
irradiation, followed by unrelated donor stem cell transplantation, followed by unrelated donor lymphocyteinfusions in patients with hematologic malignancies.
NCI-G01-1916. Jonsson Comprehensive Cancer Center,
Contact: Michael Maris, MD. Phone: 206-667-2480.
UCLA. Phase II/III randomized study of monoclonalantibody ABX-CBL versus anti-thymocyte globulin in NCI-G00-1793. Fred Hutchinson Cancer Research Center.
patients with steroid resistant acute graft-versus-host Phase II study of anti-thymocyte globulin and tumor disease. Contact: Mary Carol Territo, MD. Phone: 310- necrosis factor receptor IgG chimera in patients with MDS.
Contact: H. Joachim Deeg, MD. Phone: 206-667-5985.
NCI-H98-0023. Johns Hopkins Oncology Center. Phase I
NCI-G00-1801. Dana-Farber Cancer Institute. Phase I study
study of total body irradiation, tacrolimus, and of HLA haploidentical bone marrow transplantation after ex mycopheno-late mofetil with HLA-identical related-donor vivo exposure to anti-B7 antibodies in patients with refractory, bone marrow transplantation. Contact: E. Fuchs, MD.
high risk hematologic malignancies or bone marrow failure.
Contact: Eva Guinan, MD. Phone: 617-632-4932.
NCI-H99-0028. Phase II study of iodine I 131 mono-clonal
NCI-G00-1815. Memorial Sloan-Kettering Cancer Center.
antibody BC8 plus cyclophosphamide and total body Phase I study of Yttrium Y 90 humanized monoclonal irradiation followed by HLA matched related or unrelated bone marrow transplantation in patients with advanced NCI-T99-0080. Division of Clinical Sciences. Phase I study
acute myeloid leukemia or MDS. Contact: D.C. Matthews, of arsenic trioxide in pediatric patients with refractory leukemia or lymphoma. Contact: Frank Milton Balis, MD.
Phone: 301-496-0085.
NCI-H99-0031. Phase II study of donor lymphocyte infusion
in patients with relapsed malignancies after allogeneic
NCI-T99-0092. Johns Hopkins Oncology Center. Phase I
hematopoietic transplantation. Contact: M.E.D. Flowers, study of azacitidine in combination with phenylbutyrate in patients with recurrent, refractory, or untreated AML or NCI-H00-0051. Memorial Sloan-Kettering Cancer Center.
MDS. Contact: Carole Miller, MD. Phone: 410-955-8603.
Phase I study of suberoylanilide hydroxamic acid (SAHA) NCI-V96-0809. Memorial Sloan-Kettering Cancer Center.
in patients with advanced malignancies. Contact: William Phase II study of T-cell-depleted marrow grafts with G- CSF-stimulated, CD34-selected, E rosette-depleted PBPC NCI-H00-0054. Fred Hutchinson Cancer Research Center.
from HLA haplotype-matched related donors for patients Phase II study of bone marrow transplantation using with leukemia who lack an HLA-matched related or unrelated donors incompatible for 1 HLA locus antigen in unrelated donor. Contact: R. O’Reilly, MD. Phone: 212- patients with hematologic malignancies. Contact: Claudio NCI-V96-0848. University of Washington Medical Center.
NCI-H01-0067. Fred Hutchinson Cancer Research Center.
Phase I trial of subcutaneous outpatient interleukin-2 for Phase I/II study of beclomethasone in patients with patients with MDS. Contact: John Thompson, MD. Phone: intestinal graft-versus-host disease with contraindication to high-dose immunosuppressive therapy. Contact: David NCI-V96-0941. Memorial Sloan-Kettering Cancer Center.
Hockenbery, MD. Phone: 206-667-4611.
Phase II study of high-dose cytarabine with a single high NCI-P97-0097. Cancer and Leukemia Group B. Phase I/II
dose of idarubicin for newly diagnosed acute myelo- study of omega-3 fatty acids in advanced cancer patients genous leukemia: the AML-3 protocol. Contact: P. Maslak, with cachexia. Contact: C.P. Burns, MD. Phone: 319-356-2038.
NCI-P00-0168. North Central Cancer Treatment Group.
NCI-V96-0950. Temple University Cancer Center. Phase II
Phase III randomized study of ondansetron in patients with study of unrelated bone marrow transplantation with advanced cancer and chronic nausea and emesis not due cyclophosphamide and total-body irradiation for hemato- to antineoplastic therapy. Contact: Steven R. Alberts, MD.
logic malignancies/disorders. Contact: K. Mangan, MD.
NCI-T97-0027. Indiana University Cancer Center. Phase I
NCI-V97-1361. Ireland Cancer Center at Case Western
study of recombinant human interleukin-12 (IL-12) after Reserve University. Phase II study of busulfan, cyclo- high-dose chemotherapy and autologous hematopoietic phosphamide, and allogeneic bone marrow trans- stem cell support in patients with hematologic plantation in patients with leukemia, MDS, multiple malignancies and solid tumors. Contact: M. Robertson, myeloma, or lymphoma. Contact: H. Lazarus, MD. Phone: NCI-T98-0001. MD Anderson Cancer Center. Phase I study
NCI-V98-1387. Johns Hopkins Oncology Center. Phase I
of Dolastatin 10 in patients with refractory or relapsed acute study of combined chemotherapy and donor lymphocyte leukemia, MDS, or chronic myelogenous leukemia in blast infusion for aggressive hematologic malignancies in phase. Contact: J. Cortes, MD. Phone: 713-794-5783.
relapse after allogeneic bone marrow transplantation.
NCI-T98-0017. University of Texas–MD Anderson Cancer
Contact: B. Mookerjee, MD. Phone: 410-614-6025.
Center. Phase I/II randomized study of PR1 leukemiapeptide vaccine and montanide ISA-51 in patients with NCI-V98-1433. Marlene and Stewart Greenebaum Cancer
chronic myeloid leukemia, AML, or MDS. Contact: Jeffrey J.
Center at University of Maryland. Phase IV study of allogeneic bone marrow transplantation depleted of T cellsby CD34 selection in patients undergoing transplantation NCI-T98-0068. Johns Hopkins Oncology Center. Phase I
with a matched or mismatched antigen donor. Contact: M.
study of phenylbutyrate and tretinoin in patients with Myelodysplastic Syndromes, chronic myelomonocyticleukemia, or acute myeloid leukemia. Contact: Steven D.
NCI-V98-1447. Phase II Study of amifostine and high dose
cytarabine and mitoxantrone in patients with high risk andrelapsed acute myeloid leukemia and blast crisis chronic NCI-T99-0013. Cancer Research Campaign, Glasgow.
myelogenous leukemia. Contact: H.D. Preisler, MD. Phone: Phase I/II study of geldanamycin analogue (AAG) in patients with advanced malignancies. Contact: S.B. Kaye,MD. Phone: 011-1-41-221-2824.
NCI-V98-1455. Phase I/II study of high dose melphalan
NCI-T99-0069. University of Michigan Comprehensive
with autologous peripheral blood stem cell support and Cancer Center. Phase II study of azacitidine plus amifostine cytoprotection in cancer patients. Contact: G.L.
amifostine in patients with MDS. Contact: Harry Paul Erba, NCI-V98-1460. Johns Hopkins Oncology Center. Study of
NCI-T-99-0071. Mayo Clinic Cancer Center. Phase I study
stem cell-augmented, elutriated grafts for prevention of of PS-341 in patients with advanced malignancies or B-cell graft-versus-host disease in patients undergoing allogeneic lymphoproliferative disorders. Contact: Alex A. Adjei, MD.
bone marrow transplantation. Contact: P. O’Donnell, MD.
NCI-V98-1485. Allegheny University Hospitals. Phase I/II
study of topotecan, fludarabine, cytarabine, and filgrastim
Membership Information
(T-FLAG) induction therapy followed by maintenancetherapy of either peripheral blood stem cells or isotretinoin The MDS Foundation would like to have you as a member.
in patients with poor-prognosis acute myeloid leukemia,MDS, and recurrent or refractory acute lymphocytic Membership is US$35 a year for physicians and other leukemia. Contact: E. Besa, MD. Phone: 215-842-6980.
professionals. Patients, their families, and others interested NCI-V98-1501. San Antonio Cancer Institute. Phase I study
in MDS may join at the reduced rate of $20.
of R115777 with gemcitabine in patients with advanced Membership benefits include quarterly issues of the MDS cancer. Contact: S.G. Eckhardt, MD. Phone: 210-616-5798.
News, a special subscription rate of $105 for Leukemia NCI-V99-1527. Phase II/III study of standard and novel
Research (a substantial discount from the current conditioning therapy and allogeneic blood or marrow subscription rate of $1,193), and the worldwide Centers transplantation in patients with severe aplastic anemia orhematologic malignancy. Contact: P.L. McCarty, Jr, MD.
of Excellence patient referral service.
If you would like additional information, please NCI-V99-1533. Phase II study of amifostine, topotecan and
cytarabine in patients with poor risk MDS. Contact: H.C.
Fung, MD. Phone: 626-359-8111.
NCI-V99-1545. Phase II study of arsenic trioxide in patients
with recurrent or refractory acute myeloid leukemia, blastcrisis chronic myeloid leukemia, or MDS. Contact: Janice P.
NCI-V00-1588. Marlene & Stewart Greenebaum Cancer
Center. Phase I pilot study of combined chemotherapy and donor lymphocyte infusion in patients with hematologicmalignancies in relapse after allogeneic stem celltransplantation. Contact: Bijoyesh Mookerjee, MD. Phone:410-614-6025.
NCI-V00-1608. Washington University Barnard Cancer
NCI-951. Johns Hopkins Oncology Center. Phase I study
Center. Phase I/II study of arsenic trioxide with or without of Bryostatin 1 and Sargramostim (GM-CSF) in patients tretinoin in patients with refractory hematologic malignancies.
with refractory myeloid malignancies. Contact: B. Douglas Contact: Randy A. Brown, MD. Phone: 314-454-8227.
NCI-V00-1624. Marlene & Stewart Greenebaum Cancer
NCI-99-C-0143. National Cancer Institute. Phase I pilot
Center, University of Maryland. Phase II study of study of donor Th2 cells for prevention of graft-versus-host nonmyeloablative conditioning regimen followed by HLA disease following non-myeloablative, HLA-matched matched sibling donor peripheral blood stem cell allogeneic peripheral blood stem cell transplantation in transplantation in patients with hematologic malignancies.
patients with hematologic malignancies. Contact: Michael Contact: Bijoyesh Mookerjee, MD. Phone: 410-328-7394.
NCI-2. Rush Cancer Institute. Phase II study of azacitidine
in patients with relapsed or refractory acute myelogenous
PHARMACEUTICAL TRIALS LISTED WITH NCI
leukemia or Myelodysplastic Syndrome. Contact: HarveyD. Preisler, MD. Phone: 312-563-2190.
SUGEN-SU541. Called for institution. Phase II study of
SU5416 in patients with advanced or refractory hemato-
NCI-38. Stanford University Medical Center. Phase I/II
logic malignancies. Contact: Paul Scigalla, MD. Phone: study of R115777 in patients with myeloproliferative disorders. Contact: Peter L. Greenberg, MD. Phone: 650-725-8355.
CHIMERIC-HM01. Chimeric Therapies Incorporated.
Phase II/III randomized study of processed versus
NCI-42. University of Chicago Cancer Research Center.
unprocessed unrelated bone marrow transplantation in Phase I randomized study of R115777 in patients with patients with acute or chronic leukemia or Myelodysplastic advanced hematologic malignancies. Contact: Mark J.
Syndrome. Contact: James N. Lowder, MD. Phone: 949- NCI-94. University of Texas–MD Anderson Cancer Center.
Phase I study of PS-341 in patients with refractory or
*For more information on NCI trials, contact cancernet. relapsed AML, acute lymphoblastic leukemia, MDS, or chronic myeloid leukemia in blast phase. Contact: JorgeCortes, MD. Phone: 713-794-5783.
OTHER U.S. TRIALS
NCI-450. University of Texas–MD Anderson Cancer Center.
Phase I study of BMS-214662 in patients with acute
CLB-69803. Cancer and Leukemia Group B. Phase I study
leukemia, Myelodysplastic Syndrome, or chronic myeloid of 506U78 in patients with hematologic malignancies and leukemia in blast phase. Contact: Jorge Cortes, MD.
renal or hepatic impairment. Contact: Todd S. Zimmerman, Cedars-Sinai Medical Center. 104864-A/201. Phase III
Eastern Cooperative Oncology Group. E-1996. Phase III
open-label multicenter, randomized, comparative study of study of epoetin alfa with or without filgrastim (G-CSF) vs topatecan, Ara-C and G-CSF (TAG) VS idarubicin, Ara-C supportive therapy alone in patients with Myelodysplastic and G-CSF (IDAG) in patients with RAEB (high risk), RAEB- Syndromes. Contact: Kenneth B. Miller, MD. Phone: 617- t or in patients with AML from a preceding phase of MDS.
Contact: M. Lill, MD. Phone: 310-423-2997.
Eastern Cooperative Oncology Group. E-2998. Phase III
Children’s Cancer Group. CCG-2951. Children’s Hospital
randomized study of Flt3 ligand in patients with acute Medical Center. Phase II study of salvage chemotherapy myeloid leukemia in second or subsequent complete for acute myeloid leukemia or MDS in first relapse or remission. Contact: Richard L. Schilsky, MD. Phone: 773- refractory to initial remission-induction therapy and for secondary acute myeloid leukemia. Contact: R. Wells, MD.
Fred Hutchinson Cancer Research Center. FRCRC
#1536. Transplantation of peripheral blood stem cells from Children’s Cancer Group. CCG-2961. Multicenter. Phase
related or unrelated volunteer donors in patients with “less III randomized study for untreated pediatric acute myelo- advanced” MDS. Conditioning therapy includes busulfan genous leukemia and MDS: intensively timed induction (targeted to a pre-determined plasma level) and cytoxan chemotherapy followed by consolidation with the same (targeted BUCY); patients up to 65 years of age. Contact: chemotherapy versus fludarabine/cytarabine/idarubicin followed by intensification either with high-dose cytarabine/ Fred Hutchinson Cancer Research Center. FHCRC #1006.
asparaginase with versus without subsequent IL-2 or with Autologous stem cell transplantation for myelofibrosis A1 BMT. Contact: B. Lange, MD. Phone: 215-590-2249. following conditioning with busulfan. Patients up to 70 years Children’s Cancer Group. CCG-A2971. Phase III study of
of age. Contact: H.J. Deeg, MD. Phone: 206-667-4324.
children with Down Syndrome and transient myelo- Fred Hutchinson Cancer Research Center. FHCRC
proliferative disorder, AML, or MDS. Contact: Alan Scott #1032. Transplantation for myelofibrosis from related or unrelated donors after conditioning with busulfan plus Children’s Cancer Group. CCG-B942. Detection of minimal
cytoxan or busulfan plus TBI. Patient age limit 65. Contact: residual disease in children receiving therapy for AML or MDS. Contact: E. Sievers, MD. Phone: 206-667-5757.
Fred Hutchinson Cancer Research Center. FHCRC
City of Hope National Medical Center. IRB #97128.
#1463. Low-dose TBI and fludarabine followed by unrelated Molecular pathogenesis of MDS and AML in the elderly.
donor stem cell transplantation for patients with hema- Contact: R. Bhatia, MD. Phone: 626-359-8111, x 2683.
tological malignancies. This multi-center trial targets older City of Hope National Medical Center. IRB #99041.
(>55 years) patients, and patients who, because of Phase II study of IV busulfan combined with 12cGy of concurrent medical problems, cannot tolerate a traditional fractionated TBI and etoposide (VP-16) as a preparative transplant. Patients from the following diagnoses are eligible regime for allogeneic bone marrow transplantation for for therapy: CML, AML, ALL, MDS, multiple myeloma, and patients with advanced RAEB and RAEB-t hematological lymphoma. Contact: M. Maris, MD. Phone: 206-288-1024.
malignancies. Contact: A. Stein, MD. Phone: 626-359- Fred Hutchinson Cancer Research Center. #1519.
Transplantation of peripheral blood stem cells from relatedor unrelated donors in patients with “advanced” MDS.
City of Hope National Medical Center. IRB #99045.
Autologous stem cell transplantation for MDS in first remission.
Conditioning consists of fludarabine and busulfan Contact: H. Fung, MD. Phone: 626-359-8111, x2405.
(targeted to a predetermined plasma level). Patients up to65 years are eligible. Contact: Claudio Anasetti, MD.
City of Hope National Medical Center. IRB 398056.
Treatment of poor risk MDS with the combination of Fred Hutchinson Cancer Research Center. #1555.
amifostine, topotecan and Ara-C as a phase II study.
Transplantation of peripheral blood stem cells from related Contact: H. Fung, MD. Phone: 626-359-8111, x 2405.
or unrelated donors for the treatment of “advanced” MDS Cleveland Clinic. SMC-101-1020. Phase IIb study of thymo-
(CD33+). Conditioning includes Mylotarg (for two doses), globulin in transfusion dependent patients with RA or RAEB.
fludarabine and 200 cGy of total body irradiation. Patients Contact: Matthew Kalaycio, MD. Phone: 216-444-3705. are being evaluated individually for eligibility. Contact: Eric Dana Farber Cancer Institute. DFCI 99-249. Vaccine
trial–phase I–patients with MDS or relapsed acute myelo- Fred Hutchinson Cancer Research Center. #1596.
genous leukemia. Cells will be harvested via bone marrow Transplantation from related donors for high risk patients biopsy and aspirate or phersis. Injection will be with MDS. Conditioning includes a "non-myeloblative" administered via sub-Q at specified times. Contact: D.
regimen of fludarabine and 200 cGy of total body irradiation. Patients are evaluated individually for eligibility.
Duke University Medical Center. Multicenter trial of
Contact: David Maloney, MD, PhD. Phone: 206-288-1024.
induction-type chemotherapy for patients with high-risk Fred Hutchinson Cancer Research Center. FHCRC
MDS as defined by the International Prognostic Scoring #1478. Non-transplant therapy for “less advanced” MDS System. Contact: C. de Castro, MD. Phone: 919-684-8964.
with ATG plus Enbrel. No age restrictions. Contact: H.J.
Duke University Medical Center. Phase II study of
amifostine in patients with MDS. Contact: C. de Castro, MD.
Guthrie Clinic, Ltd. ECOG 1996. Phase III evaluation of
EPO with or without G-CSF versus supportive therapy alone in the treatment of MDS. Contact: Michele Chaborek, MCP Hahneman University. T-MDS-001. A randomized,
double blind, placebo-controlled trial composing best Hahnemann University at MCP.
supportive care and thalidomide for the treatment of combination study of topotecan, fludarbine, cytosine, anemic patients with MDS followed by an open-label arabinoside and G-CSF (TFLAG) induction therapy in treatment with thalidomide. Contact: Emmanuel Besa, MD.
patients with poor prognosis AML, MDS and relapsed/ refractory ALL. Contact: E. Besa, MD. Phone: 215-842-6980.
MD Anderson Cancer Center. ID99-059. ATG +/–
Hoosier Oncology Group. Phase II trial of topotecan in
cyclosporin +/– fludarabine in RA, RARS, RAEB <10% patients with MDS. Contact: Paul Walker, MD. Phone: 765- blasts Contact: Jeff Mollaren, MD. Phone: 713-745-4820. MD Anderson Cancer Center. DM 00-101. Mylotarg +/–
Indiana University Medical Center. B3T-MC-JTAH(a). Phase
IL-II in AML, RAEB, RAEB-t, CMML, >10% blasts in II study of LY335979 plus daunorubicin and cytarabine in patients 65 years and older with normal cytogenetics.
subjects with de nova high risk acute myelogenous Contact: Elihu Estey, MD. Phone: 713-794-7544. leukemia or relapsed/refractory acute myelogenous MD Anderson Cancer Center. Idarubicin and Ara-C CI in
leukemia. Contact: L. Cripe, MD. Phone: 317-274-3545.
AML, RAEB, RAEB-t, CMML, with >10% blasts in patients Indiana University Medical Center. IU #9907-25. Induction
65 years and older with abnormal cytogenetics. Contact: Chemotherapy with the addition of a new MDR inhibitor for patients with RAEB-t or AML that has progressed from a MD Anderson Cancer Center. DM00-186. Thalidomide in
documented phase of MDS. Contact: L. Cripe, MD. Phone: RA, RARS, MDS with low to intermediate risk IPSS.
Contact: Deborah Thomas, MD. Phone: 713-745-4616. Indiana University School of Medicine. Phase II trial of
MD Anderson Cancer Center. IDP00-269. Reverse
subcutaneously administered recombinant human inter- transcriptase inhibitors in refractory or relapsed MDS, AML, leukin-11 in thrombocytopenic patients with MDS. Contact: MPD. Contact: Hagop Kartarjian, MD. Phone: 713-792-7026. MD Anderson Cancer Center. DM99-142. Oral Topotecan
James Haley Veterans Hospital-Tampa. SMC-101-1029.
in hematologic myeloid malignancies Contact: Miloslav Phase IIb study of thymoglobulin in transfusion dependent patients with RA or RAEB. Contact: Hussain Saba, MD.
Phone: 813-972-7582. MD Anderson Cancer Center. ID95-124. 9-Nitrocamp-
tothecin in MDS, CML, MPD. Contact: Jorge Cortes, MD.
Johns Hopkins Oncology Center. J0051. Phase I trial:
GM-CSF and Bryostatin-1 in combination to treat MDS,AML, and other myeloid malignancies. Therapy is designed MD Anderson Cancer Center. Idarubicin and Ara-C
to enhance differentiation of myeloid progenitors and blasts double induction in AML, RAEB, RAEB-t, CMML with >10% to improve marrow function and eliminate tumor cell clone.
blasts in patients < 50 years old. Contact: Elihu Estey, MD.
Cotnact: Douglas Smith, MD. Phone: 410-614-5068.
Johns Hopkins Oncology Center. J9852. GM-CSF after
MD Anderson Cancer Center. Mylotarg and BID
T-lymphocyte-depleted allogeneic BMT for MDS. Contact: Fludarabide/Ara-C and cyclosporin in AML, RAEB, P. O’Donnell, MD, PhD. Phone: 410-614-0205. RAEB-t, CMML with .10% blasts in patients aged 50–64years. Contact: Elihu Estey, MD. Phone: 713-792-7544. Johns Hopkins Oncology Center. J9845. Non-myelo-
ablative allogeneic BMT for hematologic malignancies.
Medical College of Wisconsin. MCW 91-126. Marrow
Contact: Ian W. Flinn, MD. Phone: 410-955-8781. transplantation for patients with hematologic malignancies.
Contact: D. Vesole, MD. Phone: 414-805-4646.
Johns Hopkins Oncology Center. Opening March 2000. A
phase I, dose finding trial of sodium phenylbutyrate in
Medical College of Wisconsin. MCW 93-23. Allogeneic
combination with all transretinoic acid in patients with MDS marrow transplantation for patients with hematologic and AML. Contact: Steven Gore, MD. Phone: 410-955-8781. malignancies and marrow failure states from genotypicallyhaplo-identical family members. Contact: D. Vesole, MD.
Mayo Clinic. 0-215-98. A pilot study of antithymocyte
globulin in anemic patients with RA or RAEB. Contact:Doctors A. Tefferi, M. Elliott, L. Letendre, M. Litzow, D.
Medical College of Wisconsin. MCW 95-18. T-cell
depletion in unrelated-donor marrow transplantation.
Contact: D. Vesole, MD. Phone: 414-805-4646.
MCP Hahneman University.
randomized study of the safety and efficiency of 2 dose Medical College of Wisconsin. MCW 97-137. Amifostine/
schedules of Gentuzumab Ozogomicin (mylotarg) in pentoxifylline/ciprofloxacin/dexamethasone for low-risk patients with Intermediate-2 or High Risk MDS. Contact: MDS. Contact: D. Vesole, MD. Phone: 414-805-4646.
Medical College of Wisconsin.
MCP Hahneman University. A Phase II study of a
Amifostine/topotecan versus pentoxifylline/ciprofloxacin/ combination of topetecan, fludirabine, ARA-C and G-CSF CT- dexamethasone for high-risk MDS. Contact: D. Vesole, Flag. Contact: Emmanuel Besa, MD. Phone: 215-842-6980. MCP Hahneman University. E1996. Phase III evaluation of
Medical College of Wisconsin. MCW 99-10. Total
EPO with or without G-CSF versus supportive therapy lymphoid irradiation, melphalan and fludarabine for T-cell- alone in the treatment of MDS. Contact: Emmanuel Besa, depleted allogeneic peripheral-blood stem cell trans- plantation. Contact: D. Vesole, MD. Phone: 414-805-4646.
Memorial Sloan Kettering Cancer Center. 190. Phase II
RAEB-t; (c) high risk MDS defined by IPSS of 2.0; or (d) study of Arsenic Trioxide in relapsed or refractory, CML.
AML which has evolved from a pre-existing MDS. Contact: Contact: David Scheinberg, MD. Phone: 212-639-5010.
C. Hesdorffer, MD. Phone: 212-305-4907.
Multicenter. SMC-101-1020. Phase IIb study of thymo-
Pediatric Oncology Group. POG-9720. Phase II study of
glogulin in transfusion dependent patients with RA or RAEB.
idarubicin and cladribine in children with recurrent or Contact: Elizabeth Squiers, MD. Phone: 510-789-4535. refractory AML. Contact: Craig A. Hurwitz, MD. Phone: 207- National Heart, Lung and Blood Institute. NHLBI-99-H-
0050. Phase II study of nonmyeloablative allogeneic Pediatric Oncology Group. POG-9362. Phase II study of
peripheral blood stem cell transplantation in patients with IFN-A for pediatric HIV-related malignancies. Contact: V.M.
hematologic disease or cancer. Contact. R.W. Childs, MD.
Rush Cancer Institute. MDS-9914. A pilot study of
National Heart Lung and Blood Institute. Phase II study of
thalidomide combined with pentoxifylline, ciprofloxacin, leucovorin in patients with 5q- syndrome. MDS subtypes and dexamethasone (PCD) in patients with MDS. Contact: RA, RARS, and RAEB are eligible. Patients must have 5q- as their sole cytogenetic abnormality and meet criteria for Rush Cancer Institute. MDS 9906. A pilot study of anti-CD-
moderate to severe cytopenias. Phone: 301-496-5150.
20 monoclonal antibody (Rituxan) in the treatment of patients National Heart Lung and Blood Institute. Clinical
with MDS. Contact: A. Raza, MD. Phone: 312-455-8474.
protocol studying the use of G-CSF-mobilized T-depleted Rush Cancer Institute. MDS 2000-02. Combination of
donor peripheral blood progenitor/stem cells followed by thalidomide and topetecan in the treatment of patients with delayed donor T cells to optimize graft-verses-tumor high risk MDS. Contact: A. Raza, MD. Phone: 312-455-8474.
effects in patients with hematologic malignancies. Phone: Rush Cancer Institute. MDS 2000-03. Combination of
etanercept (TNFR:Fc) and thalidomide in the treatment of National Heart Lung and Blood Institute. Phase II study
patients with MDS. Contact A. Raza, MD. Phone: 312- of antithymocyte globulin (ATG) and cyclosporine in patients with MDS (RA, RARS, RAEB) who have moderate Rush Cancer Institute. MDS 2000-04. An open label,
to severe cytopenias. Contact: Laura B. Wisch, RN.
prospective, randomized, stratified, controlled, multi- center, phase Iib study of the impact of thymoglobulin New York Medical College. 30/38. A phase III, open-label,
therapy on transfusion needs of patients with early MDS.
multicenter, randomized, comparative study of topetecan, Contact: A. Raza, MD. Phone: 312-455-8474.
Ara-C and G-Csf (TAG) versus idarubicin, Ara-C and G- Rush Cancer Institute. MDS 2000-05. A three year
CSF (IDAG) in MDS patients RAEB (high risk), RAEB-t or in evaluation of the overall and leukemic free survival of patients with AML from a preceding phase of MDS.
patients who received thymoglobulin therapy for early Contact: Karen Seiter, MD. Phone: 914-493-8374. MDS. Contact: A. Raza, MD. Phone: 312-455-8474.
New York Medical College. 0012-2000. An open-label,
Rush Cancer Institute. 0903B1-207-US. A randomized
prospective, stratified, randomized, controlled, multicenter, study of the safety and efficacy of two dose schedules of phase IIB study of the impact of thymoglobulin therapy on gemtuzumab ozogamacin in patients with intermediate-2 or transfusion needs of patients with early MDS. Contact: high risk MDS. Contact: A. Raza, MD. Phone: 312-455-8474.
Rush Cancer Institute. MDS 2000-08. A pilot study to test
New York Medical Hospital. SMC-101-1020. Phase IIb
the efficacy of glivec (ST1571) in patients with chronic study of thymoglobulin in transfusion dependent patients myelomoncytic leukemia. Contact: A. Raza, MD. Phone: with RA or RAEB. Contact: Michael Schuster, MD. Phone: Rush Presbyterian. SMC-101-1020. Phase IIb study of
New York Presbyterian Hospital – Columbia Medical
thymoglobulin in transfusion dependent patients with RA or Center. 104864-A/201 Study. Phase III open label,
RAEB. Contact: Azra Raza, MD. Phone: 312-455-8474. randomizes comparative study of topotecan, Ara-C and G-CSF (TAG) vs. idarubicin, Ara-C and GCSF (IDAG) in MDS.
Southwest Oncology Group. SWOG-S9920. Phase III
Over the age of 18 with either: (a) RAEB; (b) RAEB-t; (c) randomized study of total body irradiation (TBI) plus high risk MDS defined by IPSS of 2.0; or (d) AML which has busulfan versus TBI plus cyclophosphamide followed by evolved from a pre-existing MDS. Contact: Charles allogeneic peripheral blood stem cell transplantation in patients with advanced MDS or MDS related AML. Contact:Charles A. Coltman, Jr., MD. Phone: 210-616-5580.
New York Presbyterian Hospital – Columbia Medical
Center. Camp 026. Autologous peripheral stem cell
Texas Cancer Center. SMC-101-1020. Phase IIb study of
harvesting and transplantation for high risk MDS. IPS score thymoglobulin in transfusion dependent patients with RA or greater than 2.0, no allo match, age 18–70. Idarubicin/Ara- RAEB. Contact: Craig Rosenfeld, MD. Phone: 972-566-7790. C for mobilization followed by BMT with a BU/Cy regimen.
University of Connecticut Health Center.
Contact: Charles Hesdorffer, MD. Phone: 212-305-4907. Cooperative Group Trial. EPO+/– GCSF VS. supportive care New York Presbyterian Hospital – Columbia Medical
alone. Contact: B. Greenberg, MD. Phone: 860-679-2100.
Center. 104864-A/201 Study. Phase III open label,
University of Connecticut Health Center. 99-285. Partial
randomizes comparative study of topotecan, Ara-C and matched related donor allogeneic stem cell transplant with G-CSF (TAG) vs. Idarubicin, Ara-C and GCSF (IDAG) in a non-myeloablative preparative regimen. Contact: R.
MDS. Over the age of 18 with either: (a) RAEB; (b) University of Connecticut Health Center. 99-262. Non-
University of Texas Health Science Center. IRB # 978-
myeloablative therapy followed by adoptive immuno- 5008-302. Sequential antithymocyte globulin (ATG) and therapy with allogeneic HLA matched stem cell transplant.
amifostine for the treatment of MDS. ATG is given as an Contact: R. Bona, MD. Phone: 860-679-2257.
intravenous infusion in the hospital over 4 days. Skin University of Chicago. UC 9581. Allogeneic peripheral
testing for sensitivity to ATG performed prior to the first blood stem cell transplantation using a non-myeloblative dose. Amifostine is given as an IV pus. Contact: J.
preparative regimen for patients with hematologic malig- nancies. Contact: R.A. Larson, MD. Phone: 773-702-2070.
University of Washington, Seattle Cancer Care Alliance.
University of Florida. SMC-101-1020. Phase IIb study of
95-04570-A 05. Determining safety, tolerance, and maximum thymoglobulin in transfusion dependent patients with RA tolerated dose of SC Interleukin-2 in MDS patients.
or RAEB. Contact: Katarzyna Finiewicz, MD. Phone: 352- Contact: John A. Thompson, MD. Phone: 206-288-2041. Wake Forest. SMC-101-1020. Phase IIb study of thalido-
University of Iowa Hospitals and Clinics. Cancer and
mide in transfusion dependent patients with RA or RAEB.
Leukemia Group B. CLB-69803. Phase I study of 506U78 in Contact: Kenneth Zamkoff, MD. Phone: 336-716-7972. patients with hematologic malignancies and renal or Washington University in St. Louis. 95-0384. Washington
hepatic impairment. Contact: Todd M. Zimmerman, MD.
University School of Medicine. A phase II study to evaluate the tumor response rate and toxicity of granulocyte-colony University of Maryland Greenebaum Cancer Center.
stimulating factor (G-CSF) primed donor leukocyte infusion UMGCC 0050. Phase I trial of oral medication MS-275, administered to patients with relapsed hematologic given for 28 days to reinstate the expression of genes malignancy occurring after allogeneic bone marrow or which cause cells to mature. Contact: Judith E. Karp, MD.
peripheral blood stem cell transplant. Contact: D.R.
University of Maryland Greenebaum Cancer Center.
Washington University in St. Louis. 95-0763. Washington
UMGCC 0052. Flavopiridol’s role in cell death (apoptosis) University School of Medicine. High dose rate/low total and proliferation in order to increase sensitivity to Ara-C dose-single exposure total body irradiation as conditioning and mitoxantrone. Contact: Judith E. Karp, MD. Phone: for related donor allogeneic peripheral blood stem celltransplantation. A phase II study to evaluate engraftment and duration of neutropenia. Contact: D. Adkins, MD.
University of Maryland Greenebaum Cancer Center.
UMGCC 0001. The use of topetecan, Ara-C, and Washington University in St. Louis. 97-0793. Washington
mitoxantrone TST in aggressive MDS. Contact: Judith E.
University School of Medicine. High dose rate/low total dose-single exposure total body irradiation as conditioning University of Maryland Greenebaum Cancer Center.
for unrelated and mismatched related donor bone marrow UMGCC 0076. Use of bevacizumab to inhibit vascular transplantation: A phase II study to evaluate engraftment.
endothelial growth factor (VEGF) production after Contact: D. Adkins, MD. Phone: 314-454-8490.
chemotherapy with Ara-C and Mitoxantrone. Contact: Washington University in St. Louis. 98-0502. Washington
Judith E. Karp, MD. Phone: 410-328-7394. University School of Medicine. Stem cell transplantation for University of Michigan Comprehensive Cancer Center.
Aplastic Anemia and various malignancies. Contact: R.
UMCC 0068. A randomized study of the safety and efficacy of two dose schedules of gemtuzumab ozogamicin Washington University in St. Louis. 101-1020. An open-
(Mylotarg) in patients with intermediate-2 or high risk MDS label, prospective, stratified, randomized, controlled, Contact: Harry P. Erba, MD, PhD. Phone: 734-647-8921. multicenter, phase IIB study of the impact of thymoglobulin University of Michigan Medical Center. UMCC 9906.
therapy on transfusion needs of patients with early MDS.
Combination of azacitadine and amifostine in the treatment Contact: John F. DiPersio, MD, PhD. Phone: 314-454-8317.
of adults with MDS. Contact: Harry P. Erba, MD. Phone: 734-647-8921. JoAnn Goodson, Data Manager. Washington University in St. Louis. 101-1022. A three
University of Michigan Medical Center. Clinical treatment
year evaluation of the overall and leukemic free survival of via bone marrow transplant for hematological malignancies.
patients who received thymoglobulin therapy for early Contact: Dr. Harry D. Erba, MD, PhD. Phone: 734-647-8921.
MDS. Contact: John F. DiPersio, MD, PhD. Phone: 314- University of Rochester Cancer Center. 18400. A phase
2 study of SU5416 in patients with hematologic malignancies, Westchester Medical Center, New York Medical College.
including refractory acute myeloid leukemia, myelodysplasia, 008/2000. Non-myeloblative chemotherapy with pentostatin, refractory acute lymphocytic leukemia, philadelphia nega- mitoxantrone and cytarabine for engraftment of allogeneic tive myeloproliferative disorders or chronic myelogenous hematopoietic progenitor cells in patients with hemato- leukemia. Contact: Wanda Bates, Administrative Assistant.
logical malignancies. Contact: Delong Liu, MD and Karen

Source: http://www.mds-foundation.org/pdf/spring-2001.pdf