New strategies of DLI in the management of relapse of hematological malignancies after allogeneic hematopoietic SCT

Abstract

DLI is an effective strategy for patients with recurrent hematological malignancies after allogeneic hematopoietic SCT (allo-HSCT). DLI has been widely applied to boost the graft vs tumor (GVT) or GVL effects. However, given the potentially severe complications associated with conventional DLI and transient GVL effect, new strategies for DLI are emerging. In this review, we have discussed the recent important studies on DLI as a prophylactic or therapeutic modality for relapsed hematological disorders after allo-HSCT. The strategies to separate GVL from GVHD have also been discussed. Leukemia-targeting therapy and lymphodepletion combined with DLI, and prophylactic DLI after allo-HSCT are often employed for patients with high risk of relapse, which has been reviewed as well. In addition, we have also discussed the issues on DLI to be further addressed, such as the doses, timing and frequency of DLI in different clinical settings, leukemic antigen-specific DLI as well as how to augment GVL effect while attenuating GVHD.

Donor Lymphocyte Infusion for Relapsed Hematological Malignancies after Unrelated Allogeneic Bone Marrow Transplantation Facilitated by the Japan Marrow Donor Program

“…Nevertheless, the results of the present study indicate that UDLI has efficacy in inducing a GVT effect, even at 100 days after treatment. As reported previously, the present study revealed that UDLI was most effective for the treatment of CML [2,4,8,19], although recent reports have shown that post-transplantation TKIs might be effective for relapse as well as reducing the incidence of relapse for patients with Philadelphia-positive leukemia [20][21][22][23][24]. A particularly strong effect was also observed in patients with low tumor burden, such as those with cytogenetic/molecular relapse or the onset of acute GVHD after UDLI.…”

“…Nevertheless, because mortality associated with a second allo-HSCT for relapsed recipients is considered to be much higher, DLI therapy may represent a viable alternative to second allo-HSCT. Thus, DLI has been applied in the treatment of various hematological malignancies [6][7][8], such as leukemias [9,10], lymphoma [11][12][13], and myeloma [14,15]. In particular, patients who have relapsed after unrelated allo-HSCT because of lack of HLA-matched related sibling donors may also benefit from unrelated DLI (UDLI) [16].…”

Graft-versus-Host Disease–Free, Relapse-Free Survival after Allogeneic Stem Cell Transplantation for Myelodysplastic Syndrome

“…Those that can induce graft-versus-leukemia effects are under development [43]. Until their introduction into real clinical practice, currently available cellular therapy for the induction of GVHD aiming to evoke graft-versus-leukemia effects could be considered even at the expense of morbidities related to GVHD [44]. For disease that outpaces the development of GVHD, pretransplant debulking treatment or post-transplant maintenance chemotherapy could be an option [19,45,46].…”

Leukocytapheresis in nonmobilized donors for cellular therapy protocols: Evaluation of factors affecting collection efficiency of cells

“…In the field of HPC transplantation, the target is the collection of CD34+ cells. 6 In contrast, in other cell therapy protocols, the target is the collection of lymphocytes for donor lymphocyte infusions 21 or the collection of monocytes in order to generate monocyte-derived dendritic cells. 4 In ECP, there is no minimum of cells to collect because there are contradictory results regarding the amount of cells treated and the response to ECP.…”