HLA-haploidentical T cell-depleted allogeneic hematopoietic stem cell transplantation in children with Fanconi anemia.
We report the outcome of 12 consecutive pediatric patients with Fanconi anemia (FA) who had neither an HLA-identical sibling nor an HLA-matched unrelated donor and who were given T cell-depleted, CD34(+) positively selected cells from a haploidentical related donor after a reduced-intensity, fludarabine-based conditioning regimen. Engraftment was achieved in 9 of 12 patients (75%), and the cumulative incidence of graft rejection was 17% (95% confidence interval [CI], 5% to 59%). Cumulative incidences of grades II to IV acute and chronic graft-versus-host disease were 17% (95% CI, 5% to 59%) and 35% (95% CI, 14% to 89%), respectively. The conditioning regimen was well tolerated, with no fatal regimen-related toxicity and 3 cases of grade III regimen-related toxicity. The cumulative incidence of transplant-related mortality was 17% (95% CI, 5% to 59%). The 5-year overall survival, event-free survival, and disease-free survival were 83% (95% CI, 62% to 100%), 67% (95% CI, 40% to 93%), and 83% (95% CI, 62% to 100%), respectively. These data demonstrate that a fludarabine-based conditioning regimen, followed by infusion of high doses of T cell-depleted stem cells, is able to ensure engraftment with good overall survival and disease-free survival, confirming the feasibility of haploidentical hematopoietic stem cell transplantation in FA. To the best of our knowledge, this is the largest series of hematopoietic stem cell transplantation from a haploidentical related donor in FA patients reported to date.
Oncoematologia Pediatrica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Marco
M
Zecca
Oncoematologia Pediatrica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Luisa
L
Strocchio
Dipartimento di Oncoematologia Pediatrica, IRCCS Ospedale Pediatrico Bambino Gesù, Roma, Italy.
Daria
D
Pagliara
Oncoematologia Pediatrica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Patrizia
P
Comoli
Dipartimento di Oncoematologia Pediatrica, IRCCS Ospedale Pediatrico Bambino Gesù, Roma, Italy.
Alice
A
Bertaina
Oncoematologia Pediatrica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Giovanna
G
Giorgiani
Servizio di Immunoematologia e Medicina Trasfusionale, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Cesare
C
Perotti
Struttura Complessa di Radioterapia Oncologica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Franco
F
Corbella
Dipartimento di Oncoematologia Pediatrica, IRCCS Ospedale Pediatrico Bambino Gesù, Roma, Italy.
Letizia
L
Brescia
Dipartimento di Oncoematologia Pediatrica, IRCCS Ospedale Pediatrico Bambino Gesù, Roma, Italy; Department of Pediatric Science, Università degli Studi di Pavia, Italy. Electronic address: franco.locatelli@opbg.net.
Franco
F
Locatelli
D000293:Adolescent; D018952:Antigens, CD34 / Q000276:immunology; D002648:Child; D005199:Fanconi Anemia / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality / Q000473:pathology; D006680:HLA Antigens / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D008212:Lymphocyte Depletion; D008297:Male; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D011446:Prospective Studies; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D061349:Unrelated Donors; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D018952:Antigens, CD34; D006680:HLA Antigens; D019653:Myeloablative Agonists; D014740:Vidarabine; C024352:fludarabine
Fanconi anemia; Haploidentical stem cell transplantation; Reduced-intensity conditioning; T cell depletion