pentostatin and 2-chloro-3--deoxyadenosine

Hairy cell leukemia represent 2% of all the leukemias. The etiology is unknown. The diagnosis is based on the peripheral blood examination, showing characteristic lymphoid B cells, with loose lacy chromatin and unconstant cytoplasmic projections. The abnormal lymphoid cells express CD19, CD20, CD22, CD79a, CD25 and CD103. The tumor cells are Sig + with clonal light chain restriction. The treatment is based on recombinant IFN: we discuss the interest and the risks of second malignancy related to the prescription of the purine analogues.

Topics: 2-Chloroadenosine; Antigens, CD; Antimetabolites, Antineoplastic; Antineoplastic Agents; B-Lymphocytes; Bone Marrow; Clinical Trials as Topic; Deoxyadenosines; Humans; Immunologic Factors; Interferon Type I; Leukemia, Hairy Cell; Neoplasm Proteins; Neoplasms, Second Primary; Neoplastic Stem Cells; Pentostatin; Receptors, Antigen, T-Cell, gamma-delta; Recombinant Proteins; Splenectomy; Vidarabine

Hairy cell leukemia (HCL) is a chronic B-cell malignancy, typically seen in middle-aged men, characterized by pancytopenia, splenomegaly, immunologic abnormalities, and morphologically typical neoplastic mononuclear cells in the blood, bone marrow, liver, spleen, and other tissues. Diagnosis is confirmed by demonstration of hairy cells in biopsy specimens from the bone marrow or spleen or in peripheral blood. The natural history of this lymphoproliferative disorder varies. Patients may die early during the initial phase of therapy; others may require no therapy; and for some, splenectomy alone, without further treatment, may suffice for many years. Recently, the nucleosides pentostatin (2'-deoxycoformycin) (DCF) and 2'-chlorodeoxyadenosine (2-CdA) have been shown to produce greater numbers of durable complete remissions with curative potential in patients with HCL. The treatment options, with emphasis on major therapeutic advances with alpha-interferon, DCF, and 2-CdA, are reviewed in this article.. Studies on HCL published from 1958 to 1992 were reviewed using the Cancerline and Medline retrieval systems and other bibliographies.. Management of HCL has changed in the last decade as a result of three new effective agents: alpha-interferon DCF, and 2-CdA. DCF has produced an overall response rate of 86% and a complete remission rate of 62%. 2-CdA has yielded an overall response rate of 95% and a complete remission rate of 82%. Alpha-interferon has given an overall response rate of 82% and a complete remission rate of 8%. Other agents with limited activities include chlorambucil, cyclophosphamide, cytarabine, vincristine, doxorubicin, and zorubicin hydrochloride. The effects of lithium carbonate, immunotherapy, splenic irradiation, androgens, and leukaphoresis are minimal and transient.. Modern management of HCL with 2-CdA and DCF is now potentially curative rather than palliative in some patients; however, the optimal therapeutic approach remains uncertain. Alpha-interferon has been approved by the Food and Drug Administration as the first-line drug therapy, followed by DCF in non-responding patients. 2-CdA remains an experimental therapy, but its higher response rate and ease of administration may make it the first-line treatment of choice. Additional research into the biology of HCL and further clinical trials are needed to determine the optimal treatment strategy for this disorder. Therefore, the best therapeutic approach at the current time is to include patients with HCL in ongoing clinical trials.

Topics: 2-Chloroadenosine; Deoxyadenosines; Forecasting; Granulocyte Colony-Stimulating Factor; Humans; Interferons; Leukemia, Hairy Cell; Male; Pentostatin; Splenectomy; Vidarabine

Not all patients with B-cell chronic lymphocytic leukemia require therapy. Patients with stable early stage disease do not need treatment, whereas those with progressive early stage disease or advanced stage disease do. The standard initial therapeutic regimen is orally administered chlorambucil and prednisone. The overall response rate to initial chemotherapy is approximately 80%; the median duration of response is 2 years. Conventional chemotherapy, however, does not provide long-term remission for patients in whom the disease becomes refractory to chlorambucil. For such patients, alternative treatment approaches including the use of purine nucleoside analogues or bone marrow transplantation may be considered. Fludarabine, 2-chlorodeoxyadenosine, and pentostatin are three analogues of the naturally occurring deoxypurine nucleoside, deoxyadenosine, and all have shown activity in chronic lymphocytic leukemia. Overall response rates of 57 to 79% have been reported with use of fludarabine. A dose-related toxic effect is myelosuppression. Experience with bone marrow transplantation is limited. The number of eligible patients with histocompatible sibling donors is low. The future role of allogeneic bone marrow transplantation in patients with B-cell chronic lymphocytic leukemia will depend on the ability to identify poor-risk groups and the long-term therapeutic efficacy of the purine nucleoside analogues or other new agents.

Topics: 2-Chloroadenosine; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Bone Marrow Transplantation; Chlorambucil; Deoxyadenosines; Dose-Response Relationship, Drug; Histocompatibility Testing; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Pentostatin; Prednisone; Prognosis; Survival Rate; Vidarabine

We describe the occurrence of myelodysplastic changes (hypogranular myeloid series and Pelger cells, dyserythropoiesis with ring sideroblasts) in five of 31 patients with chronic lymphoproliferative disorders after treatment with purine analogues. The bone marrows of 31 patients with chronic lymphoproliferative disorders before and after treatment with purine analogues were reviewed. The majority of patients had received extensive prior treatment, but none had dysplastic changes prior to treatment with purine analogues. We suggest that a purine analogue may have been responsible for dysplastic change and that further follow-up of this phenomenon is warranted.

Topics: 2-Chloroadenosine; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Deoxyadenosines; Female; Humans; Lymphoproliferative Disorders; Male; Myelodysplastic Syndromes; Pentostatin; Vidarabine

Topics: 2-Chloroadenosine; Antibodies, Monoclonal; Deoxyadenosines; Humans; Immunoconjugates; Immunotoxins; Leukemia, Hairy Cell; Lymphoma; Pentostatin; Ricin