Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
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Biol. Blood Marrow Transplant. · Jan 2016
Clinical TrialDynamic Detection of Anti-Human Leukocyte Antigen (HLA) Antibodies but not HLA-DP Loci Mismatches Can Predict Acute Graft-versus-Host Disease and Overall Survival in HLA 12/12-Matched Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplantation for Hematological Malignancies.
The National Marrow Donor Program and Center for International Blood and Marrow Transplant Research provided guidelines for the use of anti-HLA antibodies and HLA-DP-mismatched loci in unrelated donor hematopoietic stem cell transplantation (HSCT). However, a deeper understanding of other potentially useful biomarkers for predicting clinical outcomes in HLA-A, -B, -C, -DRB1, -DQB1, and -DQA1 (12/12)-matched unrelated donor HSCT is needed to further improve clinical outcomes. We tested HLA genotyping for 123 pairs of patients and donors. ⋯ Furthermore, HLA-DP loci-matched subgroup showed a trend towards a lower rate of acute GVHD and a higher OS in the anti-HLA Abs-negative group. Our results suggest that dynamic changes of anti-HLA antibodies independently predict for a negative outcome of HSCT, independent of HLA-DP loci mismatches. Routine monitoring for anti-HLA antibody dynamics should be conducted before and after HSCT.
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Biol. Blood Marrow Transplant. · Jan 2016
Comparative StudyRisk Factors for Acute and Chronic Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation with Umbilical Cord Blood and Matched Sibling Donors.
Allogeneic hematopoietic cell transplantation is often complicated by graft-versus-host disease (GVHD). We analyzed the incidences and risk factors for acute (aGVHD) and chronic GVHD (cGVHD), and their impact on disease relapse and survival, among recipients of single umbilical cord blood (sUCB, n = 295), double umbilical cord blood (dUCB, n = 416), and matched sibling donor (MSD, n = 469) allografts. The incidences of grades II to IV aGVHD and chronic GVHD among dUCB, sUCB, and MSD were 56% and 26%, 26% and 7%, 37% and 40%, respectively. ⋯ This large contemporary analysis suggests distiinct risks and consequences of GVHD for UCB and MSD recipients. Limiting the severity of aGVHD remains important in all groups. Increasing the cord blood inventory or developing strategies that reduce the cell-dose threshold and thereby increase the chance of identifying an adequately dosed, better HLA-matched sUCB unit may further limit risks of aGVHD after UCB transplantation.
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Biol. Blood Marrow Transplant. · Jan 2016
Multicenter StudyPhase II Trial of Reduced-Intensity Busulfan/Clofarabine Conditioning with Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Acute Myeloid Leukemia, Myelodysplastic Syndromes, and Acute Lymphoid Leukemia.
Clofarabine has potent antileukemia activity and its inclusion in reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (HSCT) for acute leukemia could potentially improve outcomes. We conducted a phase II study of busulfan (.8 mg/kg i.v. twice daily on days -5, -4, -3, and -2) with clofarabine (40 mg/m(2) i.v. daily on days -5, -4, -3, and -2) conditioning before allogeneic 8/8 HLA-matched related or unrelated HSCT. The primary endpoint was donor neutrophil engraftment by day +40. ⋯ The 2-year PFS was 50% (95% CI, 32 to 65) and OS was 56% (95% CI, 38 to 71). For patients with AML in first complete remission, 2-year PFS and OS were both 82% (95% CI, 55 to 94). RIC with busulfan and clofarabine leads to successful engraftment with acceptable rates of NRM and GVHD.
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Biol. Blood Marrow Transplant. · Jan 2016
Adenovirus Viremia in Adult CD34(+) Selected Hematopoietic Cell Transplant Recipients: Low Incidence and High Clinical Impact.
Adenovirus (ADV) infections after hematopoietic cell transplantation (HCT) range in severity from self-limited to fatal. We have previously reported high mortality rates in CD34(+) selected T cell-depleted (TCD) HCT recipients using symptomatic testing and culture methods for ADV detection. We report rates and outcomes of ADV viremia in 215 adult recipients of TCD HCT using the CliniMACS CD34(+) selection system. ⋯ Early ADV viremia was infrequent (8%) among adult HCT recipients of CD34(+) selected allografts. Among viremic patients, rate of ADV disease was 33% and ADV attributable mortality was 22%. Further studies are needed to assess the impact of preemptive treatment with brincidofovir on improving outcomes of ADV infections in this patient population.
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Biol. Blood Marrow Transplant. · Jan 2016
Predicted Indirectly ReCognizable HLA Epitopes Class I Promote Antileukemia Responses after Cord Blood Transplantation: Indications for a Potential Novel Donor Selection Tool.
Unrelated cord blood transplantation (UCBT) provides a curative therapy for patients with hematological malignancies. The effect of HLA mismatches in UCBT is currently the subject of debate. HLA-mismatched UCBT may lead to improved leukemia control but also to graft-versus-host disease (GVHD), resulting in nonrelapse mortality (NRM). ⋯ Both PIRCHE-I and -II were not associated with other clinical outcomes, including GVHD and NRM. These data suggest that high PIRCHE-I may lead to improved graft-versus-tumor effects after UCBT, without an accompanying GVHD risk. Inclusion of PIRCHE in UCB selection criteria may enhance UCBT outcome, which needs to be tested in prospective studies.