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3952 Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia with Hyperdiploid Complex Karyotype: A Study from the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT)

Program: Oral and Poster Abstracts
Session: 732. Allogeneic Transplantation: Disease Response and Comparative Treatment Studies: Poster III
Hematology Disease Topics & Pathways:
Biological, Adults, AML, Clinically Relevant, Diseases, Therapies, Myeloid Malignancies, Study Population, Transplantation
Monday, December 13, 2021, 6:00 PM-8:00 PM

Xavier Poiré, MD, PhD1*, Myriam Labopin2,3*, Emmanuelle Polge, M.Sc4*, Arnold Ganser, MD5, Gerard Socie, M.D.6,7, Tobias Gedde-Dahl8*, Edouard Forcade, MD, PhD9, Jürgen Finke Sr., MD, PhD10, Yves Chalandon, MD11, Claude-Eric Bulabois, MD12*, Ibrahim Yakoub-Agha13, Mahmoud Aljurf14, Nicolaus Kröger, MD15*, Igor Wolfgang Blau, MD16*, Arnon Nagler, M.D.3,17, Jordi Esteve, MD, PhD18 and Mohamad Mohty, MD, PhD19,20

1Section of Hematology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
2EBMT Paris study office; Department of Haematology,, Saint Antoine Hospital; INSERM UMR 938, Sorbonne University, Paris, France
3Acute Leukemia Working Party of EBMT, Paris, France
4ALWP of the EBMT Paris office, Saint Antoine Hospital; INSERM UMR 938, Sorbonne University, Paris, France
5Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
6Hopital St. Louis, Dept.of Hematology – BMT, Paris, France
7Assistance Publique Hôpitaux de Paris, Hôpital Saint-Louis, Paris, France
8Oslo University Hospital, Oslo, Norway
9Service d’hematologie et thérapie Cellulaire, CHU Bordeaux, Hôpital Haut-Leveque, Pessac, France
10Department of Medicine I, University Medical Center Freiburg, Freiburg, Germany
11Geneva University Hospitals, Geneva, Switzerland
12Service d'Hematologie, CHU Grenoble Alpes-Universite Grenoble Alpes, Grenoble, France
13Centre Hospitalier Universitaire de Lille LIRIC, INSERM U1286, Université de Lille, Lille, France
14Oncology, Section of Adult Haematolgy/BMT, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
15Department of Stem Cell Transplantation, University Hospital Hamburg-Eppendorf, Hamburg, Germany
16Department of Hematology, Oncology, and Tumor Immunology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
17Division of Hematology, Chaim Sheba Medical Center, Tel Hashomer, Israel
18Hospital Clínic, Barcelona, Spain
19Department of Clinical Hematology and Cellular Therapy, Saint Antoine Hospital, Paris, France
20Acute Leukemia Working Party, Paris Study office, European Society for Blood and Marrow Transplantation, Paris, France

Introduction: Cytogenetics remains one of the most important prognostic factors in acute myeloid leukemia (AML) patients, even for outcomes after allogeneic hematopoietic cell transplantation (allo-HCT). Complex karyotype (CK) constitutes a cytogenetic category with a very adverse prognosis in this setting. However, CK is a heterogenous and loosely defined category which comprises a high diversity of cytogenetic subtypes, which is highly enriched with specific cytogenetic subtypes characterized by losses of chromosomal material at critical regions known to confer a poor prognosis per se, such as monosomal karyotype, del(7q)/-7, del(5q)/-5 or abnormalities leading to 17p region loss. On the contrary, rare AML cases characterized with only multiple numerical abnormalities known as pure hyperdiploid karyotype (HDK), have a controversial prognosis. We hypothesized that pure complex HDK AML has a distinct and much better prognosis after allo-HCT compared to non-HDK, CK AML.

Methods: We selected from the EBMT registry adult patients with AML and a full cytogenetic report. HDK was defined by the presence of 49 chromosomes or more. Patients were then stratified by pure HDK (pHDK) and HDK with other cytogenetic abnormalities (HDK+), characterized by HDK and the presence of a prognostic-defining cytogenetic abnormality such as del(5q)/-5, del(7q)/-7, del(17p)/-17/i(17q), inv(3q21-26)/t(3;3)(q21;q26) or t(9;22). We included only first allo-HCT from a sibling or unrelated donor (UD) performed between 2000 and 2018.

Results: A total of 236 patients were identified as having HDK. There were 95 pHDK and 141 HDK+. Median age at transplantation was 53 years (range, 18-74) and median follow-up was 43 months (range, 35-56). A diagnosis of secondary AML was reported in 48 patients (20%). At the time of allo-HCT, 180 patients (76%) were in first remission (CR1), and 56 were beyond CR1 (24%). Eighty-five (39%) patients received an allo-HCT from a sibling donor, with more matched unrelated donors (MUD) in HDK+ patients (p=0.02). Most patients (70%) had a Karnofsky performance status (KPS) score of more than 90% at the time of transplantation. A myeloablative conditioning regimen was administered in 46% of the patients. In vivo T-cell depletion was part of the regimen in 66% of the patients. The most frequent trisomies were trisomy 8, 21, 13, and 22.

The 2-year probability of non-relapse mortality (NRM) was 26% for the entire cohort. The 2-year probability of LFS was 50% for pHDK and 31% for HDK+ (p=0.003). The 2-year probability of overall survival (OS) was 57% for pHDK and 36% for HDK+ (p=0.007). The 2-year cumulative incidence of relapse (RI) was 22% for pHDK and 44% for HDK+ (p=0.001) (Figure 1). The cumulative incidence of grade II-IV acute graft-versus-host disease (GvHD) and chronic GvHD was 34% and 33%, respectively, for the entire cohort. Finally, the 2-year probability of GvHD and relapse-free survival (GRFS) was 36% for pHDK and 21% for HDK+ (p=0.01). On multivariate analysis, pHDK remained associated with significantly better LFS, OS and GRFS and higher RI (all p-values<0.004). Age was associated with lower OS (p=0.05). Being in remission at the time of allo-HCT was associated with better LFS, OS and GRFS, and lower NRM and RI (all p-values<0.02). Secondary AML, donor type, KPS, and conditioning regimen intensity were not associated with any outcome in multivariate analysis.

Conclusions: AML with pHDK has a better outcome after allo-HCT in terms of RI, LFS, OS and GRFS. pHDK AML constitutes probably a distinct cytogenetic entity from HDK+ or other non-hyperdiploid CK AML. CK remains a strong indication for allo-HCT, but the type of abnormalities included in CK significantly influences the outcome and should guide how to manage patients after allo-HCT in terms of immunosuppression withdrawal or prophylactic/preemptive post-transplant interventions such as use of hypomethylating agents or donor lymphocyte infusions.

Disclosures: Labopin: Jazz Pharmaceuticals: Honoraria. Ganser: Jazz Pharmaceuticals: Honoraria; Novartis: Honoraria; Celgene: Honoraria. Socie: Alexion: Research Funding. Forcade: Novartis: Other: travel grant. Chalandon: Incyte, BMS, Pfizer, Abbie, MSD, Roche, Novartis, Gilead, Amgen, Jazz, Astra Zenec: Other: Travel EXpenses, Accomodation; Incyte, BMS, Pfizer, Abbie, MSD, Roche, Novartis, Amgen: Other: Advisory Board; Incyte: Speakers Bureau. Yakoub-Agha: Jazz Pharmaceuticals: Honoraria. Kröger: Novartis: Research Funding; Riemser: Honoraria, Research Funding; Sanofi: Honoraria; Neovii: Honoraria, Research Funding; Jazz: Honoraria, Research Funding; Gilead/Kite: Honoraria; Celgene: Honoraria, Research Funding; AOP Pharma: Honoraria. Esteve: Jazz: Consultancy; Bristol Myers Squibb/Celgene: Consultancy; Abbvie: Consultancy; Novartis: Consultancy, Research Funding; Astellas: Consultancy; Pfizer: Consultancy; Novartis: Research Funding. 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.

*signifies non-member of ASH