Key Points• Nilotinib plus multiagent chemotherapy was feasible and showed a comparable outcome to previous results with imatinib for Ph-pos ALL.• The achievement of deep MR with nilotinib at postremission correlated well with the clinical outcomes for Ph-pos ALL.We investigated the effects of nilotinib plus multiagent chemotherapy, followed by consolidation/maintenance or allogeneic hematopoietic cell transplantation (allo-HCT) for adult patients with newly diagnosed Philadelphia-positive (Ph-pos) acute lymphoblastic leukemia (ALL). Study subjects received induction treatment that comprised concurrent vincristine, daunorubicin, prednisolone, and nilotinib. After achieving complete hematologic remission (HCR), subjects received either 5 courses of consolidation, followed by 2-year maintenance with nilotinib, or allo-HCT. Minimal residual disease (MRD) was assessed at HCR, and every 3 months thereafter. The molecular responses (MRs) were defined as MR3 for BCR-ABL1/G6PDH ratios £10 23 and MR5 for ratios <10 25. Ninety evaluable subjects, ages 17 to 71 years, were enrolled in 17 centers. The HCR rate was 91%; 57 subjects received allo-HCT. The cumulative MR5 rate was 94%; the 2-year hematologic relapse-free survival (HRFS) rate was 72% for 82 subjects that achieved HCR, and the 2-year overall survival rate was 72%. Subjects that failed to achieve MR3 or MR5 were 9.1 times (P 5 .004) or 6.3 times (P 5 .001) more prone to hematologic relapse, respectively, than those that achieved MR3 or MR5. MRD statuses just before allo-HCT and at 3 months after allo-HCT were predictive of 2-year HRFS. Adverse events occurred mainly during induction, and most were reversible with dose reduction or transient interruption of nilotinib. The combination of nilotinib with high-dose cytotoxic drugs was feasible, and it effectively achieved high cumulative complete molecular remission and HRFS rates. The MRD status at early postremission time was predictive of the HRFS. This trial was registered at www.clinicaltrials.gov as #NCT00844298. (Blood. 2015;126(6):746-756)

The doses of donor-derived natural killer (NK) cells that can be given safely after human leukocyte antigen (HLA)-haploidentical hematopoietic cell transplantation (HCT) remain to be defined. Forty-one patients (ages 17 to 75 years) with hematologic malignancy underwent HLA-haploidentical HCT after reduced-intensity conditioning containing busulfan, fludarabine, and antithymocyte globulin. Cell donors (ages 7 to 62 years) underwent growth factor-mobilized leukapheresis for 3 to 4 days. Cells collected on the first 2 to 3 days were used for HCT, whereas those collected on the last day were CD3-depleted and cultured into NK cells using human interleukins-15 and -21. These NK cells were then infused into patients twice at 2 and 3 weeks after HCT at an escalating doses of .2 × 10(8) cells/kg of body weight (3 patients), .5 × 10(8) cells/kg (3 patients), 1.0 × 10(8) cells/kg (8 patients), and ≥ 1.0 × 10(8) cells/kg or available cells (27 patients). At all dose levels, no acute toxicity was observed after NK cell infusion. After HLA-haploidentical HCT and subsequent donor NK cell infusion, when referenced to 31 historical patients who had undergone HLA-haploidentical HCT after the same conditioning regimen but without high-dose NK cell infusion, there was no significant difference in the cumulative incidences of major HCT outcomes, including engraftment (absolute neutrophil count ≥ 500/μL, 85% versus 87%), grade 2 to 4 acute graft-versus-host disease (GVHD, 17% versus 16%), moderate to severe chronic GVHD (15% versus 10%), and transplantation-related mortality (27% versus 19%). There was, however, a significant reduction in leukemia progression (74% to 46%), with post-transplantation NK cell infusion being an independent predictor for less leukemia progression (hazard ratio, .527). Our findings showed that, when given 2 to 3 weeks after HLA-haploidentical HCT, donor-derived NK cells were well tolerated at a median total dose of 2.0 × 10(8) cells/kg. In addition, they may decrease post-transplantation progression of acute leukemia.