Liberatore Carmine, Stanghellini Maria Teresa Lupo, Lorentino Francesca, Vago Luca, Carrabba Matteo Giovanni, Greco Raffaella, Marktel Sarah, Assanelli Andrea, Farina Francesca, Corti Consuelo, Bernardi Massimo, Peccatori Jacopo, Sockel Katja, Middeke Jan Moritz, Schetelig Johannes, Bergmann Anika, Rautenberg Christina, Ciceri Fabio, Bornhäuser Martin, Schroeder Thomas, Stölzel Friedrich
Haematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Ther Adv Hematol. 2022 Jun 17;13:20406207221090882. doi: 10.1177/20406207221090882. eCollection 2022.
Azacitidine (AZA) either single-agent or with donor lymphocytes infusions (DLI) has been used as a salvage treatment for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) relapsing after allogeneic hematopoietic stem cell transplantation (HSCT). To date, the majority of data come from patients relapsed after HSCT from full-matched donors.
We report a multicenter, collaborative, retrospective analysis of 71 patients with hematologic ( = 40, 56%) and molecular relapse ( = 31, 44%) of myeloid neoplasms after HSCT from alternative donors (mismatched unrelated, = 39, 55%; haploidentical, = 29, 41%) consecutively treated at three European centers with AZA ± DLI.
Median time from HSCT to relapse was 9 months. Additional DLI were given to 33 patients (46%). After a median of four cycles, overall response rate (ORR) was 49% and complete response (CR) rate was 38%. CR lasted for a median of 17 months (range 5-89 months). Median follow-up in the entire cohort was 11 months (range 1-115 months). Event-free survival (EFS) and overall survival (OS) at 1 year were 26% and 53%, respectively. Treatment of molecular relapse granted higher CR rate (65% 15%; 0.0001), 1-year EFS (43% 13%; = 0.006), and 1-year OS (79% 34%; < 0.001) compared to hematologic relapses. Addition of DLI resulted in significantly higher responses and longer 1-year EFS and OS (Mantel-Byar test, = 0.004 and 0.002, respectively). When applied to our cohort, the APSS-R score confirmed its ability to stratify patients into distinct prognostic groups with significantly different response rates ( 0.0005) and survival ( < 0.0001). Treatment was well tolerated, with the incidence of late acute and chronic graft-versus-host disease of 27% and 18%, respectively.
AZA ± DLI proved feasible and effective in AML and MDS relapsing after HSCT from alternative donors. Despite modest efficacy among hematologic relapses, pre-emptive treatment with AZA ± DLI fared better in molecular relapse. Additional DLI contributed to improving efficacy and ensuring longer survival.
阿扎胞苷（AZA）单药治疗或联合供体淋巴细胞输注（DLI）已被用作异基因造血干细胞移植（HSCT）后复发的急性髓系白血病（AML）和骨髓增生异常综合征（MDS）的挽救治疗。迄今为止，大多数数据来自全相合供体HSCT后复发的患者。
我们报告了一项多中心、协作性的回顾性分析，纳入了71例髓系肿瘤患者，这些患者在接受来自替代供体（不相合无关供体，n = 39，55%；单倍体相合供体，n = 29，41%）HSCT后出现血液学复发（n = 40，56%）和分子学复发（n = 31，44%），并在三个欧洲中心连续接受AZA±DLI治疗。
从HSCT到复发的中位时间为9个月。33例患者（46%）接受了额外的DLI。经过中位4个周期的治疗后，总缓解率（ORR）为49%，完全缓解（CR）率为38%。CR持续时间的中位数为17个月（范围5 - 89个月）。整个队列的中位随访时间为11个月（范围1 - 115个月）。1年时的无事件生存率（EFS）和总生存率（OS）分别为26%和53%。与血液学复发相比，分子学复发的治疗获得了更高的CR率（65%对15%；P < 0.0001）、1年EFS（43%对13%；P = 0.006）和1年OS（79%对34%；P < 0.001）。添加DLI导致缓解率显著更高，1年EFS和OS更长（Mantel-Byar检验，P分别为0.004和0.002）。当应用于我们的队列时，APSS-R评分证实了其将患者分层为不同预后组的能力，这些组的缓解率（P < 0.0005）和生存率（P < 0.0001）有显著差异。治疗耐受性良好，晚期急性和慢性移植物抗宿主病的发生率分别为27%和18%。
AZA±DLI在替代供体HSCT后复发的AML和MDS中被证明是可行且有效的。尽管在血液学复发中的疗效一般，但AZA±DLI的抢先治疗在分子学复发中效果更好。额外的DLI有助于提高疗效并确保更长的生存期。
