Cases Of Leukemia Research Articles

Evaluation of the level of tumor necrosis factor-alpha and lactate dehydrogenase in acute lymphoblastic leukemia patients

Abstract: BACKGROUND: Acute lymphoblastic leukemia (ALL) is an abnormal clonal proliferation of early hemopoietic precursor cells in bone marrow (BM). There are certain cytokines like tumor necrosis factor alpha ( TNF-α) which plays a crucial role in the development and progression of malignant process, and other enzymes like lactate dehydrogenase (LDH) which has prognostic value. OBJECTIVE: The aims of this study were to evaluate the level of serum TNF-α and LDH in ALL patients at diagnosis and post-induction chemotherapy. PATIENTS, MATERIALS, AND METHODS: This was an observational–analytical study, which was done in Ibn-Sina Teaching Hospital in the period between May 2023 and November 2023. It included 22 newly diagnosed patients with ALL. All patients underwent complete blood count, bone marrow examination, flowcytometry, serum TNF-α and LDH at diagnosis and post induction chemotherapy. RESULTS: In 22 patients with ALL, at diagnosis, the means of serum TNF-α (97.89 ± 52.945 ng/l), serum lactate dehydrogenase(1138.94 ± 430.10 IU/l), and percentage of blasts cells in BM (0.742 ± 0.181) in B-ALL. The means of serum TNF-α (165.33 ± 23.437 ng/l), serum lactate dehydrogenase (1633.33 ± 497.426 iu/l), and percentage of blasts cells in BM (0.816 ± 0.125) in T-ALL were statistically higher than those among the controls (s.TNF-a (18.09 ± 6.795 ng/l), s.LDH (142.59 ± 61.626 IU/l), and percentage of blasts cells in BM 0.0 ± 0.0) with P = 0.000 for all parameters mentioned, respectively. After induction phase chemotherapy in B-cell ALL , there were a significant reduction noted for serum TNF-α (29.26 ± 18.648 ng/l) and LDH levels (245.47 ± 154.592 IU/l) and a significant decrease in the percentage of blasts cells (0.07 ± 0.060).also in T-cell ALL there were a significant reduction noted for serum TNF-a (26.00 ± 11.135 ng/l) serum LDH (347.66 ± 160.300 IU/l) and percentage of blasts cells in bone marrow (0.06 ± 0.046). All of the postchemotherapy acute leukemia cases with lower TNF-α levels had complete remission (100%). CONCLUSIONS: There were significant increases in serum TNF-α and LDH in ALL patients at diagnosis; while after induction, there was a significant reduction in their levels. Complete remission from the disease was associated with lower levels of serum TNF-α in newly diagnosed patients.

Comparative Evaluation of the Immunophenotypic Profile of Acute Lymphoblastic Leukaemia in Adult and Paediatric Age Groups in Iraq

Background: Immunophenotyping is a primary tool for investigating acute lymphoblastic leukemia (ALL). Acute lymphoblastic leukemia accounts for 75 - 80% of pediatric leukemia cases and 14% of adult leukemia cases. However, the prognostic factors, treatment strategies, and pathogenic pathways differ between these groups. Objectives: This study aims to compare the pattern of antigen expression between adult and pediatric ALL patients in the Iraqi population and to evaluate the frequency of aberrant myeloid antigen expression in both groups. Methods: A total of 131 patients with de-novo ALL were studied from May 2014 to May 2015. The diagnosis of ALL was confirmed by morphology and immunophenotyping of peripheral blood and bone marrow aspirate specimens using a panel of fluorochrome-labeled antibodies in 6 - colored flow cytometry. Results: The B-ALL phenotype was prevalent in 44 (68.7%) of adult patients compared to 51 (76.1%) in the pediatric group. CD10 expression was present in 49 (76.6%) of adults, mostly with B-ALL. The pediatric group had lower CD10 expression in T-ALL (P = 0.039). CD20 expression was significantly lower in adults compared to children. In T-ALL, significant differences between adult and pediatric groups were observed in CD1a and CD2 expression. Aberrant myeloid antigen expression was present in 29 (45.3%) adults and 30 (44.8%) pediatric patients, with CD33 and CD13 being the most prevalent in both groups. Conclusions: There was an increased T-cell lineage and aberrant antigen expression in both adult and pediatric ALL cases in this Iraqi sample. Adults with ALL tend to display higher levels of CD20 and lower levels of CD1a and CD2 compared to children, markers associated with poorer prognoses.

Medical- and Implant-Related Complications Following Total Joint Arthroplasty in Patients Who Have Chronic Lymphocytic Leukemia

BackgroundChronic lymphocytic leukemia (CLL) is highly prevalent in the Total Joint Arthroplasty (TJA) age group but has not been properly evaluated. This study aims to assess: 1) 90-day medical complications; 2) implant-related complications; 3) healthcare utilization; and 4) time to revision in CLL and non-CLL TJA. MethodsChronic Lymphocytic Leukemia cases undergoing total knee arthroplasty (TKA) and total hip arthroplasty (THA) were identified using diagnostic and procedural codes. CLL TKA and THA patients were matched 1:5 with controls based on demographics and comorbidities. Outcomes included 90-day medical complications, 2-year implant complications, length of stay (LOS), 90-day readmission, and time to revision. ResultsThe CLL TKA patients had significantly higher odds of 90-day medical complications compared to controls, notably pneumonia (OR, 9.2; CI, 7.1 to 12.0; P < 0.001) and myocardial infarction (OR, 5.5; CI, 3.9 to 7.9; P < 0.001). Similarly, CLL THA patients had greater odds of 90-day medical complications, especially pneumonia (OR 10.0; CI 8.2 to 12.2; P < 0.001) and acute kidney injury (AKI) (OR 6.3; CI 5.1 to 7.8; P < 0.001). CLL TKA patients faced higher odds of periprosthetic fracture, mechanical loosening, and prosthetic joint infection, while THA patients had increased periprosthetic fractures. Revisions occurred earlier for THA than TKA (337 ± 547 days versus 643 ± 774 days). CLL patients had longer LOS (TKA: 5.9 ± 6.5 versus 3.1 ± 1.6 days; P < 0.001) (THA: 6.3 ± 12.9 versus 3.0 ± 2.4; P < 0.001) and higher 90-day readmission rates (OR, 1.3; CI, 1.1 to 1.5, P < 0.001). ConclusionsOrthopaedic surgeons should consider CLL status for informed patient counseling and complications mitigation.

Recent Developments and Evolving Therapeutic Strategies in KMT2A-Rearranged Acute Leukemia.

Rearrangements of the histone-lysine-N-methyltransferase (KMT2A), previously referred to as mixed-lineage leukemia (MLL), are among the most common chromosomal abnormalities in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), involving numerous different fusion partners. KMT2A-rearranged (KMT2A-r) leukemia is characterized by a rapid onset, aggressive progression, and significantly worse prognosis compared to non-KMT2A-r leukemias. Even with contemporary chemotherapeutic treatments and hematopoietic stem cell transplantations (HSCT), patients with KMT2A-r leukemia typically experience poor outcomes and limited responses to these therapies. This review aims to consolidate recent studies on the general gene characteristics and associated mechanisms of KMT2A-r acute leukemia, as well as the cytogenetics, immunophenotype, clinical presentation, and risk stratification of both KMT2A-r-AML and KMT2A-r-ALL. Particularly, the treatment targets in KMT2A-r acute leukemia are examined. A comprehensive review was carried out by systematically synthesizing existing literature on PubMed, using the combination of the keywords 'KMT2A-rearranged acute leukemia', 'lymphoblastic leukemia', 'myeloid leukemia', and 'therapy'. The available studies were screened for selection based on quality and relevance. Studies indicate that KMT2A rearrangements are present in over 70% of infant leukemia cases, approximately 10% of adult AML cases, and numerous instances of secondary acute leukemias, making it a disease of critical concern to clinicians and researchers alike. The future of KMT2A-r acute leukemia research is characterized by an expanding knowledge of the disease's biology, with an emphasis on personalized therapies, immunotherapies, genomic advancements, and innovative therapeutic combinations. The overarching aim is to enhance patient outcomes, lessen the disease burden, and elevate the quality of life for those affected. Ongoing research and clinical trials in this area continue to offer promising opportunities for refining treatment strategies and improving patient prognosis.

Aeromonas veronii-associated bacteremia in the course of treatment of acute myeloid leukemia: a case report and review of the literature

PurposeThis study aimed to report a case of acute myeloid leukemia (AML) complicated by Aeromonas veronii infection-induced bacteremia and to review relevant literature on the etiology, prevention, treatment, and prognosis of bacteremia in immunocompromised populations, aiming to reduce mortality in individuals with hematologic and other end-stage diseases and improve patient outcomes.Methods and resultsWe reported the case of a 23-year-old male patient with relapsed AML characterized by AML1:ETO and ASXL positivity, classified as a high-risk group. The patient presented with fever, abdominal pain, diarrhea, nausea, and vomiting after consuming partially cooked fish. The patient was admitted with high leucocytes, C-reactive protein, procalcitonin, and interleukin-6 levels. Peripheral blood high-throughput sequencing (Next-Generation Sequencing NGS) confirmed infection with Aeromonas veronii, while an abdominal CT scan indicated a liver abscess with gas formation. Culture of the drainage fluid from the ultrasound-guided liver abscess puncture demonstrated growth of Aeromonas veronii. Based on the sensitivity results, the patient was treated with intravenous ciprofloxacin and cefoperazone-sulbactam. After treatment with antibiotics, blood transfusion, liver protection, and azacitidine 100 mg ih, combined with dry white sand(interferon alpha-1B, interleukin-2, and thalidomide), the critical condition of the patient improved, and he was discharged. This study was approved by the Ethics Committee of Medical Research in the Second Affiliated Hospital of Henan University of Science and Technology. Informed consent was obtained from this patient and we have obscured the patient's identifying information. All methods were carried out in accordance with relevant guidelines and regulations.ConclusionWhen patients with a recurrence of AML have a history of consuming or contacting aquatic products, clinicians should be vigilant about Aeromonas veronii infection. The presence of Aeromonas veronii in peripheral blood must alert clinicians to the possibility of severe sepsis and septic shock. Early diagnosis and prompt treatment are crucial to reducing patient mortality.

Clinical features of 20 cases with Pneumocystis jirovecii pneumonia after allogeneic hematopoietic stem cell transplantation

This study included 20 patients with hematological diseases who developed Pneumocystis jirovecii pneumonia (PJP) after receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) from April 2014 to October 2022 at Peking University People's Hospital. The 20 patients comprised 13 males (65.0% ) and seven females (35.0% ), with a median age of 34 (19-60) years. Eleven cases (55.0% ) of acute myeloid leukemia, four cases (20.0% ) of acute lymphocytic leukemia, two cases (10.0% ) of myelodysplastic syndrome, one case (5.0% ) of chronic myelomonocytic leukemia, one case (5.0% ) of non-Hodgkin lymphoma, and one case (5.0% ) of aplastic anemia were analyzed. Three cases (15.0% ) of HLA-identical sibling hematopoietic stem cell transplantation, three cases (15.0% ) of matched unrelated donor hematopoietic stem cell transplantation, and 14 cases (70.0% ) of haploid hematopoietic stem cell transplantation were identified. The median onset time of PJP was 353 (74-1121) days after transplantation. The clinical symptoms mainly included fever, cough, expectoration, and dyspnea. All patients presented signs of infection based on the CT scan, including bilateral diffuse ground-glass opacities, patchy shadows, and solid nodules. Nine patients (45.0% ) required respiratory support via nasal catheter oxygen inhalation, while seven patients (35.0% ) required ventilator-assisted breathing. Seven (35.0% ) severe infections and 13 (65.0% ) mild to moderate infections were recorded. Moreover, eight patients (40.0% ) were complicated with human cytomegalovirus infection, whereas two patients were complicated with EB virus infection. Furthermore, all 20 patients received treatment with compound sulfamethoxazole (standard dose, 11 cases; low dose, 9 cases). Furthermore, 19 patients survived and one patient died.

Efficacy of nebulized GM-CSF inhalation in preventing oral mucositis in patients undergoing hematopoietic stem cell transplantation: A retrospective study

ObjectiveTo study the efficacy of oxygen atomization inhalation of granulocyte-macrophage colony-stimulating factor (GM-CSF) for preventing oral mucositis in patients following hematopoietic stem cell transplantation. MethodsData from patients who received hematopoietic stem cell transplantation and were treated with GM-CSF for the prevention/treatment of oral mucositis in our hospital from June 2021 to June 2023 were collected. The enrolled patients were divided into an observation group and a control group according to the use of GM-CSF. The WHO Mucositis Scale Assessment Criteria were utilized to evaluate the characteristics of patients with oral mucositis (OM) from the beginning of the pretreatment period until they were discharged from the hospital. The general data, preconditioning protocol, transplantation method, overall grade and duration of oral mucositis, pain score, nutritional score and number of days of parenteral nutrition use, oral mucosal infection status and antibiotic use intensity, the granulocyte and megakaryocyte reconstruction time, and adverse reaction reports of the patients were collected and summarized through the medical records system. ResultsA total of 143 patients were included in this study, including 75 patients in the observation group. In the observation group, there were 36 males and 39 females aged 22–67 years. There were 45 patients who received autologous transplantation and 30 patients who received allogeneic transplantation. In terms of the disease distribution, there were 33 cases of leukemia, 24 cases of lymphoma, 11 cases of multiple myeloma, and 8 other cases (3 cases of aplastic anemia, 2 cases of myelodysplastic syndrome, 2 cases of myelofibrosis, 1 case of POEMS syndrome). There were 68 patients in the control group, including 33 males and 35 females; the control group patients were aged 25–74years. Forty-one patients received autologous transplantation, and 27 patients received allogeneic transplantation. The disease distribution included 29 cases of leukemia, 17 cases of lymphoma, 12 cases of multiple myeloma, and 7 other cases (3 cases of aplastic anemia, 2 cases of myelodysplastic syndrome, 1 case of myelofibrosis, 1 case of POEMS syndrome). There were no significant differences between the two groups concerning age, sex, disease distribution or the transplantation method (P > 0.05). In the observation group, 13 cases did not develop oral mucositis, and 32 cases developed oral mucositis (16 cases of Grade I, 14 cases of Grade II, 2 cases of Grade III, and 0 cases of Grade IV). In the control group, there were 5 cases without mucositis and 36 cases with oral mucositis (6 cases of Grade Ⅰ, 16 cases of Grade Ⅱ, 8 cases of Grade Ⅲ, and 6 cases of Grade Ⅳ), the difference was statistically significant (P < 0.05). The pain score and duration of mucositis in the observation group were significantly lower than those in the control group (P < 0.05). In addition, the oral infection rate, antibiotic use intensity, nutritional score, per capita number of days of parenteral nutrition use and hematopoietic reconstruction time in the observation group were significantly lower than those in the control group (P < 0.05). In the observation group, 8 patients did not develop oral mucositis, and 22 patients developed oral mucositis (13 cases of Grade I, 7 cases of Grade II, 1 case of Grade III, and 1 case of Grade IV). In the control group, 1 case did not develop mucositis, and 26 cases developed oral mucositis (3 cases of Grade Ⅰ, 10 cases of Grade Ⅱ, 9 cases of Grade Ⅲ, and 4 cases of Grade Ⅳ). The difference was statistically significant (P < 0.05). The pain score and duration of mucositis in the observation group were significantly lower than those in the control group (P < 0.05). In addition, the oral mucosal infection rate, antibiotic use intensity, nutritional score, per capita number of days of parenteral nutrition use and hematopoietic reconstruction time in the observation group were significantly lower than those in the control group (P < 0.05). No adverse reactions were reported in either group. ConclusionIn both autologous transplantation and allogeneic transplantation patients, GM-CSF atomized inhalation can improve the prevention and treatment of oral mucositis in stem cell transplantation patients, reduce the incidence of oral infection, reduce the intensity of antibiotic use and the number of days of parenteral nutrition use, and thus promote the process of hematopoietic reconstruction.

Positive rates and distribution characteristics of pre-existing anti-human-leukocyte-antigen antibodies in patients with different hematological diseases

Clinical data of 1 494 patients with hematological diseases who were scheduled to receive allogeneic hematopoietic stem cell transplantation and received the anti-human-leukocyte-antigen (HLA) antibody test for the first time at the First Affiliated Hospital of Soochow University from 2016 to 2018 was collected to analyze the positive rates and distribution characteristics of different types of pre-existing anti-HLA antibodies in patients with different hematological diseases. Among 1 494 patients with hematological diseases, there were 849 males and 645 females, aged [31 (17, 45)] years, and included 577 cases of acute myeloid leukemia (AML), 373 cases of acute lymphocytic leukemia (ALL), 234 cases of aplastic anemia (AA), 175 cases of myelodysplastic syndrome (MDS), and 135 cases of other diseases. The total positive rate of pre-existing anti-HLA antibodies was 25.1% (375/1 494), among which the positive rates of anti-HLA class Ⅰ, anti-HLA class Ⅱ, and anti-HLA class Ⅰ+Ⅱ antibodies were 11.2% (168/1 494), 4.9% (73/1 494), and 9.0% (134/1 494), respectively.The total positive rates of pre-existing anti-HLA antibodies in patients with MDS、AA、AML、ALL and other diseases were 40.6% (71/175), 30.8% (72/234), 26.2% (151/577), 12.3% (46/373), and 25.9% (35/135), respectively, with statistically significant difference (P<0.001). The positive rates of anti-HLA class Ⅰ, anti-HLA class Ⅱ, and anti-HLA class Ⅰ+Ⅱ antibodies in patients with different hematological diseases showed statistically significant differences (all P<0.001). Given the varying positive rates and distribution characteristics of pre-existing anti-HLA antibodies among patients with different hematological diseases, anti-HLA antibody test should be performed before receiving hematopoietic stem cell transplantation.

Diagnostic and Therapeutic Challenge Caused by Candida albicans and Aspergillus spp. Infections in a Pediatric Patient as a Complication of Acute Lymphoblastic Leukemia Treatment: A Case Report and Literature Review.

Fungal infections constitute a significant challenge and continue to be a predominant cause of treatment failure in pediatric leukemia cases. Despite the implementation of antifungal prophylaxis, these infections contribute to approximately 20% of cases in children undergoing treatment for acute lymphoblastic leukemia (ALL). The aim of this study is to highlight the diagnostic and therapeutic challenges associated with invasive fungal infections (IFIs). We also present a review of the epidemiology, risk factors, treatment, and a clinical presentation of IFI in patients with ALL. This case report details the clinical course of confirmed Candida albicans (C. albicans) and Aspergillus spp. infections during the consolidation phase of ALL treatment in a 5-year-old pediatric patient. This male patient did not experience any complications until Day 28 of protocol II. Then, the patient's condition deteriorated. Blood culture detected the growth of C. albicans. Despite the implementation of targeted therapy, the boy's condition did not show improvement. The appearance of respiratory symptoms necessitated a computed tomography (CT) of the chest, which revealed multiple nodular densities atypical for C. albicans etiology. In spite of ongoing antifungal treatment, the lesions depicted in the CT scans showed no regression. A lung biopsy ultimately identified Aspergillus species as the source of the infection. Overcoming fungal infections poses a considerable challenge; therefore, an accurate diagnosis and the prompt initiation of targeted therapy are crucial in managing these infections in patients with leukemia.

A Lethal Case of Chronic Myeloid Leukemia in Accelerated Phase Presenting in Labor

A Lethal Case of Chronic Myeloid Leukemia in Accelerated Phase Presenting in Labor

Resolution of Anterior Uveal Infiltration of Acute Lymphoblastic Leukemia After Chimeric Antigen Receptor T-Cell Therapy

Purpose: To present a case of acute B-cell lymphoblastic leukemia (B-ALL) ocular relapse treated with chimeric antigen receptor T-cell (CAR T) therapy. Methods: A retrospective case review was evaluated. Results: A 69-year-old woman with a history of B-ALL presented with bilateral hypopyons and 3+ anterior chamber cells that responded to topical prednisolone. Six months later, she developed recurrent hypopyons, iris neovascularization, and iris nodularity in both eyes. A fine-needle aspiration biopsy confirmed ocular infiltration of B-ALL. A single infusion of CAR T therapy resulted in remission of the systemic and ocular findings. The clinical course was complicated by cytokine release syndrome and neurotoxicity, which improved with medical management. The patient remained in remission for 7 months after a single CAR T infusion. Conclusions: CAR T therapy may be effective in treating systemic leukemia and uveal infiltration, with an ocular side-effect profile and visual outcomes. The systemic side effects of CAR T therapy may be managed medically.

Familial Cases of Acute Leukemia in Children in Uzbekistan

Familial Cases of Acute Leukemia in Children in Uzbekistan

Evaluation of Hi-C Sequencing for Detection of Gene Fusions in Hematologic and Solid Tumor Pediatric Cancer Samples.

Hi-C sequencing is a DNA-based next-generation sequencing method that preserves the 3D genome conformation and has shown promise in detecting genomic rearrangements in translational research studies. To evaluate Hi-C as a potential clinical diagnostic platform, analytical concordance with routine laboratory testing was assessed using primary pediatric leukemia and sarcoma specimens. Archived viable and non-viable frozen leukemic cells and formalin-fixed paraffin-embedded (FFPE) tumor specimens were analyzed. Pediatric acute myeloid leukemia (AML) and alveolar rhabdomyosarcoma (A-RMS) specimens with known genomic rearrangements were subjected to Hi-C to assess analytical concordance. Subsequently, a discovery cohort consisting of AML and acute lymphoblastic leukemia (ALL) cases without known genomic rearrangements based on prior clinical diagnostic testing was evaluated to determine whether Hi-C could detect rearrangements. Using a standard sequencing depth of 50 million raw read-pairs per sample, or approximately 5X raw genomic coverage, we observed 100% concordance between Hi-C and previous clinical cytogenetic and molecular testing. In the discovery cohort, a clinically relevant gene fusion was detected in 45% of leukemia cases (5/11). This study provides an institutional proof of principle evaluation of Hi-C sequencing to medical diagnostic testing as it identified several clinically relevant rearrangements, including those that were missed by current clinical testing workflows.

Global burden, risk factor analysis, and prediction study of leukaemia from 1990 to 2030.

Leukaemia is a devastating disease with an incidence that progressively increases with advancing age. The World Health Organization has designated 2021-30 as the decade of healthy ageing, highlighting the need to address age-related diseases. We estimated the disease burden of leukaemia and forecasted it by 2030. Based on the Global Burden of Disease 2019 database, we systematically analysed the geographical distribution of leukaemia and its subtypes. We used Joinpoint regression and Bayesian age-period-cohort models to evaluate incidence and mortality trends from 1990 to 2019 and projections through 2030. We analysed five leukaemia subtypes and the impact of age, gender, and social development. Decomposition analysis revealed the effects of disease burden on ageing and population growth. We used frontier analysis to illustrate the potential of each country to reduce its burden based on its development levels. Globally, the absolute numbers of leukaemia incidence and mortality have increased, while the age-standardised rates (ASRs) have shown a decreasing trend. The disease burden was more pronounced in men, the elderly, and regions with a high socio-demographic index (SDI), where ageing and population growth played varying roles across subtypes. From 2000 to 2006, disease burdens were most effectively controlled. Global ASRs of incidence might stabilise, while ASRs of death are expected to decrease until 2030. Frontier analysis showed that middle and high-middle SDI countries have the most improvement potential. Smoking and high body mass index were the main risk factors for leukaemia-related mortality and disability-adjusted life years. The absolute number of leukaemia cases has increased worldwide, but there has been a sharp decline in ASRs over the past decade, primarily driven by population growth and ageing. Countries with middle and high-middle SDI urgently need to take action to address this challenge.

Transformation into acute myeloid leukemia with t(8;21)(q22;q22.1); RUNX1::RUNX1T1 from JAK2-mutated essential thrombocythemia: a case report

BackgroundBlast transformation is a rare but well-recognized event in Philadelphia-negative myeloproliferative neoplasms associated with a poor prognosis. Secondary acute myeloid leukemias evolving from myeloproliferative neoplasms are characterized by a unique set of cytogenetic and molecular features distinct from de novo disease. t(8;21) (q22;q22.1); RUNX1::RUNX1T1, one of the most frequent cytogenetic abnormalities in de novo acute myeloid leukemia, is rarely observed in post-myeloproliferative neoplasm acute myeloid leukemia. Here we report a case of secondary acute myeloid leukemia with t(8;21) evolving from JAK2-mutated essential thrombocythemia.Case presentationThe patient was a 74-year-old Japanese woman who was referred because of thrombocytosis (platelets 1046 × 109/L). Bone marrow was hypercellular with increase of megakaryocytes. Chromosomal analysis presented normal karyotype and genetic test revealed JAK2 V617F mutation. She was diagnosed with essential thrombocythemia. Thrombocytosis had been well controlled by oral administration of hydroxyurea; 2 years after the initial diagnosis with ET, she presented with leukocytosis (white blood cells 14.0 × 109/L with 82% of blasts), anemia (hemoglobin 91 g/L), and thrombocytopenia (platelets 24 × 109/L). Bone marrow was hypercellular and filled with 80% of myeloperoxidase-positive blasts bearing Auer rods. Chromosomal analysis revealed t(8;21) (q22;q22.1) and flow cytometry presented positivity of CD 13, 19, 34, and 56. Molecular analysis showed the coexistence of RUNX1::RUNX1T1 chimeric transcript and heterozygous JAK2 V617F mutation in leukemic blasts. She was diagnosed with secondary acute myeloid leukemia with t(8;21)(q22;q22.1); RUNX1::RUNX1T1 evolving from essential thrombocythemia. She was treated with combination chemotherapy with venetoclax and azacytidine. After the first cycle of the therapy, blasts disappeared from peripheral blood and decreased to 1.4% in bone marrow. After the chemotherapy, RUNX1::RUNX1T1 chimeric transcript disappeared, whereas mutation of JAK2 V617F was still present in peripheral leukocytes.ConclusionsTo our best knowledge, the present case is the first one with JAK2 mutation preceding the acquisition of t(8;21). Our result suggests that t(8;21); RUNX1::RUNX1T1 can be generated as a late event in the progression of JAK2-mutated myeloproliferative neoplasms. The case presented typical morphological and immunophenotypic features associated with t(8;21) acute myeloid leukemia.

Targeted lipidomics-based study of radiation-induced metabolite profiles changes in plasma of total body irradiation cases

Purpose Lipidomics is an important tool for triaging exposed individuals, and helps early adoption of prevention and control strategies. The purpose of this study was to screen significantly perturbed lipids between pre- and post-irradiation of human plasma samples after total body irradiation (TBI) and explore potential radiation biomarkers for early radiation classification. Methods Plasma samples were collected before and after irradiation from 22 hospitalized cases of acute myeloid leukemia (AML) prepared for bone marrow transplantation. Acute total-body γ irradiation was performed at doses of 0, 4, 8, and 12 Gy. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) with multiple reaction monitoring (MRM) method was utilized. Self-paired studies before and after irradiation were performed to screen potential lipid categorization markers and markers of dose-response relationships for radiation perturbation in humans. Based on the screened potential markers, a human TBI dose estimation model was developed. Results In total, 426 individual lipids from 14 major classes were quantified and 152 potential biomarkers with categorical characteristics were screened. A total of 80 lipids (32 TGs, 29 SMs, 9 FAs, 5 CEs, 5 PIs) were upregulated at 4 Gy, and a total of 91 lipids (39 SMs, 18 TGs, 15 HexCers, 7 CEs, 6 Cers, 3 LacCers, 2 LPEs, 1 PI) were upregulated at 12 Gy. Comparison of the ROC curves between the non-exposed and exposed groups at different doses showed AUC values ranging from 0.807 to 0.876. The metabolic pathways of potential lipid markers are mainly sphingolipid and glycerolipid metabolism, unsaturated fatty acid biosynthesis, fatty acid degradation and biosynthesis. Among the 13 dose-dependent radiosensitive lipids, CE (20:5), CE (18:1) and PI (18:2/18:2) were gradually incorporated into the TBI dose estimation model. Conclusion This study suggested that it was feasible to acquire quantitative lipid biomarker panels using targeted lipidomics platforms for rapid, high-throughput triage. Lipidomics strategies for radiation biodosimetry in humans were established with lipid biomarkers with good dose-response relationship.

Human Leukocyte Antigen-DR and Cluster Designation 34: Double-negative Acute Myeloid Leukemias – Our Experience in Clinical Setting

Abstract Introduction: Dual negativity for cluster designation (CD) 34 and human leukocyte antigen (HLA)-DR antigen in leukemia panel is an important finding in clinical practice. The combination of this finding though seen classically in acute promyelocytic leukemia (APL) is not specific to it but can be seen in many other myeloid leukemias like the ones associated with nucleophosmin 1 (NPM1) or FMS-related tyrosine kinase 3 gene-internal tandem duplication (FLT3-ITD) abnormalities. It is important to identify APL from non-APL leukemia as treatment and prognosis vary. Aims and Objectives: We analyzed CD 34 and HLA-DR dual-negative acute myeloid leukemia (AML) cases presented to us over 2.5 years (26 cases) and segregated them into APL and non-APL groups to study their morphological/flow cytometric and cytogenetic profile and correlation with treatment response. Materials and Methods: It was a prospective study including all newly diagnosed AMLs showing CD 34 and HLA-DR dual negativity in flow cytometry profile. Cases in which complete information/cytogenetics/molecular profile were not available, were excluded from the study. The patients were followed up till the end of induction to look for morphological response to induction therapy. The clinical and treatment records were pulled out from the patient database after ethical committee clearance. Results: A total of 139 new AML cases were encountered during the study period out of which 28 (20%) were found to be dual negative for CD34 and HLA-DR. The non-APL group showed higher mean age, TLC at baseline, variable morphology, and more number of aberrant expression on flow cytometry profile. No significant difference was noted in terms of gender, presence of hepatosplenomegaly, DIC as complication, or percentage of blasts/blasts equivalent at baseline. Our study found that while all APL patients had PML-RARA, the associated molecular abnormalities were much lesser as compared to the non-APL group which showed a variety of abnormalities such as NPM1, FLT3, RAS mutation, and mutations involving epigenetic modifiers. The response rate to induction therapy was significantly lower in the non-APL group as compared to the APL group. Conclusion: The non-APL myeloid leukemia which is dual negative is commonly found to be associated with cup-shaped morphology, NPM, or FLT3-ITD mutation along with other abnormalities. These patients were older in age, showed higher TLC and higher blast counts, associated with poorer response to induction therapy as compared to the APL group.

Chronic myeloid leukemia: 2025 update on diagnosis, therapy, and monitoring.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm with an annual incidence of two cases/100 000. It accounts for approximately 15% of newly diagnosed cases of leukemia in adults. CML is characterized by a balanced genetic translocation, t(9;22) (q34;q11.2), involving a fusion of the Abelson murine leukemia (ABL1) gene from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2. This rearrangement is known as the Philadelphia chromosome. The molecular consequence of this translocation is the generation of a BCR::ABL1 fusion oncogene, which in turn translates into a BCR::ABL1 oncoprotein. Four tyrosine kinase inhibitors (TKIs), imatinib, dasatinib, bosutinib, and nilotinib, are approved by the United States Food and Drug Administration (FDA) for first-line treatment of newly diagnosed CML in the chronic phase (CML-CP). Clinical trials with second and third-generation TKIs in frontline CML-CP therapy reported significantly deeper and faster responses but had no impact on survival prolongation, likely because of their potent efficacy and the availability of effective TKIs salvage therapies for patients who have a cytogenetic relapse with frontline TKI therapy. All four TKIs are equivalent if the aim of therapy is to improve survival. In younger patients with high-risk disease and in whom the aim of therapy is to induce a treatment-free remission status, second-generation TKIs may be favored. For CML post-failure on frontline therapy, second-line options include second and third-generation TKIs. Although potent and selective, these TKIs exhibit unique pharmacological profiles and response patterns relative to different patient and disease characteristics, such as patients' comorbidities and financial status, disease stage, and BCR::ABL1 mutational status. Patients who develop the T315I "gatekeeper" mutation display resistance to all currently available TKIs except ponatinib, asciminib, and olverembatinib. Allogeneic stem cell transplantation remains an important therapeutic option for patients with CML-CP and failure (due to resistance) of at least two TKIs and for all patients in advanced-phase disease. Older patients who have a cytogenetic relapse post-failure on all TKIs can maintain long-term survival if they continue a daily most effective/least toxic TKI, with or without the addition of non-TKI anti-CML agents (hydroxyurea, omacetaxine, azacitidine, decitabine, cytarabine, and others).

Patterns of the Leukemia Records that were Referred to the Regional Laboratory in Makkah, Saudi Arabia.

Leukemia is the fifth most common cancer in Saudi Arabia. The aim of this study was to assess the various patterns of leukemia associated with age, gender, and nationality in this region. This cross-sectional study was conducted at the regional laboratory in Makkah, Saudi Arabia, from April to November 2023. Descriptive statistics were presented as frequencies and percentages by using the GraphPad Prism software. This study included 107 patients, and the results showed that leukemia cases were higher in males than females and more prevalent in older patients (above 50 years of age). Overall, acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) were the most common types of leukemia among Saudi patients. In addition, AML was the most prevalent type of leukemia in males and females, followed by ALL. Data also revealed that ALL was the most common type in the younger population, whereas AML was highly prevalent in older patients. In conclusion, this study provides valuable information about the patterns of leukemia reported at the regional laboratory in Makkah and will help in designing management and preventive approaches for these patients. This epidemiological investigation is also valuable for establishing proper medical databases.

Leucémie à plasmocytes secondaire : à propos d’un cas rare et revue de littérature Secondary plasma cell leukemia: a rare case report and review of the literature

Plasma cell leukemia is a hematological malignancy characterized by monoclonal proliferation of plasma cells in the peripheral blood and bone marrow. It is defined by a blood plasma count greater than 2 × 109/L (2G/L) and/or the presence of more than 20% plasma cells in the white blood cell count. There are two forms: the primary or de novo form, which manifests itself immediately as leukemia, and the secondary form , which corresponds to the evolution of a known multiple myeloma. It is a highly aggressive form of plasma cell neoplasm, with a poor prognosis despite therapeutic advances. In this context, we present a rare case of secondary plasma cell leukemia in a 56-year-old female patient, diagnosed at the hematology laboratory of the Hassan II University Hospital in Fez. The patient was being followed for multiple myeloma, for which she was put on chemotherapy according to the Velcade + Thalidomide + Dexamethasone protocol. Six months later, the patient presented with a febrile hemorrhagic syndrome. The blood count showed hyperleukocytosis at 39.4 G/L and bicytopenia (Hemoglobin = 7.9 g/dl, Platelets = 58 G/L). Blood smear showed a 36% plasma cell count suggestive of secondary plasma cell leukemia. At the end of this observation, we underline the crucial importance of regular monitoring by careful cytological examination of the blood smear in all patients followed for multiple myeloma.