Hematology Clinic Research Articles

P04 A vexing case of polymyalgia rheumatica

Abstract Introduction VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a recently described autoinflammatory condition characterised by somatic mutations in the UBA1 gene, resulting in significant morbidity. Disease presentation can mimic several rheumatological conditions, delaying diagnosis and appropriate management. This case report presents the clinical course of a patient with a complex history of musculoskeletal symptoms and systemic inflammation, first diagnosed with polymyalgia rheumatica (PMR), who was later identified as having VEXAS syndrome almost six years after first referral to the rheumatology clinic. It illustrates the importance of considering rare autoinflammatory conditions in patients with atypical presentations of common rheumatological disorders. Case description A 76-year-old gentleman was referred from the haematology clinic where he had undergone investigation for pancytopenia and raised inflammatory markers. Initial investigations under the haematology team revealed normal CT chest, abdomen and pelvis, unremarkable bone marrow biopsy and cytogenetics. He presented with muscle stiffness and proximal limb girdle pain. Additional symptoms included fatigue and a diffuse non-specific erythematous rash. There was no significant past medical history and he was previously very fit and active. Rheumatology investigations were normal, apart from persistently elevated inflammatory markers (ESR 86 mm/h and CRP 70 mg/L). A diagnosis of polymyalgia rheumatica was made and prednisolone 15 mg was started. Although he initially had a good response to this, he continued to experience significant inflammatory and constitutional symptoms. These included small joint polyarthritis, night sweats and weight loss. He was pancytopenic with associated reduced exercise tolerance, requiring transfusions and erythropoietin. To exclude other differentials, a repeat bone marrow biopsy was performed. This revealed dysplasia likely secondary to underlying inflammation, although no clonal abnormalities or vacuoles were detected. MRI right hand showed synovitis, and he was therefore treated for myalgic-onset rheumatoid arthritis. Prednisolone dose was increased temporarily and methotrexate was added, resulting in temporary improvement of his ESR 16 mm/h and CRP 25 mg/L. The patient continued to have ongoing constitutional symptoms and developed new ataxia. Further investigations, including MRI head, gastroscopy and Whipple’s PCR were all normal. Repeat CT chest, abdomen and pelvis and PET-CT were unremarkable. His symptoms and inflammatory markers were responsive to steroids. Given his symptoms and macrocytosis, he was tested for ubiquitin-activating enzyme UBA1 gene which was positive, confirming the diagnosis of VEXAS syndrome. Methotrexate was stopped due to worsening cytopenia, prednisolone continued and tocilizumab started. He showed significant improvement in pancytopenia and symptoms following initiation of tocilizumab. Discussion VEXAS is characterised by somatic mutations in the UBA1 gene; its pathogenesis leads to malfunctioning methionine-41, an enzyme that initiates ubiquitylation. This leads to increased activation of innate immune pathways and induces systemic inflammation, manifesting in a variable clinical presentation. This variability makes the diagnosis challenging and leads to a median diagnostic delay of 5.5 years, similar to our patient’s six-year delay. Our patient was initially managed as PMR due to his clinical presentation and lack of an obvious alternative diagnosis. This misdiagnosis is not unique. Often, patients later diagnosed with VEXAS are first managed as either inflammatory conditions, notably polychondritis, vasculitis or Sweet’s syndrome, or myelodysplastic syndrome (MDS). VEXAS is hallmarked by haematological dysfunction as much as it is by inflammatory features. In fact, our patient’s first signs included a mild cytopenia which later developed into a progressive macrocytic anaemia. This is classical of VEXAS. Other haematological manifestations include thrombotic events and MDS, with minimal response to EPO-stimulating agents as seen here. His ongoing deterioration triggered an alternative diagnosis to be sought. VEXAS is unusual as an autoinflammatory disease: its causative mechanism is a somatic mutation acquired later in life. Its diagnosis can be confirmed by inactivation of the x-linked UBA1 gene. This case highlights the need for UBA1 testing when dealing with an unexplained inflammatory phenotype, especially in men with cytopenia, multiorgan autoinflammation or MDS-like features. VEXAS presents a management challenge. The term ‘haeamatoinflammatory’ has been created to reflect its unique nature, warranting input from both specialist teams as well as the wider MDT. Key learning points • VEXAS should be considered as a differential when dealing with unexplained inflammatory symptoms, especially in men, multiorgan autoinflammation, vasculitis and/or MDS-like features. • VEXAS is often progressive and transfusion-dependence is associated with a poorer prognosis. A macrocytic anaemia is a prominent feature of the condition. • The absence or low proportion of vacuoles in bone marrow should not prevent us from testing for VEXAS if clinically indicated. • No established protocols for VEXAS yet exist. Haematological management is supportive. Anti-inflammatory treatment is based on collective observed evidence, including the use of tocilizumbab (anti-IL6) and janus kinase (JAK) inhibitors. Allogenic haemopoietic stem cell transplantation has been successful in few patients and may represent an option for patients with severe disease.

Quality of Life and Symptoms of Hospitalized Hematological Cancer Patients

Patients with hematological malignancies undergo intensive treatment and prolonged hospitalization, thus having a variety of physical and psychosocial symptoms and worse quality of life (QOL). This study aimed to assess the QOL and investigate the symptoms of hospitalized hematological cancer patients. A cross-sectional study was conducted in the hematology clinics and day units of two general hospitals of Heraklion, Crete. Adult patients with hematological malignancy and an adequate understanding of the Greek language participated. A demographic questionnaire, the European Organization for Research and Treatment for Cancer quality assessment questionnaire (EORTC QLQ-C30), and the MD Anderson Symptom Inventory (MDASI) were used. The sample consisted of 120 patients—42.5% were women, with a mean age of 65.6 years. The mean time from diagnosis was 33 months. The global health status of QoL had an average value of 47.1. The highest levels of QOL were found in the subscale of cognitive function (72.8) and the lowest in the role function (46.1). For the EORTC QLQ-C30 symptoms scale, the lowest score was found in nausea-vomiting (11.0) and the highest in fatigue (59.1). In the MDASI, in part I (core symptoms), higher levels but also medium intensities were reported at fatigue (78.3%, mean 3.5), drowsiness (65.0, mean 3.3), and distress (65.8%, mean 2.8). In part II, enjoyment of life (85.8%, mean 5.1) had the highest, and relation with other people (67.5%, mean 3.7) had the lowest scores. The increase in the severity of the core symptoms (part I) was related to females (rho = 0.193, p <0.05) and comorbidities (rho = 0.220, p < 0.05). It was also associated with a significant decrease in all functional domains and increased fatigue (rho = 0.571, p < 0.05) in the EORTC QLQ-C30 questionnaire. The increased global health status was related to males (rho = −0.185, p < 0.05) and physical functioning with younger age (rho = −0.331, p < 0.05), higher education (rho = 0.239, p < 0.05), fewer months from diagnosis (rho = −0.199, p < 0.05), and low comorbidity (rho = −0.209, p < 0.05). Finally, multiple linear regression analysis revealed that the total average symptom score of the MDASI was the most significant factor influencing the global health status of the EORTC QLQ-C30 (β = −4.91, p < 0.001). The increased global health status of the EORTC QLQ C30 was not significantly related (p > 0.05) to the social characteristics of the patients, such as education or employment, which requires further validation. The QoL of hematological cancer patients significantly decreases during treatments due to a considerable number of symptoms that must be taken into consideration for high-quality, individualized care.

Ivosidenib (Tibsovo)

We recommend that Tibsovo in combination with azacitidine be reimbursed by public drug plans for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) with an IDH1 R132 mutation who are not eligible to receive intensive induction chemotherapy, if certain conditions are met. Tibsovo in combination with azacitidine should only be covered to treat adult patients with newly diagnosed AML with an IDH1 R132 mutation who are considered ineligible for standard intensive induction chemotherapy and are aged at least 75 years; have an Eastern Cooperative Oncology Group (ECOG) performance status of 2; have severe organ dysfunction in the heart, lungs, kidneys, or liver; and/or have any other comorbidity judged to be incompatible with intensive induction chemotherapy. Tibsovo in combination with azacitidine should only be reimbursed if prescribed by clinicians with expertise in managing patients with AML in a specialized hematology or oncology clinic, and the treatment should be supervised and delivered in institutions with expertise in systemic therapy delivery. The total drug cost of ivosidenib plus azacitidine should not exceed that of venetoclax plus azacitidine. Lastly, it must be feasible to test patients for IDH1 R132

Candidemia in Pediatric-Clinic: Frequency of Occurrence, Candida Species, Antifungal Susceptibilities, and Effects on Mortality (2020-2024).

Objective: Invasive candidiasis is defined as an important infection that increases the duration of patients' hospital stay, costs, mortality and morbidity. In this study, we aimed to investigate the frequency of candidiasis in blood cultures of pediatric hematology patients, Candida species, antifungal susceptibilities, and their effects on mortality. Materials and Methods: Patients with Candida growth in their blood cultures at follow-up in the pediatric hematology clinic of our hospital between 2020 and 2024 were included in the study. Age, gender, primary diseases and risk levels, subtypes and antifungal susceptibilities of Candida grown in blood cultures, the presence of neutropenia in patients, the antifungals used for prophylaxis and treatment, the duration of infection, other bacteria grown additionally during the fungal infection period, the local infection source and the patients' discharge status were obtained from medical records. These constituted the study data. Results: Blood cultures were requested for 594 patients from the Pediatric hematology Clinic, and Candida was grown in only 37 (6.7%) of them. A total of 43.2% of them were the Candida parapsilosis complex, 29.7% were Candida albicans and 8.1% were the Candida haemulonii complex. Antifungal susceptibilities were over 90% for anidulafungin, micafungin, caspofungin, posaconazole, itraconazole and amphotericin B, followed by 86.7% for fluconazole and 84.4% for voriconazole. The mean age of the patient group was 6.8 years, 50.5% of whom were female and 40.5% of whom were male. The Candida infections developed on the 12.1th day of the neutropenia process on average. The mean invasive Candida infection period was 7 days. A total of 18.9% had a second bacterial infection and 13.5% had a local infection. A total of 51.4% had a single antifungal, 18.9% had two antifungals and 2.1% had more than two antifungals. A total of 35.1% of the patients with invasive candidiasis died. The primary diagnosis of the disease, Patient risk level, and the female gender were important factors affetting mortality. Conclusions: In a pediatric hematology clinic, the non-albicans group in invasive candidiasis infections was notable, with the C. parapsilosis complex occurring most frequently. There was still a high sensitivity to echinocandin antifungals and a decreased sensitivity to triazoles. It was found that the factor of the clinical diagnosis, being in the high-risk group and being female had significant effects on the survival rate of patients with candidiasis infections.

Prescribing Hydroxyurea in Sickle Cell Disease Patients: The Pattern and Association with Co-Prescribed Medications Used to Manage the Disease Complications.

Background and Objectives: Hydroxyurea (HU) is an effective medication used to reduce the frequency of painful crises associated with sickle cell disease (SCD). However, data describing its prevalence among SCD patients in the Eastern Region of Saudi Arabia are scarce. This is a multi-center, retrospective, cross-sectional study that aims to investigate the pattern of prescribing HU in SCD patients and to determine the association between prescribing HU and other co-prescribed medications used to manage SCD complications. Methods: Data were collected from patients who visited the hematology clinics of Al-Qatif Central Hospital (QCH) and King Fahad Hospital in Hofuf (KFHH) between June 2021 to May 2023. The data included demographics, prescribed medications, and recent laboratory test results, all of which were collected from patients' medical records. Descriptive statistics were utilized to assess the difference between HU users vs. non-users. A binary logistic regression model was used to determine the association between prescribing HU and co-prescribed medications used to manage SCD complications. The results are presented as the odds ratio (OR) and 95% confidence interval (95% CI). Results: This study included 2816 SCD patients with a 56% prevalence of HU prescription. HU was prescribed for young age groups more often compared to old age group patients. Young males were more likely to be prescribed with HU compared to females, and it becomes dominant in females after the age of 36. HU users were more likely to have paracetamol (69% vs. 53%, OR = 1.9, 95% CI 1.6-2.2), NSAIDs (50% vs. 35%, OR = 1.7, 95% CI 1.5-2), and opioids (41% vs. 37%, OR = 1.3, 95% CI 1.1-1.6) co-prescribed, and less often to have laxatives (8% vs. 5%, OR = 0.66, 95% CI 0.48-0.9) and anticoagulants (22% vs. 15%, OR = 0.56, 95% CI 0.46-0.68) co-prescribed compared to non-users. Conclusions: The pattern of prescribing HU, supported by the association findings, raises concerns about patients' compliance and adherence to HU therapy. Early health education, specifically to young female SCD patients, is warranted to increase the success rate of HU therapy.

The “flipped visit”: an innovative method to improve medical student self-efficacy through a structured approach in clinic

BackgroundSpecialty clinics can be challenging for students on the internal medicine clerkship. They often lack the specialized knowledge necessary to fully engage in the clinic and may be pushed into an observational role, rather than being afforded meaningful opportunities. These peripheral roles undermine self-efficacy, and, therefore, education and interest. We sought to improve self-efficacy of students attending non-malignant hematology clinic, as well as to enhance interest in hematology and internal medicine.MethodsWe developed a flipped visit model analogous to the flipped classroom. Students each received pre-readings accompanied and pre-assigned cases with delineated reasons for referral and learning objectives. This model allowed students to prepare the hematology content for visits prior to arrival and then focus their time in clinic on executing visits. Participating students completed pre- and post-clinic surveys. These surveys covered core concepts in self-efficacy and interest in hematology and internal medicine on a five-point Likert scale.ResultsOf 103 students attending hematology clinic, 38 students (37%) opted to participate. Two of the 38 did not complete the post-clinic survey. Students had a statistically significant increase in four of six measures of self-efficacy: evaluation of research relevant to patient care and practicing cost-effective care (p = 0.008 and 0.001, respectively); and creation of a differential diagnosis and treatment plan specific to hematology (both p < 0.001). While pre-clinic student responses expressed interest in more exposure to hematology or a possible career in hematology or internal medicine, this was not changed post-clinic. When comparing their experience to other clinics, 75% and 71% students rated hematology clinic slightly or much better than other medicine clinics and non-medicine clinics, respectively. The flipped visit improved self-efficacy both specific to hematology and more generally. While students rated the experience more highly than other clinics, there was no impact on career interest in hematology or internal medicine.ConclusionA flipped visit approach to incorporating medical students into hematology clinic that included pre-assigned cases and readings improved self-efficacy and was preferred by students. They may be adopted easily in other ambulatory education settings.

Process improvements related to new patient scheduling.

26 Background: With over 530 physicians across 280 locations, the new patient time to first appointment varied across the state, with results ranging from 1 to 33 average days to schedule. Beginning in January 2021, a new patient scheduling model was developed to improve access to care and the patient experience. A new patient scheduling model was developed. The program was structured to support both on site and remote scheduling. Methods: Provider scheduling cards detailing physician preferences for scheduling, required records and prioritization for the type of diseases seen was implemented. Physicians were required to designate new patient time slots in their clinics tied to new patient volume trends. New patient scheduling workflows and required record guidelines were standardized and revised. Reporting and tracking metrics were created – average days to schedule, average days to appointment, referral fulfillment rate, referral to appointment ratio, true cancellation rate. Physicians were eligible to participate in a yearly bonus if time to first appointment goals were met. Utilized Virtual and in-person APPs provided benign hematology consults to address capacity constraints. Results: New patient true cancellation rates decreased from 9.84% to 5.22% resulting in capture of over 800 patients a month. There was a 56% increase in patient retention with a 138% increase in referral volume. The Practice realized a 69% reduction in average days to schedule from 9 to 3 days. The average time to first appointments improved from 23 to 14 days; a 38% decrease. Conclusions: With increasing numbers of new cancer patients, increasing numbers of cancer survivors and shortages of medical oncologists, it is essential to maintain access to timely cancer care. New models helped improve patient experience and practice retention of new cancer patients, by focusing on administrative staff to implement these programs. APP benign hematology clinics freed up physician time for new cancer patient consults. Physician support was obtained with education, frequent outreach, and financial incentives. 2021 Q1 2021 Q2 2021 Q3 2021 Q4 2022 Q1 2022 Q2 2022 Q3 2022 Q4 2023 Q1 2023 Q2 2023 Q3 2023 Q4 2024 Q1 Referral Volume 44,305 54,379 57,282 57,475 67,890 75,111 79,281 75,843 85,419 91,811 94,286 88,396 100,115 Avg. Days to Scheduled 9.1 6.9 5.4 6.2 5.8 4.9 3.9 4.0 3.7 4.0 3.8 3.6 3.3 Avg. Days to Appointment 22.4 24.3 23.3 22.9 20.9 21.8 20.0 19.2 17.0 17.5 17.1 16.7 14.9

Antibiotic Lock Therapy for Port Catheter-Related Infections of Children with Acute Leukemia.

Port catheters facilitate the administration of chemotherapy, antibiotics, blood products, fluid, and parenteral nutrition to pediatric patients with hematological malignancies. However, as its use has become widespread, local and systemic, catheter-related infections have emerged as important causes of morbidity and mortality. In our study, we aimed to evaluate the success of antibiotic lock therapy in port catheter-related infections of pediatric patients followed up with acute leukemia. Port catheter cultures taken from a total of 182 pediatric patients with acute lymphoblastic/myeloblastic leukemia who were followed up at Ankara City Hospital Pediatric Hematology Clinic between August 2019 and August 2023 were evaluated retrospectively. Bacterial growth was identified in 739 port catheter culture specimens of 182 patients. Closure or removal of the port was required in 91, and removal of the port catheters in 49 patients due to port catheter-related infections. Antibiotic lock therapy was started in 56 patients with bacterial growth in the port catheter. With antibiotic lock therapy, port catheter-related infections of 42 patients were eradicated, and their catheters began to be used again. As a result, the port catheter-related infections of 42 of 56 (75%) patients whose ports were closed and also received systemic antibiotic therapy were eradicated, and no infection recurrence was observed. Adding antibiotic lock therapy to systemic antibiotics in pediatric patients may be beneficial in terms of catheter salvage.

The effects of spiritual wellbeing on life satisfaction in hematologic cancer patients aged 65 and older in Turkey: mediating role of hope.

The mediating role of hope in the effects of spiritual wellbeing on life satisfaction in elderly haematologic cancer patients in Turkey was investigated in the present study. The study was conducted in a descriptive, cross-sectional and correlational design. The study was conducted with 150 patients aged 65 and older who were diagnosed with haematologic cancer and who were referred to a university hospital haematology clinic and outpatient clinic. Research data were collected with Descriptive Information Form, Dispositional Hope Scale (DHS), Spiritual Well-being Scale (FACIT-Sp-12) and Satisfaction with Life Scale (SWLS). FACIT-Sp-12 score was 37.25 ± 7.29; DHS score was 40.42 ± 8.29, SWLS score was 16.24 ± 8.79. FACIT-Sp-12 (β = 0.668) and DHS (β = 0.226) were found to affect SWLS positively. In terms of the effect of FACIT-Sp-12 on SWLS, DHS has a mediating role and makes the positive effect of FACIT-Sp-12 on SWLS stronger (β = 0.771). Spiritual wellbeing levels of the participants in our study were found to be high, while their levels of satisfaction with life and hope were found to be moderate. It was also concluded that spiritual wellbeing had a direct effect on satisfaction with life and an indirect effect through the mediating role of hope.

Understanding the physical literacy development of 8- to 12-year-old children living with chronic medical conditions: A comprehensive, mixed methods inquiry.

Physical literacy is a concept used to describe the combined physical, affective and cognitive capacities facilitating an active lifestyle. Physical activity participation is essential for children living with chronic medical conditions, but knowledge of physical literacy among this group is scarce. An explanatory, sequential mixed methods design was used to comprehensively describe the physical literacies of children with chronic medical conditions (CMCs). Participants were recruited from paediatric cardiology, respirology/cystic fibrosis, neurology, haematology and endocrinology outpatient clinics. All participants completed the Canadian Assessment of Physical Literacy (2nd Edition), and those with higher and lower scores were invited to a semi-structured interview. A deductive-inductive thematic analysis was applied using Margaret Whitehead's conceptualization of physical literacy. Using normative strata, 80.0% of the 99 children assessed (mean age = 9.97 ± 1.3years, 48% girls) were considered beginning or progressing in their overall physical literacy (mean score = 56.5 ± 13.8/100). Meanwhile, physical literacy informed participants' approach to new, active experiences and may have contributed to a strong sense of self. There was a significant difference between endocrinology and haematology patients on total physical literacy score (p = 0.03) but not domain scores. Participants scored high on motivation/confidence (mean = 22.9 ± 5.0/30) but obtained low physical competence (mean = 11.8 ± 5.6/30) and daily behaviour scores (n = 72, mean = 15.5 ± 7.1/30). Main themes represent salient experiences of children with CMCs within the domains of physical literacy, including their need to evaluate active contexts, self-regulate activity intensity and manage physical limitations. Children with CMCs can achieve recommended levels of physical literacy without meeting normative standards for physical competence. Participants would benefit from a physical literacy intervention that targets the development of bodily self-regulation skills and risk evaluation in active settings.

The investigation of janus kinase 2 and calreticulin mutations in patients with essential thrombocytosis

Aims: The aims of this study were to investigate the frequency of Janus Kinase 2 (JAK2) and calreticulin (CALR) mutations in patients with essential thrombocytosis (ET) and primary myelofibrosis (PMF) and to compare the data of each group with JAK2 and CALR mutations (+) and (-). Methods: The research group consisted of 80 patients with chronic myeloproliferative disease (CMPD) followed in Gazi University Hospital of Medical Faculty, Hematology Clinic. Results: Of the patients included in the study, 66.2% had ET and 33.8% had PMF. JAK2 mutation (+) was detected in 60% and CALR mutation (+) was found in 22.5% of the patients. JAK2 mutation (+) was detected in 60.4% of patients with ET and 59.3% of patients with PMF. In JAK2 (-) patients, CALR was detected as (+) in 11 patients (52.4%) with ET and 7 patients (63.6%) with PMF. Conclusion: Studies in the literature have shown that the incidence of CALR mutations in patients with CMPD is between 28% and 80% and that the mutation is mostly seen in patients with ET. As a result of our study, it was concluded that the laboratory findings of patients with CALR mutations (+) were similar to those in the literature and were more common in women and ET patients.

The Experience of Timisoara Hematology Clinic on the Management of Aggressive Non-Hodgkin Lymphoma Patients

Objectives. One of the most prevalent types of malignant lymphoproliferative disorders is non-Hodgkin lymphoma (NHL), which has shown an increased frequency worldwide of roughly 168% since 1975, coinciding with a decline in the age at diagnosis. Despite a ten-year improvement in overall survival, NHL accounts for approximately 3% of all cancer-related deaths. Delays in diagnosis and the emergence of related comorbidities are caused by the diverse symptomatology and symptoms associated with NHL. Thus, the purpose of this study was to assess patients treated at Timisoara's Clinical Emergency Municipal Hospital who had been diagnosed with aggressive HNL. Material and methods. This cross-sectional study comprised 76 patients diagnosed with aggressive NHL between January 2020 and June 2023 who were admitted to Timisoara's Clinical Emergency Municipal Hospital. Biopsy along with histopathologic examination served as the basis for the diagnosis. As part of the first assessment, bone marrow biopsy and imaging studies (PET/CT) were carried out in addition to laboratory tests. The NHL was staged using the Ann Arbour classification. The present protocols were followed in the establishment of the treatment. PET/CT was used to assess the response to treatment. Results. In this study cohort 72% were stage 4 of NHL at the diagnosis, 16% were stage 3, 5% were stage 2, while only 2% were stage 1. B symptoms were present in 69% of cases. In patients with 4th stage of NHL, bone marrow represents the most frequent extranodal site. 57 patients finished minimum a complete chemotherapy line, from which 90% of the patients had complete (63%) or partial (24%) remission after first-line treatment. Conclusion. The importance of this study was to emphasize the heterogeneity of NHL and to evaluate the treatment response and survivance of aggressive NHL patients.

Association between immune system parameter and clinical characteristics among patients with solid cancer

BACKGROUND Lymphopenia has been reported to be a major predictor of chemotherapy-related toxicity. This study aimed to investigate the correlation between neutrophils, lymphocytes, CD4, and CD8 in solid cancer patients and cancer clinical characteristics. METHODS This was a cross-sectional study of patients who will undergo chemotherapy at the Hematology and Medical Oncology Clinic, Cipto Mangunkusumo Hospital, from June to September 2023. Clinical characteristics, CD4 and CD8 levels, and neutrophil and lymphocyte counts were assessed at the first visit. A comparative test was carried out on the patients’ average CD4, CD8, neutrophil, and lymphocyte counts. RESULTS Types of cancer were associated with CD4 levels. Patients with head and neck cancer had lower CD4 levels (411.3 [119.3–1,427.5] cells/mm³) compared with colorectal (514.7 [129.2–861.3] cells/mm³), breast and gynecological (567.5 [180.1–939 cells/mm³), and other cancers (681.4 [175.1–2,056.9] cells/mm³), with p = 0.009. Patients aged ≥40 years had higher CD8 levels than those aged &lt;40 years (376.4 [142.8–1,293.1] cells/mm³ versus 565.3 [185.9–1,944] cells/mm³, p = 0.01). Additionally, lymphocyte count was associated with cancer type, with the lowest number in head and neck cancer (1,380 [280–2,660] μl, p = 0.044). CONCLUSIONS CD4 levels and lymphocyte counts were associated with the cancer type, whereas CD8 levels were influenced by age.

Invasive pulmonary aspergillosis evaluation in hematology patients: Three years results of tertiary hospital.

Invasive pulmonary aspergillosis (IPA) is the most frequent invasive fungal disease occurring in patients with hematological malignancies. Serum galactomannan (GM) antigen monitoring is thought to be helpful in the diagnosis of IPA. The aim of this study was to determine the role of a GM assay in serum samples for the diagnosis of IPA in patients with hematological disease. The data of 366 immunosuppressed patients that were hospitalized and followed up in the hematology clinic from January 2017 to December 2019 were retrospectively analyzed. The clinical and radiological findings of the patients and the GM results, requested twice a week, were evaluated. In this study, the incidence of probable and possible IPA was determined to be 15.3% (56/366). Of the cases detected, 28 (50.0%) were patients diagnosed with acute myeloid leukemia (AML), and 34 (60.7%) patients who had compatible clinical and examination findings were started on antifungal treatment. Additionally, area under the curve (AUC) values were calculated by receiver operating characteristic (ROC) analysis, and it was determined that the diagnostic efficiency was more predictive when the cut-off was 0.5 in the GM test for IPA disease. The detection of GM antigen in serum is a very useful and rapid method for diagnosing IPA disease in immunosuppressed hematology patients. However, GM results should be evaluated together with clinical and radiological findings for early diagnosis, and the treatment approach should be determined accordingly.

Imatinib Mesylate Causes Potential Cardiac Dysfunction in Patients With Chronic Myeloid Leukemia: the Results of a Case-control Study.

Unlike second-generation tyrosine kinase inhibitors, effects of imatinib on the cardiovascular (CV) system are debatable. The current case-control study aimed to evaluate the CV effects of imatinib in patients with chronic myeloid leukemia (CML) using non-invasive 2D-echocardiography testing. Patients with CML ≥ 13 years attending the adult haematology clinic of a tertiary care hospital in north India were prospectively enrolled over 1.5 years. The study population (n = 110) consisted of 35 newly diagnosed patients (treatment-naïve group) and 75 patients under imatinib therapy ≥ 1 year (treated group). All the eligible patients were subjected to 2D-echocardiography to calculate pulmonary artery systolic pressure (PASP), left ventricular ejection fraction (LVEF) and deceleration time (DT). These parameters were compared between the two groups. P-value < 0.05 was considered statistically significant. The median age of study population was 40 years (range, 13-73) and M:F ratio was 1.14:1. Both the groups had similar demographics at the diagnosis including CV risk factors. The median PASP of the treated group was 2 mm Hg higher than the treatment-naïve group (25 vs 23 mm Hg, p-value = 0.919). The median LVEF of the treated group was 3.2% lower than the treatment-naïve group (58.5% vs 61.72%, p-value = 0.577). The median DT of the treated group was 7 ms shorter than treatment-naïve group (211 vs 204 ms, p-value = 0.411). Imatinib causes potential cardiac dysfunction in patients with CML. Large scale prospective follow-up trials in the same cohort of patients are needed to validate the findings of our study.

The Clinical Significance of the Platelet Membrane Glycoproteins in Children with Primary Immune Thrombocytopenia

Abstract Background Primary immune thrombocytopenia (ITP) is an acquired immune-mediated disorder characterized by isolated thrombocytopenia. Although decreased platelet count is believed to be the main cause of hemorrhage in ITP, it is a poor predictor of bleeding risk by itself. Aim of the Work to measure CD62p and CD42b level in the pediatric ITP patients by using flow cytometer, measurement of platelet parameters in the pediatric ITP patients and to study its correlations to bleeding score. Patients and Methods sixty children with ITP were recruited and assessed for eligibility at the out-patients Hematology clinic – Pediatric Hospital at Ain Shams University, and compared with age and sex matched thirty healthy subjects. Results Pediatric ITP patients had a significant increase in the mean platelet volume, platelet distribution width and a significant decrease in plateletcrit among the ITP patient group in comparison with the control group (P value&amp;lt;0.001). The chronic ITP subgroup had significant increase of platelet count and plateletcrit in comparison with the acute ITP subgroup (P value&amp;lt;0.001). Pediatric ITP patients had significant increase in CD42b and a significant decrease in CD62p among the ITP patient group in comparison with the control group (P value&amp;lt;0.001). No statistically significant difference found between the acute, persistent and chronic ITP subgroups regarding CD42b and CD62p (P value&amp;gt;0.05). Conclusion Platelet function, platelet parameters and platelet glycoprotein CD62p, CD42b expression can be used as a clinical biomarkers in pediatric ITP.

Analysis of the pharmacoeconomic effectiveness of the tyrosine kinase inhibitors therapy in patients with chronic myeloid leukemia in a Single Hematology Center in Plovdiv, Bulgaria

Summary: Chronic myelogenous leukemia (CML) is a pluripotent hemopoietic stem cell malignancy characterized by the presence of a BCR-ABL1 fusion gene derived from a balanced translocation between the long arms of chromosomes 9 and 22 [t(9;22) (q34; q11)] known as the Philadelphia (Ph) chromosome. CML is an acquired hematopoietic stem cell disease common to myelo- and lymphopoiesis, characterized by uncontrolled proliferation of granulopoiesis (Shuvaev et al. 2015; Yordanov and Varbanova 2019). Relevance and goals: Second-generation tyrosine kinase inhibitors (TKIs) (nilotinib, dasatinib, and bosutinib) have an advantage over imatinib (first-generation) in the frequency and speed of achieving cytogenetic and molecular responses in the treatment of chronic myelogenous leukemia (CML), but they cause severe adverse effects and are much more expensive than imatinib, especially if we compare them to the prices of the registered generic products of Imatinib and Dasatinib. “Novartis Tasigna® trial shows superior results to Glivec® in patients with early-stage chronic myeloid leukemia”, reported on 10/20/2021 by Pierre Perrin-Montlouis. In the first direct comparison of these two oral therapies back in 2009 (Тasigna (nilotinib) 2009), as first-line treatment for CML, the results of Tasigna showed statistically significant improvement over Glivec in every measure of efficacy, including major molecular response (MMR), complete cytogenetic response (CCyR) and prevention of progression to accelerated or blast phase, with responses achieved faster in the Tasigna group than in the Glivec group. Furthermore, in the last ten years, CML patients who have achieved a stable deep molecular response for at least 2 years have been included in clinical trials for the management of treatment-free remission (TFR) (Kim et al. 2013; Saußele et al. 2016). On the other hand, the ever-increasing costs of diagnosis, treatment and monitoring of the response of CML to the various therapeutic strategies require conducting pharmacoeconomic analyses of the cost-effectiveness and cost-utility types in order to evaluate which are the cost-effective strategies with a view to introducing them into therapeutic practice. The present study aims to analyze the pharmacoeconomic efficiency of the TKI inhibitors used by the patients with CML-CP in the first and second lines, treated in the hematology clinic at UMHAT “St. George”, MU- Plovdiv during the period 2018–2022. Methods: An economic analysis of the medicinal use of TKIs for a 5-year period (2018–2022) was performed at the national level according to data from the National Health Insurance Fund and the availability, accessibility, and usability of original and generic TKIs in Bulgaria were evaluated. The direct medical costs for the therapy of all patients were calculated, including the costs of the TKI therapy, laboratory tests, and monitoring of the molecular response for the entire treatment period from the appointment of the TKI therapy until the end of 2022. A comparative analysis was conducted to assess the cost-effectiveness of the different therapeutic strategies with TKIs on the first and second lines of treatment of patients with CML-CP in the hematology clinic at UMHAT “St. George” Medical University, Plovdiv, using the decision analysis method and conducting one-way and probalistic sensitivity analyses. Results: The sensitivity analyzes of all pharmacoeconomic models showed the robustness and reliability of the obtained results. The threshold limits of medical costs and the frequency of achieving a deep molecular response determining the choice of first- and second-generation tyrosine kinase inhibitors as first- and second-line therapy for patients with chronic myeloid leukemia in the chronic phase have been determined. Prescribing doctors prefer the original MPs to generic analogues, which is also assumed by the current regulations, according to which even for expensive MPs dispensing by protocols, the prescription is by trade and not by international non-proprietary names (INN), which is why the use of the much cheaper generic MPs is negligibly low compared to original MPs. A personalized approach to the patient’s therapy and monitoring the patient’s molecular response to it, as well as stopping therapy in 25–30% of patients suitable to stop it safely when in TFR phase with a probability of more than 50% of not having a relapse will save additional costs that, by improving the cost-effectiveness of therapy for patients with CML, will be directed towards the treatment of new patients with this or other diseases. Conclusion: These pharmacoeconomic models can be applied to improve diagnostic and therapeutic standards in clinical practice and for the efficient use of the very limited resources for health care in countries like Bulgaria. The conducted cost-effectiveness analyses confirmed that the hematologists at the University Center in Plovdiv adhere to the recommendations of Leukemia Net and the Bulgarian Medical Society of Hematology and achieve not only good therapeutic but also pharmacoeconomic efficiency in the treatment of CML-СР patients in first- and second- line therapy.

Can Machine Learning Assist in Diagnosis of Primary Immune Thrombocytopenia? A Feasibility Study.

Primary Immune Thrombocytopenia (ITP) is a rare autoimmune disease characterised by the immune-mediated destruction of peripheral blood platelets in patients leading to low platelet counts and bleeding. The diagnosis and effective management of ITP are challenging because there is no established test to confirm the disease and no biomarker with which one can predict the response to treatment and outcome. In this work, we conduct a feasibility study to check if machine learning can be applied effectively for the diagnosis of ITP using routine blood tests and demographic data in a non-acute outpatient setting. Various ML models, including Logistic Regression, Support Vector Machine, k-Nearest Neighbor, Decision Tree and Random Forest, were applied to data from the UK Adult ITP Registry and a general haematology clinic. Two different approaches were investigated: a demographic-unaware and a demographic-aware one. We conduct extensive experiments to evaluate the predictive performance of these models and approaches, as well as their bias. The results revealed that Decision Tree and Random Forest models were both superior and fair, achieving nearly perfect predictive and fairness scores, with platelet count identified as the most significant variable. Models not provided with demographic information performed better in terms of predictive accuracy but showed lower fairness scores, illustrating a trade-off between predictive performance and fairness.

Erythrocytosis: Diagnosis and investigation.

An absolute erythrocytosis is present when the red cell mass is greater than 125% of the predicted. This is suspected when the hemoglobin or hematocrit is above the normal range. An erythrocytosis can be classified as primary or secondary and congenital or acquired. The commonest primary acquired disorder is polycythemia vera. The diagnostic criteria for PV have evolved over time and this is the main diagnosis managed in hematology clinics. There are a variety of rare congenital causes both primary and secondary. In particular in young patients and/or those with a family history a congenital cause is suspected. There remains a larger cohort with acquired erythrocytosis mainly with non-hematological pathology. In order to explore for a cause of erythrocytosis, measurement of the erythropoietin level is a first step. A low erythropoietin level indicates a primary cause and a normal or elevated level indicates a secondary etiology. Further investigation is then dictated by initial findings and includes mutational testing with PCR and NGS for those in whom a congenital cause is suspected. Following this possibly bone marrow biopsy, scans, and further investigation as indicated by history and initial findings. Investigation is directed toward the identification of those with a hematological disorder which would be best managed following guidelines in hematology clinics and referral elsewhere in those for whom there are non-hematological reasons for the elevated hemoglobin.

Comparison of Echocardiography and Multi-Planar Gated Acquisition Scans for Predicting Cancer-Treatment-Related Cardiovascular Dysfunction

Current guidelines recommend using sequential cardiac imaging to monitor for cancer treatment-related cardiac dysfunction (CTRCD) in patients undergoing potentially cardiotoxic chemotherapy. Multiple different imaging cardiac modalities are available and there are few prospective head-to-head comparative studies to help guide treatment. To perform an exploratory prospective cohort study of "real-world" CTRCD comparing multigated acquisition nuclear ventriculography (MUGA) at the referring cancer specialist's discretion with a novel echocardiographic strategy at an Australian tertiary hospital. Patients were recruited from haematology and oncology outpatient clinics if they were scheduled for treatment with anthracyclines and/or trastuzumab. Patients underwent simultaneous MUGA-based cardiac imaging (conventional strategy) at a frequency according to evidenced-based guidelines in addition to researcher-conducted echocardiographic imaging. The echocardiographic imaging was performed in all patients at time points recommended by international society guidelines. Outcomes included adherence to guideline recommendations, concordance between MUGA and echocardiographic left ventricular ejection fraction (LVEF) measurements, and detection of cardiac dysfunction (defined as >5% LVEF decrement from baseline by three-dimensional [3D]-LVEF). A secondary end point was accuracy of global longitudinal strain in predicting cardiac dysfunction. In total, 35 patients were recruited, including 15 with breast cancer, 19 with haematological malignancy, and one with gastric cancer. MUGA and echocardiographic LVEF measurements correlated poorly with limits of agreement of 30% between 3D-LVEF and MUGA-LVEF and 37% for 3D-LVEF and MUGA-LVEF. Only one case (2.9%) of CTRCD was diagnosed by MUGA, compared with 12 (34.2%) cases by echocardiography. Four (4) patients had >10% decrement in 3D-LVEF that was not detected by MUGA. Global longitudinal strain at 2 months displayed significant ability to predict CTRCD (area under the curve, 0.75, 95% confidence interval, 0.55-0.94). The MUGA correlates poorly with echocardiographic assessment with substantial discrepancy between MUGA and echocardiography in CTRCD diagnosis. Echocardiographic and MUGA imaging strategies should not be considered equivalent for imaging cancer patients, and a single imaging modality should ideally be used per patient to prevent misdiagnosis by inter-modality variation These findings should be considered hypothesis-generating and require confirmation with larger studies.