Platelet-lysate-expanded mesenchymal stromal cells as a salvage therapy for severe resistant graft-versus-host disease in a pediatric population.
Despite advances in graft-versus-host-disease (GVHD) treatment, it is estimated that overall survival (OS) at 2 years for hematopoietic cell transplantation (HCT) recipients who experience steroid-resistant GVHD is 10%. Among recent therapeutic approaches for GVHD treatment, mesenchymal stromal cells (MSCs) hold a key position. We describe a multicenter experience of 11 pediatric patients diagnosed with acute or chronic GVHD (aGVHD, cGVHD) treated for compassionate use with GMP-grade unrelated HLA-disparate donors' bone marrow-derived MSCs, expanded in platelet-lysate (PL)-containing medium. Eleven patients (aged 4-15 years) received intravenous (i.v.) MSCs for aGVHD or cGVHD, which was resistant to multiple lines of immunosuppression. The median dose was 1.2 x 10(6)/kg (range: 0.7-3.7 x 10(6)/kg). No acute side effects were observed, and no late side effects were reported at a median follow-up of 8 months (range: 4-18 months). Overall response was obtained in 71.4% of patients, with complete response in 23.8% of cases. None of our patients presented GVHD progression upon MSC administration, but 4 patients presented GVHD recurrence 2 to 5 months after infusion. Two patients developed chronic limited GVHD. This study underlines the safety of PL-expanded MSC use in children. MSC efficacy seems to be greater in aGVHD than in cGVHD, even after failure of multiple lines of immunosuppression.
Lucchini
Giovanna
G
Clinica Pediatrica, Università Milano Bicocca, Ospedale San Gerardo, Via Donizetti 106, Monza, MI, Italy.
Introna
Martino
M
Dander
Erica
E
Rovelli
Attilio
A
Balduzzi
Adriana
A
Bonanomi
Sonia
S
Salvadè
Agnese
A
Capelli
Chiara
C
Belotti
Daniela
D
Gaipa
Giuseppe
G
Perseghin
Paolo
P
Vinci
Paola
P
Lanino
Edoardo
E
Chiusolo
Patrizia
P
Orofino
Maria Grazia
MG
Marktel
Sarah
S
Golay
Jose
J
Rambaldi
Alessandro
A
Biondi
Andrea
A
D'Amico
Giovanna
G
Biagi
Ettore
E
D000293:Adolescent; D001792:Blood Platelets / Q000166:cytology / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D057176:Compassionate Use Trials; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000628:therapy*; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology*; D016879:Salvage Therapy / Q000379:methods*; D017154:Stromal Cells / Q000166:cytology / Q000276:immunology*