Prolonged Survival in Adults with Acute Lymphoblastic Leukemia (ALL) Following Reduced Intensity Conditioning and Allogeneic Transplantation

Reduced intensity conditioning (RIC) and allogeneic hematopoietic cell transplantation (HCT) for adult patients with ALL may improve the tolerance and outcomes following allografting. We studied 22 consecutive patients (2001–2008) who received RIC HCT. Indications for RIC regimens included: age > 55 years (for matched related donor [MRD], >45 years for unrelated or umbilical cord [UCB]), Karnofsky index <80%, impaired organ function or prior autologous/allogeneic HCT. The median age was 49 years (24–68), median diagnostic WBC 20×10⁹/L (1.4–248) and median comorbidity index of 3 (range: 0–8) at HCT. All patients had high risk disease, including 14 patients (64%) with Ph⁺ ALL, 10 patients (46%) in 2^nd or subsequent remission. Five patients (23%) were treated with tyrosine kinase inhibitors pre-HCT. Uniform conditioning (Cyclophosphamide 50 mg/kg; Flu 200 mg/m2; total body irradiation (TBI) 200cGy, n=21) and graft versus host disease (GvHD) prophylaxis (Cyclosporin/MMF) was followed by MRD (n=4) or UCB donor (n=18) grafts. All patients had sustained donor neutrophil engraftment (median 10 days, range 0–28) and reached 100% donor chimerism at median day 23 post-transplantation (range 14–99 days). At 3 years, treatment related morality relapse and overall survival (OS) were 27% (95% confidence interval [CI]: 9–45%), 36% (95% CI: 14–58%) and 50% (95% CI: 27–73%), respectively. There were no relapses beyond 2 years. After a median follow-up of 33 months (range 5–77) the cumulative incidence of acute II–IV, III–IV and chronic graft versus host disease were 55%, 20% and 45%. Lower TRM for HCT in CR1 vs ≥ CR2 (8% vs. 50%; p<0.04) led to improved 3 year OS in the CR1 cohort (81% vs. 15% (p<0.01)). HCT using either MRD or UCB resulted in similar risks of GVHD, relapse and OS. These data suggest that RIC allogeneic HCT using either related or UCB donors for adults with ALL can result in modest TRM, and only limited risks of relapse and promising leukemia-free survival. Further study, especially for patients in CR1, will better define the utility of this approach for patients unsuited for more intensive, myeloablative conditioning.