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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 Feb; 80(2):115-26.EJ

Abstract

OBJECTIVES

Patients with primary refractory AML and with early relapses have unfavorable prognoses and require innovative therapeutic approaches. Purine analogs fludarabine (FA) and cladribine (2-CdA) increase cytotoxic effect of Ara-C in leukemic blasts and inhibit DNA repair mechanisms; therefore its association with Ara-C and mitoxantrone (MIT) results in a synergistic effect. In the current report, we present the final results of multi-center phase II study evaluating the efficacy and toxicity of CLAG-M salvage regimen in poor risk refractory/relapsed AML patients.

METHODS

The induction chemotherapy consisted of 2-CdA 5 mg/m2, Ara-C 2 g/m2, MIT 10 mg/m2, and granulocyte-colony stimulating factor. In the case of PR, a second CLAG-M was administered. Patients in CR received consolidation courses based on high doses of Ara-C and MIT with or without 2-CdA.

RESULTS

One hundred and eighteen patients from 11 centers were registered; 78 primary resistant and 40 relapsed. Sixty-six patients (58%) achieved CR after one or two courses of CLAG-M, 49 (35%) were refractory, and 8 (7%) died early. WBC >10 g/L and age >34 yr were factors associated with increased risk of treatment failure. Hematological toxicity was the most prominent toxicity of this regimen. The probability of OS at 4 yr was 14% (95% CI 4-23%). OS was influenced by age, WBC >10 g/L and poor karyotype in both univariate and multivariate analyses. The probability of 4 yr DFS was 30% for all 66 patients in CR (95% CI 11-49%). Poor karyotype was the only factor associated with decreased probability of DFS.

CONCLUSIONS

We conclude that CLAG-M is a well-tolerated and highly effective salvage regimen in poor risk refractory/relapsed AML.

Authors+Show Affiliations

Department of Hematology, Medical University, Lodz, Poland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18076637

Citation

Wierzbowska, Agnieszka, et al. "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." European Journal of Haematology, vol. 80, no. 2, 2008, pp. 115-26.
Wierzbowska A, Robak T, Pluta A, et al. 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):115-26.
Wierzbowska, A., Robak, T., Pluta, A., Wawrzyniak, E., Cebula, B., Hołowiecki, J., Kyrcz-Krzemień, S., Grosicki, S., Giebel, S., Skotnicki, A. B., Piatkowska-Jakubas, B., Kuliczkowski, K., Kiełbiński, M., Zawilska, K., Kłoczko, J., & Wrzesień-Kuś, A. (2008). 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. European Journal of Haematology, 80(2), 115-26.
Wierzbowska A, et al. 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):115-26. PubMed PMID: 18076637.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Wierzbowska,Agnieszka, AU - Robak,Tadeusz, AU - Pluta,Agnieszka, AU - Wawrzyniak,Ewa, AU - Cebula,Barbara, AU - Hołowiecki,Jerzy, AU - Kyrcz-Krzemień,Sławomira, AU - Grosicki,Sebastian, AU - Giebel,Sebastian, AU - Skotnicki,Aleksander B, AU - Piatkowska-Jakubas,Beata, AU - Kuliczkowski,Kazimierz, AU - Kiełbiński,Marek, AU - Zawilska,Krystyna, AU - Kłoczko,Janusz, AU - Wrzesień-Kuś,Agata, AU - ,, Y1 - 2007/12/11/ PY - 2007/12/14/pubmed PY - 2008/2/6/medline PY - 2007/12/14/entrez SP - 115 EP - 26 JF - European journal of haematology JO - Eur J Haematol VL - 80 IS - 2 N2 - OBJECTIVES: Patients with primary refractory AML and with early relapses have unfavorable prognoses and require innovative therapeutic approaches. Purine analogs fludarabine (FA) and cladribine (2-CdA) increase cytotoxic effect of Ara-C in leukemic blasts and inhibit DNA repair mechanisms; therefore its association with Ara-C and mitoxantrone (MIT) results in a synergistic effect. In the current report, we present the final results of multi-center phase II study evaluating the efficacy and toxicity of CLAG-M salvage regimen in poor risk refractory/relapsed AML patients. METHODS: The induction chemotherapy consisted of 2-CdA 5 mg/m2, Ara-C 2 g/m2, MIT 10 mg/m2, and granulocyte-colony stimulating factor. In the case of PR, a second CLAG-M was administered. Patients in CR received consolidation courses based on high doses of Ara-C and MIT with or without 2-CdA. RESULTS: One hundred and eighteen patients from 11 centers were registered; 78 primary resistant and 40 relapsed. Sixty-six patients (58%) achieved CR after one or two courses of CLAG-M, 49 (35%) were refractory, and 8 (7%) died early. WBC >10 g/L and age >34 yr were factors associated with increased risk of treatment failure. Hematological toxicity was the most prominent toxicity of this regimen. The probability of OS at 4 yr was 14% (95% CI 4-23%). OS was influenced by age, WBC >10 g/L and poor karyotype in both univariate and multivariate analyses. The probability of 4 yr DFS was 30% for all 66 patients in CR (95% CI 11-49%). Poor karyotype was the only factor associated with decreased probability of DFS. CONCLUSIONS: We conclude that CLAG-M is a well-tolerated and highly effective salvage regimen in poor risk refractory/relapsed AML. SN - 1600-0609 UR - https://www.unboundmedicine.com/medline/citation/18076637/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_ L2 - https://doi.org/10.1111/j.1600-0609.2007.00988.x DB - PRIME DP - Unbound Medicine ER -