Outcome after Allogeneic Stem Cell Transplant in Adults with Inherited Myeloid Malignancies - a Multicenter Retrospective Analysis on Behalf of the German Cooperative Transplant Study Group
Year: 2024
Type: conference-abstract
Abstract: Background: The application of novel sequencing techniques has facilitated the recognition that pathogenic germ line variants drive the development of myeloid neoplasms also in a relevant proportion of adult patients. These patients with hereditary myeloid malignancies (HMMs) receive similar standard therapies including allogeneic stem cell transplantation (allo-SCT) as those with sporadic disease. Still, the evidence from the literature about the management of such adult patients with HMMs in the context of allo-SCT and their post-transplant outcome is restricted to one multicenter analysis (Saygin et al. Blood Advances, 2022) and smaller case series often focusing on germline variants in a specific gene. To expand this evidence, we ask centers participating in the German Cooperative Transplant Study Group to report their transplant experience in adult patients with HMMs. Methods: We performed a retrospective analysis of adult patients with confirmed HMMs, who received a first allo-SCT at 11 German transplant centers. Patients', disease- and transplant-related data including information on the specific germline variant, method and tissue source of detection as well as family history were collected together with post-transplant outcome data. Results: Overall, we identified 38 patients with HMMs, who received an allo-SCT from a matched (n=24, 63%) or mismatched unrelated (n=8, 21%), related (n=3, 8%) or haploidentical (n=3, 8%) donor following standard-dose (n=6, 16 %) or reduced-intensity conditioning (n=32, 84%) between 2005 and 2024. The majority of patients suffered from an AML (n=26, 68%), while 11 (29%) and 1 (3%) patients suffered from MDS or MPN, respectively. Among AML and MDS patients, 74% were stratified as adverse or high/very high risk according to ELN 2022 or IPSS-R. Overall, in 9 patients the disease (24%) was classified as therapy-related myeloid neoplasm and 42% had a first degree relative with a cancer history. In 19 patients (50%) a deleterious DDX41 germline variant was present, while in the other 19 patients (50%) germline variants in several other genes known to be associated with HMMs (GATA-2 n=4, RUNX1 n=3, NF1 n=2, TP53 n=2, BRCA1 n=2, BRCA2n=2, TET2 n=1, SBDS n=1, TERC n=1, PALB2 n=1) were found. In those with available information (n=31, 82%), the germline origin of these variants was confirmed by investigation of buccal swabs (n=13, 42%), nails (n=8, 26%), saliva (n=4,13%), hematopoietic tissue (n=4, 13%) or hair follicles (n=2, 6%) and 70% of patients received genetic counselling. With a median follow-up of 14 months, the estimated 2-year overall survival (OS), non-relapse mortality (NRM) and cumulative incidence of relapse (CIR) rate of the entire cohort were 59%, 19% and 23% respectively. Engraftment of neutrophils and platelets was observed in 100% and 97% both in median after 14 days, while incidences of acute and chronic GvHD were 42% and 28%, respectively. As expected, patients carrying DDX41 mutations were significantly older than patients with other HMMs (64 vs. 44 years, p<0.0001), but did not differ with regard to other patient-, disease- and transplant-related characteristics. Despite these similiarities, the 2-year OS rate of DDX41 mutated patients was substantially higher than of those patients with other HMMs (87% vs. 44%, p=.057). This survival advantage was not related to differences in NRM (DDX41 14% vs. others 18% at 2 years, p=.997), but to a significantly lower CIR (0% vs. 42% at 2 years, p=.047). Only one patient with DDX1 mutation ‘relapsed’ as donor cell leukemia at month 27 after transplant. Conclusion: These data advocate for further standardization of peri-transplant management and reporting of patients with HMMs undergoing allo-SCT in the future. Furthermore, our analysis suggests that among patients with HMMs those with DDX41 mutations seem to have low relapse rates and excellent outcome after allo-SCT, but this requires confirmation in larger data sets.
Source: Blood
Authors: Tim Lohmann, Matthias Stelljes, Caroline Pabst, Stefan Klein, Johanna Tischer, Alessia Fraccaroli, Leo Ruhnke, Laura Groneck, Alexander Denk, Friedrich Stölzel, Daniel Wolff, Judith Schaffrath, Fabian Beier, Maher Hanoun, Johannes Schetelig, Martin Bornhäuser, Artur Schneider, Hans Christian Reinhardt, Christina Rautenberg, Thomas Schroeder
Institutions: Essen University Hospital, University of Münster, University Hospital Heidelberg, Heidelberg University, University Medical Centre Mannheim, Ludwig-Maximilians-Universität München, University Hospital Carl Gustav Carus, Klinikum Bremen-Mitte, University Hospital Regensburg, Martin Luther University Halle-Wittenberg, Universitätsklinikum Aachen, Technische Universität Dresden, University of Duisburg-Essen
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4405042919