title: Reduced-intensity allogeneic hematopoietic stem cell transplantation in metastatic colorectal cancer as a novel adoptive cell therapy approach. The European group for blood and marrow transplantation experience.
abstract: Reduced-intensity conditioning (RIC) regimens for allogeneic hematopoietic stem cell transplantation (HCT) allowed the existence of an allogeneic cell-mediated antitumor effect in metastatic colorectal cancer (mCRC) to be explored. We report on 39 patients with progressing mCRC treated with different RIC regimens in a multicenter clinical trial of the European Bone Marrow Transplantation Group. Disease status at transplant was progressive disease (PD) in 31 patients (80%), stable disease (SD) in 6 (15%), and partial response (PR) in 2 (5%). All patients engrafted (median donor T cell chimerism of 90% at day +60). Transplant-related morbidities were limited. Grades II-IV acute graft-versus-host disease (aGVHD) occurred in 14 patients (35%) and chronic GVHD (cGVHD) in 9 patients (23%). Transplant-related mortality occurred in 4 patients (10%). The best tumor responses were: 1 complete response (CR) (2%), 7 PR (18 %), and 10 SD (26%), giving an overall disease control in 18 of 39 patients (46%). Allogeneic HCT after RIC is feasible; the collected results compared favorably in terms of tumor response with those observed using conventional approaches beyond second-line therapies. The study of an allogeneic cell based therapy in less advanced patients is warranted.
authors.affiliation: Division of Medical Oncology, Department of Oncological Sciences, Institute for Cancer Research and Treatment, Candiolo and University of Torino Medical School, Turin, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Aglietta
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Barkholt
authors.forename: Fabrizio Carnevale
authors.initials: FC
authors.lastname: Schianca
authors.forename: Daniela
authors.initials: D
authors.lastname: Caravelli
authors.forename: Brigitta
authors.initials: B
authors.lastname: Omazic
authors.forename: Coludia
authors.initials: C
authors.lastname: Minotto
authors.forename: Francesco
authors.initials: F
authors.lastname: Leone
authors.forename: Patrik
authors.initials: P
authors.lastname: Hentschke
authors.forename: Giovanni
authors.initials: G
authors.lastname: Bertoldero
authors.forename: Antonio
authors.initials: A
authors.lastname: Capaldi
authors.forename: Giovannino
authors.initials: G
authors.lastname: Ciccone
authors.forename: Dietger
authors.initials: D
authors.lastname: Niederwieser
authors.forename: Olle
authors.initials: O
authors.lastname: Ringdén
authors.forename: Tanner
authors.initials: T
authors.lastname: Demirer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods; D014916:Whole-Body Irradiation; D055815:Young Adult