Swinnen L J, Mullen G M, Carr T J, Costanzo M R, Fisher R I
Division of Hematology/Oncology, Loyola University Chicago, Maywood, IL 60153, USA.
Blood. 1995 Nov 1;86(9):3333-40.
Posttransplant lymphoproliferative disorder (PTLD) is a frequently fatal complication of organ transplantation, occurring in 2% to 6% of cardiac recipients. Treatment remains poorly defined. Reduction in immunosuppression is effective in a proportion of cases, but mortality on the order of 80% is reported for patients requiring chemotherapy. The reason for such poor outcomes is unclear, but may be partly caused by the concomitant use of immunosuppressives. Nineteen consecutive cardiac recipients with PTLD were studied retrospectively in terms of clinical features and outcome. Patients were managed according to a uniform treatment approach. Initial therapy was a trial of reduced immunosuppression with concomitant acyclovir followed, if unsuccessful, by aggressive combination chemotherapy. The regimen used was predominantly ProMACE-CytaBOM. Six patients with phenotypically polyclonal PTLD presented less than 6 months after transplantation (median 6 weeks). Only 1 of 4 (25%) treated patients responded to reduced immunosuppression; the remainder died of multiorgan failure. Thirteen patients presented with phenotypically monoclonal disease > or = 6 months after transplantation. In 8 of 12 (75%) treated patients initial therapy was reduction in immunosuppression. None achieved complete remission (CR) and 2 experienced fatal rejection. Two patients achieved durable surgical CR. The remaining 8 patients received chemotherapy; 2 of 8 (25%) died during treatment, 6 of 8 (75%) achieved CR. None have relapsed, at a median duration of follow-up of 38 months. Neutropenic sepsis and subclinical doxorubicin cardiotoxicity at a mean cumulative dose of 63 mg/m2 were the principal toxicities. Our data indicate that aggressive chemotherapy is both feasible and effective in phenotypically monoclonal PTLD refractory to reduced immunosuppression. ProMACE-CytaBOM is well suited to cardiac recipients, minimizing doxorubicin exposure and obviating the need for concurrent immunosuppressives.
移植后淋巴细胞增生性疾病（PTLD）是器官移植常见的致命并发症，在2%至6%的心脏移植受者中发生。治疗方法仍不明确。减少免疫抑制在部分病例中有效，但据报道，需要化疗的患者死亡率约为80%。这种不良预后的原因尚不清楚，但可能部分是由于同时使用免疫抑制剂所致。对19例连续的心脏移植受者伴发PTLD进行回顾性临床特征及预后研究。患者均按照统一的治疗方法进行处理。初始治疗是尝试减少免疫抑制并同时使用阿昔洛韦，若治疗失败，则采用积极的联合化疗。主要使用的化疗方案是ProMACE-CytaBOM。6例表型为多克隆性PTLD的患者在移植后不到6个月出现（中位时间为6周）。4例接受治疗的患者中只有1例（25%）对减少免疫抑制有反应；其余患者死于多器官功能衰竭。13例患者在移植后≥6个月出现表型为单克隆性疾病。12例接受治疗的患者中有8例（75%）初始治疗为减少免疫抑制。无一例达到完全缓解（CR），2例发生致命性排斥反应。2例患者通过手术达到持久CR。其余8例患者接受化疗；8例中有2例（25%）在治疗期间死亡，8例中有6例（75%）达到CR。在中位随访时间38个月时均未复发。中性粒细胞减少性脓毒症和平均累积剂量为63mg/m²的亚临床阿霉素心脏毒性是主要的毒性反应。我们的数据表明，对于对减少免疫抑制无效的表型为单克隆性PTLD，积极化疗既可行又有效。ProMACE-CytaBOM非常适合心脏移植受者，可减少阿霉素暴露并避免同时使用免疫抑制剂的必要性。
