Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
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Biol. Blood Marrow Transplant. · Sep 2019
Multicenter Study Clinical TrialImpact of T Cell Dose on Outcome of T Cell-Replete HLA-Matched Allogeneic Peripheral Blood Stem Cell Transplantation.
Data on whether the T cell dose of allogeneic peripheral blood stem cell (PBSC) products influences transplantation outcomes are conflicting. Using the Center for International Blood and Marrow Transplant Research database, we identified 2736 adult patients who underwent first allogeneic PBSC transplantation for acute leukemia or myelodysplastic syndrome between 2008 and 2014 using an HLA-matched sibling donor (MSD) or an 8/8-matched unrelated donor (MUD). We excluded ex vivo and in vivo T cell-depleted transplantations. ⋯ Subanalysis of CD4+ T cells, CD8+ T cells, and CD4+/CD8+ ratio failed to identify cutoff values predictive of transplantation outcomes; however, using the log-rank test, the sample size was suboptimal for identifying a difference at this cutoff cell dose. In this registry study, the CD3+ T cell dose of PBSC products did not influence the risk of aGVHD or cGVHD or other transplantation outcomes when using an MSD or an 8/8-matched MUD. Subset analyses of CD4+ and CD8+ T cell doses were not possible given our small sample size.
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Biol. Blood Marrow Transplant. · Sep 2019
Characterization of Viral Infections after Antithymocyte Globulin-Based Conditioning in Adults Undergoing Allogeneic Hematopoietic Stem Cell Transplantation.
Antithymocyte globulin (ATG) has been shown to reduce the incidence of graft-versus-host-disease (GVHD) after matched related donor (MRD) and matched unrelated donor (MUD) hematopoietic stem cell transplantation (HCT); however, because of increased risks of infection and relapse, this use has not translated into a significant improvement in post-transplant survival. The goal of this single-center, retrospective cohort analysis was to quantify the incidence of viral reactivation and viral end-organ disease (EOD) within the first 100 days after MUD HCT with ATG-based conditioning compared with MRD HCT without ATG. Fifty-nine adult patients underwent ATG-based MUD HCT compared with 64 patients receiving MRD HCT without ATG. ⋯ There were no significant differences in either relapse-free survival (RFS; 62% versus 78%, P = .07) or overall survival (OS; 72% versus 86%, P = .07) at 6 months post-HCT. However, when using the final time point of 21 months in the MUD/ATG group and 23 months in the MRD/no ATG group, MUD patients who received ATG had inferior survival (OS: 27% versus 77%, P = .009; RFS: 40% versus 59%, P = .042). Our results add to and further quantify the infectious risks associated with the use of ATG in MUD transplants and promote the implementation of more intensive preemptive viral monitoring practices in patients receiving ATG-based MUD transplants.
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Biol. Blood Marrow Transplant. · Aug 2019
Meta AnalysisNutritional and Post-Transplantation Outcomes of Enteral versus Parenteral Nutrition in Pediatric Hematopoietic Stem Cell Transplantation: A Systematic Review of Randomized and Nonrandomized Studies.
Hematopoietic stem cell transplantation (HSCT) involves the administration of chemotherapy followed by the infusion of donor stem cells. After treatment, children can consequently experience nausea, vomiting, diarrhea, anorexia, and mucositis, which negatively impact oral intake, leading to rapid deterioration in nutritional status and risk of malnutrition. Nutrition support therefore becomes necessary to circumvent these adverse effects. ⋯ Some studies were more than 15 years old. Despite the limited number and poor quality of identified studies, results support the growing body of pediatric evidence that EN is feasible during HSCT. Similar differences regarding many nutritional and post-transplantation outcomes were seen in both forms of nutrition support, but EN could provide benefits above PN including reduced incidence of aGVHD and faster platelet engraftment.
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Biol. Blood Marrow Transplant. · Aug 2019
Clinical TrialStandard Antithymocyte Globulin Dosing Results in Poorer Outcomes in Overexposed Patients after Ex Vivo CD34+ Selected Allogeneic Hematopoietic Cell Transplantation.
Antithymocyte globulin (ATG) use mitigates the risk of graft rejection and graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (allo-HCT), but ATG overexposure in the setting of lymphopenia negatively affects immune recovery. We hypothesized that standard empiric weight-based dosing of ATG, used to prevent graft rejection in ex vivo CD34-selected allo-HCT, may lead to serious adverse consequences on outcomes in certain patients. We evaluated 304 patients undergoing myeloablative-conditioned ex vivo CD34-selected allo-HCT with HLA-matched donors for the treatment of hematologic malignancies. ⋯ Among all patient and HCT characteristics in multivariable analyses, receipt of a total dose of ATG >450 mg was associated with an increased risk of NRM (hazard ratio [HR], 2.9; P = .01), shorter DFS (HR, 2.0; P = .03), and inferior OS (HR, 2.1; P = .01). In summary, the use of weight-based ATG at a time of relative lymphopenia before ex vivo CD34-selected allo-HCT results in overdosing in heavier patients, leading to higher NRM and lower DFS and OS. Further pharmacokinetic investigation in this setting is critical to determining the optimal dosing strategy for ATG.
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Biol. Blood Marrow Transplant. · Aug 2019
Clinical TrialEfficacy, Toxicity, and Infectious Complications in Ruxolitinib-Treated Patients with Corticosteroid-Refractory Graft-versus-Host Disease after Hematopoietic Cell Transplantation.
Corticosteroid-refractory graft-versus-host disease (SR-GVHD) remains a significant source of morbidity after allogeneic hematopoietic cell transplantation. No standard therapy exists in this setting; however, recent studies have demonstrated a very promising role for ruxolitinib, an oral Janus kinase 1/2 inhibitor. With increasing evidence of efficacy for SR-GVHD, limited data exist describing complications of ruxolitinib use, specifically infectious complications during use in SR-GVHD. ⋯ This study supports the use of ruxolitinib in SR-GVHD, with impressive responses observed in both acute and chronic SR-GVHD. Infectious complications were particularly frequent among patients treated for acute SR-GVHD, and nearly all these patients were concurrently on high-dose steroids while on ruxolitinib. This study suggests careful monitoring for viral reactivation is required for patients initiated on ruxolitinib, supports the role of continuing prophylactic antimicrobial measures in ruxolitinib-treated GVHD patients, and raises the question of whether bacterial prophylaxis should be considered among patients initiated on ruxolitinib for acute SR-GVHD, particularly while on high-dose steroids.