Belkacémi Y, Pène F, Touboul E, Rio B, Leblond V, Gorin N C, Laugier A, Gemici C, Housset M, Ozsahin M
Department of Radiation Oncology, Hôpital Tenon, Paris, France.
Strahlenther Onkol. 1998 Feb;174(2):92-104. doi: 10.1007/BF03038482.
In order to assess the influence of total-body irradiation (TBI) on the outcome and incidence of complication after bone marrow transplantation (BMT), we retrospectively analyzed our patients treated for acute leukemia and conditioned with TBI prior to BMT.
Between 1980 and 1993, 326 patients referred to our department with acute non-lymphoblastic leukemia (ANLL, n = 182) and acute lymphoblastic leukemia (ALL, n = 144) in complete remission underwent TBI either 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 on 3 consecutive days, and 9 Gy to the lungs [FTBI]) before BMT. The male-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 according to 3 instantaneous dose rate groups: 118 patients in the LOW group (< or = 0.048 Gy/min), 188 in the MEDIUM group (> 0.048 and < or = 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, allogeneic and autologous BMT were realized respectively in 118 and 208 patients. Median follow-up period was 68 months (mean: 67 +/- 29, range: 24 to 130 months).
Five-year survival, LFS, RI and TRM rates were 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 group, 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 the different TBI techniques. When analyzing separately the influence of fractionation and the instantaneous dose rate either in ANLL or ALL patients, no difference in terms of survival and LFS was observed. Fractionation did not influence the 5-year RI both in ANLL and ALL patients. 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 RI in ALL patients. The 5-year TRM rate was significantly higher in allogeneic 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, respectively). The 5-year estimated interstitial pneumonitis (IP) and cataract incidence rates were 22% and 19%, respectively, in all patients. IP incidence seemed to be higher in the HIGH group (46%) than the MEDIUM (19%, p = 0.05) or LOW (25%, p = 0.15) groups. Furthermore, cataract incidence was significantly influenced by fractionation (STBI vs. FTBI, 29% vs. 9%; p = 0.003) and instantaneous dose rate (LOW vs. MEDIUM vs. HIGH, 0% vs. 27% vs. 33%; p < 0.0001). Multivariate analyses revealed that the best factors influencing the survival were 1st CR (p = 0.0007), age < or = 40 years (p = 0.003), and BMT after 1985 (p = 0.008). The RI was influenced independently only by the remission status (p = 0.0002). On the other hand, the TRM rate was lower 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 only independent factor involved in the development of IP (p = 0.01). When considering the cataract incidence, the only independent factor was the instantaneous dose rate (p = 0.0008).
The outcome of BMT patients conditioned with TBI for acute leukemia was not significantly influenced by the TBI technique, and TRM seemed to be lower in patients treated after 1985. On the other hand, cataract incidence was significantly influenced by the instantaneous dose rate.
为了评估全身照射（TBI）对骨髓移植（BMT）后结局及并发症发生率的影响，我们回顾性分析了在BMT前接受TBI预处理的急性白血病患者。
1980年至1993年间，326例处于完全缓解期的急性非淋巴细胞白血病（ANLL，n = 182）和急性淋巴细胞白血病（ALL，n = 144）患者转诊至我科，在BMT前接受了单次剂量的TBI（190例患者：中平面给予10 Gy，肺部给予8 Gy [单次全身照射（STBI）]）或分6次给予的TBI（136例患者：连续3天给予12 Gy，肺部给予9 Gy [分次全身照射（FTBI）]）。男女比例为204/122（1.67），中位年龄为30岁（平均：30±11，范围：3至63岁）。患者根据3个即时剂量率组进行分析：低剂量组（≤0.048 Gy/min）118例患者，中剂量组（> 0.048且≤0.09 Gy/min）188例患者，高剂量组（> 0.09 cGy/min）20例患者。预处理化疗中，250例患者仅使用环磷酰胺（CY），54例患者使用CY及其他药物，22例患者使用不含CY的联合方案进行预处理。TBI后，118例和208例患者分别接受了异基因和自体BMT。中位随访期为68个月（平均：67±29，范围：24至130个月）。
5年生存率、无白血病生存率（LFS）、复发率（RI）和移植相关死亡率（TRM）分别为42%、40%、47%和24%。STBI组的5年LFS为36%，FTBI组为45%（p = 0.17）。低剂量组为36%，中剂量组为42%，高剂量组为30%（p>0.05）。STBI组的5年RI为50%，FTBI组为43%，低剂量组为55%，中剂量组为41%，高剂量组为44%（STBI与FTBI比较，p = 0.48；低剂量组与中剂量组比较，p = 0.03；中剂量组与高剂量组比较，p = 0.68）。不同的TBI技术对TRM无显著影响。分别分析ANLL或ALL患者中分次照射和即时剂量率的影响时，在生存率和LFS方面未观察到差异。分次照射对ANLL和ALL患者的5年RI均无影响。然而，在ANLL患者中，低剂量组的5年RI显著高于中剂量组（58%对31%，p = 0.001），而即时剂量率对ALL患者的RI无显著影响。异基因BMT组的ANLL（37%）和ALL（37%）患者的5年TRM率均显著高于自体BMT组（ANLL：15%，ALL：18%；p分别为0.002和0.02）。所有患者的5年间质性肺炎（IP）和白内障发生率分别为22%和19%。高剂量组的IP发生率似乎高于中剂量组（19%，p = 0.05）或低剂量组（25%，p = 0.15）（46%）。此外，白内障发生率受分次照射（STBI与FTBI，分别为
