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.
OBJECTIVE
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.
Wierzbowska
Agnieszka
A
Department of Hematology, Medical University, Lodz, Poland.
Robak
Tadeusz
T
Pluta
Agnieszka
A
Wawrzyniak
Ewa
E
Cebula
Barbara
B
Hołowiecki
Jerzy
J
Kyrcz-Krzemień
Sławomira
S
Grosicki
Sebastian
S
Giebel
Sebastian
S
Skotnicki
Aleksander B
AB
Piatkowska-Jakubas
Beata
B
Kuliczkowski
Kazimierz
K
Kiełbiński
Marek
M
Zawilska
Krystyna
K
Kłoczko
Janusz
J
Wrzesień-Kuś
Agata
A
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017338:Cladribine / Q000008:administration & dosage*; D003561:Cytarabine / Q000008:administration & dosage*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage*; D015999:Multivariate Analysis; D016017:Odds Ratio; D011044:Poland; D012008:Recurrence; D016879:Salvage Therapy / Q000379:methods*; D033581:Stem Cell Transplantation; D016896:Treatment Outcome
D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D017338:Cladribine; D008942:Mitoxantrone