Complete recovery of marrow function after treatment with anti-lymphocyte globulin is associated with high, whereas early failure and development of paroxysmal nocturnal haemoglobinuria are associated with low endogenous G-CSA-release.
24 patients who were treated with antilymphocyte globulin (ALG) for severe aplastic anaemia (SAA) were tested for endogenous release of granulocyte colony stimulating activity (G-CSA) prior to, and at various intervals after treatment. CSA-production in vitro was induced with autologous serum as a source of 'releaser' activity, avoiding the use of plant mitogens. Before treatment, G-CSA-release was highly variable. Though mean values were higher in the 17 patients who subsequently responded to ALG treatment than in the six non-responders, this difference was not statistically significant. In the 17 responders, G-CSA-release strongly increased prior to improvement of peripheral blood counts. In one responder patient tested-before, and at regular intervals after ALG, CSA-release was high before, abnormally low at 7 d and increased again to high values before the onset of bone marrow reconstitution. In six patients who did not respond to ALG-treatment, G-CSA release decreased after treatment, and a second course of ALG was ineffective when given during this low CSA-phase. Five of the 24 patients developed paroxysmal nocturnal haemoglobinuria (PNH) at 9 months to 3 years after ALG-treatment. In all, the onset of PNH was associated with very low G-CSA-release, whether it had been high or low before treatment. We conclude that low-CSA-release after ALG treatment is a poor prognostic sign. It either indicates progression of marrow failure or heralds PNH. Such patients may be candidates for early bone marrow transplantation or treatment with G-CSF or GM-CSF.
Nissen
C
C
Department of Research, University Hospital Basel, Switzerland.
Moser
Y
Y
dalle Carbonare
V
V
Gratwohl
A
A
Speck
B
B
D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000097:blood / Q000188:drug therapy; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D001853:Bone Marrow / Q000503:physiopathology*; D002648:Child; D003115:Colony-Stimulating Factors / Q000378:metabolism*; D005260:Female; D006098:Granulocytes / Q000378:metabolism*; D006457:Hemoglobinuria, Paroxysmal / Q000209:etiology*; D006801:Humans; D008297:Male; D011379:Prognosis; D013997:Time Factors
D000961:Antilymphocyte Serum; D003115:Colony-Stimulating Factors