非清髓性、相关hla -单倍体或不相关外周血移植和移植后环磷酰胺后的短时间免疫抑制治疗

Amy E. DeZern , Hany Elmariah , Marianna Zahurak , Gary L. Rosner , Douglas E. Gladstone , Syed Abbas Ali , Carol Ann Huff , Lode J. Swinnen , Phil Imus , Ivan Borrello , Nina D. Wagner-Johnston , Richard F. Ambinder , Robert A. Brodsky , Kenneth Cooke , Leo Luznik , Ephraim J. Fuchs , Javier Bolaños-Meade , Richard J. Jones
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引用次数: 15

摘要

移植后环磷酰胺(PTCy)作为移植物抗宿主病(GVHD)预防,非清髓性(NMA) hla -单倍同型(haplo)和hla匹配的血液或骨髓移植(BMT)具有相似的结果。先前的报道表明,在输注PTCy骨髓单倍体移植后60天停止免疫抑制(IS)是可行的。在某些疾病中,外周血(PB)可能比BM更受青睐,但鉴于PB伴GVHD的发生率较高,过度的GVHD越来越值得关注。我们报告了一项完整的前瞻性单中心试验,该试验在NMA PB干细胞移植(PBSCT)后90天和60天停止IS。在2015年12月至2018年7月期间,117例连续接受NMA条件BMT和PTCy后移植物失败率较高的血液恶性肿瘤患者接受了NMA PB同种异体移植物的试验。本研究的主要目的是评估缩短持续时间IS的安全性和可行性(在D90队列中从第5天到第90天,在D60队列中从第60天)。117例患者(中位年龄64岁;范围22 - 78岁),最常见的诊断是骨髓增生异常综合征(33%)、急性髓性白血病(伴有少量残留疾病或由既往疾病引起)(32%)、骨髓增生性肿瘤(19%)、骨髓瘤(9%)和慢性淋巴细胞白血病(7%)。总的来说,缩短IS在75例(64%)患者中是可行的。最常见的原因是GVHD(17例),其次是早期复发(11例),非复发死亡率(NRM)(7例),患者/医生偏好(4例)或移植物失败(3例)。在D90队列的57例患者中,33例(58%)患者按计划提前停药;在D60队列的60例患者中,42例(70%)患者按计划提前停药。移植失败率为2.6%。在IS停止后,D90组诊断为II-IV级急性GVHD的中位时间为21天,D60组为32天,几乎所有病例都在40天内发展。大约三分之一的患者恢复了IS。两个队列的所有结局指标和我们在180天IS的历史结局相似。III-IV级急性GVHD的累积发病率较低,D90组为2%,D60组为7%。2年时严重慢性GVHD的发生率在D90组中为9%,在D60组中为5%。D90组和D60组的2年总生存率均为67%。D90组和D60组的2年无进展生存率分别为47%和52%,两个组的无gvhd、无复发生存率均为35%。这些数据表明,在接受NMA PBSCT合并PTCy的患者中,缩短持续时间的IS是可行的,并且具有可接受的安全性。©2020美国移植和细胞治疗学会。Elsevier Inc.出版。
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Shortened-Duration Immunosuppressive Therapy after Nonmyeloablative, Related HLA-Haploidentical or Unrelated Peripheral Blood Grafts and Post-Transplantation Cyclophosphamide

With post-transplantation cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis, nonmyeloablative (NMA) HLA-haploidentical (haplo) and HLA-matched blood or marrow transplantation (BMT) have comparable outcomes. Previous reports have shown that discontinuation of immunosuppression (IS) as early as day 60 after infusion of a bone marrow (BM) haplo allograft with PTCy is feasible. There are certain diseases in which peripheral blood (PB) may be favored over BM, but given the higher rates of GVHD with PB, excessive GVHD is of increased concern. We report a completed, prospective single-center trial of stopping IS at days 90 and 60 after NMA PB stem cell transplantation (PBSCT). Between 12/2015-7/2018, 117 consecutive patients with hematologic malignancies associated with higher rates of graft failure after NMA conditioned BMT and PTCy, received NMA PB allografts on trial. The primary objective of this study was to evaluate the safety and feasibility of reduced‐duration IS (from day 5 through day 90 in the D90 cohort and through day 60 in the D60 cohort). Of the 117 patients (median age, 64 years; range, 22 to 78 years), the most common diagnoses were myelodysplastic syndrome (33%), acute myelogenous leukemia (with minimal residual disease or arising from an antecedent disorder) (32%), myeloproliferative neoplasms (19%), myeloma (9%), and chronic lymphoblastic leukemia (7%). Shortened IS was feasible in 75 patients (64%) overall. Ineligibility for shortened IS resulted most commonly from GVHD (17 patients), followed by early relapse (11 patients), nonrelapse mortality (NRM) (7 patients), patient/ physician preference (4 patients) or graft failure (3 patients). Of the 57 patients in the D90 cohort, 33 (58%) stopped IS early as planned, and among the 60 patients in the D60 cohort, 42 (70%) stopped IS early as planned. The graft failure rate was 2.6%. After IS cessation, the median time to diagnosis of grade II-IV acute GVHD was 21 days in the D90 cohort and 32 days in the D60 cohort, with almost all cases developing within 40 days. Approximately one-third of these patients resumed IS. All outcome measures were similar in the 2 cohorts and our historical outcomes with 180 days of IS. The cumulative incidence of grade III-IV acute GVHD was low, 2% in the D90 cohort and 7% in the D60 cohort. The incidence of severe chronic GVHD at 2 years was 9% in the D90 cohort and 5% in the D60 cohort. The 2-year overall survival was 67% for both the D90 and D60 cohorts. The 2-year progression-free survival was 47% for the D90 cohort and 52% for the D60 cohort, and the GVHD-free, relapse-free survival was <35% for both cohorts. These data suggest that reduced-duration IS in patients undergoing NMA PBSCT with PTCy is feasible and has an acceptable safety profile.

© 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

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来源期刊
CiteScore
6.60
自引率
0.00%
发文量
1061
审稿时长
3-6 weeks
期刊介绍: Biology of Blood and Marrow Transplantation publishes original research reports, reviews, editorials, commentaries, letters to the editor, and hypotheses and is the official publication of the American Society for Transplantation and Cellular Therapy. The journal focuses on current technology and knowledge in the interdisciplinary field of hematopoetic stem cell transplantation.
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