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Immunosuppression for 6–8 weeks after modified donor lymphocyte infusion reduced acute graft-versus-host disease without influencing graft-versus-leukemia effect in haploidentical transplant

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Background In haploidentical hematopoietic stem cell transplantation (HSCT), the duration of graft-versus-host disease (GVHD) prophylaxis after modified donor lymphocyte infusion (DLI) was the only risk factor of DLI-associated grades 3–4 acute GVHD. However, the successful application of modified DLI depended not only on the reduction of severe GVHD, but also on the preservation of graft-versus-leukemia (GVL) effect. Therefore, this study was performed to compare the impact of prophylaxis for 6–8 weeks and prophylaxis for <6 weeks on GVL effect after modified DLI in haploidentical HSCT. Methods A total of 103 consecutive patients developing hematological relapse or minimal residual disease (MRD)-positive status after haploidentical HSCT and receiving modified DLI were investigated retrospectively. Fifty-two patients received prophylaxis for 6–8 weeks after modified DLI; the remaining 51 patients received prophylaxis for <6 weeks. Results First, compared with prophylaxis for <6 weeks, prophylaxis for 6–8 weeks reduced incidence of relapse in total patients (26.6% vs. 69.0%, P <0.001). Besides, prophylaxis for 6–8 weeks also reduced incidence of relapse in 54 patients developing hematological relapse post-transplant (P=0.018) and in 49 patients developing MRD-positive status post-transplant (P <0.001). Second, prophylaxis for 6–8 weeks reduced incidence of acute GVHD (P <0.05), reduced the therapeutic application of immunosuppressive agents (P=0.019), but increased the incidence of chronic GVHD (P<0.05). Third, prophylaxis for 6–8 weeks improved overall survival and disease-free survival in total patients, as well as in patients developing hematological relapse post-transplant and in patients developing MRD-positive status post-transplant (P <0.05). Conclusions In haploidentical HSCT, prophylaxis for 6–8 weeks after modified DLI does not reduce GVL effect, but reduces the incidence of DLI-associated acute GVHD compared with prophylaxis for <6 weeks. This strategy will probably improve the safety and efficacy of modified DLI further.
Title: Immunosuppression for 6–8 weeks after modified donor lymphocyte infusion reduced acute graft-versus-host disease without influencing graft-versus-leukemia effect in haploidentical transplant
Description:
Background In haploidentical hematopoietic stem cell transplantation (HSCT), the duration of graft-versus-host disease (GVHD) prophylaxis after modified donor lymphocyte infusion (DLI) was the only risk factor of DLI-associated grades 3–4 acute GVHD.
However, the successful application of modified DLI depended not only on the reduction of severe GVHD, but also on the preservation of graft-versus-leukemia (GVL) effect.
Therefore, this study was performed to compare the impact of prophylaxis for 6–8 weeks and prophylaxis for <6 weeks on GVL effect after modified DLI in haploidentical HSCT.
Methods A total of 103 consecutive patients developing hematological relapse or minimal residual disease (MRD)-positive status after haploidentical HSCT and receiving modified DLI were investigated retrospectively.
Fifty-two patients received prophylaxis for 6–8 weeks after modified DLI; the remaining 51 patients received prophylaxis for <6 weeks.
Results First, compared with prophylaxis for <6 weeks, prophylaxis for 6–8 weeks reduced incidence of relapse in total patients (26.
6% vs.
69.
0%, P <0.
001).
Besides, prophylaxis for 6–8 weeks also reduced incidence of relapse in 54 patients developing hematological relapse post-transplant (P=0.
018) and in 49 patients developing MRD-positive status post-transplant (P <0.
001).
Second, prophylaxis for 6–8 weeks reduced incidence of acute GVHD (P <0.
05), reduced the therapeutic application of immunosuppressive agents (P=0.
019), but increased the incidence of chronic GVHD (P<0.
05).
Third, prophylaxis for 6–8 weeks improved overall survival and disease-free survival in total patients, as well as in patients developing hematological relapse post-transplant and in patients developing MRD-positive status post-transplant (P <0.
05).
Conclusions In haploidentical HSCT, prophylaxis for 6–8 weeks after modified DLI does not reduce GVL effect, but reduces the incidence of DLI-associated acute GVHD compared with prophylaxis for <6 weeks.
This strategy will probably improve the safety and efficacy of modified DLI further.

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