Overall Survival in Patients with Ccus Depends on Presence of Anemia

• Published in: Blood 2023-11, Vol.142 (Supplement 1), p.1864-1864
• Main Authors: Træden, Dicte, Tulstrup, Morten, Johansen, Morten Munk, Ørskov, Andreas Due, Marcher, Claus, Raaschou-Jensen, Klas, Stidsholt Roug, Anne, Severinsen, Marianne Tang, Porse, Bo, Theilgaard-Mönch, Kim, Jespersen, Jakob, Cowland, Jack B., Sjö, Lene, Andersen, Mette Klarskov, Grønbæk, Kirsten, Hansen, Jakob Werner
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2023-177879

Introduction Clonal cytopenia of undetermined significance (CCUS) is a recently recognized hematological disorder characterized by the presence of one or more cytopenias, evidence of clonal hematopoiesis and not fulfilling the criteria for a myeloid neoplasm. In contrast to myelodysplastic syndromes (MDS) where 95% of the patients are anemic at time of diagnosis, that is only the case for around 60% of patients with CCUS (Weeks et al. Prediction of Risk for Myeloid Malignancy in Clonal Hematopoiesis. NEJM Evid. 2023). Furthermore, as recent studies on survival in CCUS primarily included younger patients (Weeks et al. NEJM Evid. 2023) or population-based cohorts not specifically referred for diagnostic work up of unexplained cytopenia (UC) (Rossi et al. Clinical relevance of clonal hematopoiesis in persons aged ≥80 years, Blood 2021) additional survival data on patients with CCUS are warranted. In this study, we investigated survival outcomes in patients with CCUS referred for primary work up of UC. Methods We included 241 patients with CCUS and compared them to 144 patients with low-risk MDS, defined as having less than 5% blasts in the bone marrow. Bone marrow biopsies and next-generation sequencing (NGS) were performed in all patients and cytogenetic analyses using G-band karyotyping was done in 362 (94%) of cases. For NGS, we used a gene panel with the most commonly mutated genes in MDS. The patients were included at 6 different institutions in Denmark from 2013 and onwards. A cut-point of 5 years follow-up was chosen for more robust survival data, and patients were censored at this time point if followed for more than 5 years. Patients with CCUS were stratified into 3 groups dependent on the type of cytopenia present at diagnosis. CCUS patients with pancytopenia (n = 35), and CCUS patients without pancytopenia were split based on whether they were anemic (n = 143) or not (n =63). We compared overall survival between the CCUS groups and low-risk MDS in a Cox proportional hazards model adjusted for age, sex, number of variants and presence of high-risk variants. Results Of the 241 CCUS patients, 178 (74%) were anemic (hemoglobin < 12 and 13 g/dL for women and men, respectively), while this was the case for 130 (90%) of the patients with MDS. A total of 772 variants were identified in the entire cohort with a median of 2 (IQR: 1-3) per patient for both CCUS and MDS patients. The overall survival at 5 years was 45% for low-risk MDS patients and 62% for CCU