Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
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Biol. Blood Marrow Transplant. · Apr 2016
Granulocyte Colony-Stimulating Factor-Mobilized Allografts Contain Activated Immune Cell Subsets Associated with Risk of Acute and Chronic Graft-versus-Host Disease.
We defined associations among immune cell subsets in granulocyte colony-stimulating factor (G-CSF)-mobilized allografts and clinical outcomes after allogeneic hematopoietic cell transplantation (alloHCT). Fresh peripheral blood stem cell (PBSC) aliquots from 238 G-CSF-mobilized allografts were extensively characterized by immunophenotype. Subset-specific transplanted cells were correlated with acute graft-versus-host disease (aGVHD), chronic GVHD (cGVHD), malignant disease relapse, nonrelapse mortality, and overall survival. ⋯ In conclusion, activated NK cells within PBSC allografts associate with lower aGVHD risk, whereas HLA-DR(+) T cells associate with higher aGVHD and cGVHD risk. NKT cells and early activated T cells are associated with lower relapse risk in AML and MDS patients. These findings may have implications in therapeutic targeting of select populations in the allograft to minimize incidence of GVHD.
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Biol. Blood Marrow Transplant. · Mar 2016
Genotype-Directed Dosing Leads to Optimized Voriconazole Levels in Pediatric Patients Receiving Hematopoietic Stem Cell Transplantation.
Invasive fungal infections are a significant cause of morbidity and mortality in recipients of hematopoietic stem cell transplantation (HSCT), warranting antifungal prophylaxis as a standard of care in these patients. Voriconazole is commonly used in this setting because of its broad-spectrum activity and available dosage forms. There is wide well-known inter- and intrapatient variability in voriconazole concentrations, in part because concentrations are affected by common CYP2C19 polymorphisms. ⋯ Overall, the median time to reach the target concentration with genotype-guided dosing was 6.5 days compared with a median time of 29 days when all patients were started on the same dose regardless of CYP2C19 genotype (P < .001). Our data show that traditional voriconazole dosing does not lead to timely achievement of target levels for fungal prophylaxis. However, a genotype-directed dosing algorithm allows patients to reach the voriconazole target range significantly sooner, providing better prophylaxis against fungal infections in the immediate post-transplant period.
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Biol. Blood Marrow Transplant. · Mar 2016
Multicenter Study Clinical TrialInfluence of Differently Licensed KIR2DL1-Positive Natural Killer Cells in Transplant Recipients with Acute Leukemia: A Japanese National Registry Study.
Licensing by self MHC class I ligands is required for proper natural killer (NK) cell response. NK cells with inhibitory killer cell immunoglobulin-like receptors for nonself MHC exhibit transient alloreactivity after hematopoietic stem cell transplantation (HSCT). We analyzed 3866 recipients in the Japan national registry who underwent their first allogeneic HSCT for acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) from HLA-A, -B, and -DRB1 allele-genomatched unrelated donors. ⋯ This difference was not observed in HLA-C-matched HSCT for ALL. Compared with HLA-C-matched HSCT, significantly higher mortality was observed in HLA-C1/C1 AML patients who received transplants from HLA-C-mismatched HLA-C1/C1 donors (HR, 1.37; P = .001) and in HLA-C1/C1 ALL patients who received transplants from HLA-C2-positive donors (HR, 2.13; P = .005). In conclusion, donor selection based on leukemic subtype and donor HLA-C group matching improves transplantation outcome after HLA-C-mismatched HSCT.
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Biol. Blood Marrow Transplant. · Feb 2016
Review Historical ArticleA Review of Hematopoietic Cell Transplantation in Australia and New Zealand, 2005 to 2013.
This report describes hematopoietic cell transplantation (HCT) activity and outcome in Australia and New Zealand during the years 2005 to 2013. In 2013, 1018 autologous, 221 allogeneic with related donors, and 264 allogeneic with unrelated donors HCT were performed in 40 centers in Australia, with corresponding figures of 147, 39, and 47 in 6 centers in New Zealand. Annual numbers of HCT in 2013 increased, compared to 2005, by 25% in Australia and by 52% in New Zealand. ⋯ Major indications for transplantation were acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), plasma cell disorders, and non-Hodgkin lymphoma (NHL). Overall survival probabilities at 5 years after transplantation for adult (16+) allogeneic first HCT recipients were 54.2% for ALL, 46.0% for AML, 48.4% for myelodysplastic syndromes, and 58.6% for NHL. Consistent patterns over time include a steady increase in HCT, particularly for older recipients, relatively constant numbers of allografts using cord blood, and a recent increase in the number of allografts with 2 or more HLA-mismatched related donors.
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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.