Junghanss Christian, Boeckh Michael, Carter Rachel A, Sandmaier Brenda M, Maris Michael B, Maloney David G, Chauncey Thomas, McSweeney Peter A, Little Marie-Térèse, Corey Lawrence, Storb Rainer
Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109-1024, USA.
Blood. 2002 Mar 15;99(6):1978-85. doi: 10.1182/blood.v99.6.1978.
Nonmyeloablative allogeneic hematopoietic stem cell transplantation (HSCT) is increasingly being explored as therapy in patients who are not eligible for conventional myeloablative HSCT. Whether these transplants are associated with reduced risk of transplantation-related infections is unknown. We analyzed the incidence of posttransplantation cytomegalovirus (CMV) infections in 56 consecutive mycophenolate mofetil (MMF) patients with hematologic malignancies who underwent nonmyeloablative HSCT (TBI, 2Gy, day 0; MMF/cyclosporine after transplantation). In addition, 18 of 56 patients received 30 mg/m(2)/d fludarabine on days -4 to -2. Most donors were HLA matched and related (93%). Each case patient was matched to 2 controls who were treated by conventional HSCT during the same time period (January 1997 through April 2000). Matching criteria included CMV risk group, HSC source, donor type, age, and underlying diseases. No CMV disease occurred in the low (donor and recipient serologically negative) and intermediate (donor serologically positive and recipient negative) CMV risk groups during the first 100 days. Among cases at high risk for CMV (seropositive recipients), trends to less CMV antigenemia (P =.11), viremia (P =.16), and disease (P =.08) compared with controls were observed; all severe manifestations combined (CMV viremia and disease) were significantly reduced among cases (P =.01). However, by day 365, the overall incidence of CMV disease became similar in both groups. The onset of CMV disease was significantly delayed among case patients compared with controls (median, 130 days versus 52 days; P =.02). It was concluded that CMV disease was significantly delayed in nonmyeloablative cases, but that the overall 1-year incidence was similar to myeloablative HSCT patients. Therefore, nonmyeloablative HSCT patients should receive CMV surveillance beyond day 100 and pre-emptive ganciclovir treatment similar to that of myeloablative HSCT patients.
非清髓性异基因造血干细胞移植(HSCT)正越来越多地被探索用于那些不适合传统清髓性HSCT的患者。这些移植是否与降低移植相关感染的风险相关尚不清楚。我们分析了56例接受非清髓性HSCT(移植前第0天全身照射2Gy;移植后使用霉酚酸酯/环孢素)的血液系统恶性肿瘤患者,连续使用霉酚酸酯(MMF)后移植后巨细胞病毒(CMV)感染的发生率。此外,56例患者中有18例在移植前第-4天至-2天接受了30mg/m²/d的氟达拉滨治疗。大多数供者为HLA配型相合且为亲属供者(93%)。每例病例患者与2例在同一时期(1997年1月至2000年4月)接受传统HSCT治疗的对照者进行匹配。匹配标准包括CMV风险组、造血干细胞来源、供者类型、年龄和基础疾病。在低CMV风险组(供者和受者血清学均为阴性)和中CMV风险组(供者血清学阳性而受者阴性)中,在移植后的前100天内未发生CMV疾病。在CMV高风险组(受者血清学阳性)的病例中,与对照组相比,观察到CMV抗原血症(P = 0.11)、病毒血症(P = 0.16)和疾病(P = 0.08)有减少的趋势;病例组中所有严重表现(CMV病毒血症和疾病)的综合发生率显著降低(P = 0.01)。然而,到第365天时,两组中CMV疾病的总体发生率变得相似。与对照组相比,病例组患者CMV疾病的发病明显延迟(中位数分别为130天和52天;P = 0.02)。得出的结论是,在非清髓性移植病例中CMV疾病明显延迟,但1年的总体发生率与清髓性HSCT患者相似。因此,非清髓性HSCT患者在100天后应接受CMV监测,并与清髓性HSCT患者一样接受抢先使用更昔洛韦治疗。