Gisselbrecht C, Oksenhendler E, Tirelli U, Lepage E, Gabarre J, Farcet J P, Gastaldi R, Coiffier B, Thyss A, Raphael M
Department of Hematology, Hôpital Saint Louis, Paris, France.
Am J Med. 1993 Aug;95(2):188-96. doi: 10.1016/0002-9343(93)90259-r.
An increased risk of high-grade non-Hodgkin's lymphoma is observed in patients who are seropositive for human immunodeficiency virus (HIV). Treatment of such patients is complicated by their underlying acquired immunodeficiency syndrome (AIDS). Intensive strategies such as those used in non-HIV-related lymphoma may be poorly tolerated. However, patients without severe AIDS may derive significant benefits from such an approach. In a prospective multicenter study, treatment outcomes were assessed in 141 cases of HIV-seropositive lymphomas submitted to aggressive chemotherapy.
Adult patients with lymphoma with a performance status less than 3 and no active opportunistic infection were consecutively treated with three cycles of doxorubicin 75 mg/m2, cyclophosphamide 1,200 mg/m2, vindesine 2 mg/m2 for 2 days, bleomycin 10 mg for 2 days, and prednisolone 60 mg/m2 for 5 days (ACVB). This treatment was followed by a consolidation phase of high-dose methotrexate plus leucovorin, ifosfamide, etoposide, asparaginase, and cytarabine (LNH84). Central nervous system prophylaxis with intrathecal methotrexate was routinely used. Zidovudine maintenance therapy was started after chemotherapy. Ninety-three patients had high-grade lymphomas (59 Burkitt's type) and 48 had intermediate-grade lymphomas. Disseminated stage III-IV was present in 86 patients, meningeal involvement in 29, and bone marrow infiltration in 30; 62 patients had more than 2 extranodal localizations. Lactate dehydrogenase levels were above the normal value in 95 cases. The median CD4-positive lymphocyte count was 227 x 10(6)/L.
Eighty-nine patients (63%) achieved complete remission (CR) and 19 (13%) partial remission, whereas 13 did not respond and 20 (14%) died during the course of ACVB, 8 of them from progressive disease. With a median follow-up of 28 months, median survival and disease-free survival were 9 and 16 months, respectively. Median survival for nonresponders was 5 months; 23 patients died of opportunistic infections while in persistent CR. In multivariate analysis, four factors were strongly associated with shorter survival: (1) CD4 count less than 100 x 10(6)/L, (2) performance status greater than 1, (3) immunoblastic lymphoma, and (4) prior AIDS. In the absence of all risk factors, the probability of survival at 2 years was 50%.
In a selected group of HIV-related lymphomas, intensive chemotherapy with LNH84 is feasible and yields a high CR rate. Survival is short due to death from HIV-related infections; however, in a subgroup of patients without adverse prognostic factors, long-term remission was observed.
在人类免疫缺陷病毒（HIV）血清学阳性的患者中，观察到高级别非霍奇金淋巴瘤的风险增加。此类患者的治疗因潜在的获得性免疫缺陷综合征（AIDS）而变得复杂。诸如用于非HIV相关淋巴瘤的强化治疗策略可能耐受性较差。然而，没有严重AIDS的患者可能从这种方法中获得显著益处。在一项前瞻性多中心研究中，对141例接受积极化疗的HIV血清学阳性淋巴瘤患者的治疗结果进行了评估。
连续对141例淋巴瘤成年患者进行治疗，这些患者的体能状态小于3且无活动性机会性感染，接受三个周期的多柔比星75mg/m²、环磷酰胺1200mg/m²、长春地辛2mg/m²，连用2天，博来霉素10mg，连用2天，泼尼松龙60mg/m²，连用5天（ACVB方案）。该治疗之后是高剂量甲氨蝶呤加亚叶酸钙、异环磷酰胺、依托泊苷、天冬酰胺酶和阿糖胞苷的巩固阶段（LNH84方案）。常规采用鞘内注射甲氨蝶呤进行中枢神经系统预防。化疗后开始齐多夫定维持治疗。93例患者为高级别淋巴瘤（59例为伯基特型），48例为中级别淋巴瘤。86例患者处于播散性III - IV期，29例有脑膜受累，30例有骨髓浸润；62例患者有超过2个结外部位受累。95例患者的乳酸脱氢酶水平高于正常值。CD4阳性淋巴细胞计数中位数为227×10⁶/L。
89例患者（63%）实现完全缓解（CR），19例（13%）部分缓解，而13例无反应，20例（14%）在ACVB治疗过程中死亡，其中8例死于疾病进展。中位随访28个月，中位生存期和无病生存期分别为9个月和16个月。无反应者的中位生存期为5个月；23例患者在持续CR期间死于机会性感染。在多变量分析中，四个因素与较短生存期密切相关：（1）CD4计数小于100×10⁶/L，（2）体能状态大于1，（3）免疫母细胞淋巴瘤，（4）既往有AIDS。在没有所有危险因素的情况下，2年生存率为50%。
在一组选定的HIV相关淋巴瘤患者中，采用LNH84方案进行强化化疗是可行的，且完全缓解率高。由于死于HIV相关感染，生存期较短；然而，在一个没有不良预后因素的亚组患者中，观察到了长期缓解。
