Lower intensity conditioning regimens for haploidentical blood or marrow transplantation (BMT) are safe and efficacious for adult patients with hematologic malignancies. We report data for pediatric/young adult patients with high-risk hematologic malignancies (n=40) treated with nonmyeloablative haploidentical BMT with post-transplantation cyclophosphamide (PT/Cy) from 2003–2015. Patients received a preparative regimen of fludarabine, cyclophosphamide, and total body irradiation. Post-transplant immunosuppression consisted of cyclophosphamide, mycophenolate mofetil, and tacrolimus. Donor engraftment occurred in 29/32 (91%), with median time to engraftment of neutrophils >500/μL of 16 days (range 13–22) and platelets >20,000/μL without transfusion of 18 days (range 12–62). Cumulative incidences of acute GVHD grades II–IV and grades III–IV at day 100 were 33% and 5%, respectively. Cumulative incidence of chronic GVHD was 23%, with 7% moderate-severe chronic GVHD according to NIH consensus criteria. Transplant related mortality (TRM) at 1 year was 13%. The cumulative incidence of relapse at 2 years was 52%. With a median follow-up of 20 months (range 3–148), 1-year actuarial overall and event-free survival are 56% and 43%, respectively. Thus, we demonstrate excellent rates of engraftment, GVHD, and TRM in pediatric/young adult patients treated with this regimen. This approach is a widely-available, safe, and feasible option for pediatric and young adult patients with high risk hematologic malignancies, including those with a prior history of myeloablative BMT and/or those with co-morbidities or organ dysfunction that preclude eligibility for myeloablative BMT.
uCB-unit. The median follow-up was 42 (range 0.3-131) months. Seventeen patients (13%) did not receive ATG. Indications were equally distributed over the 3 ATG exposure groups. Lower AUC of active ATG after CBT (continuous variable) was the best predictor for successful IR (HR 0.97, p¼0.0001; In Fig 1a depicted in the 4 groups). In multivariate analyses, successful IR is associated with higher OS (HR 0.33, p¼0.0020; fig 1b), EFS (HR 0.38, p¼0.0016) and TRM (HR 0.31, p¼0.008). Low active-ATG exposure after CBT (continuous) predicted higher EFS (HR 1.005, p¼0.015), and showed a trend to higher OS (p¼0.08). High ATG exposure before CBT was a predictor for a lower incidence of acute GvHD 2-4 (HR 0.40, p¼0.031). Acute-GvHD 3-4 (12% @ 180d), extensive chronic-GvHD (6% @ 1yr) and GF (12% @ 1yr) were not associated with ATG exposure, possibly due to the low incidence. Low exposure of active-ATG after CBT is a predictor for IR and EFS, while presence of IR is associated with higher OS and EFS chances. Individualized dosing of ATG targeted to optimal exposures before and after CBT may result in better survival chances. A clinical trial investigating the influence of individualized dosing of ATG on IR is recruiting in the Netherlands.
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