Gabarre J, Lepage E, Thyss A, Tubiana R, Bastion Y, Schlaifer D, Sebban C, Ribrag V, Fereres M, Raphael M
Department of Hematology, Hopital Pitie Salpetriere, France.
Ann Oncol. 1995 Dec;6(10):1025-32. doi: 10.1093/oxfordjournals.annonc.a059067.
The treatment of patients with non-Hodgkin's lymphoma related to the human immunodeficiency virus (HIV-NHL) is complicated by the underlying acquired immunodeficiency syndrome (AIDS). Patients without adverse prognostic factors (no AIDS prior to lymphoma, CD4+ lymphocyte counts greater than 100 x 10(6)/l and good performance status) can be cured of lymphoma and experience long-term survival. Our previous study with the intensive chemotherapy LNH84 regimen yielded a 63% complete response (CR) rate but median survival was only nine months, half of the patients died of AIDS and the other half of their lymphoma. We report here the results of a phase II study combining the same chemotherapy with zidovudine and GM-CSF. Our goal was to improve the treatment outcome over that of our previous study; GM-CSF was expected to decrease the hematological toxicity of chemotherapy and thus permit a dose intensity increase, while zidovudine was supposed to slow down the evolution of AIDS.
A phase II non-randomized prospective clinical trial in 7 centres.
Thirty-two consecutive adult patients presenting HIV-NHL and performance status of less than three without active opportunistic infection underwent three cycles of doxorubicin 75 mg/m2, cyclophosphamide 1,200 mg/m2, vindesine 2 mg/m2 for two days, bleomycin 10 mg for two days and prednisolone 60 mg/m2 for five days (ACVB). Chemotherapy was associated with zidovudine (5 mg/kg/d) and GM-CSF (5 mu g/kg/d). The induction phase was followed by a four-month consolidation phase.
CR and PR > 75% were observed in 56% of patients; 25% of the patients died during the induction phase. These results were analogous to those of the previous study (63% and 14%, respectively). Neither hematological tolerance nor dose intensity were improved. With a mean follow-up of 23.5 months, median survival was 6.7 months. The rate of non-NHL AIDS-related death during CR was not reduced (22% in our study vs. 16% in our previous one).
GM-CSF failed to reduce significantly the cumulative hematological toxicity of chemotherapy and zidovudine. New antiviral agents without hematological toxicity would perhaps be useful in this setting.
人类免疫缺陷病毒相关非霍奇金淋巴瘤（HIV-NHL）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。没有不良预后因素（淋巴瘤发生前无AIDS、CD4+淋巴细胞计数大于100×10⁶/l且体能状态良好）的患者可治愈淋巴瘤并长期存活。我们之前采用强化化疗LNH84方案的研究获得了63%的完全缓解（CR）率，但中位生存期仅9个月，一半患者死于AIDS，另一半死于淋巴瘤。我们在此报告一项将相同化疗与齐多夫定和粒细胞巨噬细胞集落刺激因子（GM-CSF）联合应用的II期研究结果。我们的目标是比之前的研究改善治疗结果；GM-CSF预期可降低化疗的血液学毒性，从而允许增加剂量强度，而齐多夫定应减缓AIDS的进展。
在7个中心进行的一项II期非随机前瞻性临床试验。
32例连续的成年HIV-NHL患者，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连用两天、博来霉素10mg连用两天及泼尼松龙60mg/m²连用五天（ACVB）。化疗联合齐多夫定（5mg/kg/d）和GM-CSF（5μg/kg/d）。诱导期后为四个月的巩固期。
56%的患者观察到CR和PR>75%；25%的患者在诱导期死亡。这些结果与之前的研究类似（分别为63%和14%）。血液学耐受性和剂量强度均未改善。平均随访23.5个月，中位生存期为6.7个月。CR期间非NHL AIDS相关死亡的发生率未降低（我们的研究中为22%，之前的研究中为16%）。
GM-CSF未能显著降低化疗和齐多夫定的累积血液学毒性。无血液学毒性的新型抗病毒药物在这种情况下可能有用。
