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132 VARIABLE INTENSITY CONDITIONING IS ASSOCIATED WITH LESS TRANSPLANT-RELATED MORTALITY THAN NONMYELOABLATIVE CONDITIONING IN UNRELATED AND RELATED ALLOGENEIC TRANSPLANT RECIPIENTS
  1. C. L. Bigelow,
  2. S. Elkins,
  3. C. L. Hardy,
  4. J. C. Files
  1. Jackson, MS., 1Helsinki University Hospital

Abstract

For the past four years, our adult allogeneic transplant program has employed two alternative approaches to standard recipient conditioning, the use of nonmyeloablative “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 nonmyeloablative (Group 1) or variable intensity (Group 2) conditioning. Twenty patients with a median age of 49 (range 27-64, Group 1) and 18 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 four protocols: fludarabine 30 mg/m2 × 3 d and TBI 200 cGY; fludarabine × 6 d, busulfan 4 mg/kg × 2 d and ATG 40 mg/kg × 4 d; fludarabine × 5 d and cyclophosphamide 60 mg/kg × 2 d; fludarabine, cyclophosphamide, ATG. Group 2 regimen consisted of Campath 20 mg/d either 5 or 3 days, fludarabine × 5 d and melphalan 140 mg/m2 × 1 d. 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 were manipulated. Relapse rate was 16% in Group 1 and 33% in Group 2. Day + 100 survival and one-year survival were 55% and 25%, respectively, in Group 1 vs 69% and 42% 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 7 had grades III-IV (39%). Graft failure occurred in four 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 nonmyeloablative conditioning. This regimen requires some modification to enhance its tumoricidal properties; however, its treatment-related toxicity is minimal and allows us to offer this therapy to patients with comorbid conditions and older age.

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