Morra E, Lazzarino M, Brusamolino E, Pagnucco G, Castagnola C, Bernasconi P, Orlandi E, Corso A, Santagostino A, Bernasconi C
Chair of Hematology University of Pavia, Italy.
Cancer. 1993 Jul 15;72(2):439-45. doi: 10.1002/1097-0142(19930715)72:2<439::aid-cncr2820720220>3.0.co;2-4.
Given the good penetration of systemic high-dose cytarabine (HDara-C) into the cerebrospinal fluid (CSF), this approach was used to treat patients with central nervous system (CNS) leukemia, either isolated or with concurrent extraneurologic disease (END).
From 1983 to 1991, 46 adults with CNS involvement were treated with systemic HDara-C: 25 had acute lymphoblastic leukemia (ALL), 15 had high-grade non-Hodgkin lymphoma (NHL), 5 had acute myelogenous leukemia (AML), and 1 had lymphoid blast crisis of chronic myelogenous leukemia. Induction consisted of HDara-C 3 g/m2 every 12 hours, by 3-hour infusion, for 8 doses (30 patients), or 6 doses (16 patients), followed by 4 doses at day 21.
Of 46 patients, 29 (63%) achieved complete remission (CR): 15/15 with isolated CNS leukemia, and 14/31 (45%) with CNS and concurrent marrow or lymph node disease. Of 17 patients not meeting CR criteria because of persistent END, 11 showed complete CNS response. The first 10 remitters were consolidated with monthly 4-dose courses of HDara-C. The remaining 19 received postinduction multidrug chemotherapy (including vincristine, doxorubicin, cyclophosphamide, L-asparaginase, etoposide plus intermediate-dose ara-C, mitoxantrone plus HDara-C) and intrathecal methotrexate (MTX) +/- cranial radiation therapy. One patient underwent autologous and one allogeneic bone marrow transplant. Median CR duration was 7 months (range, 2-56+): 8 months for patients with isolated CNS leukemia, and 4 months for those with concurrent END: In only two patients was CNS the primary site of relapse. Three patients with isolated CNS leukemia are disease-free at 23, 40, and 56 months. The main toxicity was myelosuppression. No patient showed dose-limiting neurologic toxicity.
Systemic HDara-C appears effective therapy for CNS leukemia, maximally in cases with isolated CNS involvement. HDara-C may be combined safely with cranial radiation therapy and intrathecal MTX. This approach for CNS leukemia, however, needs to be combined with additional treatments to eradicate residual disease in extraneurologic compartments.
鉴于全身大剂量阿糖胞苷（HDara-C）可有效穿透进入脑脊液（CSF），该方法被用于治疗中枢神经系统（CNS）白血病患者，包括孤立性CNS白血病或合并有神经系统外疾病（END）的患者。
1983年至1991年期间，46例有CNS受累的成人患者接受了全身HDara-C治疗：25例患有急性淋巴细胞白血病（ALL），15例患有高级别非霍奇金淋巴瘤（NHL），5例患有急性髓细胞白血病（AML），1例患有慢性髓细胞白血病的淋巴母细胞危象。诱导治疗方案为每12小时给予HDara-C 3 g/m²，通过3小时静脉输注，共8剂（30例患者）或6剂（16例患者），然后在第21天给予4剂。
46例患者中，29例（63%）达到完全缓解（CR）：15例孤立性CNS白血病患者中有15例达到CR，31例合并CNS及骨髓或淋巴结疾病的患者中有14例（45%）达到CR。17例因持续性END未达CR标准的患者中，11例显示CNS完全缓解。前10例缓解者接受每月4剂疗程的HDara-C巩固治疗。其余19例接受诱导后多药化疗（包括长春新碱、阿霉素、环磷酰胺、L-天冬酰胺酶、依托泊苷加中剂量阿糖胞苷、米托蒽醌加HDara-C）和鞘内甲氨蝶呤（MTX）+/-头颅放射治疗。1例患者接受了自体骨髓移植，1例接受了异基因骨髓移植。CR持续时间的中位数为7个月（范围为2 - 56 +）：孤立性CNS白血病患者为8个月，合并END的患者为4个月。仅2例患者CNS是复发的主要部位。3例孤立性CNS白血病患者分别在23、40和56个月时无病生存。主要毒性为骨髓抑制。无患者出现剂量限制性神经毒性。
全身HDara-C似乎是治疗CNS白血病的有效方法，在孤立性CNS受累的病例中效果最佳。HDara-C可安全地与头颅放射治疗和鞘内MTX联合使用。然而，这种治疗CNS白血病的方法需要与其他治疗相结合，以根除神经系统外区域的残留疾病。
