pentostatin and Hodgkin-Disease

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

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

Patients who undergo allogeneic stem cell transplantation and subsequent radiation therapy uncommonly develop graft-versus-host disease within the irradiated area. We quantified the incidence of this complication, which is a novel contribution to the field. From 2010 to 2014, 1849 patients underwent allogeneic stem cell transplantation, and 41 (2 %) received radiation therapy afterward. Of these, two patients (5 %) developed graft-versus-host disease within the irradiated tissues during or immediately after radiation therapy.. The first patient is a 37-year-old white man who had Hodgkin lymphoma; he underwent allogeneic stem cell transplantation from a matched unrelated donor and received radiation therapy for an abdominal and pelvic nodal recurrence. After 28.8 Gy, he developed grade 4 gastrointestinal graft-versus-host disease, refractory to tacrolimus and steroids, but responsive to pentostatin and photopheresis. The other patient is a 24-year-old white man who had acute leukemia; he underwent allogeneic stem cell transplantation from a matched related donor and received craniospinal irradiation for a central nervous system relapse. After 24 cobalt Gy equivalent, he developed severe cutaneous graft-versus-host disease, sharply delineated within the radiation therapy field, which was responsive to tacrolimus and methylprednisolone.. We conclude that graft-versus-host disease within irradiated tissues is an uncommon but potentially serious complication that may follow radiation therapy in patients who have undergone allogeneic stem cell transplantation. Clinicians must be aware of this complication and prepared with strategies to mitigate risk. Patients who have undergone allogeneic stem cell transplantation represent a unique population that may offer novel insight into the pathways involved in radiation-related inflammation.

Topics: Adult; Anti-Inflammatory Agents; Antineoplastic Agents; Fatal Outcome; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Immunosuppressive Agents; Leukemia, Biphenotypic, Acute; Male; Methylprednisolone; Pentostatin; Photopheresis; Radiotherapy, Adjuvant; Tacrolimus; Transplantation, Homologous; Young Adult

Topics: Adult; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Combined Modality Therapy; Drug Administration Schedule; Hodgkin Disease; Humans; Infusions, Intravenous; Male; Neoplasm Staging; Pentostatin; Positron-Emission Tomography; Recurrence; Remission Induction; Sensitivity and Specificity; Transplantation, Autologous; Treatment Outcome

Purine analogs, particularly pentostatin and cladribine, are highly effective in hairy cell leukemia (HCL). Both of these drugs induce responses in approximately 80-95% of patients. However, it is not yet determined if treatment with these drugs can induce second malignancies. Hodgkin's lymphoma is very rare as a second malignancy and there are only 3 reported cases concerning the association of this lymphoma with HCL. We describe a patient with longstanding HCL in complete remission after cladribine, in whom extranodal Hodgkin's lymphoma appeared 8 years after the diagnosis of HCL. Magnetic resonance imaging revealed diffuse intra-osseal neoplastic infiltration of the corpora of the whole spinal column and extra-osseal propagation from the fifth thoracic vertebra into the spinal canal with spinal cord compression. Histological and immunohistochemical analysis of the extradural tumor, which was completely excised, disclosed nodular sclerosis Hodgkin's lymphoma with typical Reed-Sternberg cells that were positive for CD30, CD15, bcl-6, Ki67, p53, EBV LPM-1 and IgG, and negative for CD45, CD20, DBA44, kappa, lambda light chains and IgM. In addition, immunohistochemical analysis of the bone marrow in 1999 showed infiltration with positivity for IgM and negative for kappa light chains and IgG. These findings (expression of different immunoglobulins and light chains on the cells) suggest an independent origin of these 2 B-cell neoplasms. After neurosurgery the patient received 6 courses of the MP-ABVD protocol and achieved a complete remission, which has lasted 16 months thus far.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cladribine; Hodgkin Disease; Humans; Leukemia, Hairy Cell; Male; Middle Aged; Neoplasms, Second Primary; Pentostatin