Leukemia Patients Research Articles

Integrating eugenol with intensive care in leukemia patients: exploration of pro-apoptotic potential against HL-60, human leukemia cell line

Objective: The objective of this in-vitro study was to explore the pro-apoptotic potential of eugenol (4-allyl-2-methoxyphenol) on Human Leukemia-60 (HL-60) cell line as a potent phytochemical in intensive care setting to leukemia patients. Methodology: After formal approval by all of the respective ethical committees, this study was simultaneously conducted at all respective institutional departments. The study included culturing HL-60 cell line and its treatment with serial concentrations of eugenol for calculation of subsequent IC50 values (half-maximal inhibitory concentration) via MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay, expression analysis of gene, comparative analysis of relative gene fold (Intrinsic Biomarkers Caspase-3, Caspase-9) as apoptosis mediator markers followed by RT-qPCR. Cellular apoptotic morphology was confirmed via Hoechst 333258 staining. Results: For HL-60 cell line, the IC50 of eugenol (14.1 uM) showed high gene expression of pro-apoptotic biomarkers (Caspase-3 and Caspase-9). Hoechst 333258 staining showed prominent apoptotic bodies leading to nuclear fragmentations. Conclusion: Eugenol proved to possess robust pro-apoptotic potential leading to diagnostic efficacy against leukemia HL-60 cell line. Further studies would help in identifying key mechanisms by which eugenol exhibits anti-cancer potential against HL-60 cell lines. Abbreviations: HL-60 - Human Leukemia-60; IC50 - Half-Maximal Inhibitory Concentration Keywords: Eugenol, Pro-apoptotic Effects, Intensive Care, Anti-Cancer Mechanisms, HL-60, Natural Chemotherapeutics Citation: Khaliq HMH, Bughio R, Nangdev P, Aziz O, Javed W. Integrating eugenol with intensive care in leukemia patients: exploration of pro-apoptotic potential against HL-60, human leukemia cell line. Anaesth. pain intensive care 2024;28(5):871−875; DOI: 10.35975/apic.v28i5.2491 Received: June 18, 2024; Reviewed: August 03, 2024; Accepted: August 11, 2024

Inhibition of Acute Myeloid Leukaemia Development by Bittersweet Based on miR-let-7a Regulating Vascular Endothelial Growth Factor A Resistance Mechanism

Acute myeloid leukaemia (AML) is closely related to regulation of miR-let-7a and vascular endothelial growth factor A (VEGFA). Picrasidine is a traditional Chinese medicine extract with antitumour effects, but its mechanism of action in AML is unclear. This study investigated picloram’s effect on AML and its relationship with miR-let-7a regulation of VEGFA resistance mechanism. Bone marrow samples from leukaemia patients in the Department of Haematology of our hospital were collected, and RT-PCR detected miR-let-7a and VEGFA expression in the bone marrow of healthy individuals and leukaemia patients. At the same time, cell culture of AML-resistant cell line K562/ADM was performed, which was divided into NC group, Picrasidine L group, Picrasidine M group, Picrasidine H group, si-NC group, Picrasidine H+miR-let-7a inhibitor group, Picrasidine H+miR-let-7a mimic group, miR-let-7a mimic+hVEGF-IN-1 group, miR-let-7a inhibitor+hVEGF-IN-1 group, and Picrasidine H+miR-let-7a mimic+hVEGF-IN-1 group. Cell proliferation and apoptosis was detected and correlation between miR-let-7a and VEGFA was analyzed by clinical samples. Picrasidine had a significant ameliorative effect on acute myeloid leukaemia in a dose-dependent manner. miR-let-7a was lowly expressed and VEGFA was highly expressed in AML patients. miR-let-7a and VEGFA showed significant correlation in human AML disease staging, and there was a statistically significant difference (p <0.05). That is to say, picloram promotes miR-let-7a expression, thus achieving inhibition of VEGFA, which in turn promotes apoptosis of AML drug-resistant cell line K562/ADM and inhibits its proliferation. The ameliorative effect of Picrasidine on acute myeloid leukaemia was achieved by upregulating miR-let-7a and downregulating VEGFA.

Population pharmacokinetic analysis of quizartinib in patients with newly diagnosed FLT3-internal-tandem-duplication-positive acute myeloid leukemia.

The population pharmacokinetics (PK) of quizartinib and its pharmacologically active metabolite AC886 have been previously described in healthy volunteers (HV) and relapsed/refractory (R/R) FLT3-internal-tandem-duplication-positive (FLT3-IDT-positive) acute myeloid leukemia (AML) patients receiving quizartinib monotherapy. In this analysis, we characterized the population PK of quizartinib and AC886 in newly diagnosed FLT3-ITD-positive AML patients receiving standard induction and consolidation chemotherapy as background treatment, using data from the Phase 3 QuANTUM-First trial and 12 earlier studies. Quizartinib PK were best described by a three-compartment model with sequential zero- and first-order absorption and first-order elimination. A two-compartment model with first-order metabolite formation and first-order elimination best fitted AC886 data. The PK of both moieties showed large interindividual variability (approximately 70% coefficient of variation for systemic clearances). The use of strong cytochrome P450 3A (CYP3A) inhibitors had the largest impact on exposure, increasing the steady-state area under the curve during the dosing interval (AUCss) by 1.8-fold. This is consistent with observations in HV and R/R AML patients and confirms the need for dose adjustments during coadministration. A novel finding in newly diagnosed AML patients was the phase-dependent change in steady-state quizartinib exposure: dose-normalized AUCss values were 0.6-fold during induction, similar during consolidation, and 1.4-fold during continuation compared to R/R AML patients receiving quizartinib monotherapy. The present analysis highlighted the comparison of quizartinib and AC886 PK between newly diagnosed AML patients and previously studied populations, informed dose modifications needed with strong CYP3A inhibitors, and supported the use of derived individual exposure metrics in separate exposure-response analyses.

Copy number alterations in pediatric B-cell precursor acute lymphoblastic leukemia patients and their association with patients' outcome.

Genetic abnormalities provide diagnostic and prognostic information for pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients. The aim of this study was to determine the effects of genetic CNAs and RUNX1 gene abnormalities on the outcome of pediatric BCP-ALL patients. This study included 78 de novo-BCP-ALL pediatric patients who presented to the Pediatric Oncology Department of the National Cancer Institute (NCI), Cairo University. We aimed to study the impact of copy number alteration (CNA) of 8 of the most altered genes in BCP-ALL patients, in addition to RUNX1 gene abnormalities, on patient survival and response to treatment. Multiplex ligation-dependent probe amplification (MLPA) was used to detect CNA, while RUNX1 gene alterations were detected by fluorescence in situ hybridization (FISH). CNA of the PAX5 gene was significantly associated with worse overall survival (OS) and event-free survival (EFS) (P = 0.012 and P = 0.025, respectively). An increase in the CNA of ETV6 was associated with an increase in minimal residual disease (MRD) on day 15 (P = 0.041). Although RUNX1 gene abnormalities were not a predictor of shorter OS or EFS, an interesting significant association was found between PAX5 CNA and RUNX1 gene gain and translocation (P = 0.017 and P = 0.041, respectively). PAX5 CNA is an adverse prognostic factor. ETV6 CNA is associated with high MRD on day 15.

Molecular Secrets Revealed: How Diabetes may be Paving the Way for Leukemia.

Type 2 Diabetes Mellitus (T2DM) and leukemia are two major global health concerns, both contributing significantly to morbidity and mortality. Epidemiological evidence demonstrates a strong correlation between T2DM and an increased risk of leukemia, particularly driven by insulin resistance, hyperglycemia, and the resultant metabolic dysregulation. Key shared risk factors, including obesity and chronic inflammation, create a conducive environment for leukemogenesis, intensifying cancer cell proliferation and resistance to standard therapies. Insulin resistance, in particular, triggers oncogenic pathways such as PI3K/AKT and MAPK, exacerbating the aggressive phenotype seen in leukemia patients with T2DM. Additionally, clonal hematopoiesis of indeterminate potential (CHIP) is implicated in the higher leukemia risk observed in diabetic populations, especially among the elderly. Molecular mechanisms like the insulin-like growth factor (IGF) system further highlight the intricate link between these diseases, promoting survival and proliferation of leukemia cells. The coexistence of T2DM in leukemia patients is associated with poorer prognostic outcomes, including increased susceptibility to infections, reduced survival, and greater treatment resistance. Antidiabetic agents, notably metformin and pioglitazone, show promise in enhancing chemotherapy efficacy and improving patient outcomes by targeting metabolic pathways. These results highlight the need for comprehensive treatment approaches that target both metabolic abnormalities and cancer-related mechanisms in patients suffering from both T2DM and leukemia.

Clinical Utility of a Novel Triplex Digital PCR Assay for Clone Monitoring in Sequential and Relapsed Pediatric B-Cell Acute Lymphoblastic Leukemia Patients.

Digital polymerase chain reaction (PCR) studies for clonal disease monitoring in B-acute lymphoblastic leukemia patients are currently limited due to the heterogeneous nature of mutations, which limit cost-effective assay designs. In this study, 70 samples (14 relapse and 56 sequential therapy samples) were tested for 13 recurrent mutations identified on deep sequencing in our published cohort (KRAS, NRAS, NT5C2, PMS2, UHRF1, KMT2D, and TP53 genes) via a novel triplex digital PCR assay. A total of seven major clones of NRAS [five] and NT5C2 [two] were noted in six out of 14 (43%) relapse patients, accounting for 44% of early relapses. In addition, 10 minor clones (PMS2 [two], NRAS [four], NT5C2 [three], and TP53 [one]) were noted in five out of 14 (36%) patients. In the 56 sequential therapy samples, six major clones were noted (NRAS [five], KRAS [one]) in four out of 14 (28.5%) patients, with two increasing in size in maintenance samples, leading to subsequent relapse in both cases. In addition, therapy-acquired minor clones in NT5C2 [four] and PMS2 [one] were seen to emerge in maintenance samples in four out of 14 (28.5%) patients, with concordant detection of such major and minor clones in unpaired relapse samples, indicating the need for their active surveillance during therapy. Overall, digital PCR validated NRAS and NT5C2 major clones in one-third (10 out of 27; 37%) of cases, driving nearly half of early relapses.

Plasma concentrations of venetoclax and Pharmacogenetics correlated with drug efficacy in treatment naive leukemia patients: a retrospective study

Venetoclax (VEN) was the only Bcl-2 inhibitor approved yet and showed large differences in clinical efficacy. The aim of the study was to explore the relationships between the plasma concentration and efficacy of VEN, and identify potential influencing factors. A retrospective cohort study was conducted and a total of 76 trough (C0h) and 91 6 h post-dose plasma concentration (C6h) blood concentrations of VEN were collected in 54 patients. C6h/D concentration of VEN was found to be significantly correlated with treatment efficacy (p = 0.006) in leukemia patients with good or intermediate prognosis stratification. A ROC curve was then established and the cut-off value was calculated as 0.2868 μg/ml (AUC = 0.7097, p = 0.1081). Besides, patients co-administered with triazoles or carrying CYP3A5 rs776746 AA/AG genotypes were prone to induce higher VEN plasma concentration regardless of whether VEN dosage was reduced or not. Through LASSO-logistic regression and nomogram analysis, chemotherapy regimens and neutrophil percentages were identified as the critical elements that may predict drug response. Above all, in addition to identify prognostic stratification, AML patients taken with VEN were suggested to test plasma concentration routinely so as to achieve desired efficacy, especially when co-administered with triazoles or carried with CYP3A5 rs776746 AA/AG.

Soluble CD206 and CD163 as novel prognostic biomarkers in adult acute myeloid leukemia

BackgroundDespite advances in chemotherapy, the prognosis of adult acute myeloid leukemia (AML) patients remains poor, with a 5-year survival rate below 25%. In the tumor microenvironment of AML, tumor-associated macrophages (TAMs) are very important in the microenvironment of AML tumors because they help leukemic cells to survive, grow and migrate. They also play a key role in how the disease progresses. M2 macrophages highly express both CD206 (mannose receptor, C type I, and CD163 (hemoglobin scavenger receptor), a monocyte/macrophage receptor, as markers for M2 macrophages. Soluble CD206 (sCD206) and CD163 (sCD163) emerge as prognostic players for hematopoietic neoplasms. This study aimed to assess the prognostic potential of sCD206 and sCD163 as serological markers in AML. The study included 60 AML patients and 20 healthy volunteers as controls. The levels of serological markers sCD206 and sCD163 were measured by ELISA, and their prognostic values were evaluated.ResultsSerum levels of sCD206 and sCD163 were statistically significantly (P < 0.001) higher in AML cases than in controls. AML patients were categorized into two subgroups based on the response outcome to induction therapy: 36 patients (60%) had complete response (CR), and the other 24 patients (40%) had refractory disease. Interestingly, based on response outcome, serum levels of sCD206 and sCD163 as well as total leukocytic count (TLC), absolute neutrophils count (ANC) and absolute lymphocyte count (ALC) were significantly higher (all P < 0.001) in refractory group than in CR group. Further, a significant positive correlation of both sCD206 and sCD163 with TLC, ANC and ALC was observed (all P < 0.001).ConclusionLevels of sCD206 and sCD163 emerge as promising prognostic biomarkers for AML outcome and progression.

Dynamics of measurable residual disease for risk stratification and guiding allogeneic transplant in acute myeloid leukaemia patients with myelodysplasia-related mutations in first remission.

Accurate classification and risk prediction are critical for therapeutic decision-making in patients with acute myeloid leukaemia (AML). Myelodysplasia-related (MR) gene mutations are classified as adverse genetic factors by the European LeukaemiaNet-2022 guidelines. However, their prognostic value in de novo AML remains controversial. This study retrospectively analysed 188 patients with de novo AML-MR, stratifying them into four subgroups based on dynamic measurable residual disease (MRD) after induction, one or two courses of consolidation chemotherapy. The median follow-up was 36.8 months (4.6-73.7). Patients with persistent or recurrent MRD positivity after the second consolidation had the poorest 3-year relapse-free survival (RFS), overall survival (OS) and cumulative incidence of relapse compared to the other groups (p < 0.001). Multivariable analysis identified this high-risk group as an independent risk factor for both RFS and OS. We observed significant heterogeneity of OS benefit from allogeneic stem cell transplantation (allo-SCT) by MRD-risk groups, with substantial OS advantage for patients in subgroup D (3-year OS: allo-SCT 70.0% vs. 18.2% without, p < 0.001) but no benefit for others (p = 0.047 for interaction). This study underscores the importance of dynamic MRD in refining risk stratification and identifying de novo AML patients with MR mutations who would benefit from allo-SCT during the first complete remission.

Molecular, Cytogenetic, and Hematological Monitoring and Response to Treatment for Chronic Myeloid Leukemia Patients

Molecular, Cytogenetic, and Hematological Monitoring and Response to Treatment for Chronic Myeloid Leukemia Patients

Nelarabine-combined chemotherapy improves outcome of T-cell acute lymphoblastic leukemia but shows more severe neurotoxicity: JALSG T-ALL213-O.

We investigated the effectiveness and safety of nelarabine (NEL)-combined chemotherapy for newly diagnosed adult T-cell acute lymphoblastic leukemia (T-ALL) patients. We conducted a phase II trial, T-ALL213-O, where adult T-ALL patients aged 25 to 64 were treated by a regimen based on that used in our previous study, ALL202-O. The main modifications from ALL202-O to T-ALL213-O were as follows: (1) NEL-combined chemotherapy, instead of consolidation (C)1, was used for non-complete remission (CR) patients after induction therapy (IND)1 as IND2; (2) NEL treatments were inserted into C3 and C5 on day 29. Twenty-four patients were analyzed. Ten patients did not receive NEL treatment due to therapy termination prior to C3. Three-year event-free survival (EFS) was 70%, with 52% as the lower limit of its 90% confidence interval, which exceeded the threshold of 25%; thus, the study treatment was considered effective. The CR rates by IND1, IND2, and both were 75%, 100%, and 88%, respectively. The 5-year EFS and 5-year overall survival rates were 66% and 70%, respectively, with median follow-ups of 7.7 and 7.8 years. The addition of NEL improved the CR rate but not survival, compared with T-ALL patients in ALL202-O. Severe neuropathy after NEL administration was observed at a high frequency. Seven (50%) of 14 patients treated with NEL showed grade 3 peripheral neuropathy and/or gait disturbance. The neurotoxicity was considered stronger than that previously reported. Combination therapy of NEL at this dose and intensive multidrug chemotherapy is associated with a high risk of severe neurotoxicity (JALSG T-ALL213-O, UMIN000010642).

Investigating the influence of germline ATM variants in chronic lymphocytic leukemia on cancer vulnerability.

Chronic lymphocytic leukemia (CLL) patients have an increased risk of secondary cancers, along with predisposition to CLL in their relatives. We have previously identified germline ATM variants as associated with CLL risk; here, we present their impact on predisposition to secondary neoplasms in CLL patients and their relatives. Patients enrolled in our tissue bank who had germline ATM status available were mailed a questionnaire between April 2022 and May 2023. Of the 333 patients who replied to the questionnaire, 283 patients (85%) reported at least one relative with a cancer history. The prevalence of family history of B-cell lymphoproliferative disorders was significantly higher (p=0.02) in patients with germline ATM variants (32%) compared to those without germline ATM variants (21%) including familial CLL (25% vs 18%) (p=0.04). No significant difference in the prevalence of secondary cancers was found between patients with and without germline ATM variants (p=0.73), although the role for individual ATM variants in other malignancies could not be excluded given the small sample size. Time to first CLL treatment (TTFT) was shorter in patients harboring somatic ATM events while no difference was observed in patients with germline ATM variants. In conclusion, we demonstrate a higher prevalence of B-cell lymphoproliferative disorders, including familial CLL, in relatives of CLL patients carrying germline ATM variants. The presence of these germline variants did not impact TTFT compared to patients harboring somatic ATM mutations.

Acute myeloid leukemia drug tolerant persister cells survive chemotherapy by transiently increasing plasma membrane rigidity, that also increases their sensitivity to immune cell killing.

Resistance to chemotherapy remains a major hurdle to the cure of Acute Myeloid Leukemia (AML) patients. Recent studies indicate a minority of malignant cells, termed drug-tolerant persisters (DTPs), stochastically upregulate stress pathways to evade cell death upon acute exposure to chemotherapy without acquiring new genetic mutations. This chemoresistant state is transient and the cells return to baseline after removal of chemotherapy. Yet, the mechanisms employed by DTPs to resist chemotherapy are not well understood and it is largely unknown whether these mechanisms are also seen in patients receiving chemotherapy. Here, we used leukemia cell lines, primary AML patient samples and samples from patients with AML receiving systemic chemotherapy to study the DTP state. We demonstrated that a subset of AML cells transiently increases membrane rigidity to resist killing due to acute exposure to Daunorubicin and Ara-C. Upon removal of the chemotherapy, membrane rigidity returned to baseline and the cells regained chemosensitivity. Although resistant to chemotherapy, the increased membrane rigidity, rendered AML cells more susceptible to T-cell mediated killing. Thus, we identified a novel mechanism by which DTP leukemic cells evade chemotherapy and a strategy to eradicate these persistent cells.

Molecular Analysis of Genes CEBPA, NPM1, IDH1, and RUNX1 Polymorphisms as Biomarker Potential in Leukemia Patients.

Leukemia is found in approximately 2.3 million people worldwide and causes many deaths all over the world. This research study was conducted to figure out the link of single nucleotide polymorphisms of genes CEBPA (rs34529039), NPM1 (rs753788683), IDH1 (of rs11554137) and RUNX1 (rs13051066) polymorphisms as biomarker potential in leukemia patients. A total of 600 subjects were included in the study which included 300 patients and 300 healthy controls with age and gender matched. After DNA extraction, PCR was carried out to analyze polymorphisms of selected genes. A significant association with increased risk of leukemia by almost twofolds is observed in homozygous mutant (AA) of rs34529039 SNP of gene CEBPA (odds ratio [OR] = 1.71; 95% confidence interval [CI] = 1.04-2.82; p = 0.03) while highly significant association but with decrease risk of leukemia is observed in heterozygote genotype (CA) of same SNP (OR = 0.36; 95% CI = 0.22-0.59; p = 0.0001). A highly significant association with increased risk of leukemia up to twofolds is observed in heterozygote genotype (AG) of rs753788683 of gene NPM1 (OR 2.10: 95% CI 1.32-3.36 p = 0.0017) while increasing risk by two-fold and show significant association in homozygous mutant (AA) (OR = 1.75; 95% Cl = 1.09-2.79; p = 0.01). Leukemia risk increases by twofold and shows significant association in the homozygous mutant (AA) of rs11554137 (OR = 1.75; 95%Cl = 1.09-2.79; p = 0.01). Leukemia risk increases by twofold and shows significant association in the homozygous mutant (AA) of rs13051066 of gene RUNX1 (OR = 0.63; 95%Cl = 0.39-1.63; p = 0.06).

The Effect of Cordia myxa Mouthwash on the Incidence and Severity of Stomatitis in Leukemia Patients Undergoing Chemotherapy: A Protocol Study

Background: Stomatitis, or oral inflammation, is one of the common complications in patients undergoing chemotherapy, causing pain, discomfort, infection, and prolonged hospitalization. Objectives: The purpose of this study is to investigate the effect of Cordia myxa mouthwash on preventing stomatitis in patients undergoing chemotherapy. Methods and Result: This study will be a double-blind, single-center, randomized controlled clinical trial focusing on 60 patients undergoing chemotherapy. The samples will be randomly divided into intervention and control groups. In addition to receiving the routine Betadine mouthwash, participants in the intervention group will receive a solution of 30 drops of 5% C. myxa formulation in 20 cc of water, and they will be asked to put the solution in their mouth, swirl it for a minute, and then spit it out. In the control group, in addition to Betadine mouthwash, a sterile water placebo (with the same taste and smell) will be used. The data will be analyzed based on statistical tests using SPSS version 22. Conclusions: If this intervention proves effective in improving access and adherence to treatment, it would represent a step forward in addressing a chronic health problem common among leukemia patients undergoing chemotherapy. Given its natural essence and the fact that it is not associated with any complications, C. myxa mouthwash can be used safely alongside the main treatment to prevent and reduce the severity of mouth ulcers caused by chemotherapy.

A 12-week WeChat education, relaxing, and care program relieves anxiety, depression, insomnia, and posttraumatic stress disorder in parents of childhood lymphoma patients

ABSTRACT Objectives In our previous study, we conducted a 6-month WeChat education and care program for parents of pediatric acute lymphoblastic leukemia patients, which was effectively alleviated anxiety, depression, and insomnia. This study implemented a 12-week WeChat education, relaxing, and care program (WERC) to investigate its effect on psychological disorders and insomnia in parents of childhood lymphoma patients. Methods Totally, 112 parents of 56 childhood lymphoma patients were randomized at a 1:1 ratio into WERC (N = 56) or normal care (NC) (N = 56) groups to receive corresponding 12-week interventions. The self-rating anxiety/depression scale (SAS/SDS), Athens insomnia scale (AIS), and impact of events scale-revised (IES-R) scores were assessed at enrollment (W0) and 12 weeks after the initiation of the intervention (W12); score changes (W0–W12) were also calculated. Results Scores of the scales at W0 did not differ between groups (all P > 0.05). The WERC group showed a lower SAS score at W12 (P = 0.045) and greater change in SAS score (P < 0.001) than the NC group. The SDS score at W12 was not different (P = 0.119), while SDS score change was numerically greater (P = 0.076) in the WERC group than the NC group. Compared with the NC group, the WERC group tended toward a decreased AIS score at W12 (P = 0.054) and a greater AIS score change (P < 0.001). The IES-R score at W12 was lower (P = 0.040), and the IES-R score change was greater (P = 0.013) in the WERC group than the NC group. Conclusion A 12-week WERC ameliorates psychological disorders and insomnia better than NC in parents of childhood lymphoma patients.

Subacute onset rhino-orbital mucormycosis caused by Cunninghamella in a Chinese leukemia patient: A case report and literature review

Purpose We herein report a case of subacute-onset rhino-orbital mucormycosis (ROM) in an acute leukemia patent caused by the rare but most lethal pathogenic fungus - Cunninghamella. To the best of our knowledge, this is the first case of ROM caused by Cunninghamella reported in China. Case description A 50-year-old Chinese female with acute leukemia (M2 type) who, following the completion of two cycles of chemotherapy, began to exhibit naso-ocular symptoms. The patient was initially diagnosed with extramedullary leukemia. As the disease progressed, the patient began to develop specific black crust-like necrosis of the right eyelids. Following multidisciplinary treatment (MDT) consultation and tissue biopsy, the patient was finally diagnosed with a rare type of ROM caused by Cunninghamella infection. Although the mortality associated with Cunninghamella infection was significantly greater than that associated with infections caused by other Mucorales, the infection was eventually controlled through the adjustment of the antifungal drug regimen and timely surgical intervention. Conclusions ROM infection with Cunninghamella is an extremely rare and fatal fungal infection, and early recognition and diagnosis of the disease is critical to the prognosis. The subacute nature of this case may have been a positive factor in the patient's preservation of life.

An analytical study of ophthalmological manifestations in hematological malignancies in a tertiary care centre, India

: The objective of the study was to describe the ophthalmological manifestations associated with various haematological malignancies at a tertiary care centre. This analytical cross-sectional study was conducted with 60 patients diagnosed with various types of haematological malignancies, including leukaemia, lymphomas, and multiple myeloma. Patients who had ocular media opacities which precluded fundus view like dense corneal opacity, cataracts, absolute glaucoma, and systemic conditions like hypertension, and diabetes were excluded from this study. All 60 patients underwent a comprehensive ocular examination and the collected data were analysed using IBM SPSS software version 25. Out of the 60 patients with haematological malignancies, 27 (45%) exhibited ocular features. Ocular involvement was more common in males (63%) and in the paediatric age group (1-10 years) (100%). Ocular findings were prevalent in leukaemia patients especially with chronic myeloid leukaemia showing the highest incidence (80%), compared to lymphomas and multiple myeloma. The most common ocular manifestations were in the posterior segment, such as retinal haemorrhages and Roth spots, observed across all age groups. Neurological involvement, specifically III and VI cranial nerve palsy, were also notable. At the time of presentation, the majority of patients with ocular features had good visual acuity, ranging from 6/6 to 6/9 (43%). With advancements in diagnostic and therapeutic methods, the survival rates for patients with haematological malignancies have considerably improved. This has led to an increase in the variability of ocular presentations. Consequently, routine ocular examination is essential at the time of diagnosis of haematological malignancies to prevent vision-threatening complications and improve the overall quality of life for these patients.

Delineation of features, responses, outcomes, and prognostic factors in pediatric PDGFRB-positive acute lymphoblastic leukemia patients: A retrospective multicenter study.

PDGFRB fusions in acute lymphoblastic leukemia (ALL) is rare. The authors identified 28 pediatric PDGFRB-positive ALL. They analyzed the features, outcomes, and prognostic factors of this disease. This multicenter, retrospective study included 6457 pediatric patients with newly diagnosed PDGFRB fusion ALL according to the CCCG-ALL-2015 and CCCG-ALL-2020 protocols from April 2015 to April 2022 in 20 hospitals in China. Of these patients, 3451 were screened for PDGFRB fusions. Pediatric PDGFRB-positive ALL accounted for only 0.8% of the 3451 cases tested for PDGFRB. These patients included 21 males and seven females and 24 B-ALL and 4 T-ALL; the median age was 10 years; and the median leukocyte count was 29.8 × 109/L at baseline. Only one patient had eosinophilia. Three patients had an IKZF1 deletion, three had chromosome 5q31-33 abnormalities, and one suffered from a complex karyotype. The 3-year event-free survival (EFS), overall survival (OS), and cumulative incidence of relapse (CIR) were 33.1%, 65.5%, and 32.1%, respectively, with a median follow-up of 25.5 months. Twenty patients were treated with chemotherapy plus tyrosine-kinase inhibitors (TKIs) and eight were treated without TKI. Complete remission (CR) rates of them were 90.0% and 63.6%, respectively, but no differences in EFS, OS, or CIR. Univariate analyses showed patients with IKZF1 deletion or measurable residual disease (MRD) ≥0.01% after induction had inferior outcomes (p<.05). Pediatric PDGFRB-positive ALL has a poor outcome associated with high-risk features. Chemotherapy plus TKIs can improve the CR rate, providing an opportunity for lower MRD levels and transplantation. MRD ≥0.01% was a powerful adverse prognostic factor, and stratified treatment based on MRD may improve survival for these patients. Pediatric acute lymphoblastic leukemia patients with PDGFRB fusions are associated with high-risk clinical features such as older age, high white blood cell count at diagnosis, high measurable residual disease after induction therapy, and increased risk of leukemia relapse. Chemotherapy plus tyrosine-kinase inhibitors can improve the complete remission rate and provide an opportunity for lower measurable residual disease (MRD) levels and transplantation for pediatric PDGFRB-positive acute lymphoblastic leukemia (ALL) patients. The MRD level was also a powerful prognostic factor for pediatric PDGFRB-positive ALL patients.

Current Understanding of the Role of Autophagy in the Treatment of Myeloid Leukemia.

The most important issues in acute myeloid leukemia are preventing relapse and treating relapse. Although the remission rate has improved to approximately 80%, the 5-year survival rate is only around 30%. The main reasons for this are the high relapse rate and the limited treatment options. In chronic myeloid leukemia patients, when a deep molecular response is achieved for a certain period of time through tyrosine kinase inhibitor treatment, about half of them will reach treatment-free remission, but relapse is still a problem. Therefore, potential therapeutic targets for myeloid leukemias are eagerly awaited. Autophagy suppresses the development of cancer by maintaining cellular homeostasis; however, it also promotes cancer progression by helping cancer cells survive under various metabolic stresses. In addition, autophagy is promoted or suppressed in cancer cells by various genetic mutations. Therefore, the development of therapies that target autophagy is also being actively researched in the field of leukemia. In this review, studies of the role of autophagy in hematopoiesis, leukemogenesis, and myeloid leukemias are presented, and the impact of autophagy regulation on leukemia treatment and the clinical trials of autophagy-related drugs to date is discussed.