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)

Wrzesień‐Kuś, Agata; Robak, Tadeusz; Lech‐Marańda, Ewa; Wierzbowska, Agnieszka; Dmoszyńska, Anna; Kowal, Małgorzata; Hołowiecki, Jerzy; Kyrcz‐Krzemień, Sławomira; Grosicki, Sebastian; Maj, Stanisław; Hellmann, Andrzej; Skotnicki, Aleksander B.; Jędrzejczak, Wiesław Wiktor; Kuliczkowski, Kazimierz

doi:10.1034/j.1600-0609.2003.00122.x

Cited by 52 publications

(39 citation statements)

References 26 publications

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“…As alternative reinduction chemotherapy, CLAG [14,15] and CLAG-M [16] were respectively used in Studies 1 and 2. In the former, patients with intermediate or high cytogenetic risk and those patients requiring two induction treatments to achieve CR were qualified for allo-HSCT.…”

Section: Methodsmentioning

confidence: 99%

Assessing the efficacy of allogeneic hematopoietic stem cells transplantation (allo‐HSCT) by analyzing survival end points in defined groups of acute myeloid leukemia patients: A retrospective, multicenter Polish Adult Leukemia Group study

et al. 2015

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The importance of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for survival outcomes in patients with acute myeloid leukemia (AML) currently remains unclear. The study aimed to compare measures of clinical treatment for patients with AML in CR1 (the first complete remission) with or without being subjected to allo-HSCT. These consisted of leukemia-free survival (LFS), overall survival (OS), cumulative incidence of relapse (CIR), and non-relapse mortality disease (NRM). Subjects were 622 patients, median age of 44, forming part of the prospective, randomized, and multicenter clinical Polish Adult Leukemia Group trials during 1999-2008. The Mantel-Byar approach was used to assess allo-HSCT on survival endpoints, accounting for a changing transplant status. Undergoing allo-HSCT significantly improved the LFS and OS for the entire group of patients with AML in CR1, along with the DAC induction subgroup and for the group with unfavorable cytogenetics aged 41-60. The CIR demonstrated that allo-HSCT reduced the risk of relapse for patients with AML in CR1 and those with an unfavorable cytogenetic risk. In addition, the NRM analysis showed that allo-HSCT significantly reduced the risk of death unrelated to relapse for the entire group of AML patients in CR1 and aged 41-60. The allo-HSCT treatment particularly benefitted survival for the AML in CR1 group having an unfavorable cytogenetic prognosis.

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Section: Methodsmentioning

confidence: 99%

Assessing the efficacy of allogeneic hematopoietic stem cells transplantation (allo‐HSCT) by analyzing survival end points in defined groups of acute myeloid leukemia patients: A retrospective, multicenter Polish Adult Leukemia Group study

et al. 2015

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“…The results obtained in adults were more encouraging. In our study 2-CdA with high dose Ara-C and G-CSF (CLAG regimen) was used in refractory or relapsed AML patients, showing 50% CR rate [253]. High activity of regimen consisting of 2-CdA, Ara-C and IDA in previously untreated, elderly patients has been recently reported [254].…”

Section: Acute Leukemiasmentioning

confidence: 94%

“…2-CdA-based combination treatment was also introduced in AML patients [252][253][254][255]. The efficacy of the combination of 2-CdA and Ara-C was assessed in relapsed or refractory childhood AML, with disappointing results (no CR, 1/8 PR) [252].…”

Section: Acute Leukemiasmentioning

confidence: 99%

Purine Nucleoside Analogues for the Treatment of Hematological Malignancies: Pharmacology and Clinical Applications

Robak

Korycka²,

Kasznicki

et al. 2005

CCDT

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The purine nucleoside analogues (PNAs), fludarabine (FA), 2-CdA (2-chlorodeoxyadenosine, 2-CdA) and pentostatin (2'-deoxycoformycin, DCF) represent a group of cytotoxic agents with high activity in lymphoid and myeloid malignancies. PNAs share similar chemical structure and mechanism of action. Several mechanisms could be responsible for their cytotoxicity both in proliferating and quiescent cells, such as inhibition of DNA synthesis, inhibition of DNA repair and accumulation of DNA strand breaks. Induction of apoptosis through the mitochondrial pathway, direct binding to apoptosome or modulation of p53 expression all lead to apoptosis, which is the main end-point of PNA action. However, individual PNAs exhibit significant differences, especially in their interaction with enzymes involved in adenosine and deoxyadenosine metabolism. Synergistic interactions between PNAs and other cytotoxic agents (alkylating agents, anthracycline antitumor antibiotics, cytarabine, monoclonal antibodies) have been demonstrated in both preclinical and clinical studies. PNAs are highly effective in chronic lymphoid leukemias and low grade B- and T-cell non-Hodgkin's lymphomas, including Waldenström's macroglobulinemia. DCF and 2-CdA are currently the drugs of choice in hairy cell leukemia. Moreover, clinical studies have confirmed the efficacy of PNAs alone or in combination protocols in the treatment of acute myeloid leukemia and myelodysplastic syndromes. Finally, PNAs, especially FA, play an important role in non-myeloablative conditioning regimens for allogenic stem cell transplantation in high-risk patients. The toxicity profiles of PNAs are similar for all agents and consist mainly of dose-limiting myelotoxicity and prolonged immunosuppression. Three other compounds: clofarabine, nelarabine and immucillin-H are currently being evaluated clinically.

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“…The PALG has demonstrated that CLAG is an effective therapy, achieving a CR rate of 50% in R/R AML patients [17]. Walker et al [18] conducted a study including 15 relapsed AML patients treated by CLAG, and they obtained a CR of 43.8%.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Efficacy and Prognostic Factors of CLAG Treatment in Chinese Patients with Refractory or Relapsed Acute Myeloid Leukemia

Wang

Tian

et al. 2018

Acta Haematol

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Background/Aims: The aim of this work was to investigate the efficacy and predictive factors of CLAG treatment in refractory or relapsed (R/R) acute myeloid leukemia (AML) patients. Methods: Sixty-seven R/R AML patients were enrolled in this prospective cohort study and treated by a CLAG regimen: 5 mg/m²/day cladribine (days 1–5), 2 g/m²/day cytarabine (days 1–5), and 300 μg/day filgrastim (days 0–5). The median follow-up duration was 10 months. Results: A total of 57 out of 67 patients were evaluable for remission after CLAG therapy, of whom 57.9% achieved a complete remission (CR) and the overall remission rate was 77.2%. The median overall survival (OS) was 10.0 months, with a 1-year OS of 40.3 ± 6.0% and 3-year OS of 16.7 ± 5.7%. CR at first induction after the initial diagnosis was associated with a favorable CR. Age above 60 years, high risk stratification, second or higher salvage therapy, and bone marrow (BM) blasts ≥42.1% were correlated with an unfavorable CR. Secondary disease, age ≥60 years, high risk stratification, and second or higher salvage therapy were associated with worse OS. Patients developed thrombocytopenia (41, 61%), febrile neutropenia (37, 55%), leukopenia (33, 49%), neutropenia (18, 27%), and anemia (9, 13%). Conclusion: CLAG was effective and well tolerated for R/R AML. BM blasts ≥42.1%, age ≥60 years, high risk stratification, and second or higher salvage therapy were independent factors for a poor prognosis.

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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)

Abstract: CLAG regimen has significant anti-leukemic activity and an acceptable toxicity in refractory AML. The addition of 2-CdA to the first-line induction treatment may worsen the results of salvage with CLAG. The high CR rate in patients with MDS preceding AML deserves further observation.

Cited by 52 publications

References 26 publications

Assessing the efficacy of allogeneic hematopoietic stem cells transplantation (allo‐HSCT) by analyzing survival end points in defined groups of acute myeloid leukemia patients: A retrospective, multicenter Polish Adult Leukemia Group study

Assessing the efficacy of allogeneic hematopoietic stem cells transplantation (allo‐HSCT) by analyzing survival end points in defined groups of acute myeloid leukemia patients: A retrospective, multicenter Polish Adult Leukemia Group study

Purine Nucleoside Analogues for the Treatment of Hematological Malignancies: Pharmacology and Clinical Applications

Analysis of Efficacy and Prognostic Factors of CLAG Treatment in Chinese Patients with Refractory or Relapsed Acute Myeloid Leukemia

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