Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine via the Group C protocol mechanism of the National Cancer Institute: a report of 979 patients.

Cheson, Bruce D.; Sorensen, John M.; Vena, Don; Montello, Michael; Barrett, Jane; Damasio, E; Tallman, Martin S.; Annino, Luciana; Connors, J M; Coiffier, B; Lauria, F

doi:10.1200/jco.1998.16.9.3007

Cited by 144 publications

(102 citation statements)

References 24 publications

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“…[6][7][8][9][10] In general, 2CdA is tolerated in indolent lymphoproliferative disease although a secondary malignancy requires additional follow-up evaluation. 2CdA is considered to be the best agent for the treatment of hairy cell leukemia.…”

Section: Discussionmentioning

confidence: 99%

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2-Chloro-2′-deoxyadenosine induces apoptosis through the Fas/Fas ligand pathway in human leukemia cell line MOLT-4

et al. 2000

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The mechanism of apoptosis induced by 2-chloro-2Ј-deoxyadenosine (2CdA) in human leukemia cell line MOLT-4 was investigated. 2CdA induced increases of 3Ј-OH ends of genomic DNA, ladder-like DNA fragmentation and phosphatidylserine translocation to the outer membrane, which are apoptotic characteristics. These apoptotic phenomena induced by 2CdA were inhibited by cycloheximide (CHX; a protein synthesis inhibitor), deoxycytidine (dC; a substrate of deoxycytidine kinase), acetyl Ile-Glu-Thr-Asp aldehyde (Ac-IETD-CHO; a caspase-8 inhibitor) and acetyl Asp-Glu-Val-Asp aldehyde (Ac-DEVD-CHO; a caspase-3 inhibitor). The protein synthesisdependent expression of Fas and Fas ligand (Fas-L) was detected by treatment with 2CdA. The proteolytic processing of procaspases-8 and -3 to produce active fragments, caspases-8 (p18) and -3 (p17), respectively, was observed after treatment with 2CdA, and suppressed by cycloheximide. Increases in the activities of caspases-8 and -3 were observed after 2CdA treatment. Their activation was also dependent on protein synthesis. These results indicated that 2CdA-induced apoptosis was triggered by phosphorylation of 2CdA followed by the protein synthesis-dependent expression of Fas and Fas-L and activation of caspases-8 and -3. Leukemia (2000) 14, 299-306.

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Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5][6][7][8][9][10][11] However, the mechanism of 2CdA-induced cytotoxity remains unclear. In our previous study, treatment with 2CdA was found to induce DNA double-strand breaks, inhibition of DNA repair and cell death in Chinese hamster V79 cells.…”

Section: Introductionmentioning

confidence: 99%

2-Chloro-2′-deoxyadenosine induces apoptosis through the Fas/Fas ligand pathway in human leukemia cell line MOLT-4

et al. 2000

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“…23 It has been previously reported that DCF, as other purines analogs, induces a severe and long-lasting immunosuppression state by decreasing CD4 + lymphocytes and this may have increased the incidence of secondary malignancies and herpes zoster infection. 24 In the present data, 16 patients had herpes infection, and 18 developed a second malignancy (7.5%), a figure slightly lower than the 10% rate reported by Ribeiro et al 11 and Finn et al 17 Recently the Italian group reported data on 1022 patients treated by splenectomy and/or IFN, and showed that the cumulative risk of development of a second cancer was 5%, 10%, and 14% at 5, 10, and 15 years, respectively, but not associated with a significant increased risk of additional second malignancies. 25 Kurzrock et al 20 demonstrated an increase in the number of second cancers, however it was not associated with therapy.…”

Section: Figurementioning

confidence: 99%

Long-term outcome with pentostatin treatment in hairy cell leukemia patients. A French retrospective study of 238 patients

Maloisel¹,

et al. 2003

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With the introduction of new drugs such as alpha-interferon (IFN) and purine analogs, the management of hairy cell leukemia (HCL) patients has changed. However, deoxycoformycin (DCF) produced higher complete remission rates than IFN. The current study was undertaken to provide long-term data on duration of overall survival (OS) and disease-free survival (DFS) and incidence of subsequent malignancies. We retrospectively analyzed the data of patients treated with DCF (4 mg/m 2 /day, every 2 weeks) from 39 French centers. In 84 of 238 included patients, DCF was the first-line therapy. Pretreatment variables influencing the achievement of complete remission, DFS, and OS were identified by multivariate analysis. Two hundred and thirty-eight patients received a median of nine cycles (range, 1-19 cycles). A complete remission was obtained in 182 of 230 evaluable patients (79%) and a partial response was obtained in 38 patients, for an overall response rate of 95.6%. In the multivariate analysis hemoglobin level less than 100 g/l and leukocytes less than 2 × 10 9 /l were parameters adversely influencing complete remission achievement. With a median followup of 63.5 months (range, 0.39-138.4 months), disease recurrence was observed in 34 of 220 responding patients (15%). The estimated 5-years and 10-years DFS was 88.1% and 68.8%, respectively. Hemoglobin level less than 100 g/l and leukocytes less than 2 × 10 9 /l were the pre-treatment variables associated with a shorter DFS. The estimated 5-year and 10-year OS were 89.4% and 88.7%, respectively. Hemoglobin level less than 100 g/l, leukocytes less than 2 × 10 9 /l, and adenopathy were significant factors of reduced survival. Hematologic toxicity was the main side-effect, followed by infection and emesis. During the period of follow-up, 18 patients developed second cancer, but the standardized incidence ratio was 0.95. Pentostatin is a highly effective regimen for hairy cell leukemia that produces durable complete responses. Toxicity of DCF is acceptable. Subsequent malignancies do not appear to be increased with pentostatin treatment.

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“…1 CdA has been proven to be highly effective in the treatment of several indolent lymphoid malignancies, including HCL. [2][3][4][5][6] DCF is the first treatment modality capable of inducing complete and long-lasting remission in patients with HCL. [7][8][9][10][11] These two purine analogs produce faster responses and higher response rates than interferon-␣.…”

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confidence: 99%

Deoxycoformycin in the treatment of patients with hairy cell leukemia

Rafel

Cervantes

Beltrán

et al. 2000

Cancer

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Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine via the Group C protocol mechanism of the National Cancer Institute: a report of 979 patients.

Cited by 144 publications

References 24 publications

2-Chloro-2′-deoxyadenosine induces apoptosis through the Fas/Fas ligand pathway in human leukemia cell line MOLT-4

2-Chloro-2′-deoxyadenosine induces apoptosis through the Fas/Fas ligand pathway in human leukemia cell line MOLT-4

Long-term outcome with pentostatin treatment in hairy cell leukemia patients. A French retrospective study of 238 patients

Deoxycoformycin in the treatment of patients with hairy cell leukemia

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