Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
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Biol. Blood Marrow Transplant. · Feb 2015
Allogeneic hematopoietic cell transplantation outcomes in acute myeloid leukemia: similar outcomes regardless of donor type.
The use of alternative donor transplants is increasing as the transplantation-eligible population ages and sibling donors are less available. We evaluated the impact of donor source on transplantation outcomes for adults with acute myeloid leukemia undergoing myeloablative (MA) or reduced-intensity conditioning (RIC) transplantation. Between January 2000 and December 2010, 414 consecutive adult patients with acute myeloid leukemia in remission received MA or RIC allogeneic transplantation from either a matched related donor (n = 187), unrelated donor (n = 76), or umbilical cord blood donor (n = 151) at the University of Minnesota or Hôpital St. ⋯ Relapse was increased with RIC and lowest in younger patients receiving MA conditioning (hazard ratio, 1.0 versus 2.5 or above for all RIC age cohorts), P < .01. Transplantation-related mortality was similar across donor types. In summary, our data support the use of alternative donors as a graft source with MA or RIC for patients with acute myeloid leukemia when a sibling donor is unavailable.
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Biol. Blood Marrow Transplant. · Feb 2015
Feasible outcomes of T cell-replete haploidentical stem cell transplantation with reduced-intensity conditioning in patients with myelodysplastic syndrome.
Even with the recent optimization of haploidentical stem cell transplantation (SCT), its role for patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia evolving from MDS (sAML) should be validated. We analyzed the outcomes of consecutive 60 patients with MDS or sAML who received T cell-replete haploidentical SCT after reduced-intensity conditioning with fludarabine, busulfan, and rabbit antithymocyte globuline ± 800 cGy total body irradiation. Patients achieved a rapid neutrophil engraftment after a median of 12 days (range, 8 to 23) and an early immune reconstitution without high incidences of acute graft-versus-host disease (GVHD) II to IV and chronic GVHD (36.7% and 48.3%, respectively). ⋯ In multivariate analysis, the disease status at peak was a significant predictor for relapse (lower-risk MDS versus higher-risk MDS or sAML; hazard ratio [HR], 5.69; 95% confidence interval [CI], 1.45 to 22.29; P = .013) and disease-free survival (HR, 4.44; 95% CI, 1.14 to 17.34; P = .032). Chronic GVHD was an additional significant predictor for relapse (no versus yes; HR, 2.87; 95% CI, 1.03 to 7.51; P = .043). Our T cell-replete haploidentical SCT may be a feasible option for patients with MDS and sAML without conventional donors.
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Biol. Blood Marrow Transplant. · Feb 2015
Prevalence and impact of financial hardship among New England pediatric stem cell transplantation families.
Poverty is correlated with negative health outcomes in pediatric primary care and subspecialties; its association with childhood hematopoietic stem cell transplantation (HSCT) patterns of care and clinical outcomes is not known. We describe family-reported financial hardship at a primary referral center in New England and explore the relationship between measures of poverty and patterns of care and clinical outcomes. Forty-five English-speaking parents of children after allogeneic HSCT in the prior 12 months completed a 1-time survey (response rate 88%). ⋯ In univariate analyses, 11 (61%) low-income children experienced graft-versus-host disease (GVHD) of any grade in the first 180 days after HSCT compared with 2 (7%) wealthier children (P = .004). We conclude that low income and, in particular, material hardship, are prevalent in a New England pediatric HSCT population and represent targets for improvement in quality of life. The role of poverty in mediating GVHD deserves further investigation in larger studies that can control for known risk factors and may provide a targetable source of transplantation-associated morbidity.
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Biol. Blood Marrow Transplant. · Feb 2015
The impact of amino acid variability on alloreactivity defines a functional distance predictive of permissive HLA-DPB1 mismatches in hematopoietic stem cell transplantation.
A major challenge in unrelated hematopoietic stem cell transplantation (HSCT) is the prediction of permissive HLA mismatches, ie, those associated with lower clinical risks compared to their nonpermissive counterparts. For HLA-DPB1, a clinically prognostic model has been shown to be matching for T cell epitope (TCE) groups assigned by cross reactivity of T cells alloreactive to HLA-DPB1∗09:01; however, the molecular basis of this observation is not fully understood. Here, we have mutated amino acids (aa) in 10 positions of HLA-DPB1∗09:01 to other naturally occurring variants, expressed them by lentiviral vectors in B cell lines, and quantitatively measured allorecognition by 17 CD4(+) T cell effectors from 6 unrelated individuals. ⋯ Experimental confirmation of the in silico TCE group classification was successfully performed for 7 of 7 of these alleles. Our findings have practical implications for the applicability of TCE group matching in unrelated HSCT and provide new insights into the molecular mechanisms underlying this model. The innovative concept of FD opens new potential avenues for risk prediction in unrelated HSCT.
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Biol. Blood Marrow Transplant. · Jan 2015
Multicenter StudyLong-term survival and late effects among one-year survivors of second allogeneic hematopoietic cell transplantation for relapsed acute leukemia and myelodysplastic syndromes.
We analyzed the outcomes of patients who survived disease-free for 1 year or more after a second allogeneic hematopoietic cell transplantation (HCT) for relapsed acute leukemia or myelodysplastic syndromes between 1980 and 2009. A total of 1285 patients received a second allogeneic transplant after disease relapse; among these, 325 were relapse free at 1 year after the second HCT. The median time from first to second HCT was 17 and 24 months for children and adults, respectively. ⋯ Among patients with acute leukemia and myelodysplastic syndromes who receive a second allogeneic HCT for relapse and survive disease free for at least 1 year, many can be expected to survive long term. However, they continue to be at risk for relapse and nonrelapse morbidity and mortality. Novel approaches are needed to minimize relapse risk and long-term transplantation morbidity in this population.