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.

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.