TY - JOUR
T1 - Full donor chimerism without graft-versus-host disease
T2 - the key factor for maximum benefit of pre-emptive donor lymphocyte infusions (pDLI)
AU - Feliu, Jesus
AU - Potter, Victoria
AU - Grimaldi, Francesco
AU - Clay, Jennifer
AU - Floro, Lajos
AU - Saha, Chandan
AU - Barber, Linda
AU - Orti, Guillermo
AU - Alnagar, Ahmad Abdel Raheem
AU - Garcia-Muñoz, Ricardo
AU - Kenyon, Michelle
AU - Krishnamurthy, Pramila
AU - de Lavallade, Hugues
AU - Raj, Kavita
AU - McLornan, Donal
AU - Pagliuca, Antonio
AU - Mufti, Ghulam J.
PY - 2019/9/26
Y1 - 2019/9/26
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85074055403&partnerID=8YFLogxK
U2 - 10.1038/s41409-019-0695-x
DO - 10.1038/s41409-019-0695-x
M3 - Article
C2 - 31558789
AN - SCOPUS:85074055403
SN - 0268-3369
JO - Bone Marrow Transplantation
JF - Bone Marrow Transplantation
ER -