Transplantation-related mortality, graft failure, and survival after reduced-toxicity conditioning and allogeneic hematopoietic stem cell transplantation in 100 consecutive pediatric recipients.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) with myeloablative conditioning is associated with a 10%-40% risk of day +100 transplantation-related mortality (TRM). We evaluated the feasibility and safety of reduced-toxicity conditioning and allo-HSCT in 100 consecutive children and adolescent recipients (mean age, 9.2 ± 6.8 years). The mean duration of follow-up was 1278 ± 1042 days. Fifty patients had malignant disease. The median time to neutrophil recovery was 18 days, and the median time to platelet recovery was 43 days. Median donor chimerism in engrafted patients was 98% on day +100 and 98% on day +365. The cumulative incidence of acute graft-versus-host disease (GVHD) was 20% (95% confidence interval [CI], 12.1%-27.9%), and that of chronic GVHD was 13.5% (95% CI, 6.6%-20.4%). TRM was 3% (95% CI, 0%-6.4%) by day +100 and 13.6% (95% CI, 6.7%-20.5%) for the entire study period. The incidence of primary graft failure (PGF) was 16% overall, 31.4% after umbilical cord blood transplantation (UCBT), and 0% after allo-HSCT with matched unrelated or matched sibling donors (P < .0001). The incidence of PGF in UCBT recipients was 46.7% (14 of 30) in chemotherapy-naive recipients, versus 9.5% (2 of 21) in non-chemotherapy-naive recipients (P = .019). Five-year event-free survival was 59.5% ± 5%, and 5-year overall survival was 72.9% ± 5%. Only PGF and poor-risk disease status were significantly associated with decreased overall survival (P = .03). Reduced-toxicity conditioning allo-HSCT in pediatric recipients is associated with low TRM; however, chemotherapy-naive UCBT recipients have a significantly higher incidence of PGF.

Reduced-intensity conditioning allogeneic stem cell transplantation in pediatric patients and subsequent supportive care.

PURPOSE/OBJECTIVES: To determine if children undergoing reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation (RIC-AlloHSCT) have lower incidence of acute toxicities and, subsequently, require less supportive care than is required with myeloablative conditioning (MAC)-AlloHSCT. An additional purpose is to examine later outcomes by comparing 100-day transplantation-related mortality (TRM). DESIGN: Retrospective chart and electronic medical records review. SETTING: A pediatric care center in the northeastern United States. SAMPLE: 86 patients who underwent AlloHSCT from January 2004 through March 2008. METHODS: Charts were retrospectively reviewed. The comparison between groups was done by t test (continuous variables) and chi-square test (categorical variables). The logistic regressions, Kaplan-Meier product-limit estimator, log rank test, and Cox proportional hazards model were used. MAIN RESEARCH VARIABLES: Days requiring total parenteral nutrition (TPN), patient-controlled analgesia (PCA), incidence of mucositis, days with fevers, number of infections, transfers to pediatric intensive care unit (PICU), blood product infusions, and 100-day TRM, all for 30 days post-transplantation. FINDINGS: When comparing pediatric patients undergoing RIC-AlloHSCT (n = 43) versus MAC-AlloHSCT (n = 43) in the first 30 days post-transplantation, a statistically significant decreased incidence was noted for mucositis, infections, transfers to PICU, days on TPN and PCA, and days with fever, as well as 100-day TRM. CONCLUSIONS: For pediatric patients, RIC-AlloHSCT is associated with significantly lower acute post-transplantation toxicities and TRM than MAC-AlloHSCT. IMPLICATIONS FOR NURSING: For nurses to correctly educate their patients and family members, and to aid nurses in anticipating patient's needs, an understanding of the potential different acute toxicities and supportive care between pediatric patients undergoing RIC- versus MAC-AlloHSCT is vital.

Anti-prostate-specific membrane antigen-based radioimmunotherapy for prostate cancer.

Despite recent advances, advanced prostate cancer is suboptimally responsive to current chemotherapeutic agents. Radiolabeled monoclonal antibody therapy that targets prostate-specific membrane antigen (PSMA) shows promise and is an area of active investigation. J591 is a deimmunized IgG monoclonal antibody developed to target the extracellular domain of PSMA. Preclinical and early phase clinical studies using radiolabeled J591 have demonstrated efficacy in targeting tumor cells and decreasing levels of prostate-specific antigen. Radiolabeled J591 is well-tolerated, nonimmunogenic, and can be administered in multiple doses. The dose-limiting toxicity is reversible myelosuppression with little nonhematologic toxicity. Future studies will include approaches to optimize patient selection and incorporate novel strategies to improve the success of anti-PSMA radioimmunotherapy.