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3462 The Optimal Alternative Donor Transplant for Pediatric Patients with Acute Leukemia: A Comparison between Alfa-Beta T-Cell and B-Cell Depleted Haplo-SCT and UCBTClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 732. Clinical Allogeneic Transplantation: Results: Poster II
Hematology Disease Topics & Pathways:
Biological, AML, Leukemia, Diseases, Therapies, Lymphoid Malignancies, Clinically relevant, Myeloid Malignancies, transplantation
Sunday, December 2, 2018, 6:00 PM-8:00 PM
Hall GH (San Diego Convention Center)

Franco Locatelli1, Myriam Labopin, MD2*, Nicole Santoro3*, Jean-Hugues Dalle, MD, PhD4, Amal Al-Seraihy, MD5*, Fernanda Volt6*, Mikhail Maschan, PhD7*, Charlotte Jubert, MD8*, Marco Zecca, MD9*, Eefke J. Petersen, MD, PhD10, Miguel Ángel Díaz Pérez, Physician11*, Gerard Michel, MD12*, Elena Skorobogatova13*, Cristina Díaz de Heredia, MD, PhD14*, Tracey OBrien15*, Chantal Kenzey16*, Vanderson Rocha, MD, PhD16*, Eliane Gluckman, MD, PhD16*, Peter Bader, MD, PhD17 and Annalisa Ruggeri, MD1*

1Department of Pediatric Hematology and Oncology, IRCCS Ospedale Pediatrico Bambino Gesu, Rome, Italy
2Acute Leukemia Working Party of EBMT, Paris, France, Paris, France
3Universita di Perugia, Perugia, Italy
4Paediatric Disease Working Party of European Society for Blood and Marrow Transplantation, Paris, France
5Paediatric SCT Program, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
6Centre Scientifique de Monaco, Monacord, Monaco, Monaco
7Department of Hematopoietic Stem Cell Transplantation №1, Dmitry Rogachev Federal Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation
8Hemato Pediatrics, CHU Bordeaux, Bordeaux Cedex, France
9Pediatric Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
10Hematology, University Medical Center Utrecht, Utrecht, NLD
11Department of Hematology, Hospital Niño Jesús, Madrid, Spain
12Department of Pediatric Hematology, Aix Marseille University, Marseille, France
13The Russian Children's Research Hospital, Moscow, Russian Federation
14Servei Oncologia i Hematologia Pediàtriques, Hospital Universitari Vall d’Hebron Vall d’Hebron, Barcelona, Spain
15Sydney, Sidney, Australia
16Eurocord, Hôpital Saint Louis, Université Paris Diderot, IUH, Paris, France
17Department for Children and Adolescents, University Children's Hospital Frankfurt, Frankfurt, Germany

Children with acute leukemia (AL) in need of an allograft and lacking an HLA-identical sibling and an HLA-matched unrelated donor, could benefit either from unrelated cord blood transplantation (UCBT) or T-cell depleted haploidentical (haplo) stem cell transplantation (SCT).

Different techniques of T-cell depletion have been developed for improving immune reconstitution and for enhancing the graft-versus-leukemia (GvL) effect. Locatelli et al. (Blood 2017) reported remarkable results for children with AL given haplo-SCT after a novel method of graft manipulation based on selective, negative depletion of alfa-beta T and B cells.

On behalf of Eurocord, CTIWP, and PDWP of EBMT, we compared outcomes of patients < 18 years with AL undergoing either single-UCBT (n=444) or haplo-SCT after alfa-beta T-cell and B-cell-depletion (n=99) from 2012 to 2016 using a myeloablative conditioning regimen (MAC).

Median age at SCT was 6 (range 0.3-18) and 8 (range 0.6-18) years, and median follow-up was 36 and 14 months (p<0.05) for UCBT and haplo-SCT recipients, respectively. Compared to UCBT, haplo-SCT were performed more recently (median year 2016 vs 2012, p<0.05). Acute lymphoblastic leukemia (ALL) was the most frequent diagnosis (62% versus 55%), while 38% and 45% of patients had acute myeloid leukemia (AML) in the UCBT and haplo-SCT group, respectively. Cytogenetics was mainly at intermediate risk for UCBT (54%) and haplo-SCT (73%, p<0.05); 49% and 54% of patients were in CR1 at time of the allograft in UCBT and haplo-SCT group, respectively (p=0.45). In vivo T-cell depletion with ATG was more frequently adopted in haplo-SCT recipients (90% versus 81%, p=0.05). For UCBT recipients, HLA compatibility was 6/6 matched for 19% of patients, 5/6 for 58% and 4/6 for 23%. Cord blood graft contained a median TNC count at cryopreservation of 7.02x10e7/Kg (range 2.63-43) and at infusion of 5.3x10e7/Kg (range 0.3-39).

Conditioning regimen varied according to the type of transplant: for haplo-SCT recipients Fludarabine+TBI (28%) and Thiotepa+Busulfan+fludarabine (TBF) (24%) were the most frequent MAC. In UCBT, Busulfan+Cyclophosphamide (Cy), or Cy+Fludarabine+TBI or TBF were used in 19%, 15% and 13% of patients, respectively.

Haplo-SCT recipients did not receive any additional pharmacological post-transplant graft-versus-host disease (GvHD) prophylaxis, while CyclosporineA (CSA)+ steroids and CSA+mycophenolate mofetil were used in 38% and 32% of UCBT recipients.

The 60-day probability of neutrophil engraftment was 91% vs 93% (p<0.05) for UCBT and haplo-SCT. The cumulative incidence (CI) of grade II-IV and grade III-IV acute (a) GvHD was 38% vs 12% (p<0.05) and 17% vs 4% (p<0.05) in UCBT and haplo-SCT recipients, respectively. The 2-year CI of relapse (RI) was similar following from UCBT and haplo-SCT (22% vs 25%, p=0.75), as well as non-relapse mortality (NRM) (18% vs 10%, p=0.07), respectively. Disease recurrence was the most common causes of death in both groups, with infections and GvHD being the most frequent transplant-related fatalities.

According to donor type, no differences were found in overall survival (OS) (65% vs 68%, p=0.17) and leukemia-free survival (LFS) (61% vs 65%, p=0.24), while a lower GvHD-free, relapse-free survival (GRFS) was observed in UCBT compared to haplo-SCT (49% vs 60%, p<0.05). OS was 67% and 58% for patients with AML and ALL respectively, p=0.11.

In multivariate analysis, UCBT was associated with higher risk of NRM (HR 2.36, p<0.05), while RI was not associated with type of allograft. Higher risk of grade II-IV aGVHD was observed in UCBT (HR 2.81, p<0.05), with no difference for cGVHD among the two groups (HR 0.68, p=0.31). OS (HR 1.52, p=0.10) and LFS (HR 1.28, p=0.28) were comparable between UCBT and haplo-SCT, while GRFS resulted lower for UCBT (HR 1.58, p<0.05). No others factors were associated with outcomes.

Our results showed that RI, LFS, OS and cGVHD were comparable between UCBT and haplo-SCT recipients, while better NRM, aGVHD and GRFS were observed in patients transplanted from a family donor. These data confirm that alfa-beta T-cell and B-cell depleted haplo-SCT is a valid alternative for patients in need of an urgent allograft. Costs of manipulation in the haplo-SCT setting and costs of cord blood procurement should be further investigated. Technical expertise with this refined approach of graft manipulation and center experience are important to optimize patient’s outcome.

Disclosures: Zecca: Chimerix: Honoraria. Bader: Medac: Patents & Royalties, Research Funding; Cellgene: Consultancy; Neovii: Research Funding; Riemser: Research Funding; Novartis: Consultancy, Speakers Bureau.

*signifies non-member of ASH