IntroductionVEXAS syndrome (Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic) is a recently identified disorder associated with somatic mutations in the UBA1 gene. Predominantly affecting adult males, it is characterized by a wide range of autoinflammatory symptoms and hematologic abnormalities.MethodsWe present three cases from Latin America, marking the first reported occurrences in this region, to illustrate the clinical variability and diagnostic challenges of VEXAS syndrome.ResultsEach patient exhibited unique clinical presentations, including refractory autoinflammatory symptoms, myelodysplastic syndrome, and bone marrow vacuolization. All cases were confirmed via genetic testing, revealing pathogenic UBA1 mutations alongside other genetic variants commonly linked with myeloid neoplasms.DiscussionThese findings underscore the importance of considering VEXAS syndrome in patients with unexplained inflammatory and hematologic symptoms. The coexistence of UBA1 mutations with other genetic variants suggests a potential overlap with clonal hematopoiesis, complicating the clinical picture. These cases contribute to the understanding of VEXAS syndrome and highlight the need for increased awareness and diagnostic testing in diverse populations to ensure early and accurate diagnosis.

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematological malignancies characterized by ineffective hematopoiesis, resulting in cytopenias, morphologic dysplasia in hematopoietic lineages, and a variable risk of progression to acute myeloid leukemia. Significant advances in the understanding of MDS have been made in recent years, largely due to the implementation of molecular tools. Latin America is a highly diverse region, both ethnically and racially, and often faces resource limitations that challenge the broad applicability of recent advances in MDS. In this review, we discuss the key genes implicated in the pathogenesis and classification of MDS, and their relevance to diagnosis, prognosis, and potential therapeutic targets. We also explore the challenges associated with the identification of germline predisposition to MDS in Latin America and discuss the current availability and limitations of molecular diagnostic tools in the region.

Abstract Myelodysplastic syndromes (MDSs) are clonal disorders of the bone marrow characterized by ineffective hematopoiesis, cytopenia, and an increased risk of progression to acute myeloid leukemia. The phenotypic variability of the disease, driven by genetic abnormalities, poses challenges to its management and prognosis. Although traditional cytogenetic analysis detects chromosomal abnormalities in ∼50% of cases, next-generation sequencing (NGS) identifies genetic mutations in 70% to 90% of patients, providing critical prognostic insights. However, data on the genetic landscape of MDS in Latin America, including Uruguay, remain limited. This study investigates the role of NGS in detecting copy number variants (CNVs) alongside somatic mutations to refine prognostic evaluations. Among 52 patients analyzed, NGS-based CNV detection identified abnormalities in 38% of cases, including deletions on chromosomes 5 and 7 and gains on chromosome 8, many of which were missed by conventional karyotyping in real-world settings. Integrating CNV data with karyotyping into established risk models significantly improved prognostic accuracy. Furthermore, somatic mutation profiling revealed mutations in 75% of patients, with TP53, DNMT3A, TET2, ASXL1, and SF3B1 being the most frequently identified. Notably, TP53 mutations were strongly correlated with poor clinical outcomes. The International Prognostic Scoring System–Molecular model restratified 42.3% of patients, offering enhanced risk assessment and prognostic precision. By integrating CNV analysis with somatic mutation profiling, this study highlights the feasibility and utility of a NGS single-run approach that improves diagnostic accuracy and optimizes workflows, particularly in resource-constrained settings.

Germline variants in RUNX1 and DDX41 are well-established contributors to hereditary myeloid neoplasms and are increasingly recognized as critical predisposing factors in the developing myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). This case report details a 51-year-old male diagnosed with MDS with excess blasts-1 (MDS-EB1), who harbored a rare combination of pathogenic germline variants in RUNX1 and a novel potentially pathogenic variant in DDX41 variant, alongside a somatic DDX41 mutation. The coexistence of these germline variants highlights the genetic complexity underlying hereditary myeloid neoplasms and reinforces the necessity of comprehensive genomic testing to ensure accurate diagnosis and informed clinical management. The interplay between RUNX1 and DDX41 variants may drive leukemogenesis, with the germline RUNX1 variant potentially fostering a cellular environment that enables the acquisition of somatic DDX41 mutations, leading to hematological malignancies. Conversely, the germline DDX41 variant may disrupt hematopoiesis and, when combined with RUNX1 dysfunction, contribute to disease progression. This case underscores the importance of screening germline variants in patients with myeloid neoplasms. It emphasizes the need to confirm the origin of these variants in non-hematopoietic tissues, such as fibroblasts (gold standard), to avoid misinterpretation caused by clonal hematopoiesis. Further research is warranted to elucidate the molecular mechanisms driving the interaction between RUNX1 and DDX41 variants and their collective impact on disease progression, treatment outcomes, and familial risk.

Background: Accurate risk stratification in acute myeloid leukemia (AML) increasingly depends on integrated cytogenetic and molecular profiling, as outlined in recent WHO and ELN (2022) classifications. However, data from Latin America remain scarce. While comprehensive genetic testing is standard in high-resource settings, its implementation across the region is limited. This multicentric prospective cohort study aimed to characterize the utility of NGS and cytogenetic testing in risk stratification of adult AML patients in Uruguay and to evaluate how the integration of somatic variant and copy number variations (CNV) findings enhances prognostic classification. Methods: We enrolled 61 adult AML patients from 12 Uruguayan hematology centers (2021–2023). Clinical data and diagnostic bone marrow samples were collected. gDNA was analyzed using a 63-gene myeloid panel (SOPHiA DDM® on Illumina MiSeq) to detect SNVs, indels, and CNVs. Conventional cytogenetics was performed in all cases; FISH in 65%. Results: We included 61 AML patients (median age 56 [39–58] years; 47% male); 38 (62.3%) were fit for intensive chemotherapy and 23 (37.7%) unfit. Among fit patients, ELN 2022 classified 25% (9) as favorable, 47.2% (17) intermediate, and 27.8% (10) high risk. Compared to ELN 2017, 27% were reclassified, mostly up-staged (18.4% from intermediate to high). Cytogenetic abnormalities were found in 31.6% (12), with high-risk features in 15.7%. (6) In contrast, CNVs were detected by NGS in 39.4%, prompting reclassification in 26%—including 5 with normal karyotypes. CNV detection showed 78% sensitivity (95% CI: 54.0–93.8) and 87% specificity (95% CI: 60.4–89.3) vs. conventional methods. Somatic mutations were found in 89.5% (median 3 per patient, IQR 1–4); most frequent were NPM1 (34.2%), FLT3-ITD (28.9%), DNMT3A and NRAS (26.3% each), IDH1/2 (18.4%), TP53 (10.5%, 80% multi-hit), CEBPA BZIP (7.9%), and RUNX1 (7.9%). Targetable mutations (FLT3 or IDH1/2) were present in 52.2%. All received 7+3 chemotherapy; 21% also received midostaurin. CR was achieved in 71% after 1–2 inductions. Median OS was 23 months (95% CI: 17–32). ELN 2022 risk groups stratified survival, and TP53 or myelodysplasia-related mutations were independently associated with worse OS (p = 0.022 and p = 0.021). Among unfit patients (median age 69 [IQR 67–75]), ELN 2024 classified 54.5% (12) as favorable, 13.6% (3) intermediate, and 31.8% (7) high risk. Cytogenetic abnormalities were present in 38.9%, while NGS-detected CNVs appeared in 56.6%, prompting risk reclassification in 26% with normal karyotypes. Somatic mutations were found in 95.7% (median 3 per patient, range 2–4), with STAG2 (34.8%), DNMT3A (30.4%), RUNX1 and TP53 (26.1% each), SRSF2 (21.7%), and IDH1/2 (17.3%) being most common. TP53 mutations were multi-hit in 83% of cases. Treatments included azacitidine alone (43.5%) or with venetoclax (47.8%), achieving CR/CRi in 56.1%. Median OS was 15 months (95% CI: 12–17). ELN 2024 risk categories correlated with outcomes (p = 0.032), and RAS, FLT3-ITD, and TP53 mutations were each significantly associated with inferior OS (p = 0.026, 0.026, and 0.001, respectively). Conclusions: This is the first comprehensive study to evaluate both somatic mutations and CNVs through targeted NGS in Uruguayan AML patients, and one of the few such efforts in Latin America, where available data are limited to small series from Brazil and Mexico. Conducted nationwide in a country with ~100 new AML cases per year, this cohort is representative and contributes valuable regional insight. Incorporating CNV analysis via NGS significantly improved the detection of clinically relevant genetic abnormalities. Additionally, somatic mutation profiling enabled refined prognostic stratification, with 27% of patients reclassified under ELN 2022, leading to potential changes in therapeutic management. The integration of CNV and somatic profiling enhanced diagnostic precision—particularly in cases with technically limited cytogenetics—reducing the size of the intermediate-risk group and supporting more tailored therapeutic decisions. High-risk molecular features, including multi-hit TP53 and myelodysplasia-related mutations, were associated with inferior survival, while targetable mutations were frequent. Overall, our findings support the feasibility and utility of a single-run NGS-based approach to improve diagnostic accuracy and optimize workflows in resource-limited settings.

Background: The shift to virtual learning has become essential in medical education, particularly in specialized fields such as hematological cytology. This study describes the development, implementation and rating of an asynchronous online course in hematological cytology for undergraduate medical students. Methods: The course integrated multimedia resources such as virtual microscopy, interactive videos, and self-assessment tools. Over three years, 174 students enrolled, with a 91.4% completion rate. The effectiveness of the course was evaluated through student surveys, which assessed course organization, content, and student satisfaction. Results: The average student satisfaction rating for course organization was 9.7 ± 0.73. The virtual microscope, a key tool in the course, received a high rating of 9.0 ± 0.93. The course was divided into seven modules, progressing from basic to more complex topics. The most highly rated modules were "Microscopy, Cytological Smears, and Staining Techniques" and "Normal Bone Marrow". More advanced modules, such as "Acute Leukemias and Myelodysplastic Syndromes," received lower ratings, indicating a need for additional support in complex topics. Conclusions: The online course successfully replicated key aspects of hands-on cytology education, demonstrating that virtual tools can effectively enhance student engagement and learning outcomes. The high completion and satisfaction rates highlight the potential of virtual learning in medical education, paving the way for future innovations in specialized training.

Background: Despite advances in treatment of AML pts considered fit for intensive therapy, significant unmet medical needs remain. Early end points for survival can accelerate the approval of novel therapies. MRD has been recently accepted as an early end point in other hematological malignancies, but important questions remain unanswered to support its acceptance in AML. Is multiparameter flow cytometry (MFC) more sensitive than the morphological definition of complete remission (CR)? Are MRD kinetics more prognostic than a single assessment? Are there genetic risk groups in whom MRD is not informative? Is the prognostic value of MRD independent of induction and consolidation therapy? Are MRD negative rates achieved with each therapy associated with different survival? Aim: Investigate the potential role of MRD assessed by MFC as an early endpoint for survival in AML pts treated with intensive therapy. Methods: The PETHEMA registry had 2,623 newly-diagnosed AML pts treated in routine practice and clinical trials, who had at least one MRD assessment at first CR using local MFC methods. Pts were mainly treated with 3+7 (n=2,160), followed by 3+7 plus a FLT3 inhibitor (n=137), FLAG-based regimens (n=97). Additional treatments included CPX-351 (n=59), 3+7+Etoposide (n=44), 3+7+GO (n=37), and others (n=89). Pts were stratified into low (CBF, n=348), intermediate-low (CEBPA/NPM1+ and FLT3-, n=392), intermediate-high (MRC 2010 intermediate or normal karyotype with FLT3- and NPM1-, n=738) and high (MRC 2010 high or FLT3+, n=784) genetic risk. Relapse-free (RFS) and overall survival (OS) were landmarked at the time of MRD assessment. Results: Of the 2623 pts in CR1, 1256 (48%) showed MRD ≥0.1% and 532 (20%) had MRD levels ≥0.01% - <0.1%. When compared to pts with <0.01% MRD (n=835, 32%), those with MRD levels ≥0.01% - <0.1% and ≥0.1% showed inferior RFS (medians of 35, 23 and 17, p<.001) and OS (medians of 94, 55 and 33 months, p<.001). Hence, the 0.01% cutoff was selected to define negative vs positive MRD status. Positive MRD was associated with inferior RFS (HR= 1.3, p<.001) and OS (HR= 1.4, p<.001). The respective global odds ratio estimated by the bivariate Plackett Copula model were 8.0 (95% CI, 5-16.7) and 9.8 (95% CI, 5.7-27.8), which indicates a strong correlation between MRD status at CR1 and survival outcomes. Of note, a sub-analysis in pts with ≥2 MRD assessments (n=322) showed that MRD kinetics are more prognostic than a single MRD test. When compared to pts with sustained MRD negativity and those having positive and negative MRD result, pts who were systematically MRD positive showed inferior RFS (median of 61, 48 and 16 months, p<.001) and OS (median 96 vs 105 vs 35 months, p<.001). In multivariate analysis adjusted for genetic risk and the different treatments, MRD status retained independent prognostic value for RFS (HR= 1.3, p<.001) and OS (HR= 1.3, p<.001). MRD status predicted different outcome in pts with genetic high-risk and was borderline significant in those with low-risk. By contrast, there were no differences in intermediate-risk groups, which could be partially associated with MRD-guided intensification. Accordingly, pts who were not transplanted showed different OS according to MRD status. By contrast, MRD status at CR1 was not prognostic in pts undergoing autologous or allogeneic transplant. The association between the treatment effect in MRD and survival was investigated in the three most frequent induction regimens. MRD negative rates were higher after 3+7 plus a FLT3 inhibitor vs 3+7 vs FLAG-based regimens (42% vs 31% vs 29%, p=.02). The higher MRD negative rates preceded longer RFS (median 32 vs 21 vs 14 months, p=.01) and OS (median 58 vs 47 vs 22 months, p=.01) with 3+7 plus a FLT3 inhibitor vs 3+7 vs FLAG-based regimens. Conclusion: MRD assessment by MFC proved to be more sensitive than CR and showed a strong patient-level association with survival. MRD negative rates achieved with each treatment were also associated with differences in survival. While these results qualify MRD as a potential early end point of treatment efficacy in AML pts considered fit for intensive therapy, attention should be paid to genetically-defined intermediate risk groups in whom MRD status may guide treatment decisions that could ameliorate the poor prognosis of positive MRD. MRD kinetics may be required to improve prognostication of such pts, particularly in those who are transplanted.

Timeline and genetic analysis of a 55-year-old female with a family history of gastric cancer and multiple myeloma, who was diagnosed with AML and a germline CEBPA variant.

BackgroundDespite advancements in treatment, patients with Systemic Lupus Erythematosus (SLE) frequently experience disease flares, which contribute to organ damage and increase the risk of premature death. Assessing disease activity is essential for optimizing treatment and preventing further organ damage. This study aimed to investigate the relationship between levels of progenitor and circulating endothelial cells and SLE disease activity, as well as accumulated organ damage.MethodsWe conducted a case-control study measuring levels of CD34+CD45low/- progenitor cells, CD34+CD45low/-CD133+ progenitor cells, Endothelial Progenitor Cells (EPC), and Circulating Endothelial Cells (CEC) in peripheral blood using flow cytometry.ResultsThe study included 32 SLE patients and 28 matched controls. SLE patients exhibited significantly lower levels of CD34+CD45low/- progenitor cells (p = .001), CD34+CD45low/-CD133+ progenitor cells (p = .016), EPC (p = .018), and CEC (p < .001) compared to controls. Additionally, the cell subpopulations correlated with SLE activity biomarkers, with CD34+CD45low/- progenitor cells showing a moderate negative correlation with C3 and C4 levels. Notably, patients with an SDI score ≥1 had significantly higher levels of CD34+CD45low/- progenitor cells, CD34+CD45low/- CD133+ progenitor cells, EPC, and CEC compared to those without organ damage (p = .0073, p = .018, p = .018, and p = .020, respectively).ConclusionOur findings reveal that CD34+CD45low/- progenitor cells, CD34+CD45low/-CD133+ progenitor cells, EPC, and CEC are significantly reduced in SLE patients and are associated with disease activity and organ damage. These results suggest that CD34+CD45low/- progenitor cells, in particular, could serve as potential biomarkers for monitoring disease activity and organ damage in SLE patients. Prospective studies are warranted to confirm these findings.

Background:The Molecular International Prognostic Scoring System (IPSS-M) has improved the prediction of clinical outcomes for myelodysplastic syndromes (MDS). The Artificial Intelligence Prognostic Scoring System for MDS (AIPSS-MDS), based on classical clinical parameters, has outperformed the IPSS, revised version (IPSS-R). For the first time, we validated the IPSS-M and other molecular prognostic models and compared them with the established IPSS-R and AIPSS-MDS models using data from South American patients. Methods:Molecular and clinical data from 145 patients with MDS and 37 patients with MDS/myeloproliferative neoplasms were retrospectively analyzed. Results:Prognostic power evaluation revealed that the IPSS-M (Harrell's concordance [C]-index: 0.75, area under the receiver operating characteristic curve [AUC]: 0.68) predicted overall survival better than the European MDS (EuroMDS; C-index: 0.72, AUC: 0.68) and Munich Leukemia Laboratory (MLL) (C-index: 0.70, AUC: 0.64) models. The IPSS-M prognostic discrimination was similar to that of the AIPSS-MDS model (C-index: 0.74, AUC: 0.66) and outperformed the IPSS-R model (C-index: 0.70, AUC: 0.61). Considering simplified low- and high-risk groups for clinical management, after restratifying from IPSS-R (57% and 32%, respectively, hazard ratio [HR]: 2.8; P=0.002) to IPSS-M, 12.6% of patients were upstaged, and 5% were downstaged (HR: 2.9; P=0.001). The AIPSS-MDS recategorized 51% of the low-risk cohort as high-risk, with no patients being downstaged (HR: 5.6; P<0.001), consistent with most patients requiring disease-modifying therapy. Conclusions:The IPSS-M and AIPSS-MDS models provide more accurate survival prognoses than the IPSS-R, EuroMDS, and MLL models. The AIPSS-MDS model is a valid option for assessing risks for all patients with MDS, especially in resource-limited centers where molecular testing is not currently a standard clinical practice.

Breast cancer is the most frequent cancer and the leading cause of cancer-related mortality in women in Uruguay. Recent therapeutic advances had led to important survival increments highlighting the importance of long-term complications in survivors such as second malignancies. Treatment related myelodysplastic syndromes and acute myeloid leukemias are associated with chemotherapy and radiotherapy exposure in the previous 5 to 10 years. The aim of this study was to establish cytopenia prevalence in patients with a history of breast cancer who received radiotherapy and/or chemotherapy up to 10 years ago. We carried out an observational cross sectional, descriptive, cohort study which included women with early-stage breast cancer treated at the Hospital de Clinicas Dr. Manuel Quintela's Breast Cancer Unit. We studied 45 patients with mean age at diagnosis of 57.7 years. Stage II was the most frequent stage followed closely by stage I, and the most common histological type was invasive ductal carcinoma, with the majority being ER-positive, PR-positive and HER2-negative. Three patients presented pure anemia (6.7%), two of them moderate and one mild. None other cytopenia were diagnosed. This study allowed us to know cytopenia prevalence among early stage breast cancer patients exposed to chemotherapy andorradiotherapy in the last ten years. Our results are inconcordance with international reports.

Introduction Myelodysplastic syndromes (MDS) are a heterogeneous group of neoplasms characterized by ineffective hematopoiesis, bone marrow failure, and progression to acute myeloid leukemia. According to the IPSS-R scoring system, they are divided into two major groups for treatment purposes: low-risk (≤3.5 points, LR-MDS) and high-risk (>3.5 points, HR-MDS). Currently, the only approved therapy for high-risk cases is hypomethylating agents, with a median overall survival of 16 months. Given the observed synergy and results with azacitidine and venetoclax (AZA + VEN) in acute myeloid leukemia and the unresolved need in this orphan disease, our objective was to describe the real-world experience in a Latin American cohort using AZA + VEN in HR-MDS patients, who currently have no effective treatment options. Methods Patients with HR-MDS from Argentina, Brazil, Colombia, Ecuador, Mexico, and Uruguay were retrospectively recruited from 2019 to 2023 and included in the Re-GLAM (Latin American MDS Registry). Inclusion criteria were: having HR-MDS with less than 20% blasts and having received at least one cycle of azacitidine with venetoclax. The treatment groups were: 1) HMA + VEN as first-line treatment with the goal of leading to a hematopoietic stem cell transplant (HSCT), and 2) HMA + VEN as second-line treatment. Response was defined using the 2006 IWG criteria, with response (R) being the sum of complete response(CR), partial response(PR), and stable disease(SD), and the rest being considered non-response (NR). Overall survival (OS) was defined from diagnosis to death or last follow-up, and leukemia-free survival (LFS) from the start of treatment to progression to leukemia. Results We recruited 49 MDS patients, 45 (91,8%) with primary MDS, and 34 (69.4%) were men. 98,0% (n=48) had an ECOG ≤2. According to the 2022 WHO classification, the majority had excess blasts type 1 (n=29, 59.2%), with all patients having an IPSS-R score >3.5. The median blasts in bone marrow aspirate was 11% (range;0-19). All received treatment with a hypomethylating agent (48 with azacitidine and 1 with decitabine) plus venetoclax. As first-line treatment in 34 patients (69.4%) and as second-line treatment in the remaining patients. Venetoclax ramp-up dosing was not used, and there were no episodes of tumor lysis syndrome. 95.7% (n=44) received a dose of 400mg, of which 20 adjusted the dose due to antifungal use. 65.3% (n=32) used venetoclax for 14 days. Sixteen patients (32.7%) reached HSCT with a median number of treatment cycles before HSCT of [median 2 (1-12)]. The median follow-up was 41 months (rango; 3-124months). At the last follow-up, 26patients (53,1%) had died. The median OS was 21,9 months (95% CI; 11,6-32,2). When OS was separated by treatment line, no significant difference was found (OS for first-line: 26.96 months (95% CI; 5,4-28,0) vs OS for second-line: 23.8 months (95% CI; 10,7-33,2), p=0.932. The overall response rate (ORR) in the first-line treatment was 67,6% [23/34] (CR 65,2% (15/23), PR 21,7% (5/23), and SD 13,0% (3/23). The median OS for those achieving CR was not achieved (NA) months (95% CI; NA-NA) vs NR:10.71months (95% CI;9.75-11.67), p<0.001. Patients who reached HSCT showed improved OS compared to those who did not (OS: NA months (95% CI; NA-NA) vs 13.11months (95% CI;13.04-30.4), p=0.040. The median LFS was NA months (95% CI NA-NA). The ORR in the second-line treatment was 60,0% [9/15] (CR 55,6% (5/9), PR 33,3% (3/9), and SD 11,1% (1/9)). The median OS for those achieving CR was NA months (95% CI; NA-NA) vs NR: 14.26 months (95% CI 7.84-20.68), p=0.115. The median LFS was 11.76 months (95% CI;7.97-15.56). Conclusion Our real-world evidence (RWE) study includes one of the longest follow-ups of AZA + VEN use in HR-MDS patients. These results suggest that the group that benefits most from the AZA + VEN combination is those who reach HSCT, as it improves OS. The group that does not reach HSCT has a better OS to that observed with azacitidine alone, but onlu in those patients who achieve a CR. No predictive factors of response to AZA + VEN were found, although myeloid mutations were not evaluated, which could potentially explain response probability as seen in other studies.

Myelodysplastic Syndromes (MDS) constitutes an heterogenous group of hematological malignancies. Reaching an accurate diagnosis, represents in an important number of cases, a major challenge that requires different diagnostic tools. In order to acknowledge the scope of access to those tools in our country, we performed a survey addressed to Uruguayan hematologists who care for MDS patients in their clinical practice. The survey was carried out in 2016 and 2019 among Uruguayan Hematology Society members. Response rate was 32.5% and 26.6% respectively. Access to bone marrow biopsy, cytogenetics, FISH and flow cytometry was accessible to more than 90% of physicians. Less than 10% of respondents were able to request next generation sequencing (NGS) studies and in that case, they have to send them abroad. IPSS and R-IPSS were the most frequently used risk scores. Support treatment such as growth factors and transfusions are widely accessible. Azacytidine and allogenic transplant are available as well. However, access to decitabine, lenalidomide and iron chelating drugs is scarce and there are no clinical trials to include patients who fail or do not respond to conventional treatments. This survey, carried out in two periods, describes the reality and its evolution in our country in terms of accessibility to diagnostic and therapeutic tools that can be extrapolated to other oncohematological pathologies. We were able to get to know our country reality regarding diagnostic and therapeutic tools for MDS patients. This, would represent an important input in order to design health strategies aiming to improve clinical care for our patients.

Background:Common variable immunodeficiency disorders (CVIDs), which are primary immunodeficiencies characterized by the failure of primary antibody production, typically present with recurrent bacterial infections, decreased antibody levels, autoimmune features, and rare atypical manifestations that can complicate diagnosis and management. Although most cases are sporadic, approximately 10% of the patients may have a family history of immunodeficiency. Genetic causes involving genes related to B-cell development and survival have been identified in only a small percentage of cases.Case presentation:We present the case of a family with two brothers who presented with mycosis fungoides as an exclusive symptom of a common variable immunodeficiency disorder (CVID). Whole-exome sequencing of the index patient revealed a pathogenic variant of the NFKB2 gene. Based on this diagnosis and re-evaluation of other family members, the father and brother were diagnosed with this rare immune and preneoplastic syndrome. All CVID-affected family members presented with mycosis fungoides as their only symptom, which is, to the best of our knowledge, the first case to be reported.Conclusion:This case highlights the importance of high-throughput sequencing techniques for the proper diagnosis and treatment of hereditary hematological disorders.

Background: The5 th (2022) edition of the WHO Classification for MDS recognizes MDS patients into two groups: MDS with defining genetic abnormalities and MDS morphologically defined. Further, the revised International Prognostic Scoring system (IPSS-R) assigns MDS patients into one of prognostic groups with distinct survival probabilities. However, both the IPSS-R and the 2022 WHO classification were developed based on data largely generated from patients in the high-income countries. There are limited data of how these systems perform in patients from developing and middle-income countries (LMIC). The primary objective of this study was to compare the performance of the two WHO classification: the revised 4 th (2016) and 5 th (2022) editions in IPSS-R defined Lower-Risk MDS Cohort of patients from LMIC in the GLAM registry. Methods: TheGlam Registry enrolls patients from 16 Latin-American countries, For this analysis, we selected Lower risk MDS (defined as IPSS <3.5) patients from Argentina, Brazil, Chile, Colombia, Mexico, Paraguay, and Uruguay. Patients with CMML and higher-Risk MDS were excluded. The study was conducted in compliance with local regulations, and all subjects signed inform consents. Descriptive statistics, Sankey Diagram, Kaplan Meier methods and the Confidential Interval for the 5-year survival probability were used to report the results. Overall survival (OS) was measured from time of diagnosis to last contact or death, and progression-free survival (PFS) was measured from time of diagnosis to disease progression, progression to acute myeloid leukemia (AML), or death. Results: A total of 223 LR-MDS patients were included in this analysis. Baseline characteristics and demographics are described in Table 1. Median age was 69 years, 47% were males, and 71% were non-Hispanic whites. The median blast count was 1% (range, 0-8%), and only 7% had therapy-related MDS. According to WHO-2016 edition, patients were classified as MDS-RS-SLD (n = 15 [6.72 %]); MDS-RS-MLD (n = 23 [10.3 %]); MDS-RS-T (n = 6 [2.7 %]), MDS-del(5q) (n = 15 [6.7 %]), MDS-SLD (n = 34 [15.2 %]), MDS-MLD (n = 116 [52 %]), MDS-EB1 (n = 11 [4.9 %]), MDS-EB2 (n = 0 [0 %]), and MDS-U (n = 3 [0.66 %]). According to WHO-2022 classification, subjects were classified as: MDS-del(5q) (n = 15 [6.7 %]), MDS-LB-SF3B1-RS (n = 40 [17.9% %]), MDS-biTP53 (n = 0 [0 %]), MDS-LB (n = 131 [58.7 %]), MDS-h (n = 27 [12.1 %]), MDS-IB1 (n = 10 [4.4 %]), MDS-IB2 (n = 0 [0 %]) and MDS-f (n = 0). Figure 1 represents the shifts in classification of patients between the 2016 and 2022 version. The 5-year survival probabilities (%) of MDS-SLD vs MDS-MLD (WHO-2016) was 62.5% (95CI 37.8-79.7) vs. 54.6% (95CI 39.9-65.6), and the 5-year PFS probabilities (%) for MDS-SLD vs MDS-MLD were 62.5% (95CI 37.8-79.7) vs 53.6% (95CI 39.9-65.6) respectively. There were no cases of biTP53-mutation among the 12.1% of patients who had testing for TP53. Three patients were re-classified from MDS-RS-MLD (WHO-2016) to MDS-LB (WHO-2022) because SF3B1 mutation was associated with complex karyotype, del(5q), del(7q) and/or TP53 monoallelic. Four patients with MDS-U (WHO-2016) were re-classified to MDS-LB (WHO-2022). MDS-LB category (WHO-2022) was a large and a very heterogeneous group with an OS and LFS of 5.2 years. Conclusions: Our study, to our knowledge, provides one of the first, if not the first, datasets from LMIC to describe characteristics of IPSS-R lower-risk MDS pts and their re-classification and corresponding survival according to the WHO 2016 and 2022 classifications. Limited availability of molecular analysis in real-life settings (e.g., TP53 mutations) highlights some of the challenges of using the 2022 WHO classification (as well as IPSS-M) LMIC. Understanding the epidemiology of MDS pts in LMIC is important especially as some of the newly approved agents for lower risk MDS are starting to be used in these countries.

El trasplante de progenitores hematopoyéticos (TPH) autólogo es una alternativa terapéutica para pacientes con mieloma múltiple y linfomas. Su éxito depende del número de células progenitoras adecuadamente movilizadas, cosechadas e infundidas. En los pacientes pobres movilizadores no se logra obtener un número adecuado de células con la estimulación clásica con factor estimulante de colonias de granulocitos (G-CSF). Con la incorporación de plerixafor se ha logrado superar esta dificultad y reducir el número de movilizaciones. El objetivo de nuestro trabajo es evaluar y describir la efectividad y seguridad de la movilización con G-CSF y plerixafor con leucoaféresis de gran volumen, en 71 pacientes pobres movilizadores para posterior autotrasplante. Esta estrategia logró en el 100% de los pacientes valores adecuados de CD34+ en periferia y en la cosecha de células madre se obtuvo una mediana de 4,6 (rango 3,4 - 6,2) x 106/kg de células CD34+. El injerto fue adecuado, con una mediana de recuperación post trasplante, de neutrófilos > 500/ μL de 11 días (rango 10 - 11), y de plaquetas > 20.000/ μL de 13 días (rango, 12 - 15). Con G-CSF y plerixafor se logró trasplantar a pacientes pobres movilizadores con buenos resultados.