Pain Management in Childhood Leukemia: Diagnosis and Available Analgesic Treatments

Coluzzi, Flaminia; Rocco, Monica; Gladden, Rula Green; Persiani, P.J.; Hill, Joshua A.; Milano, Filippo

doi:10.3390/cancers12123671

Cited by 13 publications

(9 citation statements)

References 86 publications

(99 reference statements)

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“…In China, leukemia is the most common malignant tumor in children. According to the survey, there are about 15000 new leukemia children in China every year, of which 70% to 80% are ALL [ 13 ]. It is gratifying to note that over the past half a century, with the continuous development of immunology, molecular biology, and genetic technology, human beings have gained a deeper understanding of the etiology and pathogenesis of leukemia.…”

Section: Discussionmentioning

confidence: 99%

A Retrospective Cohort Study of the Efficacy, Safety, and Clinical Value of 6-TG versus 6-MP Maintenance Therapy in Children with Acute Lymphoblastic Leukemia

Zhang

et al. 2022

BioMed Research International

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Objective. To explore the efficacy, safety, and clinical value of 6-TG versus 6-MP when treating childhood acute lymphoblastic leukemia (ALL). Methods. The study period was from January 2017 to June 2021. The subjects of this study were 100 children with ALL who were treated in our hospital. According to different intervention methods, the children who received 6-MP maintenance therapy were selected as the control group, with a total of 57 cases. Children with TG maintenance therapy were included in the research group, a total of 43 cases. The ICNS recurrence rate, non-ICNS recurrence rate, first remission mortality rate, secondary malignant tumor, and other indicators were compared. Results. First of all, we compared the effective rate: complete remission (CR), partial remission, and nonremission in the study group, and the effective rate was 87.5%. In the control group, there were CR, partial remission, and no remission, and the effective rate was 65.5%. The effective rate of the study group was higher, and the difference between groups was statistically significant ( P < 0.05 ). There were 55 cases of failure in the study group, with an incidence of 21.91%. There were 42 cases of total failure events in the control group, the incidence rate was 18.02%, and there exhibited no remarkable difference ( P > 0.05 ). In the study group, 6 cases died in the first remission, with a fatality rate of 2.39%, while there exhibited no death in the control group. The mortality in the first remission period in the study group was lower ( P < 0.05 ). The overall recurrence rate of the study group was 5.57%, while that of the control group was 11.15%. The overall recurrence rate of the study group was lower, and the difference between groups was statistically significant ( P < 0.05 ). The recurrence rate of ICNS was 2.14% in the study group and 2.98% in the control group, and there exhibited no remarkable difference ( P > 0.05 ). The non-ICNS recurrence rate was 3.43% in the study group and 7.17% in the control group. There exhibited no remarkable difference ( P > 0.05 ). The incidence of secondary malignant tumor events was 0.85% in the study group and 1.59% in the control group. There exhibited no remarkable difference ( P > 0.05 ). The incidence of hepatic vein occlusive disease was 7.29% in the study group and 2.39% in the control group. The incidence of hepatic vein occlusive disease in the study group was higher, and the difference between groups was statistically significant ( P < 0.05 ). Finally, we compared the incidence of adverse reactions. In the study group, there were 12 cases of oral mucosal damage, 7 cases of liver function damage, 6 cases of infection, 10 cases of myelosuppression, 9 cases of gastrointestinal reaction, and 4 cases of skin damage; the incidence rate was 23.17%. In the control group, there were 12 cases of oral mucosal damage, 7 cases of liver function damage, 6 cases of infection, 10 cases of myelosuppression, 9 cases of gastrointestinal reaction, and 4 cases of skin damage, with an incidence of 19.12%. There exhibited no remarkable difference in the incidence of adverse reactions ( P > 0.05 ). Conclusion. 6-TG maintenance therapy in children with ALL can enhance the overall effective rate, can reduce the first remission mortality and the total recurrence rate, and will not increase the overall incidence of adverse reactions, but the incidence of reversible or irreversible hepatic veno-occlusive disease is remarkably increased, which has a certain clinical value. Background. Treatment-related hepatotoxicity and myelosuppression remain formidable challenges for clinicians. Pharmacokinetic studies found that 6-TG has a more direct intracellular activation pathway, shorter cytotoxic time, and stronger potency than 6-MP. Therefore, this study investigated the efficacy, safety, and clinical value of 6-TG and 6-MP in the treatment of children with ALL.

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Section: Discussionmentioning

confidence: 99%

A Retrospective Cohort Study of the Efficacy, Safety, and Clinical Value of 6-TG versus 6-MP Maintenance Therapy in Children with Acute Lymphoblastic Leukemia

Zhang

et al. 2022

BioMed Research International

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“…Acute lymphoblastic leukemia (ALL) is the most common neoplasm in children, accounting for about 30 percent of all pediatric malignancies (Coluzzi et al, 2020). High-dose methotrexate (HDMTX) is commonly defined as an intravenous dose greater than 500 mg/m 2 (Howard et al, 2016), and HDMTX is recommended as an essential component of chemotherapy for ALL and non-Hodgkin lymphoma (NHL) in clinical guidelines (National Comprehensive Cancer Network, 2021a;.…”

Section: Introductionmentioning

confidence: 99%

The Role of Genetic Polymorphisms in High-Dose Methotrexate Toxicity and Response in Hematological Malignancies: A Systematic Review and Meta-Analysis

Song

Liu

et al. 2021

Front. Pharmacol.

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Objective: High-dose methotrexate (HDMTX) is a mainstay therapeutic agent for the treatment of diverse hematological malignancies, and it plays a significant role in interindividual variability regarding the pharmacokinetics and toxicity. The genetic association of HDMTX has been widely investigated, but the conflicting results have complicated the clinical utility. Therefore, this systematic review aims to determine the role of gene variants within the HDMTX pathway and to fill the gap between knowledge and clinical practice.Methods: Databases including EMBASE, PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and the Clinical Trials.gov were searched from inception to November 2020. We included twelve single-nucleotide polymorphisms (SNPs) within the HDMTX pathway, involving RFC1, SLCO1B1, ABCB1, FPGS, GGH, MTHFR, DHFR, TYMS, and ATIC. Meta-analysis was conducted by using Cochrane Collaboration Review Manager software 5.3. The odds ratios (ORs) or hazard ratios (HRs) with 95% confidence interval (95% CI) were analyzed to evaluate the associations between SNPs and clinical outcomes. This study was performed according to the PRISMA guideline.Results: In total, 34 studies with 4102 subjects were identified for the association analysis. Nine SNPs involving MTHFR, RFC1, ABCB1, SLCO1B1, TYMS, FPGS, and ATIC genes were investigated, while none of studies reported the polymorphisms of GGH and DHFR yet. Two SNPs were statistically associated with the increased risk of HDMTX toxicity: MTHFR 677C>T and hepatotoxicity (dominant, OR=1.52, 95% CI=1.03-2.23; recessive, OR=1.68, 95% CI=1.10–2.55; allelic, OR=1.41, 95% CI=1.01–1.97), mucositis (dominant, OR=2.11, 95% CI=1.31–3.41; allelic, OR=1.91, 95% CI=1.28–2.85), and renal toxicity (recessive, OR=3.54, 95% CI=1.81–6.90; allelic, OR=1.89, 95% CI=1.18–3.02); ABCB1 3435C>T and hepatotoxicity (dominant, OR=3.80, 95% CI=1.68-8.61), whereas a tendency toward the decreased risk of HDMTX toxicity was present in three SNPs: TYMS 2R>3R and mucositis (dominant, OR=0.66, 95% CI=0.47–0.94); RFC1 80A>G and hepatotoxicity (recessive, OR=0.35, 95% CI=0.16–0.76); and MTHFR 1298A>C and renal toxicity (allelic, OR=0.41, 95% CI=0.18–0.97). Since the data of prognosis outcomes was substantially lacking, current studies were underpowered to investigate the genetic association.Conclusions: We conclude that genotyping of MTHFR and/or ABCB1 polymorphisms prior to treatment, MTHFR 677C>T particularly, is likely to be potentially useful with the aim of tailoring HDMTX therapy and thus reducing toxicity in patients with hematological malignancies.

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“…Adequate pain management in children with ALL is an indispensable supportive care tool. In these patients, pain often occurs in connection with osteonecrosis, peripheral neuropathy caused by vincristine or mucosal or gastrointestinal side-effects (e.g., mucositis, enteritis, obstipation) and must be administered in the correct dose for the respective indication, regardless of the substances' possible off-label use in children ( 113 ). Going into detail about pain medication in pediatric oncology would exceed the scope of this review.…”

Section: Supportive Care In Conventional Childhood All Therapymentioning

confidence: 99%

Supportive methods for childhood acute lymphoblastic leukemia then and now: A compilation for clinical practice

et al. 2022

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Survival of childhood acute lymphoblastic leukemia has significantly improved over the past decades. In the early years of chemotherapeutic development, improvement in survival rates could be attained only by increasing the cytostatic dose, also by modulation of the frequency and combination of chemotherapeutic agents associated with severe short- and long-time side-effects and toxicity in a developing child's organism. Years later, new treatment options have yielded promising results through targeted immune and molecular drugs, especially in relapsed and refractory leukemia, and are continuously added to conventional therapy or even replace first-line treatment. Compared to conventional strategies, these new therapies have different side-effects, requiring special supportive measures. Supportive treatment includes the prevention of serious acute and sometimes life-threatening events as well as managing therapy-related long-term side-effects and preemptive treatment of complications and is thus mandatory for successful oncological therapy. Inadequate supportive therapy is still one of the main causes of treatment failure, mortality, poor quality of life, and unsatisfactory long-term outcome in children with acute lymphoblastic leukemia. But nowadays it is a challenge to find a way through the flood of supportive recommendations and guidelines that are available in the literature. Furthermore, the development of new therapies for childhood leukemia has changed the range of supportive methods and must be observed in addition to conventional recommendations. This review aims to provide a clear and recent compilation of the most important supportive methods in the field of childhood leukemia, based on conventional regimes as well as the most promising new therapeutic approaches to date.

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Pain Management in Childhood Leukemia: Diagnosis and Available Analgesic Treatments

Cited by 13 publications

References 86 publications

A Retrospective Cohort Study of the Efficacy, Safety, and Clinical Value of 6-TG versus 6-MP Maintenance Therapy in Children with Acute Lymphoblastic Leukemia

A Retrospective Cohort Study of the Efficacy, Safety, and Clinical Value of 6-TG versus 6-MP Maintenance Therapy in Children with Acute Lymphoblastic Leukemia

The Role of Genetic Polymorphisms in High-Dose Methotrexate Toxicity and Response in Hematological Malignancies: A Systematic Review and Meta-Analysis

Supportive methods for childhood acute lymphoblastic leukemia then and now: A compilation for clinical practice

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