Full donor chimerism without graft-versus-host disease: the key factor for maximum benefit of pre-emptive donor lymphocyte infusions (pDLI).,Bone Marrow Transplantation

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Full donor chimerism without graft-versus-host disease: the key factor for maximum benefit of pre-emptive donor lymphocyte infusions (pDLI).
Bone Marrow Transplantation ( IF 4.5 ) Pub Date : 2019-09-26 , DOI: 10.1038/s41409-019-0695-x
Jesus Feliu ₁ , Victoria Potter ₂ , Francesco Grimaldi ₃ , Jennifer Clay ₄ , Lajos Floro ₂ , Chandan Saha ₅ , Linda Barber ₆ , Guillermo Orti ₇ , Ahmad AbdelRaheem Alnagar ₈ , Ricardo Garcia-Muñoz ₁ , Michelle Kenyon ₂ , Pramila Krishnamurthy ₂ , Hugues de Lavallade ₂ , Kavita Raj ₂ , Donal McLornan ₂ , Antonio Pagliuca ₂ , Ghulam J Mufti ₂

Affiliation

Compared to standard-conditioned regimens, reduced-intensity conditioning and T-cell depletion deliver lower transplant-related mortality and decreased graft-vs-host disease after allogeneic hematopoietic stem-cell transplantation. These advantages may however be mitigated by increased relapse rates and delays in achievement of full donor chimerism (FDC). Pre-emptive donor lymphocyte infusions (pDLI) facilitate the conversion of mixed (MDC) to FDC. However, there is a lack of published data on the risk/benefit analysis of this intervention. We performed a retrospective analysis of 119 patients who received 276 pDLI doses for falling CD3 chimerism, CD3 < 50% or mixed XX/XY karyotype. 71/119(60%) Patients achieved FDC, with only one reverting to MDC. Cumulative incidence (CI) of relapse at 5 years was significantly lower in the FDC group (16.0 vs 41.4%, p < 0.001). Those patients who achieved FDC had improved EFS (p < 0.001) and OS (p < 0.001). Interestingly, patients with FDC who developed DLI-induced graft-vs-host disease (GvHD) showed a similar outcome to those with MDC. The majority of patients who receive pDLI convert to FDC and retain that status. Achievement of FDC after pDLI impacts on survival, and those patients who achieve FDC without GvHD, experience maximum clinical benefit. Strategies to minimise DLI-induced GvHD should be considered to maximise the therapeutic potential of this intervention.

中文翻译：

完全的供体嵌合，无移植物抗宿主病：先发性供体淋巴细胞输注（pDLI）最大化获益的关键因素。

与标准条件疗法相比，强度降低的条件疗法和T细胞耗竭可降低同种异体造血干细胞移植后与移植相关的死亡率，并降低移植物抗宿主病。但是，增加复发率和延迟完全捐赠者嵌合（FDC）的实现可能会减轻这些优势。抢先的供体淋巴细胞输注（pDLI）有助于将混合（MDC）转换为FDC。但是，缺乏有关该干预措施的风险/收益分析的公开数据。我们对119例因CD3嵌合下降，CD3 <50％或XX / XY混合核型下降而接受276 pDLI剂量的患者进行了回顾性分析。71/119（60％）患者达到了FDC，只有一名恢复为MDC。FDC组5年复发的累积发生率（CI）明显较低（16。0比41.4％，p <0.001）。那些达到FDC的患者的EFS（p <0.001）和OS（p <0.001）均有改善。有趣的是，发展为DLI诱导的移植物抗宿主病（GvHD）的FDC患者显示出与MDC类似的结果。接受pDLI的大多数患者会转换为FDC并保持该状态。pDLI后FDC的实现会影响生存率，而那些没有GvHD的FDC患者将获得最大的临床收益。应考虑将DLI诱导的GvHD降至最低的策略，以最大限度地提高这种干预的治疗潜力。接受pDLI的大多数患者会转换为FDC并保持该状态。pDLI后FDC的实现会影响生存率，而那些没有GvHD的FDC患者将获得最大的临床收益。应考虑将DLI诱导的GvHD降至最低的策略，以最大限度地提高这种干预的治疗潜力。接受pDLI的大多数患者会转换为FDC并保持该状态。pDLI后FDC的实现会影响生存率，而那些没有GvHD的FDC患者将获得最大的临床收益。应考虑将DLI诱导的GvHD降至最低的策略，以最大限度地提高这种干预的治疗潜力。

更新日期：2019-09-26

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