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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)

Research output: Contribution to journalArticle

Jesus Feliu, Victoria Potter, Francesco Grimaldi, Jennifer Clay, Lajos Floro, Chandan Saha, Linda Barber, Guillermo Orti, Ahmad Abdel Raheem Alnagar, Ricardo Garcia-Muñoz, Michelle Kenyon, Pramila Krishnamurthy, Hugues de Lavallade, Kavita Raj, Donal McLornan, Antonio Pagliuca, Ghulam J. Mufti

Original languageEnglish
JournalBone Marrow Transplantation
Early online date26 Sep 2019
DOIs
Publication statusE-pub ahead of print - 26 Sep 2019

King's Authors

Abstract

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.

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