2-Chlorodeoxyadenosine (Cladribine) in the treatment of patients with chronic lymphocytic leukemia 55 years old and younger

Abstract

The aim of the study was to determine the effectiveness of 2-chlorodeoxyadenosine (2-CdA) administered in 2-h i.v. infusions in the treatment of B cell chronic lymphocytic leukemia (B-CLL) in patients 55 years old and younger. One hundred and thirteen patients received three to 10 courses of 2-CdA administered at a dose of 0.12 mg/kg daily for 5 consecutive days. Sixty-seven patients were previously treated with chlorambucil and prednisone, COP and some of them also with CHOP, and 46 were untreated. Complete remission (CR) was achieved in 21 (18.6%) (19 in untreated and two in previously treated) patients and partial response (PR) in 38 (33.6%) (23 and 15, respectively) giving an overall response rate in 52.2%. The differences in CR and overall response rate between previously treated and untreated patients were statistically significant (P = 0.001). Surface immunophenotyping by flow cytometry using dual-color staining on the peripheral blood and/or bone marrow was performed in 38 patients who responded to 2-CdA therapy. Residual disease had been demonstrated in five out of 17 (29.4%) patients who were in CR and in all 21 investigated PR patients. 2-CdA-induced thrombocytopenia occurred in 24 (35.8%) of previously treated and in 13 (28.3%) previously untreated patients (P = NS). Neutropenia was observed in eight (11.9%) and in five (10.9%) patients, respectively (P = NS). Severe infections, including pneumonia and sepsis, occurred more often in previously treated (44.8%) than untreated patients (26.1%) (P Ͻ 0.05). Twenty-seven (23.9%) patients died, 11 because of infections, five because of drug-related thrombocytopenia and hemorrhage, one because of second malignancy and eight because of disease progression. In conclusion, our results indicate that 2-CdA is an effective agent in younger patients with B-CLL, especially used as a first line therapy.

2-Chloro-2′-deoxyadenosine inhibits DNA repair synthesis and potentiates UVC cytotoxicity in chronic lymphocytic leukemia B lymphocytes

“…6,8,12,13 2-Chloro-2′-deoxyadenosine (CdA) is an adenosine deaminase-resistant analogue of deoxyadenosine, with major anti- tumor activity in indolent lymphoid malignancies, including B-CLL. 14,15 Intracellularly, CdA is phosphorylated by deoxycytidine kinase (dCK) into its 5′-monophosphate, which is thereafter converted into its 5′-diphosphate and eventually into 2-chloro-2′-deoxyadenosine-5′-triphosphate (CdATP), the active form of CdA. Among other effects, CdATP has been shown to interfere with DNA synthesis through inhibition of ribonucleotide reductase (RR) and DNA polymerase ␤.…”

Cladribine combined with cyclophosphamide and mitoxantrone as front-line therapy in chronic lymphocytic leukemia

“…A similar evaluation was performed in the CLL patients treated with 2-CdA in monotherapy and MRD was diagnosed in five out of 17 (29.4%) patients with CR. 3 These data indicate that the combined therapy with CMC does not appear to reduce the incidence of MRD more than 2-CdA in monotherapy.…”

“…5,8 On the other hand, both FAMP and 2-CdA administered as single agents can induce immunophenotypic and molecular remission, which is especially important in younger patients in order to qualify these patients for bone marrow transplantation and offer the possibility of recovery. 3,9 Combined use of purine analogs with other cytotoxic agents may increase the CR rate and, possibly, suppress minimal residual disease and prolong survival. Some preclinical studies and early clinical reports may support such a hypothesis.…”

Alkylating agents and nucleoside analogues in the treatment of B cell chronic lymphocytic leukemia

“…91,92 Recent clinical observations have demonstrated that the combinations of FAMP or 2-CdA with mitoxantrone, doxorubicin or epirubicin are effective in CLL. 56,[93][94][95][96] Combined treatment with NA, mitoxantrone and CY has been undertaken both in previously treated and untreated patients with B-CLL. 93,97,98 However, the efficacy of these regimens seem to be similar to that observed after treatment with FAMP or 2-CdA alone.…”