Subject(s)
Antibodies, Monoclonal/administration & dosage , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute/therapy , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Adult , Allografts , Female , Humans , Leukemia, Myeloid, Acute/metabolism , Leukemia, Myeloid, Acute/pathology , Male , Middle Aged , Nivolumab , Programmed Cell Death 1 Receptor/metabolism , RecurrenceABSTRACT
Non-relapse mortality after Allo-SCT has significantly decreased over the last years. Nevertheless, relapse remains a major cause for post SCT mortality in patients with AML and high-risk myelodysplastic syndrome (MDS). In this retrospective single-center analysis, we have analyzed the treatment outcomes of 108 patients with AML or MDS, who relapsed after Allo-SCT. Seventy of these patients (65%) were treated with salvage therapies containing chemotherapy alone, allogeneic cell-based treatment or the combination of both. Thirty-eight patients (35%) received palliative treatment. Median OS after diagnosis of relapse was 130 days. Compared with patients who received chemotherapy alone, response to salvage therapy was significantly improved in patients treated with a combination of chemo- and allogeneic cell-based therapy (CR rate 57% vs 13%, P=0.002). Among risk factors concerning pretreatment characteristics, disease status before first Allo-SCT, and details of transplantation, only the time interval from Allo-SCT to relapse was an independent predictor of response to salvage therapy and OS. These data confirmed that time to relapse after transplantation is an important prognostic factor. Up to now, only patients eligible for treatment regimens containing allogeneic cell-based interventions achieved relevant response rates.
Subject(s)
Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/therapy , Myelodysplastic Syndromes/mortality , Myelodysplastic Syndromes/therapy , Salvage Therapy , Adolescent , Adult , Aged , Allografts , Disease-Free Survival , Female , Humans , Male , Middle Aged , Recurrence , Retrospective Studies , Survival Rate , Time FactorsABSTRACT
Antigenic peptides are translocated by the TAP peptide transporter from the cytosol into the endoplasmic reticulum (ER) for loading onto MHC class I molecules. Peptides that fail to bind need to be removed from the ER. Here we provide evidence that peptide export utilizes the Sec61p translocon as demonstrated by blocking this channel with bacterial exotoxin. Peptide export interferes with the retrotranslocation of beta2-microglobulin from the ER to the cytosol, suggesting similar pathways for the disposal of proteins and oligopeptides. Peptide export requires ATP supply to the ER lumen but is independent of ATP hydrolysis.
