Relapse alter allogeneic bone marrow transplantation for refractory anemiais increased by shielding lungs and liver during total body irradiation

Patients with the refractory anemia (RA) subtype of myelodysplastic syndrom e who undergo allogeneic bone marrow transplantation (BMT) have a low risk of relapse, but they have a high risk of nonrelapse mortality when prepared with conventional preparative regimens. To try to reduce nonrelapse mortal ity, we treated 14 RA patients with a modified approach to total body irrad iation (TBT) followed by cyclophosphamide (CY) and HLA-identical sibling BM T. Median patient age was 44 years (range, 28 to 65 years). Patients receiv ed TBI with shielding of the right lobe of the liver and both lungs followe d by electron beam boosts to shielded ribs. Total radiation exposure in non shielded areas was 12 Gy (n = 10), 10 Gy (n = 3), or 6 Gy (n = 1). After TB I, patients received CY at 120 mg/kg over 2 days, followed by transplantati on of unmanipulated bone marrow. All patients initially achieved engraftmen t with donor cells, although 2 patients had subsequent reemergence of host hematopoiesis without evidence of disease relapse. Five patients died of tr ansplantation-related causes between 22 and 1262 days post-BMT. Four patien ts relapsed between 157 and 1096 days post-BMT. These 14 patients were comp ared with 46 historical controls with RA who received conventional CY/TBI o r busulfan/CY preparative regimens. Patients in the experimental group had a similar nonrelapse mortality rate compared with the historical control gr oup (29% versus 37%, respectively; P =.8), but a higher relapse rate (34% v ersus 2%, P =.0004) and a lower disease-free survival (38% versus 61%, P =. 16). We conclude that this modified TBI approach is associated with an unac ceptably high risk of relapse for patients with RA undergoing BMT.