Min C K, Kim D W, Lee J W, Min W S, Kim C C
Catholic Hemopoietic Stem Cell Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Acta Haematol. 2000;104(4):185-92. doi: 10.1159/000046513.
In this study we retrospectively evaluated the effect and outcome of a boost dose of donor stem cells without additional chemotherapy or total body irradiation. Between March 1983 and August 1999, 20 of 788 (2.5%) patients receiving allogeneic bone marrow transplantation (BMT) were treated with an additional boost dose of donor cells. The reasons for the use of the boost treatment were primary graft failure (early rejection; n = 7), secondary graft failure including late rejection (n = 10), refractory pure red cell aplasia caused by the remaining recipient cells producing anti-erythrocyte antibodies (n = 2), and donor lymphocyte infusion induced pancytopenia (n = 1). The patients were aged from 17 to 48 years (median age 31 years). The underlying diseases of the patients were severe aplastic anemia in 12 patients, acute myelogenous leukemia in 3, acute lymphocytic leukemia in 3, and chronic myelogenous leukemia in 2. The donors were human leukocyte antigen-identical siblings in 18 cases, 1 mismatched related donor, and 1 unrelated donor. The cell source was bone marrow in 6 cases and peripheral blood progenitor cells in 14. The median interval between BMT and the boost treatment was 7 weeks (range 1-124). No conditioning regimen was given prior to the boost treatment for 11 patients, while 4 received total nodal irradiation (TNI) plus antithymocyte globulin (ATG), 3 ATG alone, and 2 TNI plus steroid. The median infused booster mononuclear cell dose was 2.55 x 10(8)/kg (range 0.28-37.0). Fifteen (75%) patients achieved a hematological recovery. After the boost treatment, 6 of 20 (30%) patients developed acute graft-versus-host disease (GVHD) > or = grade II, 3 of whom had had prior GVHD. Five (31.3%) of the evaluable 16 patients developed chronic GVHD. The GVHDs were easily controlled using immunosuppressive agents except in the case of 1 patient. Five patients died after the boost treatment; 2 within 30 days, 2 within 60 days, and 1 after 32 months. The causes of death were: 3 engraftment failures, 1 late rejection, and 1 infection following GVHD. With a median follow-up of 31.5 months (range 6-92), the Kaplan-Meier method estimated that the overall survival rate 1 and 3 years after the boost treatment was 80 and 71%, respectively. The survival of patients with primary graft failure was determined to be significantly lower compared to that of patients with secondary graft failure, using the log rank test (p = 0.0176). Disease category, stem cell source, conditioning prior to a boost treatment, and year of boost treatment did not have an influence on survival. We conclude that the reinfusion of donor stem cells is frequently successful in achieving engraftment with rare occurrence of fatal GVHD. Furthermore, relatively good long-term survival was demonstrated.
在本研究中，我们回顾性评估了在不进行额外化疗或全身照射的情况下给予供体干细胞加强剂量的效果和结局。1983年3月至1999年8月期间，788例接受异基因骨髓移植（BMT）的患者中有20例（2.5%）接受了额外的供体细胞加强剂量治疗。采用加强治疗的原因包括原发性移植物失败（早期排斥；n = 7）、继发性移植物失败包括晚期排斥（n = 10）、由残留受者细胞产生抗红细胞抗体导致的难治性纯红细胞再生障碍（n = 2）以及供体淋巴细胞输注引起的全血细胞减少（n = 1）。患者年龄为17至48岁（中位年龄31岁）。患者的基础疾病为严重再生障碍性贫血12例、急性髓系白血病3例、急性淋巴细胞白血病3例、慢性髓系白血病2例。供体为18例人类白细胞抗原匹配的同胞、1例1个位点不匹配的相关供体和1例无关供体。细胞来源为6例骨髓和14例外周血祖细胞。BMT与加强治疗之间的中位间隔时间为7周（范围1 - 124周）。11例患者在加强治疗前未接受预处理方案，4例接受了全淋巴结照射（TNI）加抗胸腺细胞球蛋白（ATG），3例仅接受ATG，2例接受TNI加类固醇。输注的加强单核细胞剂量中位数为2.55×10⁸/kg（范围0.28 - 37.0）。15例（75%）患者实现了血液学恢复。加强治疗后出现急性移植物抗宿主病（GVHD）≥Ⅱ级的患者有6例（20例中的30%），其中3例既往有GVHD。16例可评估患者中有5例（31.3%）发生了慢性GVHD。除1例患者外，GVHDs使用免疫抑制剂易于控制。5例患者在加强治疗后死亡；2例在30天内、2例在60天内、1例在32个月后死亡。死亡原因分别为：3例植入失败、1例晚期排斥和1例GVHD后感染。中位随访31.5个月（范围6 - 92个月），采用Kaplan - Meier法估计加强治疗后1年和3年的总生存率分别为80%和71%。采用对数秩检验确定，原发性移植物失败患者的生存率显著低于继发性移植物失败患者（p = 0.0176）。疾病类别、干细胞来源、加强治疗前的预处理以及加强治疗年份对生存率均无影响。我们得出结论，再次输注供体干细胞通常能成功实现植入，且致命性GVHD发生率较低。此外，还显示出相对良好的长期生存率。
