Recipients Of Unrelated Bone Marrow Research Articles

The impact of graft cell source on bloodstream infection in the first 100 days after allogeneic hematopoietic cell transplantation.

Bloodstream infection (BSI) is a major infectious complication after allogeneic hematopoietic cell transplantation (HCT). To clarify the impact of graft cell source on the incidence of BSI after transplantation, we retrospectively examined 782 adult patients receiving their first allogeneic HCT: 122 recipients of related peripheral blood stem cells or bone marrow, 215 recipients of unrelated bone marrow, and 445 recipients of unrelated umbilical cord blood (U-CB). The cumulative incidence of BSI was 42.5% at 100 days after transplantation (95% confidence interval, 39.0-46.0). Gram-positive cocci were present in 64.2% of detected isolates. Among the pre-transplant factors including age, performance status, primary disease, disease status, graft cell source, sex and ABO blood type matching, and the intensity of conditioning regimen, U-CB use was identified as the most significant risk factor for BSI by multivariate analysis (hazard ratio, 1.76; 95% confidence interval, 1.40-2.22; p < 0.00001). Among the U-CB recipients, those who are not in remission at the time of transplantation were at the greatest risk of BSI (hazard ratio, 1.69; 95% confidence interval, 1.14-2.50; p < 0.01). The study makes it clear that graft cell source has an impact on BSI development after allogeneic HCT.

Myeloablative intravenous busulfan-containing regimens for allo-HSCT in AML or MDS patients over 54years old: combined results of three phase II studies.

An optimal pretransplant conditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in older adults has not been established. Three prospective multicenter phase II studies were conducted, in which 142 patients older than 54years (median age, 61years; range 55-70years) with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) received a myeloablative dose of intravenous busulfan (ivBu, 12.8mg/kg) along with fludarabine (180mg/m2) ± low dose total body irradiation for allo-HSCT between September 2009 and February 2013. A total of 103 AML and 39 MDS patients including 21 related bone marrow (BM) or peripheral blood (PB), 50 unrelated BM, and 71 unrelated cord blood (UCB) transplantation were enrolled. Grade 3 or greater toxicities were observed in 105 patients. Neutrophil engraftment was achieved in 70 out of the 71 related PB/BM or unrelated BM recipients, and 61 out of the 71 UCB recipients. The cumulative incidence rates of relapse and non-relapse mortality after 2years were 24.0 and 24.1%, respectively. The overall and event-free survival rates at 2years were 53.3 and 47.4%, respectively. The myeloablative dose of ivBu was well tolerated without increased toxicity-related mortality in older adults who underwent allo-HSCT with any donor source.

Immune Reconstitution Kinetics as an Early Predictor for Mortality using Various Hematopoietic Stem Cell Sources in Children

The severity of complications of allogeneic hematopoietic stem cell transplantation (HSCT) is governed mainly by the status of immune reconstitution. In this study, we investigated differences in immune reconstitution with different cell sources and the association between the kinetics of immune reconstitution and mortality. Immunophenotyping was performed every 2 weeks in children who had undergone HSCT between 2004 and 2008 at University Medical Center Utrecht. Lymphocyte reconstitution in the first 90 days after HSCT was studied in relation to mortality in 3 HSCT groups: matched sibling bone marrow (BM) recipients (35 patients), unrelated BM recipients (32 patients), and unrelated cord blood recipients (36 patients). The median age of recipients was 5.9 years (range, 0.1-21 years). The nature and speed of T cell, B cell, and natural killer (NK) cell reconstitution were highly dependent on the cell source. In the first 90 days after HSCT, faster B cell and NK cell reconstitution and delayed T cell reconstitution were shown in unrelated cord blood recipients compared with matched sibling BM and unrelated BM recipients. Of the lymphocyte subsets investigated, a large number of NK cells and a more rapid CD4+ immune reconstitution over time, resulting in sustained higher CD4+ counts, were the only predictors of a lower mortality risk in all cell sources. The final model showed that during the first 90 days, patients with an area under the CD4+ cell receiver- operating curve of >4,300 cells/day and no peak in CD4+ cell counts had the highest likelihood of survival (hazard ratio for mortality, 0.2; 95% confidence interval, 0.06-0.5). Our data indicate that CD4+ kinetics may be used to identify patients at greatest risk for mortality early after HSCT.

Comparison of Unrelated Cord Blood Transplantation and HLA-Mismatched Unrelated Bone Marrow Transplantation for Adults with Leukemia

Recent advances in unrelated cord blood transplantation (UCBT) and high-resolution typing of human leukocyte antigen (HLA) from an unrelated donor have increased choices in alternative donor/stem cell source selection. We assessed HLA-mismatched locus-specific comparison of the outcomes of 351 single-unit UCB and 1,028 unrelated bone marrow (UBM) adult recipients 16 years old or older at the time of transplantation who received first stem cell transplantation with myeloablative conditioning for acute leukemia or myelodysplastic syndromes. With adjusted analyses, HLA 0 to 2 mismatched UCBT showed similar overall mortality (relative risk [RR] = 0.85, 95% confidence interval [CI], 0.68-1.06; P = .149) compared with that of single-HLA-DRB1-mismatched UBMT. UCBT showed inferior neutrophil recovery (RR = 0.50, 95% CI, 0.42-0.60; P < .001), lower risk of acute graft-versus-host disease (RR = 0.55, 95% CI, 0.42-0.72; P < .001), and lower risk of transplantation-related mortality (RR = 0.68, 95% CI, 0.50-0.92; P = .011) compared with single-HLA-DRB1-mismatched UBMT. No significant difference was observed for risk of relapse (RR = 1.28, 95% CI, 0.93-1.76; P = .125). HLA 0 to 2 antigen-mismatched UCBT is a reasonable second alternative donor/stem cell source with a survival outcome similar to that of single-HLA-DRB1-mismatched or other 7 of 8 UBMT.

Defective Anti-Bacterial Carbohydrate Antibody Production after Unrelated HSC Transplantation.

Protective levels of anti-bacterial carbohydrate antibodies are necessary to protect HSC transplantation recipients from severe infections with encapsulated bacteria. Recipients of unrelated HSC transplants are at increased risk of severe infections regardless of their history of graft versus host disease (GVHD). Antibodies to a naturally occurring, prototypic bacterial carbohydrate antigen, polyribose phosphate (PRP), present in Hemophilus influenza type b and K100 stains of E. coli, were measured in the recipients of unrelated bone marrow (UBMT) and unrelated cord blood transplants (UCBT). UBMT and UCBT recipients, who were not on immunosuppressive therapy, were analyzed with follow-ups of 12 and 7 years, respectively. Of 20 UBMT recipients, only 3 had protective anti-PRP antibody levels. All 3 recipients with protective antibody levels were younger than 1 year old at the time of transplantation and did not have a history of GVHD. No recipients, who were older than 1 year old at the time of transplantation, had protective levels of anti-carbohydrate antibody. Of 16 UCBT recipients, 7 had protective antibody levels, including recipients as old as 53 at the time of UCBT. All unrelated recipients, who did not have protective levels of anti-carbohydrate antibodies, were able to produce protective levels of antibodies to a protein antigen, tetanus toxoid, after immunization. Therefore, the inability of the recipients of unrelated HSC to produce protective levels of anti-bacterial carbohydrate antibody is not part of a generalized antibody deficiency state, but is a specific defect. Since bacterial carbohydrate antigens are T lymphocyte-dependent antigens in humans, the results indicate that thymic and T lymphocyte function are greater in UCBT recipients than in UBMT recipients (p=.008 for protective anti-PRP antibody levels in recipients older than age 1). Defects in protective anti-bacterial carbohydrate antibody production are common in the recipients of HSC unrelated transplants regardless of the source of HSC. The recipients of unrelated HSC transplants, especially UBMT, should be tested for their capacity to produce anti-carbohydrate antibody, and, if deficiencies are detected, appropriate prophylactic measures undertaken to reduce the likelihood of severe bacterial infections.

TRANSPLANTATION OF PERIPHERAL BLOOD PROGENITOR CELLS FROM UNRELATED DONORS

TRANSPLANTATION OF PERIPHERAL BLOOD PROGENITOR CELLS FROM UNRELATED DONORS