We evaluated the safety and efficacy of high-dose, posttransplantation cyclophosphamide (Cy) to prevent graft rejection and graft-versus-host disease (GVHD) after outpatient nonmyeloablative conditioning and T cell-replete bone marrow transplantation from partially HLA-mismatched (haploidentical) related donors. Patients with advanced hematologic malignancies (n = 67) or paroxysmal nocturnal hemoglobinuria (n = 1) received Cy 50 mg/kg i.v. on day 3 (n = 28) or on days 3 and 4 (n = 40) after transplantation. The median times to neutrophil (>500/microL) and platelet recovery (>20,000/microL) were 15 and 24 days, respectively. Graft failure occurred in 9 of 66 (13%) evaluable patients, and was fatal in 1. The cumulative incidences of grades II-IV and grades III-IV acute (aGVHD) by day 200 were 34% and 6%, respectively. There was a trend toward a lower risk of extensive chronic GVHD (cGVHD) among recipients of 2 versus 1 dose of posttransplantation Cy (P = .05), the only difference between these groups. The cumulative incidences of nonrelapse mortality (NRM) and relapse at 1 year were 15% and 51%, respectively. Actuarial overall survival (OS) and event-free survival (EFS) at 2 years after transplantation were 36% and 26%, respectively. Patients with lymphoid malignancies had an improved EFS compared to those with myelogenous malignancies (P = .02). Nonmyeloablative HLA-haploidentical BMT with posttransplantation Cy is associated with acceptable rates of fatal graft failure and severe aGVHD or cGVHD.

SUMMARYA topic that has received attention in both the statistical and medical literature is the estimation of the probability of failure for endpoints that are subject to competing risks. Despite this, it is not uncommon to see the complement of the Kaplan-Meier estimate used in this setting and interpreted as the probability of failure. If one desires an estimate that can be interpreted in this way, however, the cumulative incidence estimate is the appropriate tool to use in such situations. We believe the more commonly seen representations of the Kaplan-Meier estimate and the cumulative incidence estimate do not lend themselves to easy explanation and understanding of this interpretation. We present, therefore, a representation of each estimate in a manner not ordinarily seen, each representation utilizing the concept of censored observations being 'redistributed to the right.' We feel these allow a more intuitive understanding of each estimate and therefore an appreciation of why the Kaplan-Meier method is inappropriate for estimation purposes in the presence of competing risks, while the cumulative incidence estimate is appropriate.

Background We tested the hypothesis that changes in our transplant practice have improved outcomes over the last decade. To explore correlates of improved outcomes, we analyzed the frequency and severity of graft-versus-host disease and hepatic, renal, pulmonary and infectious complications. Methods During 1993–1997 and 2003–2007, 1418 and 1148 patients received their first allogeneic transplants at our Center. Outcome measures included non-relapse mortality, recurrent malignancy, overall mortality, and the frequency and severity of major complications across this decade. Components of the Pretransplant Assessment of Mortality (PAM) score were used in regression models to adjust for severity of illness at the time of transplantation. Results In comparing outcomes during 1993–1997 and 2003–2007, we observed statistically significant decreases in the hazards of day -200 non-relapse mortality (by 60%), overall non-relapse mortality (by 52%), relapse or progression of malignancy (by 21%), and overall mortality (by 41%), after adjusting for components of the PAM score. Similar results were seen when the analyses were confined to patients receiving myeloablative conditioning therapy. We found statistically significant declines in the risk of more severe GVHD, disease caused by infections (viral, bacterial, and fungal), and damage to the liver, kidneys, and lungs. Conclusions We document a substantial reduction in the hazard of death related to allogeneic hematopoietic cell transplantation as well as improved long-term survival over the last decade. Improved outcomes appear to be related to reductions in organ damage, infection, and severe acute GVHD.