Mandanas R A, Saez R A, Selby G B, Confer D L
Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City 73104, USA.
J Hematother. 1998 Oct;7(5):449-56. doi: 10.1089/scd.1.1998.7.449.
Eight patients who relapsed with acute leukemia within a year after allogeneic BMT were treated with G-CSF-mobilized donor leukocyte infusions (mDLI) to induce GvHD as a form of immunotherapy. Prior to mDLI, 7 who had systemic relapse received one (2 AML, 1 ALL, 1 CML myeloid blast crisis) or two (2 AML, 1 ALL) rounds of conventional dose induction chemotherapy, and 1 patient with isolated central nervous system (CNS) lymphoid blast crisis CML received intrathecal chemotherapy followed by craniospinal irradiation. G-CSF (10 microg/kg/day) was given to original HLA-matched sibling donors for 4-5 days before leukapheresis of at least 6.0 x 10(8) mononuclear cells per kilogram of recipient weight. No GvHD prophylaxis was used when mDLI was given in 6 patients at the nadir of hematologic counts and in 2 who were in hematologic remission. There was no regimen-related mortality, as pancytopenic patients had rapid recovery of neutrophil counts (6-18 days after mDLI). All patients developed moderate to severe GvHD (5 grade III/IV, 3 grade II) at a median of 30 days (range 22-59) after mDLI. Two patients died of complications from refractory GvHD while in remission. The other 6 had short remissions lasting 2.2-9.4 months until leukemic relapse as their GvHD was reversed by corticosteroids with or without cyclosporine. Patients who relapse with acute leukemia within a year after BMT still have a poor prognosis. The success of GvHD as a form of immunotherapy in these patients may depend on the ability to control it to a state that is both safe and continually exerting an antileukemia effect.
8例异基因骨髓移植（BMT）后1年内复发急性白血病的患者接受了粒细胞集落刺激因子（G-CSF）动员的供者白细胞输注（mDLI），以诱导移植物抗宿主病（GvHD）作为一种免疫治疗形式。在进行mDLI之前，7例发生全身复发的患者接受了一（2例急性髓细胞白血病、1例急性淋巴细胞白血病、1例慢性髓细胞白血病髓系原始细胞危象）或两（2例急性髓细胞白血病、1例急性淋巴细胞白血病）轮常规剂量诱导化疗，1例孤立性中枢神经系统（CNS）淋巴细胞原始细胞危象慢性髓细胞白血病患者接受鞘内化疗，随后进行颅脑脊髓照射。在采集至少每千克受者体重6.0×10⁸个单核细胞的白细胞单采前4 - 5天，给原HLA匹配的同胞供者给予G-CSF（10μg/kg/天）。6例患者在血液学计数最低点进行mDLI，2例处于血液学缓解期的患者进行mDLI时未使用预防GvHD的措施。没有与治疗方案相关的死亡，因为全血细胞减少的患者中性粒细胞计数迅速恢复（mDLI后6 - 18天）。所有患者在mDLI后中位30天（范围22 - 59天）出现中度至重度GvHD（5例Ⅲ/Ⅳ级，3例Ⅱ级）。2例患者在缓解期死于难治性GvHD的并发症。其他6例患者缓解期短暂，持续2.2 - 9.4个月，直至白血病复发，因为他们的GvHD通过使用或不使用环孢素的皮质类固醇得到逆转。BMT后1年内复发急性白血病的患者预后仍然很差。GvHD作为这些患者的一种免疫治疗形式的成功可能取决于将其控制在既安全又能持续发挥抗白血病作用的状态的能力。
