INTERSTITIAL PNEUMONITIS FOLLOWING AUTOLOGOUS BONE-MARROW TRANSPLANTATION CONDITIONED WITH CYCLOPHOSPHAMIDE AND TOTAL-BODY IRRADIATION

Purpose: To assess the influence of different total-body irradiation ( TBI) regimens on interstitial pneumonitis (IP), we retrospectively ana lyzed our clinical data concerning an homogeneous group of patients co nditioned with cyclophosphamide (CY) alone and single-dose or fraction ated TBI before autologous bone-marrow transplantation (ABMT). Methods and Materials: One hundred eighty-six patients with acute nonlymphobl astic leukemia (n = 101), acute lymphoblastic leukemia (n = 62), chron ic myeloid leukemia (n = 11), non-Hodgkin's lymphoma (n = 10), and mul tiple myeloma (n = 2) referred to our department between May 13, 1981 and September 16, 1992, underwent TBI before ABMT. The male-to-female ratio was 123:63 (1.95), and mean and median age was 33 +/- 12 (6-63 y ears) and 35 years, respectively. Cyclophosphamide alone (60 mg/kg/day on each of 2 successive days) was used as conditioning chemotherapy i n all patients. Patients were irradiated according to two techniques: either with single-dose (STBI) (n = 124; 10 Gy administered to the mid plane at the level of L4, and 8 Gy to the lungs) or with fractionated (FTBI) (n = 62; 12 Gy in 6 fractions over 3 consecutive days to the mi dplane at the level of L4, and 9 Gy to the lungs) TBI. The mean instan taneous dose rate was 0.057 +/- 0.0246 Gy/min (0.0264-0,1692 Gy/min). It was less than or equal to 0.048 Gy/min in 48 patients (LOW group), > 0.048 and less than or equal to 0.09 Gy/min in 129 patients (MEDIUM group), and > 0.09 Gy/min in 9 patients (HIGH group). The median follo w-up period was 5 years (24-120 months). Results: In January 1994, the 5-year overall (including all causes of death) and disease-free survi val (DFS) rates were 50 and 48%, respectively. The 5-year DFS was 47.9 % in the STBI group, and 47.8% in the FTBI group (p = 0.77). It was 44 % in the HIGH group, 53% in the MEDIUM group, and 34% in the LOW group GLOW vs. MEDIUM, p = 0.009). The 5-year IP incidence was 17% in all p atients, 16% in the STBI group and 18% in the FTBI group (p = 0.37), b ut it was significantly higher in patients receiving high instantaneou s dose rate TBI (56% in the HIGH, 13% in the MEDIUM, 20% in the LOW gr oups; HIGH vs. MEDIUM, p = 0.002). However, sex (p = 0.37), age (18% f or > 20 vs. 10% for less than or equal to 20 years, p = 0.37), and bod y weight (> 60 kg vs. less than or equal to 60 kg, p = 0.09) did not i nfluence the IP incidence in univariate analyses, Multivariate analysi s (Cox model) revealed that the instantaneous dose rate (p = 0.05), an d the age (p = 0.04) were the two independent factors influencing the incidence of TP. Conclusion: This retrospective study including only t he patients transplanted with ABMT conditioned with CY alone and STBI or FTBI concluded that instantaneous dose rate and age significantly i nfluenced the incidence of IF, whereas sex, body weight, and fractiona tion did not.