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
A Pilot Study of Continuous Infusion of Mycophenolate Mofetil for Prophylaxis of Graft-versus-Host-Disease in Pediatric Patients.
Mycophenolate mofetil (MMF), an ester prodrug of mycophenolic acid (MPA), is used increasingly for graft-versus-host disease (GVHD) prophylaxis. Empiric fixed-dose-escalation strategies in pediatric hematopoietic cell transplantation (HCT) recipients have failed to achieve target MPA exposure. We evaluated the safety and feasibility of a pharmacokinetics-based dosing approach using a novel continuous infusion (CI) method of administration of MMF in pediatric HCT recipients. ⋯ In this pilot study of pharmacokinetically directed MMF dosing, we observed no toxic deaths, excellent engraftment, and low rates of grades III to IV acute and chronic GVHD. We found significantly lower half-life and higher drug clearance in pediatric HCT recipients compared with stable pediatric renal transplant patients or adult transplant patients. This regimen deserves further validation in a larger cohort of pediatric patients undergoing myeloablative transplantation.
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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
Multicenter Study Clinical TrialParent Outlook: How Parents View the Road Ahead as They Embark on Hematopoietic Stem Cell Transplantation for Their Child.
Pediatric hematopoietic stem cell transplantation (HSCT) offers cure for high-risk malignancies and other conditions, but carries a risk of complications. Parental outlook regarding their child's transplantation course and future health has been largely unexplored. This report presents the Parent Outlook Scale, describes its properties, and examines the outlook of parents embarking on their child's transplantation course and the associated variables. ⋯ Clinical factors (solid tumor diagnosis and unrelated donor transplant) and a parent factor (worse emotional functioning) were associated with higher scale and subscale scores. Our findings show that the outlook of parents embarking on their child's HSCT course is varied and not solely a product of clinical factors readily apparent to clinicians. Referring and transplantation clinicians should create opportunities to explore with parents their perspectives and concerns before and during the course of HSCT.