GATA2 deficiency syndrome is a heterogeneous disorder characterized by a high risk of developing myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML). We conducted a meta-analysis of the literature to explore the prognostic significance of GATA2 mutations in patients diagnosed with MDS/AML, as previous studies have yielded conflicting findings regarding the impact of GATA2 mutations on patient outcomes. We conducted a comprehensive literature search of databases such as PubMed, Embase, the Cochrane Library, and the Web of Science to obtain studies on the prognostic significance of GATA2 mutations in patients with MDS/AML that were published through January 2024. We extracted the hazard ratio (HR) and 95% confidence interval (CI) for overall survival (OS), disease-free survival (DFS), and event-free survival (EFS). The meta-analysis was conducted by choosing either a fixed-effect model or a random-effect model, depending on the variability observed among the studies. A total of 13 cohort studies were included in the final meta-analysis, including 2714 patients with MDS, of whom 644 had GATA2 mutations. The results revealed that GATA2 mutations had an adverse impact on OS (HR = 1.54, 95% CI = 1.08-2.18, P = 0.02) and EFS (HR = 1.32, 95% CI = 1.01-1.72, P = 0.04), but no significant effect on DFS (HR = 1.21, 95% CI = 0.89-1.64, P = 0.23). GATA2 mutations were associated with a significantly shorter OS in MDS patients (HR = 2.56, 95% CI = 1.42-4.06, P = 0.002) but not in AML patients (HR = 1.08, 95% CI = 0.92-1.26, P = 0.37). Our meta-analysis revealed that GATA2 mutations are associated with unfavourable outcomes in patients with MDS/AML. Furthermore, patients harbouring these mutations should be prioritized for aggressive therapeutic interventions.

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Myelodysplastic neoplasms (MDS) with ring sideroblasts (RS) are diagnosed via bone marrow aspiration in the presence of either (i) ≥15% RS or (ii) 5-14% RS and an SF3B1 mutation. In the MEDALIST trial and in an interim analysis of the COMMANDS trial, lower-risk MDS-RS patients had decreased transfusion dependency with luspatercept treatment. A total of 6817 patients with suspected hematologic malignancies underwent molecular testing using a next-generation-sequencing-based genetic assay and 395 MDS patients, seen at our centre from 1 January 2018 to 31 May 2023, were reviewed. Of these, we identified 39 evaluable patients as having lower-risk MDS with SF3B1 mutations: there were 20 (51.3%) males and 19 (48.7%) females, with a median age of 77 years (range of 57 to 92). Nineteen (48.7%) patients had an isolated SF3B1 mutation with a mean variant allele frequency of 35.2% +/- 8.1%, ranging from 7.4% to 46.0%. There were 29 (74.4%) patients with ≥15% RS, 6 (15.4%) with 5 to 14% RS, one (2.6%) with 1% RS, and 3 (7.7%) with no RS. Our study suggests that a quarter of patients would be missed based on the morphologic criterion of only using RS greater than 15% and supports the revised 2022 definitions of the World Health Organization (WHO) and International Consensus Classification (ICC), which shift toward molecularly defined subtypes of MDS and appropriate testing.

Vacuoles, E1 syndrome, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a chronic inflammatory disorder that affects various organ systems. It is associated with hematologic malignancies and is generally refractory to therapies. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be considered for selected patients. We report a case wherein systemic and hematological manifestations completely resolved in a patient with VEXAS and associated myelodysplastic syndrome (MDS), following the administration of fludarabine and cyclophosphamide as part of the preparation for allo-HSCT. We conducted a systematic literature review and included 86 patients with VEXAS syndrome and associated MDS. Most cases presented with musculoskeletal involvement (71%) and anemia (72%) with lower-risk MDS. Most patients responded to corticosteroids (CS) but had a recurrence of symptoms with CS taper and were refractory to other immunosuppressive agents. Hypomethylating agents and Janus kinase inhibitors achieved a complete response in some cases. Further research is needed to develop more effective treatment strategies.

We conducted a systematic review and meta-analysis to evaluate outcomes after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) in TP53-mutated myelodysplastic syndromes (MDS). A literature search was performed on PubMed, Cochrane, Embase, and Clinicaltrials.gov. After screening 626 articles, eight studies were included. Data were extracted following the PRISMA guidelines and analyzed using the meta-package by Schwarzer et al. We analyzed 540 patients. The pooled median 3 (1-5) year overall survival was 21% (95% CI 0.08-0.37, I2=91%, n=540). The pooled relapse rate was 58.9% (95% CI 0.38-0.77, I2=93%, n=487) at a median of 1.75 (1-3) years. The pooled 4-year progression- free survival was 34.8% (95% CI 0.15-0.57, I2=72%, n=105). Outcomes of Allo-HSCT for TP53-mutated MDS patients remain poor, with 21% OS at three years; however, Allo-HSCT confers a survival advantage as compared to non-transplant palliative therapies. Our findings suggest the need to explore novel therapeutic agents in prospective clinical trials.

OBJECTIVE: Myelodysplastic syndromes (MDS) are myeloid neoplasms characterized by ineffective hematopoiesis due to stem cell abnormalities. Monosomy 7q aberrations are a common cytogenetic abnormality in MDS. Specifically, an unbalanced translocation der(1;7)(q10;p10) [der(1;7)] has been identified in MDS patients, which is a monosomy 7q aberration variant like -7/del(7q). However, knowledge of der(1;7)\'s features remains limited. Existing studies have compared the clinical and genetic characteristics of der(1;7) to those of -7/del(7q) but yielded inconsistent findings. Accordingly, we conducted meta-analyses comparing der(1;7) to -7/del(7q).
METHODS: Publications were searched from the following databases up to January 10, 2023: Pubmed, Web of Science, Embase, Cochrane, and ClinicalTrials.gov. Eligible studies were assessed for risks of bias. Relevant data were extracted from included studies and analyzed using random-effects models. Publication bias was evaluated and sensitivity analyses were performed.
RESULTS: The comparative meta-analyses included 405 MDS patients with der(1;7) from nine studies. The analysis revealed that der(1;7) was associated with a greater male preponderance (86.1% vs. 68.3%, Odds Ratios (ORs) 2.007, p < 0.01) than -7/del(7q), lower platelets counts compared to del(7q), higher hemoglobin levels than -7, lower absolute neutrophil counts, and higher percentage of patients with non-excess blasts (66.9% vs. 41.3%, ORs 2.374, p = 0.01) in comparison with -7/del(7q). The der(1;7) existed more as a sole karyotype aberration (55.6% vs. 37.0%, ORs 2.902, p = 0.02), co-occurred more often with +8 (22.7% vs. 4.2%, ORs 5.714, p = 0.04) whereas less -5/del(5q) (1.5% vs. 41.3%, ORs 0.040, p < 0.01) and complex karyotype (7.3% vs. 54.8%, OR 0.085, p < 0.01). The der(1;7) was associated with higher frequencies of RUNX1 (40.8% vs. 12.3%, ORs 4.764, p < 0.01), ETNK1 (28.1% vs. 2.5%, ORs 42.106, p < 0.01) and EZH2 (24.8% vs. 6.9%, ORs 3.767, p = 0.02) mutations, but less TP53 mutation (2.4% vs. 45.3%, ORs 0.043, p < 0.01). Moreover, der(1;7) patients had longer time to progression (Hazard Ratios (HRs) 0.331, p = 0.02), better overall survival (OS) than -7 patients (HRs 0.557, p < 0.01), but similar OS with del(7q) patients (HRs 0.837, p = 0.37).
CONCLUSIONS: The findings revealed distinct clinical, cytogenetic, and molecular characteristics distinguishing der(1;7) from -7/del(7q), indicating der(1;7) defines a unique subtype within MDS with monosomy 7q. These findings support classifying der(1;7) as a separate MDS entity in future.

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The diagnosis of myelodysplastic syndrome (MDS) is complex. Flow cytometric analysis of the myelomonocytic compartment can be helpful, but it is highly subjective and reproducibility by non-specialized groups is unclear. Analysis of the erythroid lineage by flow cytometry is emerging as potentially more reproducible and easier to conduct, while keeping a high diagnostic performance.
We review the evidence in this area, including 1) the use of well-established markers - CD71 and CD36 - and other less well-established markers and parameters; 2) the use of flow cytometric scores for the erythroid lineage; and 3) additional aspects, including the emergence of computational tools and the roles of flow cytometry beyond diagnosis. Finally, we discuss the limitations with the current evidence, including 1) the impact of the sample processing protocol and reagents on the results, 2) the lack of a standard gating strategy, and 3) conceptualization and design issues in the available publications.
We end by offering our recommendations for the current use - and our personal take on the value - of the analysis of erythroid lineage by flow cytometry.

UNASSIGNED: Arsenic trioxide (ATO) might be effective for myelodysplastic syndrome (MDS) by apoptosis induction and demethylation. But ATO has not been widely recommended for small sample and conflicting conclusion of existing trials. This review aimed to systematically evaluate the efficacy of regimens containing ATO for the MDS and explore optimal combination.
UNASSIGNED: Randomized clinical trials (RCTs) about ATO regimens were retrieved from China National Knowledge Infrastructure, Embase and PubMed. With odds ratio (OR) as the effect size, network meta-analysis (NMA) and component network meta-analysis (CNMA) were conducted by R and \'netmeta\' package, after study selection, quality assessment and data extraction.
UNASSIGNED: Thirty-night RCTs were included with a total of 2125 patients, including 1235 treated by ATO containing regimen. With support therapy alone as reference, no inconsistency and heterogeneity were observed. Although NMA did not demonstrate better efficacy of ATO alone, the result of CNMA indicated that ATO was effective in the improvement of overall remission (ORR) [OR = 2.09(1.61, 2.71)] and complete remission (CR) [OR  = 1.66(1.25, 2.21)]. Five ATO-containing regimens reported could effectively improve ORR, some of them benefit in CR or hematological improvement (HI) as well. ATO + Traditional Chinese Medicine (TCM), ATO + Thalidomide (T)+TCM, ATO + Chemotherapy (Chem)+T + TCM were regarded as the optimal combination, which improved both ORR, CR and HI in theory. ATO did not increase the risk of common adverse events compared to supportive therapy [(OR = 0.90(0.67, 1.21)].
UNASSIGNED: ATO may be an effective and well-tolerant option for patients with myelodysplastic syndrome.

BACKGROUND: Currently, there is no standard treatment for managing relapse in patients with acute myeloid leukemia and myelodysplastic syndrome (AML/MDS) after allogeneic hematopoietic cell transplantation. Venetoclax-based therapies have been increasingly used for treating post-transplantation relapse of AML. The aim of this systematic review and meta-analysis was to evaluate the efficacy and adverse events of Venetoclax combined with hypomethylating agents (HMAs) for AML/MDS relapse post-transplantation.
METHODS: We searched PubMed, Web of Science, Excerpta Medica Database, Cochrane Library, and Clinical. gov for eligible studies from the inception to February 2022. The Methodological Index for Non-Randomized Studies was used to evaluate the quality of the included literatures. The inverse variance method calculated the pooled proportion and 95% confidence interval (CI).
RESULTS: This meta-analysis included 10 studies involving a total of 243 patients. The pooled complete response and complete response with incomplete blood count recovery rate of Venetoclax combined with HMAs for post-transplantation relapse in AML/MDS was 32% (95% CI, 26-39%, I2 = 0%), with an overall response rate of 48% (95% CI, 39-56%, I2 = 37%). The 6-month survival rate was 42% (95% CI, 29-55%, I2 = 62%) and the 1-year survival rate was 23% (95% CI, 11-38%, I2 = 78%).
CONCLUSIONS: This study demonstrated a moderate benefit of Venetoclax in combination with HMAs for patients with relapsed AML/MDS post-transplantation (including those who have received prior HMAs therapy), and may become one of treatment options in the future. Large-scale prospective studies are needed to confirm the potential benefit from venetoclax combined with HMAs.