Marrow transplants from unrelated donors for patients with aplastic anemia: Minimum effective dose of total body irradiation
Marrow transplants from unrelated donors for patients with aplastic anemia: Minimum effective dose of total body irradiation
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DOI：
10.1053/bbmt.2001.v7.pm11349807
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发表时间：
2001-01-01
影响因子：
4.3
通讯作者：
Mueller, B
中科院分区：
文献类型：
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作者：
Deeg, HJ;Amylon, MD;Mueller, B
没有合适的HLA匹配的相关供体的再生障碍性贫血患者通常接受免疫抑制治疗作为一线治疗，并且只有当他们对免疫抑制治疗无效时才考虑从无关供体移植。在这种情况下，移植相关的发病率和死亡率一直很高。我们进行了一项前瞻性研究，以确定当与3个周期的30 mg/kg抗胸腺细胞球蛋白（ATG）和4个周期的50 mg/kg环磷酰胺（CY）联合使用时，足以实现持续植入的全身照射（TBI）的最小剂量。我们还想确定该方案的耐受性和毒性。TBI的起始剂量为CY/ATG后2天内给予3 x 200 cGy。如果在无抑制性毒性的情况下发生移植物失效，则TBI剂量以200 cGy的增量递增，如果在无移植物失效的情况下发生毒性，则TBI剂量递减。21名女性和29名男性患者，年龄为1.3至46.5岁（中位年龄为14.4岁），在14个医疗中心接受了移植。从诊断到移植的时间间隔为2.8至264个月（中位数，14.5个月）。所有患者均接受过多次输血，并且均接受过1至11个疗程（中位数，4个疗程）的免疫抑制治疗和其他治疗方式。38例供者与患者HLA-A、-B、-DR表型匹配，12例供者与受体表型相差1个HLA抗原。不匹配移植的受体被单独考虑TBI剂量调整，这项研究仍在进行中。7名患者不耐受ATG，并通过6 x 200 cGy的TBI针120 mg/kg CY进行准备。在用CY/ ATG/TBI制备的HLA匹配的受者中，所有20名接受3 x 200或2 x 200 cGy TBI的受者均实现了植入，10名存活。在接受I x 200 cGy TBI的13例患者中，1例植入失败，8例存活。接受HLA不一致移植的10名患者中的每一名都实现了植入，接受3 x 200 cGy TBI的6名患者中有3名存活，接受2 x 200 cGy TBI的4名患者中有4名存活。30名同时接受3 x 200或2 x 200 cGy TBI和200 mg/kg ATG和CY的患者中有8名发生肺毒性，13名接受1 x 200 cGy TBI的患者中有2名发生肺毒性，这一模式表明毒性随TBI剂量降低而降低。在诊断后1年内接受移植的患者中观察到的存活率最高（73%），与在较长时间的疾病后接受移植的患者相比。此外，年轻患者（年龄小于或等于20岁）比老年患者（年龄>20岁）更有可能存活。因此，对于具有HLA匹配的无关供体的患者，200 cGy的TBI剂量（与CY/ATG组合）足以允许植入而不诱导抑制性毒性。在以前的研究中，患者年龄和移植前疾病持续时间仍然是重要的预后因素。
Patients with aplastic anemia who do not have suitably HLA-matched, related donors generally receive immunosuppressive treatment as first-line therapy and are considered for transplantation from an unrelated donor only if they fail to respond to immunosuppressive treatment. In this setting, rates of transplantation-related morbidity and mortality have been high. We conducted a prospective study to determine the minimal dose of total body irradiation (TBI) sufficient to achieve sustained engraftment when it is used in combination with 3 cycles of 30 mg/kg of antithymocyte globulin (ATG) and 4 cycles of 50 mg/kg of cyclophosphamide (CY). We also wanted to determine the tolerability and toxicity of the regimen. The starting dosage of TBI was 3 x 200 cGy given over 2 days following CY/ATG. The TBI dose was to be escalated in increments of 200 cGy if graft failure occurred in the absence of prohibitive toxicity, and de-escalated for toxicity in the absence of graft failure. Twenty-one female and 29 male patients aged 1.3 to 46.5 years (median age, 14.4 years) underwent transplantation at: 14 medical centers. The time interval from diagnosis to transplantation was 2.8 to 264 months (median, 14.5 months). All patients had been transfused multiple times and all had received 1 to 11 courses (median, 4 courses) of immunosuppressive treatment and other modalities of treatment. In 38 cases, the donors were HLA-A, -B and -DR phenotypically matched with the patients, and, in 12 cases, the donor phenotype differed from that of the recipient by 1 HLA antigen. Recipients of mismatched transplants were considered separately for TBI dose modification, and this study is still ongoing. Seven patients did not tolerate ATG and were prepared viith 6 x 200 cGy of TBI pins 120 mg/kg of CY. Of the HLA-matched recipients prepared with CY/ ATG/TBI, all 20 who received 3 x 200 or 2 x 200 cGy of TBI achieved engraftment, and 10 are alive. Of the 13 patients who received I x 200 cGy of TBI, 1 failed to engraft, and 8 are alive. Each of 10 patients who received an HLA-nonidentical transplant achieved engraftment, and 3 of 6 who were given 3 x 200 cGy of TBI, and 4 of 4 who were given 2 x 200 cGy are alive. Pulmonary toxicity occurred in 8 of 30 patients who were given 3 x 200 or 2 x 200 cGy of TBI concurrently with ATG and CY at 200 mg/kg, and in 2 of 13 patients who received 1 x 200 cGy of TBI, a pattern that suggests a decrease in toxicity with TBI dose de-escalation Overall, the highest probability of survival (73%) was observed among patients who underwent transplantation within 1 year of diagnosis, compared with patients who underwent transplantation after a longer period of disease. In addition, younger patients (aged less than or equal to 20 years) were more likely to survive than older patients (aged >20 years). Thus, for patients with an HLA-matched, unrelated donor, a TBI dose of 200 cGy tin combination with CY/ATG) was sufficient to allow for engraftment without inducing prohibitive toxicity. As in previous studies, patient age and pretransplantation disease duration remain important prognostic factors.