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.
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.
Aglietta
Massimo
M
Division of Medical Oncology, Department of Oncological Sciences, Institute for Cancer Research and Treatment, Candiolo and University of Torino Medical School, Turin, Italy.
Barkholt
Lisbeth
L
Schianca
Fabrizio Carnevale
FC
Caravelli
Daniela
D
Omazic
Brigitta
B
Minotto
Coludia
C
Leone
Francesco
F
Hentschke
Patrik
P
Bertoldero
Giovanni
G
Capaldi
Antonio
A
Ciccone
Giovannino
G
Niederwieser
Dietger
D
Ringdén
Olle
O
Demirer
Tanner
T
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