Background/Objectives: Myeloid sarcoma (MS) is a rare extramedullary manifestation of myeloid blasts, with limited systematic data, particularly regarding molecular (NGS) concordance between MS tissue and bone marrow. We hypothesized that clonal heterogeneity may exist between these sites due to their distinct biological environments. Methods: We conducted a systematic review and meta-analysis of 85 studies encompassing 7241 MS patients, to evaluate clinical characteristics, mutational profiles, treatment patterns, and outcomes. Mutational concordance or discordance between MS and bone marrow was assessed in a subset of 112 patients. Results: Male predominance (59%) and skin/soft tissue localization (31%) were most common. NPM1 (25%) and FLT3 (20%) were the most frequently reported mutations. Among 112 patients with paired sequencing, 56% showed discordance in mutational profiles. NPM1 was significantly enriched in MS sites compared to bone marrow (35% vs. 21%, p = 0.02) and was associated with skin involvement. Discordance was more frequent in isolated and secondary MS. Venetoclax with hypomethylating agents achieved a 44% response rate, mainly in secondary MS. Post-transplant isolated extramedullary relapse occurred in 46% of relapsed patients and was linked to high rates of graft-versus-host disease. The pooled median overall survival was 12.8 months. Conclusions: MS demonstrates significant molecular heterogeneity. Routine site-specific NGS profiling may guide targeted therapy in this rare disease.

Background: While NPM1-mutated AML in the absence of FLT3-ITD generally carries a favorable prognosis, large registry studies suggest the positive prognostic benefit may not extend to patients > 65 years of age. We examined this preferential, age-dependent prognostic impact through a real-world analysis of 2811 adult AML patients. Results: The median overall survival (OS) was significantly better in NPM1^MT compared to NPM1^WT patients [20.86 vs. 17 mo., p = 0.003]. When stratified by age, NPM1^MT patients had higher OS than NPM1^WT patients in the 55–65-year age group (28.62 vs. 16.3 mo., p ≤ 0.0001). This OS benefit was heterogenous and prevailed most strikingly in the 55–60 (68.3 vs. 15.6 mo., p = 0.002), and up to the 60–65-year group (mOS not estimable vs. 20 mo., p = 0.007), but not beyond 65 y. Notably, the ≤65 cohort was more enriched with dominant NPM1 (21% vs. 15%, p ≤ 0.001), while the >65 cohort was enriched with abnormal karyotype (20% in >65 years vs. 16% in ≤65 years, p = 0.001), and co-occurring SRSF2 and ASXL1 mutations (18.7% vs. 7.5%, p ≤ 0.0001 and 13.5% vs. 4.1%, p ≤ 0.0001 resp.). Conclusions: We demonstrate that in a real-world setting, the prognostic benefit of NPM1 does not extend beyond age 65, underscoring the need for age-adapted risk stratification models. This granular approach could prevent the potential overestimation of prognosis in older patients with NPM1^MT AML and inform therapeutic decision making.

We report two cases of pancytopenia in patients after recovering from a mild COVID-19, now presenting as paroxysmal nocturnal hemoglobinuria (PNH) and aplastic anemia. These cases illustrate a common pathway whereby a viral trigger causes the clonal expansion of a hematological disorder. Although the association of both cases with COVID-19 is temporal and COVID-19 may be an incidental diagnosis, the growing evidence related to the hematological effects of SARS-CoV-2 infection highlights the need for further investigation into the hematological consequences of COVID-19, particularly in the post-pandemic era.

We report two cases of pancytopenia in patients after recovering from a mild COVID-19, now presenting as paroxysmal nocturnal hemoglobinuria (PNH) and aplastic anemia. These cases il-lustrate a common pathway whereby a viral trigger causes clonal expansion of a hematological disorder. Although the association in both cases are temporal, and that COVID-19 may be an in-cidental diagnosis, the growing evidence related to hematological effects of SARS-CoV-2 infec-tion highlights the need for further investigation into the hematological consequences of COVID-19, particularly in the post-pandemic era.