Online first
Original research article
Published online: 2024-09-30
DAC and CLAM are equally effective as early second induction in newly diagnosed AML patients with persistent leukemia in early bone marrow evaluation – a retrospective analysis of Polish Adult Leukemia Group
12
, 12, 3, 3, 4, 5, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 115, 12
, 12, 3, 3, 4, 5, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 115, 12
DOI: 10.5603/ahp.101972
Abstract
The study presents a retrospective analysis of patients with acute myeloid leukemia <60 years of age, who had ≥10% blasts in the early bone marrow evaluation at day 14th of the DAC (Daunorubicin + AraC + Cladribine) first induction cycle. Patients included in this analysis were treated according to the PALG-AML-1/2012 and PALG AML-1/2016 studies. As the 2nd early induction, 22 patients received DAC and 35 patients received CLAM (Cladribine + AraC + Mitoxantrone). There was no significant difference between patients treated with CLAM and DAC chemotherapy in terms of overall survival (OS after 2 years 52% vs. 76% for DAC, HR 0.68, 95%CI: 0.26, 1.77, p=0.4). Furthermore, there was no significant difference in cCR rates between both treatment regimens: 60% (21/35) for CLAM and 54.6% (12/22) for DAC (p>0.05). Both treatment regimens had a similar toxicity profile and early death rate.
Keywords: refractory AMLearly second inductiontreatmentcladribine
References
- Döhner H, Weisdorf DJ, Bloomfield CD. Acute Myeloid Leukemia. N Engl J Med. 2015; 373(12): 1136–1152.
- Roboz GJ. Novel approaches to the treatment of acute myeloid leukemia. Hematology Am Soc Hematol Educ Program. 2011; 2011: 43–50.
- Park S, Cho BS, Kim HJ. New agents in acute myeloid leukemia (AML). Blood Res. 2020; 55(S1): S14–S18.
- Yates JW, Wallace HJ, Ellison RR, et al. Cytosine arabinoside (NSC-63878) and daunorubicin (NSC-83142) therapy in acute nonlymphocytic leukemia. Cancer Chemother Rep. 1973; 57(4): 485–488.
- Holowiecki J, Grosicki S, Robak T, et al. Polish Adult Leukemia Group (PALG). Addition of cladribine to daunorubicin and cytarabine increases complete remission rate after a single course of induction treatment in acute myeloid leukemia. Multicenter, phase III study. Leukemia. 2004; 18(5): 989–997.
- Libura M, Bialopiotrowicz E, Giebel S, et al. Polish Adult Leukemia Group, Polish Adult Leukemia Group, Polish Adult Leukemia Group (PALG), Polish Adult Leukemia Group. A multicenter, open, non-comparative, phase II study of the combination of cladribine (2-chlorodeoxyadenosine), cytarabine, and G-CSF as induction therapy in refractory acute myeloid leukemia - a report of the Polish Adult Leukemia Group (PALG). Eur J Haematol. 2003; 71(3): 155–162.
- Browman G, Preisler H, Raza A, et al. Use of the day 6 bone marrow to alter remission induction therapy in patients with acute myeloid leukaemia: a leukemia intergroup study. Br J Haematol. 1989; 71(4): 493–497.
- Liso V, Albano F, Pastore D, et al. Bone marrow aspirate on the 14th day of induction treatment as a prognostic tool in de novo adult acute myeloid leukemia. Haematologica. 2000; 85(12): 1285–1290.
- Kern W, Haferlach T, Schoch C, et al. Early blast clearance by remission induction therapy is a major independent prognostic factor for both achievement of complete remission and long-term outcome in acute myeloid leukemia: data from the German AML Cooperative Group (AMLCG) 1992 Trial. Blood. 2003; 101(1): 64–70.
- El Gammal MM, Owaidat HM, Rashed RA, et al. Prognostic and Therapeutic Value of Day 14 Bone Marrow Aspiration in Adult Acute Myeloid Leukemia Patients. Clin Lymphoma Myeloma Leuk. 2019; 19(7): e406–e413.
- National Comprehensive Cancer Network. Acute myeloid leukemia (Version 1.2024). https://www.nccn.org/professionals/physician_gls/pdf/aml.pdf (17.03.2024).
- Othus M, Mukherjee S, Sekeres MA, et al. Prediction of CR following a second course of '7+3' in patients with newly diagnosed acute myeloid leukemia not in CR after a first course. Leukemia. 2016; 30(8): 1779–1780.
- Rowe JM, Kim HT, Cassileth PA, et al. Adult patients with acute myeloid leukemia who achieve complete remission after 1 or 2 cycles of induction have a similar prognosis: a report on 1980 patients registered to 6 studies conducted by the Eastern Cooperative Oncology Group. Cancer. 2010; 116(21): 5012–5021.
- de la Rubia J, Regadera A, Martín G, et al. FLAG-IDA regimen (fludarabine, cytarabine, idarubicin and G-CSF) in the treatment of patients with high-risk myeloid malignancies. Leuk Res. 2002; 26(8): 725–730.
- Visani G, Petti MC, Cenacchi A, et al. MEC (mitoxantrone, etoposide and intermediate dose cytarabine): an effective induction regimen for previously untreated acute non-lymphocytic leukemia. Leuk Lymphoma. 1995; 19(5-6): 447–451.
- Hiddemann W, Kreutzmann H, Straif K, et al. High-dose cytosine arabinoside and mitoxantrone: a highly effective regimen in refractory acute myeloid leukemia. Blood. 1987; 69(3): 744–749.
- Wierzbowska A, Robak T, Pluta A, et al. Polish Adult Leukemia Group. Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group. Eur J Haematol. 2008; 80(2): 115–126.
- Pluta A, Robak T, Brzozowski K, et al. Early induction intensification with cladribine, cytarabine, and mitoxantrone (CLAM) in AML patients treated with the DAC induction regimen: a prospective, non-randomized, phase II study of the Polish Adult Leukemia Group (PALG). Leuk Lymphoma. 2020; 61(3): 588–603.
- Wierzbowska A, Pluta A, Libura M, et al. A Polish Acute Leukemia Group Prospective Multicenter Clinical Trial to Compare the Efficacy of Two Standard Induction Therapies (DA-90 vs DAC) and Two Standard Salvage Regimens (FLAG-IDA vs CLAG-M) in Acute Myeloid Leukemia (AML) Patients ≤ 60 Years Old (PALG-AML1/2016). Blood. 2020; 136(Supplement 1): 3–4.
- Wiernik PH, Gordon LI, Oken MM, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982; 5(6): 649–655.
- Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987; 40(5): 373–383.
- Fernandez HF, Sun Z, Yao X, et al. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med. 2009; 361(13): 1249–1259.
- Wrzesień-Kuś A, Robak T, Wierzbowska A, et al. Polish Adult Leukemia Group. A multicenter, open, noncomparative, phase II study of the combination of cladribine (2-chlorodeoxyadenosine), cytarabine, granulocyte colony-stimulating factor and mitoxantrone as induction therapy in refractory acute myeloid leukemia: a report of the Polish Adult Leukemia Group. Ann Hematol. 2005; 84(9): 557–564.
- Russell N, Thomas A, Hills R, et al. MRD Directed Treatment Intensification with Either FLAG-Ida or DA-Cladribine Improves Survival in Older AML Patients: Results from the NCRI AML18 Randomised Trial. Blood. 2023; 142(Supplement 1): 830–830.
- Ferrara F, Izzo T, Criscuolo C, et al. Day 15 bone marrow driven double induction in young adult patients with acute myeloid leukemia: feasibility, toxicity, and therapeutic results. Am J Hematol. 2010; 85(9): 687–690.
- De Witte T, Suciu S, Selleslag D, et al. Salvage treatment for primary resistant acute myelogenous leukemia consisting of intermediate-dose cytosine arabinoside and interspaced continuous infusions of idarubicin: a phase-II study (no. 06901) of the EORTC Leukemia Cooperative Group. Ann Hematol. 1996; 72(3): 119–124.
- Walti C, Halpern A, Xie Hu, et al. Infectious Complications after Intensive Chemotherapy with CLAG-M or '7+3' for Adults with Acute Myeloid Leukemia and Other High-Grade Myeloid Neoplasms. Blood. 2021; 138(Supplement 1): 2339–2339.