Impact of induction chemotherapy with intermediate-dosed cytarabine and subsequent allogeneic stem cell transplantation on the outcome of high-risk acute myeloid leukemia.

Abstract

BACKGROUND:

Acute myeloid leukemia (AML) with antecedent hematological disease (s-AML) and treatment-related AML (t-AML) predicts poor prognosis. Intensive treatment protocols of those high-risk patients should consider allogeneic stem cell transplantation (allo-HSCT) in first complete remission (CR). Despite allo-HSCT, relapse rate remains high. Induction chemotherapy with liposomal cytarabine and daunorubicin (CPX-351) has been approved for patients with AML with myeloid-related changes (AML-MRC) or t-AML based on improved survival and remission rates compared to standard 7 + 3 induction.

PATIENTS AND METHODS:

110 patients with newly diagnosed s-AML or t-AML at a university hospital were analyzed retrospectively. Median age was 62 years (24-77 years). A total of 65 patients with s-AML after MDS (59%) and 23 patients (20.9%) with t-AML were included. Induction chemotherapy consisted of intermediate-dosed cytarabine (ID-AraC) in combination with idarubicin (patients up to 60 years) or mitoxantrone (patients over 60 years). In patients subsequently undergoing allo-HSCT, reduced conditioning regimens (RIC) were applied prior to transplantation in 47 of 62 patients (76%).

RESULTS:

Induction chemotherapy with ID-AraC resulted in an overall response rate of 83% including complete remission (CR/CRi) in 69 patients (63%) with a low rate of early death (2.7%). Most relevant non-hematologic toxicity consisted of infectious complications including sepsis with need of intensive care treatment in five patients (4.5%) and proven or probable invasive fungal disease in eight patients (7.2%). Relapse-free survival (RFS), event-free survival (EFS) and overall survival (OS) of the whole cohort were 19 months (0-167), 10 months (0-234) and 15 months (0-234), respectively (p < 0.0001). A significant improvement of OS was observed in patients who underwent allo-HSCT compared to those without subsequent allo-HSCT: 9 vs. 46 months, p < 0.0001. Rate of transplantation-related mortality (TRM) in the early phase post allo-HSCT was low (0.9% at day 30 and 1.8% at day 90, respectively). RIC conditioning results in OS rate of 60% after 60 months post allo-HSCT (median OS not reached).

CONCLUSION:

S-AML and t-AML patients receiving induction chemotherapy with intermediate-dosed cytarabine showed satisfactory response rate and consolidation therapy with allo-HSCT after full or reduced-intensity conditioning further improved survival in these patients with similar outcome as reported for CPX-351.

• Authors: Maximilian Fleischmann, Ulf Schnetzke, Jochen J Frietsch, Herbert G Sayer, Karin Schrenk, Jakob Hammersen, Anita Glaser, Inken Hilgendorf, Andreas Hochhaus, Sebastian Scholl
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 148 Issue 6 Pg. 1481-1492 (Jun 2022) ISSN: 1432-1335 [Electronic] Germany
• PMID: 34297206 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s).

Chemical References

• Cytarabine

Topics

• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Cytarabine
• Hematopoietic Stem Cell Transplantation
• Humans
• Induction Chemotherapy (methods)
• Leukemia, Myeloid, Acute (drug therapy)
• Middle Aged
• Prognosis
• Remission Induction
• Retrospective Studies