Is veno-occlusive disease incidence influenced by the total-body irradiation technique?

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.