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Objectives: To analyze the efficacy, safety, prognostic factors, factors affecting treatment continuation, suitable treatment candidates, and optimal administration schedule in patients with acute myeloid leukemia(AML)treated with venetoclax plus azacitidine(VEN+AZA)., Methods: We performed a retrospective analysis of the data of 39 patients with untreated or relapsed/refractory AML., Results: The median duration of follow-up was 6 months, and the median number of treatment cycles was 2. The composite complete remission(CRc)achievement rate(complete remission+complete remission with incomplete hematological recovery)was 61.5%. The treatment discontinuation rate was 76.9%, the median overall survival (OS)was 7.7 months, and event-free survival(EFS)was 4.8 months. In subgroup analyses, significant differences in the OS were observed between subgroups stratified according to the cytogenetic risk, CRc achievement rate, and Charlson comorbidity index(CCI)(≤7 vs <7). A significant difference in the EFS was also observed between subgroups stratified according to the cytogenetic risk and CRc achievement rate. The response rate tended to be lower in the adverse cytogenetic risk subgroup. Patients who received VEN for 21 days or less in the first treatment cycle tended to have a better OS., Conclusions: A lower OS and EFS were associated with a higher treatment discontinuation rate, lower number of treatment cycles, and lower CRc achievement rate than those observed in the VIALE-A trial. We considered that treatment continuation was important to improve the prognosis. We also concluded that it is important to select candidates suitable for VEN+AZA treatment and to modify the administration schedule.

An 84-year-old woman was diagnosed as having acute promyelocytic leukemia(APL)in July Year X-3. The test for promyelocytic leukemia- retinoic acid receptor alpha(PML-RARA)mRNA was positive, while that for CD56 was negative. Since her white blood cell( WBC) count was <3,000/μL, with a count of APL cells of <1,000/μL, she was started on monotherapy with all-trans retinoic acid(ATRA). In September Year X-3, complete hematological remission(CHR)was confirmed. she refused to provide consent for receiving consolidation therapy. In February Year X-2, hematological relapse occurred. She was started on re-induction therapy with arsenite(ATO), and in June Year X-2, complete molecular remission(CMR)was achieved. She was started on post-remission therapy with ATO. In August Year X-1, she developed molecular relapse and was started on tamibarotene(Am80). In October Year X-1, hematological relapse was detected, and the test for CD56 was positive. She was started on combined venetoclax(VEN)+azacitidine(AZA)(VEN+AZA). After completion of 1 course of treatment, CMR was achieved, but she developed hematological relapse after 5 courses of treatment. She died of gastrointestinal hemorrhage. This is considered a valuable case for accumulating information on the treatment of CD56-positive APL resistant to ATRA and ATO.

We report a case of FLT3-mutated APL who developed disease relapse despite all-trans retinoic acid (ATRA) + chemotherapy, and re-induction chemotherapy with arsenic trioxide (ATO) and high-dose (HD) cytarabine (Ara-C) therapy failed to yield complete remission. Because the leukemic cells were resistant to all the aforementioned therapies, we started the patient on monotherapy with gilteritinib, a selective FLT3-inhibitor, as an alternative re-induction treatment option rather than further intensive chemotherapy. The patient showed complete hematologic remission in response to this therapy. This case serves as supporting evidence for the use of single-agent therapy with gilteritinib as a bridge to transplantation in patients with refractory FLT3 -mutated APL., Competing Interests: The authors declare that they have no conflicts of interest regarding the publication of this paper., (Copyright © 2023 Hirofumi Kobayashi et al.)

Allogeneic hematopoietic cell transplantation (HCT) offers a possible cure for patients with relapsed and refractory non-Hodgkin lymphoma (NHL) through potentially beneficial graft versus lymphoma effects. However, allogeneic HCT is associated with high nonrelapse mortality (NRM). Fludarabine with reduced-intensity busulfan (Flu/Bu2) and myeloablative busulfan (Flu/Bu4) are commonly used in conditioning regimens for allogeneic HCT; however, data on their use in patients with NHL is limited. We investigated the effect of busulfan dose on outcomes by comparing Flu/Bu2 and Flu/Bu4 in patients with NHL who underwent allogeneic HCT. Our study included 415 adult patients with NHL who received Flu/Bu2 (315 patients) or Flu/Bu4 (100 patients) between January 2008 and December 2019. All patients were enrolled in the Transplant Registry Unified Management Program 2 of the Japanese Data Center for Hematopoietic Cell Transplantation. The primary endpoint was the 5-year overall survival (OS). To minimize potential confounding factors that may influence outcomes, we performed propensity score matching. The 5-year OS was 50.6% (95% confidence interval (CI), 39.4%-60.8%) and 32.2% (95% CI, 22.4-42.4%) in the Flu/Bu2 and Flu/Bu4 groups, respectively (p = 0.006). The hazard ratio comparing the two groups was 2.13 (95% CI, 1.30-3.50; p = 0.003). Both groups had a similar 5-year cumulative incidence of relapse (38.2% vs 41.3%; p = 0.581), and the Flu/Bu4 group had a higher cumulative incidence of 5-year NRM (15.7% vs 31.9%; p = 0.043). In this study, Flu/Bu4 was associated with worse OS compared with Flu/Bu2 because of high NRM in patients with NHL., (© 2023. The Author(s).)