Classical Hodgkin lymphoma concurrently evolving in a patient with marginal zone B-cell lymphoma of the spleen.

Combination of the splenic marginal zone B-cell lymphoma (SMZL) and classical Hodgkin lymphoma (cHL) is extremely rare. We report a unique case with concurrent SMZL and cHL. The patient was a 63-year-old man who presented with fatigue and anemia, showing a splenomegaly and retroperitoneal lymphadenopathy. A splenectomy revealed monotonous marginal zone lymphocytic infiltrates and numerous large Reed-Sternberg-like cells. Flow cytometry revealed a kappa light-chain-restricted CD5 (-), CD23 (-) B-cell population. DNA polymerase chain reaction analysis confirmed the presence of clonal rearrangement of the immunoglobulin heavy-chain gene. Immunohistochemical studies revealed that the large atypical cells were CD30 (+), CD15 (weakly +), CD20 (-), CD45 (-), Pax5 (weakly +), BOB.1 (-), and Oct2 (-), indicating the coexistence of SMZL with cHL. After the chemotherapy, the patient achieved a clinical/radiologic remission, whereas cHL was detected in liver and bone marrow subsequently. The case indicates that both components of lymphoma can present concurrently as a composite form of lymphoma and both need to be treated adequately.

Human endogenous retrovirus (HERV-K) particles in megakaryocytes cultured from essential thrombocythemia peripheral blood stem cells.

OBJECTIVE: The aim of this study was to determine the extent of human endogenous retrovirus (HERV) gene translation in megakaryocytes cultured from peripheral blood stem cells of patients with essential thrombocythemia previously reported with platelet-associated HERV sequences and reverse transcriptase activity. MATERIALS AND METHODS: Terminally differentiated megakaryocytes derived from circulating stem cells in serum-free medium supplemented with stem cell factor and thrombopoietin were processed for electron microscopic immunostaining using a monoclonal antibody against the gag protein of HERV-K10 and an electron dense gold-labeled secondary antibody. RESULTS: We found that HERV-K gag protein was detected as clusters in the cytoplasm as well as associated with viral particles budding from the cell membrane and into intracellular vacuoles in megakaryocytes from two patients with essential thrombocythemia. None of these structures was observed in megakaryocytes from a normal control or from a patient with chronic myelocytic leukemia. CONCLUSION: This is the first evidence of HERV-K protein synthesis (gene translation) in human tissue other than seminomas, placenta, or fetal tissue. Translation of the HERV-K gag gene with subsequent packaging of the protein product into viral particles adds a new and important dimension to future studies on the role of HERVs in the myeloproliferative diseases.

Modified VAD and PSC-833 in the treatment of resistant or relapsing chronic lymphocytic leukemia (E4996): a trial of the Eastern Cooperative Oncology Group.

BACKGROUND & METHOD: The role of multidrug resistance (MDR) was investigated in patients with relapsed chronic lymphocytic leukemia (CLL). PSC-833 was added to modified VAD (a 4-day infusion of vincristine, doxorubicin, with oral dexamethasone, every 3 weeks), in an attempt to improve the response rate (21%) in a prior study. Laboratory tests to determine MDR and apoptosis proteins were correlated with response. RESULTS: Two of the seven MDR-positive cases and one of the four MDR-negative patients achieved a partial response (no significant difference). No significant correlation with response was found in any of the laboratory tests for apoptosis. CONCLUSION: VAD plus PSC-833 had the same (21%) partial response rate as a prior ECOG study without PSC-833. No correlation of response with MDR or apoptosis testing was found. Other drug resistance factors must play a significant role in determining the response of relapsed patients with CLL.

High-dose cyclophosphamide as salvage therapy for severe aplastic anemia.

OBJECTIVE: The treatment options for patients with aplastic anemia who do not respond to conventional immunosuppression are limited. The aim of this study was to evaluate high-dose cyclophosphamide in patients with refractory severe aplastic anemia (SAA). MATERIALS AND METHODS: We treated 17 SAA patients with high-dose cyclophosphamide (50 mg/kg/day for 4 consecutive days) who previously did not respond to one or more courses of immunosuppressive therapy. Median age was 31 years (range 6-58); median disease duration was 14 months (range 6-58), and 8 patients met criteria for very severe aplastic anemia (absolute neutrophil count <0.2 x 10(9)/L) at the time of treatment. RESULTS: At median follow-up of 29 months, 10 patients (59%) are alive. Nine patients (53%) achieved a drug-free remission after high-dose cyclophosphamide; 4 patients achieved a complete remission and 5 patients currently meet criteria for a partial remission but continue to improve. One nonresponder to high-dose cyclophosphamide developed paroxysmal nocturnal hemoglobinuria; another nonresponder developed a myelodysplastic syndrome. In responding patients, median time to 500 neutrophils was 54 days (range 35-119), median time to the last platelet transfusion was 99 days (range 51-751), and median time to the last red cell transfusion was 125 days (range 63-796). CONCLUSION: High-dose cyclophosphamide shows promise for salvaging patients with refractory SAA.

High-dose cyclophosphamide for refractory autoimmune hemolytic anemia.

High-dose cyclophosphamide, without stem cell rescue, has been used successfully to treat aplastic anemia and other autoimmune disorders. To determine the safety and efficacy of high-dose cyclophosphamide among patients with severe refractory autoimmune hemolytic anemia, we treated 9 patients with cyclophosphamide (50 mg. kg(-1). d(-1) for 4 days) who had failed a median of 3 (range, 1-7) other treatments. The median hemoglobin before treatment was 6.7 g/dL (range, 5-10 g/dL). The median time to reach an absolute neutrophil count of 500/microL or greater was 16 days (range, 12-18 days). Six patients achieved complete remission (normal untransfused hemoglobin for age and sex), and none have relapsed after a median follow-up of 15 months (range, 4-29 months). Three patients achieved and continue in partial remission (hemoglobin at least 10 g/dL without transfusion support). High-dose cyclophosphamide was well tolerated and induced durable remissions in patients with severe refractory autoimmune hemolytic anemia.