Ratanatharathorn V, Uberti J, Karanes C, Abella E, Lum L G, Momin F, Cummings G, Sensenbrenner L L
Division of Hematology, Wayne State University/Detroit Medical Center Bone Marrow Transplant Program, MI.
Blood. 1994 Aug 15;84(4):1050-5.
A prospective comparative trial of allogeneic versus autologous bone marrow transplant (BMT) was conducted. Sixty-six consecutive patients (median age, 41; range, 15 to 60; female:male ratio = 21:45) entered this clinical trial. Priority for allogeneic BMT was given to patients who were 55 or younger and had a major histocompatibility complex-matched or 1-antigen-disparate sibling donor. Autologous BMT was offered to all other patients whose age was 60 or younger. Patients who had no sibling donor and who had BM involvement at the time of evaluation were not eligible. Thirty-one patients received an allograft, and 35 patients received an autograft. Thirteen patients received a BM graft purged with 4-hydroperoxycyclophosphamide because of previous BM involvement. Patients who had previous radiation to the thoracic and/or abdominal areas of more than 20 Gy received a preparative regimen consisting of cyclophosphamide (1,800 mg/m2/d for 4 days), VP-16 (200 mg/m2 every 12 hours for 8 doses), and 1,3-bis(2-chloroethyl)-1-nitrosourea (600 mg/m2 as 1 dose). Other patients received cyclophosphamide 1,800 mg/m2/d for 4 days followed by total body irradiation of 12 Gy administered as a single daily fraction over 4 days. With a median follow-up of 14 months, the progression-free survival (PFS) for autograft and allograft recipients was 24% +/- 8% (+/- SE) and 47% +/- 9%, respectively, (P = .21). However, the probability of disease progression was significantly higher in the autologous group (69% +/- 9%) than in the allogeneic group (20% +/- 10%; P = .001). When other confounding prognostic factors were adjusted in the multivariate analysis, chemosensitive disease and allograft were found to have a significant favorable influence on probability of disease progression (P = .03 and .003), but only chemosensitive disease had a significant influence on the PFS (P < .002). Our results suggest the existence of graft-versus-lymphoma effect and also support the rationale of using immunotherapy after autologous BMT. Allogeneic BMT should be preferable to autologous BMT in younger patients with lymphoma.
开展了一项异基因与自体骨髓移植（BMT）的前瞻性对照试验。66例连续患者（中位年龄41岁；范围15至60岁；女性与男性比例为21:45）进入该临床试验。异基因BMT优先用于年龄在55岁及以下且有主要组织相容性复合体匹配或1个抗原不相合的同胞供者的患者。自体BMT提供给所有其他年龄在60岁及以下的患者。没有同胞供者且在评估时骨髓受累的患者不符合条件。31例患者接受了同种异体移植，35例患者接受了自体移植。13例因既往骨髓受累而接受用4-氢过氧环磷酰胺净化的骨髓移植的患者。既往胸部和/或腹部接受超过20 Gy放疗的患者接受由环磷酰胺（1800 mg/m²/天，共4天）、依托泊苷（200 mg/m²，每12小时1次，共8剂）和1,3-双（2-氯乙基）-1-亚硝基脲（600 mg/m²，1剂）组成的预处理方案。其他患者接受环磷酰胺1800 mg/m²/天，共4天，随后在4天内每天单次给予12 Gy全身照射。中位随访14个月时，自体移植和同种异体移植受者的无进展生存期（PFS）分别为24%±8%（±SE）和47%±9%（P = 0.21）。然而，自体移植组疾病进展的概率（69%±9%）显著高于异基因移植组（20%±10%；P = 0.001）。在多变量分析中对其他混杂的预后因素进行调整后，发现化疗敏感疾病和同种异体移植对疾病进展概率有显著的有利影响（P = 0.03和0.003），但只有化疗敏感疾病对PFS有显著影响（P < 0.002）。我们的结果提示存在移植物抗淋巴瘤效应，也支持自体BMT后使用免疫治疗的理论依据。在年轻淋巴瘤患者中，异基因BMT应优于自体BMT。
