Shah Ami J, Kapoor Neena, Crooks Gay M, Weinberg Kenneth I, Azim Hisham Abdel, Killen Renna, Kuo Lily, Rushing Teresa, Kohn Donald B, Parkman Robertson
Department of Pediatrics, Keck School of Medicine, Los Angeles, California, USA.
Biol Blood Marrow Transplant. 2007 May;13(5):584-93. doi: 10.1016/j.bbmt.2007.01.076. Epub 2007 Mar 23.
Graft-versus-host disease (GVHD) is a cause of serious morbidity and mortality in >50% of recipients of unrelated hematopoietic stem cell transplantation (HSCT). We performed a trial using Campath 1 H pre- and post-HSCT in an attempt to decrease the incidence of GVHD without increasing the risk of infection or relapse. Patients were retrospectively compared to a population of patients who received antithymocyte globulin (ATG) pre- and post-HSCT. Twenty-seven patients were evaluated for this study. Fourteen patients received Campath 1H and 13 patients received ATG. Demographics of patients who received Campath 1H consisted of 9 males and 5 females, with a median age of 13 years (3-17.8 years). Thirteen patients received unrelated bone marrow and 1 patient received unrelated PBSC. Demographics of patients receiving ATG consisted of 9 males, 4 females with a median age of 7.4 years (21 months-19 years). Twelve patients received unrelated bone marrow and 1 patient received unrelated PBSC. Diagnoses were similar between the 2 groups. Patients who received Campath1H received a total dose of 52 mg/m(2) pre-HSCT and 20 mg/m(2) post-HSCT. Patients who received ATG received a total dose of 60 mg/kg pre-HSCT and 100 mg/kg post-HSCT. GVHD prophylaxis and supportive care measures were similar in both groups, including aggressive antimicrobial therapy. There was a significant difference in the incidence of severe (grade III and grade IV) GVHD between the 2 groups (Campath [0 of 14] versus ATG [6 of 13], P = .006). Among the patients who were transplanted for leukemia, there was no significant difference between the 2 groups in terms of relapse (Campath [2 of 14] versus ATG [4 of 9], P = 0.16). The 100-day survival between the 2 groups was not significantly different. Patients receiving Campath 1H had the presence of CD3(+) T cells (>30 cells/mL) in their peripheral blood later than in those who received ATG (64.5 days [Campath 1H] versus 27days [ATG], P = .001). The median time to the development of a normal PHA response occurred later in the Campath 1H arm (283 days[(Campath 1H] versus 88 days [ATG], P = .0001). The median time to an antigen specific response also occurred later in those receiving Campath 1H (365 days [Campath 1H] versus 150 days [ATG], P = .004). There was no significant difference between the 2 groups in terms of fungal or viral infections. Campath 1H is effective in decreasing the incidence of GVHD without increasing the risk of relapse. Although there is a significant delay in immune reconstitution, there was no increase in infectious complications or relapse in recipients of Campath 1H. Further studies are warranted to assess if a lack of difference in infection rates are still demonstrated in larger cohorts.
移植物抗宿主病（GVHD）是超过50%的非血缘造血干细胞移植（HSCT）受者发生严重发病和死亡的原因。我们进行了一项在HSCT前后使用Campath 1 H的试验，试图降低GVHD的发生率，同时不增加感染或复发风险。将患者与在HSCT前后接受抗胸腺细胞球蛋白（ATG）的患者群体进行回顾性比较。本研究评估了27例患者。14例患者接受了Campath 1H，13例患者接受了ATG。接受Campath 1H的患者人口统计学特征为9名男性和5名女性，中位年龄13岁（3 - 17.8岁）。13例患者接受了非血缘骨髓移植，1例患者接受了非血缘外周血干细胞移植。接受ATG的患者人口统计学特征为9名男性、4名女性，中位年龄7.4岁（21个月 - 19岁）。12例患者接受了非血缘骨髓移植，1例患者接受了非血缘外周血干细胞移植。两组的诊断情况相似。接受Campath1H的患者在HSCT前接受的总剂量为52 mg/m(2)，HSCT后为20 mg/m(2)。接受ATG的患者在HSCT前接受的总剂量为60 mg/kg，HSCT后为100 mg/kg。两组的GVHD预防和支持治疗措施相似，包括积极的抗菌治疗。两组在重度（III级和IV级）GVHD发生率上存在显著差异（Campath组[14例中的0例] vs ATG组[13例中的6例]，P = 0.006）。在因白血病接受移植的患者中，两组在复发方面无显著差异（Campath组[14例中的2例] vs ATG组[9例中的4例]，P = 0.16）。两组的100天生存率无显著差异。接受Campath 1H的患者外周血中CD3(+) T细胞（>30个细胞/mL）出现的时间晚于接受ATG的患者（64.5天[Campath 1H] vs 27天[ATG]，P = 0.001）。在Campath 1H组，出现正常PHA反应的中位时间较晚（283天[(Campath 1H] vs 88天[ATG]，P = 0.0001）。接受Campath 1H的患者出现抗原特异性反应的中位时间也较晚（365天[Campath 1H] vs 150天[ATG]，P = 0.004）。两组在真菌感染或病毒感染方面无显著差异。Campath 1H可有效降低GVHD的发生率，且不增加复发风险。尽管免疫重建有显著延迟，但接受Campath 1H的受者感染并发症或复发并未增加。有必要进行进一步研究，以评估在更大队列中是否仍显示感染率无差异。
