Uckun F M, Song C W, Nesbit M, Kersey J H, Ramsay N K
Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Health Sciences Center, Minneapolis 55455.
Int J Radiat Oncol Biol Phys. 1992;24(4):705-12. doi: 10.1016/0360-3016(92)90718-w.
In the preclinical arm of our study, the radiobiologic features of primary malignant cells from newly diagnosed and relapsed T-lineage acute lymphoblastic leukemia/non-Hodgkin's lymphoma patients were analyzed using clonogenic assays. A marked heterogeneity existed relative to the intrinsic radiation sensitivity of clonogenic T-lineage ALL/NHL cells from 42 patients. The mean SF2 (surviving fraction at 200 cGy) and alpha values (initial slope of the survival curve) were 0.36 +/- 0.04, and 0.558 +/- 0.079 Gy-1. Fourteen cases had SF2 values of > or = 0.50 and alpha values of < or = 0.2 Gy-1, consistent with a marked intrinsic radiation resistance at the level of clonogenic leukemia/lymphoma cells. Of these 14 radiation resistant cases, 12 were CD3+. Furthermore, the SF2 and D0 values of the 28 CD3+ cases were significantly higher than the SF2 and D0 values of the 14 CD3- cases (SF2: 0.441 +/- 0.048 versus 0.189 +/- 0.045, p = 0.002; D0: 189.6 +/- 26.3 cGy versus 108.7 +/- 18.2 cGy, p = 0.047) and CD3+ cases had smaller alpha values than CD3- cases (0.454 +/- 0.087 versus 0.765 +/- 0.152, p = 0.06). Thus, clonogenic cells from CD3+ T-lineage ALL/NHL patients were more resistant to radiation than clonogenic cells from CD3- T-lineage ALL/NHL patients. In the clinical arm of our study, 33 T-lineage ALL/NHL patients received autologous bone marrow transplants during remission. Pretransplant conditioning consisted of total body irradiation combined with high dose chemotherapy. The expression of CD3 antigen predicted the outcome of relapsed T-lineage ALL/NHL patients undergoing autologous bone marrow transplantation following total body irradiation plus high dose chemotherapy. Overall, the Kaplan-Meier estimate and standard error of the probability of remaining in remission at 3.5 years was 11 +/- 9% with a median relapse-free interval of 102 days. The disease-free survival at 3.5 years was 8 +/- 7% with a median disease-free survival time of 96 days. Notably, the expression of CD3 antigen on T-lineage ALL/NHL cells correlated with the probability of relapse after bone marrow transplantation. While 16 of 19 CD3+ patients relapsed after bone marrow transplantation, only 3 of 8 CD3- patients relapsed. The Kaplan-Meier estimates and standard errors of the probability of remaining in remission at 1 year after bone marrow transplantation were 7 +/- 6% (median relapse-free interval = 74 days) for CD3+ patients (n = 19) and 63 +/- 17% for CD3- patients (n = 8) (p = 0.006).(ABSTRACT TRUNCATED AT 400 WORDS)
在我们研究的临床前阶段，使用克隆形成试验分析了新诊断和复发的T系急性淋巴细胞白血病/非霍奇金淋巴瘤患者的原发性恶性细胞的放射生物学特征。来自42例患者的克隆形成性T系ALL/NHL细胞的内在辐射敏感性存在明显异质性。平均SF2（200 cGy时的存活分数）和α值（存活曲线的初始斜率）分别为0.36±0.04和0.558±0.079 Gy-1。14例患者的SF2值≥0.50且α值≤0.2 Gy-1，这与克隆形成性白血病/淋巴瘤细胞水平的明显内在辐射抗性一致。在这14例辐射抗性病例中，12例为CD3阳性。此外，28例CD3阳性病例的SF2和D0值显著高于14例CD3阴性病例的SF2和D0值（SF2：0.441±0.048对0.189±0.045，p = 0.002；D0：189.6±26.3 cGy对108.7±18.2 cGy，p = 0.047），且CD3阳性病例的α值小于CD3阴性病例（0.454±0.087对0.765±0.152，p = 0.06）。因此，CD3阳性T系ALL/NHL患者的克隆形成细胞比CD3阴性T系ALL/NHL患者的克隆形成细胞对辐射更具抗性。在我们研究的临床阶段，33例T系ALL/NHL患者在缓解期接受了自体骨髓移植。移植前预处理包括全身照射联合高剂量化疗。CD3抗原的表达预测了接受全身照射加化疗后进行自体骨髓移植的复发T系ALL/NHL患者的预后。总体而言，3.5年时仍处于缓解状态的概率的Kaplan-Meier估计值和标准误差为11±9%，无复发生存期的中位数为102天。3.5年时的无病生存率为8±7%，无病生存时间的中位数为96天。值得注意的是，T系ALL/NHL细胞上CD3抗原的表达与骨髓移植后的复发概率相关。骨髓移植后，19例CD3阳性患者中有16例复发，而8例CD3阴性患者中只有3例复发。骨髓移植后1年仍处于缓解状态的概率的Kaplan-Meier估计值和标准误差，CD3阳性患者（n = 19）为7±6%（无复发生存期中位数 = 74天），CD3阴性患者（n = 8）为63±17%（p = 0.006）。（摘要截断于400字）
