诱导aGVHD策略的异基因造血干细胞移植治疗难治复发性急性白血病的初步临床报告

Induction of aGVHD after Allogeneic Hematopoietic Stem Cell Transplantation for Refractory or Relapsed Acute Leukemia

背景与目的:异基因造血干细胞移植治疗难治复发性急性白血病,因移植后复发率和移植相关死亡率高而预后仍较差。本研究旨在探讨异基因造血干细胞移植治疗难治复发性急性白血病的过程中,主动诱导急性移植物抗宿主病(acutegraft-versus-hostdisease,aGVHD)对防止复发的作用。方法:30例成人难治复发性急性白血病,其中急性淋巴细胞白血病16例,急性非淋巴细胞白血病10例,混合性急性白血病4例。移植时第一次完全缓解4例,第二次完全缓解9例,部分缓解12例,未缓解5例。分别实施亲缘性同胞外周血干细胞移植24例(全相合者21例和不相合者3例),非亲缘性全相合移植6例(骨髓移植5例和外周血干细胞移植1例)。所有病例均接受清髓性预处理而强化清除残留白血病细胞的作用。亲缘性全相合者单用环孢素A,亲缘性不相合者或非亲缘性全相合者采取环孢素A+甲氨蝶呤+骁悉+小剂量ATG方法预防aGVHD。移植后+3至+60天仍无aGVHD者,采取每周20%～30%比例逐步减少环孢素A维持剂量及预制性供者淋巴细胞输注等方法诱导移植后早期aGVHD的发生。结果:移植后中位随访18.1月,aGVHD发生率80%(24/30),其中Ⅲ～Ⅳ度aGVHD发生率13.3%(4/30)。在可评价的19例患者中慢性移植物抗宿主病(cGVHD)发生率57.9%(11/19),其中广泛性cGVHD发生率15.8%(3/19)。

BACKGROUND &OBJECTIVE: Patients with refractory or relapsed acu te leukemia after allogeneic hematopoietic stem cell transplantation had a poor pr ognosis with high death rate due to relapse or transplant-related mortality (TR M). The purpose of this paper was to clarify the role of inducing acute graft-v ersus-host disease (aGVHD) during transplantation in preventing relapse. METHOD S: Thirty adult patients with refractory or relapsed leukemia were acute lymphob lastic leukemia (n=16), acute myelogenous leukemia (n=10), and acute mixed leuke mia (n=4). They were in first complete remission (n=4), second complete remissio n (n=9), partly remission (n=12), and non-response (n=5) at the time of transpl antation. Patients underwent allogeneic peripheral blood stem cell transplantati on (allo-PBSCT) from HLA-identical siblings (n=21), mismatched siblings donors (n=3), and allogeneic bone marrow transplantation (n=5) or allo-PBSCT (n=1) fr om unrelated HLA matched donors. All patients received myeloablative regimens fo r eliminating residual leukemic cell. For aGVHD prophylaxis the patients with HL A-identical siblings donors received cyclosporine (CSA) alone, and the patients with mismatched siblings or unrelated donors received CSA, methotrexate, mycoph enolate mofetil, and low-dose ATG. For inducing aGVHD after transplantation, pa tients were scheduled to be quickly reduced the maintenance dose of CSA at 20%t o 30%off every week or treated with pre-emptive donor leukocyte infusion if th ere was no appearance of aGVHD at +30 days to 60 days after transplantation. RE SULTS: After a median follow-up of 18.1 months, there were 24/30 (80%) patient s developed aGVHD (grade 3 or 4 had 4/30, 13.3%). There were 11/19 (57.9%) pat ients developed chronic GVHD (cGVHD), with 3/19 (15.8%) had extensive cGVHD. Ei ghteen patients are alive with disease-free survival (18/30, 60%) and 12 patie nts have died of relapse (5/28, 17.9%) and TRM (7/30, 23.3%). CONCLUSION: Indu ction of aGVHD after transplantation is feasible and effective to prevent relaps e in patients with refractory or relapsed acute leukemia.