Plasma exchange in chronic inflammatory demyelinating polyneuropathies.

Chronic Inflammatory Demyelinating Polyneuropathies (CIDP) are characterized by demyelination of peripheral nerves with mononuclear cell infiltrates, electrical conduction slowing or block and elevated cerebrospinal fluid protein with no cells. An immune mediated pathogenesis has been suggested. Immune suppressive therapy, as well as plasmapheresis and intravenous immunoglobulins have been used with variable success. Our objective was to review our results of plasma exchange in this disease in 20 patients with very different underlying diseases, none of them eligible for the Canadian CIDP plasmapheresis study, and define certain guidelines of predictability for the effectiveness of plasma exchange. Five patients had monoclonal gammopathies of unknown significance, two had lung cancer, one breast cancer, one hairy cell leukemia and later carcinoma of the pancreas; two had hepato-splenomegaly and hemolytic anemia; nine were idiopathic (two with autoimmune markers). Plasmapheresis varied from 4 to 31 plasma volumes and procedures with a median of 12, always with 5% albumin. Two excellent responses, one very good, two moderate transient and 12 had no change in clinical or conduction status. Best response occurred in paraproteinemias. Thus immune modulation with plasma exchange may be useful in CIDPs with paraproteinemias and autoimmune manifestations.

Randomized phase II comparison of standard CHOP with weekly CHOP in elderly patients with non-Hodgkin's lymphoma.

PURPOSE: To determine whether modifying the standard regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) from full doses given every 3 weeks to one-third doses given weekly (chop) increases the received chemotherapy dose-intensity in elderly patients with advanced-stage intermediate-grade lymphoma. PATIENTS AND METHODS: Consenting patients, age > or = 65 years who had acceptable cardiac, renal, and liver function and an Eastern Cooperative Oncology Group (ECOG) performance status less than 4, were stratified by bone marrow and performance status and randomized to receive standard CHOP or weekly chop. Drug doses were attenuated or escalated according to a defined dose-modification schedule. The primary outcome was average relative received dose-intensity. Secondary outcomes included response, progression-free and overall survival, toxicity, and performance status. RESULTS: Nineteen patients were allocated to each group. No difference in received dose-intensity was seen. When dose-intensity was calculated for the first six cycles of therapy, average relative received dose-intensity was .92 with CHOP versus .89 with weekly chop (P = .5); when calculated for the first 18 weeks of therapy, values were .88 with CHOP versus .89 with weekly chop (P = .8). The complete response rate was 68% with CHOP versus 74% with weekly chop (P = .9). At 2 years, the progression-free survival rate was 57% with CHOP versus 46% with weekly chop (P = .16) and the survival rate was 74% with CHOP versus 51% with weekly chop (p = .05). More myelotoxicity was seen with CHOP. CONCLUSION: We conclude that CHOP can be given in sufficient doses to elderly patients and that weekly chop does not increase received dose-intensity. Progression-free and overall survival are unlikely to be superior with weekly chop, and may be worse. CHOP should remain the standard against which new therapies for elderly patients with intermediate-grade lymphoma are compared.

Monocyte-macrophage (M-M) functions in asymptomatic hemophiliacs and supertransfused thalassemics.

Patients suffering from acquired immune deficiency syndrome (AIDS) succumb to opportunistic infections due to a generalized failure of their cell-mediated immune defenses. The monocyte-macrophage (M-M) system plays an important role in host defense against viruses, protozoa, mycobacteria, and tumours, all potentially involved in the terminal stages of AIDS. We studied M-M functions in 55 asymptomatic hemophiliacs, 20 supertransfused thalassemics, and 9 von Willebrand's syndrome patients over a period of 17 months to establish the part played by chronic repeated blood component transfusions on the macrophage defense system. We found a significant impairment of chemotaxis in 24 out of 55 hemophiliacs, 13 out of 20 thalassemics, and 4 out of 9 von Willebrand's patients. In contrast, Candida pseudotropicalis killing was markedly increased in all 3 patient groups, while Candida phagocytosis was most significantly diminished in thalassemics. Fc-receptor-dependent erythrophagocytosis showed wide variations in all patients, with a significant decrease only in thalassemics. Phorbol ester-activated nitroblue tetrazolium (NBT) reduction to formazan was normal in most cases, but background spontaneous NBT was often much higher than in the controls. Monocyte adhesion to plastic appeared impaired in hemophiliacs and von Willebrand's Syndrome patients, yet was of no statistical significance. It thus appears that continuous, repeated blood component transfusions cause an alteration of M-M functions. This may be either due to chronic, recurrent antigenic stimulation by foreign proteins transfused, or oncogenic and known immune suppressive viruses, like cytomegalovirus, Epstein-Barr virus, hepatitis, and human T cell lymphotropic virus III. This in turn may increase susceptibility to AIDS.