Bone marrow histopathology of patients with severe aplastic anaemia before treatment and at follow-up.
Pretreatment bone marrow biopsies of 63 patients with severe aplastic anaemia (SAA) who were not transplanted and of whom 55 received ATG, were evaluated according to the amount and character of residual haematopoiesis ('genuine' aplasia/intermediate/hypoplastic myelodysplasia (MD], inflammatory infiltrate (Te Velde & Haak, 1977, grade I/II/III), and number of mast cells (normal or slightly increased/increased). Of 61 evaluable biopsies, 47 were 'genuine' aplastic, 11 intermediate and three hypoplastic MD. Inflammatory infiltrates were graded as III in 36/60 evaluable biopsies, as II in 21 and I in three. A moderate to marked increase of mast cells was seen in 19/61. Of grade III patients, 86% had a less than 90 d interval between diagnosis and administration of ATG, versus 50% of grade I/II patients (P less than 0.01). No other correlations with pretreatment characteristics were found. No significant prognostic value for survival or response to ATG of any of these three criteria has been identified. More patients with grade III inflammation tended to show adequate recovery at 4 and 6 months after ATG. Stem cell damage, not identifiable morphologically, and/or impairment of accessory cells might play a major role in eventual outcome of SAA patients. Thirty-five patients are currently alive, median 3.8 years (up to 12.4) after ATG. Follow-up bone marrow aspirates and biopsies of 32 patients were evaluable and none showed normal haematopoiesis. One patient revealed persistent aplasia. Of the remaining 31, haematopoiesis was decreased in 14 and increased in eight. All had dyserythropoiesis, 28 dysplastic myelopoiesis and in 16/29 with evaluable megakaryocytes, dysmegakaryopoiesis was found. Sixteen patients had normo- to hypercellular bone marrows with two dysplastic cell lines (consistent with myelodysplastic syndrome (MDS) according to the FAB-group). The prognostic impact of the dysplastic abnormalities found in these patients needs longer follow-up. Close observation is indicated in view of the previously recognized, albeit uncommon, evolution of SAA to MDS/acute non-lymphocytic leukaemia.
de Planque
M M
MM
Department of Haematology/Immunohaematology, University Hospital, Leiden, The Netherlands.
van Krieken
J H
JH
Kluin-Nelemans
H C
HC
Colla
L P
LP
van der Burgh
F
F
Brand
A
A
Kluin
P M
PM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000741:Anemia, Aplastic / Q000401:mortality / Q000473:pathology*; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D001853:Bone Marrow / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006410:Hematopoiesis; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013601:T-Lymphocytes / Q000276:immunology*
D000961:Antilymphocyte Serum