Why Do Children with Acute Lymphoblastic Leukemia Fare Better Than Adults?

Neaga, Alexandra; Jimbu, Laura; Mesaros, Oana; Bota, Mădălina; Lazar, Diana Raluca; Căinap, Simona; Blag, Cristina; Zdrenghea, Dumitru

doi:10.3390/cancers13153886

Cited by 26 publications

(16 citation statements)

References 81 publications

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“…Furthermore, differences in the pharmacokinetics of immunosuppressive drugs ( 40 ) and differences in gut microbiome ( 41 ) have been described. Data on differences in the paediatric vs. the adult population are emerging from studies investigating how a paediatric-like treatment protocol works in younger adult patients with leukaemia and lymphoma: multiple factors related to biology but also therapy intensity affects the balance between tolerability and efficacy ( 42 – 44 ). These differences in pathophysiology by patient age have to be kept in mind when children are transplanted in clinical units, where both, adults and children are being treated, or when results of clinical trials performed predominantly in adult populations are used as the basis for clinical decisions in children.…”

Section: Differences In the Pathophysiology Of Agvhd Between Adults And Childrenmentioning

confidence: 99%

Current Prophylaxis and Treatment Approaches for Acute Graft-Versus-Host Disease in Haematopoietic Stem Cell Transplantation for Children With Acute Lymphoblastic Leukaemia

et al. 2022

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Acute graft-versus-host disease (aGvHD) continues to be a leading cause of morbidity and mortality following allogeneic haematopoietic stem cell transplantation (HSCT). However, higher event-free survival (EFS) was observed in patients with acute lymphoblastic leukaemia (ALL) and grade II aGvHD vs. patients with no or grade I GvHD in the randomised, controlled, open-label, international, multicentre Phase III For Omitting Radiation Under Majority age (FORUM) trial. This finding suggests that moderate-severity aGvHD is associated with a graft-versus-leukaemia effect which protects against leukaemia recurrence. In order to optimise the benefits of HSCT for leukaemia patients, reduction of non-relapse mortality—which is predominantly caused by severe GvHD—is of utmost importance. Herein, we review contemporary prophylaxis and treatment options for aGvHD in children with ALL and the key challenges of aGvHD management, focusing on maintaining the graft-versus-leukaemia effect without increasing the severity of GvHD.

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Section: Differences In the Pathophysiology Of Agvhd Between Adults And Childrenmentioning

confidence: 99%

Current Prophylaxis and Treatment Approaches for Acute Graft-Versus-Host Disease in Haematopoietic Stem Cell Transplantation for Children With Acute Lymphoblastic Leukaemia

et al. 2022

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“…A plethora of factors are responsible for the different outcomes, including socio-economic factors, resistance, disease heterogeneity, host responses, therapeutic treatment, etc. [ 147 ]. Resistance is one of the main factors leading to variables among ALL patients of different ages.…”

Section: Special Considerations Of Resistance In Pediatric Cancer Tre...mentioning

confidence: 99%

The Battlefield of Chemotherapy in Pediatric Cancers

Wang

et al. 2023

Cancers

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The survival rate for pediatric cancers has remarkably improved in recent years. Conventional chemotherapy plays a crucial role in treating pediatric cancers, especially in low- and middle-income countries where access to advanced treatments may be limited. The Food and Drug Administration (FDA) approved chemotherapy drugs that can be used in children have expanded, but patients still face numerous side effects from the treatment. In addition, multidrug resistance (MDR) continues to pose a major challenge in improving the survival rates for a significant number of patients. This review focuses on the severe side effects of pediatric chemotherapy, including doxorubicin-induced cardiotoxicity (DIC) and vincristine-induced peripheral neuropathy (VIPN). We also delve into the mechanisms of MDR in chemotherapy to the improve survival and reduce the toxicity of treatment. Additionally, the review focuses on various drug transporters found in common types of pediatric tumors, which could offer different therapeutic options.

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“…Knockdown of MEF2D inhibits the development and progression of B-cell acute lymphoblastic leukemia frontline regimens for ALL treatment have resulted in a 5-year overall survival (OS) rate of 90% in pediatric patients (3,4) but less than 45% in adults (4)(5)(6). In older patients (>60 years), the 5-year OS rate is under 20% (7).…”

Section: Original Articlementioning

confidence: 99%

Knockdown of MEF2D inhibits the development and progression of B-cell acute lymphoblastic leukemia

Chang¹,

Feng²,

Liao³

et al. 2023

Transl Cancer Res

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Background: Myocyte enhancer factor 2D (MEF2D) is involved in the progression of various malignant tumors. However, its impact on B-cell acute lymphoblastic leukemia (B-ALL) has not been elucidated. Methods: In this study, the expression level of MEF2D in B-ALL patients was validated through the Gene Expression Omnibus (GEO) database and clinical specimens. MEF2D-knockdown B-ALL cell lines were constructed by lentivirus transfection, and the effects of MEF2D on the viability, apoptosis, cycle progression, and drug sensitivity of B-ALL cells were verified by Cell Counting Kit-8 (CCK-8) and flow cytometry (FCM). The effect of MEF2D on the proliferation of B-ALL cells in vivo was verified via the construction of a xenograft mouse model. The mechanism of MEF2D regulating B-ALL cells was explored by RNA sequencing analysis, quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemical (IHC). Results: In this study, overexpression of MEF2D was observed in B-ALL patients and was remarkably correlated to disease progression in ALL patients. The knockdown of MEF2D expression suppressed cell viability, induced cell apoptosis, blockaded cell cycle progression, enhanced drug sensitivity of B-ALL cells in vitro, and reduced the tumor load in vivo. Furthermore, mechanistic studies revealed that MEF2D knockdown downregulated the expression of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)protein kinase B (AKT) signaling pathway.Conclusions: Our research demonstrated that MEF2D was markedly expressed in B-ALL. MEF2D knockdown inhibited cancer progression of B-ALL both in vitro and in vivo, which may be related to the downregulation of the PI3K-AKT signaling pathway. The data suggest that MEF2D plays a vital role in the process of tumorigenesis and may be a potential novel target for B-ALL therapy.

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Why Do Children with Acute Lymphoblastic Leukemia Fare Better Than Adults?

Cited by 26 publications

References 81 publications

Current Prophylaxis and Treatment Approaches for Acute Graft-Versus-Host Disease in Haematopoietic Stem Cell Transplantation for Children With Acute Lymphoblastic Leukaemia

Current Prophylaxis and Treatment Approaches for Acute Graft-Versus-Host Disease in Haematopoietic Stem Cell Transplantation for Children With Acute Lymphoblastic Leukaemia

The Battlefield of Chemotherapy in Pediatric Cancers

Knockdown of MEF2D inhibits the development and progression of B-cell acute lymphoblastic leukemia

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