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Acta Haematologica Jun 2024Introduction Promotion of self-efficacy can enhance engagement with healthcare and treatment adherence in patients with cancer. We report the outcomes of a pilot trial...
Effect of Digital Health Coaching on Self-Efficacy and Patient Reported Outcomes in Individuals with Acute Myeloid and Chronic Lymphocytic Leukemia: A Pilot Randomized Controlled Trial.
Introduction Promotion of self-efficacy can enhance engagement with healthcare and treatment adherence in patients with cancer. We report the outcomes of a pilot trial of a digital health coach intervention in patients with leukemia with the aim of improving self-efficacy. Methods Adult patients with newly diagnosed acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) were randomized 1:1 to a digital health coach intervention or standard of care. The primary outcome of self-efficacy was measured by the Cancer Behavior Inventory (CBI) score. Results One-hundred and forty-seven patients (37 AML, 110 CLL) were enrolled from July 2020 to December 2022. In the AML cohort, there was a mean increase in CBI score of 7.03 in the digital health coaching arm compared to a mean decrease of -3.57 in the control arm at 30 days (p=0.219). There were no significant associations between the intervention and other patient reported outcomes for patients with CLL. Conclusion There were numerical, but not statistically significant increases in self-efficacy metrics in AML patients who received digital health coaching. Although this trial was underpowered due to enrollment limitations during a pandemic, digital health coaching may provide benefit to patients with hematologic malignancy and warrants further investigation.
PubMed: 38861934
DOI: 10.1159/000539756 -
Infection Prevention in Practice Sep 2024Gastroenteritis accounts for about 10% of the deaths among children, especially in immunocompromised children. Few studies on the prevalence of gastrointestinal...
BACKGROUND
Gastroenteritis accounts for about 10% of the deaths among children, especially in immunocompromised children. Few studies on the prevalence of gastrointestinal infections caused by RNA viruses have been done in Iran. The aim of the study was to evaluate the detection of RNA viruses causing diarrhoea using a multiplex PCR.
METHODS
Stool samples were collected from 130 paediatric patients with diarrhoea who had acute lymphocytic leukaemia, non-Hodgkin lymphoma, and retinoblastoma. After RNA extraction and synthesis of cDNA, multiplex PCR was done to evaluate the presence of rotavirus, norovirus, astrovirus, and enterovirus.
RESULTS
There were 9 (6.9%), 7 (5.4%), 3 (2.3%), and 6 (4.6%) cases of rotavirus, norovirus, astrovirus, and enterovirus detected, respectively. One case of co-infection with astrovirus and norovirus was observed.
CONCLUSIONS
This is the first report from Iran which identified the presence of common RNA viruses causing diarrhoea in immunocompromised children. Increased awareness of these viruses will enable healthcare professionals to improve strategies and policies to control spread and infection caused by these viruses.
PubMed: 38855735
DOI: 10.1016/j.infpip.2024.100370 -
European Journal of Pharmacology Aug 2024Acute lymphoblastic leukemia (ALL), a complex malignancy, displays varying expression profiles of PIP4K2-related genes in adult patients. While PIP4K2A expression is...
Acute lymphoblastic leukemia (ALL), a complex malignancy, displays varying expression profiles of PIP4K2-related genes in adult patients. While PIP4K2A expression is elevated in ALL bone marrow cells compared to healthy bone marrow cells, PIP4K2B is downregulated, and PIP4K2C remains relatively unchanged. Despite the correlation between increased PIP4K2A expression and increased percentage of peripheral blood blasts, clinical outcomes do not strongly correlate with the expression of these genes. Here we investigated the therapeutic potential of three PIP4K2 inhibitors (THZ-P1-2, a131, and CC260) in ALL cell models. THZ-P1-2 emerges as the most effective inhibitor, inducing cell death and mitochondrial damage while reducing cell viability and metabolism significantly. Comparative analyses highlight the superior efficacy of THZ-P1-2 over a131 and CC260. Notably, THZ-P1-2 uniquely disrupts autophagic flux and inhibits the PI3K/AKT/mTOR pathway, indicating a distinct molecular mechanism. In summary, our findings elucidate the differential expression of PIP4K2-related genes in ALL and underscore the potential role of PIP4K2A in disease pathogenesis. The therapeutic promise of THZ-P1-2 in ALL treatment, along with its distinct effects on cell death mechanisms and signaling pathways, enriches our understanding of PIP4K2's involvement in ALL development and offers targeted therapy prospects.
Topics: Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Phosphotransferases (Alcohol Group Acceptor); Cell Line, Tumor; Signal Transduction; Proto-Oncogene Proteins c-akt; Antineoplastic Agents; TOR Serine-Threonine Kinases; Autophagy; Cell Survival; Phosphatidylinositol 3-Kinases; Enzyme Inhibitors; Protein Kinase Inhibitors; Apoptosis
PubMed: 38851560
DOI: 10.1016/j.ejphar.2024.176723 -
Indian Journal of Public Health Jan 2024Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Immunophenotype (IPT) and cytogenetics are essential for diagnosis, risk stratification, and...
BACKGROUND
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Immunophenotype (IPT) and cytogenetics are essential for diagnosis, risk stratification, and management for ALL.
OBJECTIVES
Evaluating the burden of immunophenotypic and cytogenetic profile of pediatric ALL patients.
MATERIALS AND METHODS
A descriptive cross-sectional study was conducted on 100 patients of ALL (1-18 completed years) attending a tertiary-care center in Kolkata, Eastern India.
RESULTS
Ninety-six percent of patients had B-cell ALL (94.00% pre-B ALL and 2.00% Pro-B ALL) and 4.0% had T-ALL. 60% B-cell ALL were CD19/CD10 positive, 10% were CD79a positive, 9% were only CD19 positive, and 7% were only CD10 positive. Thirty-three percent of T-ALL were CD3+, whereas 22% were positive each for CD4 and CD7. 51.0% of patients had diploid, 46.0% hyperdiploid, and 3.0% hypodiploid karyotype. Among hyperdiploids, 98% had good prednisolone response and 89% had measurable residual disease (MRD) <0.01.
CONCLUSION
The most commonly diagnosed ALL by IPT was pre-B ALL. Among the detectable cytogenetic abnormalities, t(12; 21) ETV6-RUNX1 was the most common. ZNF-384 gene arrangement was also detected in our study. t(12;21) ETV6-RUNX1 had a good treatment response, while t(9;22) BCR-ABL, t(1;19) TCF3-PBX1, iAMP-21, MLL gene rearrangement, and ZNF-384 gene arrangement had poor treatment response in terms of MRD.
Topics: Humans; India; Child; Male; Female; Child, Preschool; Adolescent; Cross-Sectional Studies; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Immunophenotyping; Infant; Cytogenetic Analysis
PubMed: 38847628
DOI: 10.4103/ijph.ijph_889_23 -
Leukemia Jul 2024Recent trials show 5-year survival rates >95% for ETV6::RUNX1 Acute Lymphoblastic Leukemia (ALL). Since treatment has many side effects, an overview of cumulative drug... (Meta-Analysis)
Meta-Analysis
Recent trials show 5-year survival rates >95% for ETV6::RUNX1 Acute Lymphoblastic Leukemia (ALL). Since treatment has many side effects, an overview of cumulative drug doses and intensities between eight international trials is presented to characterize therapy needed for cure. A meta-analysis was performed as a comprehensive summary of survival outcomes at 5 and 10 years. For drug dose comparison in non-high risk trial arms, risk group distribution was applied to split the trials into two groups: trial group A with ~70% (range: 63.5-75%) of patients in low risk (LR) (CCLSG ALL2004, CoALL 07-03, NOPHO ALL2008, UKALL2003) and trial group B with ~45% (range: 38.7-52.7%) in LR (AIEOP-BFM ALL 2000, ALL-IC BFM ALL 2002, DCOG ALL10, JACLS ALL-02). Meta-analysis did not show evidence of heterogeneity between studies in trial group A LR and medium risk (MR) despite differences in treatment intensity. Statistical heterogeneity was present in trial group B LR and MR. Trials using higher cumulative dose and intensity of asparaginase and pulses of glucocorticoids and vincristine showed better 5-year event-free survival but similar overall survival. Based on similar outcomes between trials despite differences in therapy intensity, future trials should investigate, to what extent de-escalation is feasible for ETV6::RUNX1 ALL.
Topics: Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Core Binding Factor Alpha 2 Subunit; ETS Translocation Variant 6 Protein; Oncogene Proteins, Fusion; Proto-Oncogene Proteins c-ets; Repressor Proteins; Antineoplastic Combined Chemotherapy Protocols; Survival Rate
PubMed: 38844578
DOI: 10.1038/s41375-024-02287-7 -
Journal For Immunotherapy of Cancer Jun 2024The bispecific T cell-binding antibody blinatumomab (CD19/CD3) is widely and successfully used for the treatment of children with relapsed or refractory B-cell precursor... (Clinical Trial)
Clinical Trial
Blinatumomab as postremission therapy replaces consolidation and substantial parts of maintenance chemotherapy and results in stable MRD negativity in children with newly diagnosed B-lineage ALL.
The bispecific T cell-binding antibody blinatumomab (CD19/CD3) is widely and successfully used for the treatment of children with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Here, we report the efficacy of a single course of blinatumomab instead of consolidation chemotherapy to eliminate minimal residual disease (MRD) and maintain stable MRD-negativity in children with primary BCP-ALL.Between February 2020 and November 2022, 177 children with non-high-risk BCP-ALL were enrolled in the ALL-MB 2019 pilot study (NCT04723342). Patients received the usual risk-adapted induction therapy according to the ALL-MB 2015 protocol. Those who achieved a complete remission at the end of induction (EOI) received treatment with blinatumomab immediately after induction at a dose of 5 μg/m/day for 7 days and 21 days at a dose of 15 μg/m/day, followed by 12 months of maintenance therapy. MRD was measured using multicolor flow cytometry (MFC) at the EOI, then immediately after blinatumomab treatment, and then four times during maintenance therapy at 3-month intervals.All 177 patients successfully completed induction therapy and achieved a complete hematological remission. In 174 of these, MFC-MRD was measured at the EOI. 143 patients (82.2%) were MFC-MRD negative and the remaining 31 patients had varying degrees of MFC-MRD positivity.MFC-MRD was assessed in all 176 patients who completed the blinatumomab course. With one exception, all patients achieved MFC-MRD negativity after blinatumomab, regardless of the MFC-MRD score at EOI. One adolescent girl with high MFC-MRD positivity at EOI remained MFC-MRD positive. Of 175 patients who had completed 6 months of maintenance therapy, MFC-MRD data were available for 156 children. Of these, 155 (99.4%) were MFC-MRD negative. Only one boy with t(12;21) (p13;q22)/ became MFC-MRD positive again. The remaining 174 children had completed the entire therapy. MFC-MRD was examined in 154 of them, and 153 were MFC-MRD negative. A girl with hypodiploid BCP-ALL showed a reappearance of MFC-MRD with subsequent relapse.In summary, a single 28-day course of blinatumomab immediately after induction, followed by 12 months of maintenance therapy, is highly effective in achieving MRD-negativity in children with newly diagnosed non-high risk BCP-ALL and maintaining MRD-negative remission at least during the treatment period.
Topics: Adolescent; Child; Child, Preschool; Female; Humans; Infant; Male; Antibodies, Bispecific; Consolidation Chemotherapy; Maintenance Chemotherapy; Neoplasm, Residual; Pilot Projects; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 38844406
DOI: 10.1136/jitc-2023-008213 -
Cancer Letters Aug 2024Relapse and treatment resistance pose significant challenges in the management of pediatric B cell acute lymphoblastic leukemia (B-ALL) and acute myeloid leukemia (AML)....
Relapse and treatment resistance pose significant challenges in the management of pediatric B cell acute lymphoblastic leukemia (B-ALL) and acute myeloid leukemia (AML). The efficacy of immunotherapy in leukemia remains limited due to factors such as the immunosuppressive tumor microenvironment (TME) and lack of suitable immunotherapeutic targets. Thus, an in-depth characterization of the TME in pediatric leukemia is warranted to improve the efficacy of immunotherapy. Here, we used single-cell RNA sequencing (scRNA-seq) to characterize the TME of pediatric B-ALL and AML, focusing specifically on bone-marrow-derived T cells. Moreover, we investigated the transcriptome changes during the initiation, remission, and relapse stages of pediatric AML. Our findings revealed that specific functional expression programs correlated with fluctuations in various T cell subsets, which may be associated with AML progression and relapse. Furthermore, our analysis of cellular communication networks led to the identification of VISTA, CD244, and TIM3 as potential immunotherapeutic targets in pediatric AML. Finally, we detected elevated proportions of γδ T cells and associated functional genes in samples from pediatric patients diagnosed with B-ALL and AML, which could inform the development of novel therapeutic approaches, potentially focusing on γδ T cells.
Topics: Humans; Tumor Microenvironment; Single-Cell Analysis; Child; Leukemia, Myeloid, Acute; Transcriptome; Hepatitis A Virus Cellular Receptor 2; Gene Expression Profiling; Child, Preschool; Male; Female; B7 Antigens; Adolescent; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Gene Expression Regulation, Leukemic
PubMed: 38844062
DOI: 10.1016/j.canlet.2024.217018 -
Journal of Pharmaceutical and... Sep 2024Therapeutic drug monitoring of pegylated L-asparaginase (ASNase) ensures the drug effectiveness in childhood acute lymphoblastic leukaemia (ALL) patients. The biological...
Improved HPLC method with automated pre-column sample derivatisation for serum pegylated L-asparaginase activity measurement in paediatric acute lymphoblastic leukaemia patients.
Therapeutic drug monitoring of pegylated L-asparaginase (ASNase) ensures the drug effectiveness in childhood acute lymphoblastic leukaemia (ALL) patients. The biological drug property with variable immunogenic host clearance, and the prescription of its generic formulation urge the need for a reliable assay to ensure an optimal treatment and improve outcome. This study aimed to optimise an existing isocratic reversed-phase high performance liquid chromatography (RP-HPLC) method with an automated pre-column sample derivatisation and injection program, and a computational algorithm for measuring serum pegylated ASNase activity in children with ALL. Nath et al.'s method in 2009 was adopted and modified using a pegylated ASNase. A set of Microsoft Excel macros was developed for the serum drug activity computation. An Agilent InfinityLab LC Series 1260 Infinity II Quaternary System with fluorescence detection was employed with an Agilent Poroshell 120 EC-C18 4.6×100 mm, 2.7 µm analytical column. System flow rate was optimised to 2.0 mL/min with 40×10/bar pump compressibility. The O-phthaldialdehyde (OPA) solution composition was optimised to 1 % o-phthaldialdehyde, 0.8 % 2-mercaptoethanol, 7.13 % methanol, and 1.81 % sodium tetraborate. The pre-column derivatisation program mixed 0.1 µL sample with 25 µL OPA solution before the automated injection. Method validation was according to the ICH guidelines. Total analysis time was 15 min, with L-aspartic acid eluted at 0.96 min and internal standard at 4.7 min. The calibration curves showed excellent linearity (R ≥0.9999). Interday precision for the drug activity at 0.1 IU/mL, 0.5 IU/mL, and 1 IU/mL were 4.15 %, 3.05 %, and 3.09 % (n = 6). Mean %error for the drug activity at 0.1 IU/mL, 0.5 IU/mL, and 1 IU/mL were 0.90±4.41 %, -1.37±3.04 %, and -3.03±3.02 % (n = 6). Limit of quantitation was 0.03 IU/mL. Majority of the patients' serum drug activity fell within the assay calibration range. Our improved method is automated, having shorter analysis time with a well-maintained separation resolution that enables a high-throughput analysis for application.
Topics: Asparaginase; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Humans; Chromatography, High Pressure Liquid; Child; Polyethylene Glycols; Drug Monitoring; Antineoplastic Agents; Reproducibility of Results; Chromatography, Reverse-Phase; Calibration
PubMed: 38843612
DOI: 10.1016/j.jpba.2024.116243 -
Blood Jun 2024
Topics: Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Hydrogen-Ion Concentration
PubMed: 38842859
DOI: 10.1182/blood.2024024465 -
Pediatric Blood & Cancer Aug 2024Acute appendicitis (AA) in pediatric patients with acute leukemia mandates prompt treatment. Diagnosis presents challenges, relying on clinical and radiological...
Acute appendicitis (AA) in pediatric patients with acute leukemia mandates prompt treatment. Diagnosis presents challenges, relying on clinical and radiological assessments, often leading to treatment delays that may disrupt leukemia management. Our study on 14 such cases underscores the pivotal role of swift intervention. While conservative AA treatment may pose no risk to healthy children, our findings mandate the performance of laparoscopic appendectomy within 24 hours of diagnosis. This strategy yielded successful surgical outcomes while ensuring uninterrupted leukemia care. Our experience contributes important insights to the limited understanding of navigating this complex clinical scenario.
Topics: Humans; Appendicitis; Child; Male; Female; Adolescent; Appendectomy; Child, Preschool; Acute Disease; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Laparoscopy; Prognosis
PubMed: 38840423
DOI: 10.1002/pbc.31114