Marrow transplantation for paroxysmal nocturnal hemoglobinuria

Abstract

Between 1971 and 1990, nine patients ranging in age from 14-38 years received marrow transplants for paroxysmal nocturnal hemoglobinuria (PNH). Six were transplanted for aplastic complications of PNH. Four of these were from HLA-identical siblings, and the patients were conditioned with cyclophosphamide. One graft was form a syngeneic twin without conditioning, and one from a two HLA-antigen nonidentical father after conditioning with cyclophosphamide and total body irradiation. Three of the four recipients of allogeneic marrow developed acute and two chronic graft-versus-host disease (GVHD). Five of six transplanted for severe aplastic anemia are long-term survivors with follow-up ranging from more than 6.2 to more than 19.1 years. The HLA nonidentical transplant recipient experienced graft rejection and died of a pulmonary hemorrhage. Three patients were transplanted for nonaplastic complications of PNH consisting of life threatening recurrent thromboses or refractory hemolysis. Two of these patients received marrow grafts from HLA-identical siblings after conditioning with busulfan and cyclophosphamide. They are surviving with normal hemograms greater than 2.2 and greater than 2.5 years and had mild chronic GVHD which resolved, although one has biochemical evidence of PNH in 15% of the red cells. One received a syngeneic marrow graft without conditioning but reverted to PNH. He is alive greater than 8.6 years after transplantation. Marrow transplantation for aplastic complications of PNH is successful, well tolerated, and compatible with long-term survival when an HLA-identical sibling or a syngeneic donor is available. For patients without aplasia, one must weigh the complications of transplantation with the life threatening nature of thrombotic episodes and hemolysis.

Identical twin marrow transplantation for venous thrombosis in paroxysmal nocturnal hemoglobinuria; long-term complete remission as assessed by flow cytometry

“…Our patient has attained very long follow-up such that all cell types examined, including long-lived lymphocyte populations, were normal in CD59 density. While transplantation for this disorder is well described with twin and histocompatible or haploidentical donors, 10,19 the majority of cases were transplanted for aplastic anemia or a severe cytopenia. Less common reasons for transplantation include recurrent hemolytic episodes, red cell alloantibodies, difficulty with transfusion support, abdominal pain and one case described as life-threatening deep vein thrombosis, neurologic symptoms and persistent anemia (Ref.…”

“…2,9 These considerations have led to the use of bone marrow transplantation, both syngeneic and allogeneic, in PNH associated with aplasia. 10 As patients with PNH in 'chronic phase' may live for years, with a median survival estimated at 10 years in one study, 9 there has been a reluctance to proceed with transplantation unless aplasia has also developed. As management in marrow transplantation has improved however, other 'chronic' hematologic diseases with significant morbidity and mortality, such as the thalassemias, are now being considered.…”

Conditioning with high-dose cyclophosphamide may not be sufficient to provide a long-term remission of paroxysmal nocturnal hemoglobinuria following syngeneic peripheral blood stem cell transplantation

“…Unfortunately, we could not determine the characteristics of relapsed PNH clone because we did not evaluate the underlying PIG-A mutation. 5,9 Second, allogeneic transplantation following non-myeloablative conditioning regimens has cured PNH regularly 1,6,10 whereas relapse is common after syngeneic transplantation. [2][3][4][5] This suggest that an allo-reactive mechanism might contribute to the success of BMT for PNH, either by helping to eradicate autoreactive T cells, or the PNH clone, or both.…”

“…In this case, therefore, we have performed syngeneic transplantation by using the same conditioning regimen that has been used in allogeneic BMT. 1 …”

“…In very rare circumstances in which the patient has a syngeneic donor, syngeneic BMT will be preferable to allogeneic BMT, because of the absence of GVHD. Among five reported cases of syngeneic BMT without a conditioning regimen, only one case achieved long-term survival 1 and four cases showed a return to pathologic hematopoiesis. [2][3][4][5] These data suggest that simple BM infusion without conditioning in PNH may not be an effective therapeutic option as noted in aplastic anemia.…”