Cladribine Research Articles

Oral cladribine was more effective than placebo for relapsing–remitting multiple sclerosis

Source Citation Giovannoni G, Comi G, Cook S, et al. A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis. N Engl J Med. 2010;362:416-26. 20089960

Significant efficacy of 2-CdA with or without rituximab in the treatment of splenic marginal zone lymphoma (SMZL).Ann Oncol. 2010 Apr;21(4):851-4. Epub 2009 Oct 13.

Significant efficacy of 2-CdA with or without rituximab in the treatment of splenic marginal zone lymphoma (SMZL).Ann Oncol. 2010 Apr;21(4):851-4. Epub 2009 Oct 13.

Cladribine, cyclophosphamide, mitoxantrone effective for CLL

Cladribine, cyclophosphamide, mitoxantrone effective for CLL

Progress in the treatment of non-Hodgkin's lymphomas

The authors analyze the progress achieved in the treatment of low-grade as well as of high-grade non-Hodgkin's lymphomas. The challenging task in the treatment of low-grade or indolent lymphomas still is to decide whether watchful waiting is sufficient or whether chemotherapy is necessary and how aggressive this treatment should be. Among the new chemotherapeutic agents the role of purine analogues should be emphasized, fludarabin is especially important in the treatment of chronic lymphocytic leukemia and follicular lymphoma, while pentostatin and cladribine have revolutionized the treatment of hairy cell leukemia. Treatment with monoclonal antibodies, radioimmunoconjugates as well as autologous or allogeneic stem cell transplantation are potential new therapeutic options in the treatment of low-grade non-Hodgkin's lymphomas. In the case of aggressive non-Hodgkin's lymphomas risk-adapted strategies help the choice between standard or more intensive treatment options. In patients with relapsed high-grade lymphomas stem cell transplantation is indicated. In patients with marginal zone lymphoma the combination of hyperCVAD protocol + stem cell transplantation greatly improves prognosis.

Five Years Follow-Up after 2-Chloro Deoxyadenosine Treatment in Thirty Patients with Hairy Cell Leukemia: Evaluation of Minimal Residual Disease and CD4+ Lymphocytopenia after Treatment

Between March 1992 and August 1993, thirty patients with hairy cell leukemia (HCL) were treated in a single institution with 2-chlorodeoxyadenosine (2-CdA) for one course (N=27) or two courses at six month intervall (N=3). Sixteen patients were previously untreated, 14 had been treated with alpha interferon (alpha IFN) (N=5), alpha IFN and splenectomy (N=8) and splenectomy, alpha IFN and Deoxycoformycin (N=1). Overall results in 29 evaluable patients were: 25 CR (86%), 3 PR (10%), one failure. The three PR patients relapsed after 18, 24 months and five years. Two were retreated successfully. Two CR patients relapsed after five years. Careful clinical survey, sequential bone marrow biopsies (BMB) with DBA44 immunostaining for assessment of response and detection of residual disease and serially evaluation of lymphocyte subsets counts were performed. Results of bone marrow biopsies study show 1) a progressive reduction in hairy cell infiltration during the first six months after therapy and not after that indicating that the best moment for the evaluation of response may be the sixth month, 2) the persistence of a very small number of DBA44 + cells (80% of BMB). There was a correlation between the presence of > 5% DBA44 positive cells on 6th month BMB and relapse.60% had an absolute CD4+ lymphocyte count less than 0.2 109/1 at least on one examination after treatment. CD4+ lymphocyte level persisted less than baseline level in 8/18 patients tested after four and/or five years. Lymphopenia was less marked in splenectomized patients: 7/7 splenectomized patients tested have recovered a CD4+ lymphocyte count equal to pretherapy level compared to 3/11 non splenectomized patients (p: 0.004). Three opportunistic infections were observed early (first 6 months) after 2CdA therapy: Pneumocystis pneumonia, retinitis due to toxoplasma in the patient who failed and legionella pneumonia in a patient retreated after relapse. Two patients developed a second carcinoma 6 and 12 months after therapy. Five patients died, three from a cause unrelated to HCL, one from HCL and one from infection while in second CR. At five years, overall survival is 83% and progression free survival is 66%. Our study shows 1) long-lasting response in the majority of patients after 2-CdA, 2) a correlation between persistent minimal residual disease detected with DBA44 immunostaining and occurence of relapse and 3) a profound and persistent CD4+ lymphopenia more marked in non splenectomized patients.

Purine nucleoside analogues: fludarabine, pentostatin, and cladribine

Purpose. The primary objective of this article is to continue the discussion of the pharmacology, phar macokinetics, clinical use, and adverse effects of the currently approved adenosine analogues, focusing on pentostatin. This is part two of a three part series. Data Sources. We reviewed the literature through a MEDLINE search from 1986 to 1996. Rele vant articles cited in the literature obtained by MED LINE searching also were considered. We searched the following terms: fludarabine, cladribine, pentosta tin, apoptosis, and adenosine analogues. The search was restricted to the English language. Data Extraction. We have reviewed the current literature in regard to the chemistry, mechanisms of action and pharmacology, pharmacokinetics, clinical use, adverse effects, drug interactions, indications, formulation, dosage, administration, and pharmaceu tical issues of the currently approved adenosoine analogues, focusing on pentostatin. Data Synthesis. The adenosine analogues are structurally similar agents used in the management of hematological malignancies. Pentostatin and cladrib ine are both active agents in the treatment of hairy cell leukemia. There are no comparative clinical trials between the agents, and we have provided compari sons based on pharmacology, clinical experience, adverse effects, and cost.

Cutaneous reactions after treatment with 2-chlorodeoxyadenosine.

2-chlorodeoxyadenosine (2-CdA) is a new purine analogue which has shown great efficacy in the treatment of hairy cell leukemia. Only one case of cutaneous reaction after this treatment has previously been reported. The data from 33 patients treated with 2-CdA were retrospectively reviewed. Seven of these (21%) developed a disseminated eruption during the month following 2-CdA. One had toxic epidermal necrolysis. A reaction to the associated antibiotic therapy seemed "likely" or "very likely" in 5 out of the 7 cases. The incidence of adverse drug reactions may be increased after 2-CdA, and the role of CD4+ lymphocytopenia in these reactions is discussed.

2-Chlorodeoxyadenosine as treatment of severe acute graft-versus-host disease [letter

2-Chlorodeoxyadenosine as treatment of severe acute graft-versus-host disease [letter

Cladribine's usefulness in CML may be limited

Cladribine's usefulness in CML may be limited

2-Chlorodeoxyadenosine: a new nucleoside agent effective in the treatment of lymphoid malignancies.

(1993). 2-Chlorodeoxyadenosine: A New Nucleoside Agent Effective in the Treatment of Lymphoid Malignancies. Leukemia & Lymphoma: Vol. 10, No. sup1, pp. 43-49.

New antimetabolites in the treatment of human malignancies.

Several new antimetabolites have been evaluated in clinical trials in recent years. Those with the most promising activity include the structurally related purine analogs fludarabine, 2-chlorodeoxyadenosine, and 2'-deoxycoformycin. These compounds have shown impressive activity against a broad spectrum of indolent lymphoproliferative disorders, including hairy-cell leukemia, chronic lymphocytic leukemia, and low-grade non-Hodgkin's lymphomas. They may also be useful in the treatment of acute leukemias. In contrast, they lack activity against common solid tumors. They have been generally well tolerated in large clinical trials; however, each of them is myelosuppressive and immunosuppressive. It is unlikely that any one of these drugs, when used as a single agent, will provide optimal therapy for any disease other than, possibly, hairy-cell leukemia. Combinations with other cytotoxic agents and biologics are in development, and perhaps they will lead to more effective regimens in the future.