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)

Key Points Higher allelic burden at day 21 of post-HCT is associated with higher risk of relapse and mortality. Longitudinal tracking of AML patients receiving HCT is feasible and provides clinically relevant information.

The genetics behind the progression of myelodysplasia to secondary acute myeloid leukemia (sAML) is poorly understood. In this study, we profiled somatic mutations and their dynamics using next generation sequencing on serial samples from a total of 124 patients, consisting of a 31 patient discovery cohort and 93 patients from two validation cohorts. Whole-exome analysis on the discovery cohort revealed that 29 of 31 patients carry mutations related to at least one of eight commonly mutated pathways in AML. Mutations in genes related to DNA methylation and splicing machinery were found in T-cell samples, which expand at the initial diagnosis of the myelodysplasia, suggesting their importance as early disease events. On the other hand, somatic variants associated with signaling pathways arise or their allelic burdens expand significantly during progression. Our results indicate a strong association between mutations in activated signaling pathways and sAML progression. Overall, we demonstrate that distinct categories of genetic lesions play roles at different stages of sAML in a generally fixed order.

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Several studies have suggested the possibility of a prognostic relationship between Epstein–Barr virus (EBV) and diffuse large B‐cell lymphoma (DLBCL). The clinical outcome of EBV‐associated DLBCL is not clear, especially since the introduction of rituximab. We retrospectively analyzed 222 elderly patients (≥50 years) with DLBCL who received R‐CHOP chemotherapy and evaluated the state of EBV‐encoded RNA‐1 (EBER). Eighteen cases (8.1%) were EBER‐positive (+). After a median of six cycles of R‐CHOP chemotherapy, the response rate (≥partial response) was 72.2% (13/18) in the EBV (+) patients and 90.2% (184/204) in the EBV (−) DLBCL patients (P = 0.021). Four of 18 (22.2%) EBV (+) DLBCL patients received two or fewer cycles of R‐CHOP chemotherapy. R‐CHOP chemotherapy was also interrupted early more frequently compared with the EBV (−) group (2.5%) (P = 0.00). At a median follow‐up of 32.8 months, there was no significant difference in the overall survival between the groups (P = 0.627). The EBV (+) DLBCL patients with early interruption of R‐CHOP chemotherapy showed a trend toward a high EBV‐DNA titer (≥1,000 copies/mL) (P = 0.091). The results suggest that the EBV (+) tumoral status of elderly DLBCL patients who undergo R‐CHOP chemotherapy does not predict their survival but that their EBV status may contribute to the early interruption of R‐CHOP chemotherapy. Am. J. Hematol. 88:774–779, 2013. © 2013 Wiley Periodicals, Inc.