Abstract in English:

ABSTRACT We investigated the predictive capacity of six prognostic indices [Karnofsky Performance Status (KPS), Hematopoietic Cell Transplant-Specific Comorbidity Index (HCT-CI), Disease Risk Index (DRI), European Bone Marrow Transplantation (EBMT) and Revised Pre-Transplantation Assessment of Mortality (rPAM) Scores and Endothelial Activation and Stress Index (EASIX)] in 205 adults undergoing post-transplant cyclophosphamide (PTCy)-based allo-HCT. KPS, HCT-CI, DRI and EASIX grouped patients into higher and lower risk strata. KPS and EASIX maintained appropriate discrimination for OS prediction across the first 2 years after allo-HCT [receiver operating characteristic curve (area under the curve (AUC) > 55 %)]. The discriminative capacity of DRI and HCT-CI increased during the post-transplant period, with a peak of prediction at 2 years (AUC of 61.1 % and 61.8 %). The maximum rPAM discriminative capacity was at 1 year (1-year AUC of 58.2 %). The predictive capacity of the EBMT score was not demonstrated. This study validates the discrimination capacity for OS prediction of KPS, HCT-CI, DRI and EASIX in PTCy-based allo-HCT.

Abstract in English:

ABSTRACT Introduction: The treatment of elderly multiple myeloma (MM) patients with autologous stem cell transplantation (ASCT) is a controversial procedure. Most clinical trials evaluating the safety and efficacy of ASCT have primarily included patients younger than 65 years. Design and methods: This was a retrospective analysis of patients with MM who underwent ASCT between 2008 and 2018. Patients at or over 65 years were compared with patients under 65 years. We analyzed treatment-related mortality (TRM), response rate, progression-free survival (PFS) and overall survival (OS). Results: Two hundred and twenty-one patients were included: 50 patients at or over 65 years, (median age 68 years), including 7 patients over 70 years and 151 patients under 65 years, (median age 57 years). No differences were found in the neutrophil and platelet engraftment, median days of hospitalization and life support requirement during the hospitalization period for the ASCT. No statistically significant differences were found in the incidence of TRM between both groups at 100 days post-transplant (2% vs. 2.9%, p = 0.322). The ASCT improved complete response and stringent complete response rates (44% vs. 37%, p < 0.001). Survival was not modified by age: after a median follow-up of 53 months, the estimated PFS rates at three years were 63% and 60% (p = 0.88) and the OS rates at five years were 75% and 74% (p = 0.72), respectively. Conclusion: Our data suggest that the ASCT is feasible in selected elderly patients with MM over 65 years of age, achieving response and survival rates similar to those of younger patients.

Abstract in English:

ABSTRACT Introduction: Diffuse large B-cell lymphoma (DLBCL) treatment in older patients is challenging. The Determination and Management of Risks for Practices and Procedures in the Elderly (DRIPP) is a multidimensional evaluation program that involves patients undergoing oncological treatments. Objective: We aimed to evaluate the overall survival and progression-free survival (PFS) of patients evaluated and those not evaluated by the DRIPP. Materials and methods: Retrospective cohort study, patients > 65 years with DLBCL were included. They were divided into 3 groups: patients with a diagnosis prior to the DRIPP implementation (pre-DRIPP), patients with the DRIPP (DRIPP) and patients with a diagnosis after the DRIPP implementation, but who did not undergo the evaluation (non-DRIPP). Results: A total of 125 patients were analyzed. Fourteen (11%) patients in the pre-DRIPP group, 74 (59%) in the DRIPP group, and 37 (30%) in the non-DRIPP group. In 43 (58%) patients of the DRIPPgroup,somedrugdoseadjustmentsweremadevs. 19 (15%) in the non-DRIPP (p = 0.03). There were no significant differences in terms of discontinuation of treatment or hematological toxicity between groups. The OS and PFS in one year was 64% (95%CI 34–83) and 50% (95%CI 23–72) for the pre-DRIPP group, 82% (95%CI 71–89) and 72% (95%CI 60–81) for the DRIPP group, 58% (95% CI 41–72) and 56% (95% CI 38–70) for the non-DRIPP group, (p = 0.08). The analysis was adjusted for probable confounders and no differences were found. Conclusions: This is the first study to evaluate the DRIPP as a decision-making tool in patients with lymphoma and showed a trend towards improvement in the OS in evaluated patients.

Abstract in English:

ABSTRACT Introduction: The expression pattern of CD27 and CD44 was found to correlate with the differentiation stages of B cell precursors, which were known to be involved in a variety of immunological responses. Aim of the study: This study aimed to determine the biological significance of CD27 and CD44 expression in patients with B-precursor acute lymphoblastic leukemia (B-ALL), as well as their association with standard prognostic factors and therapeutic response. Patients and methods: This case-control study included 60 pediatric patients newly diagnosed with B-ALL and 30 pediatric controls. The patient CD27 and CD44 levels were measured using the Beckman Coulter Navios Flow Cytometer. Results: Most malignant cells (91.6 %) expressed CD44, but only 50 % of the patients had CD27 expressed. The positive CD 44 expression was associated with unfavorable prognostic markers, including a decrease

Abstract in English:

ABSTRACT Introduction: High-dose methotrexate (HDMTX) is an essential part of chemotherapy regimens for hematologic neoplasms. The incidence of acute kidney injury (AKI) after HDMTX in unmonitored outpatient infusion had not been reported in adults yet. In this study, we evaluated toxicity data after outpatient administration of HDMTX without drug monitoring. Methods: Patients 16 years old or over with acute lymphoblastic leukemia and non-Hodgkin lymphoma who received at least one outpatient infusion of HDMTX without drug level monitoring were included. This is a retrospective, nested case-control study, in which the cases comprised patients who developed AKI after HDMTX. Methods: Patients 16 years old or over with acute lymphoblastic leukemia and non-Hodgkin lymphoma who received at least one outpatient infusion of HDMTX without drug level monitoring were included. This is a retrospective, nested case-control study, in which the cases comprised patients who developed AKI after HDMTX. Results: Overall, 302 patients were included, encompassing 840 infusions. Hospitalization occurred in 8.6 %. A total of 25 patients presented AKI after HDMTX administration, corresponding to 3 % of the methotrexate (MTX) infusions and 8.3 % of the patients. HIV-associated Burkitt lymphoma was more common in patients who presented AKI (18 vs. 6.8 %, p = 0.03). Baseline factors related to AKI after HDMTX were age > 44 y, body surface area ≥ 1.76 m2, body mass index (BMI) ≥ 23.8 kg/m2, glomerular filtration rate, and thrombocytopenia (< 150×109/L). Multivariable analysis for adjusting such factors found that BMI was independently related to AKI after HDMTX (OR 3.8). Death after AKI occurred in 56 %. Conclusion: Our data showed a similar rate ofAKI after HDMTX to that reported in the literature, even without drug monitoring. However, patients who developed AKI in our cohort fared worse than expected, with more hospitalizations and death. A higher BMI was associated with the MTX-induced AKI in our cohort, suggesting a differential drug clearance and the need for specific guidelines for obese patients.

Abstract in English:

ABSTRACT Introduction: An intracellular parasite of mononuclear phagocytes, mainly distributed in the bone marrow and the spleen, causes visceral leishmaniasis. Complete blood count (CBC) reveals the poorly understood pathogenesis of anemia, leukopenia and thrombocytopenia. Our study aimed to compare the CBC with bone marrow cytomorphological features and their association with clinical outcomes to clarify this relevant issue. Methods: The CBC and bone marrow of 118 patients were described by two hematologists and compared to check their association with each other and mortality. Results: Peripheral cytopenias were common findings, particularly anemia, as seen in almost all patients. No relationship was found between values of hemoglobin, neutrophils and platelet count with fatal outcomes. The bone marrow was normocellular in 61.9% of the cases. Dysplasia figures were frequent and 49.1% of the samples had dysgranulopoiesis. Additionally, erythroid hyperplasia was found in 72% of the patients with severe anemia. Patients with reduced bone marrow cellularity, erythroid hypercellularity and dyserythro-poiesis seem to have a riskier disease. Conclusion: The study results suggest that the bone marrow of patients with visceral leish-maniasis manifests a reactional pattern to the inflammatory event, thereby modulating cytokines and other colony growth factors. This compensatory response may be dysplastic and ineffective and generate peripheral cytopenias of varying intensity. Further studies are needed to clarify the signaling pathways involved, which may be used as therapeutic tools in the future.

Abstract in English:

ABSTRACT Introduction: The bone marrow (BM) microenvironment plays a significant role in acute myeloid leukemia (AML) genesis and there is evidence that BM mesenchymal stromal cells (BMMSCs) can support leukemia progenitor cell proliferation and survival and provide resistance to cytotoxic therapies. Hypothesis and method: Nevertheless, currently unknown are the relevance of the spatial localization of AML cells relative to the BMMSCs and whether BMMSCs from patients with AML and healthy subjects have similar properties. To address these issues, we performed a differential gene expression analysis using RNA-sequencing data generated from healthy donors (HDs) and leukemic BMMSCs. Results: The Gene Set Enrichment Analysis (GSEA) revealed that leukemic BMMSCs were associated with the terms "positive regulation of cell cycle", "angiogenesis" and "signaling by the estimated glomerular filtration rate (eGFR)", whereas healthy donor (HD)-derived BMMSCs were associated with "programmed cell death in response to the reactive oxygen species (ROS)", "negative regulation of the cytochrome C from the mitochondria" and "interferon signaling". Next, we evaluated the mitochondrial superoxide production in AML cells in a co-culture layered model. The superoxide production was reduced in leukemic cells in close contact (adhered to the surface or beneath the cell layer) with BMMSCs, indicating lower oxidative stress. Conclusion: Taken together, our results suggest that AML-derived BMMSCs are transcriptionally rewired and can reduce the metabolic stress ofleukemic cells.

Abstract in English:

ABSTRACT Objectives: To assess the prognostic value of C-Reactive Protein (CRP), at diagnosis and during follow-up, of patients with Hodgkin's Lymphoma treated at the Hematology Service of the Santa Casa de Saão Paulo Hospital, and to correlate serum CRP levels with disease stage and treatment response. Methods: A retrospective study involving review of 71 medical records of patients diagnosed with Hodgkin's Lymphoma between February 2012 and January 2016 was performed. Three patients were subsequently excluded, giving a total of 68 patients for analysis. A level of CRP > 1 mg/dl was considered elevated. Results: Patients were predominantly male (61.8 %) and mean age was 34 years. Fifty-three (78 %) patients had advanced stage and (76.5 %) had B symptoms. Elevated baseline CRP was associated with greater likelihood of B symptoms (p = 0.02) and of advanced stage (p = 0.015). Patients with Low CRP level after 5th and 6th cycles of chemotherapy was associated with complete response (p = 0.04 and p = 0.03, respectively). Treatment-refractory patients had greater risk ofdeath (p = 0.002). Conclusion: CRP is clinically important for follow-up of patients with Hodgkin's Lymphoma, where high levels were associated with advanced disease and/or presence of B symptoms. CRP level was considered a predictor of treatment response. Persistence of high CRP values during treatment was associated with refractoriness.

Abstract in English:

ABSTRACT Introduction: Hematopoietic stem cell transplantation (HSCT) is a widely used therapy, but its success largely depends on the number and quality of stem cells collected. Current evidence shows the complexity of the hematopoietic system, which implies that, in the quality assurance of the apheresis product, the hematopoietic stem cells are adequately characterized and quantified, in which mass cytometry (MC) can provide its advantages in high-dimensional analysis. Objective: This research aimed to characterize and enumerate CD45dim/CD34+ stem cells using the MC in apheresis product yields from patients with chronic lymphoid malignant diseases undergoing autologous transplantation at the Abu Dhabi Stem Cells Center. Methods: An analytical and cross-sectional study was performed on 31 apheresis products from 15 patients diagnosed with multiple myeloma (n = 9) and non-Hodgkin lymphomas (n = 6) eligible for HSCT. The MC was employed using the MaxPar Kit for stem cell immuno-phenotyping. The analysis was performed manually in the Kaluza and unsupervised by machine learning in Cytobank Premium. Results: An excellent agreement was found between mass and flow cytometry for the relative and absolute counts of CD45dim/CD34+ cells (Bland-Altman bias: -0.029 and -64, respectively), seven subpopulations were phenotyped and no lineage bias was detected for any of the methods used in the pool of collected cells. A CD34+/CD38+/CD138+ population was seen in the analyses performed on four patients with multiple myeloma. Conclusions: The MC helps to characterize subpopulations of stem cells in apheresis products. It also allows cell quantification by double platform. Unsupervised analysis allows results completion and validation of the manual strategy. The proposed methodology can be extended to apheresis products for purposes other than HSCT.

Abstract in English:

ABSTRACT Introduction: Flumatinib, a highly selective ABL kinase inhibitor, exhibits stronger inhibition of intracellular BCR-ABL tyrosine kinase activity, compared to Imatinib. However, there is limited research comparing the real-world efficacy and safety of flumatinib and dasatinib in patients with Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Objective: Investigating the differences in therapeutic efficacy and safety between flumatinib and dasatinib in combination with multi-drug chemotherapy for the treatment of newly diagnosed Ph+ ALL. Method: In this study, we assessed 43 patients with newly diagnosed Ph+ ALL (20 in the flumatinib group, 23 in the dasatinib group). Results: There were no significant differences in gender, age, fusion gene type, initial blood routine, bone marrow blast cell ratio or chromosome karyotype between the two groups. Within 1 month, there were no significant differences in the complete response (CR), major molecular response (MMR) or minimal residual disease (MRD) negativity rate between the flumatinib and dasatinib groups. Similarly, within 3 months, there were no significant differences in CR or MMR rates between the two groups. However, the rates of complete molecular response (CMR) and MRD negativity within 3 months were significantly higher in the flumatinib group, compared to the dasatinib group (P < 0.05). Additionally, the flumatinib group exhibited fewer adverse reactions compared to the dasatinib group. Conclusion: These findings suggest that flumatinib is a safe and effective tyrosine kinase inhibitor (TKI) for achieving CMR and MRD negativity in patients with Ph+ ALL, as supported by this small series of patients.

Abstract in English:

ABSTRACT Background: T315I mutations of the BCR::ABL1 gene lead to resistance to tyrosine kinase inhibitors (TKIs). This study evaluated the performance of digital droplet polymerase chain reaction (ddPCR) in quantifying T315I mutations and their frequency in Philadelphia chromosome (Ph) positive hematological patients. Methods: The course of disease and BCR::ABL1 fusion transcripts (e13a2, e14a2 and e1a2) were retrospectively reviewed in 21 patients with acute lymphoblastic leukemia (ALL) and 85 patients with chronic myeloid leukemia (CML). T315I mutation analysis was carried out using ddPCR and the limit of detection was assessed using mutant T315I DNA at varying variant allele fractions. Results: T315I mutations were found in two ALL patients and one CML patient without remission in molecular biology and with mutation burdens of 29.20%, 40.85%, and 3.00%, respectively. The mutation burden of ALL patients was higher than that of CML patients, but there was no significant difference between the two (p-value = 0.0536). The test’s limit of detection was 0.02% with a correlation coefficient greater than 0.99 between the expected and actual detection abundances. Conclusion: T315I mutations have a high incidence in Ph-positive ALL patients even if the course of disease is short. In molecular biology, T315I mutation detection is indicated for CML patients not in remission.

Abstract in English:

ABSTRACT Background: Sarcopenia, characterized by decreased muscle mass, strength, and function, is associated with adverse outcomes. The prevalence of sarcopenia and the effect of the inflammatory response on muscle strength loss in children undergoing hematopoietic stem cell transplantation (HSCT) are unknown. This study aimed to estimate the prevalence of sarcopenia on admission and its associated clinical factors in children and adolescents undergoing HSCT and to determine the extent to which the systemic inflammatory response during hospitalization affects muscle strength. Method: This was a prospective study of patients aged 6–18 years old undergoing HSCT. The outcome variables were the prevalence of sarcopenia on admission (loss of strength and skeletal muscle mass) and the loss of handgrip strength during hospitalization. Potential explanatory variables included age, sarcopenia, nutritional status and systemic inflammation as measured by serum C-reactive protein, albumin and ferritin concentrations. Results: Eighty patients with a mean age of 11.5 (± 3.5) years were included. The main diagnoses were acute lymphocytic leukemia, acute myeloid leukemia and aplastic anemia. Eleven percent of patients had sarcopenia upon admission. Female sex, sarcopenia on admission (β coefficient: 0.70; 95% CI: -1.30 to –0.12; p-value = 0.018) and serum C-reactive protein concentration (β coefficient: –0.10; 95% CI: –0.16 to –0.04; p-value = 0.001) were associated with handgrip strength loss from admission to 14 days after HSCT. Conclusion: Sarcopenia on admission and the degree of systemic inflammatory response are associated with decreased handgrip strength during hospitalization in pediatric patients undergoing HSCT. Further studies using the same criteria for diagnosing sarcopenia are required to enhance our understanding of these relationships.

Abstract in English:

ABSTRACT Background: Efficient classification of T-acute lymphoblastic leukemia (T-ALL) involves considering various factors, such as age, white blood cell count, and chromosomal alterations. However, studying protein markers are crucial to improving T-ALL patients’ diagnosis and treatment. A study analyzing the expression of proteomes was conducted to identify promising early-stage biomarkers for T-ALL patients Methods: Label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze the blood proteins of both patients and healthy individuals to identify new biomarkers for T-ALL. The findings were validated by RT-PCR, ELISA and computational analysis Results: The study identified 1467 proteins in the blood, of which nine were upregulated and 35 were downregulated by more than 2-fold. T-ALL patients showed a significant increase in specific disease-related proteins, such as eleven-nineteen lysine-rich leukemia protein, triggering receptor expressed on myeloid cells 1, cisplatin resistance-associated-overexpressed protein, X-ray radiation resistance-associated protein 1, tumor necrosis factor receptor superfamily member 10D, protein S100-A8, and copine-4, by more than 3-fold Conclusion: The findings of this study provide a valuable protein map of leukemic cells and identify potential biomarkers for leukemic aggressiveness. However, further studies using larger T-ALL patient samples must confirm these preliminary results.

Abstract in English:

ABSTRACT Multiple myeloma (MM) is a prevalent hematological malignancy with high recurrence and no definitive cure. The current study revisits the role of the IGF1/IGF1R axis in MM, introducing a novel inhibitor, NT157. The IGF1/IGF1R pathway is pivotal in MM, influencing cell survival, proliferation, and migration and impacting patient survival outcomes. NT157 targets intracellular proteins such as IRS and STAT proteins and demonstrates antineoplastic potential in hematological malignancies and solid tumors. In the present study, we assessed IGF1R signaling-related gene expression in MM patients and healthy donors, unveiling significant distinctions. MM cell lines displayed varying expression patterns of IGF1R-related proteins. A gene dependence analysis indicated the importance of targeting receptor and intracellular elements over autocrine IGF1. NT157 exhibited inhibitory effects on MM cell viability, clonal growth, cell cycle progression, and survival. Moreover, NT157 reduced IRS2 expression and STAT3, STAT5, and RPS6 activation and modulated oncogenes and tumor suppressors, fostering a tumor-suppressive molecular profile. In summary, our study demonstrates that the IGF1/IGF1R/IRS signaling axis is differentially activated in MM cells and the NT157’s capacity to modulate crucial molecular targets, promoting antiproliferative effects and apoptosis in MM cells. NT157 may offer a multifaceted approach to enhance MM therapy.

Abstract in English:

ABSTRACT Introduction: Early Death (ED) remains challenging in newly diagnosed acute promyelocytic leukemia (APL), especially in developing countries. The clinical and laboratory profile at diagnosis were evaluated and causes and risk factors were investigated in adult APL patients. Method: A retrospective real-life analysis of 141 medical records was performed of patients diagnosed with APL between 2007 and 2018, whether they were treated with the IC-APL 2006 protocol or not. Risk factors were assessed by univariate and multivariate analysis. Main results: Overall, 112 patients were included in the study. ED occurred in 22.3% of cases, surpassing clinical trial reports, with non-protocol-eligible patients presenting notably higher rates (60%), potentially due to their clinical status. Hemorrhage (60%) and infection (33.3%) were the leading causes of ED. Univariate analysis associated ED to the ECOG score; white blood cell (WBC) count; body mass index; levels of hemoglobin, albumin, uric acid, and creatinine, aPTT and INR and FLT3 mutations. Multivariate analysis identified ECOG score ≥2 and elevated WBC count as independent risk factors. Conclusion: ED remains a substantial challenge in APL, especially in real-world settings with hemorrhage and infection being the leading causes. ECOG status and WBC count emerged as independent risk factors, while age and platelet count lacked a 30-day prognostic correlation. Evaluating prognostic enhancement tools in controlled trials and real-life settings is pivotal to improving APL outcomes.

Abstract in English:

ABSTRACT Background/aim: There are several complications of hematopoietic stem cell transplantation. Without any doubt, most important of these is aGvHD that increases transplant-related mortality. The aim of this study is to investigate whether ST-2 and Reg3α levels measured at an early stage in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation can be individual biomarkers identifying future GvHD and predicting treatment response. Materials and methods: From January 2019 to January 2021, 27 patients undergoing hematopoietic stem cell transplantation for primary immunodeficiency or hematopoietic diseases formed the study group. During their follow-up, the patients were classified into two groups as those developing and those not developing aGvHD. Nineteen healthy volunteers from a similar age group who needed their blood samples drawn for other reasons and who did not have any history of chronic disease, infection or medication use formed the control group. Blood samples of patients scheduled to have allogeneic HSCT were obtained before the administration of the preparative regimen, on Day +7 post-transplant and on the day of diagnosis if they developed aGvHD. Serum samples were stored at -20°C until the day of processing. ST2 and Reg3α levels were measured using the ELISA method. Results: For patients who developed aGvHD (n = 13), ST2 levels obtained before the transplantation, on Day +7 post-transplant and on the day of aGvHD diagnosis (in patients developing GvHD) were significantly higher compared to the healthy Control Group (p-value <0.05). As regards to the samples obtained on the same days, ST2 levels did not differ significantly among patients who developed and those who did not develop GvHD (n = 14; p-value >0.05). ST2 levels of samples obtained on the days that acute skin and gastrointestinal tract GvHD developed did not differ significantly between these two groups (p-value >0.05). Reg3α levels of the pre-transplant samples, on Day +7 after the transplantation and on the day of aGvHD diagnosis did not show any difference between any of the groups (p-value >0.05). As only two patients died after transplantation, thus correlation ofST2 and Reg3α levels with transplant-related mortality could not be proven. Conclusion: The results of this study suggest that ST2 and Reg3α levels are neither diagnostic nor prognostic or predictive biomarkers of aGvHD, steroid resistance or transplant-related mortality in pediatric patients. This study can be regarded as a pilot study because of the small patient population; more research involving a larger patient population is required.

Abstract in English:

ABSTRACT Background: Acute myeloid leukaemia (AML) is considered a costly disease. Depending on the risk stratification, the patient may receive consolidation with cycles of intermediate doses of cytarabine, auto-HSCT or allo-HSCT according to availability in each service and the availability of a compatible donor. Literature data indicate that safety and effectiveness do not differ between consolidation therapy with intermediate-dose cytarabine or auto-HSCT, and so the cost can help physicians and health managers in their choice. Method: The cost of the second consolidation was compared in 18 to 60-year-old patients with de novo AML who were included in the International Consortium of Acute Myeloid Leukaemia (ICAML) protocol. Patients treated with auto-HSCT or intermediate doses of cytarabine (IDAC) were analysed during four years using the microcosting methodology. Results: The mean costs for auto-HSCT and IDAC were BRL$ 34,900.95 (range: 23,611.36 -41,229.59) and 15,231.64 (range: 6,546.36-23,253.53), respectively. The mean duration of in-hospital stay was 88.4 (93-133) and 94 (50-153) days, respectively. The mean cost of the four cycles of treatment was BRL$ 114.212,78 for auto-HSCT and BRL$ 121.980,93 for the chemotherapy group. Regardless of the type of treatment, the input that had the greatest economic impact was hospital admission, mainly due to infections. Conclusion: Auto-HSCT had a lower average cost per patient and hospitalization rate than chemotherapy.

Abstract in English:

ABSTRACT Introduction: Common side effects after stem cell transplantation (SCT), such as anorexia, nausea, and vomiting, can disrupt the quality of life of patients. Therefore, this study aimed to determine the effect of self-care education with smart phone applications on the severity of nausea and vomiting after SCT in leukemia patients. Materials and methods: In this clinical trial study, using the blocked randomization method 104 leukemia patients undergoing SCT were assigned to two groups, intervention and control. The patients of the Control Group received routine care, and the Intervention Group received self-care education with a smart mobile phone application, in addition to routine care. Two weeks, one month, and three months after the start of the intervention, the severity of nausea and vomiting was evaluated using the visual analog scale (VAS) and the Khavar Oncology scale, both of which were completed by both Control and Intervention Groups. Data were analyzed using chi-square, Fisher’s exact, Mann-Whitney, and Friedman tests using the Statistical Package for Social Sciences version 25 software. Results: The severity of nausea and vomiting in leukemia patients undergoing SCT was significantly different in the two groups at all three timepoints (two weeks, one month, and three months) after transplantation (p-value = 0.000). Conclusion: The severity of nausea and vomiting after SCT in leukemia patients was improved by self-care education with a smart phone application. Therefore, this method is recommended to reduce the severity of nausea and vomiting in leukemia patients who undergo transplantation.

Abstract in English:

ABSTRACT Background: Autologous stem cell transplantation is a treatment modality for several diseases. Prediction of successful mobilization may be useful to optimize hematopoietic stem cell collection. Study design and methods: This was a retrospective study with data from transplantation candidates between September 2015 and December 2021 being analyzed. The medical record of each patient was reviewed to mine mobilization information. The laboratory data analyzed were CD34+ cell enumeration and pre-collection peripheral blood cell count. The primary outcome, good mobilization, was defined as a CD34+ cell count ≥20/μL. Results: This study included 807 patients. Increased patient weight, low mean corpuscular volume, high nucleated red blood cells, peripheral blood mononuclear cell and immature granulocyte counts were significantly associated with good mobilization. In addition, patients diagnosed with multiple myeloma were two times more likely to be good mobilizers than patients with lymphoma. The model was applied to a validation set to identify patients who underwent apheresis (CD34+ cell count ≥10 μL), resulting in a sensitivity of 69 %, a specificity of 95 %, positive predictive value of 98 %, and a negative predictive value of 50 %. Conclusion: Success in mobilization was greater in patients who underwent the first mobilization cycle and who had a diagnosis of multiple myeloma. Furthermore, higher body weight, and nucleated red blood cells, immature granulocytes and mononuclear cell counts, as well as low mean corpuscular volumes, were associated with successful mobilization.

Abstract in English:

ABSTRACT Introduction: Different factors affect the quality and viability of cord blood stem cells, and therefore the efficacy of umbilical cord stem cell transplantation. Fetal distress is one factor affecting the quantity of CD34+ cells in cord blood. This study was designed to compare the viability and yield of the umbilical cord blood stem cells of women who have undergone emergency lower segment caesarean section for fetal distress or for other causes. Materials and methods: This cross-sectional analytical study was performed at a tertiary care hospital facility with a total sample size of 68: 34 participants had undergone emergency C-section for fetal distress, and 34 had undergone emergency C-section for other causes. Umbilical cord blood was collected ex-utero in a 350 mL bag with citrate-phosphate-dextrose solution with adenine. Three milliliter of blood were transferred to an ethylenediaminetetraacetic acid (EDTA) tube for cell counts and flow cytometry testing for CD34+. The chisquare test was used to compare the total mononuclear cell, CD34+, and viability between the groups. Results: The CD34+ count [mean 4.9 versus 1.1 (× 106 cells/unit)] and total nucleated cell count [mean 14.2 versus 7.5 (× 108/unit)] were significantly higher in cord blood units collected from women who delivered by C-section for fetal distress (p-value <0.05). However, the volume of umbilical cord stem cells and viability of stem cells did not vary significantly based on the presence or absence of fetal distress (p-value >0.05). Conclusion: The current study shows that umbilical cord blood collected during fetal distress has a significantly higher content of stem cells and total nucleated cells than the non-fetal distress group

Abstract in English:

ABSTRACT Introduction: Secondary genetic alterations, which contribute to the dysregulation of cell cycle progression and lymphoid specialization, are frequently observed in B-cell precursor acute lymphoblastic leukemia (B-ALL). As IKZF1 and BTG1 deletions are associated with a worse outcome in B-ALL, this study aimed to address whether they synergistically promote glucocorticoid resistance. Methods: Small interfering RNA was used to downregulate either IKZF1, or BTG1, or both genes in the 207 B-ALL cell line. Cell viability was investigated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and trypan blue exclusion assays. The expression levels of IKZF1, BTG1 and glucocorticoid-responsive genes (DUSP1, SGK1, FBXW7 and NR3C1) were evaluated by real time quantitative real time polymerase chain reaction (PCR). Results: Isolated silencing of BTG1, IKZF1, or both genes in combination under dexamethasone treatment increased cell viability by 24%, 40% and 84%, respectively. Although BTG1 silencing did not alter the expression of glucocorticoid-responsive genes, IKZF1 knockdown decreased the transcript levels of DUSP1 (2.6-fold), SGK1 (1.8-fold), FBXW7 (2.2-fold) and NR3C1 (1.7-fold). The expression of glucocorticoid-responsive genes reached even lower levels (reducing 2.4-4 fold) when IKZF1 and BTG1 silencing occurred in combination. Conclusions: IKZF1 silencing impairs the transcription of glucocorticoid-responsive genes; this effect is enhanced by concomitant loss of BTG1. These results demonstrate the molecular mechanism by which the combination of both genetic deletions might contribute to higher relapse rates in B-ALL.

Abstract in English:

ABSTRACT Background: A lower dosage of tyrosine kinase inhibitors (TKIs) in patients with chronic myeloid leukaemia (CML) has shown efficacy in managing short-term toxicity and maintaining a deep molecular response in patients who fail to achieve treatment-free remission. Method: From over 700 patients with CML who were treated at two centres over the last three decades, this retrospective study identified eight patients characterised by long-term treatment failure and simultaneous prolonged significant haematologic toxicity that prevented the use of the standard tyrosine kinase inhibitor dosage. Results: Patients had a high or intermediate ELTS risk score, and most had significant comorbidities. Two patients were treated previously with busulfan, and four were aged over 70, which might explain the reduced pool of normal haematopoietic stem cells. However, concomitant myelodysplastic syndrome or the presence of clonal haematopoiesis of indeterminate potential was not demonstrated. Despite prolonged treatment failure, the survival of these patients (who were ineligible for stem cell transplantation) ranged from 45-396 months. Neither mutations in the ABL kinase domain nor additional cytogenetic abnormalities developed during the treatment of these patients, prompting speculation about the low selective pressure of low-dose tyrosine kinase inhibitors and/or the absence of mutations at diagnosis. Conclusion: It is important not to stop treatment with tyrosine kinase inhibitors at a low personalised dosage in CML patients with prolonged significant haematologic toxicity despite long-term treatment failure.

Abstract in English:

ABSTRACT Introduction: The scenario of adult patients with acute lymphoblastic leukemia treated in Brazil has not been well described yet. Methods: Four hundred patients diagnosed with acute lymphoblastic leukemia from 1981 to 2019, registered in the Brazilian lymphoma and leukemia association (ABRALE) or their caregivers were interviewed by telephone to evaluate patient-reported perceptions of diagnosis, treatment and adverse effects. Results: Overall, 203 were male with a mean age of 15.7 years and median follow-up of 6.2 years. Main presenting symptoms were fever (39 %), bleeding/ecchymosis (38 %), intense fatigue (30 %), and musculoskeletal pain (28 %). The proportion of patients diagnosed within one week of symptoms onset differed between public (17.9 %) and private healthcare (31.1 %; p-value = 0.019). Additionally, diagnostic difficulties were higher in public care: 35 % versus 22.6 % (p-value = 0.034). Only 36 patients were able to report their treatment protocols; from a list of eight reported protocols, the most common were the Brazilian Childhood Cooperative Group for Treatment of Acute Lymphoblastic Leukemia in Children (GBTLI -10/ 27.8 %) and Berlin-Frankfurt-Münster (BFM - 8/22.2 %). Seventy patients (17.5 %) required treatment modification, 37.1 % due to severe adverse effects; 21.7 % received short treatment duration (≤6 months) and 16 % proceeded to allogeneic hematopoietic stem cell transplantation with 17/64 (27 %) reporting difficulties in this step, characterized as >3 months delay. Indication for transplantation was related to minimal residual disease and cranial radiotherapy; 41.7 % reported treatment-related adverse effects (range: 1-6), in particular: mood disorders (26.3 %), neurologic deficit (13.8 %), cognitive/memory impairment (12 %), and lung disease (15 %). Risk factors for adverse effects were age, indication of transplantation and living in a large city. Treatment disparities such as diagnostic and transplantation delays remain challenges in these patients. Conclusions: Urgent interventions are needed to optimize healthcare and reduce adverse effects, especially in adolescent and young adult patients.

Abstract in English:

ABSTRACT Background: Providing quality supportive therapy for children with cancer is essential to reduce the high mortality rates in low- and middle-income countries. Febrile neutropenia is the most common life-threatening complication of cancer in children. The objective of this study was to evaluate the long-term effectiveness of the ‘Golden Hour’ intervention in reducing the time to administer antibiotics and its impact on clinical outcomes in a Mexican hospital. Methods: A comparative study of children with febrile neutropenia who attended the emergency department at the Hospital Universitario “Dr. José Eleuterio González” was performed between January 2017 and December 2022. In May 2019, this center joined the collaborative ‘Mexico in Alliance with St. Jude’ project. An adapted improvement program was developed based on the implementation of an algorithm comprising institutional guidance, supplies kit, standardization of sample processing, training of healthcare providers, and patient education. The time to antibiotic administration was compared with clinical outcomes between the historical control and post-intervention groups. Results: A total of 291 patients were included, 122 in the pre-intervention period and 169 in the intervention period. Only 5.7 % of the pre-intervention group received the first dose of antibiotics within 60 min of presenting to the emergency department compared to 84.6 % in the intervention group (p-value <0.000). The median times to antibiotic administration in the pre-intervention and post-intervention periods were 269.4 and 50.54 min, respectively (p-value <0.000). Clinical deterioration and admission to the pediatric intensive care unit decreased significantly from 6.6 % to 2.3 % (p-value = 0.03). Conclusions: Sustainability of the quality improvement project ‘Golden Hour’ in low- to mid-income countries demonstrated high effectiveness in reducing time to antibiotic administration among children with febrile neutropenia and improved clinical outcomes over three years of implementation.

Abstract in English:

ABSTRACT Introduction: Plasma cell quantification in bone marrow is important for diagnosis, prognosis, and treatment of plasma cell diseases. It can be performed by several methods such as aspiration, imprint and flow cytometry, and biopsy. Objectives: To compare plasma cell counts at diagnosis of plasma cell diseases using different methods. Methods: An observational study was carried out of laboratory results of adult patients with plasma cell diseases, who underwent aspiration, imprint cytology, flow cytometry (CD38, C138) and biopsy in a single institution between January 2015 and May 2021. The intraclass correlation coefficient was used to assess agreement between different methods with results stratified into three groups: <10%; 10-59% and ≥60% of infiltration. Results: Sixty-seven cases were studied: 59.7% were men with a median age of 70 (range: 32 -85) years. The diagnoses were multiple myeloma in 61%, gammopathy of undetermined significance in 25.4%, smoldering myeloma in 6% and other plasma cell dyscrasias in 7.6%. Less than 10% infiltration was found in 32 (47.7%), 35 (52.2%), 44 (65.7%) and 25 (37.3%) of patients, respectively by aspiration, imprint cytology, flow cytometry and biopsy. Infiltration ≥60% was detected in 7 (10.4%), 4 (6.0%), 2 (3.0%) and 21 (31.3%) cases, respectively. There was disagreement between the results in 37 (55.2%) of patients. Of these, 28 had greater infiltration in biopsies. The concordance (Kappa index) of biopsy with aspiration, imprint and flow cytometry was 0.501, 0.408 and 0.17; of aspiration with imprint and flow cytometry, it was 0.738 and 0.541 and between imprint and flow cytometry, it was 0.573%. Conclusions: Only aspiration and imprint cytology results agreed. Biopsy showed greater infiltrations than the other methods, but aspiration, and imprint and flow cytometry provided additional data in the diagnosis and thus should also be performed.

Abstract in English:

ABSTRACT Objective: Bacteremia is a serious complication in patients undergoing allogeneic hematopoietic stem cell transplantation. The aim of this study was to determine the frequency, epidemiological profile, and risk factors of bacteremia early after allogeneic hematopoietic stem cell transplantation. Methods: An observational descriptive retrospective study was conducted in patients who received transplants between January 2016 and December 2021. Early bacteremia was defined as blood stream infection occurring between Day 0 and Day 100 after transplantation. Results: Forty episodes of early bacteremia occurred in 36/245 transplanted patients. Fifteen episodes (37.5%) were due to gram-positive bacteria and 25 (62.5%) to gram-negative bacteria. The most frequent species isolated were coagulase negative staphylococci (CoNS) in gram-positive bacteremia (n = 8/15), and Klebsiella species (8/25) and Pseudomonas species (8/25) in gram-negative bacteremia. Twenty-nine episodes of bacteremia (72.5%) occurred during the first 30 days after transplantation with a median time of nine days (range: 0-90 days). Coagulase negative staphylococci were methicillin-resistant in 75% of cases, the only Staphylococcus aureus isolated was methicillin-resistant. All gram-positive bacilli were penicillin-resistant. Gram-negative bacilli were multidrug resistant in 61.5% of cases. In multivariate analysis, bone marrow as source of graft (p-value = 0.02) and cytomegalovirus reactivation (p-value = 0.02) were significantly associated with an increased risk of bacteremia. Mortality attributable to bacteremia was 2.8%. The one-year overall survival was not significantly different between those with and without bacteremia. Conclusions: Bacteremia was more frequent within the first 30 days after transplantation indicating the crucial role of neutropenia. An increase in multidrug resistant gram-negative bacteremia was noted.

Abstract in English:

ABSTRACT The central role of the control of apoptosis in the pathophysiology of Philadelphia chromosome-negative myeloproliferative neoplasms has recently been reinforced in genetic and pharmacological studies. The inhibitor of apoptosis protein family has eight members and plays an important role in apoptosis, with the most studied being survivin (BIRC5) and X-linked inhibitor of apoptosis (XIAP). YM155 is a small molecule with antineoplastic potential that has been described as a suppressant of survivin and XIAP. In the present study, BIRC5 expression was significantly increased in primary myelofibrosis patients compared to healthy donors. On the other hand, XIAP expression was reduced in myeloproliferative neoplasms patients. In JAK2V617F cells, YM155 reduces cell viability and autonomous clonal growth and induces apoptosis, cell cycle arrest, and autophagy. HEL cells that show greater malignancy are more sensitive to the drug than SET2 cells. In the molecular scenario, YM155 modulates apoptosis-, cell cycle-, DNA damage- and autophagy-related genes. Protein expression analysis corroborates the observed cellular phenotype and exploratory gene expression findings. In summary, our results indicate that survivin/BIRC5 and XIAP are differently expressed in myeloproliferative neoplasms and YM155 has multiple antineoplastic effects on JAK2V617F cells suggesting that inhibitor of apoptosis proteins may be a target for pharmacological interventions in the treatment of these diseases.

Abstract in English:

ABSTRACT Background: Neuroblastomas account for 8–10 % of all cancer diagnoses among children. Most patients present with advanced, high-risk disease and 90 % are less than five years old. The burden of morbidity and mortality is high and is quantifiable by measures of health-related quality of life (HRQL). Measuring quality of life in under five-year-old children is a particular challenge that has been met with the development of the Health Utilities Pre-School (HuPS) instrument. Quality of life studies in children with cancer are scarce in low- and middle-income countries and are usually conducted at a single center, thus limiting any conclusions drawn. This pilot study aimed to assess the health-related quality of life of children at the time of diagnosis of high-risk neuroblastomas. Method: This prospective cross-sectional multicentric study assessed the quality of life of children with high-risk neuroblastoma. The Health Utilities Pre-School instrument was applied to under five-year-olds, and the related Health Utilities Index Mark 3 instrument to over five-year olds. Main Results: Eleven patients participated in this study. There was a high burden of morbidity at diagnosis, often equating to severe disability, indicative of states of health with scores worse than being dead in two under five-year-old children. Conclusion: The results of the current study will help to set research priorities for subsequent investigations and provide a basis to improve supportive care for children with high-risk neuroblastoma.

Abstract in English:

ABSTRACT Background: Citrate-related hypocalcemia is the most common adverse event linked with peripheral blood progenitor cell apheresis. A previous retrospective study highlighted the prophylactic effectiveness of oral calcium drinks before apheresis, supplemented with intravenous calcium gluconate. Consequently, this study is a randomized controlled trial comparing oral calcium with placebo drinks Study Design and Methods: Healthy donors were randomized to receive either oral calcium (Cohort A) or placebo (Cohort B) drinks. If symptoms emerged, all donors were given calcium drinks to counteract hypocalcemia. The primary endpoint centered on the incidence of Grade 1 or higher citrate-related symptoms. Analyses were performed using the crude model and doubly robust estimation. Results: Forty-two healthy donors participated from January 2021 to July 2022. Case distribution (Cohort A: Cohort B) stood at 3:7 (Grade 1), 2:2 (Grade 2), and 1:0 (Grade 3); no Grade 4 cases were identified. There was no statistical significance in the incidence of Grade 1 or higher and Grade 3 citrate-related symptoms. Discussion: The cumulative incidence of citrate-related side effects was less pronounced than in the previous research. This could stem from absence of blinding, and the decision to administer calcium drinks to the untreated group upon symptom detection. Although preemptive oral calcium intake before peripheral blood progenitor cell apheresis is not wholly effective, providing calcium-rich beverages to symptomatic donors may stave off symptom intensification.

Abstract in English:

ABSTRACT Introduction: Circulating tumor DNA (ctDNA) can be obtained from cell-free DNA (cfDNA) andis a new technique for genotyping, response assessment and prognosis in lymphoma. Methods: Eighteen patients with samples at diagnosis (ctDNA1), after treatment (ctDNA2) and extracted from diagnostic tissue (FFPE) were evaluated. Results: In all patients, at least one mutation in cfDNA was detected at diagnosis. CREBBP was the most frequent mutated gene (67 %). In 12 of the 15 patients with complete remission, the mutation attributed to the disease found at diagnosis cleared with treatment. A reduction in the ctDNA was observed after treatment in 14 patients, 12 of whom achieved complete remission. Correlations were found between the ctDNA at diagnosis and total metabolic tumor volume (r = 0.51; p-value = 0.014) and total lesion glycolysis 2.5 (r = 0.47; p-value = 0.024) by PET at diagnosis and between ctDNA at diagnosis and radiomic features of the lesions with the largest standardized uptake value. There was a strong inverse correlation between ∆ctDNA1 and ∆SUVmax by PET/CT (r = –0.8788; p-value = 0.002). Conclusion: Analysis of ctDNA and PET/CT in large B-cell lymphoma are complementary data for evaluating tumor burden and tumor clearance after treatment. Analysis of radiomic data might help to identify tumor characteristics and their changes after treatment.

Abstract in English:

ABSTRACT Introduction: The BV-AVD (Brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine) combination for first-line treatment of advanced stage Hodgkin’s lymphoma has been approved by regulatory authorities and included in international guidelines. However, several factors influence its incorporation as standard of care. Materials and Methods: A group of experts from different institutions was identified and, using the Delphi method, an analysis of the results of the ECHELON 1 trial for the indication of BV-AVD over ABVD (doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, dacarbazine) in patients with Hodgkin’s lymphoma Stages III and IV in Argentina was done. The clinical and academic experience of the authors and the context of the Argentine healthcare system were considered. Results and discussion: Seven statements on general aspects of the management of Hodgkin’s lymphoma and nine on specific aspects related to the use of BV-AVD over ABVD reached a consensus of agreement. There was a strong expert consensus in favor of indicating BV-AVD in the presence of extranodal disease or pulmonary disease. Moderate to severe neuropathy, pregnancy and drug allergy were considered absolute contraindications to prescribe BV. Conclusions: The authors agreed that BV-AVD could be considered a new treatment option in high-risk patients. However health system-dependent factors (such as high cost, lack of availability, reimbursement difficulties, irregular delivery, and issues with granulocyte-colony stimulating factor availability) could pose limitations for this prescription. While awaiting new data from clinical trials and real-world studies, these recommendations can represent a useful tool for hematologists in different parts of the world.

Abstract in English:

ABSTRACT Background: Sickle cell disease is the most common inherited blood disorder in the world with the birth of approximately 300,000 newborns screened each year. In 2009, the World Health Organization ranked the fight against sickle cell disease among the priorities for the Africa regions. The best way to prevent this incurable disease remains, on one hand systematic screening at birth, and on the other the proscription of risky union between heterozygous subjects. Aim: The aim of this study was to analyze the epidemiological profile of sickle cell disease and other hemoglobinopathies in Benin and determine more up-to-date prevalence rates of the disease within the population. Methods: The hemoglobin profiles of 2910 study participants were determined by quantitative electrophoresis. Samples with abnormal hemoglobin results were subjected to a complete blood count. Results: Our study population was balanced between males (1528) and females (1382) with a sex ratio of 1.1. The mean age ranged from eight years in the pediatric group to 26 years in adults. The hemoglobin electrophoresis profiles found were as follows: 59.7 % Hb AA (normal), 21.7 % Hb AS, 10.2 % Hb AC, 3.1 % Hb SS, 3.7 % Hb SC, and 1.6 % of the rare phenotypes (Hb AD, Hb AE, Hb AF, Hb A/β-thal, Hb SD, Hb SF, Hb CC and Hb C/β-thal). Participants with abnormal hemoglobin presented a normochromic normocytic anemia. A total of 356 (12 %) people knew their profile compared to 2554 (88 %) who did not. Conclusion: The high prevalence of hemoglobinopathies found in this study highlights in importance of screening in the Benin population.

Abstract in English:

ABSTRACT Introduction: Childhood acute lymphoblastic leukemia survivors receiving multiple packed red blood transfusions may be at risk of vital organ iron deposition causing long-term complications. This study was undertaken to assess the prevalence and severity of iron overload in the liver and heart by magnetic resonance imaging. Methods: A case-control study was conducted on 60 acute lymphoblastic leukemia survivors aged from 6 to 18 years and 60 healthy, age- and sex-matched children as a control group. The hematological profile, and serum ferritin was assessed and the iron content of the liver and heart was measured by T2* magnetic resonance imaging. Results: Twenty-six (43.3 %) and two (3.3 %) patients had elevated liver and myocardial iron concentrations, respectively. The statistics show a significantly positive correlation between liver T2* magnetic resonance and serum ferritin. The total volume of blood transfused and duration of follow up were associated with elevated liver iron concentrations (p-values = 0.036 and 0.028 respectively). Myocardial T2* magnetic resonance lacked correlation with serum ferritin and transfusion therapy Conclusion: Liver iron overload was detected in children and adolescents after acute lymphoblastic leukemia therapy. The risk of iron overload was related mainly to the transfusion burden during therapy. These patients need monitoring after therapy to assess their need for future chelation therapy.

Abstract in English:

ABSTRACT Background: It is known that the rapid clearance of cold-stored platelets is attributed to various storage lesions, including an abnormal increase in reactive oxygen species when platelets are exposed to cold temperatures. As an antioxidant, N-acetylcysteine exhibits some significant effects on scavenging various reactive oxygen species and inhibiting cell damage and apoptosis. Aims: This study aimed to investigate the effects of N-acetylcysteine on reducing reactive oxygen species production and protecting cold-stored platelets from phagocytosis and clearance, and to determine the optimal concentration of N-acetylcysteine. Methods: Platelet concentrates were divided into three groups: room-temperature-stored platelets, cold-stored platelets, and cold-stored platelets with the addition of different concentrations of N-acetylcysteine. After five days of storage, reactive oxygen species production, lipid peroxidation levels, activation marker expressions, GPIb/α desialylation with exposure of glycan residues and other quality parameters of platelets were measured and compared between the groups. Phagocytosis of platelets was detected by phorbol 12-myristate 13-acetate-activated THP-1 or Hep G2 cells. Moreover, the recovery of infused platelets was measured in severe combined immunodeficient mice at different timepoints. Results: After 5 days of storage, cytoplasmic reactive oxygen species significantly increased in chilled compared to non-chilled platelets; they were notably reduced with the addition of N-acetylcysteine, particularly at a concentration of 5 mM. Compared with chilled platelets, the P-selectin and phosphatidylserine expressions, as well as exposure of GPIb/α glycan residues, were significantly reduced with 5 mM of N-acetylcysteine. Phagocytosis of platelets by THP-1 or Hep G2 cells was significantly lower in 5 mM of N-acetylcysteine compared to cold-stored platelets without N-acetylcysteine. Conclusions: This study demonstrated correlations between reactive oxygen species production and their pro-oxidant effects on platelet clearance after cold storage. The addition of N-acetylcysteine at an appropriate concentration do not only protects chilled platelets from storage lesions caused by reactive oxygen species overproduction but also prevents platelet phagocytosis in vitro and clearance in vivo, thereby extending circulating time.

Abstract in English:

ABSTRACT Background: In transfusion-related iron overload, macrophage/reticuloendothelial cells are the first site of haem-derived iron accumulation. The prevention of haem-induced cytotoxicity in macrophages may represent a target for iron overload treatment. Deferasirox, an oral iron chelator, has been used to treat transfusion-related iron overload however, low adherence to the therapy is an issue. Statins, which are widely used for the prevention of atherosclerotic cardiovascular diseases, also have anti-oxidative and anti-inflammatory effects independent of their lipid lowering ones. Whether statins can suppress hemin-induced cytotoxicity and enhance the cytoprotective effects of deferasirox are important considerations to improve transfusion-related iron overload treatment. This study also evaluated the effects of eltrombopag, a thrombopoietin receptor agonist. Materials and methods: Human monocytic THP-1 cells were pretreated with statins, deferasirox, and/or eltrombopag, followed by treatment with hemin. Cell viability, reactive oxygen species generation, and the intracellular labile iron pool were measured using flow cytometry. Results: Fluvastatin and another four statins suppressed hemin-induced cell death, reactive oxygen species generation, and increases in the labile iron pool. Moreover, fluvastatin enhanced the suppressive effect of deferasirox on hemin-induced cell death. The effects of eltrombopag were similar to those of the statins. Conclusion: The safety of statins is well established. When used in combination with fluvastatin or other statins, the suppressive effects of deferasirox on hemin-induced cytotoxicity in THP-1 cells were amplified. Further research is necessary to see whether statins will act in the same way in uiuo or in human primary monocytes/macrophages.

Abstract in English:

ABSTRACT Background: Engraftment after hematopoietic stem cell transplantation is the recovery rate of neutrophils and platelets. This study aimed to test the impact of the patient's general characteristics, pre-transplantation factors, and quality parameters of hematopietic stem cell products on hematopietic recovery and to define predictive factors for engraftment in children. Methods: This retrospective study included 52 patients aged from 1 to 18 years old treated with autologous transplantation at the Mother and Child Health Care Institute of Serbia "Dr. Vukan Čupić" in Belgrade, from January 2013 until December 2018. Data were collected from medical records and apheresis procedure protocols. SPSS 20.0 software package was used for statistical data processing. Results: The median neutrophil engraftment was 18.0 (16.0-22.5) days, while the median platelet engraftment was 11.0 (10.0-18.0) days. Statistically significant correlations were found between neutrophil engraftment and patient's age (p-value = 0.050), body weight (p-value = 0.021), diagnosis (p-value = 0.023), source of stem cells (p-value = 0.001), and the number of CFU-GM/kg (p-value = 0.018). A statistically significant correlation was found between platelet engraftment and the time from diagnosis to the transplantation (p-value = 0.043), source of stem cells (p-value = 0.009), and the number of CD34+ cells/kg (p-value = 0.014). Conclusions: Predictive factors for hematopoietic recovery in this study were the patient's age, body weight, diagnosis, time from diagnosis to hematopoietic stem cell transplantation, source of hematopietic stem cells, the number of CD34+ cells/kg, and the number of CFU-GM/kg.

Abstract in English:

ABSTRACT Background: Because knowledge of blood donor motivation is crucial in guiding recruitment and retention efforts, the present study aimed at developing and validating a new scale as a multidimensional measure of blood donation motivation from the perspective of the self-determination theory. Methods: This study was conducted in three phases from September 2022 to May 2023. The first phase involved developing a draft scale based on a literature review. In the second phase, face and content validity were performed. The third phase used a cross-sectional design to assess the construct validity and internal consistency of the initial scale following administration to blood donors with a history of at least one previous whole blood donation who visited the largest blood transfusion center in Iran. Of the 420 subjects who were recruited using a mixed sampling method, 343 who fully completed the initial version of the scale were subjected to an construct validity assessment using exploratory factor analysis with Equamax rotation and internal consistency using McDonald's omega coefficient. Main results: The initial version of the scale consisted of 30 survey items with both a content validity ratio and a content validity index of 0.99. Exploratory factor analysis identified 24 items; grouped in six regulation factors (non-regulation, external regulation, introjected regulation, identified regulation, integrated regulation, and intrinsic regulation). The factors demonstrated adequate internal consistency with ω values ranging from 0.60 to 0.79. Conclusion: The present study provides psychometric support for the newly developed questionnaire to evaluate donation motivation among blood donors in Iran or in other countries with similar language, and religious and cultural values.

Abstract in English:

ABSTRACT Introduction: Chimeric antigen receptor T (CAR-T) cell therapy is an innovative technology that has shown promising results in clinical trials. Treatment is based on modifying the patient's own T cells to express artificial surface receptors to specifically recognize and attack the tumor cells. Objective: To synthesize available evidence on the incidence and management strategies of cytokine release syndrome in patients with diffuse large B-cell lymphoma who received CAR-T cell therapy. Methods: This is a systematic literature review. The search was conducted in the PubMed, Scopus, and Web of science databases. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The systematic review protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO) database under number CRD42022359258. Results: Nineteen studies were included with a total of 1193 patients who received CAR-T cell therapy. Of these patients, 804 (67%) developed some degree of cytokine release syndrome. The frequencies of Grade 3 and 4 cytokine release syndrome were 10% and 3%, respectively. The regimen most used in the management of the syndrome included tocilizumab and/or glucocorticoids. Conclusion: The results obtained in this review demonstrate high rates of cytokine release syndrome in patients with diffuse large B-cell lymphoma treated with CAR-T cell therapy, however these events are manageable, supporting the conclusion that this therapy is safe in these patients.

Abstract in English:

ABSTRACT Primary effusion lymphoma (PEL) is an aggressive and rare type of diffuse large B-cell lymphoma (DLBL) that commonly presents itself as pleural, pericardial or peritoneal effusion without lymph node or extranodal involvement in immunosuppressed patients, such as HIV-positive or transplanted receptors. On rare occasions, it may be found in solid sites without effusion, in an immunophenotypically and morphologically similar neoplasm well-known as extracavitary PEL (EC-PEL). Both PEL and EC-PEL are associated with extremely poor prognosis. Due to the rarity of these entities, ther e are no gold standard treatments . Here we discuss the role of autologous bone marrow transplant (auto-BMT) in the treatment of these patients as well as report the case of a young HIV-positive male diagnosed with both PEL and EC-PEL, who underwent a salvage therapy with auto-BMT and achieved complete and sustained remission eight years after the diagnosis.

Abstract in English:

ABSTRACT Background: Based on the VIALE-A and VIALE-C studies, the Food and Drug Administration approved venetoclax in 2020 in combination with azacitidine or low-dose cytarabine for the treatment of patients with acute myeloid leukemia ineligible for intensive chemotherapy. After the publication of these studies, venetoclax/azacitidine was assumed to be superior to venetoclax/low-dose cytarabine; however, these studies were not designed to demonstrate superiority between these combinations. Therefore, we conducted a systematic review to describe overall survival, complete remission rate, and composite complete remission rate to assess response of these two regimens in patients with newly diagnosed acute myeloid leukemia who are ineligible for intensive chemotherapy. Materials and methods: The PubMed and Web of Science databases were searched for retrospective studies and complete remission, composite complete remission, and overall survival rates were recorded. Results: Only 11 of the 815 publications identified were eligible to be included n this review, ten studies evaluated the venetoclax/azacitidine combination and one study evaluated the venetoclax/low-dose cytarabine combination. The median overall survival for venetoclax/ azacitidine was 10.75 months, whereas for venetoclax/low-dose cytarabine the median overall survival had not been reached at the time of publication. Composite complete remission was 63.3 % for venetoclax/azacitidine and 90 % for venetoclax/low-dose cytarabine. Adverse events were similar for both combinations. Conclusions: A limited number of studies investigating the venetoclax/low-dose cytarabine combination exist. Based on the available data, the superiority of venetoclax/azacitidine over venetoclax/low-dose cytarabine cannot be assumed for all acute myeloid leukemia patients who are ineligible for intensive chemotherapy. Venetoclax/low-dose cytarabine can still be considered as an option for the drug combinations currently under investigation.

Abstract in English:

ABSTRACT Background: Acute lymphoblastic leukemia is the predominant neoplastic ailment in childhood. Prior research has already established noteworthy connections between CDKN2A polymorphisms and susceptibility to this childhood leukemia, however, substantial associations are still awaiting validation. This investigation was undertaken to examine the correlation between CDKN2A polymorphisms and the risk of acute lymphoblastic leukemia in children. Methods: Acquisition of information encompassed the exploration of diverse databases including PubMed, Scopus, EMBASE, and China National Knowledge Infrastructure (CNKI) until January 10, 2024. An estimation of associations was achieved utilizing odds ratios with 95% confidence intervals. Results: A total of 22 case-control studies encompassing 10,203 cases of acute lymphoblastic leukemia and 36,424 healthy controls were included. Within this pool of studies, 14 focused on rs3731217, comprising 5396 cases and 15,787 controls, whereas eight studies investigated rs3731249, comprising 4807 cases and 20,637 controls. The aggregated data showed that the rs3731217 variant offers protection against acute lymphoblastic leukemia. Nevertheless, when subgroups are analyzed according to ethnicity, it becomes clear that the rs3731217 polymorphism significantly influences susceptibility, particularly among individuals of Caucasian and African descent with no such association being observed in children of Asian origin. Nevertheless, the rs3731249 polymorphism displayed a noteworthy correlation with vulnerability to pediatric acute lymphoblastic leukemia. Conclusion: The aggregated data revealed that the rs3731217 variation offers protection against the development of pediatric acute lymphoblastic leukemia and the rs3731249 polymorphism is significantly correlated with susceptibility.

Abstract in English:

ABSTRACT Febrile neutropenia is a major complication of the treatment of patients with hematologic diseases. Recent epidemiologic changes, with an increase in infection caused by drug-resistant bacteria, represent a major challenge for the proper management of febrile neutrope-nia. The impact of these changes in the epidemiology of infection may vary according to the region. In this document we present recommendations from the Infectious Diseases Committee of the Brazilian Association of Hematology, Blood Transfusion and Cell Therapy (ABHH) for the management of febrile neutropenia in hematologic patients. The consensus was developed by ten experts in the field, using the Delphi methodology. In the document we provide recommendations for the initial workup, prophylaxis, empiric antibiotic and antifungal therapy, modifications in the empiric regimen and criteria for discontinuing antimicrobial therapy.

Abstract in English:

ABSTRACT Additional cytogenetic abnormalities (ACA) are known to crop up in Ph+ cells of chronic myeloid leukemia (CML) patients due to cytogenetic evolution. But the frequency of molecular evolution and ACA is much less in Ph− cells of CML patients and is poorly understood. We report an interesting and rare case of Ph+ CML, who progressed to B lymphoblastic crisis, achieved remission, and later developed Ph− acute myeloid leukemia (AML) with KMT2A gene rearrangement and no detectable BCR- ABL transcripts.