Idiotype vaccination using dendritic cells after autologous peripheral blood stem cell transplantation for multiple myeloma - A feasibility study

被引:341
|
作者
Reichardt, VL
Okada, CY
Liso, A
Benike, CJ
Stockerl-Goldstein, KE
Engleman, EG
Blume, KG
Levy, R
机构
[1] Stanford Univ, Dept Med, Sch Med, Div Oncol,Med Ctr, Stanford, CA 94305 USA
[2] Stanford Univ, Med Ctr, Div Hematol, Stanford, CA 94305 USA
[3] Stanford Univ, Med Ctr, Div Bone Marrow Transplantat, Stanford, CA 94305 USA
[4] Stanford Univ, Med Ctr, Stanford Blood Ctr, Stanford, CA 94305 USA
关键词
D O I
10.1182/blood.V93.7.2411.407a24_2411_2419
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 x 10(6) 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. (C) 1999 by The American Society of Hematology.
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收藏
页码:2411 / 2419
页数:9
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