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3890 Post-Transplant Cyclophosphamide in Acute Leukemia Patients Receiving More Than 5/10 HLA-Mismatched Allogeneic Stem Cell Transplantation: A Study on Behalf of the ALWP of the EBMT

Program: Oral and Poster Abstracts
Session: 722. Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution: Poster III
Hematology Disease Topics & Pathways:
Non-Biological, Chemotherapy, Health Outcomes Research, Clinical Research, Therapies, Real World Evidence, Registries, Clinical Practice (e.g. Guidelines, Health Outcomes and Services, and Survivorship, Value; etc.)
Monday, December 13, 2021, 6:00 PM-8:00 PM

Michele Wieczorek1,2*, Myriam Labopin3*, Luca Castagna4*, Eolia Brissot, MD, PhD2*, Gerard Socié5, Anna Maria Raiola6*, Emanuele Angelucci6, Arancha Bermúdez7*, Ibrahim Yakoub-Agha8, Mahmoud Aljurf9, Charles Crawley10, Jean-Baptiste Mear11*, Maurizio Musso12*, Renato Fanin13*, Daniele Avenoso14*, Pascal Turlure15*, Cristina Tecchio1*, Jaime Sanz16*, Fabio Ciceri17*, Arnon Nagler, M.D.3,18 and Mohamad Mohty, MD, PhD3,19

1Department of Medicine, Hematology and Bone Marrow Transplant Unit, Verona University Hospital, Verona, Italy
2Department of Clinical Hematology and Cellular Therapy, Hopital Saint Antoine, Paris, France
3Acute Leukemia Working Party of EBMT, Paris, France
4Department of Oncology and Hematology, Transplantation Unit, Palermo, Italy, Italy
5Department of Hematology – BMT, Hopital St. Louis, Paris, France
6Department of Hematology II, San Martino University Hospital, Genoa, Italy
7Hematology Department, Marques de Valdecilla University Hospital, Santander, Spain
8Centre Hospitalier Universitaire de Lille LIRIC, INSERM U1286, Université de Lille, Lille, France
9Oncology, Section of Adult Haematolgy/BMT, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
10Department of Haematology, Addenbrookes University Hospital, Cambridge, United Kingdom
11Service d’Hématologie Clinique Adulte, Centre Hospitalier Universitaire de Rennes, Rennes, France
12Oncology Department, Hematology and Bone Marrow Transplant Unit, Ospedale La Maddalena, Palermo, Italy
13Division of Hematology, Udine University Hospital, Udine, Italy
14Department of Hematological Medicine, King's College Hospital, London, ENG, United Kingdom
15Hematology Department, CHRU Limoges, Limoges, France
16Department of Hematology, Hospital Universitari i Politècnic La Fe, Valencia, Valencia, Spain
17Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
18Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel-Hashomer, Israel
19Department of Clinical Hematology and Cellular Therapy, Saint Antoine Hospital, Paris, France

Background

Post-transplant cyclophosphamide (PTCy) is a powerful strategy to prevent occurrence of graft-versus-host disease (GvHD) following allogeneic hematopoietic stem cell transplantation (HSCT). Initially developed in the setting of haploidentical HSCT, PTCy has been increasingly used for fully HLA-matched transplants with favorable results.

The purpose of this retrospective multi-center study is to evaluate PTCy-based GvHD prevention for patients with acute leukemia receiving a traditionally prohibitive highly mismatched HSCT and to describe their outcome.

Methods

This is a registry-based study employing the data set of the Acute Leukemia Working Party (ALWP) of the European Society of Blood and Marrow Transplantation (EBMT). We retrospectively assessed the outcome of adult patients with acute myeloid or lymphoblastic leukemia (AML/ALL), transplanted between 2010 and 2020 with grafts from HLA-mismatched donors with more than 5/10 mismatches using PTCy-based GvHD prophylaxis.

Results

The study cohort consisted of 59 patients, with a median time of follow up of 20 (95% CI, 14-39) months. The median age was 47 (range, 18-69) years. Forty-four patients had a diagnosis of AML, 14 of ALL and one case of mixed phenotype acute leukemia. At time of transplant, 39 (66%) were in first or second complete remission, 4 (7%) were in later remission and 16 (27%) had active, relapsed or refractory, disease. Conditioning regimens were myeloablative for 54% of cases and peripheral blood was the preferred source of stem cells (64%). All donors were related. Most patients (85%) received a 4/10 HLA-matched transplant, the most commonly mismatched loci were C and DQB1, often with a double mismatch involving the same locus. Two cases of fully mismatched donors were also recorded.

PTCy was always associated with other immunosuppressive treatments, especially with the standard combination of calcineurin inhibitors and mycophenolate mofetil. In only 8 cases in vivo T-cell depletion was realized with anti-thymocyte globulin.

A large proportion of patients (86%) attained engraftment with a median time of 19 (range, 11-37) days. Only 8 patients did not reach engraftment and all of them died of infection or disease relapse in the first one-hundred days (range, 6-99) after HSCT.

Thirty-three patients (58%) did not present any sign of acute GvHD (aGvHD). Cumulative incidence of grade II-IV and grade III-IV aGvHD at day 180 were 30.3% and 14.3%, respectively. At 2 years, the cumulative incidence of chronic GvHD (cGvHD) was 21%, and 7% for extensive cGvHD.

Twenty-four patients died during the study period, mostly because of leukemia progression (n=13, 54%), infectious complications (n=6, 25%) and interstitial pneumonia (n=2, 8%). Other causes of death were hemorrhage, GvHD, and another non HSCT-related that accounted for one case (4%) each. At 2 years, the overall survival (OS), leukemia-free survival (LFS), and a GVHD and relapse free survival (GRFS) were 56%, 54% and 47% respectively. Rates of relapse incidence and non-relapse mortality were 28% and 19%, respectively.

Conclusion

According to this preliminary data overview, transplantation in a highly mismatched framework is possible, without unfavorable OS, LFS and GVHD rates. Despite the important limitation of the retrospective non-controlled nature of this analysis, these findings suggest that PTCy-based strategies could help overcome the barrier of HLA-matching and configure a new setting of transplantation, encouraging more in-depth investigations.

Disclosures: Labopin: Jazz Pharmaceuticals: Honoraria. Angelucci: Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Glaxo: Honoraria, Membership on an entity's Board of Directors or advisory committees; Crispr therapeutics: Honoraria, Other: DMC; Vertex Pharmaceuticals: Honoraria, Other: DMC; Menarini-Stemline: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: steering commitee, Speakers Bureau; Blue Bird Bio: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene BSM: Honoraria, Other: DMC; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Yakoub-Agha: Jazz Pharmaceuticals: Honoraria. Mohty: Takeda: Honoraria; Jazz: Honoraria, Research Funding; Gilead: Honoraria; Adaptive Biotechnologies: Honoraria; Sanofi: Honoraria, Research Funding; Pfizer: Honoraria; Novartis: Honoraria; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria; Amgen: Honoraria; Astellas: Honoraria.

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