losartan-potassium and Lymphoma--Mantle-Cell

Topics: Adrenal Cortex Hormones; Aged, 80 and over; Darbepoetin alfa; Erythropoietin; Hematinics; Hemolysis; Humans; Lymphoma, Mantle-Cell; Male; Syndrome; Transfusion Reaction

Erythropoietin (EPO) and EPO receptor (EPO-R) expression have been reported in solid tumors and are claimed to regulate tumor growth; however, no data have been published on this issue in B-cell malignancies or normal lymphoid cells. This report describes genomic/protein EPO-R expression and in vitro effects of recombinant human EPO (epoetin) in B-cell chronic lymphocytic leukemia (B-CLL), mantle-cell lymphoma (MCL), and multiple myeloma (MM).. Blood samples were obtained from patients with B-CLL, MCL, and healthy volunteers, and bone marrow was obtained from MM patients. EPO-R mRNA was detected by reverse transcription-PCR. EPO-R surface expression was investigated by flow cytometry using digoxigenin-labeled epoetin and polyclonal rabbit anti-EPO-R antibody for intracellular receptor. Tumor cell stimulation was determined in vitro using [(3)H]thymidine incorporation and CD69 expression after exposure to epoetin alpha or beta or darbepoetin alpha.. EPO-R mRNA was detected in mononuclear cells from 32 of 41 (78%) B-CLL and 5 of 7 (71%) MCL patients, and 21 of 21 (100%) MM samples. Expression was also detected in highly purified T cells from six of eight B-CLL patients, four of four MM patients, and normal donor B and T cells. Surface EPO-R protein was not detected. Intracellular EPO-R staining with anti-EPO-R antibodies was unspecific. No tumor-stimulatory effect was observed with high epoetin concentrations.. EPO-R gene is frequently expressed in lymphoid malignancies and normal B and T cells. However, there was no surface protein expression and no epoetin-induced in vitro stimulation of tumor B cells, indicating that epoetin therapy in vivo is likely to be safe in patients with lymphoid malignancies.

Topics: Aged; Aged, 80 and over; Antigens, CD; Antigens, Differentiation, T-Lymphocyte; Erythropoietin; Female; Flow Cytometry; Gene Expression; Humans; In Vitro Techniques; Lectins, C-Type; Leukemia, B-Cell; Lymphoma, Mantle-Cell; Male; Middle Aged; Multiple Myeloma; Receptors, Erythropoietin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

To decrease red blood cell (RBC) transfusion requirements during high-dose therapy (HDT) for hematological malignancies, we conducted a pilot study to assess the effect of recombinant human erythropoietin (rHuEpo) given during chemotherapy before HDT and autologous peripheral stem-cell transplantation (APSCT). The transfusion histories of 15 HDT and APSCT for hematological disease performed in 11 consecutive patients who received rHuEpo (10 000 U subcutaneously three times/week) were compared to those of 22 HDT and ASCT performed in 17 consecutive historical controls matched for hematological parameters. rHuEpo increased the hemoglobin (Hb) level from 10.3+/-2.3 g/dl at diagnosis to 12.9+/-2.2 g/dl at the time of HDT in 11 patients; no major adverse effects occurred. Compared to historical controls (95%, 21/22), RBC transfusion requirements were significantly lower for rHuEpo recipients (26%, 4/15) (P=0.00001) and rHuEpo responders (15%, 2/13) (P=0.000002). After HDT and APSCT, fewer RBC transfusions were needed: 3.3, 1.2 and 0.3 RBC units for controls, rHuEpo recipients and rHuEpo responders, respectively (P=0.006 and 0.00002). Therefore, rHuEpo should be administered before, and not after HDT and APSCT, to lower RBC transfusion requirements after HDT and APSCT.

Topics: Adult; Aged; Erythrocyte Transfusion; Erythropoietin; Humans; Lymphoma, Mantle-Cell; Middle Aged; Multiple Myeloma; Peripheral Blood Stem Cell Transplantation; Pilot Projects; Recombinant Proteins; Transplantation, Autologous