pentostatin and Leukemia--Prolymphocytic

Prolymphocytic leukemia (PLL) is a rare lymphoproliferative disorder characterized by marked leukocytosis and splenomegaly. PLL accounts for approximately 2% of chronic lymphoid leukemias. The clinical course is progressive in the majority of cases due to the resistance of the disease to conventional chemotherapy. The disease is divided according to the cell of origin into the B- (B-PLL) and T-cell (T-PLL) types. T-PLL and B-PLL are morphologically identical, but lymphadenopathy and skin involvement are more common in T-PLL than in B-PLL. Approximately 80% of cases are of B-cell phenotype. T-PLL has a more aggressive course, poorer response to chemotherapy, and shorter median survival than B-PLL. PLL has poorer prognosis than chronic lymphocytic leukemia (CLL), and the patients with static disease for a longer period of time are rare. In general, B-PLL patients have better prognosis than T-PLL patients. PLL is still considered an incurable disease. Similarly to CLL, treatment is not indicated in asymptomatic patients. In previous decades, splenectomy, splenic irradiation, leucapheresis, and alkylating agents used alone or in combination with other cytotoxic agents have been used for the treatment of PLL. Subsequently, purine nucleoside analogs (fludarabine, cladribine, and pentostatin) have been introduced for the therapy of these disorders. More recently, monoclonal antibodies, especially alemtuzumab, have been found more effective, especially in T-PLL. Finally, high-dose chemotherapy followed by allogenic or autologous stem cell transplantation seems to be an effective, probably curative, strategy for the treatment of selected patients with PLL. In this review, current therapeutic strategies in PLL are presented.

Topics: Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Antibodies, Neoplasm; Cladribine; Drug Therapy; Humans; Leukemia, Prolymphocytic; Pentostatin; Purine Nucleosides; Rituximab; Splenectomy; Stem Cell Transplantation; Vidarabine

Pentostatin has been shown to be active in a variety of B- and T-cell malignancies. The drug is a tight inhibitor of adenosine deaminase, a key degradative enzyme of purine metabolism present in all human tissues, with the highest levels found in the lymphoid system. Early clinical trials indicated that this agent was highly active in acute lymphoblastic leukemias with high intracellular adenosine deaminase levels. Relatively high doses of the drug were needed, which was associated with severe adverse events. Through the efforts of a few investigators, better tolerated, low-dose regimens have been shown to be extremely active in lymphoproliferative diseases with very low intracellular adenosine deaminase levels such as hairy cell leukemia, B- and T-cell chronic leukemias, T-cell cutaneous lymphomas and low-grade non-Hodgkin lymphomas. Clinical as well as experimental data have indicated that this drug induces lymphocyte-specific cytotoxicity, and myelosuppressive adverse events have been minimal. Although all the purine analogs have shown similar activity, the advantage of pentostatin is the relatively specific cytotoxicity against lymphocytes, which permits treatment even in patients with severe cytopenias. Although no direct comparisons of the purine analogs have been performed, pentostatin may be preferred due to this property.

Topics: Adenosine Deaminase Inhibitors; Antibiotics, Antineoplastic; Humans; Leukemia, Hairy Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Prolymphocytic; Pentostatin; Purine Nucleosides

Prolymphocytic leukemia is a rare chronic lymphoproliferative disorder that includes two subtypes, B cell and T cell, each with its own distinct clinical, laboratory and pathological features. T-cell prolymphocytic leukemia has an aggressive course with short median survival and poor response to chemotherapy. With the use of the purine analogue pentostatin more than half of patients will have a major response and a minority will have a complete remission, usually lasting months. With the introduction of alemtuzumab, most patients who progressed despite treatment with pentostatin had a major response with a complete remission rate higher than that obtained with pentostatin when used as a first line. Unfortunately, progression still follows shortly. We recommend alemtuzumab as initial therapy and offer stem cell transplant (SCT) to selected young, healthy patients who respond. Although B-cell prolymphocytic leukemia is also a progressive disease, some patients can achieve a prolonged progression-free-survival with fludarabine. Patients presenting with massive splenomegaly may be effectively palliated with splenic irradiation or splenectomy. Rituximab is a promising agent and further investigations are warranted to better define its role in treatment of this disorder.

Topics: Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Antibodies, Neoplasm; Antineoplastic Agents; Female; Humans; Leukemia, B-Cell; Leukemia, Prolymphocytic; Leukemia, T-Cell; Male; Pentostatin; Rituximab; Stem Cell Transplantation

T-cell prolymphocytic leukemia (T-PLL) is a rare mature T-cell lymphoproliferative disorder. While the etiology of T-PLL is unknown, recent progress in unraveling the molecular basis of leukemogenesis has been substantial and may yield novel therapeutic targets. T-PLL is a distinct disease entity and the diagnosis can be readily made based on characteristic clinical features and laboratory findings. Prior to the appearance of pentostatin and alemtuzumab in clinical protocols, outcome for T-PLL patients was exceedingly poor with median survival measured in months. While the use of alemtuzumab in particular has improved remissions, the disease remains incurable. Future collaborative efforts investigating novel treatment approaches will be crucial to improving survival for patients with this disease.

Topics: Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Antimetabolites, Antineoplastic; Chromosome Aberrations; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 14; Chromosomes, Human, Pair 8; Chromosomes, Human, X; Clinical Trials as Topic; Diagnosis, Differential; Disease Progression; Female; Humans; Immunotherapy; In Situ Hybridization, Fluorescence; Leukemia, Prolymphocytic; Leukemia, Prolymphocytic, T-Cell; Male; Pentostatin; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Receptors, Antigen, T-Cell, alpha-beta; Treatment Outcome

This review deals mainly with the essentials of hairy cell leukemia (HCL) detailing clinical aspects, laboratory findings and morphology. Rare manifestations of HCL are listed. Newer aspects relating to cytokines, soluble interleukin receptors and TNF are reviewed. Differential diagnosis including HCL-variant, SLVL, PLL and CLL/PLL are discussed. Prognostic factors and in particular therapeutic aspects are detailed with particular emphasis on the new purine analogues Pentostatin and 2-CdA. A list of suggested reading is offered.

Topics: Antineoplastic Agents; Biomarkers, Tumor; Cladribine; Diagnosis, Differential; Humans; Interferon-alpha; Leukemia, Hairy Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Prolymphocytic; Lymphoma, Non-Hodgkin; Pentostatin; Prognosis

Within this phase II trial of the European Organization for Research and Treatment of Cancer, we have investigated the safety and efficacy of pentostatin (Nipent; SuperGen, San Ramon, CA) in refractory lymphoid malignancies. Pentostatin was administered at a dosage of 4 mg/m2 every week for the first 3 weeks, then every 14 days, followed by maintenance therapy of 4 mg/m2 monthly for a maximum of 6 months. We have previously reported the results in T- and B-cell prolymphocytic leukemia, B-cell chronic lymphocytic leukemia, and hairy cell leukemia This report focuses on the outcome in T-cell malignancies: T-cell chronic lymphocytic leukemia, Sézary syndrome, mycosis fungoides, and T-zone lymphoma. Of 92 patients with these diagnoses enrolled, 76 were evaluable for response and toxicity, ie, 25 of 28 with T-cell chronic lymphocytic leukemia, 21 of 26 with Sézary syndrome, 22 of 26 with mycosis fungoides, and eight of 12 with T-zone lymphoma. All patients had progressive and advanced disease. Sixteen patients (21%) died during the first 9 weeks of treatment: 12 of progressive disease, two of infectious complications thought to be unrelated to treatment, one of myocardial infarction, and one of renal failure related to administration of intravenous contrast. Major toxicity (grades 3 and 4) included infection in 10.5% of patients, nausea/vomiting in 5%, and hepatotoxicity in 3%. One patient (1.3%) achieved a complete remission and 15 (19.7%) a partial remission. Better results were achieved in patients with Sézary syndrome or mycosis fungoides (complete remission + partial remission = 33.4% and 22.7%, respectively) than in patients with T-cell chronic lymphocytic leukemia (8%) or T-zone lymphoma (25%). We conclude that pentostatin is active in low-grade T-cell malignancies. Toxicities are mild to moderate at the dose schedule administered. Severe hematologic toxicity has not been observed. The efficacy at the present dose level is moderate. A higher dose might be necessary for some T-cell malignancies.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Cause of Death; Disease Progression; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Immunosuppressive Agents; Leukemia, Hairy Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Prolymphocytic; Leukemia, T-Cell; Lymphoma, T-Cell; Male; Middle Aged; Mycosis Fungoides; Pentostatin; Remission Induction; Sezary Syndrome; Skin Neoplasms; Treatment Outcome

B-cell prolymphocytic leukemias or T-cell prolymphocytic leukemias are aggressive variants of chronic lymphoid leukemias. The small studies conducted to date have shown median survival durations of approximately 3 years for patients who have B-cell prolymphocytic leukemia and 7.5 months for those who have T-cell prolymphocytic leukemia, compared with about 8 years for patients who have chronic lymphocytic leukemia. In chronic lymphocytic leukemia, chemotherapy consisting of alkylating agents such as cyclophosphamide and chlorambucil combined with prednisone has achieved overall response rates of 50% to 70%, but this regimen has resulted in response rates of less than 25% in prolymphocytic leukemia. Pentostatin (2'-deoxycoformycin; DCF) is a purine analogue that has shown activity in treatment of chronic lymphoid malignancies.. This prospective phase II trial by the Leukemia Cooperative Group of the European Organization for Research and Treatment of Cancer was performed to assess the activity and toxicity of DCF in prolymphocytic leukemia.. Twenty patients with B-cell or T-cell prolymphocytic leukemia were given DCF at a dosage of 4 mg/m2 intravenously once a week for 3 weeks, then every other week for three doses. Patients who had at least partial response received maintenance therapy once a month for a maximum of 6 months. Fourteen patients had B-cell prolymphocytic leukemia, and six had T-cell prolymphocytic leukemia, as evidenced by morphologic and immunologic criteria; three were previously untreated, eight had been given one or two chemotherapeutic regimens, and nine had been given more than two.. One patient died of an unknown cause during the first 6 weeks of treatment, and one died of disseminated toxoplasmosis during the period of maintenance therapy, 5 months after achieving partial remission. Nine (45% response rate) of the 20 patients achieved partial remission, including seven (50%) of 14 with B-cell prolymphocytic leukemia and two (33%) of six with T-cell prolymphocytic leukemia. The median duration of response was 9 months (range, 2-30 months); for patients with B-cell prolymphocytic leukemia, the median remission duration was 12 months. No complete remission was observed. Toxic effects included nausea and vomiting (30%), infections (30%), and transient increase in liver enzymes (35%) and in creatinine (20%) levels. Eight patients experienced thrombocytopenia, the major hematologic toxic effect; four had grade 3 or 4 toxic effects.. DCF is active in prolymphocytic leukemia, even as salvage therapy in patients who had received multiple prior chemotherapeutic regimens.. Trials using DCF or other purine analogues alone or in combination with standard chemotherapeutic agents in front-line or salvage therapy are warranted to improve the prognosis of patients with prolymphocytic leukemia.

Topics: Adult; Aged; Female; Humans; Leukemia, B-Cell; Leukemia, Prolymphocytic; Leukemia, T-Cell; Male; Middle Aged; Pentostatin; Prospective Studies; Remission Induction; Treatment Outcome

We describe the results of treatment with 2'-deoxycoformycin (DCF) in 68 patients with post-thymic (mature) T-cell malignancies. These included: prolymphocytic leukaemia (T-PLL), 31, HTLV-1 + adult T-cell leukaemia/lymphoma (ATLL), 20, cutaneous T-cell lymphoma (CTCL), comprising mycosis fungoides and Sezary syndrome, 13, and large granular lymphocytic leukaemia, four. Two-thirds of patients were refractory to previous therapy, which included four drug combinations. DCF was given intravenously at 4 mg m-2 weekly for the first 4 weeks and then every 2 weeks until maximal response. Toxicity was very low with only one death resulting from prolonged neutropenia. Overall response rates, partial (PR) and complete. (CR), were 38%, with variations according to diagnosis. Best responses, 54%, were seen in CTCL but limited to Sezary patients, one CR, six PR, whilst none of the mycosis fungoides responded. Responses in T-PLL were recorded in 48% including three CR (of 8-12 months' duration unmaintained) and 12 PR. Fifteen per cent of responses were seen in ATLL. The only ATLL responders - two CR, one PR - were those patients who received combination chemotherapy prior to DCF, with reduction of tumour bulk but short of PR. When results were analysed according to membrane phenotypes it was apparent that responses were seen mainly in cases with CD4+, CD8- T cells -22 of 47 (47%) - contrasting with only three of 19 (16%) with other T-cell phenotypes. We conclude that DCF is a useful therapy for the treatment of T-cell leukaemias, in particular Sezary syndrome and T-PLL, and should play a part in strategies to improve the natural history of this group of lymphoid malignancies.

Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Leukemia-Lymphoma, Adult T-Cell; Leukemia, Lymphoid; Leukemia, Prolymphocytic; Leukemia, T-Cell; Lymphoma, T-Cell, Cutaneous; Male; Middle Aged; Mycosis Fungoides; Pentostatin; Sezary Syndrome

Topics: Drug Evaluation; Europe; Humans; Leukemia, Hairy Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Prolymphocytic; Leukemia, Prolymphocytic, T-Cell; Mycosis Fungoides; Pentostatin; Prospective Studies; Remission Induction; Sezary Syndrome; Skin Neoplasms

Knowledge of the vital role of adenosine deaminase in lymphatic tissues has led to the development of enzyme inhibitors for treatment of lymphoid neoplasms. Deoxycoformycin is a potent ADA inhibitor and has been shown to be active in acute lymphoblastic leukemia at high doses but associated with unpredictable toxicity. In indolent lymphocytic leukemia or lymphoma with low ADA concentrations, this drug is effective at low doses with mild toxicity. The on-going EORTC trial shows that pentostatin is highly effective in hairy cell leukemia and can achieve durable complete remissions even if interferon alpha has failed. It will probably play an important role in the treatment of prolymphocytic leukemia, T- and B-cell chronic lymphocytic leukemia and Sézary syndrome.

Topics: Adenosine; Adenosine Deaminase Inhibitors; Antineoplastic Agents; Coformycin; DNA, Neoplasm; Drug Evaluation; Humans; Leukemia, Hairy Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Prolymphocytic; Multicenter Studies as Topic; Neoplasm Proteins; Pentostatin; Ribonucleosides; Sezary Syndrome

Topics: Bridged Bicyclo Compounds, Heterocyclic; Humans; Leukemia, Prolymphocytic; Leukemia, Prolymphocytic, T-Cell; Pentostatin; Sulfonamides; T-Lymphocytes

Nijmegen breakage syndrome (NBS) is characterized by growth retardation, microcephaly, mental retardation, immunodeficiency, and predisposition to malignancies, especially B-cell lymphomas. In contrast, leukemia is rare. A 23-year-old NBS patient presented with anemia, thrombocytopenia, and hyperlymphocytosis. The diagnosis of T-cell prolymphocytic leukemia (T-PLL) was confirmed by cytological and immunological assays (TdT(-), CD2(+), CD5(+), CD3m, and CD7(+)). Biological assays also showed a hemolytic anemia and a clotting factor V decrease. The patient was first treated by methylprednisone for 3 weeks. During this period the lymphocyte count decreased. The simultaneous normalization of the hemolysis and of factor V suggested that both could be related to T-PLL. Since T-PLL is refractory to conventional therapies with a poor prognosis, an intensive chemotherapy such as 2'-deoxycoformycin with anti-CDw52 monoclonal antibodies is usually favored. In the present case, however, because of the specific context (i.e., NBS-induced immunodepression, severe hemolytic anemia, and acquired factor V deficiency), he received pentostatin weekly during 1 month and in maintenance during 6 months. At last follow-up (7 months) he showed a persistent control of the lymphocytosis with no side effect.

Topics: Adolescent; Anemia, Hemolytic, Autoimmune; Antibiotics, Antineoplastic; Cytogenetic Analysis; Factor V Deficiency; Genes, Recessive; Glucocorticoids; Growth Disorders; Humans; Immunologic Deficiency Syndromes; Infant, Newborn; Intellectual Disability; Leukemia, Prolymphocytic; Leukemia, T-Cell; Male; Methylprednisolone; Microcephaly; Pentostatin; Syndrome

The hairy cell leukemia prolymphocytic variant, a subtype of hairy cell leukemia, is an extremely rare disease, especially in Japan. We report a case in which treatment with 2'-deoxycoformycin (DCF) improved the clinical features of the disease. The patient, a 70-year-old female, was first treated with 2-chlorodeoxyadenosine, but showed only transient improvement in the hematological findings. DCF was then administered every week. Following the start of this treatment, the leukemia cell count rapidly decreased and the platelet count simultaneously increased. This effect of DCF has so far been long term. More clinical studies are needed to confirm the therapeutic value of DCF.

Topics: Aged; Antibiotics, Antineoplastic; Female; Humans; Leukemia, Hairy Cell; Leukemia, Prolymphocytic; Pentostatin

Topics: Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Disease-Free Survival; Doxorubicin; Etoposide; Hematopoietic Stem Cell Transplantation; Humans; Ifosfamide; Leukemia, Prolymphocytic; Leukemia, T-Cell; Male; Methotrexate; Middle Aged; Pentostatin; Prognosis; T-Lymphocyte Subsets; Transplantation, Autologous; Vincristine

We summarize the results of our experience over the past 15 years using pentostatin (Nipent; SuperGen, San Ramon, CA) to treat a range of mature B- and T-cell malignancies. This includes 145 patients with postthymic T-cell malignancies in whom disease subtype was found to be the most significant predictor of response, with the best response rates seen in Sézary syndrome (62%) and T-prolymphocytic leukemia (45%). However, there are no long-term survivors among patients with this group of disorders, and strategies using pentostatin in combination with other therapies, such as CAMPATH-1H, are currently being explored. Among the mature B-cell diseases, pentostatin in both standard- and low-dose regimens is effective in advanced, relapsed/refractory B-chronic lymphocytic leukaemia, showing no cross-resistance with other purine analogs such as fludarabine. Our largest series treated with pentostatin consists of 165 patients with hairy cell leukemia. The follow-up period in this group extends to more than 10 years, with a projected event-free survival rate at 5 years of 60% and an overall survival rate of 97%.

Topics: Antibiotics, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Drug Resistance, Neoplasm; Follow-Up Studies; Humans; Immunosuppressive Agents; Leukemia; Leukemia, B-Cell; Leukemia, Hairy Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Prolymphocytic; Leukemia, T-Cell; Lymphoma; Lymphoma, B-Cell; Lymphoma, T-Cell; Pentostatin; Sezary Syndrome; Survival Rate; Vidarabine

Topics: Antibiotics, Antineoplastic; Dermatitis, Exfoliative; Fatal Outcome; Female; Humans; Leukemia, Prolymphocytic; Middle Aged; Pentostatin

The leukemic cells of a patient with CD4+ prolymphocytic leukemia were treated in vitro with 5 microM deoxyadenosine and 60 microM 2'-deoxycoformycin (dCF), an inhibitor of adenosine deaminase (ADA). Following treatment, the leukemic cell dATP level increased to 378 pmol/10(6) cells on day 3, after which the level plateaued. Apoptosis was apparent following 4 h of incubation, and by day 8 34% of the chromatin was fragmented. Apoptosis also occurred in control cells, but to a lesser extent than in drug-treated cells. When the patient was treated with dCF, 4 mg/M2 i.v. the leukemic cell ADA activity was inhibited 24 h following treatment, and the lymphocyte dATP content increased to 303 pmol/10(6) cells by day 6. The lymphocyte count fell 60% in 1 week, but during this time there was no evidence of apoptosis in these cells. Thus, if dCF induces apoptosis in vivo, the effete cells may be rapidly cleared from the circulation and thus elude detection.

Topics: Adenosine Deaminase Inhibitors; Aged; CD4 Antigens; Deoxyadenine Nucleotides; Deoxyadenosines; Female; Humans; Leukemia, Prolymphocytic; Pentostatin; Tumor Cells, Cultured

We describe the clinical and laboratory findings of 78 adult patients with T-prolymphocytic leukemia (T-PLL) studied over the last 12 years. The main disease features were splenomegaly (73%), lymphadenopathy (53%), hepatomegaly (40%), skin lesions (27%), and a high leukocyte count (greater than 100 x 10(9)/L in 75%) with nucleolated prolymphocytes. A variant form with small, less typical cells was recognized in 19%. Membrane markers defined a postthymic phenotype TdT-, CD2+, CD3+, CD5+, CD7+; in 65%, the cells were CD4+ CD8-, in 21%, they coexpressed CD4 and CD8, and, in 13%, they were CD4- CD8+. Serology for human T-cell leukemia/lymphoma virus Type-I (HTLV-I) was negative in the 27 cases investigated. Cytogenetic analysis in 30 cases showed a consistent abnormality of chromosome 14, usually inv (14), with breakpoints at q11 and q32 in 76% of cases. Trisomy 8, including iso8q, was shown in 53%; t (11;14)(q13;q32) was documented in one case; and one had a normal karyotype. The clinical course was progressive with a median survival of 7.5 months. Thirty-one patients were treated with 2' deoxycoformycin and 15 responded (3 complete remissions and 12 partial remissions); the response rate (48%) increased to 58% in patients with a CD4+ CD8- phenotype. The median survival of responders was 16 months and of nonresponders 10 months; other treatments were less effective. T-PLL is a distinct clinico-pathologic entity with aggressive course and characteristic chromosome abnormalities. A subgroup of patients may benefit from deoxycoformycin.

Topics: Adult; Aged; Aged, 80 and over; Antigens, CD; Chromosome Aberrations; Chromosomes, Human, Pair 14; Female; Humans; Immunophenotyping; Karyotyping; Leukemia, Prolymphocytic; Male; Middle Aged; Pentostatin; Prognosis; Remission Induction; T-Lymphocytes

Deoxycoformycin (DCF) is a specific inhibitor of adenosine deaminase (ADA) and has been shown to be active in lymphoid neoplasms. Cytotoxicity is thought to be mediated by the accumulation of deoxyadenosine (AdR) and deoxyadenosine triphosphate (dATP) which inhibits ribonucleotide reductase and DNA synthesis in rapidly proliferating cells. Others suggested mechanisms leading to cell death particularly in non-dividing cells include depletion of ATP and NAD pools, inhibition of S-adenosylhomocysteine (SAH) hydrolase and induction of DNA strand breaks. In patients with high leukemic counts who were subsequently treated with DCF, we have studied (a) the levels of ADA, ecto-5'-nucleotidase (5NT), deoxyadenosine kinase (AdR-kinase) and SAH-hydrolase in the leukemic cells; [b) the in-vitro effects of DCF on dATP, ATP, NAD, SAH-hydrolase levels and on DNA strand breaks; and (c) the correlation between these parameters with clinical response to DCF. No significant difference in ADA, 5NT, AdR-kinase and SAH-hydrolase activities could be found between responders and non-responders. Incubation of the leukemic cells in vitro with DCF caused an inhibition of ADA, an accumulation of dATP, a moderate reduction in ATP and NAD levels, a suppression of SAH-hydrolase activity and an increase in DNA strand breaks in practically all the leukemic samples, irrespective of clinical response. Our results show that neither measurement of these enzymes nor studies of these biochemical sequelae of ADA inhibition in vitro predicts clinical responsiveness to DCF therapy.

Topics: Adenosine Deaminase Inhibitors; Adenosine Triphosphate; Adenosylhomocysteinase; Antineoplastic Agents; Coformycin; Deoxyadenine Nucleotides; DNA Damage; Humans; Hydrolases; Leukemia; Leukemia, Hairy Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Prolymphocytic; Leukemia, Prolymphocytic, T-Cell; NAD; Nucleoside Deaminases; Pentostatin; Ribonucleosides