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)

BackgroundThe objective of this study was to identify prognostic factors for survival in patients with primary diffuse large B-cell lymphoma (DLBCL) of the adrenal gland.MethodsThirty one patients diagnosed with primary adrenal DLBCL from 14 Korean institutions and treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) were analyzed.ResultsComplete remission (CR) and overall response rate after R-CHOP chemotherapy were 54.8% and 87.0%. The 2-year estimates of overall survival (OS) and progression-free survival (PFS) were 68.3% and 51.1%. In patients achieving CR, significant prolongations of OS (P = 0.029) and PFS (P = 0.005) were observed. Ann Arbor stage had no influence on OS. There was no significant difference in OS between patients with unilateral involvement of adrenal gland and those with bilateral involvement. When staging was modified to include bilateral adrenal involvement as one extranodal site, early stage (I or II) significantly correlated with longer OS (P = 0.021) and PFS (P <0.001).ConclusionsContrary to prior reports, our data suggests that outcomes of primary adrenal DLBCL are encouraging using a regimen of R-CHOP, and that achieving CR after R-CHOP is predictive of survival. Likewise, our modified staging system may have prognostic value.

Following bone marrow transplantation, delayed donor leukocyte infusions (DLIs) can induce graft-versus-leukemia (GVL) effects without graft-versus-host disease (GVHD). These antitumor responses are maximized by the presence of host hematopoietic antigen-presenting cells (APCs) at the time of DLI. Using a tumor-protection model, we demonstrate here that GVL activity following administration of DLIs to established mixed chimeras is dependent primarily on reactivity to allogeneic MHC antigens rather than minor histocompatibility or tumorassociated antigens. CD8 ؉ T-celldependent GVL responses against an MHC class II-negative tumor following delayed DLI require CD4 ؉ T-cell help and are reduced significantly when host APCs lack MHC class II expression. CD4 ؉ T cells primed by host APCs were required for maximal expansion of graft-versus-host reactive CD8 ؉ T cells but not their synthesis of IFN-␥. In contrast, the GVL requirement for CD4 ؉ T-cell help was bypassed almost completely when DLI was administered to freshly irradiated recipients, indicating that the host environment is a major factor influencing the cellular mechanisms of GVL. IntroductionFollowing allogeneic bone marrow transplantation (BMT), donor T-cell alloreactivity can be co-opted to generate powerful antitumor activity, an effect termed the graft-versus-leukemia (GVL) response. 1,2 The GVL effect is associated with the presence of graft-versus-host disease (GVHD) and is linked to the degree of major MHC disparity and the presence of T cells within the graft, indicating that graft-versus-host (GVH) alloreactive donor T cells are important for this effect. 3 We have previously shown that administration of delayed donor leukocyte infusion (DLI) to established mixed chimeras (MCs; in which hematopoietic elements from both the donor and recipient are present) produces dramatically improved GVL effects compared with those seen following delayed DLI to full chimeras (FCs). 4 Host hematopoietic antigen-presenting cells (APCs) expressing MHC class I molecules are necessary for this optimization of GVL effects in MCs. 4 The importance of host APCs in inducing GVL has recently been confirmed in freshly irradiated mice, 5 and previous studies have shown their importance in inducing GVHD under such conditions. 6,7 The marked overlap of GVL and GVHD limit the wider application of allogeneic BMT, especially in those individuals who lack an HLA-identical donor. However, GVL can be achieved without GVHD by administration of DLI to established MCs that lack proinflammatory stimuli from recent conditioning. 4,8 A precise definition of the mechanisms that underlie the GVL effect of DLI in MCs will be important for the rational development of this strategy for achieving maximal GVL effects without GVHD in humans. Using a tumor protection model, we demonstrate here that GVL responses of DLI are due to alloresponses against recipient MHC antigens. We also demonstrate a requirement for CD4 ϩ T-cell help in generating maximal CD8 ϩ T-cell-mediated GVL activity against MH...

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