pentostatin and Lymphoma--T-Cell

Hepatosplenic T-cell lymphoma (HSTL) is a rare and aggressive extranodal lymphoma derived mostly from cytotoxic γδ T-cells. The peak incidence is in adolescents and young adults, and is more common in males. Up to 20% of HSTL arise in the setting of chronic immune suppression, most commonly solid organ transplantation or prolonged antigenic stimulation. Patients present with systemic symptoms (fever), abdominal pain, weakness, and marked hepatosplenomegaly in the absence of lymphadenopathy. Patients usually manifest marked thrombocytopenia, often with anaemia and leucopenia, a leukemic phase, and bone marrow involvement in 80% of cases. Lactate dehydrogenase levels are usually markedly elevated. HSTL exhibits a marked chemoresistance to currently used regimens, a rapidly progressive behavior, and dismal prognosis. Patients with post-transplant HSTL exhibit an especially poor outcome. Standard treatment has yet to be established. Anthracycline-based chemotherapy is associated with a satisfactory response in two thirds of patients, but poor long-term results. Complete remission is extremely uncommon, and most patients die from lymphoma within two years of diagnosis. A prognostic correlation between outcome and degree of thrombocytopenia has been reported. Relapsing disease is usually chemorefractory and fast growing, and patients' performance status and clinical conditions are poor. These aspects, as well as the lack of drugs with proven activity against HSTL, render salvage treatment almost impossible. A few cases of HSTL successfully treated with autologous or allogeneic stem-cell transplantation have been reported. The use of 2'-deoxycoformycin and other targeted therapies, such as alemtuzumab, anti-γδ TCR monoclonal antibodies, and anti-CD44 therapy, have shown promising results in anecdotal reports.

Topics: Alemtuzumab; Animals; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Hematopoietic Stem Cell Transplantation; Humans; Liver Neoplasms; Lymphocytes; Lymphoma, T-Cell; Pentostatin; Receptors, Antigen, T-Cell, gamma-delta; Splenic Neoplasms

CD26 is a surface glycoprotein with intrinsic dipeptidyl peptidase IV (DPPIV) enzyme activity with multiple biological roles, including being intricately involved in immunoregulation as a T-cell activation molecule and as a regulator of chemokine function. T-cell lymphoid malignancies represent a heterogeneous group of diseases that are generally aggressive and are for the most part resistant to current treatment modalities. Previous studies showed that CD26 is expressed on selected T-cell neoplasms, suggesting a potential role for CD26 in tumor development. We review herein recent classification schemes for T-cell lymphoid malignancies that take into account various facets of their clinical presentation. In addition, we discuss findings supporting the conclusion that CD26 has an essential role in human T-cell activation, as well as its ability to regulate the biological effects of selected chemokines through its DPPIV activity. Finally, we will present recent work from our laboratory that indicates a potential role for CD26 as a molecular target for novel treatment modalities for T-cell lymphoid malignancies.

Topics: Adenosine Deaminase Inhibitors; Amino Acid Sequence; Animals; Antibodies, Monoclonal; Antigens, Neoplasm; Antineoplastic Agents; Cell Cycle; Clinical Trials as Topic; Dipeptidyl Peptidase 4; Doxorubicin; Drug Design; Enzyme Inhibitors; Humans; Jurkat Cells; Leukemia, T-Cell; Lymphocyte Activation; Lymphocyte Cooperation; Lymphoma, T-Cell; Lymphoproliferative Disorders; Mice; Mice, SCID; Molecular Sequence Data; Neoplasm Proteins; Pentostatin; Prognosis; Transfection; World Health Organization

T-cell non-Hodgkin's lymphomas are a heterogeneous group of diseases that differ markedly in terms of their clinical behavior and prognosis. In recently developed classification systems, the sites of initial disease presentation assume a more prominent role in subgroup delineation. CD26, a structure with an integral role in human T-cell function that serves as the binding protein to adenosine deaminase, has been identified recently as a potential marker for certain aggressive T-cell lymphomas. To translate our knowledge of the basic biology of CD26/adenosine deaminase into clinical practice and to develop specific treatment for T-cell lymphomas based on CD26 expression, we, at M. D. Anderson Cancer Center, have initiated a phase II trial. This trial will evaluate the effect of pentostatin (Nipent), a potent adenosine deaminase inhibitor with known efficacy against T-cell malignancies, on relapsed/refractory T-cell lymphomas in relation to CD26 expression.

Topics: Antibiotics, Antineoplastic; Biomarkers, Tumor; Clinical Trials, Phase II as Topic; Dipeptidyl Peptidase 4; Humans; Lymphoma, T-Cell; Pentostatin; Prognosis; Treatment Outcome

Pentostatin (Nipent) has demonstrated significant activity as a single agent in patients with low-grade B- and T-cell lymphomas, but thus far, clinical experience with combinations of pentostatin and other agents is limited. A study of alternating administration of pentostatin and high-dose interferon-alfa-2a (Roferon A) in cutaneous T-cell lymphoma patients has been undertaken and has demonstrated a 41% response rate, with tolerable toxicity. Studies combining pentostatin with alkylating agents, including chlorambucil (Leukeran) and cyclophosphamide (Cytoxan, Neosar) in patients with chronic lymphocytic leukemia (CLL) have reported significant immunosuppression and have required dose modifications of one or both agents. Recently, a clinical trial was initiated to evaluate the combination of pentostatin and cordycepin, a novel purine analog, in patients with terminal deoxynucleotidyl transferase-positive acute lymphocytic leukemia, based on in vitro data demonstrating the significant synergy of this combination.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Deoxyadenosines; Disease-Free Survival; Dose-Response Relationship, Drug; Female; Humans; Interferons; Lymphoma, B-Cell; Lymphoma, T-Cell; Male; Middle Aged; Pentostatin; Purine Nucleosides; Treatment Outcome; Vidarabine

To examine the efficacy and safety of the combination of alemtuzumab and pentostatin in patients with T-cell neoplasms.. We treated 24 patients with a variety of T-cell leukemias and lymphomas with a combination of alemtuzumab 30 mg intravenously (IV) three times weekly for up to 3 months and pentostatin 4 mg/m(2) IV weekly for 4 weeks followed by alternate weekly administration for up to 6 months. Prophylactic antibiotics including antiviral, antifungal, and antibacterial agents were administered during the treatment and for 2 months after its completion.. The median age of patients was 57 years (range, 21 to 79 years). Eight patients were previously untreated, and 16 had a median of two prior therapies (range, one to six regimens). Thirteen patients responded to treatment (11 complete responses [CRs] and two partial responses), for an overall response rate of 54%. The median response duration was 19.5 months. Monoclonal T-cell receptor chain gene rearrangements were detected by polymerase chain reaction in bone marrow of 20 of 22 evaluable patients and became negative in five of seven evaluable patients in CR. Opportunistic infections caused by pathogens associated with severe T-cell dysfunction were common.. The combination of alemtuzumab and pentostatin is feasible and effective in T-cell neoplasms. Although infections, including cytomegalovirus reactivation, are a concern, they may be minimized with adequate prophylactic antibiotic therapy.

Topics: Adult; Aged; Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Female; Humans; Leukemia, T-Cell; Lymphoma, T-Cell; Male; Middle Aged; Neutropenia; Pentostatin; Sepsis; Survival Analysis; Thrombocytopenia; Treatment Outcome; Young Adult

The goal of the current study was to assess the toxicity, safety, and efficacy of pentostatin in patients with T-cell lymphoid malignancies.. Patients were eligible if they had biopsy-proven T-cell lymphoma or leukemia and failure to respond to previous therapy or an expected complete response rate to conventional therapy of < 20%. Pentostatin was administered at an initial dose of 3.75 or 5.0 mg/m(2) by intravenous bolus daily over a consecutive 3-day period every 3 weeks.. Forty-two of 44 patients enrolled in the study were evaluable. The median age of the patients was 62 years (range, 38-86 years). Patients received a median of 3 previous therapies (range, 0-10 previous therapies). Of these patients, 32 (76%) had mycosis fungoides/Sézary syndrome and 10 patients (24%) had other T-cell leukemias or lymphomas. The overall response rate was 54.8% (complete remission, 6 patients [14.3%]; partial remission, 17 patients [40.5%]). Durable responses were observed mainly in patients with Sézary syndrome or peripheral T-cell lymphoma. The median follow-up period for surviving patients was 20 months (range, 1-83+ months). The median duration of response was 4.3 months (range, 1-61 months). The most common toxicities were neutropenia, nausea, and CD4 suppression. A transient early "flare" of disease was observed in some responders.. At these doses, pentostatin was reasonably well tolerated and is an effective drug for the treatment of T-cell lymphomas.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Disease-Free Survival; Drug Administration Schedule; Enzyme Inhibitors; Female; Humans; Leukemia, T-Cell; Lymphoma, T-Cell; Middle Aged; Pentostatin; 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

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

Topics: Alemtuzumab; Aminopterin; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Clinical Trials as Topic; Deoxycytidine; Depsipeptides; Diphtheria Toxin; Disease Progression; Doxorubicin; Electrons; Gemcitabine; Humans; Hydroxamic Acids; Immunotherapy; Incidence; Interleukin-2; Lenalidomide; Lymphoma, T-Cell; Mycosis Fungoides; Pentostatin; Photopheresis; Polyethylene Glycols; Randomized Controlled Trials as Topic; Recombinant Fusion Proteins; Retinoids; Sezary Syndrome; Stem Cell Transplantation; Thalidomide; United States; Vorinostat

Hepatosplenic T cell lymphoma (HSTL) is a rare condition usually with an aggressive course and a poor prognosis even after extensive treatment. We describe here a patient who presented with hemophagocytosis. The lymphoma had unusual phenotypic features, an indolent course and responded to 20-deoxycoformycin therapy as a single agent. We suggest that this therapy be used in further cases as part of the treatment strategy.

Topics: Antineoplastic Agents; Female; Humans; Liver Neoplasms; Lymphoma, T-Cell; Middle Aged; Pentostatin; Remission Induction; Splenic Neoplasms

Pentostatin is an adenosine deaminase inhibitor used in the treatment of hairy cell leukemia and T-cell lymphomas. A 27-year-old man with refractory cutaneous T-cell lymphoma developed severe hyponatremia 3 days after completing his first cycle of pentostatin therapy. Shortly after hospital admission, he became disoriented and was admitted to the medical intensive care unit and treated with a combination of hypertonic saline, intravenous diuretics, and fluid restriction to reestablish normal sodium homeostasis. The mechanism by which pentostatin may have induced hyponatremia in this patient is unknown; clinical and laboratory findings represented both extrarenal sodium loss and syndrome of inappropriate antidiuretic hormone. Clinicians should be aware of the possible development of life-threatening symptomatic hyponatremia in patients receiving pentostatin.

Topics: Adult; Antibiotics, Antineoplastic; Humans; Hyponatremia; Lymphoma, T-Cell; Male; Pentostatin

We report the results of treatment with single agent 2'-deoxycoformycin (Pentostatin) in two patients with Hepatosplenic gammadelta T-cell lymphoma (HSgammadeltaTCL), a rare lymphoma subtype with a highly unfavorable prognosis. Present and previous data reviewed here demonstrates the striking cytotoxic activity of Pentostatin against gammadelta+ tumor T cells. Further studies are warranted to define the optimal strategy to fully exploit therapeutic potential of this drug in patients with HSgammadeltaTCL.

Topics: Antineoplastic Agents; Humans; Liver Neoplasms; Lymphoma, T-Cell; Pentostatin; Receptors, Antigen, T-Cell, gamma-delta; Splenic Neoplasms

Topics: Adult; Combined Modality Therapy; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Liver Neoplasms; Lymphoma, T-Cell; Male; Pentostatin; Receptors, Antigen, T-Cell, gamma-delta; Splenic Neoplasms

Topics: Adult; Bone Marrow Cells; CD3 Complex; Flow Cytometry; Humans; Immunohistochemistry; Immunosuppressive Agents; Leukocyte Common Antigens; Liver Neoplasms; Lymphoma, T-Cell; Male; Pentostatin; Receptors, Antigen, T-Cell; Splenic Neoplasms; T-Lymphocytes

We describe a patient with unusually indolent hepatosplenic gammadelta T cell lymphoma characterised by severe lassitude and high fever. No significant responses were obtained to a range of chemotherapeutic and biological agents. 2'-deoxycoformycin (dCF), however, produced a dramatic and sustained clinical and histological response. This is the second recent report of gammadelta T cell lymphoma responding to dCF, suggesting this agent may have a specific role in this condition.

Topics: Adult; Antibiotics, Antineoplastic; Female; Humans; Liver Neoplasms; Lymphoma, T-Cell; Pentostatin; Receptors, Antigen, T-Cell, gamma-delta; Remission Induction; Splenic Neoplasms

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

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

Hepatosplenic gammadelta+ T-cell lymphoma represents a rare neoplasm of post-thymic phenotype, characterized by an aggressive clinical course and a poor response to conventional chemotherapy. In the present study, we have examined the cytotoxic effects of the purine analogue 2'-deoxycoformycin (dCF) on cultured mononuclear cells and purified gammadelta+ tumour cells from bone marrow or peripheral blood of four patients with hepatosplenic gammadelta+ T-cell lymphoma. At a concentration of 10 microM, dCF, in the presence of 2'-deoxyadenosine (dAdo), displayed an early and selective cytotoxic effect on gammadelta+ tumour T cells. After 48 h of in vitro exposure to dCF, the absolute number of viable CD3+/gammadelta+ tumour T cells was reduced by more than 90% in all samples with respect to control cultures, with absolute counts of viable CD3+/alphabeta+ lymphocytes being reduced only by 6-40% of the initial cell input. Analysis of cultures after 5 d of exposure to dCF plus dAdo revealed the persistence of normal CD3+/alphabeta+ T cells, which accounted, however, for only 20-25% of the initial cell input. Accordingly, the combination of dCF (10-100 microM) plus dAdo was able to induce a dose-dependent inhibition of clonogenic growth and [3H]-thymidine incorporation in purified CD3+/CD4-/CD8- gammadelta+ tumour cells. We also report that one patient with hepatosplenic gammadelta+ T-cell lymphoma in terminal leukaemic phase showed a striking haematological response to single-agent dCF given as fourth-line treatment. In particular, the selective clearance of gammadelta+ tumour T cells in peripheral blood and bone marrow was observed starting after the second course of treatment. Our results suggest that dCF may represent a potentially active drug for the management of this aggressive form of T-cell lymphoma.

Topics: Adenosine Deaminase Inhibitors; Adult; Enzyme Inhibitors; Female; Flow Cytometry; Humans; Immunophenotyping; Liver Neoplasms; Lymphoma, T-Cell; Male; Middle Aged; Pentostatin; Receptors, Antigen, T-Cell, gamma-delta; Splenic Neoplasms; Tumor Cells, Cultured

Topics: Aged; Antibiotics, Antineoplastic; Fatal Outcome; Female; Humans; Liver Failure, Acute; Lymphoma, T-Cell; Pentostatin

To assess the results of treatment with the purine analog 2'deoxycoformycin (pentostatin [DCF]) in patients with postthymic T-cell malignancies.. One hundred forty-five patients with postthymic T-cell malignancies were given DCF intravenously at 4 mg/m2/wk for the first 4 weeks and then every 2 weeks until maximal response; the last 30 patients received weekly injections until maximal response.. The overall response rate was 32% (complete responses [CRs] plus partial responses [PRs]), with marked variation according to diagnosis. The best responses occurred in patients with Sézary syndrome (62%) and T-prolymphocytic leukemia (T-PLL) (45%), with CRs in three of 16 Sézary syndrome and five of 55 T-PLL patients. In contrast, no responses (NRs) were documented in 13 patients with other types of cutaneous T-cell lymphoma, including five mycosis fungoides. Two of five patients with large granular lymphocyte (LGL) leukemia had a CR and two of four with Sézary cell leukaemia had a PR. A low response rate was observed in 27 patients with peripheral T-non-Hodgkin's lymphoma (T-NHL) (19%) and in 25 with adult T-cell leukemia/lymphoma (ATLL) (12%). The latter included two CRs and one PR. Toxicity was low and DCF was generally well tolerated. No significant differences were observed when results were analyzed according to previous treatment. Disease subtype was the most important factor to influence results.. We conclude that DCF is effective as a single agent in T-PLL, Sézary syndrome, and LGL leukemia, but has low activity in other T-cell disorders.

Topics: Adult; Aged; Aged, 80 and over; Humans; Leukemia-Lymphoma, Adult T-Cell; Leukemia, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Middle Aged; Pentostatin; Remission Induction; Retrospective Studies; Sezary Syndrome; Survival Analysis; Treatment Outcome

A Japanese patient with adult T-cell leukemia-lymphoma (ATL) showed a disease progression from the smoldering type to the chronic type and finally to the acute type. The patient was variously treated, including 2'-deoxycoformycin, with some beneficial effects. During the chronic type he developed a composite lymphoma consisting of T-cell lymphoma (ATL) of medium-sized cells and B-cell lymphoma of diffuse large cell type. At that time, he also suffered from miliary tuberculosis and adenovirus type 11-induced hemorrhagic cystitis, indicating that he was in a marked immunodeficient state. Southern-blot analysis revealed that the two malignancies have distinct clonal origin on the basis of the following results: (1) clonally rearranged T-cell receptor beta-chain gene (TcR-beta gene) and germline configuration of immunoglobulin heavy chain gene (IgH gene) in ATL leukemic cells, (2) clonal rearrangement of IgH gene in lymphoma cells, indicating a monoclonal B-cell lymphoma, (3) monoclonal integration of HTLV-I provirus in ATL leukemic cells, (4) definite presence and monoclonal origin of EBV genome in lymphoma cells. This is the first report of secondary EBV genome carrying monoclonal B-cell lymphoma in an ATL patient. It is suggested that the immunodeficient state in the patient with ATL allows the emergence of EBV-related B-cell lymphoma.

Topics: Adult; Antigens, CD; Blotting, Southern; Cystitis; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; Herpesvirus 4, Human; HLA-DR Antigens; Human T-lymphotropic virus 1; Humans; Immunoglobulin Heavy Chains; Immunophenotyping; Leukemia, T-Cell; Lymphoma, B-Cell; Lymphoma, T-Cell; Male; Neoplasms, Second Primary; Pentostatin; Proto-Oncogene Proteins c-myc; Proviruses; Tuberculosis