Papa G, Arcese W, Mauro F R, Bianchi A, Alimena G, De Felice L, Isacchi G, Pasqualetti D, Malagnino F, Purpura M
Leuk Res. 1986;10(12):1469-75. doi: 10.1016/0145-2126(86)90015-9.
Between January 1984 to June 1985, 18 Ph1 positive chronic myeloid leukemia (CML) patients in chronic phase (CP) underwent allogeneic bone marrow transplantation (BMT) from HLA identical and MLC negative siblings. The median age was 32.5 yr and median disease duration of CML at time of BMT was 19.3 months. The pretransplant conditioning regimen consisted of cyclophosphamide (CTX) (120 mg/kg) and 10.20 Gy total body irradiation (TBI) at 6 doses of 1.7 Gy each, administered in 3 daily fractions over 2 days at a dose rate of 15-20 cGy/min. To prevent graft-vs-host disease (GvHD) we used methotrexate (MTX) in one patient and cyclosporin-A (CYA) in the other 17 patients. In addition to CYA, given until day +365, 10 patients received donor marrow depleted of T cells with CAMPATH-1. The residual marrow lymphocytes were always less than 1%. The rate of engraftment was significantly correlated with the number of nucleated cells infused. Neither GvHD nor graft failure were observed among CAMPATH-1 patients. In this group one cytogenetic and one hematologic relapse occurred. The overall actuarial survival at 24 months is 78%. Of the 10 patients treated with donor marrow depleted of T cells, 9 are alive after a median follow-up of 9 months (range 5-18), with an actuarial survival of 90%. Of the other 8 patients transplanted with untreated marrow, 5 are alive after a median follow-up of 19.3 months (range 3.7-24) and the actuarial survival is 63.8%. This pilot study seems to demonstrate that T-cell depletion of donor bone marrow with CAMPATH-1 is effective to prevent GvHD, while the risk of graft failure can be avoided using a "standard" conditioning regimen including a fractionated TBI with a fast dose rate and a prolonged administration of CYA at the maximum tolerable dosage. While the high frequency of relapses suggests the employ of more aggressive anti-leukemic conditioning regimens in CAMPATH-1 treated marrow recipients.
1984年1月至1985年6月期间，18例处于慢性期（CP）的Ph1阳性慢性髓性白血病（CML）患者接受了来自HLA相同且混合淋巴细胞培养（MLC）阴性同胞的异基因骨髓移植（BMT）。中位年龄为32.5岁，BMT时CML的中位病程为19.3个月。移植前预处理方案包括环磷酰胺（CTX）（120mg/kg）和10.20Gy全身照射（TBI），分6次给予，每次1.7Gy，在2天内分3次每日剂量给予，剂量率为15 - 20cGy/min。为预防移植物抗宿主病（GvHD），1例患者使用了甲氨蝶呤（MTX），其他17例患者使用了环孢素A（CYA）。除了给予至+365天的CYA外，10例患者接受了用CAMPATH - 1去除T细胞的供体骨髓。残留的骨髓淋巴细胞始终小于1%。植入率与输注的有核细胞数量显著相关。在接受CAMPATH - 1治疗的患者中未观察到GvHD和移植失败。该组发生了1例细胞遗传学复发和1例血液学复发。24个月时的总体精算生存率为78%。在10例接受去除T细胞的供体骨髓治疗的患者中，9例在中位随访9个月（范围5 - 18个月）后存活，精算生存率为90%。在其他8例接受未处理骨髓移植的患者中，5例在中位随访19.3个月（范围3.7 - 24个月）后存活，精算生存率为63.8%。这项初步研究似乎表明，用CAMPATH - 1对供体骨髓进行T细胞去除可有效预防GvHD，而使用包括快速剂量率的分次TBI和以最大耐受剂量长期给予CYA的“标准”预处理方案可避免移植失败的风险。虽然复发频率较高，但提示在接受CAMPATH - 1治疗的骨髓受者中应采用更积极的抗白血病预处理方案。
