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Morphology in patients with severe aplastic anemia treated with
antilymphocyte globulin
A Tichelli, A Gratwohl, C Nissen, E Signer, C Stebler Gysi and B Speck
Department of Internal Medicine, University Hospital, Basel, Switzerland.
One hundred and seventeen patients with severe aplastic anemia (SAA) were
treated at our institution between 1976 and 1990 with antilymphocyte
globulin (ALG) therapy. Seventy-nine (68%) are alive and probability of
survival at 14 years, according to Kaplan and Meier, is 62% +/- 12%.
Twenty-six patients developed a late clonal complication: 11 had a
myelodysplastic syndrome (MDS) and 17 had paroxysmal nocturnal
hemoglobinuria (PNH); two patients had both. The cumulative risk at 10
years is 42%. The development of MDS/PNH after SAA directly affects
survival. The probability of being alive at 14 years is 81% +/- 10% for
patients with stable disease and 36% +/- 13% for those with clonal
evolution (P = .001). To look for predictive signs, we reevaluated
peripheral blood and bone marrow cytomorphology at presentation, during
regeneration, and in remission. We examined the peripheral blood values for
hemoglobin, reticulocytes, granulocytes, thrombocytes, mean corpuscular
volume (MCV), and fetal hemoglobin, as well as bone marrow for cellularity,
erythropoiesis, myelopoiesis, and megakaryopoiesis. ALG therapy induces
slow and incomplete recovery. Although in "remission," ALG patients have
lower hemoglobin values, higher reticulocyte counts, lower granulocyte and
platelet values, and a higher MCV and fetal hemoglobin than normal
controls. They retain a reduced number of megakaryocytes and a persistence
of atypical monocytes in bone marrow morphology as stigmata of their
disease. Patients with late clonal complications show distinct morphologic
abnormalities: patients with PNH have higher MCVs, higher granulocyte and
reticulocyte counts, and more dyserythropoiesis at diagnosis and a lower
hemoglobin with an increased proportion of erythroblasts in the bone marrow
in "remission." Patients who later developed MDS are not different from the
total patient population at diagnosis. After therapy, these patients are
characterized by the presence of ring sideroblasts and atypical monocytes
during regeneration and by a persistent increase in MCV, a higher fetal
hemoglobin, lower granulocyte values, and megakaryocytic dysplasia during
"remission." Thus, routine morphologic follow-up examination of blood and
bone marrow can discover patients at risk for late hematologic
complications after ALG therapy.
Volume 80,
Issue 2,
pp. 337-345,
07/15/1992
Copyright © 1992 by The American Society of Hematology
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