2-Chlorodeoxyadenosine for Patients with B-Cell Chronic Lymphocytic Leukemia Resistant to Fludarabine

Delannoy, André; Hanique, G.; Ferrant, A

doi:10.1056/nejm199303183281116

Cited by 45 publications

(1 citation statement)

References 5 publications

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“…One small report suggested that cladribine (2-CDA) was effective in FAMP refractory patients but this data was disputed by larger series (Juliusson et al 1992; Delannoy et al 1993; O’Brien et al 1994). …”

Section: Introductionmentioning

confidence: 99%

Alemtuzumab in the treatment of fludarabine refractory B-cell chronic lymphocytic leukemia (CLL)

Montillo

Ricci²,

Miqueleiz³

et al. 2008

BTT

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The introduction of immunotherapeutic agents has provided renewed hope for Chronic lymphocytic leukemia fludarabine-refractory patients. Several clinical trials have shown that alemtuzumab is a more effective option compared to combination chemotherapy for treatment of patients who have relapsed or who are refractory to fludarabine, including those with poor prognostic factors. Although there are significant potential toxicities associated with alemtuzumab, such as infusional reactions and the risk of cytomegalovirus (CMV) reactivation, most are manageable. Pre-treatment anti-pyretics and anti-histamines are recommended to prevent or mitigate the acute infusional reactions associated with intravenous infusion. Recent use of alemtuzumab via the subcutaneous route has been shown to be well tolerated and has yielded similar response rates to the infusional method of administration. Prophylaxis with thrimethoprim/sulphamethoxazole (TMP/SMZ) as well as valacyclovir or a similar anti-viral can prevent many of the opportunistic infections seen in early trials. Reactivation of CMV infection can be effectively managed with monitoring and early treatment. Chemo-immunotherapy combination with alemtuzumab has been tested and demonstrated unprecedented clinical results in relapsed and refractory patients. The use of this agent earlier in the algorithm of patients with these characteristics should be considered. Future areas of research will include the use of alemtuzumab in combination with other monoclonal antibodies and other targeted therapies.

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Section: Introductionmentioning

confidence: 99%

Alemtuzumab in the treatment of fludarabine refractory B-cell chronic lymphocytic leukemia (CLL)

Montillo

Ricci²,

Miqueleiz³

et al. 2008

BTT

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Apoptosis induction with three nucleoside analogs on freshly isolated B‐chronic lymphocytic leukemia cells

et al. 1994

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The cytotoxic effects and the induction of programmed cell death (apoptosis) by Fludarabine (FLU), 2-chlorodeoxyadenosine (2-CdA), and deoxycoformycin (DCF) with/without alpha-interferon (alpha-IFN) were evaluated in vitro against freshly isolated B-chronic lymphocytic leukemia (B-CLL) cells. Cytotoxicity was evaluated according to the soluble tetrazolium/formazan assay. Regarding the cytotoxicity, FLU, 2-CdA, and DCF showed a mean antitumor activity of 45% +/- 3.39 (mean +/- S.D.), 55% +/- 4.72, and 20% +/- 3.16, respectively. alpha-IFN alone showed a mean cytotoxic activity of 10% +/- 2.72. The cytotoxicity of these purine analogues in combination with alpha-IFN was 52% +/- 2.97, 75% +/- 3.41, and 26% +/- 7.09, respectively. We observed a statistically significant increase of cytotoxicity compared to controls in FLU alone (P < 0.05), 2-CdA (P < 0.05), and their combination with alpha-IFN (P < 0.05). Apoptosis was evaluated by electrophoresis gel of DNA oligonucleosomal fragments and by a cytofluorimetric method. Only FLU and 2-CdA activated the apoptosis and DCF showed a minor apoptotic pathway amount. These apoptosis data were confirmed by both gel electrophoresis of DNA and by propidium iodide cytofluorimetric method. FLU and 2-CdA show activity in B-CLL cells by direct cytotoxic action and the induction of cell death by apoptosis; in the future, it would be interesting to utilize these in vitro assays in monitoring chemosensitivity and predicting response for the clinical use.

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Phase II study of cladribine and cyclophosphamide in patients with chronic lymphocytic leukemia and prolymphocytic leukemia

Montillo

Tedeschi

O’Brien

et al. 2002

Cancer

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BACKGROUND One of the mechanisms of action of cladribine is the inhibition of DNA repair of damage caused by radiation, alkylating agents, or other drugs. To determine its antitumor activity in combination with cyclophosphamide, we initiated a Phase II trial of the two agents in patients with advanced chronic lymphocytic leukemia (CLL) or prolymphocytic leukemia (PLL). METHODS Twenty‐nine patients with refractory or recurrent CLL or PLL received cladribine 4 mg/m2/day and cyclophosphamide 350 mg/m2/day (both administered intravenously) for 3 days every 4 weeks. RESULTS Eleven patients (38%), nine with CLL and two with PLL, had a response. The median duration of response was 12 months. Severe extrahematologic toxicity (National Cancer Institute Grade 3–4) occurred in two patients, consisting of skin rash in one patient and progressive multifocal leukoencephalopathy in the other. The most common form of hematologic toxicity was severe neutropenia, which developed after 25% of the 84 courses was administered. Severe thrombocytopenia and anemia developed after 12% and 7% of the courses, respectively, and five episodes of anemia were immunomediated. In addition, three major infections resulted in the death of one patient. CONCLUSIONS Although inferior to the combination fludarabine plus cyclophosphamide, this regimen showed interesting activity in patients with advanced CLL or PLL. Myelosuppression was the major dose‐limiting toxic effect. Cancer 2003;97:114–20. © 2003 American Cancer Society. DOI 10.1002/cncr.11000

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2-Chlorodeoxyadenosine for Patients with B-Cell Chronic Lymphocytic Leukemia Resistant to Fludarabine

Cited by 45 publications

References 5 publications

Alemtuzumab in the treatment of fludarabine refractory B-cell chronic lymphocytic leukemia (CLL)

Alemtuzumab in the treatment of fludarabine refractory B-cell chronic lymphocytic leukemia (CLL)

Apoptosis induction with three nucleoside analogs on freshly isolated B‐chronic lymphocytic leukemia cells

Phase II study of cladribine and cyclophosphamide in patients with chronic lymphocytic leukemia and prolymphocytic leukemia

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