Cull G M, Haynes A P, Byrne J L, Carter G I, Miflin G, Rebello P, Hale G, Waldmann H, Russell N H
Division of Haematology, School of Clinical and Laboratory Sciences, University of Nottingham, UK.
Br J Haematol. 2000 Mar;108(4):754-60. doi: 10.1046/j.1365-2141.2000.01879.x.
Autologous transplantation has an established role in the treatment of lymphoproliferative disorders, but allogeneic transplantation remains controversial. In an attempt to reduce the high procedure-related mortality reported with allografting in lymphoma, we have used BEAM (BCNU, etoposide, cytarabine and melphalan), a standard conditioning regimen for autologous transplantation. As BEAM may be insufficiently immunosuppressive to permit durable engraftment in the allogeneic setting, patients received additional pretransplant immunosuppression with the anti-CD52 antibody CAMPATH-1G from day -5 to day -1. Twelve patients (median age 46 years) underwent allogeneic transplantation for lymphoma (n = 11) or chronic lymphocytic leukaemia (n = 1) from HLA-identical (n = 9) or mismatched (n = 3) sibling donors. Cyclosporin A and methotrexate were used as graft-versus-host disease (GVHD) prophylaxis. One patient died of progressive lymphoma at day +12, the remaining 11 patients engrafted rapidly, with eight demonstrating full donor chimerism. One patient had an episode of rejection and received a further stem cell infusion with sustained recovery. Only one patient developed GVHD (grade I). The low incidence of acute GVHD may be in part related to persisting levels of in vivo CAMPATH-IG at the time of transplantation. Of 11 evaluable patients, nine achieved complete remission (CR), and a further patient achieved CR after donor lymphocyte infusion at 5 months. Our preliminary experience is that this regimen was well tolerated with a low risk of GVHD and appears no more toxic than a BEAM autograft. Further follow-up is required to see whether the low incidence of GVHD impacts upon relapse risk.
自体移植在淋巴增生性疾病的治疗中已确立了其作用,但同种异体移植仍存在争议。为了降低淋巴瘤同种异体移植中报道的与手术相关的高死亡率,我们采用了BEAM方案(卡莫司汀、依托泊苷、阿糖胞苷和美法仑),这是自体移植的标准预处理方案。由于BEAM可能不足以产生足够的免疫抑制作用以允许在同种异体环境中持久植入,患者从第-5天至第-1天接受了抗CD52抗体CAMPATH-1G的额外移植前免疫抑制。12例患者(中位年龄46岁)接受了淋巴瘤(n = 11)或慢性淋巴细胞白血病(n = 1)的同种异体移植,供者为HLA相同(n = 9)或不匹配(n = 3)的同胞。环孢素A和甲氨蝶呤用于预防移植物抗宿主病(GVHD)。1例患者在第+12天死于进行性淋巴瘤,其余11例患者迅速植入,其中8例显示完全供者嵌合。1例患者发生排斥反应并接受了进一步的干细胞输注,随后持续恢复。仅1例患者发生GVHD(I级)。急性GVHD的低发生率可能部分与移植时体内CAMPATH-1G的持续水平有关。在11例可评估的患者中,9例实现完全缓解(CR),另1例患者在5个月时接受供者淋巴细胞输注后实现CR。我们的初步经验是,该方案耐受性良好,GVHD风险低,且毒性似乎不高于BEAM自体移植。需要进一步随访以观察GVHD的低发生率是否会影响复发风险。