Different kinetics and risk factors for isolated extramedullary relapse after allogeneic hematopoietic stem cell transplantation in children with acute leukemia
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KünyeHazar, V., Öztürk, G., Yalçın, K., Uygun, V., Aksoylar, S., Küpesiz, A., Ok Bozkaya, I., Karagün, B. Ş., Bozkurt, C., İleri, T., Atay, D., Koçak, Ü., Karasu, G. T., Yeşilipek, A., Gökçe, M., Kansoy, S., Kintrup, G. T., Karakükcü, M., Okur, F. V., Ertem, M., … Turkish Pediatric Bone Marrow Transplantation Study Group (2021). Different kinetics and risk factors for isolated extramedullary relapse after allogeneic hematopoietic stem cell transplantation in children with acute leukemia. Transplantation and cellular therapy, S2666-6367(21)01026-5. Advance online publication. https://doi.org/10.1016/j.jtct.2021.06.023
Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the most frequent cause of posttransplant mortality. Isolated extramedullary relapse (iEMR) after HSCT is relatively rare and not well characterized, particularly in pediatric patients. We retrospectively analyzed 1527 consecutive pediatric patients with acute leukemia after allo-HSCT to study the incidence, risk factors and outcome of iEMR compared to systemic relapse. The 5-year cumulative incidence of systemic relapse either bone morrow (BM) only or combined with EMR and iEMR was 24.8% and 5.5%, respectively. The onset of relapse after allo-HSCT was significantly longer in EM sites than in BM sites (7.19 and 5.58 months, respectively; p: 0.013). CR2+/active disease at transplantation (HR, 3.1, p<0001) and prior extramedullary disease (HR, 2.3; p: 0.007) were independent risk factors for iEMR. Chronic graft-versus-host disease (GVHD) reduced the risk of systemic relapse (HR, 0.5; p: 0.043) but did not protect against iEMR. The prognosis of patients who developed iEMR remained poor but was slightly better than that of patients who developed systemic relapse (3-year overall survival, 16.5% vs 15.3%, p: 0.089). Patients experiencing their first systemic relapse continued to have further systemic relapse, but only a minority progressed to iEMR, while those experiencing their iEMR at first relapse developed further systemic and isolated extramedullary relapses with approximately similar frequencies. Second iEMR was more common after the first iEMR than after the first systemic relapse (58.8% vs 13.0%, p: 0.001) and was associated with a poor outcome. iEMR has a poor prognosis, particularly after the 2nd relapse, and effective strategies are needed to improve outcomes.