Intracranial Hemorrhage Following Oral Low-Dose Methotrexate After Multiple Toxicities Caused by High-Dose Methotrexate in Childhood Acute Lymphoblastic Leukemia

Xia, Ning; Zhou, Fen; Li, Cheng; Yan, Xiao; Jin, Runming

doi:10.3389/fphar.2019.01072

Cited by 6 publications

(4 citation statements)

References 23 publications

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“…Percutaneous cholecystostomy is the treatment option of choice for critically ill patients with acute cholecystitis, while more stable patients may undergo definitive laparoscopic cholecystectomy. [19][20][21] Xin et al [22] presented a case study of an 11-year-old patient with B-ALL who developed intracranial hemorrhage and cholecystitis after completing high-dose methotrexate chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Severe complications in the induction phase of therapy in a pediatric patient with T-cell acute lymphoblastic leukemia: A case report

Rocka,

Woźniak,

Lejman

et al. 2023

Medicine

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Rationale: Acute lymphoblastic leukemia (ALL) represents approximately 1-quarter of all new cases of childhood cancer. Although overall survival following diagnosis has improved in recent years, the toxicity of chemotherapy remains a concern. Patient concerns: We describe an 11-year-old male patient diagnosed with T-cell precursor ALL who developed compounded complications during the induction phase of chemotherapy. Patient was hospitalized in the Department of Pediatric Hematology, Oncology, and Transplantology of the Medical University of Lublin, Poland. The patient’s induction therapy was started according to the AIEOP-BFM ALL 2017 protocol IAp (International Collaborative Treatment Protocol for Children and Adolescents with Acute Lymphoblastic Leukemia). Diagnoses: Patient developed compounded complications such as cholecystitis, hepatotoxicity, pancreatitis and myelosuppression. Interventions: The patient was treated with leukapheresis, received a broad-spectrum antibiotic, potassium supplementation and hepatoprotective treatment and laparotomy cholecystectomy. Outcomes: In the available literature, there is a limited amount of similar clinical cases with multiple complications in pediatric patients with ALL. Toxicities cause delays in the treatment of the underlying disease. Lessons: In children with acute lymphoblastic leukemia, there are side effects during the treatment such as cholecystitis and pancreatitis. Complications during treatment require a quick response and modification of disease management. Abdominal ultrasound performed before treatment makes it possible to observe the dynamics of lesions. Genetic mutation analysis could allow us to more precisely respond to the possible susceptibility to and appearance of complications after the use of a given chemotherapeutic agent.

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Section: Discussionmentioning

confidence: 99%

Severe complications in the induction phase of therapy in a pediatric patient with T-cell acute lymphoblastic leukemia: A case report

Rocka,

Woźniak,

Lejman

et al. 2023

Medicine

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“…It has been revealed that the increase of dihydrofolate reductase and the damage of MTX transport are key factors in MTX resistance in childhood ALL (41). Previous studies have measured the difference in MTX resistance-related mRNA expression levels in childhood leukaemia by standardized RT-qPCR based on a competitive template, and observed that in T-ALL, compared with ordinary/pre-B-ALL, the difference in MTX resistance, dihydrofolate reductase (DHFR), thymidylate synthetase (TS) and folylpolyglutamate synthase mRNA expression levels are increased (22,42,43). The present results suggested that HSH2D is one of the important factors affecting MTX resistance, and identified via gene manipulation that HSH2D expression is necessary for HuT-78 cells resistance to MTX.…”

Section: Discussionmentioning

confidence: 99%

HSH2D contributes to methotrexate resistance in�human T‑cell acute lymphoblastic leukaemia

Wang

Xiong

2020

Oncol Rep

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Acute lymphoblastic leukaemia (ALL) is a malignant proliferative disease that originates from B-lineage or T-lineage lymphoid progenitor cells. Resistance to chemotherapy remains an important factor for treatment failure. The aim of the present study was to investigate drug resistance in T-cell ALL (T-ALL). Bioinformatics analysis of Oncomine and Gene Expression Omnibus data was performed to evaluate the expression of haematopoietic SH2 domain containing (HSH2D) in various lymphomas. HuT-78 cells with HSH2D overexpression and or knockdown were constructed, and the effect on related downstream signalling molecules was detected. To study the effect of HSH2D on methotrexate (MTX) resistance, cell cycle and apoptosis analyses were conducted using flow cytometry, and MTT and EdU assays were used to detect the effect of MTX resistance and HSH2D gene expression on the biological function of HuT-78 cells. Via the analysis of the data sets, it was identified that the expression of HSH2D was downregulated in TALL compared with B-cell ALL. Western blotting and reverse transcription-quantitative PCR demonstrated that the overexpression of HSH2 resulted in the inhibition of CD28-mediated IL-2 activation. In related experiments with drug-resistant cell lines, it was determined that HSH2D expression is necessary for HuT-78 cells to be resistant to MTX. In conclusion, the results suggested that HSH2D serves an important role in the resistance of TALL to MTX, which provides a potential research target for the study of drug resistance of TALL .

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“… 51 – 55 An increased risk of ICH and subdural hematoma (SDH) has been seen in several case series with both children and adults patients with acute lymphoblastic leukemia (ALL) undergoing oral or more often intravenous or intrathecal injection of methotrexate (MTX). 56 , 57 L -asparaginase also used for treating ALL is associated with VTE including dural sinus thrombosis and has been linked to hemorrhagic cerebrovascular events. 58 , 59 Moreover, invasive cancer surgeries and other procedures like hematopoietic stem-cell transplantation may increase the risk of both ischemic and hemorrhagic strokes.…”

Section: Potential Mechanisms Of Association Between Cancer and Strokementioning

confidence: 99%

Cancer and stroke: commonly encountered by clinicians, but little evidence to guide clinical approach

Woock

Martinez‐Majander

Seiffge

et al. 2022

Ther Adv Neurol Disord

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The association between stroke and cancer is well-established. Because of an aging population and longer survival rates, the frequency of synchronous stroke and cancer will become even more common. Different pathophysiologic mechanisms have been proposed how cancer or cancer treatment directly or via coagulation disturbances can mediate stroke. Increased serum levels of D-dimer, fibrin degradation products, and CRP are more often seen in stroke with concomitant cancer, and the clot retrieved during thrombectomy has a more fibrin- and platelet-rich constitution compared with that of atherosclerotic etiology. Multiple infarctions are more common in patients with active cancer compared with those without a cancer diagnosis. New MRI techniques may help in detecting typical patterns seen in the presence of a concomitant cancer. In ischemic stroke patients, a newly published cancer probability score can help clinicians in their decision-making when to suspect an underlying malignancy in a stroke patient and to start cancer-screening studies. Treating stroke patients with synchronous cancer can be a delicate matter. Limited evidence suggests that administration of intravenous thrombolysis appears safe in non-axial intracranial and non-metastatic cancer patients. Endovascular thrombectomy is probably rather safe in these patients, but probably futile in most patients placed on palliative care due to their advanced disease. In this topical review, we discuss the epidemiology, pathophysiology, and prognosis of ischemic and hemorrhagic strokes as well as cerebral venous thrombosis and concomitant cancer. We further summarize the current evidence on acute management and secondary preventive therapy.

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Intracranial Hemorrhage Following Oral Low-Dose Methotrexate After Multiple Toxicities Caused by High-Dose Methotrexate in Childhood Acute Lymphoblastic Leukemia

Cited by 6 publications

References 23 publications

Severe complications in the induction phase of therapy in a pediatric patient with T-cell acute lymphoblastic leukemia: A case report

Severe complications in the induction phase of therapy in a pediatric patient with T-cell acute lymphoblastic leukemia: A case report

HSH2D contributes to methotrexate resistance in�human T‑cell acute lymphoblastic leukaemia

Cancer and stroke: commonly encountered by clinicians, but little evidence to guide clinical approach

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