Establishment of erythropoiesis following bone marrow transplantation in a patient with congenital hypoplastic anemia (Diamond-Blackfan syndrome)

Abstract

Marrow transplantation was attempted in a 13-yr-old boy with congenital hypoplastic anemia who had never responded to corticosteroid therapy. Prior to the transplant, he had received 238 transfusions, at least 12 of which were from his father. He was prepared for grafting with antilymphocyte globulin, procarbazine, and total body irradiation (1000 rads). The patient, whose red cells were Group B, then received marrow cells from his Group O, histocompatible, sister. Thereafter, reticulocytes, Group O erythrocytes, and female leukocytes appeared in the peripheral blood. Erythroid precursors were seen in the patient's marrow for the first time in his life, and all lacked fluorescent Y chromosomes. Dividing cells were all female. After initially progressing well, the patient developed interstitial pneumonia and died 55 days after the transplant. The successful erythroid graft suggested that this patient's failure to produce red blood cells was due to a defective stem cell rather than to a humoral defect, plasma inhibitor, or abnormal marrow microenvironment. It suggested further that sibling marrow may be engrafted in patients who have received multiple transfusions, even from a parent.

Perspectives of current understanding and therapeutics of Diamond-Blackfan anemia

“…In 1951, corticosteroids were first reported to show therapeutic effects by Gasser [ 8 ], followed by a study of Diamond et al indicating that a group of patients could respond to corticosteroid therapy [ 9 ]. In 1976, the first known bone marrow transplantation was performed on a 13-year-old boy with DBA who never responded to corticosteroid therapy and had received 238 transfusions, but iron chelation therapy showed no effects [ 10 ]. Initially, the treatment progressed well with erythroid precursors production was detected in the patient’s marrow for the first time in his life.…”

“…Initially, the treatment progressed well with erythroid precursors production was detected in the patient’s marrow for the first time in his life. However, the patient developed interstitial pneumonia and died 55 days after the transplant [ 10 ]. Elevated erythrocyte adenosine deaminase activity (eADA) in DBA patients was first reported and suggested as a marker for DBA by Diamond et al in 1983 [ 11 ].…”

Hematopoietic cell transplantation and gene therapy for Diamond-Blackfan anemia: state of the art and science

“…Allogeneic HCT remains the only option for hematopoietic cure in patients with DBA. The first HCT for DBA was performed in 1976, proving that hematological cure is possible (35). Numerous case reports since then confirmed the feasibility of HCT in DBA.…”