Hematology Centers Research Articles

Statistical Data on Myelodysplastic Syndrome in the Russian Federation

Introduction. Myelodysplastic syndrome (MDS) is a nosology that requires examination using cytogenetic, molecular-genetic and immunophenotypic analysis of bone marrow and/or blood, as well as mandatory bone marrow trepan biopsy with pathomorphological and immunohistochemically studies. Until recently, there was no official statistical data on MDS in Russia.Aim: to present data on the incidence and prevalence of MDS in Russia based on official statistical forms.Materials and methods. Information from statistical form №7 «Information on malignant neoplasms» (SF No. 7) for 2022 and 2023 on the incidence and prevalence of MDS, updated at the initiative of the National Medical Research Center for Hematology, is presented. For the first time, additional lines (35–37) with information on the movement of patients, including MDS (code D46 according to ICD-10), have been introduced into table 2100.Results. According to SF No. 7, in 2022 and 2023, 2,827 and 3,411 cases of MDS were registered, respectively. The estimated primary incidence in the Russian Federation was 0.58 and 0.50 per 100 thousand of the adult population in 2022 and 2023, respectively, and the prevalence was 2.4 per 100 thousand of the adult population. The estimated incidence of MDS by federal districts in 2022 ranged from 0.13 to 1.05 with variations from 0.03 to 2.57 per 100 thousand of the adult population, depending on the region of residence. At the end of 2023, 3001 (88 %) patients with MDS were registered under dispensary observation, of which 860 (28.7 %) were under observation for 5 years or more.Conclusion. The obtained statistical data on the incidence and prevalence of MDS showed the high significance of the work carried out both for the subsequent improvement of the system of registration of patients with diseases of the blood system in general, and MDS, particularly the Russian Federation, and will make it possible to use this data in the planning of healthcare in the Russia.

A GIMEMA survey on therapeutic use and response rates of FLT3 inhibitors in acute myeloid leukemia: Insights from Italian real-world practice.

Given the limited data on the real-life therapeutic use of feline McDonough sarcoma (FMS)-like tyrosine kinase 3 (FLT3) inhibitors in Italy, we surveyed investigators at 59 Italian hematology centers to gain insight into the proportion of acute myeloid leukemia (AML) patients receiving FLT3 inhibitors and we collected data on the efficacy and safety of these agents. The survey results showed that in the real-life setting the response rate of the 3/7 + midostaurin regimen in newly diagnosed FLT3-mutated AML and of gilteritinib in the relapsed/refractory AML were comparable to that reported in the registrative clinical trials. The 3/7 + midostaurin treatment resulted in a 63% of complete remission (CR) rates and gilteritinib in a 44% of CR rates. The discontinuation rate of gilteritinib for intolerance or toxicity was low (accounting for 4% of treated cases).

Outcomes of Ixazomib Treatment in Relapsed and Refractory Multiple Myeloma: Insights from Croatian Cooperative Group for Hematologic Diseases (KROHEM).

Background and Objectives: Ixazomib, used in combination with lenalidomide and dexamethasone (IRd), has shown efficacy in clinical trials for relapsed/refractory multiple myeloma (RRMM). Materials and Methods: This study evaluates the real-world effectiveness and safety of IRd in Croatian RRMM patients. A retrospective analysis was conducted on 164 RRMM patients treated with ixazomib at nine Croatian haematology centres from November 2016 to February 2023. Data on patient demographics, treatment regimens, and outcomes were collected and analysed using Kaplan-Meier survival curves and Cox proportional hazards models in R. The median age at ixazomib initiation was 66 years (range 40-91). Results: The overall response rate (ORR) was 65.8%, with 42% of patients achieving a very good partial response (VGPR) or better. The median progression-free survival (PFS) was 15.4 months, while median overall survival (OS) was 28.2 months. Hematologic toxicities included anaemia (53%), neutropenia (50%), and thrombocytopenia (45%). Infective complications, primarily COVID-19 and pneumonia, were reported in 38% of patients. The safety profile was consistent with previous studies, indicating manageable adverse events. Ixazomib-based therapy is effective and well tolerated in a real-world Croatian RRMM population. Conclusions: The findings align with clinical trial results, demonstrating the applicability of ixazomib in routine clinical practice. Further studies are needed to optimise treatment sequencing and improve patient outcomes.

Health Related Quality of Life in Transfusion Dependent Patients with Beta Thalassemia at a Resource Constrained Center

Background: Beta Thalassemia is a prevalent genetic disorder of hemoglobin affecting a significant portion of the global population with approximately 3% of people worldwide being carrier of the gene. About 5% of the population in Pakistan carry the genes for Beta Thalassemia, leading to approximately 5,000 new diagnoses each year. Majority of the patients are treated with regular red blood cell transfusions combined with iron chelation, few being able to afford definitive treatment in the form of allogeneic bone marrow transplant (BMT). Due to high disease burden and lack of adequate health care facilities the patients get inadequate blood transfusions and suboptimum iron chelation leading to numerous complications, early death and quality of life (QoL) problems. Objective: To evaluate health related quality of life in transfusion dependent beta Thalassemia patients registered at a single center Study Design: Cross sectional observational study Place and duration of the study: The study was conducted on patients treated at Pakistan Thalassemia Welfare Society (Pathwel) Center of Hematology and BMT Rawalpindi, Pakistan for at least one year between January 2006 to June 2024. Methodology: We evaluated 136 patients of transfusion dependent beta thalassemia with age range of 2-35 years and registered for more than 1 year at the center. Patients with age less than 2 years, those receiving hydroxyurea, undergoing BMT or registered for less than 1 year were excluded from the study. A face to face interview with structured questionnaire was used for data collection. Caregivers were interviewed for children of less than 10 years of age. Modified version of World Health Organization Quality of Life Brief Version (WHOQoL-BREF) questionnaire assessing 4 domains of QoL i.e. physical health, psychological health, social health and environment was used. IBM SPSS statistics version 23 was used for statistical analysis. Results: The estimation of health-related quality of life (HRQoL) in beta thalassemia patients provides important insights in the disease and its management. Majority of the responders were patients themselves 52.2% vs. caregivers 47.8%. All the 136 patients were transfusion dependent, 52.2% were female, 47.8% male, 84.6% were children and 15.4% adults. Mean age of the patients was 10.72 years (range 2-35, SD = 6.85).Out of 120 school-going age patients 68.3% were attending school, 22.5% had never been to any school, 9.1% left education at some point due to health related problems. Forty one percent of the patients had access to public transport for coming to thalassemia center for treatment while 39% faced difficulty reaching hospital and used private taxis. Only 58% patients underwent regular medical checkup from their GPs, 3.7% had irregular follow up visits. Socioeconomic status was; 39% upper middle class, 39.7% lower middle class and 21.3% poor. About half of the patient's socioeconomic status was affected by their disease, 46.3% did not had any effect while 3.7% were unaware of any effect. Forty five percent patients needed once a month red cell transfusion, 38.2% twice a month and 16.9% more than twice a month. According to 69.1% responders blood at the center was easily available while 28.7% had difficulty in getting blood for transfusion. Majority of them had either Rh negative blood groups or preformed antibodies. Mean pre-transfusion hemoglobin was 7.3 g/dl (SD=1.2).Hepatitis B Vaccination status revealed; 83.1% vaccinated, 8.1% not vaccinated while 8.8% were unaware of their vaccination status. Hepatitis C positivity was seen in 25% of the patients at some point of life while 2.2% were positive for hepatitis B. Eight out of the 23 patients with transfusion requirement more than twice a month had positivity for hepatitis C. Conclusion: This study underscored the considerable negative impact of thalassemia and its treatment on health-related quality of life (HRQoL), particularly due to comorbidities, availability of the blood, low income and lack of adequate knowledge about the disease. It suggests that adjusting current thalassemia management and care practices could be beneficial. Implementing psychosocial and counseling programs could help patients discuss and accept their condition, support a normal lifestyle, and strengthen connectivity among patients, schools, families, and healthcare providers leading to improved HRQoL and academic performance.

Analysis of treatment-free remission outcomes in patients with chronic myeloid leukemia who received sequential nilotinib therapy after achieving deep molecular response to imatinib

Objective: To analyze the treatment-free remission (TFR) outcomes in patients with chronic myeloid leukemia (CML) treated sequentially with nilotinib (NIL) after achieving deep molecular response (DMR) to imatinib (IM). Methods: Retrospectively enrolled 103 CML patients from 6 hematological centers in Henan Province who chose sequential NIL therapy or continued IM therapy after achieving DMR to first-line IM from June 2, 2013 to August 30, 2022. Among them, 42 cases were treated with sequential NIL and 61 cases continued IM therapy. The 42 patients in the sequential NIL group were further divided into 3 subgroups based on the duration of DMR at switching to sequential NIL therapy: Group 1 (17 cases): DMR duration<12 months at switching to sequential NIL therapy; Group 2 (8 cases): DMR duration≥12 months to<24 months at switching to sequential NIL therapy; Group 3 (17 cases): DMR duration≥24 months at switching to sequential NIL therapy. Follow-up ended on January 9, 2024, with a median follow-up of 40 (16, 91) months for the sequential NIL group and 49 (21, 123) months for the continuous IM group. Survival curves were plotted using the Kaplan-Meier method and the log-rank test was performed to compare the TFR rates between groups. Results: There were 19 males and 23 females with a median age [M (Q1, Q3)] of 43 (31, 50) years in the sequential NIL group. There were 32 males and 29 females with a median age of 41 (31, 50) years in the continuous IM group. Kaplan-Meier survival curve analysis showed that the TFR rate was higher in the sequential NIL group than in the continuous IM group (88.1% vs 63.9%, P=0.005). The results of subgroup analysis showed that the TFR rates in Group 1, Group 2 and Group 3 were 94.1%, 87.5% and 82.4%, respectively, with no statistically significant differences (all P>0.05).The TFR rate in Group 1 was higher than in the continued IM group (P=0.017), and there were no statistically significant differences in Group 2 and Group 3 compared with the continuous IM group(all P>0.05). Conclusion: Sequential NIL therapy after achieving DMR with IM therapy can improve the TFR rate in CML patients, especially in those with DMR duration<12 months before switching to sequential NIL therapy.

Outcome of Induction Chemotherapy in Acute Lymphoblastic Leukemia in a Resource Constrained Setting

Background: Treatment of acute leukemia requires advanced healthcare setup with availability of advanced diagnostic, blood components and chemotherapeutic agents. In resource constrained settings there are suboptimal facilities for treating acute leukemias leading to early death. Pathwel center of hematology and bone marrow transplant (PATHWEL) is a recently established nonprofit facility for diagnosis and management of blood diseases. This center has adopted certain measures like intensive human resource training, optimizing the use of blood components and chemotherapeutic agents to make the treatment sustainable for poor patients in the limited available resources. Objective: To analyze the outcome of induction chemotherapy in patients with acute lymphoblastic leukemia (ALL) in a -resource constrained setting. Methods: Retrospective observational analysis Patients and Methods: All patients diagnosed as ALL and treated at PATHWEL from March 2022 till June 2024 were included. Medical records of all patients were reviewed and data was collected including patient demographics, disease subtype, induction chemotherapy regimen, response to induction chemotherapy and treatment complications. SPSS software version 23 was used for data analysis. Results: A total of 69 patients with ALL were registered at PATHWEL during the study period. Clinical data and treatment response of 49 patients was available and they were included in this analysis. Out of 49 patients, 42 (86%) were male, 7 (14%) female. Median age was 22 years (range 5 to 58). Thirty-seven patients (75.5%) were newly diagnosed, 7 (14.3%) had relapsed disease, 2 (4.1%) had refractory disease and 3 (6.1%) lymphoid blast transformation of chronic myeloid leukemia (CML). Thirty-five (71.4%) had B-ALL, 10 (20.4%) T- ALL, 3 (6.1%) patients were in lymphoid blast phase of CML and 1 (2%) had acute undifferentiated leukemia. Molecular workup was available for 41 (83.6%) patients out of which 6 (12.2%) were BCR-ABL positive including 3 (6.1%) with de novo ALL and 3 (6.1%) in CML blast transformation, 1 (2%) had TEL-AML1 and the rest had negative molecular panel. Cytogenetics reports were available for 36 (73.4%) out of which 31 (63.2%) were normal, 2 (4.1%) had complex karyotype and one each had double Philadelphia chromosome, Trisomy 8 and hyperdiploidy. All patients except 8, received multiagent induction chemotherapy based on UK-ALI-2011 Regimen B induction, 1 (2%) received modified UKALL 2011 Reg B induction, 6 (12.2%) patients received Fludarabine, cytarabine and daunorubicin/ Idarubicin (FLAG Dauno/Ida) and 2 (4.1%) patients received high dose cytarabine, vincristine, daunorubicin and dexamethasone (Hyper CVAD). Additionally, BCR ABLI positive patients received a tyrosine kinase inhibitor (TKI). The complications were mainly infectious. Twenty-one patients (42.8%) had infectious complications during induction therapy including sepsis in 13 patients (26.5%), neutropenic enterocolitis in 2 cases (4%) and one patient each of pneumocystis pneumonia, viral encephalitis, bacterial meningitis, otitis media, and septic arthritis. Other complications included cardiomyopathy in 1 patient, steroid induced hyperglycemia in 3, proximal myopathy in 1, peripheral neuropathy in 1 and hoarseness of voice with vocal cord mass in 1 case. Thirty-six patients (73.4 %) achieved remission after induction, 6 (12.2%) had refractory disease, and 2 (4%) died during induction, 1(2%) had iatrogenic hypoplasia with residual blasts. Remission status could not be assessed in 4 (8.1%) due to loss to follow up. Conclusion: Our data show encouraging early results of induction chemotherapy in ALL in resource constrained setting by optimizing the available healthcare facilities which is significant as this was a diverse patient population including relapsed and refractory patients. Long term follow up and larger studies may help to refine optimal treatment approach for patients in resource constrained settings.

Risk factors for neurologic sequelae in children and adolescents with hemophilia after intracranial hemorrhage

BackgroundIntracranial hemorrhage (ICH) is reportedly rare but has high morbidity and mortality risk in persons with hemophilia. Although the risk factors that facilitate bleeding are known, the factors affecting the sequelae are not well known. ObjectivesWe planned to investigate the risk factors for neurologic sequelae in children and adolescents with hemophilia suffering from ICH. MethodsAn invitation was sent to pediatric hematology centers via email. Clinical and laboratory findings, neurologic sequelae, and recurrence of bleeding in persons with hemophilia who developed ICH were questioned. ResultsEighty-six patients from 21 centers were evaluated. All patients were less than 18 years of age at the time of ICH. Thirteen patients had ICH in the neonatal period, while 40 patients had a known diagnosis of hemophilia before ICH, and 33 patients were undiagnosed before ICH. Five patients died, 2 of whom died in the neonatal period. The rate of neurologic sequelae was 25 of 81 (30%). The most common neurologic sequela was epilepsy (n = 11/25), followed by hemiparesis (n = 5/25). Cerebral shift (odds ratio, 3.48) and development of ICH in the neonatal period (odds ratio, 4.67) were significant for the development of neurologic sequelae in multivariate analysis. On follow-up, recurrence of ICH occurred in 8 of 81 (10%). ConclusionICH in the neonatal period and cerebral shift were the two main risk factors for the development of neurologic sequelae. Neonatal departments must be alert to the signs of bleeding. It is important for healthcare professionals to overcome the barriers to primary prophylaxis and to take trauma-related precautions.

The UK consensus supporting effective introduction of novel treatments for multiple myeloma in the National Health Service.

Multiple myeloma (MM) is a relapsing, debilitating blood cancer which remains incurable despite advances in treatments. Patients typically receive multiple lines of treatment, to which they become refractory, thereby limiting treatment options. B-cell maturation antigen (BCMA) bispecific antibodies (BsAbs) represent a novel modality of treatment that has significant efficacy for relapsed or refractory patients.The objective was to develop consensus statements for the effective implementation of BCMA BsAbs for relapsed or refractory MM patients within the National Health Service (NHS). The process employed a modified Delphi methodology. In March 2023, a literature review on the topic of novel treatments for MM was performed using the PubMed database.The process employed a modified Delphi methodology. Following a literature review, a steering group of eight expert clinicians identified and agreed on five main topics of focus and 44 statements. These were then developed into an online survey which was distributed to healthcare professionals working in Levels 1, 2 and 3 haematology centres in the United Kingdom. Results were then shared with the expert panel to determine conclusions. The threshold for consensus agreement was set at 75%. A total of 60 responses were received from all three centre levels. There was representation from all targeted centres. Consensus was achieved in 42 statements (95%) across three broad areas: the patient profile, initiation and step-up dosing, monitoring and ongoing care, the role of multidisciplinary team and service designs for optimal management, consensus was not achieved for two statements. Given the level of agreement and that the stopping criteria were met, it was decided not to undertake further Delphi rounds. This consensus provides a framework to support the effective introduction of novel treatments for MM in the NHS. The results were used to inform a checklist for use within haematology services when considering the provision of MM care specific to BCMA BsAbs.

The role and prognostic value of the interleukin 2 gene at multiple myeloma

Aim of the study. To determine the relationship of the polymorphic locus of the IL2 genetic marker (T-330G) with the risk of complicated course of multiple myeloma.Materials and methods. The molecular analysis of the IL2 (T-330G) gene was carried out in the laboratory of Molecular Genetics, cytogenetics and FISH at the Republican Specialized Scientific and Practical Medical Center of Hematology of the Republic of Uzbekistan (Tashkent city). 101 patients aged 34 to 72 years with a reliably established diagnosis of multiple myeloma were examined. IL2 polymorphism (T-330G) was genotyped by real-time PCR using primers from Litech (Russia) using an Applied Biosystems thermal cycler (USA).Results and discussion. An increased risk of complicated course of multiple myeloma compared with healthy individuals was found to be 1.6 times higher among carriers of the mutant G allele (χ2=4.3; p=0.05). Statistically significant differences between unfavorable loci in the group of patients with combined complications of multiple myeloma compared with the control were revealed.Conclusions. The risk of developing multiple myeloma compared with healthy individuals is 1.6 times higher among carriers of the mutant G allele (χ2=4.3; p=0.05) according to the polymorphism of the IL2 gene (T-330G). Along with this, a statistically significant relationship was established between unfavorable loci (G and G/G) with an increase of 2.5 (χ2=9.4; p=0.01) and 3.5 times (χ2=5.3; p=0.03) the risk of developing multiple myeloma complicated by plasmacytoma in combination with nephropathy.

Estimation of miRNA-183 expression and TGF-β level in Chronic Myeloid Leukemia

Background: MicroRNA-183 and Transforming Growth Factor Beta (TGF-β) have emerged as significant players in the pathophysiology of Chronic Myeloid Leukemia (CML). Research indicates that miRNA-183 may play a role in the regulation of cell proliferation and apoptosis in CML cells, potentially influencing disease progression and response to therapy. Elevated levels of miRNA-183 have been associated with poor prognosis, suggesting it could serve as a biomarker for disease severity. Objective: In this study, we aimed to analyze the expression of miR-183 and TGF- β level and investigate the relationship between miR-183 and level of TGF- β in CML patients. Material and Methods: The study has been carried out on 60 Iraqi patients (37 males and 23 females at age range 17 - 69 year) with chronic myeloid leukemia at chronic phase, who are referred to the National Center of Hematology/ Mustansiriyah University, Baghdad during the period from January to November 2023. Twenty of them are newly diagnosed (T0), and the other 40 patients are under treatment with TKIs (T+), Thirty age and gender-matched healthy subjects were enrolled to act as control group. TGF-β level estimates by ELISA while micrRNA-183 detection using RT- PCR. Conclusion: The elevated levels of TGF-β and miRNA-183 in CML patients, coupled with their positive correlation.

Hematologists' state of knowledge on practical aspects of hemophagocytic lymphohistiocytosis (HLH) in adult patients: A Young Hematologists' Club survey.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome with various etiologies. Its treatment is complicated by several important but not immediately obvious issues (e.g., HLH-2004 criteria are the most commonly used for diagnosis, but the recommended therapeutic regimen is HLH-94). The study aimed to assess hematologists' practical knowledge of HLH. A survey was conducted among physicians treating adult hematological patients. A 10-question paper questionnaire was distributed to physicians from various hematology centers. A total of 126 questionnaires were analyzed. Most respondents had little-to-moderate experience in caring for HLH patients: 59% treated 0-2 patients and 36% treated between 3-5 patients. Among the respondents, the preferred diagnostic criteria were HLH-2004, either in its original form (5 out of 8 criteria) for 70 respondents or its modified version (4 out of 6 available criteria when ferritin exceeds 2,000 ng/mL) for 56 respondents. The preferred treatment regimen was HLH-2004, with a full dose of etoposide in 72 responses or reduced in 39 responses. Fifty percent of respondents incorrectly answered that meeting the HLH-2004 criteria necessitates the use of the HLH-94/2004 regimen in full doses and duration. Sixty-four percent of respondents correctly identified that hemophagocytosis is not necessary for the diagnosis. This survey reveals that the majority of surveyed physicians adhere to international HLH recommendations. However, there are instances where these guidelines are not fully implemented, which underlines the need for further efforts to raise awareness and share clinical experiences about this patient group.

Early results of treatment in accordance with the NB-HR-2018 protocol in patients with high-risk neuroblastoma in the Republic of Belarus

The development of new criteria for high-risk neuroblastoma treatment optimization and the introduction of new approaches to its management are a pressing problem in modern pediatric oncology. In this study, we aimed to develop and implement new high-risk and ultra-high-risk criteria, introduce tandem autologous hematopoietic stem cell transplantation (HSCT) as consolidation therapy for high-risk neuroblastoma patients as well as to assess patient tolerability of this treatment. The study was approved by the Independent Ethics Committee and the Scientific Council of the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology. In 2018, a new protocol called NB-HR-2018 was developed and implemented at the Center for Pediatric Oncology, Hematology, and Immunology (Belarus) that included new criteria defining high-risk groups. Twenty-three patients were treated according to the new protocol, with 20 of them receiving autologous HSCT. The comparison group included 56 high-risk patients who had undergone treatment in accordance with the NB 2004 protocol. Tandem autoHSCT significantly reduces the rates of underlying disease relapse/progression (p = 0.047) and demonstrates better event-free survival rates (56 ± 12% vs 36 ± 6%; р = 0.445). The use of the new high-risk criteria and the new treatment method (tandem autologous HSCT) is concluded to be a reasonable approach since it significantly reduces disease relapse rates and is well tolerated by the patients.

The development of a tool for the assessment of oral health program in a pediatric cancer unit

Abstract Background Oral diseases and associated illnesses interfere with cancer treatment, increase morbidity, prolong hospital stay, and increase costs. Oral care of children with cancer is essential to prevent oral diseases and decrease its symptoms. Standardized oral health and hygiene (OHH) practices must be a priority and incorporated as a routine cancer care quality. To improve OHH, baseline information of practices, processes and institutional support are necessary. Here, we report the steps we followed to develop a tool for evaluating OHH practices, support, and resources available in a pediatric cancer unit. Methods We conformed a working group (WG) integrated by healthcare professionals in pediatric, infectious diseases, oncology, and dentistry acquainted with the care of children with cancer. The steps proposed by the WG included: (1) literature review of published surveys in OHH; (2) interviews with practicing healthcare providers regarding OHH in pediatrics; (3) identification, adoption and adaptation of the Hand Hygiene Self-assessment framework (HHSAF), a survey model based on the multimodal improvement strategy (MMIS); (4) building of OHH tool; (5) validation test of OHH tool; and (6) pilot testing in recruited pediatric hematology and oncology centers. Google form version 0.8. Microsoft office excel 2021 (18.0) was used to build the OHH survey and obtain the WG member responses. The final draft of the survey was approved by WG members. We will evaluate survey validity in the pilot test among members of the PRINCIPAL network, a community of pediatric infectious disease experts and preventionists of Latin America. Results We found few reports on OHH practices in children cancer surveys. The WG met virtually and monthly from March to December 2023 to build the OHH survey. Our final survey version was organized following the model of the HHSAF and integrated into five main sections. These sections had items (Q) that requested answers regarding OHH practices and resources and institutional support (6Q); training and education of patients, families, and healthcare providers (6Q); evaluation and feedback of OHH processes in pediatric oncology unit and OHH practices of patients (6Q); reminders of OHH practices in the workplace (3Q); and hospital leadership support (2Q). The survey was made up of multiple choice and Likert scale questions. Each of the answers had a weight, and if all the items were present, the total was 400 points. Based on the total points obtained, we categorized the quality of the OHH practices of the pediatric oncology unit in inadequate (0-100); basic (101-200), intermediate (201-300), advanced (&amp;gt;300). The survey tool must be answered by an assigned team of the pediatric oncology unit oral health including a family member representative, and it could take less than 15 minutes to complete. Conclusion We developed a 21-item OHH practices survey following the WHO recommendations to use a MMIS model. We found that our newly developed tool was comprehensive and potentially helpful to assess OHH practices and identify success factors in best practices in OHH in pediatric oncology units. Our next step is pilot testing to evaluate our survey tool validity and reliability.

Surveillance of fever and neutropenia episodes at Yeolyan Hematology and Oncology Center in Armenia

Abstract Background Fever and neutropenia frequently occur as complications in pediatric patients with malignancies, significantly escalating morbidity and mortality if not appropriately addressed. We implemented a fever registry to identify patient factors and outcomes associated with fever in patients undergoing treatment at our facility. Methods We conducted a single-center prospective observational study at the Pediatric Cancer and Blood Disorders Center of Armenia. All patients aged 0-21 years with a malignancy diagnosis and developing fever and neutropenia between June 25 and November 20, 2023, were included. Variables collected included age, gender, date and time of fever onset, patient symptoms, time to antibiotic administration, identified microbiologic and clinical infections, and subsequent outcomes, including mortality and requirement for critical care level interventions. Data were entered in Microsoft Excel 2016 and analyzed using descriptive statistical methods. Results Sixty-one patient episodes in 36 patients met the inclusion criteria. Of these, 22% of episodes had fever at home. The most common malignancy was acute leukemia, specifically B-ALL (21/61), followed by T-ALL (9/61), AML (7/61), and mixed T- and B-type (1/61). Eight out of 61 fever episodes occurred in patients with relapsed disease. The median time-to-antibiotics was 100 minutes (max: 24 hours 40 minutes) in patients developing fever outside the hospital; for inpatient cases, the median time-to-antibiotics was 30 minutes (max: 6 hours 45 minutes). The time-to-antibiotics was longer for patients experiencing fever at home compared to those in inpatient settings (p=0.043). 21% of patient episodes were pretreated, however 11 out of 61 patient episodes (18%) had a positive blood culture. Of 13 total positive cultures, ten were obtained at the time of the patient’s presentation. The most common pathogens identified were Staphylococcus spp. (8/13) including coagulase-negative (3/8), and Klebsiella spp. (3/13). Polymicrobial-positive cultures were observed during two fever and neutropenia episodes. During 35 episodes, patients presented with no complaints except for general weakness. Among the identified sources of infection (20/61), central-line-related bloodstream infections (n=6), bacteremia (n=5), and Clostridiodes difficile colitis (n=5) were the most common. One febrile neutropenia episode resulted in death (1.6%). Conclusion In summary, over 75% of episodes were observed among patients with hematologic malignancies, and localizing symptoms were absent in half of episodes at presentation. We have identified opportunities for quality improvement in time to administration of antibiotics in outpatient fever episodes. The adaptation of an electronic-based medical record system will simplify the tracking process for a febrile episode.

Toxoplasma qPCR kinetics to guide pre-emptive treatment of toxoplasmosis after allogeneic hematopoietic stem cell transplantation.

Recent ECIL-guidelines recommend a quantitative PCR (qPCR) guided pre-emptive treatment approach to toxoplasmosis in seropositive recipients of allogeneic hematopoietic cell transplantation (allo-HCT). While qPCR might serve as a sensitive tool for early Toxoplasma detection, its role in treatment follow-up remains unknown. We analyzed the qPCR kinetics of allo-HCT recipients experiencing either Toxoplasma infection (TI, n=71) or disease (TD, n=14) in relation to different parameters. We included 85 patients with available qPCR values expressed as quantitative cycle (Cq) from four large hematological centers from 2009 to 2023, and kinetic analysis was performed in a selection of 74 patients screened at least weekly with blood qPCR. Day 0 (D0) was the day of anti-Toxoplasma treatment start or (when untreated) day of diagnosis. Time to qPCR negativity was inversely proportional to the Cq value at D0 (p=0.0063). Not reaching negativity at D10 was associated with a significantly higher mortality at D30 (p=0.023). Patients with a high D0-parasitic load and patients with TD showed slower clearance (p<0.001, p=0.032). Time to negativity was not significantly different for patients started on prophylactic vs curative doses as first-line treatment regimen (p=0.16). This study underscores the predictive value of qPCR kinetics monitoring in allo-HCT patients with toxoplasmosis. With the aforementioned risk factors, clinicians can identify patients at high-risk for worse outcome. Our results support to consider a therapeutic change or reinforcement if the parasitic load does not decrease after 10 days, supplementing existing clinical guidelines.

Experience with luspatercept therapy in patients with transfusion-dependent low-risk myelodysplastic syndromes in real-world clinical practice: exploring the positive effect of combination with erythropoietin alfa.

Luspatercept, an inhibitor of the transforming growth factor beta (TGF-β) pathway, is a novel treatment for anemic patients with lower-risk myelodysplastic syndromes (MDS) with transfusion dependence (TD) who do not respond to erythropoiesis-stimulating agents (ESA) therapy or are not suitable candidates for this treatment. We present real-world experience with luspatercept therapy from two hematology centers in the Czech Republic. By January 2024, 54 MDS patients (33 men, 21 women) with a median age of 74 years (range, 55-95) were treated with luspatercept ± ESA at two Charles University hematology centers in Prague and Hradec Králové. According to the WHO 2016 classification, the cohort included 32 MDS-RS-MLD, seven MDS-MLD, two patients with 5q- + ring sideroblasts (RS), 12 RARS-T, and 1 patient with CMML-0 + RS. SF3B1 mutation data were available for 45 patients. All patients were in the IPSS-R and IPSS-M lower-risk groups (except four IPSS-M high). The median follow-up was 17 months (range, 1-54). All patients were transfusion-dependent. Thirty-five (64.8%) patients had a high transfusion burden (HTB) with ≥ 4 transfusion units (TU)/8 weeks, and 19 (35.2%) had a low transfusion burden (LTB) (< 4 TU/8 weeks). The median time between diagnosis and initiation of luspatercept was 27 months (range, 4-156). ESA were used prior to luspatercept in 45 patients, and luspatercept was used as first-line treatment in nine patients. Thirty-one (61%) patients were treated simultaneously with ESA. Only patients who received luspatercept for ≥ 8 weeks (51 patients) were assessed. We evaluated the achievement of transfusion independence (TI) lasting 8, 12, 16, and 24 weeks. Thirty-two (62.7%) patients achieved TI for ≥ 8 weeks, 31 (60.7%) for ≥ 12 weeks, 29 (56.8%) for ≥ 16 weeks, and 25 (49%) for ≥ 24 weeks. Hematologic improvement (HI) without TI was achieved in six patients (11.7%). Overall, HI + TI was achieved in 38 patients (74.5%). Epoetin alfa was used simultaneously in 31 patients (60.7%). In 21 (55.2%) of all responding patients, concomitant therapy with epoetin alfa led to an improved response, with 16 reaching TI. Thirteen (25.5%) patients were nonresponders. Eight (21%) patients experienced therapy failure and became transfusion-dependent again. Optimal response required a gradual increase in the luspatercept dose to 1.75 mg/kg in up to 35 patients, with 23 responders (TI + HI). Response rates varied by transfusion burden: 79% in LTB and 50% in HTB reached TI. Of RS+ patients, 70% reached TI, while only one out of five RS- patients achieved TI. Among 39 SF3B1-positive patients, 61.6% achieved TI. In the low and very low IPSS-M groups, 86% of patients responded (TI + HI), compared to 62% in the moderate-low group. Luspatercept was well-tolerated, with no adverse events higher than grade II toxicity. We have demonstrated in real-world clinical practice that luspatercept is a very effective agent, even in an unselected, pretreated, significantly TD MDS population. The effect was particularly high in the IPSS-M low and very low groups. We believe that the relatively high response rate in our patients was influenced by the frequent use of a higher dose (1.75 mg/kg) and especially by adding ESA to luspatercept in poorly responding patients.

Assessment &lt;b&gt;&lt;/b&gt;of Serum P53 Protein Level in Adult Patients with Acute Myeloid Leukemia in Correlation with Response to Treatment

Background: Acute myeloid leukemia (AML) is an adult leukemia characterized by rapid proliferation of undifferentiated myeloid precursors, leading to bone marrow (BM) failure and impaired erythropoiesis. The p53 tumor suppressor protein regulates cell division and inhibits tumor development by preventing cell proliferation of altered or damaged DNA. It orchestrates various cellular reactions, including cell cycle arrest, DNA repair, and antioxidant properties. Objectives: To investigate the relationship of P53 serum level with hematological findings, remission, and survival status in de novo AML patients. Methods: This is a cross-sectional study that enrolled 63 newly diagnosed de novo AML patients, and 15 sex- and age-matched healthy persons as a control group. Serum P53 levels were assessed using the enzyme-linked immunosorbent assay (ELISA) technique before initiating induction chemotherapy. The study was performed between November 2022 and May 2023 at the Hematology and Bone Marrow Transplant Center of the Medical City Complex in Baghdad. Results: There were significantly lower P53 serum levels in AML patients before starting chemotherapy compared to the control group. However, no substantial difference in P53 levels was identified between AML patients achieving complete remission and those exhibiting no response, nor between alive and deceased individuals. Furthermore, there was a positive yet statistically non-significant correlation between serum P53 levels and age, and no significant relationship between P53 levels and sex or various hematological parameters. Conclusion: P53 levels are low in AML patients. They are not associated with remission status or survival after six months and are not correlated with hematological values.

Sonographic Assessment of Splenic Manifestations in Sickle Cell Disease Patients and Its Relation to Hematological Parameters: A Cross-Sectional Study in Basra, Iraq.

Background Hemoglobinopathies, such as sickle cell disease (SCD), are inherited disorders of hemoglobin (Hb) synthesis.SCD presents with complex clinical manifestations, including anemia, painful episodes, andorgan damage due to recurrent vaso-occlusion. The spleen is one of the first organs affected in SCD patients, with hyposplenism typically occurring by age five. However, older patients may show variations in splenic size, which can complicate the diagnosis. Objective This study aimed to investigate the radiological manifestations of the spleen in patients with SCDusing sonographic assessment and the relationship between these manifestations and the patient's clinical and laboratory findings. Methodology This descriptive cross-sectional study was carried out at the Basra Hematology Center, which is the largest center for hematological diseases in the southern part of Iraq. It was carried out over a three-month periodfrom May 22 to August 22, 2024. A total of 81 patients aged 15 and above, diagnosed with SCD, and attending the outpatient clinic at Basra Hematology Center in Basra citywere included. Participants were identified through medical records and referrals from private outpatient clinics. Inclusion criteria ensured participants had a confirmed SCD diagnosis and met the age requirements. Exclusion criteria eliminated individuals with sickle cell trait, other hemolytic anemias, leukemia, relevant co-morbidities, or those who declined participation. After obtaining informed consent, each patient was interviewed by the research team,their blood was taken for lab tests, and then an ultrasound scan of their spleen was performed. Results Regarding the demographic characteristics of patients, age showed a statistically significant difference across the groups (p=0.017), indicating that marked splenomegaly is associated with younger individuals (mean age of 19.50 ± 4.95 years) compared to autosplenectomy, which is linked to older patients (mean age of 35.42 ± 11.84 years). Regarding radiological findings, splenic size was categorized into normal size, splenomegaly, small spleen, and autosplenectomy. Increased echogenicity is more frequently seen in the small spleen group (87.5%, p<0.001). Focal lesions, such as infarctions, were relatively uncommon and did not show significant variation across the groups. However, the presence of Gamna-Gandy bodies (GGB) was reported in a few patients and did not vary significantly among spleen status groups. The laboratory data showed notable significant differences in several key blood parameters. Hb levels were significantly lower in patients with marked splenomegaly (6.65 ± 0.21 g/dl) compared to other groups (p=0.01). White blood cell count(WBC) and platelet count(PLT) were significantly higher in the autosplenectomy group (WBC 12.29 ± 5.67 x 10³/μL; PLT 426.16 ± 222.85 x 10³/μL), both with p-values <0.001. Conclusion This study examined splenic changes in SCD patients, finding that autosplenectomy is more common in older patients, while splenomegaly is prevalent in younger ones. Increased splenic echogenicity indicated fibrosis, and patients with splenomegaly showed lower hemoglobin levels. Autosplenectomy was associated withhigher WBC and PLT levels. Although elevated HbF and certain genetic factors seemed protective against splenic atrophy, these findings were not statistically significant, warranting further research.

BAFF as a Potential Marker for Toxoplasma Gondii Seroprevalence Among Cancer Patients on Chemotherapy

Background: Toxoplasmosis is a global zoonotic disease, that is mainly asymptomatic in healthy persons, but critical and life-threatening in immunocompromised patients. The infection is caused by an opportunistic obligate intracellular parasite protozoon “Toxoplasma gondii” (T. gondii) that can cause fatal complications in immunosuppressed patients. Cancer patients are being immunocompromised from the cancer itself and on the other hand cancer therapy they receive may reactive a latent T. gondii infection that leaves them at high risk. The B-cell activating Factor (BAFF) is a cytokine that plays an essential role in the activation, maturation, and survival of B cells. It is vital for the appropriate functioning of the immune system. Monitoring BAFF levels in cancer patients undergoing chemotherapy could be important for preventing or controlling infections in these vulnerable patients. Objectives: This study aimed to detect seroprevalence of T. gondii in cancer patients receiving chemotherapy and assess the levels of BAFF in those patients. Materials and Methods: 150 serum samples were collected from oncology patients having different types of cancer and receiving chemotherapy, from different ages. And 30 samples from healthy people for control. In this cross-sectional study, samples were collected from the 1st of October 2023 to the 1st of March 2024, at Kirkuk Oncology and Hematology center. The method used was the Sandwich Enzyme-Linked Immunosorbent Assay (Sandwich-ELISA) technique. Results: the overall anti-T. gondii IgG and IgM seropositive samples were found to be 67 (37.2%) in the total study population and 67(44.7%) in cancer patients. BAFF levels were elevated in cancer patients infected with T. gondii compared with the cancer patients with no infection and the healthy control group. A significant difference was indicated with (p-value 0.0004). Conclusions: A high rate of T. gondii seroprevalence was revealed among oncology patients receiving chemotherapy with elevated levels of BAFF associated with T. gondii infection in those patients.

Liver transplantation for unresectable Klatskin tumor: experience of two centers, first distant results

Aim. Evaluation of the first distant results of the combined experience of liver transplantation for unresectable portal cholangiocarcinoma from two large specialized clinical centers.Materials and methods. In total, 23 attempts at liver transplantation for unresectable Klatskin tumor were undertaken. Out of them, 10 were conducted at the A.M. Granov Russian Research Center for Radiology and Surgical Technologies (Granov Center), and 13 were conducted at the Minsk Scientific and Practical Center for Surgery, Transplantology, and Hematology (Minsk Center). The maximum tumor size was 5 and 3 cm in patients operated at the Granov and Minsk Centers, respectively. In the Granov Center, neoadjuvant therapy included a combination of endobiliary photodynamic therapy, regional and systemic chemotherapy. Patients were included in the waiting list only in cases of decreased tumor marker levels and in the absence of disease progression and acute cholangitis. In the Minsk Center, stereotactic radiotherapy was used for neoadjuvant treatment in the absence of active cholangitis; the first 3 patients underwent liver transplantation without prior neoadjuvant treatment.Results. Due to disease progression, six patients were excluded. In three patients at the Mink Center, the diagnosis was not morphologically confirmed after liver transplantation. A total of 14 liver transplantations were performed for unresectable hilar cholangiocarcinoma. After neoadjuvant treatment at the Granov Center, normalization of the CA19-9 marker was observed in four patients, its decrease by 3–4 times was observed in two patients. Liver transplantation was performed in six patients. The average time from the onset of treatment to transplantation was 9.1 months (6–14). Out of the six patients, one was alive for 34 months, with the median overall survival being 22.2 months. Progression was the cause of death in only one patient. Out of the three patients without neoadjuvant treatment at the Minsk Center, two were alive at 16 and 134 months without progression. One patient died after transplantation from disease progression at 24 months. Stereotactic radiotherapy achieved normalization of CA19-9 in four patients; its twofold reduction was observed in one patient. The average time from the onset of treatment to transplantation was six months (3–12). The average CA19-9 tumor marker level by the time of transplantation was 11.3 IU/mL. At 20–26 months, three patients were alive without evidence of disease progression; two patients died of progression after 9 and 59 months.Conclusion. Liver transplantation for unresectable portal cholangiocarcinoma after neoadjuvant treatment regardless of the methods used is highly promising in carefully selected recipients.