Less Treatment Related Mortality with Variable Intensity Conditioning Than Non-Myeloablative Conditioning in Unrelated and Related Adult Allogeneic Transplant Recipients.

For the past four years our adult allogeneic transplant program has employed two alternative approaches to standard recipient conditioning, the use of non-myeloablative “mini” conditioning and variable intensity conditioning. We now report a retrospective comparison of relapse, day +100 and one year survival, engraftment and grades I-II and III-IV acute GVHD in unrelated as well as related recipients in these two preparative regimen groups. Patients with a variety of malignancies were not randomized to receive either non-myeloablative (Group 1) or variable intensity (Group 2) conditioning. Twenty patients with a median age of 49 (range 27–64, Group 1) and 17 patients also with a median age of 49 (range 24–58, Group 2) received either marrow or peripheral blood stem cells, usually with a 6/6 match grade; one recipient in Group 2 received a cord blood transplant (4/6 match). Group 1 regimen consisted of fludarabine 30 mg/m² x 3d and TBI 200 cGY. Group 2 regimen consisted of Campath 20 mg/d either 5 or 3 days, fludarabine x 5d and melphalan 140 mg/m² x 1d. GVHD prophylaxis was the same in both groups (standard dose cyclosporine or tacrolimus and MMF.) All patients received an adequate CD34+ cell dose and none of the products was manipulated. Relapse rate was 37% in Group 1 and 53% in Group 2. Day+100 survival and one year survival were 55% and 20%, respectively, in Group 1 vs 69% and 33% in Group 2. Only one patient in Group 2 had acute GVHD, grades I-II; none had grades III-IV. However, in Group 1, 6 patients had grades I-II and 8 had grades III-IV (40%). Graft failure occurred in five patients in Group 1, while no patients in Group 2 experienced it. We conclude, first, that in our program the application of variable intensity conditioning has been quite successful in unrelated transplant recipients, as well as in related. Second, significant treatment related mortality in the form of graft failure and acute GVHD occurred less frequently in recipients who received this conditioning than in those receiving non-myeloablative conditioning. This regimen requires some further modification to enhance its tumoricidal properties; however, its treatment-related toxicity is minimal and allows us to offer this therapy to patients with co-morbid conditions and older age.