Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
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Biol. Blood Marrow Transplant. · Aug 2015
ReviewEmerging Influence of the Intestinal Microbiota during Allogeneic Hematopoietic Cell Transplantation: Control the Gut and the Body Will Follow.
The intestinal microbiota has many critical roles in maintaining gastrointestinal epithelial and gastrointestinal systemic immune homeostasis. This review provides insight into how allogeneic hematopoietic cell transplantation (HCT) and its associated complications and supportive care therapies affect the microbiota. Additionally, the review discusses how preservation and restoration of the microbiota might be advantageous in decreasing HCT-related morbidity and mortality.
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Biol. Blood Marrow Transplant. · Aug 2015
Clinical TrialInduction Therapy with Bortezomib Followed by Bortezomib-High Dose Melphalan and Stem Cell Transplantation for Light Chain Amyloidosis: Results of a Prospective Clinical Trial.
The depth of hematologic response has been shown to correlate with survival and organ responses for patients with light chain (AL) amyloidosis. We conducted a prospective trial of 2 cycles of induction with bortezomib and dexamethasone on a twice a week schedule followed by conditioning with bortezomib and high-dose melphalan (HDM) and autologous stem cell transplantation (SCT). The objectives were hematologic responses, tolerability, and survival. ⋯ By intention-to-treat, hematologic responses occurred in 77% of patients (49% complete response, 29% VGPR). With a median follow-up of 36 months, the median overall survival and progression-free survival were not reached. In conclusion, incorporating bortezomib into induction and conditioning yielded a high rate of hematologic responses after HDM/SCT in patients with AL amyloidosis.
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Biol. Blood Marrow Transplant. · Aug 2015
Post-transplantation Cyclophosphamide and Sirolimus after Haploidentical Hematopoietic Stem Cell Transplantation Using a Treosulfan-based Myeloablative Conditioning and Peripheral Blood Stem Cells.
Haploidentical hematopoietic stem cell transplantation (HSCT) performed using bone marrow (BM) grafts and post-transplantation cyclophosphamide (PTCy) has gained much interest for the excellent toxicity profile after both reduced-intensity and myeloablative conditioning. We investigated, in a cohort of 40 high-risk hematological patients, the feasibility of peripheral blood stem cells grafts after a treosulfan-melphalan myeloablative conditioning, followed by a PTCy and sirolimus-based graft-versus-host disease (GVHD) prophylaxis (Sir-PTCy). Donor engraftment occurred in all patients, with full donor chimerism achieved by day 30. ⋯ With a median follow-up for living patients of 15 months, the estimated 1-year overall and disease-free survival (DFS) was 56% and 48%, respectively. Outcomes were more favorable in patients who underwent transplantation in complete remission (1-year DFS 71%) versus patients who underwent transplantation with active disease (DFS, 34%; P = .01). Overall, myeloablative haploidentical HSCT with peripheral blood stem cells (PBSC) and Sir-PTCy is a feasible treatment option: the low rates of GVHD and NRM as well as the favorable immune reconstitution profile pave the way for a prospective comparative trial comparing BM and PBSC in this specific transplantation setting.
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Biol. Blood Marrow Transplant. · Aug 2015
Performance of Busulfan Dosing Guidelines for Pediatric Hematopoietic Stem Cell Transplant Conditioning.
Achievement of a busulfan area-under-the-concentration versus time curve (AUC) of 900 to 1500 μM·min is associated with improved hematopoietic stem cell transplant (HSCT) outcomes. Multiple pediatric busulfan dosing guidelines aim to achieve this target. The authors' objective was to describe the AUCs achieved after simulated dosing using available pediatric i.v. busulfan dosing guidelines. ⋯ For children who are not overweight, we recommend 1 of 3 high-performing guidelines that allow individualization of the target busulfan AUC. Use of either IBW or IBWadj in overweight children improves the performance of most guidelines. Regardless of the guideline used, therapeutic drug monitoring is essential to verify achievement of the target AUC.
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Biol. Blood Marrow Transplant. · Aug 2015
Experience with Alemtuzumab, Fludarabine, and Melphalan Reduced-Intensity Conditioning Hematopoietic Cell Transplantation in Patients with Nonmalignant Diseases Reveals Good Outcomes and That the Risk of Mixed Chimerism Depends on Underlying Disease, Stem Cell Source, and Alemtuzumab Regimen.
Alemtuzumab, fludarabine, and melphalan reduced-intensity conditioning (RIC) regimens are increasingly used for the hematopoietic cell transplantation (HCT) of pediatric and young adult patients with nonmalignant diseases. Early experience suggests that these regimens are associated with good survival but a high incidence of mixed chimerism, which we have previously shown to be influenced by the alemtuzumab schedule. We hypothesized that the underlying diagnosis and donor graft source would also affect the development of mixed chimerism and that the majority of patients would survive RIC HCT without graft loss. ⋯ Three-year survival without retransplantation was 84% (95% CI, 71% to 98%) for patients who underwent transplantation with an HLA-matched sibling donor. Survival without retransplantation was negatively affected by lack of a matched related donor, increasing age, and development of grades III and IV acute graft-versus-host disease. We conclude that alemtuzumab, fludarabine, and melphalan RIC HCT offers good results for many patients and that the risk of developing mixed chimerism is influenced by underlying diagnosis, graft source, and alemtuzumab dosing.