Escalating-dose HLA-mismatched DLI is safe for the treatment of leukaemia relapse following alemtuzumab-based myeloablative allo-SCT

Abstract

Although the feasibility of using HLA-mismatched unrelated donors as an alternate graft source for haematopoietic SCT (HSCT) has been shown, little is known about the safety of HLA-mismatched DLI for the treatment of relapse. We examined the outcome of 58 consecutive leukaemia patients who received escalating-dose DLI for treatment of relapse after alemtuzumab-conditioned myeloablative unrelated donor HSCT at our institution. High-resolution HLA typing on stored DNA samples revealed mismatches in 28/58 patients who were considered HLA-matched at the time of transplantation. Following DLI from HLA-matched (10/10) (n ¼ 30) or -mismatched (7-9/10) (n ¼ 28) unrelated donors, we found no significant difference in the incidence of acute GVHD (17.2% versus 23.1%, P ¼ 0.59), probability of remission at 3 years (62.1% versus 63.9%, P ¼ 0.89) or 5-year OS (89.8% versus 77.7%, P ¼ 0.22). We conclude that escalating-dose DLI can be safely given to HLA-mismatched recipients following T-depleted myeloablative HSCT.

Immune Reconstitution after Haploidentical Hematopoietic Stem Cell Transplantation

“…Innes et al 2013 [55] Modified DLI HIT and MRDT Eight hundred and fourteen patients were enrolled, this study suggest that risk stratification-directed modified DLI may reduce relapse and improve survival of subjects with standard-risk acute leukemia after HSCT, although the effect of DLI on immune reconstitution need to be investigated.…”

“…Unfortunately, serious infections and disease relapse resulting from delayed immune reconstitution remain the 2 most frequent causes of mortality after allogeneic HSCT, particularly in patients who received extensively TCD CD34 þ cell megadose allografts [10][11][12][13][14][15]. Advances in the understanding of immune recovery profiles in haploidentical recipients [8,, along with new methods of modifying donor T cells [48][49][50] and natural killer (NK) cells [51], have made it possible to establish new strategies to improve post-transplantation immunologic reconstitution [9,[52][53][54][55][56][57][58].…”

Donor lymphocyte infusions in AML and MDS: Enhancing the graft-versus-leukemia effect

“…Although concerns rise about potential higher rates of GvHD in DLI from mismatched donors compared with matched donors, some data suggest that its use might be equally safe. Recently, Innes et al [55] reported a comparison of two cohorts (matched and mismatched donors) of 43 patients (mostly CML) who underwent a cyclophosphamide (Cy) total body irradiation in in vivo TCD (alemtuzumab) reduced intensity conditioning (RIC) allo-HCT and received DLI either for MC or relapse. They found no statistical difference between both cohorts in terms of incidence of acute GvHD, 5-year OS, and probability of remission.…”

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

“…74,75 Similarly, several retrospective studies also suggested no significant difference between unrelated and related DLI in the incidence of GVHD. [76][77][78] Limited clinical data are available on haploidentical DLI. As haploidentical HSCT has been employed worldwide, 79 it is expected that a series of studies on haploidentical DLI will be available in the near future.…”