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3344 Outcomes of Hematopoietic Stem Cell Transplantation from Non T– Cell Depleted Haploidentical Versus Matched Sibling Donor in Adult Patients with Acute Lymphoblastic Leukemia in Remission: A Study from the Acute Leukemia Working Party of the European Society for Blood and Marrowtransplantation

Program: Oral and Poster Abstracts
Session: 732. Clinical Allogeneic Transplantation: Results: Poster III
Hematology Disease Topics & Pathways:
Leukemia, ALL, Biological, Adult, Diseases, Therapies, Lymphoid Malignancies, Study Population, Clinically relevant, transplantation
Monday, December 7, 2020, 7:00 AM-3:30 PM

Arnon Nagler, MD1, Myriam Labopin, MD2*, Mohamed Houhou3*, Mahmoud Aljurf4, Ashrafsadat Mousavi5*, Rose-Marie Hamladji, MD, PhD6*, Mohsen Alzahrani7*, Sergey N. Bondarenko8*, Mutlu Arat, MD9, Emanuele Angelucci, MD10, Yener Koc11*, Zafer Gulbas, MD12*, Simona Sica, MD, PhD13*, Jean-Henri Bourhis14, Jonathan Canaani, MD15, Eolia Brissot, MD, PhD16*, Sebastian Giebel Sr.17* and Mohamad Mohty, MD, PhD18

1Division of Hematology, Sheba Medical Center, Tel Hashomer, Israel
2EBMT Paris study office; Department of Haematology,, Saint Antoine Hospital; INSERM UMR 938, Sorbonne University, Paris, France
3ALWP of the EBMT Paris office, Paris, France
4King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
5Shariati Hospital ,Hematology-Oncology and BMT Research, Tehran, Iran (Islamic Republic of)
6Service Hématologie Greffe de Moëlle, Centre Pierre Et Marie Curie, Alger, Algeria
7King Abdulaziz Medical City, Riyadh, Saudi Arabia
8Raisa Gorbacheva Memorial Institute of Children Oncology Hematology and Transplantation, First Pavlov State Medical University, Sant-Petersburg, Russian Federation
9Hematopoietic Stem Cell Transplantation Unit, Sisli Florence Nightingale Hospital,, Istanbul, Turkey
10Department of Haematology II, Genova Ospedale San Martino, Genova, Italy
11Medicana International, Istanbul, Turkey
12Anadolu Medical Center Hospital, Bone Marrow Transplantation Department, Kocaeli, Turkey
13Fondazione Policlinico A. Gemelli IRCCS, Roma, Italy; Istituto di Ematologia, Università Cattolica del Sacro Cuore, Roma, Italy, Roma, Italy
14Department of Hematology, Gustave Roussy Cancer Center, Villejuif, France
15Hematology Division, Sheba Medical Center, Givatayim, Israel
16Hematology Department, Hôpital Saint Antoine, Service d'Hématologie et Thérapie Cellulaire, Paris, France
17Department of Bone Marrow Transplantation and Hematology-Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland
18Saint Antoine Hospital, Paris, France

Background: Non T-cell depleted haploidentical hematopoietic stem cell transplantation (HaploSCT) is being increasingly used in acute lymphoblastic leukemia (ALL).We have recently reported that outcomes of adult patients (pts) with ALL in complete remission (CR) receiving HaploSCT are comparable to unrelated donor transplants (Shem-Tov N, Leukemia 2020; Al Malki MM Blood Adv. 2020 ). However, a direct comparison between HaploSCT and matched sibling donor transplants (MSD) in pts with ALL has not yet been undertaken.

Aim: To compare transplantation outcomes of HaploSCT and MSD in pts with ALL in CR.

Methods: We retrospectively analyzed adult pts (≥18 years) with ALL who underwent their first allogeneic stem cell transplantation (alloSCT) in first or second CR between 2012 to 2018, either from a Haplo or MSD donor, and whose data were reported to the acute leukemia working party (ALWP) of the European society for Blood and Marrow Transplantation (EBMT). Multivariate analysis (MVA) adjusting for differences between the groups was performed using the Cox proportional hazards regression model. Propensity score matching was also performed to reduce confounding effects.

Results: The analysis comprised 2304 pts: HaploSCT -413; MSD-1891. Median follow up was 25.0 (IQR: 12.3-45.3) months. Median age was 37 (range 18-75) and 37.7 (18-76) years, respectively. HaploSCT pts were transplanted more recently than those transplanted from MSD (2016 vs 2015, p<0.0001). A higher percentage of HaploSCT were in CR2 (33.4% vs 16.7%, p<0.0001), respectively, and fewer received myeloablative conditioning (68% vs 83.2%, p < 0.0001).Cytomegalovirus (CMV) seropositivity was lower in Haplo pts (22% vs 28%, p 0.01) and donors (27.1% vs 33%,p<0.02) and a higher percentage of the HaploSCTs were performed using a BM graft (46.2% vs 18.6%, p< 0.0001).The 2 groups did not differ with regard to gender, Karnofsky performance score (KPS), ALL phenotype, and pre alloSCT measurable residual disease (MRD). Graft versus host disease (GVHD) prophylaxis was mainly post-transplant cyclophosphamide (PTCy)-based (92.7%) in the HaploSCT setting while it was mostly pharmacologic in the setting of MSD (18.7% received ATG). Cumulative incidence of engraftment at day 60 was higher in MSD transplants compared to HaploSCT (98.7% vs 96.3%, p=0.001), respectively. Day 180 incidence of acute (a) GVHD II-IV and III-IV was higher in HaploSCT vs. MSD (36.3% vs 28.9%, p=0.002), and (15.2% vs 10.5%, p=0.005), respectively. Conversely, the 2- year chronic (c) GVHD and extensive cGVHD were 32% vs 38.8% (p=0.009), and 11.9% vs 19.5% (p=0.001) in HaploSCT vs MSD, respectively. Main causes of death were leukemia (31.8% vs 54.0%), infection (33.1% vs 19.7%), and GVHD (16.6% vs 19.7%) for HaploSCT and MSD, respectively. Two-year relapse incidence (RI), non-relapse mortality (NRM), leukemia-free survival (LFS), overall survival (OS), and GVHD free, relapse-free survival (GRFS) were 26% vs 31.6% (p=0.017); 22.9% vs 13% (p=0.001); 51% vs 55.4% p=0.07; 58.8% vs 67.4% (p=0.001), and 40.6% vs 39% (p=0.74) for HaploSCT and MSD, respectively. In MVA, RI was significantly lower in HaploSCT in comparison to MSD, hazard ratio (HR) =0.66 (95% CI 0.52-0.83, p=0.004) while NRM was significantly higher, HR=1.9 (95% CI 1.43-2.53, p<0.0001). aGVHD grade II-IV and grade III-IV were higher in HaploSCT than in MSD HR=1.53 (95% CI 1.23-1.9, p=0.0002), and HR=1.54 (95% CI 1.1-2.15, p=0.011), respectively. Extensive cGVHD was lower in HaploSCT compared with MSD, HR=0.61 (95% CI 0.43-0.88, p=0.007) while total cGVHD did not differ significantly, HR=0.94 (95% CI 0.74-1.18, p=0.58).LFS, OS and GRFS did not differ significantly between the 2 transplant groups, HR=0.96 (95% CI 0.81-1.14, p=0.66); HR=1.18 (95% CI 0.96-1.43, p=0.11), and HR=0.93 (95% CI 0.79-1.09, p=0.37), respectively. These results were confirmed in a matched-pair analysis (Figure).

Conclusions: Outcomes of adult patients with ALL in CR receiving alloSCT from haploidentical donors are not significantly different from those receiving transplants from MSD in terms of LFS, OS and GRFS.

Figure legend: Matched-pair analysis of transplantation outcome – Non-relapse mortality (NRM), relapse incidence (RI), leukemia-free survival (LFS), overall survival (OS) and GVHD-free, relapse-free survival (GRFS) in allogeneic stem cell transplantation from haploidentical (Haplo) donors and matched sibling donors (MSD).

Disclosures: Labopin: Jazz Pharmaceuticals: Honoraria. Sica: F. Hoffmann-La Roche Ltd: Other: All authors received support for third-party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland., Research Funding. Canaani: Abbvie: Consultancy, Honoraria, Research Funding. Mohty: BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Stemline: Consultancy, Honoraria, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau.

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