The syndrome of microangiopathic hemolysis associated with renal failure, neurologic impairment, or both is a recognized complication of hematopoietic stem cell transplantation. This entity is often called hemolytic uremic syndrome (HUS) or thrombotic thrombocytopenic purpura (TTP), yet it is clear that the pathophysiology of transplant-associated HUS/TTP is different from that of classic HUS or TTP. Furthermore, the incidence of this syndrome varies from 0.5% to 76% in different transplant series, primarily because of the lack of a uniform definition. The toxicity committee of the Blood and Marrow Transplant Clinical Trials Network has reviewed the current literature on transplant-related HUS/TTP and recommends that it be henceforth renamed posttransplantation thrombotic microangiopathy (TMA). An operational definition for TMA based on the presence of microangiopathic hemolysis and renal and/or neurologic dysfunction is proposed. The primary intervention after diagnosis of TMA should be withdrawal of calcineurin inhibitors. Plasma exchange, although frequently used in this condition, has not been proven to be effective. In the absence of definitive trials, plasma exchange cannot be considered a standard of care for TMA. It is hoped that these positions will improve the identification and reporting of this devastating complication after hematopoietic stem cell transplantation and facilitate future clinical studies for its prevention and treatment.
Outcomes of 159 young patients with inherited metabolic disorders (IMDs) undergoing transplantation with partially HLA-mismatched unrelated donor umbilical cord blood were studied to investigate the impact of graft and patient characteristics on engraftment, overall survival (OS), and graft-versus-host disease (GVHD). Patients received myeloablative chemotherapy (busulfan, cyclophosphamide, ATG) and cyclosporine-based GVHD prophylaxis. Infused cell doses were high (7.57 ؋ 10 7 /kg) because of the patients' young age (median, 1.5 years) and small size (median, 12 kg). Median follow-up was 4.2 years (range , 1-11 years)
BACKGROUND
Umbilical-cord blood has been used as the source of hematopoietic stem cells in an estimated 30,000 transplants. The limited number of hematopoietic cells in a single cord-blood unit prevents its use in recipients with larger body mass and results in delayed hematopoietic recovery and higher mortality. Therefore, we hypothesized that the greater numbers of hematopoietic cells in two units of cord blood would be associated with improved outcomes after transplantation.
METHODS
Between December 1, 2006, and February 24, 2012, a total of 224 patients 1 to 21 years of age with hematologic cancer were randomly assigned to undergo double-unit (111 patients) or single-unit (113 patients) cord-blood transplantation after a uniform myeloablative conditioning regimen and immunoprophylaxis for graft-versus-host disease (GVHD). The primary end point was 1-year overall survival.
RESULTS
Treatment groups were matched for age, sex, self-reported race (white vs. nonwhite), performance status, degree of donor–recipient HLA matching, and disease type and status at transplantation. The 1-year overall survival rate was 65% (95% confidence interval [CI], 56 to 74) and 73% (95% CI, 63 to 80) among recipients of double and single cord-blood units, respectively (P = 0.17). Similar outcomes in the two groups were also observed with respect to the rates of disease-free survival, neutrophil recovery, transplantation-related death, relapse, infections, immunologic reconstitution, and grade II–IV acute GVHD. However, improved platelet recovery and lower incidences of grade III and IV acute and extensive chronic GVHD were observed among recipients of a single cord-blood unit.
CONCLUSIONS
We found that among children and adolescents with hematologic cancer, survival rates were similar after single-unit and double-unit cord-blood transplantation; however, a single-unit cord-blood transplant was associated with better platelet recovery and a lower risk of GVHD.
Graft failure occurs in approximately 20% of patients after unrelated umbilical cord blood transplantation (UCBT). This could be because of inadequate potency of the cord blood unit (CBU). To this end, we investigated the impact of graft characteristics on engraftment and survival of 435 primarily pediatric (median age: 5.3 years) patients receiving a single-unit unrelated UCBT after myeloablative conditioning from 2000 to 2008. Pre-cryopreservation (pre-cryo) graft characteristics were provided by the banks. Post-thaw parameters were measured on dextran/albumin-washed grafts. Post-thaw recovery of the colony-forming unit (CFU), a biological assay reflecting functional viability of the cord blood cells was the lowest percent age (median 21.2%, mean 36.5%) of the pre-cryo value, regardless of the bank of origin. The cumulative incidences of neutrophil and platelet engraftment were 76.9% (95%, confidence interval [CI], 71.3%-82.5%) and 55% (95% CI, 49.3%-60.7%), respectively. Univariate and separate multivariate models using pre-cryo and post-thaw datasets including clinical parameters identified predictors of engraftment and survival. In multivariate modeling, higher CFU dosing was the only pre-cryo graft characteristic predictive of neutrophil (P = .0024) and platelet engraftment (P = .0063). In the post-thaw model, CFU dose best predicted neutrophil and platelet engraftment (both P < .0001). Comparatively, CD34(+) and total nucleated cell (TNC) were only weakly predictive in post-thaw neutrophil and platelet engraftment models, respectively. In conclusion, CFU dose is a strong independent predictor of engraftment after unrelated UCBT and should be used to assess potency when selecting CBUs for transplantation.
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