HYPERFRACTIONATED TOTAL LYMPHOID IRRADIATION AND CYCLOPHOSPHAMIDE FORPREPARATION OF PREVIOUSLY TRANSFUSED PATIENTS UNDERGOING HLA-IDENTICAL MARROW TRANSPLANTATION FOR SEVERE APLASTIC-ANEMIA

Purpose: To assess the immunosuppressive capacity of hyperfractionated total lymphoid irradiation and cyclophosphamide for transplantation o f unmodified allogeneic marrow in sensitized aplastic anemia patients. Methods and Materials: From February 1983 to September 1990, 23 multi ply transfused aplastic anemia patients underwent unmodified bone marr ow transplantation from HLA genotypically identical sibling donors fol lowing preparation with 6 Gy hyperfractionated total lymphoid irradiat ion and 160 mg/kg cyclophosphamide. Graft-versus-host disease prophyla xis included steroids in one patient, methotrexate in four, cyclospori ne in seven, and methotrexate/cyclosporine in 12. There were 17 males and 6 females with a median age of 13 (range: 2.5-32). Results: One pa tient died early before engraftment of bacterial sepsis. Twenty-two pa tients were evaluable for engraftment. Three experienced graft failure including one primary, and two late graft failures associated with cy closporine withdrawal. Acute graft-versus-host disease occurred in 7/2 2 (greater than or equal to grade II in 6), and chronic graft-versus-h ost disease in 3/17 patients. Except for a patient who received total body irradiation for a second transplant, no patient in this series de veloped interstitial pneumonia. Fifteen patients are alive with follow -up of 38-125 months (median 68). The overall actuarial survival at 5 years is 69%, at 8 years it is 60%, with one late death. The survival of adult patients was similar to that of younger patients (greater tha n or equal to 16 years old: 63%, < 16 years old: 55%). The development of acute graft-versus-host disease adversely influenced survival (88% with Grade 0-1, 17% with grade II-IV; p = 0.002). No hypothyroidism o r secondary malignancies have been documented in this series. Conclusi on: Pretransplant immunosuppression with 6 Gy of hyperfractionated tot al lymphoid irradiation and 160 mg/kg CY reduces but does not eliminat e the incidence of graft failure in sensitized aplastic anemia patient s. The dose and the mode of administration of total lymphoid irradiati on in this trial may be associated with a lower incidence of late side effects. Survival is comparable to that obtained using preparative re gimens without radiation.