Nonmyeloablative Conditioning Regimens

Childs et al. developed a regimen combining cyclophosphamide (120 mg/kg) and fludarabine (125 mg/m2).11,38 TRM was 12% at 1 year in metastatic renal cell carcinoma patients. Spitzer et al. showed that mixed chimerism could be achieved with a regimen combining cyclophosphamide, thymic irradiation (in patients who had not previously received mediastinal radiation therapy), and ATG.10 However, around 30% of the patients subsequently rejected their transplant.

Based on the canine allogeneic transplant model, we studied the induction of mixed chimerism jointly with other centers, using low-dose (2 Gy) pretransplant TBI combined with postgrafting immunosuppression consisting of MMF and CSP, initially in HLA-matched related recipients (Figure 96.2).9 Typically, patients did not become severely pancytopenic, and more than 50% of eligible patients were treated entirely in the outpatient setting.9 Two-year nonrelapse mortality was 7%.9 Nonfatal graft rejection was observed in 16% of

Figure 96.3 Neutrophil and platelet changes in 212 patients with malignancies conditioned with 2 Gy TBI +/— fludarabine (30 mg/m2/day X 3 days) and given HLA-matched related G-PBMC grafts. (Reprinted from Storb R: ASCO Educational Book 77-83, 2002; with permission from the American Society of Clinical Hematology.)

Figure 96.3 Neutrophil and platelet changes in 212 patients with malignancies conditioned with 2 Gy TBI +/— fludarabine (30 mg/m2/day X 3 days) and given HLA-matched related G-PBMC grafts. (Reprinted from Storb R: ASCO Educational Book 77-83, 2002; with permission from the American Society of Clinical Hematology.)

patients.9 Therefore, in subsequent patients, three doses of fludarabine (30 mg/m2/day) were added, and rejections decreased to 3%.18 We studied a similar protocol that extended the duration of postgrafting immunosuppression with MMF and CSP to 96 and 180 days, respectively, to condition patients for HLA-matched unrelated donor grafts (Figure 96.2).3941

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