Shem-Tov Noga, Saraceni Francesco, Danylesko Ivetta, Shouval Roni, Yerushalmi Ronit, Nagler Arnon, Shimoni Avichai
The Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
The Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Biol Blood Marrow Transplant. 2017 Jul;23(7):1087-1094. doi: 10.1016/j.bbmt.2017.03.023. Epub 2017 Apr 7.
Allogeneic stem cell transplantation (SCT) is curative treatment in patients with acute leukemia and myelodysplastic syndrome. However, recurrent disease is the major cause of treatment failure. Isolated extramedullary relapse (iEMR) after SCT is relatively rare and not well characterized. We performed a retrospective analysis of 566 consecutive patients with acute myeloid leukemia (n = 446) and acute lymphoblastic leukemia (ALL; n = 120) after SCT to study the incidence, risk factors, treatment options, and outcome of iEMR. The 5-year cumulative incidence of bone marrow relapse (BMR) and iEMR was 41.0% and 5.8%, respectively. iEMR occurred significantly later than BMR at 10 and 4 months, respectively (P < .001). Diagnosis of ALL (HR, 2.6; P = .05), poor cytogenetics (HR, 2.1; P = .06), and prior extramedullary disease (HR, 3.8; P = .002) were independent factors predicting iEMR. Acute and chronic graft-versus-host disease (GVHD) reduced the risk of BMR but did not protect against iEMR. Most patients with iEMR received systemic treatment combined with local radiation and donor lymphocyte infusions when feasible. The 3-year survival after relapse was 8.5% and 30.1% after BMR and iEMR, respectively (P = .002). Patients with a first iEMR continued to have recurrent EMRs, and only a minority progressed to BMR. Second iEMR was also common after first BMR and associated with longer survival than second BMR. iEMR is more frequent in patients with ALL and prior extramedullary disease. It occurs later than BMR and more commonly in patients with chronic GVHD, suggesting less effective graft-versus-leukemia effect in extramedullary sites. Second iEMR is common after a first iEMR but also after a first BMR. Long-term survival is feasible with aggressive treatment.
异基因干细胞移植（SCT）是急性白血病和骨髓增生异常综合征患者的治愈性治疗方法。然而，疾病复发是治疗失败的主要原因。SCT后孤立性髓外复发（iEMR）相对少见且特征不明。我们对566例连续接受SCT的急性髓系白血病患者（n = 446）和急性淋巴细胞白血病（ALL；n = 120）进行了回顾性分析，以研究iEMR的发生率、危险因素、治疗选择和结局。骨髓复发（BMR）和iEMR的5年累积发生率分别为41.0%和5.8%。iEMR分别在10个月和4个月时显著晚于BMR发生（P <.001）。ALL诊断（HR，2.6；P =.05）、细胞遗传学不良（HR，2.1；P =.06）和既往髓外疾病（HR，3.8；P =.002）是预测iEMR的独立因素。急性和慢性移植物抗宿主病（GVHD）降低了BMR的风险，但不能预防iEMR。大多数iEMR患者在可行时接受全身治疗联合局部放疗和供体淋巴细胞输注。复发后3年生存率在BMR和iEMR后分别为8.5%和30.1%（P =.002）。首次发生iEMR的患者继续出现复发性EMR，只有少数进展为BMR。首次BMR后第二次iEMR也很常见，且与第二次BMR相比生存期更长。iEMR在ALL患者和既往有髓外疾病的患者中更常见。它比BMR发生得晚且更常见于慢性GVHD患者，提示在髓外部位移植物抗白血病作用较差。首次iEMR后第二次iEMR常见，首次BMR后也常见。积极治疗可实现长期生存。
