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The hematopoietic defect in aplastic anemia assessed by long-term marrow
culture
JC Marsh, J Chang, NG Testa, JM Hows and TM Dexter
Department of Experimental Hematology, Paterson Institute for Cancer
Research, Christie Hospital, Manchester, England.
Thirty-two patients with aplastic anemia (AA) have been studied using the
long-term bone marrow culture (LTBMC) system. Of these patients, 26 had
been treated with immunosuppressive therapy including antilymphocyte
globulin (ALG) with or without androgens or high-dose methyl prednisolone.
The remaining six patients either required no treatment or were studied
before therapy was begun. Thirty-one of 32 patients (96%) had defective
hematopoiesis in LTBMC with little or no evidence for the generation of
primitive progenitor cells. The only exception was a patient with
spontaneous recovery of aplasia in whom the defect was less marked.
Crossover LTBMC experiments were performed in 23 cases by inoculating (1)
patient marrow hematopoietic cells that had been depleted of adherent cells
onto preformed, irradiated, normal stromas to assess the proliferative
capacity of the hematopoietic cells, and (2) normal marrow hematopoietic
cells that were depleted of adherent cells onto preformed, irradiated
stromas from patients with AA to assess stromal function. Results of these
experiments demonstrated a hematopoietic defect in all patients that was
independent of the degree of hematologic recovery after ALG therapy. Only
one patient had a probable stromal defect and this coexisted with a defect
in the regenerative capacity of hematopoietic cells. We conclude that LTBMC
is a sensitive method for detecting and defining the hematopoietic failure
in AA. We suggest that the defective hematopoiesis present in all patients
studied may be important in the pathogenesis of clonal evolution in AA.
Volume 76,
Issue 9,
pp. 1748-1757,
11/01/1990
Copyright © 1990 by The American Society of Hematology
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