Chimerism status is correlated to acute graft-versus-host disease after allogeneic stem cell transplantation

Abstract

To evaluate the correlation between chimerism status and acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic stem cell transplantation. Chimerism of peripheral blood of 124 patients was monitored at regular intervals post-transplant. The chimerism of 124 post-transplant cases of CD3(+)T lymphocytes, 107 cases of CD3(-)CD56(+)CD16(+)NK lymphocytes, 49 cases of CD15(+) granulocytes, and 27 cases of CD19(+)B lymphocytes sorted by fluorescence-activated cell sorter were analyzed by polymerase chain reaction amplification of short tandem repeats. Differences were found in the time between establishment of full donor T-cell chimerism and the occurrence of aGVHD (P = 0.035, two related samples test). Patients with ≥69 % donor chimerism on day +7 in T-cells had higher rates of aGVHD. This study may provide a rational basis for treatment with adoptive immunotherapy at an earlier time, such as day 7 after SCT, than at present to prevent aGVHD.

Monitoring of Hematopoietic Chimerism by Real-Time Quantitative PCR of Micro Insertions/Deletions in Samples with Low DNA Quantities

“…First, residual recipient hematopoiesis after myeloablative conditioning followed by HSCT correlates with graft failure and persisting disease [1,23,24]. Second, achievement of complete donor-derived hematopoiesis early after HSCT is associated with increased incidence of graft-versus-host disease [8,23,25,26]. Last, some studies corroborated a higher risk for disease relapse in patients with mixed recipient chimerism after HSCT [4,5,27].…”

“…Taken together, these data illustrate that the routine assessment of chimerism is a useful approach to evaluate post-transplantation prognosis. Importantly, chimerism status may provide the rationale for post-transplantation therapy like modulation of immunosuppression or donor lymphocyte infusions [8]. Indeed, Bader et al showed that the 3 year event-free survival was increased from 0 to 37% and from 0 to 36% after immunotherapy of patients with increasing recipient chimerism in pediatric ALL [30] and AML [31], respectively.…”

“…Moreover, several studies indicate that remaining or re-emerging recipient cells after ablation and transplantation are associated with a higher risk of disease relapse [1,2,3,4,5,6,7]. Therefore, the accurate and sensitive quantification of hematopoietic chimerism is a critical aspect of post-transplantation monitoring, since the results strongly influence the therapeutic approach such as donor lymphocyte infusions, additional chemotherapy, or re-transplantation [8]. …”

Impact of T-cell chimerism on relapse after cord blood transplantation for hematological malignancies: Nagoya Blood and Marrow Transplantation Group study

“…Although no significant differences were observed in the occurrence of acute or chronic GvHD between T-cell CDC and MC in the present study, T-cell chimerism may reflect the function of allo-reactivity in not only GVL effect, but also GvHD. Previous studies showed that higher T-cell chimerism was associated with the occurrence of acute GvHD, [10][11][12] chronic GvHD 13 or both. 14 No patient whose T-cell chimerism at day 28 was MC developed grades II-IV acute GvHD in this study.…”

Marcadores Inserção/Deleção na quantificação de quimerismo hematopoiético

“…Para a realização desta pesquisa foram analisados um total de (1)(2)(3)(4)(5)(6)(7)(8) é uma abordagem útil para avaliar o prognóstico pós-transplante e influenciar a abordagem terapêutica, como infusões de linfócitos do doador (DLIdonor leukocyte infusion), quimioterapia adicional ou retransplante (9) . Por este motivo, esforços tem sido feito no sentido de aumentar a sensibilidade das técnicas de detecção de quimerismo.…”