Better outcome with haploidentical over HLA-matched related donors in patients with Hodgkin’s lymphoma undergoing allogeneic haematopoietic cell transplantation—a study by the Francophone Society of Bone Marrow Transplantation and Cellular Therapy

Abstract

The question of the best donor type between haploidentical (HAPLO) and matched-related donors (MRD) for patients with advanced HL receiving an allogeneic hematopoietic cell transplantation (allo-HCT) is still debated. Given the lack of data comparing these two types of donor in the setting of non-myeloablative (NMA) or reduced-intensity (RIC) allo-HCT, we performed a multicentre retrospective study using graft-vs.-host disease-free relapse-free survival (GRFS) as our primary endpoint. We analysed the data of 151 consecutive HL patients who underwent NMA or RIC allo-HCT from a HAPLO (N = 61) or MRD (N = 90) between January 2011 and January 2016. GRFS was defined as the probability of being alive without evidence of relapse, grade 3-4 acute GVHD or chronic GVHD. In multivariable analysis, MRD donors were independently associated with lower GRFS compared to HAPLO donors (HR = 2.95, P < 0.001). Disease status at transplant other than CR was also associated with lower GRFS in multivariable analysis (HR = 1.74, P = 0.01). In addition, the administration of ATG was independently linked to higher GRFS (HR = 0.52, P = 0.009). In summary, we observed significantly higher GRFS in HL patients receiving an allo-HCT using the HAPLO PT-Cy platform compared to MRD.

Haploidentical‐ versus identical‐sibling transplant for high‐risk pediatric AML: A multi‐center study

“…In that study [24], among the patients receiving ISD‐SCT, relapse rate was higher in the minimal residual disease (MRD)‐positive group than in the MRD‐negative group (36% vs. 7%), whereas relapse rates were comparable between the MRD‐positive group and MRD‐negative group among patients who received HID‐SCT (13% vs. 7%); suggesting that HID‐SCT had a stronger graft versus leukemia (GVL) effect than ISD‐SCT [24]. The results from other studies also confirmed the stronger GVL effect in HID‐SCT than in ISD‐SCT [25, 26]. In theory, in HID‐SCT, stronger alloimmune response would be achieved by leukemic cells which express HLA mismatched from donors and result in a decrease in relapse rate.…”

Haploidentical donor is preferred over matched sibling donor for pre-transplantation MRD positive ALL: a phase 3 genetically randomized study

“…With the increasingly used haploidentical SCT (HIDT), HLA-identical sibling donors remain the first choice, though a number of studies have shown that treating patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) using haploidentical donors (HIDs) could achieve comparable outcomes to those who undergoing HLA-matched sibling donor transplantation (MSDT) [3,6,7]. On the other hand, using haploidentical transplants, the graft-versus-leukemia (GVL) effect may be stronger, as mismatches for HLA antigens on leukemic cells would provide allo-immune targets [4,5,[8][9][10][11][12][13]. A recent large European Society for Blood and Marrow Transplantation (EBMT) study indicated that HIDT has a lower incidence of relapse than MSDT for low-risk (HR = 0.83, P = 0.011) and intermediate-risk (HR = 0.85, P = 0.033) hematological malignancies [5].…”

“…A recent large European Society for Blood and Marrow Transplantation (EBMT) study indicated that HIDT has a lower incidence of relapse than MSDT for low-risk (HR = 0.83, P = 0.011) and intermediate-risk (HR = 0.85, P = 0.033) hematological malignancies [5]. The better relapse rate with HIDT compared to MSDT has also been observed in patients with lymphomas [8,9]. Our previous studies showed that HIDT is superior to MSDT in terms of a lower relapse rate for patients with high-risk leukemia [11].…”

“…Furthermore, for older patients with acute leukemia, offspring donors not only result in lower non-relapse mortality (NRM), but also tended to be associated with a lower risk of relapse than MSDT [12]. Although these reports have effectively proven the potential superiority of HIDT to MSDT in the context of relapse risk in treating patients with some specified subgroups of hematological malignancies [4,5,[8][9][10][11][12], they cannot inform decision-making in choosing one donor type over another for a specific patient due to the retrospective nature of the studies or highly diverse populations and various transplant regimens [4,5,[8][9][10][11][12][13].…”

“…For patients with ALL, a more recent EBMT study revealed that HIDT can obscure the negative effects of pre-HSCT MRDpos before transplantation in a subgroup analysis (CIR, 29% vs. 26% and leukemia-free survival, LFS, 50% vs. 50% for pre-HSCT MRDpos and pre-HSCT MRDneg, respectively) [16]. Though all of these findings [5,[8][9][10][11]13] suggested a benefit associated with HIDT in certain contexts, the choice of an optimal candidate in terms of a stronger GVL effect warrants further investigation. Therefore, we designed a prospective genetically randomized study to evaluate donor options by comparing the endpoints related to disease control between ALL patients with pre-HSCT MRDpos who underwent HIDT and those who received MSDT.…”