Moiseev Ivan S, Pirogova Olga V, Alyanski Alexandr L, Babenko Elena V, Gindina Tatyana L, Darskaya Elena I, Slesarchuk Olga A, Bondarenko Sergey N, Afanasyev Boris V
R.M. Gorbacheva Memorial Institute of Hematology, Oncology and Transplantation, The First Saint-Petersburg State Medical University named I.P. Pavlov, Saint-Petersburg, Russian Federation.
R.M. Gorbacheva Memorial Institute of Hematology, Oncology and Transplantation, The First Saint-Petersburg State Medical University named I.P. Pavlov, Saint-Petersburg, Russian Federation.
Biol Blood Marrow Transplant. 2016 Jun;22(6):1037-1042. doi: 10.1016/j.bbmt.2016.03.004. Epub 2016 Mar 10.
Clinical efficacy of post-transplantation cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis has been demonstrated in haploidentical and HLA-matched bone marrow but not in unrelated peripheral blood stem cell (PBSC) transplantations. Also, no direct comparisons have been published with current standard of care, combination of antithymocyte globulin (ATG), calcineurin inhibitors, and either methotrexate or mycophenolate mofetil (MMF). Eighty-six adult patients (median age 34 years; range, 18 to 59) with acute myeloblastic and lymphoblastic leukemia underwent unrelated PBSC transplantation with PTCy, tacrolimus, and MMF as GVHD prophylaxis in the single-center trial (clinicaltrial.govNCT02294552). The control group comprised 125 consecutive historical control patients who received ATG, tacrolimus, and methotrexate or MMF. Cumulative incidences of grades II to IV acute (19% versus 45%, P = .0003), grades III to IV acute (4% versus 27%, P < .0001), and chronic GVHD (16% versus 65%, P < .0001) were significantly lower in the PTCy compared with the ATG group. PTCy-based prophylaxis was associated with reduced incidence of nonrelapse mortality (16% versus 36%, P = .005; HR, .55; 95% CI, .34 to .89) and improved overall survival (69% versus 40%, P = .0007; HR, .43; 95% CI, .26 to .70), event-free survival (65% versus 38%, P = .0006; HR, .49; 95% CI, .31 to .78), and GVHD relapse-free survival (52% versus 12%, P < .0001). PTCy-based prophylaxis also had a better safety profile compared with ATG with reduced incidence of veno-occlusive disease, cytomegalovirus reactivation, invasive mycosis, and reduced severity of mucositis. In this study we demonstrated that PTCy in combination with tacrolimus and MMF is a safe and effective GVHD prophylaxis for unrelated PBSC transplantation. Although there are several limitations of the historical control approach, this study suggests the superiority of a PTCy-based approach over an ATG-based prophylaxis.
移植后环磷酰胺（PTCy）作为移植物抗宿主病（GVHD）预防措施的临床疗效已在单倍体相合及人类白细胞抗原（HLA）匹配的骨髓移植中得到证实，但在非亲缘外周血干细胞（PBSC）移植中尚未得到证实。此外，目前尚未发表与当前标准治疗方案（抗胸腺细胞球蛋白（ATG）、钙调神经磷酸酶抑制剂以及甲氨蝶呤或霉酚酸酯（MMF）联合使用）的直接比较。在这项单中心试验（clinicaltrial.govNCT02294552）中，86例成年急性髓细胞性和淋巴细胞性白血病患者（中位年龄34岁；范围18至59岁）接受了非亲缘PBSC移植，采用PTCy、他克莫司和MMF预防GVHD。对照组包括125例连续的历史对照患者，他们接受了ATG、他克莫司和甲氨蝶呤或MMF。与ATG组相比，PTCy组II至IV级急性GVHD（19%对45%，P = 0.0003）、III至IV级急性GVHD（4%对27%，P < 0.0001）和慢性GVHD（16%对65%，P < 0.0001）的累积发生率显著更低。基于PTCy的预防措施与非复发死亡率降低相关（16%对36%，P = 0.005；风险比[HR]，0.55；95%置信区间[CI]，0.34至0.89），总生存率提高（69%对40%，P = 0.0007；HR，0.43；95%CI，0.26至0.70）、无事件生存率提高（65%对38%，P = 0.0006；HR，0.49；95%CI，0.31至0.78）以及GVHD无复发生存率提高（52%对12%，P < 0.0001）。与ATG相比，基于PTCy的预防措施安全性也更好，静脉闭塞性疾病、巨细胞病毒再激活、侵袭性真菌病的发生率降低，黏膜炎严重程度减轻。在本研究中，我们证明PTCy联合他克莫司和MMF是一种用于非亲缘PBSC移植的安全有效的GVHD预防措施。尽管历史对照方法存在一些局限性，但本研究表明基于PTCy的方法优于基于ATG的预防措施。
