title: Haematopoietic and immunologic abnormalities in severe aplastic anaemia patients treated with anti-thymocyte globulin.
abstract: Thirty-five patients with severe aplastic anaemia (SAA) were extensively evaluated 0.3-12.4 years (median 3.8) after anti-thymocyte globulin (ATG) treatment. All but one were transfusion independent. Most patients revealed a normal Hb level and a granulocyte count over 1.5 x 10(9)/l but were still thrombocytopenic due to decreased platelet production. Lymphocytopenia and/or monocytopenia was found in about 30%. Two patients had a monocytosis. Although there was a great range in degree of recovery at various time intervals after ATG, patients tested more than 4 years after ATG tended to have higher cell counts. Lymphocyte counts correlated with the interval between ATG and evaluation, and with haematopoietic recovery. Qualitative abnormalities were found in all cell lines. Most patients showed a homogeneous macrocytic RBC population, and almost 50% a positive sucrose lysis test; only three patients showed evidence of haemolysis and only two of these showed a positive Ham test. Mean platelet volumes were reduced out of proportion to their number. Platelet function, determined by bleeding time and aggregometry, was impaired in over 30%. The granulocytic series showed a shift to the left in about 30%. Hypersegmentation and pseudo Pelger-Huet anomaly were seen in some patients. Lymphocyte subset distribution in blood and bone marrow was within the normal range but absolute blood levels of CD4 cells in particular were slightly decreased, and tended to increase gradually with time after ATG. IgG and IgA levels were significantly decreased. In only one patient cytogenetic analysis of unstimulated bone marrow cells revealed an abnormal karyotype, but in eight of eight patients an increased sensitivity of lymphocytes to X-rays was found. These data suggest impairment at the level of the very early haematopoietic progenitor cell in all patients up to 10 years after ATG. Since similar findings have been reported in clonal (pre-)malignant disease, SAA, improved after ATG treatment, might be prone to clonal (malignant) evolution.
authors: Department of Haematology/Immunohaematology and Bloodbank, University Hospital, Leiden, The Netherlands.
authors: M M
authors: MM
authors: de Planque
authors: A
authors: A
authors: Brand
authors: H C
authors: HC
authors: Kluin-Nelemans
authors: J G
authors: JG
authors: Eernisse
authors: F
authors: F
authors: van der Burgh
authors: A T
authors: AT
authors: Natarajan
authors: G C
authors: GC
authors: Beverstock
authors: F E
authors: FE
authors: Zwaan
authors: R
authors: R
authors: Willemze
authors: J J
authors: JJ
authors: van Rood
mesh_terms: D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000097:blood / Q000628:therapy*; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D001772:Blood Cell Count; D001792:Blood Platelets; D004912:Erythrocytes; D005260:Female; D006410:Hematopoiesis; D006801:Humans; D007621:Karyotyping; D008214:Lymphocytes / Q000145:classification; D008297:Male; D008875:Middle Aged; D010586:Phagocytes; D013601:T-Lymphocytes
chemical_list: D000961:Antilymphocyte Serum