Objective. To determine the incidence of a clonal lymphoid disease in patients with chronic rheumatoid arthritis (RA) and neutropenia.Methods. Lymphocytes from 23 RA patients with either current neutropenia or a history of this complication were studied.ResuUs. Eight patients had a clonal reaflgngement of the T cell receptor m h a h gene. Phenotypically, they showed a distinctive pattern characterized by an inverted CD4+:CD8+ cell ratio and an increased number and percentage of CD57+/CDS+ and CD3+/DR+ lymphocytes. None had evidence of a lymphoid malignancy.Conclusion. Among RA patients with neutropenia, there is a subset who have a subclinical disease resembling T y lymphoproliierative disease.
Ten patients age 13-52 years with acute lymphoblastic leukemia (ALL) in first complete remission (CR) (1), second CR (6), or relapse (3) were treated with cyclophosphamide 50 mg/kg daily x 4 and total body irradiation 3 Gy daily x 4 followed by infusion of autologous marrow purged with 4-hydroperoxycyclophosphamide (4-HC) at 100-120 micrograms/ml. The patients transplanted in relapse also received 2 mg vincristine and corticosteroids. All marrows were harvested while patients were in CR. The nucleated marrow cell dose was 3.5 +/- 0.7 x 10(8)/kg, and the CFU-GM content of the transplant was 0.4 +/- 0.5 x 10(3)/kg after purging with 4-HC. Median time from transplantation is 48 months. The neutrophil count (ANC) exceeded 1.0 x 10(9)/L at a median of 26 days and platelets exceeded 50 x 10(9)/L at 34 days. All patients were in remission after transplantation (ABMT). Five patients relapsed 2-9 months after ABMT (actuarial rate 60%). Three patients are alive and in CR at 17+, 43+, and 54+ months after ABMT. Purging marrow with 4-HC did not adversely affect engraftment, but it is not clear if the high relapse rate was due to incomplete ex vivo purging or inadequacy of the conditioning regimen.
A therapeutic trial of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was attempted in a patient with neutropenia and frequent infections secondary to T-gamma lymphoproliferative disease (T-gamma LPD). During the 14 days of subcutaneous rhGM-CSF (500 micrograms/m2/day), the absolute eosinophil count increased from 0 to 9,455/microliters. By contrast, the absolute neutrophil count decreased. Toxicity related to rhGM-CSF included arthralgia and nonspecific chest pain. The possible mechanism for the rhGM-CSF induced selective eosinophilia is discussed.
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