Kayser S, Krzykalla J, Elliott M A, Norsworthy K, Gonzales P, Hills R K, Baer M R, Ráčil Z, Mayer J, Novak J, Žák P, Szotkowski T, Grimwade D, Russell N H, Walter R B, Estey E H, Westermann J, Görner M, Benner A, Krämer A, Smith B D, Burnett A K, Thiede C, Röllig C, Ho A D, Ehninger G, Schlenk R F, Tallman M S, Levis M J, Platzbecker U
Department of Internal Medicine V, University Hospital of Heidelberg, Heidelberg, Germany.
Department of Internal Medicine V, Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ), University of Heidelberg, Heidelberg, Germany.
Leukemia. 2017 Nov;31(11):2347-2354. doi: 10.1038/leu.2017.92. Epub 2017 Mar 21.
Therapy-related acute promyelocytic leukemia (t-APL) is relatively rare, with limited data on outcome after treatment with arsenic trioxide (ATO) compared to standard intensive chemotherapy (CTX). We evaluated 103 adult t-APL patients undergoing treatment with all-trans retinoic acid (ATRA) alone (n=7) or in combination with ATO (n=24), CTX (n=53), or both (n=19). Complete remissions were achieved after induction therapy in 57% with ATRA, 100% with ATO/ATRA, 78% with CTX/ATRA, and 95% with CTX/ATO/ATRA. Early death rates were 43% for ATRA, 0% for ATO/ATRA, 12% for CTX/ATRA and 5% for CTX/ATO/ATRA. Three patients relapsed, two developed therapy-related acute myeloid leukemia and 13 died in remission including seven patients with recurrence of the prior malignancy. Median follow-up for survival was 3.7 years. None of the patients treated with ATRA alone survived beyond one year. Event-free survival was significantly higher after ATO-based therapy (95%, 95% CI, 82-99%) as compared to CTX/ATRA (78%, 95% CI, 64-87%; P=0.042), if deaths due to recurrence of the prior malignancy were censored. The estimated 2-year overall survival in intensively treated patients was 88% (95% CI, 80-93%) without difference according to treatment (P=0.47). ATO when added to ATRA or CTX/ATRA is feasible and leads to better outcomes as compared to CTX/ATRA in t-APL.
治疗相关的急性早幼粒细胞白血病(t-APL)相对罕见,与标准强化化疗(CTX)相比,关于三氧化二砷(ATO)治疗后结局的数据有限。我们评估了103例成年t-APL患者,这些患者单独接受全反式维甲酸(ATRA)治疗(n = 7)或与ATO联合治疗(n = 24)、CTX(n = 53)或两者联合治疗(n = 19)。诱导治疗后,ATRA组的完全缓解率为57%,ATO/ATRA组为100%,CTX/ATRA组为78%,CTX/ATO/ATRA组为95%。ATRA组的早期死亡率为43%,ATO/ATRA组为0%,CTX/ATRA组为12%,CTX/ATO/ATRA组为5%。3例患者复发,2例发生治疗相关的急性髓系白血病,13例在缓解期死亡,其中7例患者先前的恶性肿瘤复发。生存的中位随访时间为3.7年。单独接受ATRA治疗的患者无一例存活超过1年。如果将因先前恶性肿瘤复发导致的死亡进行 censored,基于ATO的治疗后的无事件生存率显著高于CTX/ATRA(95%,95%CI,82 - 99%)(78%,95%CI,64 - 87%;P = 0.042)。强化治疗患者的估计2年总生存率为88%(95%CI,80 - 93%),根据治疗方法无差异(P = 0.47)。在t-APL中,ATO添加到ATRA或CTX/ATRA中是可行的,并且与CTX/ATRA相比能带来更好的结局。