Comparison of total body irradiation vs busulfan in combination with cyclophosphamide as conditioning for unrelated stem cell transplantation in CML patients

We compared fractionated total body irradiation (12 Gy)/cyclophosphamide (1 20 mg/kg) with busulfan (16 mg/kg)/cyclophosphamide (120 mg/kg) as preparat ive therapy in unrelated donor stem cell transplantation of CML patients. F ifty patients with CML (1.CP = 46; aP = 4) and a median age of 36 years (ra nge 16-52) were enrolled in this sequential trial between 1994 and 1999, In both groups patients were well balanced with respect to age, disease statu s, stem cell source and CMV status, All patients received standard doses of cyclosporin A, methotrexate and anti-thymocyte globulin (ATG) as GVHD prop hylaxis, No graft failures occurred in either group. The median day of leuk ocyte engraftment was earlier in the Bu/Cy than in the TBI/Cy group (day 15 vs 17; P = 0.006). The incidence of grade II-TV GVHD was 40% in the TBI/Cy and 35% in the Bu/Cy group, whereas severe grade III/IV GVHD was only obse rved in 12% of patients in both groups, The incidence of chronic GVHD (limi ted and extensive) at 1 year was higher in the Bu/Cy arm (65% vs 30%; P = 0 .02). More toxicity grade I/II of the liver (88% vs 44%; P = 0.002) and mor e hemorrhagic cystitis (32% vs 8%; P = 0.02) were observed in the Bu/Cy reg imen. Seven relapses in the TBI and no relapse in the Bu/Cy group were obse rved after a median follow-up of 44 and 15 months, respectively. The estima ted 3 year OS and DFS was 72% (95% CI: 55-98%) and 58% (95% CI: 39-77%) in the TBI and 70% (95% CI: 51-89%) for DFS and OS in the Bu/Cy group. We conc lude that the anti-leukemic effect of the Bu/Cy regimen seems to be at leas t as effective as the TBI/Cy combination in unrelated stem cell transplanta tion of CR IL patients, with no graft failures, but that it correlates with a higher incidence of liver toxicity, hemorrhagic cystitis and chronic GVH D. Longer follow-up is necessary to determine the late relapse rate and lat e toxicity.