pentostatin and Infections

Patients with lymphoid malignancies such as chronic lymphocytic leukemia, particularly those who receive the newer purine analogs, are at increased risk for infectious morbidity and mortality. Defects in cell-mediated immunity appear to be a major predisposing factor in these patients. An expanding spectrum of pathogens associated with lymphocytopenia and depletion of CD4 has been described in the setting of therapy with purine analogs. During the past 2 years new knowledge about the immunosuppression related to that treatment has continued to accumulate.

Topics: Antimetabolites, Antineoplastic; Cladribine; Humans; Immune Tolerance; Infections; Leukemia, Lymphocytic, Chronic, B-Cell; Pentostatin; Vidarabine Phosphate

The purine analogs fludarabine, cladribine, and pentostatin are active agents in the treatment of indolent lymphoid malignancies. This report reviews the pattern, severity, and consequences of the immunosuppression and myelotoxicity associated with these agents.. The literature was searched using MedLine and Cancerline, as well as the bibliographies of published reports through the winter of 1994 and 1995.. Each of these drugs induces profound lymphocytopenia. A marked decrease in CD4 cells may persist for several years, while other mononuclear-cell populations recover more rapidly. The spectrum of infections encountered in these patients appears to be altered to include a wide range of opportunistic organisms. Factors that increase the risk of these infections include concurrent corticosteroids, extensive prior therapy, particularly with another purine analog, and poor response to purine analog treatment.. Because of the frequency of life-threatening infections with unusual pathogens that may occur in patients treated with purine analogs, aggressive and early diagnostic evaluation and appropriate use of myeloid growth factors may be necessary to ensure appropriate antimicrobial therapy.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Cladribine; Humans; Immune Tolerance; Infections; Pentostatin; Purines; Vidarabine

Acute graft-versus-host disease (aGVHD) is the primary limitation of allogeneic hematopoietic cell transplantation. Corticosteroids remain the standard initial therapy, yet only 25% to 41% of patients completely respond. This randomized, 4-arm, phase 2 trial was designed to identify the most promising agent(s) for initial therapy for aGVHD. Patients were randomized to receive methylprednisolone 2 mg/kg per day plus etanercept, mycophenolate mofetil (MMF), denileukin diftitox (denileukin), or pentostatin. Patients (n = 180) were randomized; their median age was 50 years (range, 7.5-70 years). Myeloablative conditioning represented 66% of transplants. Grafts were peripheral blood (61%), bone marrow (25%), or umbilical cord blood (14%); 53% were from unrelated donors. Patients who received MMF for prophylaxis (24%) were randomized to a non-MMF arm. At randomization, aGVHD was grade I to II (68%), III to IV (32%), and (53%) had visceral organ involvement. Day 28 complete response rates were etanercept 26%, MMF 60%, denileukin 53%, and pentostatin 38%. Corresponding 9-month overall survival was 47%, 64%, 49%, and 47%, respectively. Cumulative incidences of severe infections were as follows: etanercept 48%, MMF 44%, denileukin 62%, and pentostatin 57%. Efficacy and toxicity data suggest the use of MMF plus corticosteroids is the most promising regimen to compare against corticosteroids alone in a definitive phase 3 trial. This study is registered at http://www.clinicaltrials.gov as NCT00224874.

Topics: Acute Disease; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Child; Diphtheria Toxin; Drug Therapy, Combination; Etanercept; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin G; Infections; Interleukin-2; Methylprednisolone; Middle Aged; Mycophenolic Acid; Pentostatin; Receptors, Tumor Necrosis Factor; Recombinant Fusion Proteins; Survival Rate; Treatment Outcome

Topics: Adult; Aged; Antineoplastic Agents; Disease Management; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Hemorrhage; Humans; Infections; Leukemia, Hairy Cell; Male; Middle Aged; Neoplasm Staging; Pentostatin; Prognosis; Remission Induction

Between March 1992 and August 1993, thirty patients with hairy cell leukemia (HCL) were treated in a single institution with 2-chlorodeoxyadenosine (2-CdA) for one course (N=27) or two courses at six month interval (N=3). Sixteen patients were previously untreated, 14 had been treated with alpha interferon (alpha IFN) (N=5), alpha IFN and splenectomy (N=8) and splenectomy, alpha IFN and Deoxycoformycin (N=1). Overall results in 29 evaluable patients were: 25 CR (86%), 3 PR (10%), one failure. The three PR patients relapsed after 18, 24 months and five years. Two were retreated successfully. Two CR patients relapsed after five years. Careful clinical survey, sequential bone marrow biopsies (BMB) with DBA44 immunostaining for assessment of response and detection of residual disease and serially evaluation of lymphocyte subsets counts were performed. Results of bone marrow biopsies study show 1) a progressive reduction in hairy cell infiltration during the first six months after therapy and not after that indicating that the best moment for the evaluation of response may be the sixth month, 2) the persistence of a very small number of DBA44+ cells (80% of BMB). There was a correlation between the presence of > 5% DBA44 positive cells on 6th month BMB and relapse. 60% had an absolute CD4+ lymphocyte count less than 0.2 10(9)/l at least on one examination after treatment. CD4+ lymphocyte level persisted less than baseline level in 8/18 patients tested after four and/or five years. Lymphopenia was less marked in splenectomized patients: 7/7 splenectomized patients tested have recovered a CD4+ lymphocyte count equal to pretherapy level compared to 3/11 non splenectomized patients (p: 0.004). Three opportunistic infections were observed early (first 6 months) after 2CdA therapy: pneumocystis pneumonia, retinitis due to toxoplasma in the patient who failed and legionella pneumonia in a patient retreated after relapse. Two patients developed a second carcinoma 6 and 12 months after therapy. Five patients died, three from a cause unrelated to HCL, one from HCL and one from infection while in second CR. At five years, overall survival is 83% and progression free survival is 66%. Our study shows 1) long-lasting response in the majority of patients after 2-CdA, 2) a correlation between persistent minimal residual disease detected with DBA44 immunostaining and occurrence of relapse and 3) a profound and persistent CD4+ lymphopenia more marked in non splenectomized patie

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Bone Marrow; CD4 Lymphocyte Count; Cladribine; Combined Modality Therapy; Disease Progression; Disease-Free Survival; Female; Follow-Up Studies; Humans; Infections; Interferon-alpha; Leukemia, Hairy Cell; Male; Middle Aged; Neoplasm, Residual; Neoplasms, Second Primary; Opportunistic Infections; Pentostatin; Remission Induction; Splenectomy; Survival Rate