pentostatin and Lymphoma--T-Cell--Cutaneous

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

Topics: Antibodies, Monoclonal; Diphtheria Toxin; Humans; Interleukin-2; Interleukin-7; Lymphoma, T-Cell, Cutaneous; Pentostatin; Retinoids; Thymopentin

Topics: Adenosine Deaminase; Antimetabolites, Antineoplastic; Antineoplastic Agents; Cladribine; Humans; Lymphoma; Lymphoma, B-Cell; Lymphoma, T-Cell, Cutaneous; Pentostatin; Vidarabine; Waldenstrom Macroglobulinemia

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

To determine the side effects of and response to pentostatin in patients with T-cell lymphomas with cutaneous manifestations.. Pentostatin was administered to 28 patients who had relapsed cutaneous T-cell lymphoma or peripheral T-cell lymphoma with prominent cutaneous disease. The starting dose was between 3.75 to 5.0 mg/m(2)/d intravenous for 3 days every 3 weeks.. Of the 24 patients assessable for response, 17 (71%) achieved a partial remission (46%) or complete remission (25%). The patients had a median number of three (range, one to 12) prior therapies. Of the 86 courses of pentostatin given, 39 were administered at doses of 5.0 mg/m(2)/d and 30 at doses of 3. 75 mg/m(2)/d. Dose escalation to 6.25 mg/m(2)/d was possible in only five courses, and toxicity necessitated dose reduction to 2.8 mg/m(2)/d in 12 courses. The most common side effects were granulocytopenia, nausea, and nonneutropenic fever. Most patients developed significant lowering of CD4 counts. Herpes zoster was seen within 1 year after pentostatin in five patients (19%).. Pentostatin is an active agent in heavily pretreated T-cell lymphomas with cutaneous manifestations.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Dose-Response Relationship, Drug; Female; Humans; Infusions, Intravenous; Lymphoma, T-Cell; Lymphoma, T-Cell, Cutaneous; Male; Middle Aged; Pentostatin; Recurrence; 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

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

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: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Histiocytes; Humans; Lymphoma, T-Cell, Cutaneous; Lymphoma, T-Cell, Peripheral; Male; Middle Aged; Panniculitis; Pentostatin; Prednisone; Subcutaneous Fat; Subcutaneous Fat, Abdominal; Vincristine

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

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

Topics: Antibiotics, Antineoplastic; Hemolytic-Uremic Syndrome; Humans; Interferon-alpha; Lymphoma, T-Cell, Cutaneous; Male; Middle Aged; Pentostatin

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 44-year-old woman was admitted to our department because of fever and skin eruptions on August, 1991. Physical examination revealed superficial lymph node swelling, hepatosplenomegaly and generalized erythroderma. Laboratory findings were as follows; WBC 21,490/microliters with 67% lymphocytes including flower cells. The surface phenotype of lymphocytes was positive for CD2, CD4, CD25, CD29 suggesting helper-inducer T cell. Skin and lymph node biopsies revealed the infiltration of T cells with indented nuclei. Anti-HTLV-1 antibodies in the serum and HTLV-1 proviral DNA analysis by PCR method were negative. She was diagnosed as CTCL, and she was treated with prednisolone. However, her erythroderma deteriorated gradually, in spite of well-controlled lymphocyte counts. Combination chemotherapy, utilizing vincristine, etoposide and cyclophosphamide, was effective against organomegaly but not against generalized erythroderma. After DCF was initiated at a weekly dose of 7.5 mg, her erythroderma improved rapidly and markedly with the disappearance of severe itching, and she achieved complete remission. Our results suggest that DCF is beneficial for chemotherapy-resistant generalized erythroderma in CTCL.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Dermatitis, Exfoliative; Etoposide; Female; Humans; Lymphoma, T-Cell, Cutaneous; Pentostatin; Vincristine