Treatment of chronic myelogenous leukemia with nucleoside analogs deoxycoformycin and fludarabine

Cortes, Jorge; Kantarjian, Hagop M.; Talpaz, Moshe; O’Brien, Susan; Beran, Miloslav; Koller, Charles; Keating, Michael J.

doi:10.1038/sj.leu.2400677

Cited by 9 publications

(5 citation statements)

References 3 publications

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“…Regimens containing highdose Ara-C or Ara-C alone demonstrated an objective response rate of 25±35% (16±19, 43). The results reported in the literature concerning treatment of accelerated or blastic phase CML with nucleoside analogues are disappointing; there is a discrepancy between in vivo and in vitro studies (33,44). In our previous experience association of¯udarabine with Ara-C and G-CSF has demonstrated to be effective and well tolerated in refractory and relapsed acute myeloid (AML) and lymphoblastic leukemia (ALL) (24,25); on the basis of these results we decided to treat another set of high-risk patients with the same combination therapy.…”

Section: Discussionmentioning

confidence: 99%

Treatment of chronic myeloid leukemia in the blastic phase with fludarabine, cytosine arabinoside and G‐CSF (FLAG)

Tedeschi

Montillo

Ferrara

et al. 2000

European J of Haematology

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The present study was undertaken to evaluate the efficacy of the association of fludarabine plus Ara-C and G-CSF (FLAG) in the treatment of 15 patients with chronic myeloid leukemia in the blastic phase (CML-BP). Patients achieving a partial remission (PR) after the first course received a second FLAG. Complete remission (CR) was consolidated with another FLAG regimen. Patients were then submitted to an individualized program of treatment depending on age and suitable donors. Overall seven patients achieved CR (46.7%), three (20%) showed a primary resistant disease, while three (20%) died during remission induction therapy. Five of them received a consolidation therapy; in two cases further treatment was not performed because of severe toxicity. Median overall survival and disease-free survival were of 7.5 and 4.5 months, respectively. FLAG proved to be effective in achieving a high CR rate in patients with CML-BP. Median overall survival and disease-free survival were not significantly improved compared to previous studies. Nevertheless, the treatment was well tolerated even in a group of heavily pretreated patients, allowing further transplantation opportunities in younger patients.

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Section: Discussionmentioning

confidence: 99%

Treatment of chronic myeloid leukemia in the blastic phase with fludarabine, cytosine arabinoside and G‐CSF (FLAG)

Tedeschi

Montillo

Ferrara

et al. 2000

European J of Haematology

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“…28,29 Blast crisis CML is even more chemotherapy insensitive. [30][31][32][33] The reason is possibly due to some unknown biology of the CML stem/progenitor cells. In general, cure can only be achieved after allogeneic BM transplantation, but age and donor availability restrict this therapy to approximately 25% of patients.…”

Section: Discussionmentioning

confidence: 99%

Identification of human chronic myelogenous leukemia progenitor cells with hemangioblastic characteristics

Fang

Zheng

Liao

et al. 2005

Blood

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“…2-CdA produced 83% of hematological responses, but no cytogenetic response in 12 patients with chronic or accelerated phase of CML was observed [258]. In some patients with chronic or accelerated phase of CML, refractory to INFα, DCF induced transient decrease in the initial white blood count [18].…”

Section: Chronic Myeloproliferative Disordersmentioning

confidence: 97%

“…In contrast, FA seems to be less active in this disease. PNAs are also active in acute myeloid leukemia (AML) and chronic myelogenous leukemia (CML), especially in the blast phase [14][15][16][17][18][19]. In addition, FA was recently reported as an effective drug in patients with Richter's syndrome (RS) and refractory lymphoproliferative disorders [8,15].…”

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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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Treatment of chronic myelogenous leukemia with nucleoside analogs deoxycoformycin and fludarabine

Abstract: In vitro studies suggest that nucleoside analogs have an antipatients with CML in chronic (n = 11) or accelerated (n = 1) leukemic effect against chronic myelogenous leukemia (CML).phase, although no cytogenetic responses were observed. In according to institutional guidelines.

Cited by 9 publications

References 3 publications

Treatment of chronic myeloid leukemia in the blastic phase with fludarabine, cytosine arabinoside and G‐CSF (FLAG)

Treatment of chronic myeloid leukemia in the blastic phase with fludarabine, cytosine arabinoside and G‐CSF (FLAG)

Identification of human chronic myelogenous leukemia progenitor cells with hemangioblastic characteristics

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

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