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Blood, Vol. 93 No. 7 (April 1), 1999:
pp. 2411-2419
Idiotype Vaccination Using Dendritic Cells After Autologous Peripheral
Blood Stem Cell Transplantation for Multiple Myeloma A Feasibility
Study
Volker L. Reichardt,
Craig Y. Okada,
Arcangelo Liso,
Claudia J. Benike,
Keith E. Stockerl-Goldstein,
Edgar G. Engleman,
Karl G. Blume, and
Ronald Levy
From the Divisions of Oncology, Hematology, Bone Marrow
Transplantation and the Stanford Blood Center, Stanford University
Medical Center, Stanford, CA.
The idiotype (Id) determinant on the multiple myeloma (MM) protein
can be regarded as a tumor-specific marker. Immunotherapy directed at
the MM Id may stem the progression of this disease. We report here on
the first 12 MM patients treated at our institution with high-dose
therapy and peripheral blood stem cell transplantation (PBSCT) followed
by Id immunizations. MM patients received PBSCT to eradicate the
majority of the disease. PBSCT produced a complete response in 2 patients, a partial response in 9 patients and stable disease in 1 patient. Three to 7 months after high-dose therapy, patients received a
series of monthly immunizations that consisted of two intravenous
infusions of Id-pulsed autologous dendritic cells (DC) followed by five
subcutaneous boosts of Id/keyhole limpet hemocyanin (KLH) administered
with adjuvant. Between 1 and 11 × 106 DC were obtained by
leukapheresis in all patients even after PBSCT. The administration of
Id-pulsed DC and Id/KLH vaccines were well tolerated with patients
experiencing only minor and transient side effects. Two of 12 patients
developed an Id-specific, cellular proliferative immune response and
one of three patients studied developed a transient but Id-specific
cytotoxic T-cell (CTL) response. Eleven of the 12 patients generated
strong KLH-specific cellular proliferative immune responses showing the
patients' immunocompetence at the time of vaccination. The two
patients who developed a cellular Id-specific immune response remain in complete remission. Of the 12 treated patients, 9 are
currently alive after autologous transplantation with a minimum
follow-up of 16 months, 2 patients died because of recurrent MM and 1 patient succumbed to acute leukemia. These studies show that patients make strong anti-KLH responses despite recent high-dose therapy and
that DC-based Id vaccination is feasible after PBSCT and can induce
Id-specific T-cell responses. Further vaccine development is necessary
to increase the proportion of patients that make Id-specific immune
responses. The clinical benefits of Id vaccination in MM remain to be determined.
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108(13):
4071 - 4077.
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|
|
|
|
|
|
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106(13):
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|
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|
|
|
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106(10):
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|
|
|
|
|
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77(5):
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[Full Text]
[PDF]
|
|
|
|
|
|
|
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11(9):
3377 - 3384.
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|
|
|
|
|
|
|
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11(4):
1629 - 1638.
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|
|
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|
|
|
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2004(1):
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|
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|
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|
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|
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|
|
|
|
|
|
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|
|
|
|
|
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|
|
|
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|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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100(1):
230 - 237.
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|
|
|
|
|
|
|
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62(10):
2861 - 2868.
[Abstract]
[Full Text]
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|
|
|
|
|
|
|
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99(9):
3280 - 3285.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Bachleitner-Hofmann, A. Stift, J. Friedl, R. Pfragner, K. Radelbauer, P. Dubsky, G. Schuller, T. Benko, B. Niederle, C. Brostjan, et al.
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87(3):
1098 - 1104.
[Abstract]
[Full Text]
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|
|
|
|
|
|
|
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|
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|
|
|
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98(9):
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273 - 285.
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[Full Text]
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|
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|
|
|
|
|
|
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B. Ludewig, K. McCoy, M. Pericin, A. F. Ochsenbein, T. Dumrese, B. Odermatt, R. E. M. Toes, C. J. M. Melief, H. Hengartner, and R. M. Zinkernagel
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Y.-J. Wen, B. Barlogie, and Q. Yi
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97(6):
1750 - 1755.
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[PDF]
|
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|
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|
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A. B. Pawlowska, S. Hashino, H. McKenna, B. J. Weigel, P. A. Taylor, and B. R. Blazar
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97(5):
1474 - 1482.
[Abstract]
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[PDF]
|
|
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|
|
|
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S. H. Lim, Z. Wang, M. Chiriva-Internati, and Y. Xue
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March 1, 2001;
97(5):
1508 - 1510.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. L. Warren, S. K. Bhatia, A. M. Acosta, C. E. Dahle, T. L. Ratliff, A. M. Krieg, and G. J. Weiner
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165(11):
6244 - 6251.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
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Y. Gazitt
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November 1, 2000;
18(6):
390 - 398.
[Abstract]
[Full Text]
|
|
|
|
|
|
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60(20):
5797 - 5802.
[Abstract]
[Full Text]
|
|
|
|
|
|
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B. Pope, R. D. Brown, J. Gibson, E. Yuen, and D. Joshua
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August 15, 2000;
96(4):
1274 - 1279.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Borrello, E. M. Sotomayor, F.-M. Rattis, S. K. Cooke, L. Gu, and H. I. Levitsky
Sustaining the graft-versus-tumor effect through posttransplant immunization with granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing tumor vaccines
Blood,
May 15, 2000;
95(10):
3011 - 3019.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Vogel, S. Scheding, L. Kanz, and W. Brugger
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Stem Cells,
March 1, 2000;
18(2):
87 - 92.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
J. Pinilla-Ibarz, K. Cathcart, T. Korontsvit, S. Soignet, M. Bocchia, J. Caggiano, L. Lai, J. Jimenez, J. Kolitz, and D. A. Scheinberg
Vaccination of patients with chronic myelogenous leukemia with bcr-abl oncogene breakpoint fusion peptides generates specific immune responses
Blood,
March 1, 2000;
95(5):
1781 - 1787.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Massaia, P. Borrione, S. Battaglio, S. Mariani, E. Beggiato, P. Napoli, C. Voena, A. Bianchi, M. Coscia, B. Besostri, et al.
Idiotype Vaccination in Human Myeloma: Generation of Tumor-Specific Immune Responses After High-Dose Chemotherapy
Blood,
July 15, 1999;
94(2):
673 - 683.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
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