scholarly journals Crisis management in the treatment of childhood acute lymphoblastic leukemia: putting right what can go wrong (emergency complications of disease and treatment)

Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 251-258 ◽  
Author(s):  
Rachael Hough ◽  
Ajay Vora
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Tumor Lysis Syndrome ◽  
Treatment Delays ◽  
Life Threatening ◽  
Pediatric All ◽  
Short And Long Term ◽  
Dose Reductions ◽  
Related Mortality

AbstractThe improvement in overall survival in children with acute lymphoblastic leukemia (ALL) over the last 5 decades has been considerable, with around 90% now surviving long term. The risk of relapse has been reduced to such an extent that the risk of treatment-related mortality is now approaching that of mortality caused by relapse. Toxicities may also lead to the suboptimal delivery of chemotherapy (treatment delays, dose reductions, dose omissions), potentially increasing relapse risk, and short- and long-term morbidity, adding to the “burden of therapy” in an increasing number of survivors. Thus, the need to reduce toxicity in pediatric ALL is becoming increasingly important. This work focuses on the risk factors, pathogenesis, clinical features, and emergency management of the life-threatening complications of ALL at presentation and during subsequent chemotherapy, including leucostasis, tumor lysis syndrome, infection, methotrexate encephalopathy, thrombosis, and pancreatitis. Potential strategies to abrogate these toxicities in the future are also discussed.

Pharmacogenomics of acute lymphoid leukemia: new insights into treatment toxicity and efficacy

Hematology ◽  
2013 ◽  
Vol 2013 (1) ◽  
pp. 126-130 ◽  
Author(s):  
Mary V. Relling ◽  
Laura B. Ramsey
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Genomic Variation ◽  
Whole Genome ◽  
Lymphoid Leukemia ◽  
Interindividual Differences ◽  
Genomic Variants ◽  
Short And Long Term ◽  
Risk Of Relapse

Abstract Childhood acute lymphoblastic leukemia (ALL) provides an outstanding model for pharmacogenomic research: it is a drug-responsive disseminated cancer that is cured with medications alone in ∼ 85% of patients, but relapse remains unacceptably high for some subgroups. Inherited genomic variation contributes to the risk of relapse and to the risk of short- and long-term serious adverse effects of therapy. Our goal is to identify the inherited genomic variants that contribute to interindividual differences in response in patients with ALL. We discuss results of whole-genome interrogations of germline DNA in ALL.

Treatment-related mortality in children with acute lymphoblastic leukemia in a low-middle income country

2021 ◽  
Author(s):  
Rahat-Ul-Ain ◽  
Mahwish Faizan ◽  
Wasila Shamim
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
Tumor Lysis Syndrome ◽  
Infection Prevention And Control ◽  
Middle Income ◽  
Female Ratio ◽  
Low Middle Income Countries ◽  
Treatment Related Mortality ◽  
Related Mortality

Objective: To determine the proportion of treatment-related mortality (TRM) among mortalities of Pediatric Acute Lymphoblastic Leukemia (ALL), to identify probable causes and risk factors. Methods: An observational; retrospective, cohort study. Pediatric patients of ALL who expired during treatment were enrolled. Death due to relapse and deaths before treatment were excluded. Retrospective data was collected from ward record and analyzed in SPSS 16. Results: Total 247 patients of ALL expired while 144 patients were enrolled as per inclusion criteria. The proportion of TRM was 58.3%. Median age was 5 years. Male-to-female ratio was 1.3:1. Commonest cause of TRM was sepsis (n=126, 87.5%), followed by hemorrhagic complications (n=11, 7.6%), drug toxicity (n=4, 2.8%), tumor lysis syndrome (n=2, 1.4%) and thromboembolism (n=1, 0.7%). Significant factors associated with TRM were weight-for-age, immunophenotype, reason for admission and absolute neutrophil count. Conclusion: Treatment-related mortality though potentially avoidable is still a major cause of death among pediatric patients of ALL in low-middle income countries. Sepsis is the most common cause and infection prevention and control is vital in improving survival. Best supportive care must be made available for the patients on induction chemotherapy, with concomitant malnutrition, high-risk immunophenotype and profound neutropenia. Continuous...

scholarly journals Long Term Results for Childhood Acute Lymphoblastic Leukemia: An Institutional Review

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5161-5161
Author(s):  
Huirong Mai ◽  
Ximin Fang ◽  
Xiuli Yuan ◽  
Xiaodong Wang ◽  
Sixi Liu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Severe Infection ◽  
Long Term Results ◽  
Term Survival ◽  
Institutional Review ◽  
Pediatric All

Abstract Objective s: To exam the outcomes of children with acute lymphoblastic leukemia (ALL) treated on Berlin-Frankfürt-Münster (BFM) International ALL- based protocol, GD 2008ALL protocol. Method s : In total, 274 patients with newly diagnosed ALL age 1 to 16 years were enrolled onto GD2008ALL protocol from July 1, 2008 to June 30, 2016. Five-year overall survival (OS) rates and even-free survival (EFS) rates were examined with additional analyses of causes of relapse and death. Results:The 5-year probabilities of OS and EFS were 90.8% and 86.9%. The 5-year EFS were 91.7% in SR group, 86.5% in IR group and 82.6% in HR group, respectively. Twenty-five patients were died. Reasons for mortality included 8 cases due to relapse of leukemia, seven cases due to severe infection, one case due to hepatic failure, one case due to intracranial hemorrhage from accident, eight cases abandoned after relapse. There were 29 cases relapsed, including 22 cases (75%) relapsed of the bone marrow alone, 1 case (3.6%) CNS relapsed alone, 2 cases (7.1%) testicular relapsed and 4 cases (14.3%) relapsed of bone marrow and extramedullary. Eleven patients survived after therapy for relapse, of which 7 had received HSCT, two out of the 7 had relapsed after HSCT, and continued on CART therapy. Four out of the 11 relapsed patients received relapsed ALLR3 protocol for treatment. All 11 patients remained in remission status. Conclusion:Our single institutional review of pediatric ALL treated on GD 2008ALL Protocol was tolerated and has good long term outcomes. Although relapse is a major factor affecting long term survival, there are still have options such as HSCT or immunotherapy available for these patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Long-Term Effects of Pediatric Acute Lymphoblastic Leukemia Chemotherapy: Can Recent Findings Inform Old Strategies?

2021 ◽  
Vol 11 ◽  
Author(s):  
Zeina N. Al-Mahayri ◽  
Mohammad M. AlAhmad ◽  
Bassam R. Ali
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Cardiac Toxicity ◽  
Lymphoblastic Leukemia ◽  
Genomic Medicine ◽  
Malignant Neoplasms ◽  
Childhood All ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
Acute Neuropathy ◽  
Pediatric All

During the last few decades, pediatric acute lymphoblastic leukemia (ALL) cure rates have improved significantly with rates exceeding 90%. Parallel to this remarkable improvement, there has been mounting interest in the long-term health of the survivors. Consequently, modified treatment protocols have been developed and resulted in the reduction of many adverse long-term consequences. Nevertheless, these are still substantial concerns that warrant further mitigation efforts. In the current review, pediatric-ALL survivors’ late adverse events, including secondary malignant neoplasms (SMNs), cardiac toxicity, neurotoxicity, bone toxicity, hepatic dysfunction, visual changes, obesity, impact on fertility, and neurocognitive effects have been evaluated. Throughout this review, we attempted to answer a fundamental question: can the recent molecular findings mitigate pediatric-ALL chemotherapy’s long-term sequelae on adult survivors? For SMNs, few genetic predisposition factors have been identified including TP53 and POT1 variants. Other treatment-related risk factors have been identified such as anthracyclines’ possible association with breast cancer in female survivors. Cardiotoxicity is another significant and common adverse event with some germline variants been found, albeit with conflicting evidence, to increase the risk of cardiac toxicity. For peripheral neurotoxicity, vincristine is the primary neurotoxic agent in ALL regimens. Some germline genetic variants were found to be associated with the vincristine neurotoxic effect’s vulnerability. However, these were mainly detected with acute neuropathy. Moreover, the high steroid doses and prolonged use increase bone toxicity and obesity risk with some pharmacogenetic biomarkers were associated with increased steroid sensitivity. Therefore, the role of these biomarkers in tailoring steroid choice and dose is a promising research area. Future directions in pediatric ALL treatment should consider the various opportunities provided by genomic medicine. Understanding the molecular bases underlying toxicities will classify patients into risk groups and implement a closer follow-up to those at higher risk. Pharmacogenetic-guided dosing and selecting between alternative agents have proven their efficacy in the short-term management of childhood ALL. It is the right time to think about a similar approach for the life-long consequences on survivors.

scholarly journals Gut Microbiota Diversity and Composition Are Altered during Therapy in Pediatric Acute Lymphoblastic Leukemia Patients

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3364-3364
Author(s):  
Elizabeth Yang ◽  
Svetlana Rassulova ◽  
Dhwani Sahjwani ◽  
An Harmanli ◽  
Ryan Fassnacht ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Relative Abundance ◽  
Low Dose ◽  
Lymphoblastic Leukemia ◽  
Healthy Siblings ◽  
Pediatric All ◽  
Stool Samples ◽  
Standard Risk

Abstract Background Childhood acute lymphoblastic leukemia (ALL) has a very high cure rate, however, long-term survivors are at increased risk of chronic medical illnesses that are likely in part microbiome mediated. Previous studies comparing microbiota of pediatric ALL survivors to healthy siblings showed altered composition in survivors. Longitudinal microbiome changes through treatment leading to these alterations are unknown. Methods Children with ALL were enrolled and stool samples were collected at diagnosis and at the end of induction, consolidation, interim maintenance I, delayed intensification, interim maintenance II, as well as approximately 3 months and 6 months into maintenance. Stool samples from healthy siblings were used as controls. Clinical data were collected. DNA was extracted from stool samples and 16S rRNA was sequenced for analysis of hypervariable region V4. Differences in alpha and beta diversities and relative abundance of taxa were calculated between phases and with sibling controls. Results 35 ALL patients age 3 months-19 years were included. The diagnoses were 14 standard risk pre-B ALL, 14 high risk pre-B ALL, 6 T-ALL, and 1 relapsed pre-B ALL. Stool samples were sequenced from 19 healthy siblings. Statistically significant differences in alpha diversity (Shannon) were found between healthy siblings and ALL patients during the more intense chemotherapy phases before low dose maintenance (Figure 1A). Beta diversity (Bray-Curtis), was significantly different between microbiota of ALL patients at diagnosis and their siblings, as well as between ALL patients at diagnosis and at each of the subsequent treatment phases (Figure 1B). Longitudinal comparison using multivariate analysis showed that leukemia risk group (high risk vs standard risk) and antibiotic treatment were significant factors in beta diversity changes. The relative abundance of microbes showed that with treatment, ALL patients exhibit a significant decrease in the phylum Verrucomicrobiota, driven by the genus Akkermansia, which is beneficial to health and is associated with protection against obesity and other chronic inflammatory diseases (Figure 2). Proteobacteria and Fusobacteria, which include proinflammatory species, were increased. Conclusion Pediatric ALL patients have decreased diversity of gut microbes at diagnosis and during treatment. The types of gut microbes harbored in ALL patients are already different than their siblings at diagnosis and continue to change during treatment, but may begin to recover in low dose maintenance therapy. Taxa considered to be beneficial are depleted, while more pathogenic microbes become prominent. Microbiota changes are likely influenced by intensity of chemotherapy and antibiotic exposure. Continued longitudinal follow up is needed to determine whether these changes correlate with adverse long term health outcomes. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Targeting Kinase-activating Genetic Lesions to Improve Therapy of Pediatric Acute Lymphoblastic Leukemia

2018 ◽  
Vol 25 (24) ◽  
pp. 2811-2825 ◽  
Author(s):  
Raffaella Franca ◽  
Natasa K. Kuzelicki ◽  
Claudio Sorio ◽  
Eleonora Toffoletti ◽  
Oksana Montecchini ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Fusion Gene ◽  
Hematologic Malignancy ◽  
Lymphoblastic Leukemia ◽  
Point Of View ◽  
Lymphoid Cells ◽  
Gene Encoding ◽  
Pediatric All ◽  
Blast Cells ◽  
Tk Inhibitors

Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy in children, characterized by an abnormal proliferation of immature lymphoid cells. Thanks to risk-adapted combination chemotherapy treatments currently used, survival at 5 years has reached 90%. ALL is a heterogeneous disease from a genetic point of view: patients’ lymphoblasts may harbor in fact several chromosomal alterations, some of which have prognostic and therapeutic value. Of particular importance is the translocation t(9;22)(q34;q11.2) that leads to the formation of the BCR-ABL1 fusion gene, encoding a constitutively active chimeric tyrosine kinase (TK): BCR-ABL1 that is present in ~3% of pediatric ALL patients with B-immunophenotype and is associated with a poor outcome. This type of ALL is potentially treatable with specific TK inhibitors, such as imatinib. Recent studies have demonstrated the existence of a subset of BCR-ABL1 like leukemias (~10-15% of Bimmunophenotype ALL), whose blast cells have a gene expression profile similar to that of BCR-ABL1 despite the absence of t(9;22)(q34;q11.2). The precise pathogenesis of BCR-ABL1 like ALL is still to be defined, but they are mainly characterized by the activation of constitutive signal transduction pathways due to chimeric TKs different from BCR-ABL1. BCR-ABL1 like ALL patients represent a group with unfavorable outcome and are not identified by current risk criteria. In this review, we will discuss the design of targeted therapy for patients with BCR-ABL1 like ALL, which could consider TK inhibitors, and discuss innovative approaches suitable to identify the presence of patient’s specific chimeric TK fusion genes, such as targeted locus amplification or proteomic biosensors.

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