Epidemiology and biology of relapse after stem cell transplantation

Somatic mutation of HLA‐DRB1*04:03 in a patient with myelodysplastic syndrome at diagnosis

“…Loss of expression of HLA class II molecules on tumor cells could enable the tumor to escape from CD4+ T‐cell recognition, while tumor cells are able to avoid CD8+ cytotoxic T‐cell recognition by downregulating HLA class I‐restricted presentation of tumor‐associated antigens . Evidences showed the acquired uniparental disomy of the chromosome 6p as frequent mechanism of myeloid malignancy immune escape after haploidentical HSCT . The loss of HLA molecules targeted by haploidentical donor T‐cell alloreactivity enables to evade graft‐vs‐leukemia effect through chromosome 6p LOH.…”

“…HLA-DR gene, mutation, myelodysplastic syndrome Loss or decrease of HLA expression has been reported in various hematologic or solid malignancies [1][2][3][4][5] and in acquired aplastic anemia, [6][7][8] suggesting that it impacts the immunosurveillance escape mechanism. 1,2 HLA expression may be decreased as a result of loss of heterozygosity (LOH) of the short arm of chromosome 6 (6p) encompassing HLA genes or somatic mutations in the HLA genes.…”

“…11,16 Evidences showed the acquired uniparental disomy of the chromosome 6p as frequent mechanism of myeloid malignancy immune escape after haploidentical HSCT. [3][4][5] The loss of HLA molecules targeted by haploidentical donor T-cell alloreactivity enables to evade graft-vs-leukemia effect through chromosome 6p LOH. In our patient, the clinical impact of this previously unreported synonymous HLA-DRB1 gene mutation is unclear.…”

Immune Escape after Hematopoietic Stem Cell Transplantation (HSCT): From Mechanisms to Novel Therapies

“…Poor AML clinical outcomes are predominantly due to disease relapse and are frequently observed in patients treated with chemotherapy alone, despite the possibility of precisely defining the underlying genetic defect and the availability of novel drugs targeting peculiar molecular defects [1]. Thus, for most AML patients allo-HSCT remains the most effective curative option with the best chance of achieving durable complete remission (CR) [2]. However, even with this procedure death due to relapse occurs in about 30-40% of patients depending on the disease type and status at the time of transplant [3][4][5].…”

Learning the next-generation sequencing alphabet of immune reconstitution: factors determining CD8+ T-cell receptor α-chain repertoire dynamics after hematopoietic stem cell transplantation

“…First, patients who relapsed were explicitly excluded from the study. However, relapse remains the main cause of treatment failure in HSCT, 16 and, similar to GvHD, a central role for T cells in the therapeutic graft-versus-leukemia effect has been well established. 17 Hence, NGS-based studies of T-cell repertoire characteristics that might associate with leukemia relapse after transplantation are of the foremost importance.…”