Translation, Cultural Adaptation, and Validation into Romanian of the Myeloproliferative Neoplasm Symptom Assessment Form-Total Symptom Score (MPN-SAF TSS or MPN-10) Questionnaire.

Background: Patients with myeloproliferative neoplasms (MPNs) experience a high disease-related symptom burden. A specific instrument to evaluate quality of life (QoL), i.e., the MPN Symptom Assessment Form Total Symptom Score (MPN-SAF TSS; MPN-10), was developed. We conducted the translation, cultural adaptation, and validation into Romanian of the MPN-10. Methods: We translated the MPN-10 and tested its psychometric properties. Results: We recruited 180 MPN patients: 66 polycythemia vera (36.67%), 61 essential thrombocythemia (33.89%), 51 primary and secondary myelofibrosis (SMF) (28.33%), and 2 MPN-unclassifiable (1.11%). The mean TSS was 19.51 ± 16.51 points. Fatigue, inactivity, and concentration problems were the most cumbersome symptoms. We detected scoring differences between MPN subtypes regarding weight loss (p < 0.001), fatigue (p = 0.006), early satiety (p = 0.007), night sweats (p = 0.047), pruritus (p = 0.05), and TSS (p = 0.021). There were strong positive associations between TSS and inactivity, fatigue, and concentration problems, and moderate negative correlations between QoL scores and all MPN-10 items. Cronbach's α internal consistency coefficient was 0.855. The Kaiser-Meyer-Olkin construct validity test result was 0.870 and the Bartlett Sphericity Test was significant (p < 0.001). Symptom scores were loaded into one single factor according to the exploratory factor analysis. Conclusions: The Romanian MPN-10 version displayed excellent psychometric properties and is a reliable instrument for assessing symptom burden and QoL in Romanian MPN patients.

Complications of Brentuximab Therapy in Patients with Hodgkin's Lymphoma and Concurrent Autoimmune Pathology-A Case Series.

Background: Brentuximab Vedotin (BV) has revolutionized the treatment landscape for Hodgkin's lymphoma, yet its effects on pre-existing autoimmune disorders remain elusive. Methods: Here, we present four cases of patients with concurrent autoimmune conditions-Crohn's disease, vitiligo, type I diabetes, and minimal change disease-undergoing BV therapy for Hodgkin's lymphoma. The patients were treated with A-AVD instead of ABVD due to advanced-stage disease with high IPI scores. Results: Our findings reveal the surprising and complex interplay between BV exposure and autoimmune manifestations, highlighting the need for multidisciplinary collaboration in patient management. Notably, the exacerbation of autoimmune symptoms was observed in the first three cases where T-cell-mediated autoimmunity predominated. Additionally, BV exposure precipitated autoimmune thrombocytopenia in the vitiligo patient, underscoring the profound disruptions in immune regulation. Conversely, in the minimal change disease case, a disease characterized by a blend of B- and T-cell-mediated immunity, the outcome was favorable. Conclusions: This paper underscores the critical importance of vigilance toward autoimmune flare-ups induced by BV in patients with concurrent autoimmune conditions, offering insights for tailored patient care.

Real-World Clinical Outcomes and Adverse Events in Patients with Chronic Lymphocytic Leukemia Treated with Ibrutinib: A Single-Center Retrospective Study.

Background and Objectives: The treatment of chronic lymphocytic leukemia (CLL) has acquired new targeted therapies. In clinical trials, ibrutinib improved outcomes safely. Real-world data called for a reappraisal of ibrutinib strategies. We report on a single center's experience with ibrutinib monotherapy, aiming to explore the outcomes, tolerability, and prognosis of CLL patients in routine clinical practice. Materials and Methods: Data were collected from all CLL patients treated with ibrutinib at Fundeni Clinical Institute, Bucharest, Romania, between January 2016 and June 2021. Results: A total of one hundred twenty-three CLL adult patients were treated with ibrutinib. Of the patients, 87% had relapsed/refractory CLL. The median age at ibrutinib initiation was 65 years; 44.7% of patients were staged Rai III/IV. At 32-month median follow-up, the median progression-free survival (PFS) was 50 months, the overall survival (OS) was not reached, and the overall response rate (ORR) was 86.2%. The age or number of previous therapies did not impact outcomes or tolerability. An Eastern Cooperative Oncology Group performance status (ECOG PS) score ≥ 2 and shorter time from initiation of last therapy (TILT) before ibrutinib predicted inferior PFS. Baseline characteristics had no impact on the OS except for TILT in R/R CLL patients. Drug-related adverse events (AEs) of any grade and grade ≥ 3 AEs were reported in 82.1% and 30.9% of the patients, respectively. Infections were the most common AEs (29.3%). Drug discontinuation was permanent in 43.9% of patients, mainly due to disease progression (17.1%) and toxicity (8.9%). Patients with a Cumulative Illness Rating Scale (CIRS) score ≥ 6 had a higher risk for toxicity-related discontinuation. An ECOG PS ≥ 2 predicted an increased rate of permanent discontinuation and grade ≥ 3 AEs. Conclusions: The outcomes of this study align with the results from ibrutinib clinical trials. Our study demonstrated that poor patient fitness, early relapse before ibrutinib, and permanent ibrutinib discontinuation are essential outcome determinants. Patient comorbidity burden and fitness were significant predictors for ibrutinib intolerance.

Essential Thrombocythemia: One-Center Data in a Changing Disease.

Introduction: Essential thrombocythemia is a chronic myeloproliferative neoplasm associated with thrombo-hemorrhagic events and the progression to myelofibrosis or acute myeloid leukemia. The purpose of this article is to present real-world data on ET cases diagnosed and managed between 1998 and 2020 in the largest, tertiary hematology reference center in Romania and to evaluate the impact of thrombotic events on survival. Methods: A real-world, retrospective cohort-type study was conducted. We collected and statistically analyzed data from 168 patients who met the 2016 WHO diagnostic criteria for ET and who were managed between 1998 and 2020 in our center. Results: The median age at diagnosis of ET was 51.8 years, with a female predominance (66.07%). The JAK2V617F mutation was detected in 60.71% of patients. Leukocytosis at diagnosis was associated with a higher risk of thrombosis, and JAK2V617F-positive cases exhibited a 1.5-fold higher risk of developing thrombotic events. The average survival in ET with major thrombosis was 14.5 years versus 20.6 years in ET cases without major thrombosis. Other predictors of survival were high-risk IPSET score and age >60 years. Conclusions: Romanian patients diagnosed with ET are generally younger than 60 years and are predominantly female. The occurrence of thrombotic events was influenced by gender, leukocyte count at diagnosis and JAK2V617F positivity. Survival was impacted by age, the presence of JAK2V617F mutation, hypertension, major thrombotic complications and IPSET score. Notably, these findings warrant careful interpretation and further confirmation in the setting of prospective studies.

Littoral cell angioma of the spleen--a surprising cause of anemia.

Littoral cell angioma is a rare tumor of the spleen, usually being considered benign and typically discovered incidentally. There are three different modalities of presentation: tumoral splenomegaly, long-standing iron deficient anemia or thrombocytopenia due to hypersplenism. However, some of its manifestations could generate the suspicion of a lymphoma or other more serious condition. We present the case of a 46-year-old man with splenomegaly and iron deficiency anemia. The tumor affected the whole spleen, which was surgically removed. The histopathological examination, together with immunophenotyping, established the diagnosis. Six months after the procedure, the patient is in very good condition. Several differential diagnoses were discussed, as well as the prognostic factors. The case illustrates a rare cause of anemia and the importance of pathology in uncovering such unusual causes for this.

"In situ" mantle cell lymphoma associated with hyaline-vascular Castleman disease.

Mantle cell lymphoma (MCL) is a very rare non-Hodgkin B-cell lymphoma, with an aggressive clinical course and poor response to conventional therapy. Few cases of "in situ" MCL were reported in the last years. We present the case of a 31-year-old woman with a unique cervical lymphadenopathy. The morphologic findings are of hyaline-vascular Castleman disease (HV-CD). Immunohistochemical stain for cyclin D1 detects scattered cyclin D1+ cells within the mantle zones of few reactive-appearing lymphoid follicles, corresponding to the definition of "in situ" MCL. We also performed cyclin D1 in other 27 cases of CD (13 HV-CD and 14 plasma-cell CD) but the reported case was the only who associated "in situ" MCL. An adequate immunohistochemical panel, including a marker for cyclin D1, is required to differentiate this neoplasm from follicular hyperplasia. From our knowledge, this is the first reported case of "in situ" MCL associated with HV-CD.

Clinical and hematological aspects of chronic myelomonocytic leukemia. Study on 20 cases from a single center from Romania.

Chronic myelomonocytic leukemia (CMML) has long been recognized as a disorder with both myelodysplastic and myeloproliferative characteristics, some patients showing clinical and morphological features resembling myelodysplastic syndrome (MDS) especially refractory anemia with excess of blasts (RAEB) with monocytosis, and others leukocytosis with neutrophilia, monocytosis and splenomegaly resembling myeloproliferative syndrome (MPS). The intrinsec differences determined at first the separation of CMML in two forms, one named "dysplastic", more similar with RAEB, and the other "proliferative", closer to chronic myeloid leukemia and then included by the recent WHO classification into a separate new created group--myelodysplastic diseases (MDD)/chronic myeloproliferative diseases (CMPD). The aim of this study was the analysis of some features of 20 cases of CMML, with emphasis on the differences between the two forms. The proliferative form of CMML differed from the dysplastic one by greater white blood cells and neutrophils counts (P < 0.001), a more important monocytosis in periferal blood (P = 0.07), and by the size and frequency of splenomegaly (P = 0.03). The sex and age of the patients, the frequency of the general symptoms, the frequency of the general symptoms and signs and that of infections, the hemoglobin and hematocrit values, the platelet counts, the percentage of myeloblasts and monocytes in bone marrow, the frequency of dysplastic traits, the percentage of reticulocytes and the modified Bournemouth prognostic index were not significantly different. These findings support the concept that CMML is a heterogeneous "overlap" syndrome between MDS and CMPD.