In:
Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 3683-3683
Abstract:
The induction of a graft versus leukaemia (GvL) effect following allogenic hematopoietic stem cell transplantation (HSCT) is critical for the outcome in patients with hematological malignancies. Tumor-specific antigens as WT-1 are expressed on leukemic blasts and are major targets of the GvL effect. Therefore the generation of a WT-1 specific immune response through peptide vaccination could enhance the antileukemic effects after HSCT. In a phase I study five HLA A*0201 positive patients with high-risk AML (median age 64 yrs, range 33–67yrs) were vaccinated with the WT-1 derived peptide RMFPNAPYL (126–134) beginning at day 21 after HSCT. The vaccination protocol consisted in four biweekly vaccinations with the peptide in a dose of 0,2mg administered i.d. and s.c. with 1mg of keyhole limpet hemocyanin (KLH) as adjuvant. Concomitantly, patients received daily doses of GM-CSF (75μg/d) for four days beginning two days before vaccination. After the first four cycles, vaccine was administered monthly. When patients showed signs of GvHD or infection vaccination was discontinued. WT-1-specific T cell responses were monitored in peripheral blood using tetramer analysis. No severe acute toxicity attributable to the vaccination was observed. In all patients a local inflammatory response at the site of injection was detected, which resolved fast after ending of the vaccination cycle. In some patients a systemic inflammatory response with fever and increase of the leukocyte count were observed, which also resolved a few days after vaccination. Three patients achieved a complete remission of the AML after transplantation and did not relapse. One patient developed an intraneural relapse of the AML in the N. medianus of the left arm, which was successfully treated by irradiation. Though, she did not show a relapse in the bone marrow and maintains a full donor chimerism in bone marrow and peripheral blood 600 days after transplantation. One patient relapsed and died four months after transplantation. Two patients developed a grade I GvHD of the skin shortly after the first vaccination. Therefore vaccination was discontinued and resumed two weeks after resolution of the GvHD. No GvHD signs were observed after the subsequent vaccination cycles. One patient developed a grade III GvHD of the skin and gut after the 3rd vaccination. In this patient GvHD proved to be resistant to the common immunosuppressive agents and the patients died of septicaemia four months after transplant. One patient developed a three-system grade IV GvHD after the 2nd vaccination. Vaccination was then resumed after resolution of the GvHD. He unfortunately died in complete remission because of systemic aspergillosis ten months after transplant. In three patients WT-1 specific T cell responses were monitored in peripheral blood at different time points prior and after vaccination by tetramer analysis. Prior to vaccination none of the patients showed a positive response to WT1. In all these patients CD8+/WT1-specific T cells were detected after one (1/3, 0,66% tetramer binding CD8+ cells) or two vaccinations (2/3, 0,99% and 0,81% tetramer binding CD8+ cells, respectively). In accordance with our observations, WT1 vaccination could contribute to the maintenance of a complete remission in patients with high-risk AML after HSCT. However, it could enhance GvH reactions because of the adjuvants used. Therefore further clinical observations in a larger number of patients are needed.
Type of Medium:
Online Resource
ISSN:
0006-4971
,
1528-0020
DOI:
10.1182/blood.V108.11.3683.3683
Language:
English
Publisher:
American Society of Hematology
Publication Date:
2006
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
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