TOTAL-BODY IRRADIATION BEFORE BONE-MARROW TRANSPLANTATION FOR ACUTE-LEUKEMIA IN FIRST OR 2ND COMPLETE REMISSION - RESULTS AND PROGNOSTIC FACTORS IN 326 CONSECUTIVE PATIENTS

Aim: In order to assess the influence of total-body irradiation (TBI) on the outcome and incidence of complication after bone marrow transpl antation (BMT), we retrospectively analyzed our patients treated for a cute leukemia and conditioned with TBI prior to BMT. Patients and Meth ods: Between 1980 and 1993, 326 patients referred to our department wi th acute non-lympho blastic leukemia (ANLL, n = 182) and acute lymphob lastic leukemia (ALL, n = 144) in complete remission underwent TBI eit her in single dose (190 patients: 10 Gy administered to the midplane, and 8 Gy to the lungs [STBI]) or in 6 fractions (136 patients: 12 Gy o n 3 consecutive days, and 9 Gy to the lungs [FTBI]) before BMT. The ma le-to-female ratio was 204/122 (1.67), and the median age was 30 years (mean: 30 +/- 11, range: 3 to 63). The patients were analyzed accordi ng to 3 instantaneous dose rate groups: 118 patients in the LOW group (less than or equal to 0.048 Gy/min), 188 in the MEDIUM group (> 0.048 and less than or equal to 0.09 Gy/min), and 20 in the HIGH group (> 0 .09 cGy/min). Conditioning chemotherapy consisted of cyclophosphamide (CY) alone in 250 patients, CY and other drugs in 54, and 22 patients were conditioned using combinations without CY. Following TBI, allege neic and autologous BMT were realized respectively in 118 and 208 pati ents. Median follow-up period was 68 months (mean: 67 +/- 29, range: 2 4 to 130 months). Results: Five-year survival, LFS, RI and TRM rates w ere 42%, 40%, 47%, and 24%, respectively. Five-year LFS was 36% in the STBI and 45% in the FTBI group (p = 0.17). It was 36% in the LOW grou p, 42% in the MEDIUM group, and 30% in the HIGH group (p > 0.05). Five -year RI was 50% in STBI; 43% in FTBI, 55% in LOW, 41% in MEDIUM, and 44% in HIGH groups (STBI vs. FTBI, p = 0.48; LOW vs. MEDIUM, p = 0.03; MEDIUM vs. HIGH, p = 0.68). TRM was not influenced significantly by t he different TBI techniques. When analyzing separately the influence o f fractionation and the instantaneous dose rate either in ANLL or ALL patients, no difference in terms of survival and LFS was observed. Fra ctionation did not influence the 5-year RI both in ANLL and ALL patien ts. However, among the patients with ANLL, 5-year RI was significantly higher (58%) in the LOW group than the MEDIUM group (31%, p = 0.001), whereas instantaneous dose rate did not significantly influence the R I in ALL patients. The 5-year TRM rate was significantly higher in all ogeneic BMT group both in ANLL (37%) and ALL (37%) patients than those treated by autologous BMT (ANLL: 15%, ALL: 18%; p = 0.002 and 0.02, r espectively). The 5-year estimated interstitial pneumonitis (IP) and c ataract incidence rates were 22% and 19%. respectively, in all patient s. IP incidence seemed to be higher in the HIGH group (46%) than the M EDIUM (19%, p = 0.05) or LOW (25%, p = 0.15) groups. Furthermore, cata ract incidence was significantly influenced by fractionation (STBI vs. FTBI, 29% vs. 9%; p = 0.003) and instantaneous dose rate (LOW vs. MED IUM vs. HIGH, 0% vs. 27% vs. 33%; p < 0.0001). Multivariate analyses r evealed that the best factors influencing the survival were Ist CR (p = 0.0007), age less than or equal to 40 years (p = 0.003), and BMT aft er 1985 (p = 0.008). The RI was influenced independently only by the r emission status (p = 0.0002). On the other hand, the TRM rate was lowe r in patients who did not experience graft-vs.-host disease (GVHD, p < 0.0001), and in those treated after 1985 (p = 0.0005). GVHD was the o nly independent factor involved in the development of IP (p = 0.01). W hen considering the cataract incidence, the only independent factor wa s the instantaneous dose rate (p = 0.0008). Conclusion: The outcome of BMT patients conditioned with TBI for acute leukemia was not signific antly influenced by the TBI technique, and TRM seemed to be lower in p atients treated after 1985. On the other hand, cataract incidence was significantly influenced by the instantaneous dose rate.