title: 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.
abstract: 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.
authors.affiliation: Department of Hematology, Radboud University Nijmegen Medical Centre, Geert Grooteplein 8, Nijmegen, The Netherlands. t.levenga@hemat.umcn.nl
authors.forename: Henriëtte
authors.initials: H
authors.lastname: Levenga
authors.forename: Nicolaas
authors.initials: N
authors.lastname: Schaap
authors.forename: Frans
authors.initials: F
authors.lastname: Maas
authors.forename: Bennie
authors.initials: B
authors.lastname: Esendam
authors.forename: Hanny
authors.initials: H
authors.lastname: Fredrix
authors.forename: Annelies
authors.initials: A
authors.lastname: Greupink-Draaisma
authors.forename: Theo
authors.initials: T
authors.lastname: de Witte
authors.forename: Harry
authors.initials: H
authors.lastname: Dolstra
authors.forename: Reinier
authors.initials: R
authors.lastname: Raymakers
mesh_terms: D000328:Adult; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D005260:Female; D006085:Graft Survival / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D020350:Graft vs Tumor Effect / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000097:blood / Q000276:immunology; D007136:Immunoglobulins / Q000097:blood; D053208:Kaplan-Meier Estimate; D008213:Lymphocyte Activation / Q000276:immunology; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000276:immunology / Q000628:therapy*; D035781:Siblings; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D018183:Transplantation Chimera / Q000276:immunology; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014611:Vaccination / Q000009:adverse effects
chemical_list: D006680:HLA Antigens; D007147:Immunoglobulin Light Chains; D007136:Immunoglobulins; C009823:M-proteins (Myeloma); D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin