WT1-specific T-cell responses in high-risk multiple myeloma patients undergoing allogeneic T cell-depleted hematopoietic stem cell transplantation and donor lymphocyte infusions Journal Article


Authors: Tyler, E. M.; Jungbluth, A. A.; O'Reilly, R. J.; Koehne, G.
Article Title: WT1-specific T-cell responses in high-risk multiple myeloma patients undergoing allogeneic T cell-depleted hematopoietic stem cell transplantation and donor lymphocyte infusions
Abstract: While the emergence of WT1-specific cytotoxic T lymphocytes (WT1-CTL) has been correlated with better relapse-free survival after allogeneic stem cell transplantation in patients with myeloid leukemias, little is known about the role of these cells in multiple myeloma (MM). We examined the significance of WT1-CTL responses in patients with relapsed MM and high-risk cytogenetics who were undergoing allogeneic T cell- depleted hematopoietic stem cell transplantation (alloTCD-HSCT) followed by donor lymphocyte infusions. Of 24 patients evaluated, all exhibited WT1-CTL responses before allogeneic transplantation. These T-cell frequencies were universally correlated with pretransplantation disease load. Ten patients received low-dose donor lymphocyte infusions beginning 5 months after transplantation. All patients subsequently developed increments of WT1-CTL frequencies that were associated with reduction in specific myeloma markers, in the absence of graft-versus-host disease. Immunohistochemical analyses of WT1 and CD138 in bone marrow specimens demonstrated consistent coexpression within malignant plasma cells. WT1 expression in the bone marrow correlated with disease outcome. Our results suggest an association between the emergence of WT1-CTL and graft-versus-myeloma effect in patients treated for relapsed MM after alloTCD-HSCT and donor lymphocyte infusions, supporting the development of adoptive immunotherapeutic approaches using WT1-CTL in the treatment of MM (registered at http://clinicaltrials.gov, ID: NCT01131169). © 2013 by The American Society of Hematology.
Journal Title: Blood
Volume: 121
Issue: 2
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2013-01-10
Start Page: 308
End Page: 317
Language: English
DOI: 10.1182/blood-2012-06-435040
PROVIDER: scopus
PUBMED: 23160468
PMCID: PMC3952597
DOI/URL:
Notes: --- - "Export Date: 1 February 2013" - "CODEN: BLOOA" - "Source: Scopus"
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MSK Authors
  1. Guenther Koehne
    192 Koehne
  2. Achim Jungbluth
    388 Jungbluth
  3. Richard O'Reilly
    611 O'Reilly
  4. Eleanor M Tyler
    9 Tyler