Belkacémi Y, Ozsahin M, Rio B, Laporte J P, Leblond V, Pène F, Laugier A
Department of Radiation Oncology, Hôpital Tenon, Paris, France.
Strahlenther Onkol. 1995 Dec;171(12):694-7.
In order to assess the influence of total-body irradiation technique on veno-occlusive disease (VOD) incidence, we retrospectively analyzed our leukemia patients treated with bone-marrow transplantation conditioned using total-body irradiation and high-dose chemotherapy.
Between 1980 and 1992, 305 patients with acute non-lymphoblastic leukemia (ANLL; n = 170) and acute lymphoblastic leukemia (ALL; n = 135) were treated with bone-marrow transplantation in their first complete remission (CR; n = 223) or in second CR (n = 82). All patients underwent total-body irradiation either in single dose (n = 176; 10 Gy to L4, 8 Gy to the lungs) or in 6 fractions (n = 129; 12 Gy in 3 consecutive days to L4, 9 Gy to the lungs) before bone-marrow transplantation. Patients were analyzed in 2 instantaneous dose rate groups: 104 (34%) patients received an instantaneous dose rate < or = 4.80 cGy/min (mean: 3.07 +/- 0.60 cGy/min), and 201 (66%) > 4.80 cGy/min (mean: 6.60 cGy/min +/- 0.30). Conditioning chemotherapy consisted of cyclophosphamide alone in 231 patients, cyclophosphamide and etoposide or melphalan in 53 patients, and 21 patients were conditioned with cytosine arabinoside and melphalan. Bone-marrow transplantation was autologous in 197 patients, and allogeneic in 108 patients.
Thirty (10%) of the 305 patients experienced VOD. In univariate analyses, its incidence was not influenced by instantaneous dose rate (9.6% [10/104] in < or = 4.80 cGy/min group vs. 10% [20/201] in > 4.80 cGy/min group; p = 0.91), fractionation (11% [19/176] in single-dose total-body irradiation vs. 8.5% [11/129] in fractionated total-body irradiation, p = 0.64), age (9% [21/241] in < or = 40-year old-patients vs. 14% [9/64] in > 40-year-old patients, p = 0.29), sex (6% [7/113] in male patients vs. 12% [23/192] in female patients, p = 0.15), type of VOD prevention (16% [16/101] in patients using heparin vs. 10% [14/142] in those receiving dinoprostone and pentoxifylline combination, p = 0.23), type of bone-marrow transplantation (9% [10/108] in allogeneic bone-marrow transplantation group vs. 10% [20/197] in autologous bone-marrow transplantation group, p = 0.96), or type of acute leukemia (9.6% [13/135] in ALL vs. 10% [17/170] in ANLL, p = 0.93). However, VOD incidence was significantly lower in patients whose conditioning chemotherapy consisted of cyclophosphamide alone (6.5% [15/231] vs. 20% [15/74] by other drugs +/- cyclophosphamide, p < 0.0001), and in patients treated after 1985 (7% [16/226] vs. 18% [14/79] in those treated before 1985, p = 0.01). Multivariate logistic regression analysis revealed that the best independent factors influencing the occurrence of VOD were the male sex (p = 0.03), conditioning chemotherapy consisting of cyclophosphamide alone (p = 0.01), and bone-marrow transplantation after 1985 (p = 0.008).
In our series of 305 acute leukemia patients treated with allogenic or autologous bone-marrow transplantation, total-body irradiation technique (fractionation or instantaneous dose rate) did not seem to influence the incidence of VOD.
为了评估全身照射技术对静脉闭塞性疾病（VOD）发生率的影响，我们回顾性分析了接受全身照射和高剂量化疗预处理的骨髓移植白血病患者。
1980年至1992年间，305例急性非淋巴细胞白血病（ANLL；n = 170）和急性淋巴细胞白血病（ALL；n = 135）患者在首次完全缓解（CR；n = 223）或第二次CR（n = 82）时接受了骨髓移植。所有患者在骨髓移植前均接受了单次全身照射（n = 176；L4照射10 Gy，肺部照射8 Gy）或分6次照射（n = 129；连续3天L4照射12 Gy，肺部照射9 Gy）。患者被分为2个瞬时剂量率组：104例（34%）患者的瞬时剂量率≤4.80 cGy/min（平均：3.07±0.60 cGy/min），201例（66%）患者的瞬时剂量率＞4.80 cGy/min（平均：6.60 cGy/min±0.30）。预处理化疗中，231例患者仅使用环磷酰胺，53例患者使用环磷酰胺联合依托泊苷或美法仑，21例患者使用阿糖胞苷联合美法仑进行预处理。197例患者进行了自体骨髓移植，108例患者进行了异体骨髓移植。
305例患者中有30例（10%）发生了VOD。在单因素分析中，其发生率不受瞬时剂量率（≤4.80 cGy/min组为9.6%[10/104]，＞4.80 cGy/min组为10%[20/201]；p = 0.91）、分次照射（单次全身照射组为11%[19/176]，分次全身照射组为8.5%[11/129]，p = 0.64）、年龄（≤40岁患者为9%[21/241]，＞40岁患者为14%[9/64]，p = 0.29）、性别（男性患者为6%[7/113]，女性患者为12%[23/192]，p = 0.15）、VOD预防类型（使用肝素的患者为16%[16/101]，接受地诺前列酮和己酮可可碱联合治疗的患者为10%[14/142]，p = 0.23）、骨髓移植类型（异体骨髓移植组为9%[10/108]，自体骨髓移植组为10%[20/197]，p = 0.96）或急性白血病类型（ALL为9.6%[13/135]，ANLL为10%[17/170]，p = 0.93）的影响。然而，仅使用环磷酰胺进行预处理化疗的患者VOD发生率显著较低（6.5%[15/231]，而使用其他药物±环磷酰胺的患者为20%[15/74]，p＜0.0001），1985年后治疗的患者VOD发生率也较低（7%[16/226]，而1985年前治疗的患者为18%[14/79]，p = 0.01）。多因素逻辑回归分析显示，影响VOD发生的最佳独立因素为男性（p = 0.03）、仅使用环磷酰胺进行预处理化疗（p = 0.01）以及1985年后进行骨髓移植（p = 0.008）。
在我们这组305例接受异体或自体骨髓移植的急性白血病患者中，全身照射技术（分次照射或瞬时剂量率）似乎并未影响VOD的发生率。
