Congenital Hypoplastic Anaemia Refractory to Corticosteroids but Responding to Cyclophosphamide and Antilymphocytic Globulin

Abstract

A 7-year-old male child with congenital hypoplastic anaemia (Diamond-Blackfan), having originally responded to corticosteroids, but having subsequently become refractory and erythroblastopenic since 4 years, was treated with a combination of cyclophosphamide (CY; 2.1 g) and antilymphocytic globulin (ALG; 8 g), both by the intravenous route. Erythroblastic repopulation of the bone marrow, albeit dyserythropoietic in character, reticulocytosis and erythrocytic increment took place, but only for a short period. The significance of these findings is discussed in the light of recent progress in the understanding of the disease and of its treatment.

Treatment of Diamond‐Blackfan anaemia with haematopoietic growth factors, granulocyte‐macrophage colony stimulating factor and interleukin 3: sustained remissions following IL‐3

“…Two patients had remarkable prolonged reductions and then disappearance of transfusion requirements after IL-3 therapy. It is of interest that one of these responding patients had been previously reported to have a transient erythroid response to anti-lymphocyte globulin (Marmont, 1978), and that ALG can stimulate haematopoietic growth factor production (Gascon et al 1985). The other four patients had either transient or very minimal increases in their reticulocyte counts, without effect on transfusion requirements.…”

High-Dose Intravenous Corticosteroid for a Patient with Diamond-Blackfan Syndrome Refractory to Classical Prednisone Treatment

“…At least 2 patients with congenital PRCA refractory to steroid therapy have been treated with antimetabolic, immuno suppressant drugs, at the ages of 15 months [6 cited after 4] and 5 years [7], re spectively, and another one responded partially at 7 years of age [4], The improve ment of our patient's hematological find ings on two occasions with intravenous méthylprednisolone treatment makes spontaneous remission less likely. In the light of recent achievements [2,3], it could be interpreted that either his erythropoie tin insensitivity with marked deficiency of erythroid progenitors or the imbalance be tween T helper and suppressor cells was corrected by the very high dose of bolus méthylprednisolone.…”

“…In the light of recent achievements [2,3], it could be interpreted that either his erythropoie tin insensitivity with marked deficiency of erythroid progenitors or the imbalance be tween T helper and suppressor cells was corrected by the very high dose of bolus méthylprednisolone. When the effect of immunosuppressant, antimetabolic drugs [3][4][5] is taken into consideration, the ac tion of high-dose corticosteroid in patients with Diamond-Blackfan syndrome might be explained by the correction of T cell imbalance, as in aplastic anemia.…”

The Autoimmune Myelopathies

“…There are, however, at least three cases of constitutional red cell aplasia which re sponded to nonsteroidal immunosuppres sants; in one of them a combination of cyclophosphamide and ALG was fol lowed by a transitory and dyserythropoie tic response after complete refractoriness to glucocorticoids [110]. It may according ly be speculated either that a secondary autoimmune reaction supervenes in some cases, or that lympholytic therapy inacti vates a suppressor subpopulation which is comparatively hyperactive because of an erythroid progenitor defect.…”