法国巴黎圣路易斯医院Régis Peffault de Latour团队研究了异体移植治疗晚期皮肤T细胞淋巴瘤对患者生存期的影响。这一研究成果于2023年4月24日发表在《柳叶刀》杂志上。

晚期皮肤T细胞淋巴瘤（CTCL）是一种罕见的、通常难以治愈的致命疾病。病例系列表明，异基因造血干细胞移植（HSCT）可能改善晚期CTCL的预后。该研究旨在探讨异基因HSCT与非HSCT治疗对晚期CTCL患者预后的影响。

研究组在30家医院进行了一项前瞻性、多中心、匹配对照试验，患有晚期CTCL的参与者被分配治疗：如果他们有可用的全相合相关供体，则被分配至异基因造血干细胞移植，若没有，则被分配到非异基因造血细胞移植治疗。关键纳入标准是18-70岁的参与者，患有晚期蕈样肉芽肿或Sézary综合征，以及至少一个不良预后标准。如果参与者的病情没有完全或部分缓解，则将其排除在外。倾向评分1:1匹配替换（即，每个接受HSCT治疗的参与者都与接受非HSCT治疗倾向评分最接近的参与者匹配，即使他们已匹配）用于处理混杂因素，HSCT组和非HSCT组之间的协变量分布平衡使用标准化平均差异进行评估。主要终点是匹配意向治疗人群的无进展生存率。

2016年6月1日到2022年3月3日，共有99名参与者在法国的17个中心注册。有兄弟姐妹或匹配无关供体的参与者被分配到异基因造血干细胞移植（HSCT组，n=55[56%]），而没有供体的参与者则被分配到非异基因HSCT治疗（非HSCT组，n=44[44%]）。幸存者的中位随访时间为12.6个月。

HSCT组51名参与者（93%）与非HSCT组的参与者1:1匹配。在意向治疗分析中，HSCT组的中位无进展生存期（9.0个月）显著长于非HSCT组（3.0个月），危险比为0.38。在按方案分析人群中，HSCT组有40名参与者（78%）发生了101起严重事件，非HSCT组有29名参与者（67%）发生了70起严重不良事件。除移植物抗宿主病外，两组中最常见的严重不良事件是感染，HSCT组有30名参与者（59%），非HSCT组则有19名参与者（44%）。

总之，异基因造血干细胞移植与晚期CTCL参与者显著延长的无进展生存期相关。这些结果表明，异基因造血干细胞移植治疗应提供给移植前疾病缓解的高危、晚期蕈样肉芽肿或Sézary综合征患者。

附：英文原文

Title: Allogeneic transplantation in advanced cutaneous T-cell lymphomas (CUTALLO): a propensity score matched controlled prospective study

Author: Adèle de Masson, Marie Beylot-Barry, Caroline Ram-Wolff, Jean-Baptiste Mear, Stéphane Dalle, Michel dIncan, Saskia Ingen-Housz-Oro, Corentin Orvain, Julie Abraham, Olivier Dereure, Amandine Charbonnier, Jérme Cornillon, Christine Longvert, Stéphane Barete, Serge Boulinguez, Ewa Wierzbicka-Hainaut, Franois Aubin, Marie-Thérèse Rubio, Marc Bernard, Aline Schmidt-Tanguy, Roch Houot, Anne Pham-Ledard, David Michonneau, Pauline Brice, Hélène Labussière-Wallet, Jean-David Bouaziz, Florent Grange, Hélène Moins-Teisserenc, Katayoun Jondeau, Laurence Michel, Samia Mourah, Maxime Battistella, Etienne Daguindau, Michael Loschi, Alexandra Picard, Nathalie Franck, Natacha Maillard, Anne Huynh, Stéphanie Nguyen, Ambroise Marais, Guillaume Chaby, Patrice Ceballos, Yannick Le Corre, Sébastien Maury, Jacques-Olivier Bay, Henri Adamski, Emmanuel Bachy, Edouard Forcade, Gérard Socié, Martine Bagot, Sylvie Chevret, Régis Peffault de Latour, Adèle de Masson, Marie Beylot-Barry, Caroline Ram-Wolff, Jean-Baptiste Mear, Stéphane Dalle, Michel dIncan, Saskia Ingen-Housz-Oro, Corentin Orvain, Julie Abraham, Olivier Dereure, Amandine Charbonnier, Jérme Cornillon, Christine Longvert, Stéphane Barete, Serge Boulinguez, Ewa Wierzbicka-Hainaut, Franois Aubin, Marie-Thérèse Rubio, Marc Bernard

Issue&Volume: 2023-04-24

Abstract:

Background

Advanced-stage cutaneous T-cell lymphomas (CTCLs) are rare, usually refractory, and fatal diseases. Case series have suggested that allogeneic haematopoietic stem cell transplantation (HSCT) might improve the prognosis of advanced-stage CTCLs. The objective of this study was to investigate the effect of allogeneic HSCT compared with non-HSCT therapy on the outcome of individuals with advanced-stage CTCLs.

Methods

In this prospective, multicentre, matched controlled trial, conducted at 30 hospitals, participants with advanced CTCLs were allocated treatment: if they had an available compatible related donor they were assigned to allogeneic HSCT, or if not they were allocated to non-allogeneic HSCT therapy. Key inclusion criteria were participants aged 18–70 years, with advanced stage mycosis fungoides or Sézary syndrome, and at least one poor prognostic criteria. Participants were excluded if they were not in complete or partial remission of the disease. Propensity score 1:1 matching with replacement (ie, that each participant treated with HSCT was matched to the participant with the closest propensity score treated with non-HSCT therapy, even if they had already been matched) was used to handle confounding factors, with the balance of covariate distribution between HSCT and non-HSCT groups assessed using standardised mean differences. The primary endpoint was progression-free survival in the matched intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02520908), and is currently active but not recruiting.

Findings

From June 1, 2016, to March 3, 2022, total of 99 participants were enrolled at 17 centres in France. Participants with a sibling or matched unrelated donor were assigned to allogeneic HSCT (HSCT group, n=55 [56%]) and participants without a donor were assigned to non-allogeneic HSCT treatment (non-HSCT group, n=44 [44%]). The median follow-up among survivors was 12·6 months (IQR 11·0–35·2). In the HSCT group, 51 participants (93%) were 1:1 matched to participants from the non-HSCT group. In the intention-to-treat analysis, median progression-free survival was significantly longer in the HSCT group (9·0 months [95% CI 6·6–30·5]) than in the non-HSCT group (3·0 months [2·0–6·3]), with a hazard ratio of 0·38 (95% CI 0·21–0·69; p<0·0001). In the per-protocol population, 40 participants (78%) in the HSCT group had 101 serious events and 29 participants (67%) in the non-HSCT group had 70 serious adverse events. The most common serious adverse event other than graft-versus-host disease in both groups was infections, occurring in 30 participants (59%) in the HSCT group and in 19 participants (44%) in the non-HSCT group.

Interpretation

Allogeneic HSCT was associated with significantly longer progression-free survival in participants with advanced-stage CTCLs. These results indicate that allogeneic HSCT treatment should be made available to individuals with high-risk, advanced-stage mycosis fungoides or Sézary syndrome who achieve pre-transplant disease remission.

DOI: 10.1016/S0140-6736(23)00329-X

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00329-X/fulltext