pentostatin and Skin-Neoplasms

Sezary syndrome (SS) presents clinically as erythroderma, which may be pigmented, and pruritic, associated with peripheral lymphadenopathies. Erythroderma may also occur in a broad range of reactive and malignant conditions including T-cell prolymphocytic leukemia (T-PLL). We report a case initially diagnosed as SS but ultimately diagnosed as T-PLL based upon skin involvement.. A 70-year-old man was referred by his hematologist for management of SS. Physical examination revealed lymphadenopathies and mild diffuse erythema without infiltration. His WBC count was elevated at 8.3 G/L. A peripheral blood smear showed Sezary-like cells. Flow cytometry of peripheral blood revealed prolymphocytic T-cells staining positively for CD2, CD3, CD4 and CD7. Cytogenetic studies showed chromosomal abnormalities in terms of number and structure with missing chromosomes 6 and13, as well as deletion of chromosome 17. Finally, a diagnosis of T-PLL was made. Pentostatin was initiated pending treatment with alemtuzumab, but the patient's overall condition deteriorated rapidly and he died 10 days later.. Diagnosis of LPLT is based upon a number of factors. In the case presented herein, the clinically atypical nature of the skin lesions prompted the dermatologist to review the diagnosis. The morphology of the circulating T-lymphocytes and their immunologic and phenotypic characteristics finally ruled out the diagnosis of Sezary syndrome, while their association with compatible cytogenetic anomalies enabled a diagnosis of prolymphocytic leukemia to be made instead.. Prolymphocytic leukemia involves complex differential diagnosis with regard to Sezary syndrome, posing potential pitfalls for hematologists and dermatologists.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Capecitabine; Chromosome Deletion; Combined Modality Therapy; Delayed Diagnosis; Diagnostic Errors; Fatal Outcome; Humans; Immunophenotyping; Leukemia, Prolymphocytic, T-Cell; Male; Neoplasms, Second Primary; Pentostatin; Rectal Neoplasms; Sezary Syndrome; Skin Neoplasms; T-Lymphocytes

Cutaneous T-cell lymphoma (CTCL) is a dynamic disease with several distinct components that make it unique from other lymphomas. The components of CTCL are reviewed to provide a background for understanding the role of pentostatin (Nipent; SuperGen, San Ramon, CA) in CTCL. In CTCL the malignant T cells mimic and eventually replace their nonmalignant counterparts. This enhances the need for targeting T cells with therapy that preferentially eliminates CTCL cells while sparing nonmalignant cells. Given the similarities of CTCL with T-cell mediated chronic inflammatory diseases, therapies used for this lymphoma also may play a role in nonmalignant disease management.

Topics: Antibiotics, Antineoplastic; Autoimmune Diseases; Cell Transformation, Neoplastic; Chronic Disease; Dermatitis; Forecasting; Humans; Immunosuppressive Agents; Lymphoma, T-Cell, Cutaneous; Pentostatin; Skin; Skin Neoplasms; T-Lymphocytes

Pentostatin is a highly lymphocytotoxic agent active in hairy cell leukemia. Several studies also suggest significant activity in T cell lymphomas manifested in the skin. Herein, we will review the studies of pentostatin in these lymphomas and our most recent trial of this agent in heavily pretreated patients with cutaneous and peripheral T cell lymphomas. Overall, the data suggest that pentostatin has significant antitumor activity in these patients, with response rates ranging from 33% to over 70%. Approximately one-third of the responses are complete. The most common side effects include granulocytopenia, nausea, and renal insufficiency. CD4 suppression occurs and may result in an increased risk of herpes zoster infection. Although prolonged remissions have been seen, most responses are short-lived. These observations suggest that further exploration of this agent, in combination with other drugs active in T cell lymphomas, is warranted in this group of diseases.

Topics: Antibiotics, Antineoplastic; Female; Herpes Zoster; Humans; Lymphoma, T-Cell, Cutaneous; Male; Pentostatin; Skin Neoplasms; Treatment Outcome

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

Mycosis fungoides is an indolent primary cutaneous T-cell lymphoma (CTCL) that usually progresses from localized skin lesions to systemic disease. Sézary syndrome is a distinct variant characterized by generalized erythroderma and circulating cerebriform cells in the peripheral blood. The malignant cell in both diseases is a mature T cell, usually with a CD4-positive, CD8-negative phenotype. Among the treatment modalities used in these diseases are skin-directed therapy, single-agent and combination systemic chemotherapy, and, more recently, bioimmunotherapy. Pentostatin (Nipent), a potent inhibitor of adenosine deaminase, has activity in a wide range of lymphoid malignancies. At The Royal Marsden Hospital, we treated 29 cutaneous T-cell lymphoma patients with pentostatin, including 16 with Sézary syndrome, 5 with mycosis fungoides, and 8 with other cutaneous T-cell lymphomas. The median age of patients was 61 years (range, 26 to 87 years), with a male-female ratio of 2.5:1. The majority (N = 20) had received prior therapy. Pentostatin was administered at a dose of 4 mg/m2/wk for 4 weeks, and injections were continued every 1 to 2 weeks until maximum response. The overall response rate was 35%. However, only patients with Sézary syndrome achieved a good response, demonstrating an overall response rate of 62% (three complete responses plus seven partial responses). The median disease-free interval for responders was 9 months (range, 3 to 84 months). There was no significant treatment-related toxicity. We conclude that pentostatin is an effective single-agent therapy for patients with Sézary syndrome but not for those with other cutaneous T-cell lymphomas.

Topics: Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Female; Humans; Lymphoma, T-Cell; Male; Middle Aged; Mycosis Fungoides; Pentostatin; Sezary Syndrome; Skin Neoplasms; Treatment Outcome

Within this phase II EORTC trial, we have investigated the safety and efficacy of pentostatin in lymphoid malignancies. We have previously reported the results in T- and B-cell prolymphocytic leukemia, B-cell chronic lymphocytic leukemia (B-CLL) and hairy cell leukemia. This report focuses on the outcome in T-cell malignancies: T-CLL, Sézary syndrome (Sézary), mycosis fungoides (MF) and T-zone lymphoma (TZL).. Of the 92 patients with these diagnoses enrolled, 76 were evaluable for response and toxicity, i.e., 25 of 28 with T-CLL, 21 of 26 with Sézary, 22 of 26 with MF, and 8 of 12 with TZL. All patients had progressive and advanced disease. Pentostatin was administered at a dosage of 4 mg/m2 every week for the first 3 weeks, then 4 mg/m2 every 14 days for another 6 weeks, followed by maintenance therapy of 4 mg/m2 monthly for a maximum of 6 months.. Response rates (complete and partial responses) in patients with Sézary (n = 22) or MF (n = 21) were 33% and 23%, respectively, and in patients with T-CLL (n = 21) or TZL (n = 8) 8% and 25%, respectively. Sixteen (21%) patients died during the first ten weeks of treatment: twelve of progressive disease, two of infectious complications with progressive disease, one of myocard infarction and one of renal failure related to administration of i.v. contrast. Major toxicity (grade 3-4) included infection in 11% of patients, nausea/vomiting in 4%, diarrhea in 3%. Hematologic toxicity was mild to non-existent.. We conclude that pentostatin is active in Sézary and MF but showed marginal activity in T-CLL or TZL. Toxicities are mild to moderate at the dose schedule administered. Due to its relatively specific lympholytic effect and its favorable toxicity spectrum, pentostatin might be especially useful for the palliative treatment of T-cell malignancies.

Topics: Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Chi-Square Distribution; Disease-Free Survival; Female; Humans; Lymphoma, T-Cell, Cutaneous; Male; Middle Aged; Pentostatin; Skin Neoplasms

Twenty-four patients with advanced hairy cell leukemia treated with 2'-deoxycoformycin (dCF) were studied after achieving complete remission to determine the impact of treatment on survival, disease-free survival, long-term complications of treatment, and response to retreatment. At a median follow-up time of 82 months (range, 54 to 104 months), 23 of 24 patients remain alive. One patient has died of recurrent disease refractory to treatment. Of the remaining 23 patients, 11 have relapsed at a median time of 30 months (range, 7 to 80 months) after treatment completion. Of these 11 patients, 7 have been retreated with dCF or 2'-chlorodeoxyadenosine (2-CdA), including one patient that was retreated twice. All seven patients have responded, with five patients achieving second complete remission. Two patients have had normalization of blood cell counts, but repeat bone marrows have not been performed. No serious infections have been seen in dCF-treated patients during follow-up. One case of Hodgkin's disease and three cases of skin malignancies have developed in these 24 patients. From initiation of treatment, survival is 93 months (range, 63 to 116 months). We concluded that dCF significantly prolongs the survival of patients with advanced hairy cell leukemia without resultant long-term complications. It is too early to predict if this therapy will be curative for the patients still in remission.

Topics: Aged; Bone Marrow; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Follow-Up Studies; Hodgkin Disease; Humans; Leukemia, Hairy Cell; Neoplasms, Multiple Primary; Neoplasms, Second Primary; Pentostatin; Remission Induction; Salvage Therapy; Skin Neoplasms; Survival Analysis; Treatment Outcome

This phase II study was undertaken to assess the efficacy and toxicity of alternating administration of pentostatin (deoxycoformycin [DCF]) and interferon alfa-2a (IFN) in patients with advanced or refractory mycosis fungoides (MF) or the Sézary syndrome (SS).. Forty-one patients underwent therapy with alternating cycles of DCF 4 mg/m2 intravenously (IV) days 1 through 3 and IFN 10 million U/m2 intramuscularly (IM) day 22, and 50 million U/m2 intramuscularly (IM) days 23 through 26. Twenty-nine patients had not responded to prior chemotherapy or total-skin electron-beam irradiation (TSEB), six had not responded to topical therapies, and six had no previous treatment.. Two patients achieved a complete response (CR) and 15 achieved a partial response (PR), for an overall response rate of 41% (95% confidence interval, 26% to 58%). No responses were observed in the seven patients with visceral involvement. The median progression-free survival of patients who responded was 13.1 months. IFN-related constitutional symptoms were reported in 39% of patients; severe toxicities included cardiomyopathy in one patient, acute and chronic pulmonary dysfunction in four, and reversible mental status changes in two. Seven patients developed herpes zoster during therapy and six had staphylococcal bacteremia.. These results suggest that the combination of DCF and IFN is an active regimen in MF patients without visceral involvement.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Interferon alpha-2; Interferon-alpha; Male; Middle Aged; Mycosis Fungoides; Neoplasm Staging; Pentostatin; Recombinant Proteins; Sezary Syndrome; Skin Neoplasms; Survival Analysis; Treatment Outcome

Thirty-seven patients with refractory lymphoma or cutaneous T-cell lymphoma were treated with 2'-deoxycoformycin (pentostatin; dCF), 5 mg/m2 intravenous (IV) bolus for 3 consecutive days of every 3-week cycle in this Eastern Cooperative Oncology Group (ECOG) trial. Included were 25 with the diagnosis of non-Hodgkin's lymphoma, three with Hodgkin's disease, eight with cutaneous T-cell lymphoma (CTCL), and one with unknown subtype, of whom 31 were considered eligible. The majority had failed at least two, but no more, conventional chemotherapy regimens. Ten (32%) of the eligible patients had a partial response (PR), including patients with nodular poorly differentiated lymphocytic (NPDL), nodular mixed (NM), diffuse poorly differentiated lymphocytic (DPDL), or diffuse histiocytic (DH), lymphoma mixed-cellularity (MC), Hodgkin's disease, and unknown subtype, and in four patients with CTCL. The overall median time to treatment failure (TTF) was only 1.3 months, but the range extended to 57.3 months. The overall response duration was 16.0 months, and the range extended to 53.4 months. Overall median survival was 2.7 months, with the range extending to 63.2 months. The majority of patients had no toxicity, but there were some instances of severe or life-threatening events. Four fatal toxicities occurred, in two patients with underlying pulmonary conditions and two with prior cardiac histories. From this study, we conclude that dCF is active in refractory lymphomas and CTCLs, should be avoided in patients with a history of serious pulmonary or cardiac diseases, and warrants consideration for incorporation of a low-dosage schedule into conventional combination chemotherapy regimens, including its use with biologic response modifiers.

Topics: Adult; Aged; Aged, 80 and over; Drug Administration Schedule; Drug Evaluation; Female; Hodgkin Disease; Humans; Injections, Intravenous; Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell, Cutaneous; Male; Middle Aged; Pentostatin; Skin Neoplasms; Survival Rate

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

Topics: Antineoplastic Combined Chemotherapy Protocols; Bexarotene; Cyclophosphamide; Humans; Mycosis Fungoides; Pentostatin; Sezary Syndrome; Skin Neoplasms; Tetrahydronaphthalenes; Treatment Outcome

Topics: Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Cyclophosphamide; Dendritic Cells; Drug Therapy, Combination; Female; Humans; Pentostatin; Rituximab; Skin; Skin Neoplasms; Treatment Outcome

Topics: Adult; Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; CD8 Antigens; Cyclophosphamide; Deoxycytidine; Doxorubicin; Female; Gemcitabine; Humans; Immunophenotyping; Lymphoma, T-Cell, Cutaneous; Organoplatinum Compounds; Oxaliplatin; Pentostatin; Prednisone; Remission Induction; Salvage Therapy; Skin Neoplasms; Vincristine

Granulomatous slack skin disease (GSSD) is a rare condition characterized clinically by redundant skin folds, which show a predilection towards flexural areas, and histologically by a granulomatous T-cell infiltrate and loss of elastic fibres. The disease is often indolent, although rapid progression and transformation have been described. There is much debate as to whether this condition is a subset of mycosis fungoides or a separate disease entity in itself. We describe a case of GSSD with unique manifestations including granulomatous bone marrow involvement and hypercalcaemia. The patient has twice achieved a good response to pentostatin after failure of combination chemotherapy. This is the first report of the successful use of the purine analogue pentostatin in the management of GSSD.

Topics: Adult; Antineoplastic Agents; Bone Marrow; Granuloma; Humans; Immunosuppressive Agents; Lymphoma, T-Cell, Cutaneous; Male; Pentostatin; Skin Neoplasms

We report a case of Sezary syndrome with two abnormal CD4+ T-cell populations detected in the peripheral blood by flow cytometry immunophenotyping and DNA cell content, suggesting a biclonal T-cell lymphoproliferative disorder. Despite these findings, molecular analysis of the T-cell receptor genes was consistent with a monoclonal T-cell proliferation, supporting the existence of intraclonal diversity rather than a true biclonal disease. The patient achieved a transient response with 2-deoxycoformycin, with a selective decrease of the larger/hyperploid T-cell population; later on, an increased representation of this T-cell population was observed concomitantly with clinical relapse.

Topics: Aged; Antibiotics, Antineoplastic; CD4-Positive T-Lymphocytes; Cell Division; Flow Cytometry; Humans; Immunophenotyping; Male; Pentostatin; Phenotype; Sezary Syndrome; Skin Neoplasms; T-Lymphocyte Subsets

Cutaneous T-cell lymphoma (CTCL) comprises a constellation of diseases of malignant clonal T lymphocytes that present initially in the skin. Since biochemical studies of pentostatin suggested that T cells are more sensitive to the effects of inhibition of adenosine deaminase by purine analogs, early studies with pentostatin were conducted in patients with refractory T-cell neoplasms. Durable responses were reported in several patients on phase I studies. Of 94 CTCL patients treated on five phase II studies with single-agent pentostatin, the overall response rate was 40%, with a 7% complete response rate; the median time to progression ranged from 1.3 to 8.3 months. There was a trend toward improved response in patients with diffuse erythroderma or plaque disease. A phase II study combining pentostatin with intermittent high-dose interferon-alpha demonstrated a 41% overall response rate, with two complete responses, both in patients with Sézary syndrome and diffuse erythroderma Toxicities have been tolerable at doses of 4 to 5 mg/m2 administered weekly or for 3 consecutive days, with grade 3-4 hematologic toxicity in 31 patients, renal insufficiency in seven, nausea in 17, and conjunctivitis in three. In summary, pentostatin has demonstrated impressive activity in patients with advanced and refractory CTCL. Additional studies using pentostatin in earlier-stage CTCL or in combination with other active agents in advanced disease are warranted.

Topics: Adenosine Deaminase Inhibitors; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Disease Progression; Enzyme Inhibitors; Humans; Immunosuppressive Agents; Interferon-alpha; Lymphoma, T-Cell, Cutaneous; Pentostatin; Remission Induction; Sezary Syndrome; Skin Neoplasms; T-Lymphocytes

Pentostatin (Nipent; SuperGen, San Ramon, CA), which is highly lymphocytotoxic, is an active agent in hairy cell leukemia. We therefore initiated a trial of this agent in T-cell lymphomas. Pentostatin was administered at a dose of 3.75 or 5.0 mg/m2/d intravenously for 3 days every 3 weeks to heavily pretreated patients with cutaneous and peripheral T-cell lymphomas. To date, there are 24 evaluable patients in the trial. Seventeen of these individuals have responded (complete or partial remission). The most common toxicities included granulocytopenia, nausea, renal insufficiency, CD4 suppression, and delayed herpes zoster. Pentostatin is an active agent in this group of diseases and merits further exploration.

Topics: Adult; Aged; Agranulocytosis; Antibiotics, Antineoplastic; CD4-Positive T-Lymphocytes; Female; Herpes Zoster; Humans; Immunosuppressive Agents; Injections, Intravenous; Lymphoma, T-Cell; Lymphoma, T-Cell, Cutaneous; Lymphoma, T-Cell, Peripheral; Male; Middle Aged; Nausea; Pentostatin; Remission Induction; Renal Insufficiency; Skin Neoplasms

The treatment of patients with advanced or therapy-refractory cutaneous T-cell lymphoma (CTCL) remains a challenge. Pentostatin is a potent inhibitor of adenosine deaminase and is selectively toxic to lymphocytes. In a small number of patients with CTCL, it previously has been shown to be effective.. Our purpose was to evaluate the efficacy and safety of pentostatin in the treatment of patients with advanced and/or therapy-refractory CTCL.. Eighteen patients with stage I to IVb CTCL were treated with 4 to 5 mg/m2 of intravenous pentostatin every 1 to 4 weeks.. Two patients (11%) had complete responses of 4 months and 6 years, respectively. These patients had stage III and IVa CTCL and had previously received many different external or systemic treatments. Partial remission (50% to 99% clearing) lasting for 1.5 to 6 months occurred in five patients (28%) with stage IIa (n = 3), stage IIb, and stage IVa CTCL. These patients had received a median of three prior external or systemic treatments. No major side effects were observed, and bone marrow suppression was mild.. Single-agent pentostatin in intravenous doses of 4 to 5 mg/m2 is an effective systemic treatment of CTCL (39% objective response rate) with little toxicity.

Topics: Adenosine Deaminase Inhibitors; Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Enzyme Inhibitors; Female; Humans; Lymphoma, T-Cell, Cutaneous; Male; Middle Aged; Pentostatin; Remission Induction; Skin Neoplasms

A 65-year-old man was evaluated for pancytopenia in March 1979, and found to have hairy cell leukemia (HCL). Treatment with splenectomy and subsequently interferon produced temporary remissions. In July 1985, the patient began intravenous deoxycoformycin (DCF) therapy, and after 1 year complete peripheral blood and bone marrow remission was achieved. Fourteen months after cessation of therapy, the patient developed a skin rash and was found to have cutaneous T-cell lymphoma and Sezary syndrome. Morphologic study of the hairy cells (HC) in the peripheral blood at presentation and the Sezary cells was distinct by light and electron microscopic study. Immunophenotyping of peripheral blood mononuclear cells showed clearly that the HC were of B-cell origin (CD20+, sIg+), whereas the lymphoid population at second presentation was T-cell (CD3+, CD4+, HLA-DR-). Clonal rearrangement of T-cell antigen receptor beta-chain gene was detected by Southern analysis of the Sezary cell population, whereas immunoglobulin heavy and light chain genes remained in germ line configuration. This is the first case of Sezary syndrome developing in a patient previously treated for HCL where studies have confirmed distinct B-cell and T-cell origin of the two neoplasms. The authors suggest that treatment and disease-related immunosuppression are possible etiologic factors in the development of this second lymphoid neoplasm.

Topics: Aged; Blotting, Southern; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; Genes, Immunoglobulin; Humans; Immunophenotyping; Leukemia, Hairy Cell; Male; Neoplasms, Multiple Primary; Pentostatin; Remission Induction; Sezary Syndrome; Skin Neoplasms; T-Lymphocytes, Helper-Inducer

We report a case of prolymphocytic leukaemia which presented with annular, purpuric, erythematous plaques in the skin. Histology of the lesions showed cutaneous invasion with leukaemic cells. The lesions cleared with chlorambucil and prednisolone, and the leukaemic state responded to deoxycoformycin, an experimental anti T cell agent.

Topics: Chlorambucil; Coformycin; Humans; Leukemia, Lymphoid; Leukocyte Count; Male; Middle Aged; Pentostatin; Prednisolone; Skin; Skin Neoplasms

2'-Deoxycoformycin, a potent inhibitor of adenosine deaminase, was administered to three patients with cutaneous T cell lymphoma refractory to multiple treatment modalities. Patient 1, who received 5 mg/m2/day for 3 days at 35- to 71-day intervals, has achieved a complete remission greater than 16 months in duration. Patient 2 had progressive disease despite two courses of 2'-deoxycoformycin at a dose of 5 mg/m2/day for 3 days at 28-day intervals. The third patient, who was treated with 4 mg/m2 2'-deoxycoformycin weekly to biweekly, had an initial response, but the disease progressed after eight treatments. Only one patient had any side effects: Patient 1 developed reversible episcleritis, mild elevation of liver enzymes, and persistent nausea and vomiting. In red blood cells of all patients, there was near complete inhibition of adenosine deaminase (91% to 96%) and S-adenosylhomocysteine hydrolase (89% to 95%) activities with treatment. In peripheral blood lymphocytes, adenosine deaminase was inhibited by 85% to 98% and S-adenosylhomocysteine hydrolase by 51% to 88%. The deoxyadenosine triphosphate level, reflected by the total cellular adenine deoxyribonucleotide measurement in erythrocytes, was noted to be modestly elevated during treatment, with the highest level in the patient who demonstrated the only complete response and the only toxic effects. Low-dose 2'-deoxycoformycin appears to be safe but may be an insufficiently intensive regimen to treat refractory cutaneous T cell lymphoma. With proper biochemical monitoring, higher doses may be both safe and more effective.

Topics: Adenosine Deaminase; Adenosine Deaminase Inhibitors; Adenosylhomocysteinase; Aged; Antineoplastic Agents; Coformycin; Erythrocytes; Humans; Hydrolases; Lymphoma; Male; Middle Aged; Neoplasm Staging; Pentostatin; Ribonucleosides; Skin Neoplasms; T-Lymphocytes

Knowledge of the vital role of the purine degradative enzyme adenosine deaminase (ADA) in the differentiation of T and B lymphocytes has stimulated interest in the pharmacologic inhibition of ADA as specific cytotoxic therapy for lymphoproliferative diseases. 2'-Deoxycoformycin (DCF) is a tight-binding ADA-inhibitor and has shown activity in T and B cell neoplasms. In this phase-II study, the efficacy and toxicity of DCF in chronic T and B cell neoplasms is investigated. We report the preliminary results of treatment in 27 patients (8 with Sézary syndrome, 11 with B-chronic lymphocytic leukemia (CLL), and 8 with hairy cell leukemia (HCL)), who were refractory to conventional therapy. DCF was applied at a dosage of 4 mg/m2 weekly x 3, then 4 mg/m2 every other week x 3. Three of the 8 patients with Sézary syndrome and 3 of the 11 patients with B-CLL attained a partial remission. One complete and 7 partial remissions have been achieved thus far in the 8 patients with HCL refractory to interferon alpha treatment. Other than nausea in 10 patients (mainly grade 1 and 2), transient skin rash in 4 patients and Herpes infections in 4 patients (mainly grade 2), no other major toxicities were observed. Thus DCF is highly active in hairy cell leukemia that did not respond to interferon alpha, and shows moderate activity in refractory Sézary syndrome and B-CLL.

Topics: Antineoplastic Agents; B-Lymphocytes; Coformycin; Drug Evaluation; Humans; Leukemia; Leukemia, Hairy Cell; Leukemia, Lymphoid; Lymphoma; Pentostatin; Ribonucleosides; Sezary Syndrome; Skin Neoplasms; T-Lymphocytes