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Background Acute leukemia with mixed-phenotype blasts is associated with poor outcomes. There are no standard treatment regimens. Due to disease heterogeneity, controversy exists over whether an AML-based, ALL-based, or a combined (hybrid) AML/ALL-based regimen is most appropriate. Materials and Methods We conducted a single-center, retrospective case series review of patients with acute leukemia with mixed phenotype blasts as described by the European Group for Immunological Characterization of Leukemia (EGIL) or the 2008 WHO classification. Patients were treated from November 2014 and December 2019 with the combination chemotherapy regimen FLAG-idarubicin-vincristine-prednisone with or without rituximab. Outcomes included induction response, time to transplant, time to relapse, overall survival, time to neutrophil or platelet recovery, infection, and duration of hospitalization. Results The median age was 68 years (range 21−77). Six patients (87.5 %) had unfavorable/complex cytogenetics. All patients achieved a complete remission (CR) or complete remission with incomplete hematologic recovery (CRi). Estimated 1-year overall survival was 85.7 %. There were no deaths during induction, with a 22 day median duration of hospitalization for induction. Conclusion The combination of FLAG, idarubicin, vincristine, and prednisone (FLAG-VIPR) demonstrated favorable induction responses in a disease state with historically poor outcomes and should be studied in a prospective clinical trial.

High dose cytarabine (HIDAC) consolidation has demonstrated a survival benefit in patients with acute myeloid leukemia (AML). The increasing prevalence of obesity and the toxicity risk with this therapy renders important the quantification of potential risks with weight-based dosing in this patient population. The American Society of Clinical Oncology published recommendations on chemotherapy dosing in obese patients, but patients with leukemia were excluded from analysis. This was a retrospective comparison of safety and efficacy outcomes in obese and non-obese patients with AML who received HIDAC consolidation. Thirty-nine (41.9 %) patients received dose adjusted HIDAC in cycle 1. Nine of the 40 patients in the obese group received HIDAC dose-adjusted for obesity. The combined incidence of cycle delays, febrile neutropenia, or documented infection was 41.5 % in non-obese patients compared to 57.5 % in obese patients (p = 0.127). The median overall survival (OS) and event free survival (EFS) were not reached in both cohorts. The estimated 36-month overall survival was 76.4 % (95 % CI 0.623-0.905) in non-obese patients, compared to 66.1 % (95 % CI 0.472-0.85) in obese patients. There were no significant differences in safety or efficacy outcomes for obese versus non-obese patients who received HIDAC consolidation. For class III obesity, baseline dose-adjustments were more common.

Patients with secondary acute myeloid leukemia (sAML) have poor outcomes, with CR/CRi rates of 25-35% with standard 7 + 3 induction chemotherapy, while single center non-comparative analyses suggest promising outcomes with FLAG. We conducted a single-center, retrospective cohort study assessing outcomes in treatment-naïve patients with sAML treated with fludarabine, high-dose cytarabine, and granulocyte colony-stimulating factor (FLAG, n = 40) compared with 7 + 3 (n = 66). Median patient age was 63 years (range: 27-82) in the FLAG group and 60 years (range: 21-76) in the 7 + 3 group (P = 0.968). Patients treated with FLAG achieved higher overall response rates (CR + CRi + MLFS) compared to 7 + 3 (70% vs. 48%, P = 0.043). FLAG was well tolerated, with only one induction death (30-day mortality rate, 3% vs. 8%, P = 0.405) and no cases of cerebellar toxicity. Duration of neutropenia was significantly shorter with FLAG (median 16 vs. 23 days, P 0.001). Half of the FLAG-treated patients proceeded to consolidative therapy compared with only 27% of those who received 7 + 3 (P = 0.022). Overall survival was comparable between groups (8.5 mos, FLAG vs. 9.1 mos, 7 + 3; P = 0.798). Thus, FLAG may represent a low-cost treatment strategy in sAML that produces higher response rates and promising survival outcomes with minimal treatment-related toxicity. Further studies are required to prospectively compare FLAG to the newly FDA-approved CPX-351 in sAML.

B lymphoblastic leukemia (B-ALL) in adults has a higher risk of relapse and lower long-term survival than pediatric B-ALL, but data regarding genetic prognostic biomarkers are much more limited for adult patients. We identified 70 adult B-ALL patients from three institutions and performed genome-wide analysis via single nucleotide polymorphism (SNP) arrays on DNA isolated from their initial diagnostic sample and, when available, relapse bone marrow specimens to identify recurring copy number alterations (CNA). As B-cell developmental genes play a crucial role in this leukemia, we assessed such for recurrent deletions in diagnostic and relapse samples. We confirmed previous findings that the most prevalent deletions of these genes occur in CDKN2A, IKZF1, and PAX5, with several others at lower frequencies. Of the 16 samples having paired diagnostic and relapse samples, 5 showed new deletions in these recurrent B-cell related genes and 8 showed abolishment. Deletion of EBF1 heralded a significant negative prognostic impact on relapse free survival in univariate and multivariate analyses. The combination of both a CDKN2A/B deletion and an IKZF1 alteration (26% of cases) also showed a trend toward predicting worse overall survival compared to having only one or neither of these deletions. These findings add to the understanding of genomic influences on this comparably understudied disease cohort that upon further validation may help identify patients who would benefit from upfront treatment intensification.