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Myelodysplastic neoplasms (MDS) are characterized by cytopenia, morphologic dysplasia, and genetic abnormalities. Multiparameter flow cytometry (FCM) is recommended in the diagnostic work-up of suspected MDS, but alone is not sufficient to establish the diagnosis. Our aim was to investigate the diagnostic power of FCM in a heterogeneous population of patients with cytopenia, excluding cases with increased blast count. We analyzed bone marrow samples from 179 patients with cytopenia (58 MDS, 121 non-MDS) using a standardized 8-color FCM method. We evaluated the sensitivity, specificity, and accuracy of several simple diagnostic approaches, including Ogata score, extended Ogata score, the WHO and ELN iMDSFlow recommended \"3 aberrations in two cell compartments method,\" and the combination of the Ogata score and \"3 aberrations in two cell compartments method.\" The patients were followed until the diagnosis was confirmed, with a median follow-up of 2 months (range 0.2-27). The combination of Ogata score and \"3 aberrations in two cell compartments method\" achieved the highest diagnostic accuracy (78%) with sensitivity and specificity 61% and 86%, respectively. When using only the \"3 aberrations in two cell compartments method,\" the accuracy was 77% with a sensitivity of 72% and a specificity of 79%. The most frequently observed etiologies among the false positive cases were substrate deficiencies, inflammation/infection, or toxic effects. MDS can be excluded in all these cases after a thorough clinical evaluation and a relatively short follow-up. FCM remains an important but supplementary part in an integrated diagnostic process of MDS with low blasts. The combination of the Ogata score and the \"3 aberrations in two cell compartments method\" slightly improves accuracy compared to the detection of \"3 aberrations in two cell compartments method\" alone.

Hairy cell leukemia (HCL) is an indolent B-cell lymphoproliferative disease. Interferon-alpha (IFN-alpha) was the first successfully used drug in HCL; its favourable effect has been known since the early 1980s. However, currently the first-line treatment of the disease consists of purine nucleoside analogs. The aim of our study was to assess the efficacy of pegylated IFN-alpha in HCL patients treated with this drug at a single university center. We report the treatment characteristics and outcome of seven classical HCL patients treated with pegylated IFN-alpha at the Department of Internal Medicine and Oncology, Semmelweis University. As a result of pegylated interferon-alpha treatment, 3 of 7 patients (3/7) achieved an unconfirmed complete remission, 3 of 7 patients (3/7) achieved partial remission. One patient had stable disease while receiving pegylated IFN-alpha. Only mild adverse effects and no infectious complications were observed during our treatment. Our clinical data support that pegylated IFN-alpha in monotherapy is effective and safe even in elderly and frail HCL patients. It may also be a preferred therapeutic option in patients with profound immunosuppression and in patients with severe active infections.

Introduction: Hairy cell leukemia (HCL) is an indolent B-cell lymphoproliferative disease. BRAF V600E mutation is detected in nearly all classical HCL cases which offers the possibility of targeted therapy. Objective: The aim of our study was to assess the efficacy of low-dose vemurafenib as well as to assess the long term outcome of HCL patients treated with this drug at the Department of Internal Medicine and Oncology at Semmelweis University. Methods: We report on 10 patients with classical HCL treated with low-dose vemurafenib at our Department between 2013 and 2022. Results: As a result of fixed time low-dose vemurafenib treatment, 5 of 10 patients (5/10) achieved partial remission, 4 (4/10) had stable disease, and 1 (1/10) had MRD positivity. No patients achieved complete remission. The median progression-free survival was 28.5 months while the overall survival was 82 months. Conclusion: We confirm that low dose of vemurafenib is effective and safe in the vast majority of patients with HCL. This small-molecule oral treatment allows to gain valuable time—months or even years—before further, usually parenteral treatment options have to be given or before previous treatment has to be repeated. There are also promising data supporting the combination of vemurafenib with other drugs for the treatment of HCL patients which could provide even further possibility to bridge treatment.

Hairy cell leukaemia (HCL) is a rare B cell malignancy with an indolent course leading to pancytopaenia due to bone marrow infiltration. It has been proposed that HCL patients are at risk of developing a secondary malignancy, with a marked likelihood of the development of other hematologic malignancies including Hodgkin lymphoma and high-grade non-Hodgkin lymphomas. Here, we present the case of two patients who developed diffuse large B cell lymphoma after a long course of hairy cell leukaemia. In the case of the female patient, we report on the occurrence of a third malignant disease, which is very uncommon. With our case descriptions we contribute to the very small number of similar cases reported.

Despite remarkable improvements in the survival of pediatric acute lymphoblastic leukemia (ALL), sensitive detection and clinical management of central nervous system leukemia (CNSL) are still immensely challenging. Blast cells residing in the CNS but not circulating in the cerebrospinal fluid (CSF) remain undetected by current diagnostic methods, preventing a truly risk-adapted anti-leukemic treatment in this compartment. We examined the clinical applicability of the molecular marker microRNA (miR)-181a quantified in the cell-free CSF to evaluate the level of CNS involvement and to optimize patient stratification based on CNS status. Normalized copy number of miR-181a was longitudinally profiled using droplet digital PCR, and the results were compared with the degree of leukemic involvement of the CNS. After combining cytospin- and flow cytometry (FCM) data with miR-181a expression, we could stratify previously ambiguous cases and reclassify patients into a CNS-positive/miR-significant group (mean ± SE for miR-181a copies: 3300.70 ± 809.69) bearing remarkable infiltration as well as into CNS-minimal/miR-significant and CNS-minimal/miR-minimal groups differentiating putative, clinically significant occult CNSL cases (2503.50 ± 275.89 and 744.02 ± 86.81 copies, respectively, p = 1.13 × 10 –6 ). In summary, miR-181a expression is a promising biomarker for CNSL detection, facilitating the robust identification of patients who could benefit from intensified CNS-directed therapy.

Polycythemia indicates the pathological increase in the number of red blood cells and the rise of hematocrit values. Polyglobulia can be of primary or secondary origin, with the most common primary polycythemia being a myeloproliferative neoplasm, polycythemia vera. Polyglobulia patients may develop cardiovascular complications and thromboembolic events. The gold standard of first-line treatment in polycythemia vera is phlebotomy, which is indicated to keep the hematocrit value below 0.45. Until now the goal to be achieved in secondary polyglobulia has been similar. In secondary polyglobulia this rule of thumb needs to be re-evaluated as shown by the example of two patients suffering from different rare, genetically determined polyglobulias. In our article we present the case of these two patients and discuss the diagnostic and therapeutic principles to be applied in patients with rare, genetically determined polyglobulias. After completing the usual diagnostic algorithm for polyglobulia no cause could be identified in two of our male patients. Therefore, we set out to perform whole exome sequencing in both patients. Our analysis did not include copy number analysis. In Patient 1 the p.Ser179Pro variant in the gene was detected in the homozygous state, which is classified as likely pathogenic according to the ACMG guidelines. Homozygous mutations are implicated in Chuvash polycythemia. Segregation analysis was declined by the family. In Patient 2 the gene p.His306Gln variant was detected in the heterozygous form. The gene plays a role in pyruvate metabolism. Family screening did not detect this variant in healthy family members. We identified rare, possibly pathogenic genetic variants in two patients with polyglobulia and as a consequence of the genetic diagnosis we implemented individualized patient monitoring. We recommend the utilization of high-throughput genomic testing in cases with unexplained polyglobulia.

Abstract Objectives CD49f is an adhesion molecule present on malignant lymphoblasts in B-cell acute lymphoblastic leukemia; it is associated with a poor prognosis. CD49f expression has been proposed as a marker for measurable residual disease (MRD) marker, but this marker has yet to be implemented in clinical practice. Methods In this study, we used flow cytometry to detect CD49f expression by leukemic blasts in paired bone marrow and cerebrospinal fluid samples at diagnosis and bone marrow at day 15 of treatment. Results At diagnosis, 93% of bone marrow and 100% of cerebrospinal fluid lymphoblasts expressed CD49f. The intensity of CD49f expression statistically significantly increased during treatment (P < .001). In MRD-negative end-of-treatment samples, only a small population of hematogones expressed CD49f. Interestingly, the intensity of CD49f expression varied among the different groups of recurrent genetic abnormalities. The ETV6::RUNX1 fusion and ETV6::RUNX1 combined with the high hyperdiploid group were associated with increased expression, whereas the Philadelphia-like group showed low CD49f expression. The lower CD49f expression at diagnosis predicted a lower MRD rate at day 15 of treatment. Conclusions We concluded that CD49f can be used as an MRD marker and possible prognostic factor in B-cell acute lymphoblastic leukemia.

Myeloid sarcoma (MS) is a tumorous extramedullary proliferation of blast or blast equivalent cells (e.g., promonocytes or promyelocytes). The most frequent cutaneous presentation is often referred to as leukemia cutis (LC). These lesions, especially without the clinical context of a known bone marrow disease, pose a differential diagnostic challenge. In this retrospective multicenter clinico‐pathological study on 154 patients with MS or LC, 169 samples were analyzed by morphology, immunohistochemistry, and fluorescent in situ hybridization, and a subset by additional sequencing [ TP53 ]. The majority of cases were lysozyme positive (diffuse in 91% and focal in 5%), 51% showed diffuse and 6% focal expression of CD56, and IRF8 was strongly positive in 31% of the lesions. Lack of myeloperoxidase (MPO), CD117, and CD34 expression was observed in 27%, 39%, and 58%, respectively. PU.1 was positive in almost all instances (95%), but BRAF V600E was consistently negative. CD123 was diffusely (13%) or focally (25%) positive, which, in addition to frequent CD4 (73%) and CD56 expression, pointed to a phenotypic overlap with blastic plasmacytoid dendritic cell neoplasms. Survival analysis revealed that MS occurring at sanctuary sites (CNS, orbit, ovary, and testis) was characterized by excellent survival. Similarly to histiocytoses, there was a prognostic difference between isolated and multisystemic involvement by MS. Patients who underwent allogeneic hematopoietic stem cell transplantation showed significantly improved survival. In conclusion, this multicenter study suggests that most MS are of myelomonocytic/monoblastic origin, a high proportion of them are NPM1 mutated, and may lack expression of MPO and CD34. NPM1 mutation‐specific antibodies should be integrated into the diagnostic panels for MS or LC, while IRF8 and PU.1 are not recommended as they cannot distinguish MS from histiocytic neoplasms.

Central nervous system involvement is a rare complication of multiple myeloma with extremely poor prognosis as it usually fails to respond to therapy. We present 13 cases diagnosed at two centers in Budapest and review the current literature. The majority of our cases presented with high-risk features initially; two had plasma cell leukemia. Repeated genetic tests showed clonal evolution in 3 cases. Treatments varied according to the era, and efficacy was poor as generally reported in the literature. Only one patient is currently alive, with 3-month follow-up, and the patient responded to daratumumab-based treatment. Recent case reports show promising effectivity of pomalidomide and marizomib.