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

Patients with the refractory anemia (RA) subtype of myelodysplastic syndrome 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 mortality, we treated 14 RA patients with a modified approach to total body irradiation (TBT) followed by cyclophosphamide (CY) and HLA-identical sibling BMT. Median patient age was 44 years (range, 28 to 65 years). Patients received TBI with shielding of the right lobe of the liver and both lungs followed by electron beam boosts to shielded ribs. Total radiation exposure in nonshielded areas was 12 Gy (n = 10), 10 Gy (n = 3), or 6 Gy (n = 1). After TBI, patients received CY at 120 mg/kg over 2 days, followed by transplantation of unmanipulated bone marrow. All patients initially achieved engraftment with donor cells, although 2 patients had subsequent reemergence of host hematopoiesis without evidence of disease relapse. Five patients died of transplantation-related causes between 22 and 1262 days post-BMT. Four patients relapsed between 157 and 1096 days post-BMT. These 14 patients were compared with 46 historical controls with RA who received conventional CY/TBI or busulfan/CY preparative regimens. Patients in the experimental group had a similar nonrelapse mortality rate compared with the historical control group (29% versus 37%, respectively; P =.8), but a higher relapse rate (34% versus 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 unacceptably high risk of relapse for patients with RA undergoing BMT.