| Vol. 5, No. 2: March/April 2005 |
Read the Tandem BMT Meetings Special Edition of Advances in Transplantation (PDF).
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Low-dose TBI and cyclophosphamide can result in 100% donor chimerism
A conditioning regimen using low-dose (550-cGy), single-exposure, high dose rate (30 cGy/min) total body irradiation with cyclophosphamide can result in high rates of donor chimerism and low treatment-related mortality (TRM), according to a study in Blood. In this study of 110 unrelated donor marrow transplant patients (26 good-risk diagnoses, 84 poor-risk), fatal organ toxicity occurred in only 2% of patients, and 2-year TRM in good-risk patients and poor-risk patients was 19% and 42%, respectively. The percentage of evaluable patients achieving 100% donor chimerism at 1- and 3-years post-transplant was 94% and 100%, respectively. Overall survival in the good-risk group was 47% and was 25% in the poor-risk group at a median follow-up of 850 days.
Girgis M, et al. Blood 2005; 105(8): 3035-3041. (More) |
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Reduced-intensity transplants feasible for good-risk multiple myeloma patients
An analysis of prognostic factors of multiple myeloma patients reveals which patients could benefit most from reduced-intensity transplantation, according to a report from the chronic leukemia working party of the European Group for Blood and Marrow Transplantation (EBMT). This study examined the results of 229 multiple myeloma patients (median age 52 years) receiving allogeneic transplants at 33 EBMT centers. Conditioning regimens varied, but the majority used fludarabine and T-cell depleted grafts with anti-thymocyte globulin or alemtuzumab. One-year transplant-related mortality was 22% and 3-year overall survival and progression-free survival (PFS) were 41% and 21%, respectively. Adverse overall survival was associated with more than 1 prior transplant (RR=2.0) and chemoresistant disease (RR=2.9). The EBMT group concluded that although reduced-intensity transplants are feasible with multiple myeloma patients, "heavily pretreated patients and those with progressive disease do not benefit."
Crawley C, et al. Blood 2005; E pub ahead of print, Feb. 24. (More) |
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Intensive GVHD prophylaxis needed after non-myeloablative unrelated donor transplantation
A study of 25 patients undergoing unrelated donor non-myeloablative transplantation conditioned with fludarabine and cyclophosphamide. Six patients in Group 1 received cyclosporine (Cs) and mycophenolate mofetil (MMF) (n=5) or methotrexate (MTX) (n=1) as GVHD prophylaxis. All patients developed grade III-IV acute GVHD. Group 2 patients (n=19) received the same conditioning plus alemtuzumab, and received post-transplant Cs/MTX. Fifteen patients died: 5 of 6 deaths in Group 1 were due to acute GVHD, while deaths in Group 2 were due to infection or progressive disease (p=0.05). The researchers conclude that the combination of Cs/MMF is inadequate GVHD prophylaxis in unrelated donor non-myeloablative transplantation, and that Cs, MTX, and alemtuzumab merit further study for the elimination of severe acute GVHD.
Loren AW, et al. Bone Marrow Transplant 2005; 35(9): 921-926. (More) |
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Graft-versus-tumor effects after non-myeloablative transplantation
An analysis of the graft-versus-tumor effects seen in 322 patients receiving HLA-matched related (n=192) or unrelated (n=130) donor non-myeloablative transplants between 1998 and 2003 at four Seattle hospitals. Conditioning regimens consisted of total-body irradiation (2 Gy) with or without fludarabine (30 mg/m2/d x 3). Patients in the study had hematologic malignancies and were not candidates for conventional transplants due to age, co-morbidities, or prior high-dose transplantation. Of patients with measurable disease at transplant (221/322; 69%), 44% (98/221) achieved a complete remission, and 13% (28/221) achieved a partial remission. Grade II-IV acute GVHD had no significant impact on the risk of relapse or progression but was associated with a decreased probability of progression-free survival (PFS) and increased risk of non-relapse mortality. In contrast, extensive chronic GVHD was significantly associated with improved PFS. The authors conclude that survival in non-myeloablative transplantation could be improved by reducing the incidence of grade II-IV acute GVHD.
Baron F, et al. J Clin Oncol 2005; 23(9): 1993-2003. (More) |
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Response to post-transplant imatinib determines outcome in Ph+ ALL
This prospective multi-center study reported on 27 Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia patients (median age of 48 years) who received imatinib upon detection of post-transplant minimal residual disease, which is a strong predictor of relapse. Ph+ transcriptions became undetectable in 14 of the 27 patients (52%) after a median of 1.5 months and these patients remained in remission for the duration of their imatinib treatment. Failure to respond to imatinib shortly after starting treatment predicted relapse: 12 of 13 (92%) non-responders to imatinib relapsed after a median of 3 months. The researchers conclude that failure to respond after 2-3 months on imatinib identifies patients who will ultimately experience relapse and who should therefore receive additional anti-leukemic treatment.
Wassmann B, et al. Blood 2005; E pub ahead of print, April 7. (More) |
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Blacks have significantly higher mortality after allogeneic transplantation
A survival analysis by race/ethnicity of 3,587 consecutive patients who underwent hematopoietic cell transplantation at the Fred Hutchinson Cancer Research Center between 1992 and 2000. Race or ethnicity was not significantly associated with survival in the 1,366 patients who received autologous transplants. In 2,221 allogeneic transplant recipients (related or unrelated donors), blacks had a significantly greater mortality than whites, with an unadjusted hazard ratio of 1.65 (95% CI: 1.21-2.25). The time interval from diagnosis to transplantation of the CML patients in the study was more than twice as long for blacks than for whites, which the researchers suggest may explain the higher mortality among black patients.
Mielcarek M, et al. Biol Blood Marrow Transplant 2005; 11(3): 231-239. (More) |
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Review: What is quality in a transplant program?
Due to the diverse outcomes of a heterogeneous group of patients and the rapid growth of transplant, the field of hematopoietic cell transplantation has not yet developed a solid consensus on objective indicators of quality in transplant programs, especially as they pertain to outcomes. This review article discusses advances in this area and the issues involved in establishing objective measures of quality in transplant programs, including measuring technical expertise, measuring clinical quality, the value of accreditation, the need for standardized reporting, and accurate indicators of quality.
LeMaistre CF, et al. Biol Blood Marrow Transplant 2005; 11(4): 241-246. (More) |
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Clinical Trial News:
Follicular NHL clinical trial now enrolling
An NIH-sponsored trial through the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) is currently accruing patients with relapsed or progressive follicular non-Hodgkin's lymphoma. This trial compares the role of autologous hematopoietic stem cell transplantation (HSCT) plus rituximab maintenance therapy vs. allogeneic non-myeloablative HSCT. The treatment arm is assigned based on the availability of an HLA-matched sibling. Patient eligibility, participating centers.
Contact: Ginna G. Laport, M.D., Stanford University Medical Center Ph: 650-723-1389
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Other journal articles of note:
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