Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
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Biol. Blood Marrow Transplant. · May 2014
Clinical TrialDonor-derived natural killer cells infused after human leukocyte antigen-haploidentical hematopoietic cell transplantation: a dose-escalation study.
The doses of donor-derived natural killer (NK) cells that can be given safely after human leukocyte antigen (HLA)-haploidentical hematopoietic cell transplantation (HCT) remain to be defined. Forty-one patients (ages 17 to 75 years) with hematologic malignancy underwent HLA-haploidentical HCT after reduced-intensity conditioning containing busulfan, fludarabine, and antithymocyte globulin. Cell donors (ages 7 to 62 years) underwent growth factor-mobilized leukapheresis for 3 to 4 days. ⋯ There was, however, a significant reduction in leukemia progression (74% to 46%), with post-transplantation NK cell infusion being an independent predictor for less leukemia progression (hazard ratio, .527). Our findings showed that, when given 2 to 3 weeks after HLA-haploidentical HCT, donor-derived NK cells were well tolerated at a median total dose of 2.0 × 10(8) cells/kg. In addition, they may decrease post-transplantation progression of acute leukemia.
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Biol. Blood Marrow Transplant. · May 2014
Early cytomegalovirus reactivation leaves a specific and dynamic imprint on the reconstituting T cell compartment long-term after hematopoietic stem cell transplantation.
Human cytomegalovirus (CMV) reactivation frequently occurs during the early phase of immune recovery after allogeneic hematopoietic stem cell transplantation (HSCT). Whereas the recovery of virus-specific immunity in the early phase after HSCT is extensively studied, the impact of CMV on the reconstitution and composition of the T cell compartment long-term after HSCT is unknown. We analyzed T cell reconstitution 1 to 2 years after HSCT in 131 pediatric patients. ⋯ At 1 and 2 years after HSCT, the absolute numbers of CD8(+) naive and central memory T cells, as well as CD4(+) naive, CM, EM, and EMRA T cells, did not differ between patients with or without CMV reactivation. In the second year after HSCT, a significant contraction of the initially expanded CD8(+) EM and EMRA T cell compartments was observed in patients with early CMV reactivation. In conclusion, CMV reactivation early after pediatric HSCT leaves a specific and dynamic imprint on the size and composition of the CD8(+) T cell compartment without compromising the reconstitution of CD8(+) and CD4(+) naive and central memory T cells pivotal in the response to neo and recall antigens.
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Biol. Blood Marrow Transplant. · May 2014
Antithymocyte globulin before allogeneic stem cell transplantation for progressive myelodysplastic syndrome: a study from the French Society of Bone Marrow Transplantation and Cellular Therapy.
We investigated the impact of rabbit antithymocyte globulins (ATG) on patient outcomes after allogeneic stem cell transplantation (allo-SCT) for progressive myelodysplastic syndrome (MDS). Of the 242 consecutive patients who underwent allo-SCT for progressive MDS between October 1999 and December 2009, 93 received ATG (ATG group) at the median dose of 5 mg/kg, whereas 149 patients did not (no-ATG group). Donors were sibling (n = 153) or HLA-matched unrelated (n = 89). ⋯ ATG had no impact on overall and event-free survival or cumulative incidence of the relapse. In conclusion, the addition of ATG to allo-SCT conditioning did not increase the incidence of relapse of patients with progressive MDS. The incidence of acute GVHD was decreased without compromising outcomes.
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Biol. Blood Marrow Transplant. · May 2014
No impact of total or myeloid Cd34+ cell numbers on neutrophil engraftment and transplantation-related mortality after allogeneic pediatric bone marrow transplantation.
Although the influence of transplanted bone marrow (BM) CD34+ cells on neutrophil engraftment (NE) and transplantation outcomes has been discussed controversially, thresholds between 2 and 4 × 10(6)/kg CD34+ cells are commonly accepted. This has substantial consequences for a donor in terms of BM volume to be collected, which frequently covers up to 15 to 20 mL/kg. As the BM CD34+ compartment contains varying fractions of CD34+/CD19+ B lymphoid progenitors, we tested the hypothesis that the infused CD34+/CD45dim/CD19-/CD10- myeloid stem cells might reliably predict NE in 94 children who received BM from 37 HLA-identical sibling donors (MSD) and 57 matched unrelated donors after myeloablative conditioning. ⋯ By multivariate analysis, neither the number of total CD34+ cells (P = .605) nor of myeloid CD34+ cells (P = .981) correlated with NE, whereas transplantation from MSD (hazard ratio [HR] 3.51; P = .019) and the administration of granulocyte colony-stimulating factor (HR 2.24; P = .002) remained independent factors associated with earlier NE. Furthermore, neither total nor myeloid CD34+ cell quantities were associated with incidences of severe infections before NE (P = .271 and P = .132) or transplantation-related mortality (TRM) at day +100 (P = .294 and P = .490). Taking into account that the number of transplanted total CD34+ or myeloid CD34+ cells does not seem to have a relevant impact on time to NE, sepsis rates, or TRM, the need of certain threshold cell numbers should be revisited, at least for pediatric MSD.
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Biol. Blood Marrow Transplant. · May 2014
Metagenomic analysis of the stool microbiome in patients receiving allogeneic stem cell transplantation: loss of diversity is associated with use of systemic antibiotics and more pronounced in gastrointestinal graft-versus-host disease.
Next-generation sequencing of the hypervariable V3 region of the 16s rRNA gene isolated from serial stool specimens collected from 31 patients receiving allogeneic stem cell transplantation (SCT) was performed to elucidate variations in the composition of the intestinal microbiome in the course of allogeneic SCT. Metagenomic analysis was complemented by strain-specific enterococcal PCR and indirect assessment of bacterial load by liquid chromatography-tandem mass spectrometry of urinary indoxyl sulfate. At the time of admission, patients showed a predominance of commensal bacteria. ⋯ As a consequence of the loss of bacterial diversity, mean urinary indoxyl sulfate levels dropped from 42.5 ± 11 μmol/L to 11.8 ± 2.8 μmol/L in all post-transplant samples and to 3.5 ± 3 μmol/L in samples from patients with active GVHD. Our study reveals major microbiome shifts in the course of allogeneic SCT that occur in the period of antibiotic treatment but are more prominent in association with GI GVHD. Our data indicate early microbiome shifts and a loss of diversity of the intestinal microbiome that may affect intestinal inflammation in the setting of allogeneic SCT.