Alloreactivity: the Janus-face of hematopoietic stem cell transplantation

Abstract

Differences in major and minor histocompatibility antigens between donor and recipient trigger powerful graft-versus-host reactions after allogeneic hematopoietic stem cell transplantation (HSCT). The clinical effects of alloreactivity present a Janus-face: detrimental graft-versus-host disease increases non-relapse mortality, beneficial graft-versus-malignancy may cure the recipient. The ultimate consequences on long-term outcome remain a matter of debate. We hypothesized that increasing donor-recipient antigen matching would decrease the negative effects, while preserving antitumor alloreactivity. We analyzed retrospectively a predefined cohort of 32 838 such patients and compared it to 59 692 patients with autologous HSCT as reference group. We found a significant and systematic decrease in non-relapse mortality with decreasing phenotypic and genotypic antigen disparity, paralleled by a stepwise increase in overall and relapse-free survival (Spearman correlation coefficients of cumulative excess event rates at 5 years 0.964; P o 0.00; respectively 0.976; P o0.00). We observed this systematic stepwise effect in all main disease and disease-stage categories. The results suggest that detrimental effects of alloreactivity are additive with each step of mismatching; the beneficial effects remain preserved. Hence, if there is a choice, the best match should be donor of choice. The data support an intensified search for predictive genomic and environmental factors of 'no-graft-versus-host disease'.

Death after hematopoietic stem cell transplantation: changes over calendar year time, infections and associated factors

“…Given the long time horizons, this will require support in planning and resources s r a e y 5 r a e y 1 s y a d 0 0 1 s y a d 0 3 s t n e i t a P 0 3 + y a d t a e v i l a s t n e i t a P s t n e i t a p l l A 1 + r a e y t a e v i l a s t n e i t a P 0 0 1 + y a d t a e v i l by public health bodies [27][28][29]. Furthermore, in the era of precision medicine and targeted therapies, HSCT has to provide best outcome regarding overall survival, quality of life and costs compared to any other treatment strategy [16]. Careful and continuing analysis of large data sets will help to achieve this goal.…”

“…Donor type was analysed in 10 types as previously described: autologous, syngeneic, HLA-identical sibling donor HY -, HLA-identical sibling donor HY + , matched family donor HY -, matched family donor HY + , matched unrelated donor HY -, matched unrelated donor HY + , mismatched unrelated donor, mismatched family donor (HY + refers to a female donor for a male recipient; HYto all other donor-recipient sex combinations) [16]. Matching was used as classified by the reporting team, at the time of first report.…”

Relative Impact of HLA Matching and Non-HLA Donor Characteristics on Outcomes of Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndrome

“…Transplants of male patients from female donors (sex mismatch) has been associated with poorer outcome [20][21][22]. We therefore investigated the relevance of sex mismatch relative to HLA mismatching in the subgroup of male patients who received transplants from 10/10 MUDs or 9/10 MMUDs.…”

Individualized prediction of leukemia‐free survival after autologous stem cell transplantation in acute myeloid leukemia

“…Therefore, choosing the modality for postremission therapy (PRT) after induction is a critical decision in disease management. 1,3,[8][9][10] Furthermore, it is not associated with complications such as graft-versus-host disease, a need for long-term immunosuppression, and reduced quality of life, as seen in allo-SCT recipients. Current recommendations from European LeukemiaNet advocate the selection of allogeneic transplantation for patients with adverse-risk AML, whereas intensive chemotherapy is used for patients with AML with a favorable molecular risk profile.…”

“…1,2,[4][5][6][7] With current practice, ASCT is considered safe with a low risk for transplantation-related mortality (TRM), even in the elderly. 1,3,[8][9][10] Furthermore, it is not associated with complications such as graft-versus-host disease, a need for long-term immunosuppression, and reduced quality of life, as seen in allo-SCT recipients. [11][12][13] In addition, it may offer Cancer October 15, 2019 additional disease control in comparison with intensive chemotherapy.…”