PERSISTENT GROWTH IMPAIRMENT OF BONE-MARROW STROMA AFTER ANTILYMPHOCYTE GLOBULIN TREATMENT FOR SEVERE APLASTIC-ANEMIA AND ITS ASSOCIATION WITH RELAPSE

Bone marrow from 65 patients with aplastic anaemia (AA) was tested for stroma growth in short term cultures (2 weeks) and for colony formation by haemopoietic precursor cells during the course of their disease. In 18 untreated patients, mean stroma growth was 30%, of normal and colony formation was virtually absent. After treatment with immunosuppression (IS), as estimated from 90 examinations in 54 patients, stroma growth was approximately 50% and colony growth ,, of normal. Growth impairment of stroma and approximately 10% haemopoietic precursors persisted for 10 and more years after IS. Results of 2-week stroma cultures were compared with results of long term bone marrow cultures in 10 AA patients and 4 controls. At 2 weeks, growth of aplastic marrow was delayed compared to normal, but this difference became less evident with prolonged incubation time. In vitro growth abnormalities were compared with the clinical evolution after IS. The development of late haematological complications (paroxysmal nocturnal haemoglobinuria (PNH)) and myelodysplastic syndrome (MDS), did not correlate with the degree of stroma growth impairment. However, relapse of aplasia was associated with poor stroma growth. 8/29 patients with stroma confluence of less than or equal to 30% during haematological remission versus 1/25 with stroma confluence of >30% relapsed. We conclude that (i) the haematopoietic microenvironment is frequently coinvolved in the disease process of AA, (ii) a defect is detected in short term rather than in long term stroma cultures and, (iii) relapse is more frequent in patients with poor stroma growth.