Favorable outcomes of acute leukemias of ambiguous lineage treated with hyperCVAD: a multi-center retrospective study

Abstract

Acute leukemias of ambiguous lineage (ALAL) are rare hematologic malignancies with poor outcomes. Retrospective studies have suggested that acute lymphoblastic leukemia (ALL) regimens are more effective than acute myeloid leukemia (AML) regimens. We retrospectively examined the effectiveness of the widely-used adult ALL regimen hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyperCVAD) as initial therapy in patients with ALAL at five academic institutions. Twenty-five patients were identified, including 23 with mixed phenotype acute leukemia (MPAL) and two with acute undifferentiated leukemia. Five of 8 tested (63%) had FLT3-ITD and 3 of 25 (12%) were Philadelphia chromosome-positive. The complete remission (CR) rate was 76%, with CR with incomplete count recovery (CRi) in an additional 8%, for an overall response rate of 84%. Median number of cycles to CR/CRi was 1. There were no deaths in the first 30 days. Of the 21 patients achieving CR or CRi, 14 (66%) proceeded to allogeneic hematopoietic stem cell transplantation. With a median follow-up time of 31.6 months, median overall survival for the entire cohort was not reached, and the estimated 2-year survival was 63%. HyperCVAD can be considered an effective and tolerable front-line regimen for patients with ALAL, and warrants further prospective study.

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Authors

Contributions

VHD wrote the protocol, collected, and analyzed the data and had primary responsibility for writing the manuscript. SK participated in analyzing the data and writing the manuscript. KHB, KS, ESW, RC, DAS, ZNS, MRB, and AAK collected data and participated in editing and critically reviewing the manuscript. Availability of data and material Raw deidentified data will be made available upon request and subject to certain criteria, conditions, and exceptions.

Corresponding author

Correspondence to Vu H. Duong.

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Conflict of interest

KS has been on advisory boards for Takeda, Bristol-Myers Squibb, and Novartis; reports honoraria from Astellas and Stemline; and has received research funding from Incyte. ESW has had an advisory role with Abbvie, Astellas, Daiichi Sankyo, Dava Oncology/Arog, Genentech, Jazz, Kite Pharmaceuticals, Kura Oncology, Macrogenics, Pfizer, PTC Therapeutics, and Stemline and has been a speaker for Stemline and Pfizer. All other authors report no relevant conflicts of interest.

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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. The respective Institutional Review Boards at each study center approved this study. As this was a retrospective study, informed consent could not be obtained from all patients included in the study.

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Duong, V.H., Begna, K.H., Kashanian, S. et al. Favorable outcomes of acute leukemias of ambiguous lineage treated with hyperCVAD: a multi-center retrospective study. Ann Hematol 99, 2119–2124 (2020). https://doi.org/10.1007/s00277-020-04179-z

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Keywords

  • Acute leukemia of ambiguous lineage
  • Mixed phenotype acute leukemia
  • HyperCVAD
  • ALL
  • AML