Intensive treatment regimens for relapsed/refractory (R/R) acute myeloid leukemia (AML) generally include an anthracycline, cytarabine, with or without a purine analog. In patients who cannot tolerate an anthracycline due to comorbidities, one may consider using etoposide. Given the ongoing fludarabine shortage, it has prompted the switch to other purine analogs, such as cladribine, in combination with cytarabine and etoposide in patients who may be eligible for intensive chemotherapy but not able to tolerate an anthracycline due to comorbidities or cardiotoxicity risks. Here, we present 4 patients who received a cladribine, cytarabine, and etoposide (CCE) based regimen for R/R AML. There were no significant therapy-related adverse events, dose holds, or delays. Two out of 3 evaluable patients were successfully bridged to allogeneic transplant, and one is pending another cycle of chemotherapy as a bridge to transplant. The CCE regimen offers a potential option for patients with R/R AML in need of an anthracycline-free salvage regimen during a fludarabine shortage.

Journal Section:
Case Report
Keywords:
Acute myeloid leukemia, Stem cell transplant, Cladribine, Fludarabine shortage
1.
Döhner H, Wei AH, Appelbaum FR, Craddock C, DiNardo CD, Dombret H, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 2022;140(12):1345–77.
https://doi.org/10.1182/blood.2022016867
2.
Megías-Vericat JE, Martínez-Cuadrón D, Sanz MÁ, Montesinos P. Salvage regimens using conventional chemotherapy agents for relapsed/refractory adult AML patients: a systematic literature review. Ann Hematol. 2018;97(7):1115–53.
https://doi.org/10.1007/s00277-018-3304-y
3.
Gandhi V, Estey E, Keating MJ, Plunkett W. Fludarabine potentiates metabolism of cytarabine in patients with acute myelogenous leukemia during therapy. J Clin Oncol. 1993;11(1):116–24.
https://doi.org/10.1200/JCO.1993.11.1.116
4.
Gandhi V, Estey E, Keating MJ, Chucrallah A, Plunkett W. Chlorodeoxyadenosine and arabinosylcytosine in patients with acute myelogenous leukemia: pharmacokinetic, pharmacodynamic, and molecular interactions. Blood. 1996;87(1):256–64.
https://doi.org/10.1182/blood.v87.1.256.bloodjournal871256
5.
DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med. 2020;383(7):617–29.
https://doi.org/10.1056/NEJMoa2012971
6.
American Society of Health-System Pharmacies. Fludarabine injection. Available from: https://www.ashp.org/drug-shortages/current-shortages/drug-shortage-detail.aspx?id=622&loginreturnUrl=SSOCheckOnly [Accessed 19 December 2022].
7.
Aldoss I, Ji L, Haider M, Pullarkat V. The combination of fludarabine, cytarabine and etoposide is an active and well-tolerated regimen in relapsed/refractory acute myeloid leukemia. Acta Haematol. 2014;131(4):202–7.
https://doi.org/10.1159/000354820
8.
Westhus J, Noppeney R, Schmitz C, Flasshove M, Dührsen U, Hanoun M. Etoposide combined with FLAG salvage therapy is effective in multiple relapsed/refractory acute myeloid leukemia. Acta Haematol. 2020;143(5):438–45.
https://doi.org/10.1159/000503056
9.
DiNardo CD, Lachowiez CA, Takahashi K, Loghavi S, Kadia T, Daver N, et al. Venetoclax combined with FLAG-IDA induction and consolidation in newly diagnosed acute myeloid leukemia. Am J Hematol. 2022;97(8):1035–43.
https://doi.org/10.1002/ajh.26601
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