Induction Phase Of Chemotherapy Research Articles

Risk factors associated with sepsis in children with acute lymphoblastic leukemia and febrile neutropenia

Background Children with acute lymphoblastic leukemia (ALL), especially those with febrile neutropenia, are susceptible to sepsis. Several factors have been associated with the occurrence of sepsis in children with leukemia. Objective To identify potential risk factors associated with sepsis in children with ALL and febrile neutropenia. Methods This cross-sectional study was done in children with ALL who sought treatment at Dr. Hasan Sadikin General Hospital, Bandung, Indonesia from January 2019 to March 2022. We recorded patients’ gender, age, nutritional status, absolute neutrophil count (ANC), co-infection, prophylactic antibiotic use, and phase of chemotherapy. Results Of 131 subjects, 57.3% were male and 42.8% were wasted. Subjects had a median age of six years old and median ANC of 230 cells/mm3. Furthermore, 48.9% of subjects had co-infections, 87.8% had not received prophylactic antibiotics, and 48.9% were in the induction phase of chemotherapy. Multiple logistic regression analysis revealed that older age [OR 1.16 (95%CI 1.04 to 1.29); ?=0.149; P=0.008] and co-infection [OR 12.9 (95%CI 5.01 to 33.21); ?=2.551; P<0.001] were significantly associated with sepsis in children with ALL and febrile neutropenia. Bronchopneumonia was the most common co-infection (72.5%). Conclusion Older age and co-infection are significantly associated with sepsis in children with ALL and febrile neutropenia.

Abstract 5472: Direct cytotoxicity of hu14.18K.322A in high-risk neuroblastoma

Abstract Background: Neuroblastoma is a childhood cancer of the sympathetic nervous system and is associated with disialoganglioside GD2 overexpression. The main goal of this study is to investigate the involvement of GD2 targeting humanized antidisialoganglioside monoclonal antibody hu14.18K.322A (hu14) in high-risk neuroblastoma direct cell cytotoxicity, assess for synergy with induction chemotherapy agents, and delineate the mechanisms involved in cell death. Methods: For this study, we used a panel of GD2 expressing cell lines [SK-N-BE (2), SK-N-BE (1), LAN5, CHLA15] and a GD2 non-expressing cell line LAN6. We measured surface expression of GD2 and performed cell cycle analysis using flow cytometry. The role of hu14 in neuroblastoma cell death was assessed using cell viability assays, proliferation assays, real time PCR and western blot analysis. We measured synergy between hu14 and induction phase chemotherapy drugs. Further, we employed next generation sequencing (NGS) to analyze the transcriptomic changes in human neuroblastoma cell lines in response to hu14 treatment to understand the pathways involved and the molecular mechanisms of hu14-mediated cellular response. Results: Using a cell viability assay, we found that CHLA15 and SK-N-BE (1) cell lines were sensitive to hu14 treatment whereas SK-N-BE (2), LAN5, LAN6 were resistant. Hu14 treatment resulted in a dose dependent reduction in cell proliferation in these cell lines. We also found that hu14 treatment resulted in increased expression of apoptotic and autophagy pathway proteins, but not ferroptosis or necroptosis pathways proteins. Hu14 induced cell death was partially inhibited by a pan-caspase inhibitor, confirming that caspase-dependent pathways are involved. Western blot analysis also showed decreased levels of p53 phosphorylation in both sensitive cell lines upon hu14 treatment suggesting an important control mechanism centered on the p53 pathway. Hu14 treatment reduced the surface expression of GD2 in the sensitive cells suggesting direct inhibition of the GD2 synthesis pathway. However, PCR analysis of GD2 synthesis genes did not show any significant difference upon treatment suggesting posttranscriptional control of these genes. Furthermore, NGS analysis revealed alterations in several pathways, but these changes were distinct between the cell lines reconfirming the complexity of therapy response in high-risk Neuroblastoma. Conclusion: Taken together, our findings suggest that hu14.18K322A induces direct cell cytotoxicity in a subset of high-risk Neuroblastoma and synergizes well with standard chemotherapy drugs. Furthermore, our research highlights the complex nature of signaling pathways involved in hu14-mediated cytotoxicity that can be harnessed towards targeted therapy. Citation Format: Manu Gnanamony, Maria Thomas, Thu Hien Nguyen, Amber M. D'Souza, Pedro de Alarcon. Direct cytotoxicity of hu14.18K.322A in high-risk neuroblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5472.

Survivorship Struggles: Navigating Etiologies and Clinical Parameters of Febrile Neutropenia During Induction Chemotherapy in Acute Leukemia Patients.

Background Acute leukemia, characterized by the uncontrolled proliferation of immature white blood cell precursors, poses significant challenges during induction chemotherapy, including the elevated risk of febrile neutropenia and its associated complications. Our study aims to explain the clinical and etiological parameters of these patients in a resource-limited setting. Methods This retrospective study focused on a total of 102 adult patients with acute leukemia who developed febrile neutropenia during the induction chemotherapy phase. Patients with disease relapse, prior bone marrow transplantation, and cases of acute promyelocytic leukemia were excluded from the study. Demographical characteristics, symptoms at presentation, diagnoses, infectious causes, and outcomes were systematically reported. Infectious etiologies and detailed culture reports were meticulously tabulated, and subsequent data were analyzed. Results Of the 102 patients, 43 (42.2%) were males, with a mean age of 31.9 ± 6.5 years. During the induction chemotherapy, a total of 31 patients died of complicated febrile neutropenia. Severe vomiting was the most common symptom present in 37 (36.2%), followed by cough in 35 (34.3%) and loose stools in 28 (27.5%). Community-acquired pneumonia, neutropenic sepsis, and neutropenic colitis were among the most common etiologies of febrile neutropenia. A total of 72 (70.6%) patients had culture-proven multidrug-resistant Gram-negative bacteremia that contributed to poor outcomes. Conclusions Acute leukemia patients undergoing induction chemotherapy face high infection-associated mortality due to their immunocompromised state. Inadequate infection control measures and antimicrobial resistancecontribute to the emergence of multidrug-resistant organisms. Enhanced infection prevention strategies and evidence-based antibiotic prescription guidelines are need of time in resource-limited settings such as Pakistan to address febrile neutropenia complications and bridge the existing care gap in its management.

Serum IgG and IgA level in children with acute lymphoblastic leukaemia and its relation with outcome in induction chemotherapy

Background: Immunosuppression in children with Acute Lymphoblastic Leukaemia (ALL) escalates vulnerability to severe infectious complications which leads to higher morbidity and mortality rates among patients. Immunoglobulins are important part of defence mechanism of the body contributing to the humoral immunity. Of all the immunoglobulins, IgG and IgA represents most common type of antibody in blood circulation and provides most long-lived antibody-based immunity against invading pathogens. In earlier years, studies have shown that, serum immunoglobulins are found to be decreased during chemotherapy and this reduction is related with severe sepsis and death in patients. Early identification of immune status can be much useful for assessment of severity and better risk stratification of the patients. Objective: Evaluation of serum IgG and IgA levels in children with ALL and its relationship with sepsis in induction phase of chemotherapy. Method: This prospective observational study was conducted in the Departments of Paediatric Haematology & Oncology and Department of General Paediatrics, Bangabandhu Sheikh Mujib Medical University, Dhaka. During January 2022 to December 2022, a total 60 paediatric patients of newly diagnosed ALL were included as study population. As control, 30 patients were included in this study from General paediatrics and Paediatric Haematology & Oncology, BSMMU to compare baseline immunoglobulin levels with the study group. Complete history and physical examination of all patients were undertaken, and all prior reports were collected. Serum IgG and IgA level assay was done before starting chemotherapy and at the end of induction chemotherapy in the study group. Patients diagnosed with ALL received chemotherapy modified UK-ALL 2003 protocol. History and data of any event of sepsis, along with the symptoms of complications were taken from all patients during the course of induction chemotherapy. Results: The mean age of the cases were 5.49±3.15 (mean ± SD) years, which ranged from 1.9 to 15 years. Among the cases, 41 patients (68.3%) were male and 19 (31.7%) females. Seven (11.7%) subjects expired during induction chemotherapy. In comparison to the control group the mean IgG level in the study group was lower at baseline and even lower at the end of induction and it was statistically significant (p<0.05). The mean IgG level was low in patients with septic events in comparison with the patients with no septic events. Difference of mean of IgG between septic and aseptic patients was significant only at the end of induction chemotherapy (p<0.05). The mean IgA level was low in study group in comparison with the control group and it was statistically significant (p<0.05) only at the end of induction chemotherapy. The mean IgA level was low in patients with septic events in comparison with the patients with no septic events. Difference of mean of IgA between septic and aseptic patients was significant (p<0.05). Based on the receiver-operator characteristic (ROC) curves of change of S. IgG, with a cut off value 50% decreased from baseline having 68.8% sensitivity and 29.7% specificity for prediction of sepsis. Considering change of S. IgA with a cut off value 50% decreased from baseline having 67.6% sensitivity and 27.5% specificity for prediction of sepsis. Conclusion: In our study, the mean IgG and IgA level of the cases were low in comparison to the control group. The mean IgG and IgA level of the patients were lower who had infectious complications, and it was more marked after induction chemotherapy. Therefore, evaluation of immunoglobulin profiles is recommended to be considered in patients with ALL in further studies.

Ocular manifestations of acute myeloid leukemia during induction phase of chemotherapy: A case series

The aim of this series is to report diverse ocular features noted in patients during the induction phase in acute myeloid leukemia (AML). Three female patients undergoing induction therapy for AML reporting for various ocular complaints were examined. Detailed history, including the onset of AML and chemotherapy and any past ocular or systemic ailment, was taken. Best-corrected visual acuity, anterior segment, and posterior segment examinations were performed. Intraocular pressure was measured, and color vision was tested. Routine hematological, and biochemical investigations and imaging were done when required. Patients with abnormal parameters were referred to an oncologist for management. A varied spectrum of ocular manifestations was noted in these three female patients, including preseptal cellulitis, orbital cellulitis, and subhyaloid hemorrhages. Immediate treatment was given to patients with vision-threatening conditions in consultation with an oncologist and otorhinolaryngologist, and patients responded well to the treatment. Owing to its cytoreductive action, AML induction therapy exposes the patient to various adverse events, causing significant ocular and systemic morbidity. All the diagnosed patients of AML are recommended to undergo a baseline ocular assessment.

Assessment of the Changes in the Salivary Profile and Its Clinical Correlation in Children with Acute Lymphoblastic Leukemia Undergoing Chemotherapy: A Follow-up Study.

To assess the changes in salivary profile and its clinical correlation in patients with acute lymphoblastic leukemia (ALL) undergoing chemotherapy. Children who have been diagnosed with ALL undergoing chemotherapy at Bharati Hospital, Pune, were included in the study. Those children were included who fulfilled the following inclusion and exclusion criteria. Stimulated salivary samples were collected in sterile vials at 1-, 3-, and 6-month intervals and ware assessed for salivary pH and buffering capacity. Caries and oral manifestations were also checked at each interval. A total of 25 children with ALL undergoing chemotherapy were included to participate in the study. The results were analyzed using Statistical Package for the Social Sciences software. There was a statistically significant difference in the change in salivary pH during the 1st and 6th months of chemotherapy (p-value of 0.001). Salivary buffering capacity was also found to be low in these patients during the 1st month of chemotherapy, which gradually increased during the entire course of chemotherapy (p-value of 0.011). Progression of dental caries was seen during the entire course of treatment. All the major changes were seen in the 1st month, that is, the induction phase of chemotherapy. Hence, we can say this is the most affected phase of chemotherapy. The parents and children should be educated and motivated to maintain proper oral hygiene. Whenever possible, all preventive dental procedures should be undertaken before the start of chemotherapy to avoid future complications. Paranjape MN, Shah P, Patil S, et al. Assessment of the Changes in the Salivary Profile and Its Clinical Correlation in Children with Acute Lymphoblastic Leukemia Undergoing Chemotherapy: A Follow-up Study. Int J Clin Pediatr Dent 2023;16(S-3):S268-S271.

Malnutrition as a predictor of adverse outcomes of febrile neutropenia in children with acute lymphoblastic leukemia during induction phase chemotherapy

Background: Adequate nutrition is an important concern in children with leukemia. Malnutrition impairs immune function, leading to increased incidence of infection, poor quality of life, as well as death. Febrile neutropenia (FN) has a high prevalence in children with acute lymphoblastic leukemia (ALL) and a poor outcome as well. Methods: This prospective observational study was done in the department of pediatrics hematology and oncology (PHO), BSMMU, from January 2021 to October 2021. A total of 60 patients of ALL were selected purposively. Patients were evaluated by taking anthropometric parameters before getting chemotherapy and were prospectively followed up for the development and outcome of FN until recovery. Statistical analysis was performed by using SPSS (Statistical package for the social sciences) for Windows version 26.0. Result: Analysis of nutritional status as a risk factor for FN based on anthropometric indices, was found statistically significant for, weight for height (≤5 years) p=0.036, OR=0.24 (95% CI= 0.06-0.958), weight for age p=0.006, OR=0.23 (95% CI=0.07-0.67), but for BMI for age (>5 years) p=0.28, OD=0.28 (95% CI=0.02-3.19), and height for age p=0.513, OD=0.66 (95% CI=0.18-2.33) no statistically significant value was found. In this study, we found mortality rate was 15%. The mortality rate was significantly worse (27.3%) for patients who were malnourished at diagnosis as compared to those who were well nourished (7.9%) at diagnosis. Conclusions: FN and its complications are more common in malnourished children with ALL. Malnutrition is associated with adverse outcomes of FN in children with ALL.

Australasian Leukaemia & Lymphoma Group NHL35-Pacific: An Open Label Phase II Study of Pembrolizumab and Chemo-Immunotherapy As First-Line Therapy for Primary Mediastinal B-Cell Lymphoma - Trial in Progress

Background: Primary Mediastinal B-cell Lymphoma (PMBL) comprises 10% of Diffuse large B-cell lymphoma (DLBCL), primarily affecting young adults. Combination chemoimmunotherapy with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone (R-CHOP) is effective, however up to 10-20% of patients may have either refractory disease or experience relapse within 12 months of completing treatment. Consolidative radiotherapy has often been used following R-CHOP, with retrospective data suggesting a survival benefit compared with R-CHOP alone. However, mediastinal radiotherapy increases risk of breast cancer and cardiovascular disease and the recently reported randomised IELSG37 study demonstrated no improvement in progression free survival (PFS) with the use of consolidative radiotherapy following chemoimmunotherapy. Dose-adjusted Etoposide, Prednisolone, Vincristine, Cyclophosphamide, Doxorubicin and Rituximab (DA-EPOCH-R) without radiotherapy has demonstrated excellent activity in a small phase II study but with increased chemotherapy toxicity. In IELSG37, PFS was inferior for patients treated with R-CHOP-21 compared with other chemoimmunotherapy regimens, supporting intensification of therapy beyond R-CHOP-21 in this entity. The outcome for patients with relapsed/refractory PMBL is poor, with response rates of around 25% to second line therapy, and a 2-year overall survival of 15%. Therefore, there remains a need to improve initial therapy for patients with PMBL. Programmed-Death-1 (PD-1) ligands PD-L1/PD-L2 are commonly upregulated in PMBL. The PD-1 inhibitor Pembrolizumab blocks the interaction of PD-1 and PD-L1/2, and subsequent signalling, and has encouraging activity in relapsed/refractory PMBL, with an overall response rate of 43% (complete response 23%) and modest toxicity in a phase II study. ‘Window’ induction treatment involving delivery of checkpoint inhibitor therapy to patients with lymphoma, prior to initiation of chemotherapy has been investigated in phase II studies, showing encouraging efficacy and no safety concerns with this ‘chemotherapy-free’ initial treatment approach. The combination of Pembrolizumab and Rituximab is predicted to be synergistic, and in non-randomised trials in other B-cell lymphoma histologies, has demonstrated superior response rates to those expected with Rituximab monotherapy, suggesting synergism of the combination. There is therefore compelling rationale for combining R-CHOP and Pembrolizumab as first-line therapy for PMBL. This study investigates the efficacy and safety of this novel, time-limited, radiotherapy sparing regimen. Methods ALLG-PACIFIC (ANZCTR- ACTRN12621001529831) is a phase II, single arm, open-label study of R-CHOP in combination with Pembrolizumab. The trial is open to recruitment across Australia. Approximately 35 patients with newly diagnosed PMBL, will be enrolled to receive two cycles of Rituximab (375mg/m 2) plus Pembrolizumab (200mg) once every 21 days ('window phase') followed by six cycles of R-CHOP plus Pembrolizumab once every 21 days ('induction phase') followed by five cycles of Pembrolizumab 400mg once every 42 days ('consolidation phase') (Figure 1). Adults (≥18 years) with treatment naïve histologically confirmed PMBL and adequate organ function are eligible. Key exclusion criteria are the presence of active autoimmune disease, requiring recent immunosuppressive therapy, life-threatening or organ-compromising lymphoma symptoms requiring urgent cytoreductive therapy, and other medically significant conditions that preclude eligibility to receive R-CHOP. Patients who require urgent cytoreductive therapy following initiation of window phase treatment may proceed immediately to induction phase chemotherapy. The primary endpoint is 18-month event free survival. Key secondary endpoints include response to window phase treatment, overall survival, requirement for radiotherapy and safety of treatment including rates of early discontinuation due to treatment toxicity. Several biomarkers are also being investigated for their predictive value for treatment response including minimal residual disease status (measured by Adaptive Immunoseq and CAPP-Seq), PET-CT parameters (e.g., Metabolic tumour volume), and PD-1/PD-L1 expression and 9q24 alterations.

Rate of Cardiotoxicity in Childhood Acute Lymphoblastic Leukemia Treated with Daunorubicin Using Echocardiography and Troponin I

Background and Aim: Acute lymphoblastic leukemia (ALL) is the commonest malignancy in childhood. Childhood ALL Survivors have a lifelong increased risk for cardiovascular morbidity and mortality compared to the general population, mainly caused by chemotherapy with daunorubicin. The aim of the study is to detect the rate of daunorubicin induced cardiotoxicity in children with acute lymphoblastic leukemia during induction phase chemotherapy. Meterials & Methods : This prospective observational study was conducted in the department of Pediatric Hematology and Oncology, Bangabandhu Sheikh Mujib Medical University (BSMMU) on 40 newly diagnosed patients of ALL aged between 1 to17.9 years who got daunorubicin during induction. Complete blood count and echocardiography were done and troponin I was measured in all patients before and after completion of induction period. Result: Of the 40 patients, 8 patients (20%) had developed cardiotoxicity evidenced by reduction of left ventricular ejection fraction (LVEF) in echocardiography. Baseline LVEF was 68.80±5.98% which was then reduced to 65.32±7.07% after induction phase of chemotherapy (p=0.023). No significant alteration of troponin I was seen (P= 0.581) between baseline and after completion of induction. Total WBC count and hemoglobin had a significant difference (P<0.05) between baseline and after induction period. Male patients had a greater risk of developing cardiotoxicity than females but statistically was not significant (P=0.643). There was no significant association between age of the patients and cardiotoxicity (P=0.112).Cardiotoxicity was seen higher in patient with initial high WBC count (p=0.039). Echocardiography also reveled increased tendency of mitral regurgitation and left ventricular hypertrophy after induction phase chemotherapy. Conclusion: This study showed the rate of cardiotoxicity was 20% in ALL patients treated with daunorubicin. It also found that LVEF was decreased during therapy.Echocardiography can be used to detect early cardiotoxicity induced by daunorubicin. University Heart Journal 2023; 19(1): 20-25

Omega 3 supplementation to reduce alpha threonine kinase 1 (AKT1) levels in children with acute lymphoblastic leukemia (ALL) in the induction phase of chemotherapy

Background: Omega-3 inhibits tumor growth and progression in various cancers, but the mechanisms involved remain unclear. Omega-3 induces apoptosis, promotes cell cycle arrest, and reduces inflammation through various mechanisms, including reduced AKT phosphorylation. AKT is involved in cell growth, proliferation, and apoptosis. Acute lymphoblastic leukemia is one of the most prevalent malignancies in children with low remission levels. PI3K/AKT pathway mutations are found in acute lymphoblastic leukemia. Omega-3 is known to inhibit leukemogenesis through AKT1 signaling pathways. Objectives: To analyze omega-3’s role in AKT1 level reduction in children with acute lymphoblastic leukemia (ALL). Methods: A randomized open label pre- and post-test control group study was conducted on two groups: a treatment group receiving 1,000 mg of omega-3 orally once a day during the chemotherapy protocol’s induction phase; and a control group receiving placebos. AKT1 levels were measured before (day 0) and after the induction phase of chemotherapy was completed (day 43). The statistical analysis included paired t-tests, independent sample t-tests, and chi-square tests. Results: Twenty-six subjects included in this study were divided into 13 subjects in the control group and 13 subjects in the treatment group. There was a significant reduction in AKT levels before and after receiving omega-3 supplementation in the treatment group (p < 0.001). Meanwhile, there was a significant increase in the control group’s AKT1 levels (p< 0.001). Conclusion: Omega-3 supplementation suppressed AKT1 levels.

Omega 3 supplementation and NF-kB levels in children with acute lymphoblastic leukemia (ALL) receiving induction phase chemotherapy

Background: NF-kB plays an important role in tumorigenesis by regulating cellular apoptosis and growth processes. Activated NF-kβ complexes were found in children with acute lymphoblastic leukemia (ALL), because it is the main regulator for lymphocyte proliferation, survival and development. Several evidence showed that omega 3 fatty acid inhibit NF-kB at any type of cancers. But the effects of omega 3 supplementation to the NF-kB level on children with ALL is still limited. Purpose: Analyse omega 3 fatty acids supplementation at NF-kB level on children with ALL receiving induction phase of chemotherapy and the outcomes of chemotherapy. Methods: an open label randomized pre- and post-test control group design clinical study, conducted at October 2014 until March 2015 at inpatient unit of Haematology Oncology ward Dr. Soetomo Distric Hospital Surabaya. Subjects were divided into 2 groups: treatment group receiving omega 3 softgel 1000 mg orally once a day at the first day of the induction phase were conducted until the last day of the induction phase; and control group. NF-kB were measured before (day 0) and after induction phase (day 42) of chemotherapy. NF-kB level were measured using Human NF-kB (Elabscience®) in ng/ml and analysed statistically using paired sample t test and independent sample t-test using SPSS ver 21 (IBM, US). Results: A total of 22 subjects were included in this study, divided into 11 as the treatment group and 11 as the control group. NF-kB level were reduced at both group; 3.10 + 4.308 ng/ml to 0.76 + 0.762 ng/ml at the treatment group and 8.20 + 11.130 ng/ml to 1.748 + SD 3.072 ng/ml. There was no significant difference of NF-kB levels before and after the induction phase after omega 3 supplementation at the treatment group (p=0.065). Conclusion: There is no significant difference of NF-kB level between the subjects receiving omega 3 supplementation and the subjects who did not had omega 3 supplementation, and there is no relationship between NF-kB levels with chemotherapy outcomes.

Vincristine‑induced peripheral neuropathy in children with acute lymphoblastic leukemia: Clinical and instrumental characteristics, search for new solutions

Objective. To evaluate clinical and electroneuromyographic characteristics of vincristine polyneuropathy in children with acute lymphoblastic leukemia.Materials and methods. A single-centre prospective cohort study involved 106 children with acute lymphoblastic leukemia, aged 3 to 17 years, with vincristine polyneuropathy; clinical and electroneuromyographic data were analyzed.Results. In the majority of cases, 84.9 % (n = 90) of patients, vincristine polyneuropathy debuted during the induction phase of chemotherapy. The clinical picture was dominated by combined neurological disorders in 67.9 % (n = 72) cases, with sensory and motor disorders dominating. Sensory dysfunction was manifested predominantly by pain in the lower extremities, changes in the motor sphere were characterized by the development of distal paresis of the lower extremities. In 66.0 % (n = 70) of patients, neurological disorders corresponded to the 2nd degree of severity according to the toxicity scale (NCI-STAE). According to the ENMG study, all children had motor axonal neuropathy of the peroneal nerves.Conclusions. The results of the study showed that the clinical picture of vincristine polyneuropathy is accompanied by sensory and motor symptoms. Currently, a complex of clinical and instrumental methods is used to verify the neurotoxic complication. The main objective method of diagnosis is an electroneuromyographic study. However, its capabilities are limited for determining the clinical manifestations associated with sensory disorders.

Outcome of neutropenic enteropathy during induction phase of treatment of childhood acute lymphoblastic leukemia

BackgroundNeutropenic enteropathy is one of the important causes of death during intensive phase of chemotherapy in children with acute lymphoblastic leukemia (ALL). It follows a prolonged course of neutropenia and carries a mortality rate up to 30%. The study aimed to find out the outcomes of typhlitis during induction phase of treatment of childhood ALL. Material and methodsThis prospective case control study was conducted in the Department of Pediatric Hematology and Oncology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh from November 2018 to January 2021. Children (<19 years) with ALL who developed neutropenic enteropathy during induction phase of chemotherapy without any comorbid condition were included in this study. The clinico-radiological diagnosis of neutropenic enteropathy was based on a standard diagnostic criteria. Complete blood count, serum electrolytes, albumin, blood culture, stool culture, abdominal X-ray and ultrasonogram were performed in all the cases. ResultsThirty-six patients developed neutropenic enteropathy. 8 (22.2%) died. Thrombocytopenia (p = 0.001), hypoalbuminemia (Odd ratio 21.0, p < 0.001), positive blood culture (Odds ratio 6.11, p = 0.026). ConclusionThis study found a mortality rate of 22.2% amongst the pediatric patients with ALL who developed neutropenic enteropathy during induction chemotherapy. Thrombocytopenia, hypoalbuminemia, and a positive blood culture predicted mortality.

Impact of Zinc Supplementation in prevention of Chemotherapy Induced Oral Mucositis

Objective: To determine the impact of Zinc supplements in prevention of oral mucositis and its consequences in patients receiving chemotherapy. Study Design: Quasi experimental study Place and Duration: Department of Paediatric Oncology, Pakistan Institute of Medical Sciences (PIMS), Islamabad from 1st March, 2023 to 31 July, 2023. Methodology: A total of 60 patients (N) diagnosed of acute lymphoblastic leukemia planned for induction of treatment were included in the study. Patients were randomly divided into two groups of thirty patients each. Group-A received Zinc supplements while group-B received the usual standard of care without any additional supplement. At the end of four weeks of induction therapy, all patients were assessed for presence and severity of oral mucositis. They were also inquired about food intolerance and need for analgesics. Results: Mean age of patients included in the study was 4.723 ± 2.84 yrs. Males were34 (56.6%) and 26 (43.3%) were females. Severity of mucositis (p-Value is 0.017) and food intolerance (p-Value is 0.020) were markedly decreased in the group receiving zinc supplements. Analgesics were required by 21 (70%) patients in the group receiving zinc supplements and by 27 (90%) in the group not receiving zinc supplements. However, p-Value remained non-significant (0.104). Conclusion: Both, severity of oral mucositis and food intolerance are significantly reduced in patients prescribed zinc supplements during the induction phase of chemotherapy. Though, requirement of analgesics was also considerably reduced amongst patients taking zinc supplements, the difference was not statistically significant for this particular variable in our study. Keywords: Acute Lymphoblastic Leukemia, Zinc, Oral Mucositis, Chemotherapy, Childhood Malignancy How to Cite This: Tariq R, Manzoor R, Batool Z, Yasmeen N, Fatima SI, Ayub S. Impact of Zinc Supplementation in prevention of Chemotherapy Induced Oral Mucositis. Isra Med J. 2023; 15(1): 3-6. DOI: https://doi.org/10.55282/imj.oa1372 This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Differences in induction phase outcomes of acute lymphoblastic leukemia between well-nourished and malnourished pediatric patients

Background Leukemia is the most common malignancy in childhood. Malnutrition is the main nutritional disorder occurring in children with cancer. Nutritional supportive care is a medical modality that has been associated with improved tolerance to chemotherapy, survival, and quality of life, as well as decreased risk of infection in children undergoing cancer therapy.&#x0D; Objective To examine differences in induction phase outcomes in well-nourished and malnourished pediatric acute lymphoblastic leukemia (ALL) patients.&#x0D; Methods This prospective study was conducted in newly-diagnosed ALL patients aged 1 to 18 years who underwent induction phase chemotherapy at Haji Adam Malik General Hospital, Medan, North Sumatera. Mid-upper arm circumference (MUAC) was used to determine nutritional status. Patient characteristics such as complete blood count (CBC) at the time of diagnosis, occurrence of febrile neutropenia, duration of induction, length of hospital stay, and remission status were collected. We analyzed differences in CBC, frequency of febrile neutropenia, as well as duration of induction and hospital stay between well-nourished and malnourished patients. We also assessed the difference in remission attainment between the two groups.&#x0D; Results There were 21 subjects in each group. Compared to well-nourished subjects, malnourished ones had a higher median incidence of febrile neutropenia [1 (range 0 to 30) vs. 3 (range 0 to 4); P=0.04], longer mean induction duration [64.2 (SD 11.5) vs. 71.2 (SD 10.6) days; P=0.046], and longer median hospital stay [30 (range 19 to 56) vs. 36 (range 22 to 49) days; P=0.001] compared to well-nourished subjects. There was no significant difference in CBC parameters and remission status after induction between the two groups.&#x0D; Conclusion Malnourished pediatric ALL patients had a significantly higher incidence of febrile neutropenia, duration of induction phase, and duration of hospital stay compared to well-nourished ALL patients.

Differences in Vitamin D Levels at Diagnosis and after Induction Phase Chemotherapy in Children with Acute Lymphoblastic Leukemia in Tertiary Hospital in West Java Indonesia

Objective: We examined differences of vitamin D levels at initial diagnosis and after induction phase chemotherapy in children with Acute Lymphoblastic Leukemia (ALL). Methods: A cross-sectional study was conducted on newly diagnosed children with ALL from October 2021 until October 2022 at Dr. Hasan Sadikin Hospital−Bandung, West Java, Indonesia. Vitamin D levels were measured twice using blood samples: at initial diagnosis and after the remission induction phase of chemotherapy. A paired t-test was applied and the value of p&lt;0.05 is considered as statistically significant. Result: There were 53 subjects that fulfilled research criteria. Thirty−six subjects met the inclusion criteria while 17 were excluded. Majority of ALL patients were male (52.8%) and aged 1−10 years (83.3%). Mean vitamin D level of ALL children at initial diagnosis was 16.68±9,56 ng/mL. After the induction phase of chemotherapy, mean vitamin D level was 11.84±7,8 ng/mL. Paired t-test was performed to obtain p value = 0.000. Conclusion: The prevalence of hypovitaminosis D in ALL children is 88.8%. Vitamin D levels after chemotherapy are lower than at initial diagnosis.

Nutritional Status of Pediatric Patients With Acute Lymphoblastic Leukemia Under Chemotherapy: A Pilot Longitudinal Study.

The study investigates the nutritional status in children with acute lymphoblastic leukemia (ALL) during chemotherapy treatment because nourishment is substantial, as much as chemotherapy in children with malignant diseases. We enrolled 17 children with ALL (between 1 to 16 year-old, mean age 6.03 ± 4.04y) from 5 different centers in Istanbul between September 2013 and May 2014. Anthropometric data, prealbumin, B12, and folate levels were assessed, at diagnosis, after the induction phase of chemotherapy, and before maintenance phases of chemotherapy in a longitudinal and prospective study. Patients remarkably lost weight at the end of the induction phase ( P =0.064) and regained this loss before maintenance chemotherapy ( P =0.001). At the end of induction chemotherapy serum prealbumin level ( P =0.002), weight for height ratios ( P =0.016), weight for age ratios ( P =0.019) significantly decreased. From the end of the induction phase to the beginning of maintenance chemotherapy, weight ( P =0.001) and weight for age ( P =0.017) significantly, and weight for height were remarkably elevated ( P =0.076). At the end of the induction phase, serum prealbumin levels were significantly lower ( P =0.048) and below laboratory reference values ( P =0.009) in children younger than 60 months compared with those older. Serum folate levels increased from the end of the induction phase to the beginning of the maintenance phase ( P =0.025). Serum vitamin B12 levels did not alter significantly. There is malnutrition risk at the end of the induction phase of the ALL-BFM chemotherapy regimen; therefore, clinicians should follow up on nutrition closely, especially in under 5-year-old patients. However, before the beginning of the maintenance phase, children start to gain weight, and obesity risk occurs. Thus , further studies are needed to evaluate nutritional status during childhood ALL chemotherapy.

Exhaled phospholipids as a prognostic factor of pulmonary complications in children with acute lymphoblastic leukemia

Introduction. Pulmonary complications are common in children with acute lymphoblastic leukemia (ALL). The assessment of phospholipids (PL) in the exhaled breath condensate can provide more information about pathological processes in the lungs in children with ALL. Purpose - to assess the level of PL in the exhaled breath condensate (EBC) in children with ALL and its prognostic value. Materials and methods. 40 children with ALL aged 6-17 years were examined. 1st group included newly diagnosed children with ALL (n=18). 2nd group involved ALL survivors, who had completed the total course of chemotherapy (n=22). The control (С) group consisted of 15 healthy children. The levels of PL in the EBC were investigated by spectrophotometric thin-layer chromatography using an SPh 46 spectrophotometer. Results. The frequency of pulmonary complication was 82.5% during chemotherapy protocols and 18.4% in ALL survivals. The statistically significant increase in the level of phospholipids in 1st (150.75 (137.62; 158.45) mmol/l) and 2nd (130.12 (120.59; 138.34) mmol/l) ALL groups compared with the group C (54.80 (48.30; 60.80) mmol/l) has been detected (p1-C=0.0000; p2-C=0.0000). Children of the 1st group had significantly higher levels of PL in the EBC than children of the 2nd group (p1-2=0.002911). PL level in EBC collected during induction phase of chemotherapy &gt;132.15 mmol/l can be prognostic for the development of acute pulmonary complications (Sensitivity 93.75%; Specificity 100%). PL level in EBC collected after a complete course of chemotherapy &gt;133.28 mmol/l can be predictive for persistent pulmonary complications (Sensitivity 100.00%; Specificity 83.33%). Conclusions. PL level in EBC can be prognostic for the development of pulmonary complications, both during chemotherapy and in long-term remission after completed chemotherapy course. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Caspase 3 Expressions in Children with Acute Lymphoblastic Leukemia During Induction Phase Chemotherapy

Introduction: Caspase-3 is a crucial mediator of the extrinsic apoptosis pathway. The role of caspase-3 for extrinsic apoptosis signalling is still a challenge and should be exploited in childhood ALL. This study aimed to compare the caspase-3 expression in the patient’s bone marrow before and after the induction phase of chemotherapy in childhood ALL. It will also to correlate the mean difference in caspase-3 expression between ALL standard-risk and ALL high-risk patients. Methods: Seventeen newly diagnosed ALL subjects were enrolled in this study. Caspase-3 expression in bone marrow was assessed using flow cytometry and monoclonal antibodies. A T-test and a paired T-test were used to compare between groups. The correlation coefficient between ALL groups was evaluated using Spearman’s test and linear regression with a significant p-value of 0.05. Results: The caspase-3 expression is higher after induction therapy. However, it showed an insignificant difference (16.56+12.91% vs 27.71+12.33%; p = 0.08, p &gt; 0.05). The mean difference of caspase-3 in ALL high-risk groups was significantly higher than in ALL standard-risk groups with a positive correlation (p = 0.007, r = 0.756). Conclusion: The caspase-3 expression after induction phase chemotherapy was increased in all standard-risk and high-risk patients; other lymphoblast apoptosis markers need to be confirmed alongside caspase-3.

Effective treatment of severe forms of RSV and Pneumocystis jirovecii infections in a child with Down syndrome and acute lymphoblastic leukemia treated with chemotherapy

There has been significant progress in acute lymphoblastic leukemia (ALL) treatment throughout the previous decades. However, infectious complications are still the main problem during cancer treatment. Literature reports show that treatment-related mortality is 2–4% and is mainly related to infection. Here, the authors report a 3-year-old patient with Down syndrome and ALL who was hospitalized in the Department of Pediatric Hematology, Oncology and Transplantology of the Medical University of Lublin. The patient was treated according to the AIEOP-BFM 2017 protocol and developed a severe co-infection of Pneumocystis jiroveci and respiratory syncytial virus during the induction phase of chemotherapy and P. jiroveci re-infection while receiving Protocol II. As a result, chemotherapy was interrupted for 51 and 31 days, respectively. The patient required the administration of broad-spectrum antibiotics, antiviral and antifungal therapy and passive oxygen therapy. Due to a severe clinical condition, the patient was also temporarily hospitalized in the Intensive Care Unit. Research revealed several risk factors for infectious complications in patients with ALL including intensive chemotherapy or Down syndrome. Therefore, despite anti-infective prophylaxis, increased medical vigilance is necessary. In the case of infectious symptoms, early diagnosis and prompt treatment should be implemented to enable the continuation of the ALL therapeutic protocol.