PMID- 19835972 OWN - NLM STAT- MEDLINE DCOM- 20100528 LR - 20220317 IS - 1523-6536 (Electronic) IS - 1083-8791 (Linking) VI - 16 IP - 3 DP - 2010 Mar TI - Partial T cell-depleted allogeneic stem cell transplantation following reduced-intensity conditioning creates a platform for immunotherapy with donor lymphocyte infusion and recipient dendritic cell vaccination in multiple myeloma. PG - 320-32 LID - 10.1016/j.bbmt.2009.10.006 [doi] AB - Allogeneic stem cell transplantation (SCT) in multiple myeloma (MM) may induce a curative graft-versus-myeloma (GVM) effect. Major drawback in unmanipulated reduced-intensity conditioning (RIC) SCT is the risk of severe and longstanding graft-versus-host-disease (GVHD). This study demonstrates that transplantation with a partial T cell-depleted graft creates a platform for boosting GVM immunity by preemptive donor lymphocyte infusion (DLI) and recipient dendritic cell (DC) vaccination, with limited GVHD. All 20MM patients engrafted successfully. Chimerism analysis in 19 patients evaluable at 3 months revealed that 7 patients were complete donor, whereas 12 patients were mixed chimeric. Grade II acute GVHD (aGVHD) occurred in 7 patients (35%) and only 4 patients (21%) developed chronic GVHD (cGVHD). Fourteen patients received posttransplantation immunotherapy, 8 preemptive DLI, 5 patients both DLI and DC vaccination, and 1 patient DC vaccination only. DC vaccination was associated with limited toxicity, and none of these patients developed GVHD. Importantly, overall treatment-related mortality (TRM) at 1 year was low (10%). Moreover, the overall survival (OS) is 84% with median follow-up of 27 months, and none of the patients died from progressive disease. These findings illustrate that this novel approach is associated with limited GVHD and mortality, thus creating an ideal platform for adjuvant immunotherapy. CI - Copyright (c) 2010 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved. FAU - Levenga, Henriette AU - Levenga H AD - Department of Hematology, Radboud University Nijmegen Medical Centre, Geert Grooteplein 8, Nijmegen, The Netherlands. t.levenga@hemat.umcn.nl FAU - Schaap, Nicolaas AU - Schaap N FAU - Maas, Frans AU - Maas F FAU - Esendam, Bennie AU - Esendam B FAU - Fredrix, Hanny AU - Fredrix H FAU - Greupink-Draaisma, Annelies AU - Greupink-Draaisma A FAU - de Witte, Theo AU - de Witte T FAU - Dolstra, Harry AU - Dolstra H FAU - Raymakers, Reinier AU - Raymakers R LA - eng PT - Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20091014 PL - United States TA - Biol Blood Marrow Transplant JT - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JID - 9600628 RN - 0 (HLA Antigens) RN - 0 (Immunoglobulin Light Chains) RN - 0 (Immunoglobulins) RN - 0 (M-proteins (Myeloma)) RN - 9013-72-3 (Hemocyanins) RN - FV4Y0JO2CX (keyhole-limpet hemocyanin) SB - IM MH - Adult MH - Dendritic Cells/cytology/immunology/metabolism/*transplantation MH - Female MH - Graft Survival/immunology MH - Graft vs Host Disease/immunology/*prevention & control MH - Graft vs Tumor Effect/*immunology MH - HLA Antigens/genetics/immunology MH - Hematopoietic Stem Cell Transplantation/*methods/mortality MH - Hemocyanins/immunology MH - Humans MH - Immunoglobulin Light Chains/blood/immunology MH - Immunoglobulins/blood MH - Kaplan-Meier Estimate MH - Lymphocyte Activation/immunology MH - *Lymphocyte Depletion MH - Male MH - Middle Aged MH - Multiple Myeloma/blood/immunology/*therapy MH - Siblings MH - T-Lymphocyte Subsets/cytology/immunology MH - T-Lymphocytes/cytology/immunology/transplantation MH - Transplantation Chimera/immunology MH - Transplantation Conditioning/*methods MH - Transplantation, Homologous MH - Treatment Outcome MH - *Vaccination/adverse effects EDAT- 2009/10/20 06:00 MHDA- 2010/05/29 06:00 CRDT- 2009/10/20 06:00 PHST- 2009/06/04 00:00 [received] PHST- 2009/10/07 00:00 [accepted] PHST- 2009/10/20 06:00 [entrez] PHST- 2009/10/20 06:00 [pubmed] PHST- 2010/05/29 06:00 [medline] AID - S1083-8791(09)00462-5 [pii] AID - 10.1016/j.bbmt.2009.10.006 [doi] PST - ppublish SO - Biol Blood Marrow Transplant. 2010 Mar;16(3):320-32. doi: 10.1016/j.bbmt.2009.10.006. Epub 2009 Oct 14.