Severe aplastic anaemia: correlation of in vitro test with clinical response to immunosuppression in 20 patients.
Colony formation in agar (CFU-c) was studied in 20 patients with severe aplastic anaemia by three different assays: (1) cultures of light density untreated marrow cells; (2) cultures of marrow cells manipulated in order to enhance colony formation (pretreatment with antilymphocytic globulin, ALG, or 6-methylprednisolone, 6-MPr, T cell depletion, adherent cell (AC) depletion, depletion of both AC and T cells), and (3) co-culture of putative suppressor T cells with autologous T-depleted marrow cells. By the first assay, all patients showed poor colony formation (1 +/- 1.5 colonies/10(5) cells; normal controls 46 +/- 18 colonies/10(5) cells). By the second assay, ALG and 6-MPr had no significant effect on colony formation. Removal of adherent cells proved equally without effect on colony growth. On the contrary, removal of T cells enhanced significantly (P less than 0.001) colony formation in 10 out of 20 patients. By the third assay, colony formation of marrow cells (deprived of T lymphocytes) was inhibited by the addition of autologous T cells in six patients studied. All patients were given high dose bolus 6-MPr as first treatment on admission: only patients who had detectable suppressor T cells in their marrow achieved a complete autologous haematologic reconstitution after 6-MPr or after 6-MPr and ALG. The results of this study indicate the detection of CFU-c/suppressor T cells correlates with responses to immunosuppressive regimens, and may thus help to identify patients with immune mediated aplastic anaemia.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000188:drug therapy* / Q000276:immunology; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D002648:Child; D003114:Colony-Forming Units Assay; D005260:Female; D006801:Humans; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D008875:Middle Aged; D012397:Rosette Formation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014184:Transplantation, Homologous
D000961:Antilymphocyte Serum; D008775:Methylprednisolone