Initial Diagnosis Of Acute Lymphoblastic Leukemia Research Articles

MAJOR REASONS FOR HOSPITALIZATION TO ICU OF CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA: A LITERATURE REVIEW

Relevance: Acute lymphoblastic leukemia (ALL) is a common malignancy in children. Approximately 85% of ALLs have B-cell origin, and 15% are T-cell ALLs. Many patients diagnosed with hematologic cancer will require hospitalization in the intensive care unit (ICU) at some point in their treatment.
 The aim was to study the available literature on clinical deterioration in patients with АLL admitted to the ICU, the clinical significance and prognostic value of causes of clinical deterioration, and adverse outcomes in patients with АLL staying in the ICU.
 Methods: A descriptive cross-sectional study approach was used. We reviewed published sources from 2016 to 2023 to collect data on major reasons for ALL patients’ hospitalization to ICU.
 Results: First, the patient’s age at the time of initial diagnosis of ALL is crucial. Cure rates for B-cell ALL are higher between 1 and 9 years of age than in other age groups. Second, the initial white blood cell count during diagnosis is a prognostic indicator. Third, the specific subtype of ALL also affects prognosis. The risk factors emphasize the importance of comorbidities and infectious diseases, as well as monitoring and managing pulmonary and cardiovascular function in patients to avoid hospitalization in the ICU. The main causes of hospitalization in the ICU are complications related to chemotherapy, infection, and unplanned hospitalizations. Compared to normal-risk patients, high-risk patients had a higher rate of OIT hospitalization in the ICU. It is important to control chemotherapy and infections to reduce the number of admissions to the ICU in this group.
 Conclusion: Chemotherapy, concomitant and infectious diseases, hypoxia, and hemodynamic instability are reasons for hospitalization of these patients to ICU. The condition of various organs and systems shall be monitored.

MAJOR REASONS FOR HOSPITALIZATION TO ICU OF CHILDREN
 WITH ACUTE LYMPHOBLASTIC LEUKEMIA:
 A LITERATURE REVIEW

Relevance: Acute lymphoblastic leukemia (ALL) is a common malignancy in children. Approximately 85% of ALLs have B-cell origin, and 15% are
 T-cell ALLs. Many patients diagnosed with hematologic cancer will require hospitalization in the intensive care unit (ICU) at some point in their treatment.
 The aim was to study the available literature on clinical deterioration in patients with АLL admitted to the ICU, the clinical significance
 and prognostic value of causes of clinical deterioration, and adverse outcomes in patients with АLL staying in the ICU.
 Methods: A descriptive cross-sectional study approach was used. We reviewed published sources from 2016 to 2023 to collect data on major
 reasons for ALL patients’ hospitalization to ICU.
 Results: First, the patient’s age at the time of initial diagnosis of ALL is crucial. Cure rates for B-cell ALL are higher between 1 and 9 years of
 age than in other age groups. Second, the initial white blood cell count during diagnosis is a prognostic indicator. Third, the specific subtype of ALL
 also affects prognosis. The risk factors emphasize the importance of comorbidities and infectious diseases, as well as monitoring and managing
 pulmonary and cardiovascular function in patients to avoid hospitalization in the ICU. The main causes of hospitalization in the ICU are complications related to chemotherapy, infection, and unplanned hospitalizations. Compared to normal-risk patients, high-risk patients had a higher rate of
 OIT hospitalization in the ICU. It is important to control chemotherapy and infections to reduce the number of admissions to the ICU in this group.
 Conclusion: Chemotherapy, concomitant and infectious diseases, hypoxia, and hemodynamic instability are reasons for hospitalization of
 these patients to ICU. The condition of various organs and systems shall be monitored.

Effect of microRNA‐210 on prognosis and response to chemotherapeutic drugs in pediatric acute lymphoblastic leukemia

Many studies have demonstrated that microRNA-210 (miR-210) expression is intensively upregulated in hypoxic states and differentially regulated in most types of cancer cells. However, the clinical significance of miR-210 and its effects on the response of leukemic cells to chemotherapeutic drugs in childhood acute lymphoblastic leukemia (ALL) remain unknown. In the current study, using real-time qRT-PCR to detect miR-210 expression in bone marrow samples from 114 children at initial diagnosis of ALL, we investigated the prognostic significance of miR-210 and determined its associations with common clinical characteristics and treatment outcome. We further examined its effect on the response to chemotherapeutic drugs in the Reh and RS4;11 cell lines. Results showed that miR-210 expression was significantly lower in patients suffering from relapse and induction failure than in other patients (P < 0.001). Using the receiver operating characteristic curve, 3.8243 was selected as the cut-off value of miR-210 expression in our test cohort (38 cases). A significantly poorer treatment outcome (P < 0.05) was found in the low-expression group and verified in the validation cohort (76 cases, P < 0.05). Patients with low expression of miR-210 and positive minimal residual disease at the end of induction had a much higher rate of relapse or induction failure (P = 0.001). Increasing/decreasing miR-210 expression using agomir/antagomir could enhance or reduce the response of Reh cells and RS4;11 cells to daunorubicin/dexamethasone/L-asparaginase and daunorubicin/dexamethasone/vincristine, respectively. In conclusion, miR-210 may be a good prognostic factor and a useful predictor of drug sensitivity, and is a potential therapeutic target for pediatric ALL.

Prognostic value of genetic alterations in children with first bone marrow relapse of childhood B-cell precursor acute lymphoblastic leukemia

Despite risk-adapted treatment, survival of children with relapse of acute lymphoblastic leukemia (ALL) remains poor compared with that of patients with initial diagnosis of ALL. Leukemia-associated genetic alterations may provide novel prognostic factors to refine present relapse treatment strategies. Therefore, we investigated the clinical relevance of 13 recurrent genetic alterations in 204 children treated uniformly for relapsed B-cell precursor ALL according to the ALL-REZ BFM 2002 protocol. The most common alterations were deletions of CDKN2A/2B, IKZF1, PAX5, ETV6, fusion of ETV6-RUNX1 and deletions and/or mutations of TP53. Multivariate analysis identified IKZF1 deletion and TP53 alteration as independent predictors of inferior outcome (P=0.002 and P=0.001). Next, we investigated how both alterations can improve the established risk stratification in relapsed ALL. Intermediate-risk relapse patients with low minimal residual disease are currently considered to have a good prognosis. In this group, deletion of IKZF1 and alteration of TP53 identify patients with significantly inferior outcome (P<0.001). In high-risk relapse patients, deletion of IKZF1 is strongly predictive of a second relapse after stem cell transplantation (P<0.001). We conclude that IKZF1 and TP53 represent relevant prognostic factors that should be considered in future risk assessment of children with relapsed ALL to indicate treatment intensification or intervention.

Risk factors for readmission after initial diagnosis in children with acute lymphoblastic leukemia

Specific hospital discharge criteria following the initial diagnosis of children with acute lymphoblastic leukemia (ALL) have not been reported. This retrospective cohort study was designed to identify risk factors for readmission during induction therapy, to assist with development of discharge guidelines. We reviewed the records of 142 consecutive children with newly diagnosed B-precursor ALL and found 129 eligible patients. Chi square, t-test, and multivariate logistic regression analysis were used to compare differences in absolute neutrophil count (ANC), NCI risk status, age, type of corticosteroid administered, and other potential risk factors for readmission during induction therapy. ANC at initial hospital discharge was the only significant predictor of readmission for fever during induction therapy (P = 0.006) by multivariate analysis. Specifically an ANC <or=200/mm(3) at discharge had the strongest association with readmission for fever (OR 3.3, 95% CI 1.422, 7.729). An ANC >200/mm(3), in a clinically stable patient, is associated with minimal risk of readmission during induction therapy following the initial diagnosis of ALL.

Relationship between the intracellular daunorubicin concentration, expression of major vault protein/lung resistance protein and resistance to anthracyclines in childhood acute lymphoblastic leukemia.

In vitro resistance to anthracyclines is related to a poor prognosis in childhood acute lymphoblastic leukemia (ALL), but the underlying mechanisms are poorly understood. Using flow cytometry, we studied the contribution of daunorubicin (DNR) accumulation and retention, cell size, expression of the major vault protein/lung resistance protein (LRP), P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) to the cytotoxicity of DNR (by MTT assay) in childhood ALL. The accumulated and retained DNR content was not related to the degree of DNR resistance, nor did the content differ between 53 initial and 20 relapse ALL samples (P >0. 05), although the latter were median two-fold more resistant to DNR (P = 0.004). Leukemic cell volume correlated with resistance to the anthracyclines DNR (Rs 0.32, P = 0.012) and idarubicin (Rs 0.46, P = 0.011) but not to other classes of drugs such as prednisolone, vincristine, L-asparaginase and etoposide. Relapsed patients had 1. 5-fold larger cells than patients at initial diagnosis of ALL (P = 0. 001). After cell volume correction, the intracellular DNR concentration was lower in relapsed compared with initial ALL cells (eg 60 min accumulation, P = 0.003). Moreover, the intracellular DNR concentration inversely correlated with DNR resistance, both in the accumulation (Rs -0.44, P < 0.001) and retention (Rs -0.33, P = 0. 016) test condition. The accumulated DNR concentration inversely correlated with expression of LRP (Rs -0.36, P = 0.012) but not with P-gp and MRP. Expression of LRP, but not of P-gp and MRP, significantly correlated with DNR resistance in childhood ALL (Rs 0. 33, P = 0.03). In conclusion, the intracellular DNR concentration and the expression level of LRP may contribute to DNR resistance in childhood ALL. The strength of the correlations also indicates that resistance to anthracyclines can not be explained by one single mechanism.