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1841 Haploidentical Versus Matched Sibling Donor Hematopoietic Stem Cell Transplantation for Adult Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia: A Study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

Program: Oral and Poster Abstracts
Session: 732. Allogeneic Transplantation: Disease Response and Comparative Treatment Studies: Poster I
Hematology Disease Topics & Pathways:
Biological, ALL, Lymphoid Leukemias, Adults, Clinically Relevant, Diseases, Therapies, Lymphoid Malignancies, Study Population, Transplantation
Saturday, December 11, 2021, 5:30 PM-7:30 PM

Arnon Nagler, M.D.1, Myriam Labopin2*, Pietro Pioltelli, MD3*, Mutlu Arat, MD4, Ibrahim Yakoub-Agha5, Aleksandr D. Kulagin6*, Emanuele Angelucci7, Hakan Ozdogu, MD8*, Antonio Risitano, MD, PhD9, Fabio Ciceri, MD10*, Zubeyde Nur Ozkurt, MD11*, Jaime Sanz, MD12*, Eolia Brissot, MD, PhD13*, Zinaida Peric, MD, PhD14*, Sebastian Giebel, MD, PhD15* and Mohamad Mohty, MD, PhD16

1Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Ramat-Gan, Israel
2EBMT Paris study office; Department of Haematology,, Saint Antoine Hospital; INSERM UMR 938, Sorbonne University, Paris, France
3Ospedale San Gerardo, Clinica Ematologica dell`Universita Milano-Biocca, Monza, MB, Italy
4Hematopoietic SCT Unit, Demiroglu Bilim University Istanbul Florence Nightingale Hospital, Istanbul, Turkey
5CHU de Lille LIRIC, INSERM U995, Université de Lille, Lille, France
6Raisa Gorbacheva Memorial Research Institute for Paediatric Oncology, Hematology, and Transplantation, First Pavlov State Medical University of St. Petersburg, St Petersburg, Russian Federation
7Department of Haematology II, Ospedale Policlinico San Martino, Genoa, Italy
8Hematology Division, BMT Unit, Haemaology Reserach Laboratory, Training & Medical, Baskent University Hospital, Adana, Turkey
9A.O.R.N. MOSCATI, Avellino, Italy
10Hematology and Bone Marrow Transplantation, Ospedale San Raffaele s.r.l., Milano, Italy
11Hematology, Gazi University Faculty of Medicine, Ankara, Turkey
12Hematology Department, Hospital Universitari I politècnic La Fe, Valencia, Spain
13Service d'Hématologie Clinique et Thérapie Cellulaire, Hôpital Saint-Antoine, APHP, Paris, France
14Department of Internal Medicine, University of Zagreb School of Medicine, Zagreb, Croatia
15Department of Bone Marrow Transplantation and Hematology-Oncology, Maria Sklodowska-Curie Memorial, Gliwice, Poland
16Department of Clinical Hematology and Cellular Therapy, Saint Antoine Hospital, Paris, France

Background: Outcomes of Haploidentical transplantation (HaploSCT) in adult patients (pts) with acute relapsed/refractory lymphoblastic leukemia (Rel/Ref ALL) are comparable to unrelated donor transplants. We have recently reported that results of HaploSCT for ALL in remission are not significantly different from those receiving transplants from matched sibling donors (MSD). However, results may differ in ALL pts with active disease.

Aim: To compare outcomes of HaploSCT and MSD transplantations in pts with Rel/Ref ALL.

Methods: We retrospectively analyzed adult patients (≥ 18 years) with Rel/Ref ALL who underwent their first transplantation between 2012 and 2020, either from a T cell replete Haplo or MSD donor. Multivariate analysis (MVA) adjusting for differences between the groups was performed using the Cox proportional- hazards regression model.

Results: The analysis comprised 274 pts: HaploSCT-94 (34%); MSD-180 (66%). Median follow-up was 32 months. Median age was 33 (range 18-76) and 37 (18-76) years in HaploSCT and MSD, respectively. Median year of transplant was similar being 2015 and 2016, respectively. The percentage of pts transplanted in the primary refractory phase was lower in HaploSCT than in MSD (31.9% vs 55.0 %,), while more HaploSCT pts were in second Rel (33% vs 11.1%) , p < 0.0001. 53.3% had T ALL, 25.5% Philadelphia chromosome (Ph) negative (-) while 21.2% had Ph positive (+) B ALL, with no difference in ALL subtypes between the groups. Cytomegalovirus (CMV) seropositivity was 83.9% and 73.4% (p < 0.053), respectively. Karnofsky performance status score (KPS) (>90) did not differ between the donor groups (59.8% vs 64.7%, p < 0.43) .Fewer pts undergoing HaploSCT received myeloablative conditioning (67% vs 84%, p < 0.001) and total body irradiation (32% vs 68%, p < 0.0001). A higher proportion of the HaploSCTs were performed using a bone marrow graft (44% vs 10%, p < 0.0001). Graft-versus-host disease (GVHD) prophylaxis was mainly post-transplant cyclophosphamide (PTCy)-based (88%) in the HaploSCT setting, while it was mostly pharmacologic (96%) in the setting of MSD (25% and 23% respectively, received ATG, p =0.77). Cumulative incidence of engraftment at day 60 was higher in MSD transplants compared to HaploSCT (96% vs 87%, p = 0.005), respectively. Remission of Rel/Ref pts post HaploSCT and MSD transplants was achieved by 64% and 69%, respectively. Day 180 incidence of acute (a) GVHD II-IV did not differ between HaploSCT and MSD (28% vs 21%, p=0.25) while grade III-IV was higher in HaploSCT than in MSD (18% vs 9%, p=0.042), respectively. Conversely, the 2-year chronic (c) GVHD and extensive cGVHD rates were 17% vs 33% (p = 0.012) and 5% vs 17% (p = 0.011) in HaploSCT vs MSD, respectively. Main causes of death were leukemia (64% vs 63%), infection (16% vs 18%) and GVHD (13% vs 11%) for HaploSCT and MSD, respectively. Two-year ReI (57% vs 52%) and non-relapse mortality (NRM) (25% vs 18%) were similar between HaploSCT and MSD groups, respectively, while leukemia-free survival (LFS), overall survival ( OS) and GVHD-free, relapse-free survival (GRFS) in the HaploSCT group were lower compared to the MSD group with 18% vs 31%, p=0.023; 22% vs 38%, p=0.001, and 16% vs 19%, p=0.06, respectively. In the MVA, NRM was significantly higher in HaploSCT in comparison with MSD with a hazard ratio (HR) = 2.03 (95% CI 1.03-4.02, p = 0.042) which translated to a significantly lower OS with HaploSCT vs MSD transplants (HR = 1.72, 95% CI 1.15-2.58, p < 0.009). No difference was observed in other transplant outcomes between the two groups including Rel, LFS and GRFS: HR = 0.97 (95% CI 0.62-1.52, p = 0.89); HR =1.22 (95% CI 0.84-1.78, p = 0.3) and HR = 1.31 (95% CI 0.88-1.94, p = 0.18), respectively. Similarly, aGVHD and cGVHD did not differ significantly in MSD transplants vs HaploSCT (HR = 1.85, 95% CI 0.99-3.46, p = 0.054) and (HR = 0.56, 95% CI 0.26-1.21, p = 0.14),respectively. No interactions were observed between disease phenotype and status.

Conclusions: Two-year OS of Rel/Ref ALL pts undergoing MSD transplants is significantly better than in HaploSCT with a higher NRM with the latter. Both procedures are hampered by high (50-~60%) relapse rates which interestingly, did not differ between HaploSCT and MSD transplants. The emerging humoral and cellular immunotherapies recently approved for ALL may enable reduction of post transplantation relapse and thus improve transplantation outcomes for Rel/Ref ALL.

Disclosures: Labopin: Jazz Pharmaceuticals: Honoraria. Yakoub-Agha: Jazz Pharmaceuticals: Honoraria. Kulagin: X4 Pharmaceuticals, Alexion, Apellis, Biocad: Research Funding; Novartis, Generium, Sanofi, Roche, Johnson & Johnson, Pfizer: Speakers Bureau. Angelucci: Glaxo: Honoraria, Membership on an entity's Board of Directors or advisory committees; Crispr therapeutics: Honoraria, Other: DMC; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Blue Bird Bio: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene BSM: Honoraria, Other: DMC; Menarini-Stemline: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: steering commitee, Speakers Bureau; Vertex Pharmaceuticals: Honoraria, Other: DMC; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees. Risitano: Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Lecture fees, Research Funding, Speakers Bureau; Samsung: Membership on an entity's Board of Directors or advisory committees; Amyndas: Consultancy; RA Pharma: Research Funding; Biocryst: Membership on an entity's Board of Directors or advisory committees; Achillion: Membership on an entity's Board of Directors or advisory committees, Other: Lecture fees; Jazz: Other: Lecture fees, Speakers Bureau; F. Hoffmann-La Roche Ltd.: Membership on an entity's Board of Directors or advisory committees; Pfizer: Other: Lecture fees, Speakers Bureau; Alnylam: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Lecture fees, Research Funding, Speakers Bureau; Apellis Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Other: Lecture fees, Speakers Bureau. Ciceri: IRCCS Ospedale San Raffaele: Current Employment. Peric: Therakos: Honoraria; servier: Honoraria; MSD: Honoraria; Astellas: Honoraria; NOVARTIS: Honoraria; Abbvie: Honoraria; Pfizer: Honoraria. Giebel: Janssen: Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau. Mohty: Sanofi: Honoraria, Research Funding; Pfizer: Honoraria; Novartis: Honoraria; Takeda: Honoraria; Jazz: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Gilead: Honoraria; Celgene: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria; Astellas: Honoraria; Amgen: Honoraria; Adaptive Biotechnologies: Honoraria.

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