Characteristics and Survival Outcome of Patients with Isolated 11q Deletion Myelodysplastic Syndromes
Authors: Kekedjian Jeannot , Komrokji Rami S. , Al Ali Najla H. , Takaoka Kensuke , Sallman David , Xie Zhuoer , Padron Eric , Chien Kelly S. , Montalban-Bravo Guillermo , Braish Julie , Urrutia Samuel , Bataller Alex , Bazinet Alexandre , Kanagal-Shamanna Rashmi , Tang Guilin , Wei Yue , Yang Hui , Rodriguez Sevilla Juan Jose , Garcia-Manero Guillermo , Sasaki Koji 
Published: December 2024

Myelodysplastic syndromes (MDS) are marked by ineffective hematopoiesis and exhibit an increased risk of progression to acute myeloid leukemia (AML). The revised international prognostic scoring system (IPSS-R) identifies the deletion of the long arm of chromosome 11, del(11q), as a rare but very good risk cytogenetic abnormality. This study aims to evaluate the clinical features and the optimal management of MDS with isolated del(11q).

Patients diagnosed with MDS between 1997 and 2024 were included in the analysis. Their risk was evaluated using the International Prognostic Scoring System (IPSS), IPSS-R, and the molecular IPSS (IPSS-M). Patients were treated with either best supportive care (BSC) or a hypomethylating agent (HMA). Treatment responses were determined in accordance with the International Working Group Response Criteria for MDS 2018. Baseline characteristics were compared with the Fisher's exact test or chi-square tests. Progression-free survival (PFS) and overall survival (OS) were estimated through the Kaplan-Meier method. Survival analysis was conducted using univariate and backward multivariate Cox regression.

Among 12764 patients with MDS, 52 were found to have isolated del(11q), constituting 0.41% of the cohort. The median follow-up period was 96 months, and the median age of del(11q) detection was 69 years. As per the 2022 World Health Organization classification, 42% of patients had MDS with low blasts. According to the 2022 International Consensus Classification, 31% of patients had MDS not otherwise specified with multilineage dysplasia. According to IPSS, 69% of patients had intermediate-1 risk; 42% were very low risk and 31% were low-risk by IPSS-R; 30% were very low-risk and 33% were low-risk by IPSS-M. Patients treated with HMA were younger than those receiving BSC.

Among 26 evaluable patients receiving HMA, 11 (42%) achieved stable disease, 6 (23%) attained complete remission (CR) in the bone marrow, 3 (12%) experienced disease progression, and 2 (8%) had treatment failure. Among 19 evaluable patients classified as very low or low risk for MDS by IPSS-R, 3 (16%) achieved marrow CR, 7 (37%) had stable disease, 2 (11%) showed hematological improvement, 2 (11%) experienced disease progression, and 2 (11%) had treatment failure. Among 8 evaluable patients with intermediate and high-risk MDS, 3 (38%) had stable disease, 2 (25%) achieved both CR and hematological improvement, and 1 (13%) had progressive disease.

Univariate and backward multivariate Cox regression analysis identified age (hazard ratio [HR]: 1.050, 95% confidence interval [CI]: 1.007-1.094, P=0.022), absolute neutrophil count (HR: 1.324, 95% CI: 1.132-1.547; P&lt;0.001), hemoglobin (HR: 0.697, 95% CI: 0.540-0.900), percentage of blasts in peripheral blood (HR: 2.121, 95% CI: 1.298-3.466; P=0.003), and percentage of blasts in bone marrow (HR: 1.188, 95% CI: 1.082-1.304; P&lt;0.001) as prognostic factors for survival.

With a median follow-up of 96 months, the median survival was 71 months with a 5-year OS rate of 53% (95% CI: 40.2-70.3). The median PFS was also 71 months with a 5-year PFS rate of 53% (95% CI: 40.4-70.4). When stratified by IPSS-R, the five-year OS rates were 77% (95% CI: 58.7-99.5) for the very low risk group, 43% (95% CI: 22.9-80.0) for the low-risk group, and 27% (95% CI: 10.4-71.6) for the intermediate/high risk category (P=0.016). The 5-year OS rates were 45% (95% CI: 29.5-68.5) in the HMA group and 68% (95% CI: 49.8-93.2) in the BSC group (P=0.625).

Ten patients underwent allogeneic stem cell transplant (allo-SCT): 3 received azacytidine (AZA) maintenance therapy while 1 declined it; all 4 remained in CR. One patient continued AZA maintenance therapy because the bone marrow evaluation following the transplant showed 2% blasts with TP53, TET2, ETNK1, and SF3B1 mutations. In total, 30 patients died in the study, including 5 who passed away after progression to AML.

In conclusion, patients with isolated del(11q) MDS tend to have favorable outcomes. HMA therapy may be considered for patients exhibiting high-risk clinical and/or molecular features at the time of diagnosis. Curative allo-SCT may be considered upon progression to higher-risk MDS.