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3528 TCRαβ+/CD19+ - Depleted HLA-Haploidentical Hematopoietic Stem Cell Traansplantation in Pediatric Patient with Fanconi Anemia

Program: Oral and Poster Abstracts
Session: 721. Allogeneic Transplantation: Conditioning Regimens, Engraftment and Acute Toxicities: Poster II
Hematology Disease Topics & Pathways:
Biological therapies, Therapies, Transplantation
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Daria Pagliara, MD, PhD1*, Luisa Strocchio, MD2*, Francesca Compagno, MD3*, Mattia Algeri, MD1*, Akihiro Iguchi, MD, PhD4*, Giovanna Giorgiani5*, Francesca Del Bufalo, MD, PhD1*, Federica Galaverna, MD, PhD6*, Pietro Merli, MD7*, Cesare Perotti, MD8*, Stefania Lazzaro, MD9*, Giuseppina Li Pira, PhD10*, Valentina Bertaina, PhD1*, Daisuke Tomizawa, MD, PhD11, Marco Zecca, MD12* and Franco Locatelli, MD, PhD13

1Department of Haematology-Oncology and Cell and Gene Therapy, Bambino Gesù Children Hospital, Rome, Italy
2Department of Pediatric Hematology/Oncology, Cell and Gene Therapy, Bambino Gesù Children Hospital (IRCCS), Rome, ITA
3Pediatric Hematology-Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, ITA
4Division of Hematology, Children’s Cancer Center, National Center for Child Health and Development (NCCHD), Tokyo, Japan
5Policlinico San Matteo, Pavia, Pavia, IT, ITA
6Department of Pediatric Hematology and Oncology and of Cell and Gene Therapy, IRCCS Bambino Gesù Children's Hospital, Rome, Italy
7Hematology/Oncology, Cell and Gene Therapy, Bambino Gesù Children Hospital (IRCCS), Rome, Italy
8IRCCS Policlinico S. Matteo, Pavia, PV, ITA
9Bambino Gesù Children's Hospital, IRCCS, Rome, ITA
10Bambino Gesù Children's Hospital, Rome, ITA
11Division of Leukemia and Lymphoma, Children’s Cancer Center, National Center for Child Health and Development, Tokyo, Japan
12Pediatric Hematology-Oncology,, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
13Department of Pediatric Hematology/Oncology, Cell and Gene Therapy, IRCCS Bambino Gesù Children’s Hospital, Catholic University of the Sacred Heart, Rome, Italy


Allogeneic hematopoietic stem cell transplantation (HSCT) currently represents the only proven treatment able to rescue bone marrow failure and prevent the occurrence of clonal evolution in patients with Fanconi Anemia (FA). If HSCT from HLA-identical related donor (MRD) is reported to be associated with better outcomes, this is not available for most patients. On the other hand, the identification of a fully matched unrelated donor (MUD) may be unsuccessful, or require times incompatible with a prompt treatment of the haematological condition. For patients who lack a MRD or MUD, the preferred donor choice is debated.

HLA partially matched haploidentical donor (haplo) is virtually immediately available for all patients and haplo-HSCT has been reported over the last few years as a promising alternative for those patients.

Following the favorable results already reported from our group of a cohort of pediatric and young adult FA patients underwent haplo-HSCT, based on the selective depletion of TCRαβ+ and CD19+ cells graft manipulation, here we present the outcome of an enlarged cohort of patients who received HSCT in 3 different centers.


Patients diagnosed with FA and eligible for an allogeneic transplantation, but lacking a MRD or MUD, and with a suitable HLA-haploidentical donor were eligible to this study.

The conditioning regimen included intravenous fludarabine, cyclophosphamide and single-dose total body irradiation for most patients. Pretransplant anti-T-lymphocyte globulin was administered in all patient to control in vivo bidirectional donor-recipient alloreactivity.

Apheresis and graft manipulation were performed as previously reported (Li Pira, Biol Blood Marrow Transplant 2016).


Thirty-five patients (19 males and 16 females) underwent haplo-HSCT between September 2011 and April 2023 in 3 different centers (Bambino Gesù Children’s Hospital, Rome, Italy; Policlinico San Matteo, Pavia, Italy; Tokyo; National Center for Child Health and Development, Children’s Cancer Center, Tokyo, Japan). Twenty-four patients have been previously reported (Strocchio, Blood Adv 2021). Details on patients and donor characteristics, graft composition and conditioning regimen are listed in table 1. One patient with clonal evolution and 1 with AML received fludarabine and AraC 3 weeks before the start of the conditioning. Primary engraftment was achieved in 33 patients (94.3%), with median time for neutrophil and platelet recovery of 12 days (range, 9-20 days) and 10 days (range, 7-14 days), respectively. Primary graft failure occurred in 2 patients and both were successfully transplanted from the other haploidentical parent. The monitoring of chimerism analysis confirmed a stable engraftment of donor hemopoiesis in all engrafted patients.

Within 33 evaluable patients, 9 (27.3%) experienced grade 1-2 aGvHD (7 with stage I-II skin-only involvement, 1 with stage I lower gastrointestinal involvement) at a median time of 35.5 days (range, 16-67 days) after HSCT. One patient developed late-onset skin only grade 2 aGvHD at day +211 after HSCT. One patient (3%) experienced grade IV aGvHD (liver and gastrointestinal involvement) at day + 100 from HSCT, 4 weeks after the infusion of adenoviral-specific donor T cells; he is currently receiving ruxolitinib and the complete resolution of GvHD was obtained. Only one patient (3%), developed cGvHD with mild skin involvement. Thirteen patients (39.4%) experienced one or more viral infections or reactivations (6 cytomegalovirus, 4 herpesvirus-6, 2 adenovirus, 1 parainfluenzae); the specific antiviral treatment was administered with a complete resolution of infection in all cases.

With a median follow up of 5.5 years (range, 0.6-11.4 years) all the patients are alive and with resolution of hematological complications. Except for the already reported vulvar intraepithelial neoplasia, no additional posttransplant malignancy was observed


Our data obtained from enlarged cohort of patients previously reported, confirm excellent results in terms of survival and a good rate of engraftment also in a multicenter setting. The low incidence of acute and chronic GvHD, a particularly detrimental complication in patients with DNA repair disorder, makes this approach attractive in this patient population.

In FA patients lacking a standard donor, TCRab+/CD19+ haplo-HSCT is confirmed to be a promising strategy.

Disclosures: Algeri: Vertex Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. Merli: Amgen: Speakers Bureau; SOBI: Consultancy; JAZZ: Consultancy, Honoraria; MEDAC: Speakers Bureau.

*signifies non-member of ASH