Cortes J, O'Brien S M, Pierce S, Keating M J, Freireich E J, Kantarjian H M
Department of Hematology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Blood. 1995 Sep 15;86(6):2091-7.
Although central nervous system (CNS) leukemic relapse is frequent in adult acute lymphocytic leukemia (ALL), the need for prophylaxis in different risk groups for CNS relapse, the value of high-dose systemic and intrathecal (IT) chemotherapy, and the timing of prophylaxis are not well defined. This analysis was conducted to investigate these questions and to assess the value of a risk-oriented CNS prophylaxis approach. We analyzed the incidence of CNS leukemia after initiation of therapy in patients treated on 4 consecutive trials for adult ALL including different CNS prophylactic modalities. The treatment groups included (1) the program preceeding the vincristine-Adriamycin-dexamethasone (VAD) regimen, with no CNS prophylaxis; (2) the VAD regimen with prophylaxis using high-dose systemic chemotherapy; (3) the modified VAD program with high-dose systemic chemotherapy to all patients and IT chemotherapy for high-risk patients after achieving complete remission; and (4) the hyperCVAD program with early high-dose systemic and IT chemotherapy starting during induction to all patients, with more IT injections (16IT) administered to the high-risk group for CNS relapse compared with the low-risk group (4IT). A total of 391 patients were included, 73 of whom were treated with preVAD, 112 with VAD, 114 with modified VAD, and 92 with hyperCVAD. The overall CNS relapse rates were 31%, 18%, 17%, and 3%, respectively for the 4 groups (P < .001). For the high-risk group for CNS relapse, they were 42%, 26%, 20%, and 2%, respectively (P < .001). The differences in CNS relapse rates in the low-risk group were not statistically significant. At 3 years, the overall CNS leukemia event-free rates were 48%, 76%, and 98%, respectively (P < .001). In the high-risk group, the CNS event-free rates were 38%, 66%, 75%, and 98%, respectively (P < .001); however, there was no difference in the low-risk group. We conclude that (1) high-dose systemic chemotherapy is a useful prophylactic measure; (2) early IT chemotherapy is necessary to reduce the incidence of CNS leukemia overall and in the high-risk group; and (3) a risk-oriented approach is appropriate to tailor the intensity of CNS prophylaxis.
尽管中枢神经系统（CNS）白血病复发在成人急性淋巴细胞白血病（ALL）中很常见，但不同CNS复发风险组是否需要进行预防、大剂量全身化疗和鞘内（IT）化疗的价值以及预防时机尚不清楚。进行这项分析是为了研究这些问题，并评估以风险为导向的CNS预防方法的价值。我们分析了在连续4项针对成人ALL的试验中接受治疗的患者开始治疗后CNS白血病的发生率，这些试验采用了不同的CNS预防方式。治疗组包括：（1）在长春新碱-阿霉素-地塞米松（VAD）方案之前的方案，未进行CNS预防；（2）采用大剂量全身化疗进行预防的VAD方案；（3）对所有患者采用大剂量全身化疗，对高危患者在完全缓解后进行IT化疗的改良VAD方案；（4）对所有患者在诱导期开始时即进行早期大剂量全身化疗和IT化疗的hyperCVAD方案，与低危组（4次IT注射）相比，高危组CNS复发患者接受更多的IT注射（16次IT）。总共纳入了391例患者，其中73例接受preVAD治疗，112例接受VAD治疗，114例接受改良VAD治疗，92例接受hyperCVAD治疗。4组的总体CNS复发率分别为31%、18%、17%和3%（P <.001）。对于CNS复发高危组，复发率分别为42%、26%、20%和2%（P <.001）。低危组CNS复发率的差异无统计学意义。3年时，总体CNS白血病无事件生存率分别为48%、76%和98%（P <.001）。在高危组中，CNS无事件生存率分别为38%、66%、75%和98%（P <.001）；然而，低危组无差异。我们得出结论：（1）大剂量全身化疗是一种有用的预防措施；（2）早期IT化疗对于降低总体及高危组CNS白血病的发生率是必要的；（3）以风险为导向的方法适合调整CNS预防的强度。
