HLA-C antigen mismatch in unrelated PBSC transplant
A large-scale study of unrelated-donor peripheral blood stem cell (PBSC) transplantation has found that HLA-C antigen-mismatched donors were associated with worse outcomes compared to 8/8 HLA-matched donors. In this study of 1933 transplants between 1999 and 2006 reported to the NMDP and CIBMTR (Center for International Blood and Marrow Transplant Research), 8/8 HLA-matched patients (HLA-A, -B, -C, -DRB1 alleles, n=1243) were used as the baseline, and outcomes were adjusting for patient and transplant characteristics. HLA-C antigen mismatches (n=189) were significantly associated with lower leukemia-free survival, and increased risk of mortality, treatment-related mortality, and grade III-IV GVHD. The authors noted that these results “are not meant to imply that an HLA-mismatched graft should not be used, only that the greater risks compared with 8/8 HLA-matched grafts should be recognized when present.”
Michelle Setterholm, NMDP Director of Scientific Services, provides insight on the above article. Read commentary.
In vivo T-cell depletion not recommended in reduced-intensity HCT
Adults with hematologic malignancies undergoing reduced-intensity conditioning (RIC) transplant using T-cell replete grafts have better outcomes than those transplanted using T-cell depleted grafts, according to a study of 1676 transplants performed between 2000 and 2007 and reported to CIBMTR. In vivo T-cell depletion was achieved with pre-transplant ATG (n=584) or alemtuzumab (n=213). Although chronic GVHD was lower in alemtuzumab and ATG recipients (24% and 40%, respectively), compared with replete grafts (52%), ATG and alemtuzumab patients had increased rates of relapse. As a result, disease-free survival was lower with alemtuzumab and ATG (30% and 25%, respectively) compared with replete grafts (39%). In an accompanying editorial, Dr. Sergio Giralt notes that ”it would be reasonable to minimize the use of ATG in the RIC setting to patients at higher risk of developing GVHD (alternative donor or mismatched transplantation) and to those with lower risk of relapse.”
A study of 296 patients with severe aplastic anemia transplanted using bone marrow (BM, n=225) or peripheral blood stem cells (PBSC, n=71) from matched unrelated donors has found that better outcomes are achieved using marrow. Patients and donors were matched at HLA-A, -B, -C, -DRB1, and transplants occurred between 2000 and 2008 and were reported to CIBMTR. Mortality risks, independent of age, were higher after PBSC compared to BM transplantation (HR 1.62, 95% CI 1.01-2.58, p=0.04) and 3-year overall survival was significantly higher with BM than with PBSC: 76% vs. 61%, respectively; (p=0.02).
Better outcomes with tandem auto/allo-HCT than with auto-transplant in myeloma
A multi-center trial of 357 patients with multiple myeloma has shown that tandem autologous-allogeneic transplants yield higher overall and progression-free survival, and lower relapse than single autologous transplantation. Patients up to age 69 years underwent transplant between 2001-2005. Patients with an HLA-identical sibling donor (n=108) underwent auto-allo tandem reduced-intensity conditioning transplantation and 249 patients without a matched sibling donor underwent single autologous transplantation. Five-year progression-free survival was significantly better in the tandem transplant patients than in single autologous transplantation (35% vs. 18%, respectively; p=0.001).
A prospective study of 30 patients with chemosensitive follicular lymphoma (FL) beyond first complete response or first partial response has found that both autologous and reduced-intensity allogeneic transplantation can be appropriate therapies in these patients. In this trial by the Blood and Marrow Transplant Clinical Trials Network (BMT CTN), overall survival at a median follow-up of 36 months (range, 1-51) was 73% in autologous HCT recipients (n=22) and 100% in allogeneic HCT recipients (n=8). Progression-free survival was 63% in autologous HCT recipients and 86% in allogeneic HCT recipients. No differences in survival between the two arms was statistically significant.
A review article outlining a tool developed by the European Group for Blood and Marrow Transplantation (EBMT) that provides a risk score and prognosis for patients under consideration for hematopoietic cell transplantation (HCT). The EBMT tool evaluates five factors: age of the patient, stage of the disease, time from diagnosis, donor type, and donor-recipient sex match. The additive score from 0 (best) to 7 (worst) has been validated for all acquired hematological disorders, and is applicable for standard or reduced-intensity conditioning HCT. The author says that the EBMT score and its “risk-adapted individualized strategy” should guide decisions when choosing between HCT and a non-transplant approach.
A new NMDP-sponsored CME series is now available: Management of Advanced Non-Hodgkin Lymphomas. This four-part series reviews treatment options for follicular, mantle cell, diffuse large B-cell, and T-cell lymphomas. Learn about first- and second-line treatment options for relapsed/refractory patients, including novel agents, and both allogeneic and autologous transplantation. Access NHL CME program
Supported by an unrestricted educational grant from Otsuka America Pharmaceutical, Inc., provided to the National Marrow Donor Program through the Be The Match Foundation®, the funding partner of the NMDP.
National Marrow Donor Program, 3001 Broadway St. N.E., Minneapolis, MN 55413-1753
Advances in Transplantation is an electronic newsletter published monthly by the National Marrow Donor Program (NMDP). This newsletter is sent only to those individuals who have requested to receive clinical education updates from NMDP.
If this e-mail message was forwarded to you and you’d like Advances in Transplantation delivered directly to you, please subscribe. If you would like to stop receiving Advances in Transplantation, please unsubscribe.
If you are a member of the NMDP Be The Match Registry®, unsubscribing to the Advances in Transplantation e-newsletter does not change your status on the registry. The NMDP may still contact you by e-mail, postal mail or telephone if a patient needs you or to request that you update your address.