The impact of increasing patient weight on the dosing of high-dose methotrexate chemotherapy in aggressive non-Hodgkin lymphoma

2017 ◽  
Author(s):  
Geetpal Sandhu
Keyword(s):  
Hodgkin Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Non Hodgkin Lymphoma ◽  
Dose Methotrexate ◽  
Patient Weight ◽  
Methotrexate Chemotherapy ◽  
The Impact

scholarly journals Influence of Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphism on High-Dose Methotrexate-Related Toxicities in Pediatric Non-Hodgkin Lymphoma Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Suying Lu ◽  
Xiaoqin Zhu ◽  
Wei Li ◽  
Huimou Chen ◽  
Dalei Zhou ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Oral Mucositis ◽  
Methylenetetrahydrofolate Reductase ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Mutant Genotype ◽  
Non Hodgkin Lymphoma ◽  
Dose Methotrexate

PurposeThis retrospective study aimed to investigate the relationships between the methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C and high-dose methotrexate (HD-MTX)-related toxicities in pediatric non-Hodgkin lymphoma (NHL) patients.Patients and MethodsWe reviewed the medical records of 93 NHL patients aged under 18 years who received HD-MTX therapy at the dose of 5 g/m2 with 24-h infusion at Sun Yat-sen University Cancer Center between 2014 and 2019.ResultsThere were 61 males and 32 females, with a median age of 8.8 years (0.9–15.8 years). The tumor types included lymphoblastic lymphoma (n = 38), Burkitt’s lymphoma (n = 31), anaplastic large cell lymphoma (n = 18), diffuse large B-cell lymphoma (n = 6). Overall, 355 courses of HD-MTX therapy were prescribed. All patients were rescued with calcium folinate 12 h after the end of MTX infusion. We found that plasma MTX levels > 0.2 μmol/L at 48 h post-infusion increased the risk of developing oral mucositis (2.4% VS. 9.5%, P = 0.018). Also, patients carrying the C677T and T677T genotypes had tendencies to be more susceptible to oral mucositis (P = 0.034). Patients harboring mutant 677T allele were more likely to develop leucopenia (38.5 vs. 50.3%, P = 0.025) and thrombocytopenia (22.0 vs. 32.4%, P = 0.028). For polymorphism A1298C, the mutant genotype played a protective role in vomiting (11.1 vs. 4.3%, P = 0.018) but increased the risk of anemia (23.8 vs. 41.7%, P < 0.001) and leucopenia (38.1 vs. 50.3%, P = 0.021).ConclusionChildhood NHL patients harboring C677T genotype were more vulnerable to oral mucositis, leucopenia, and thrombocytopenia, while those with A1298C genotype were at a decreased risk of vomiting and more likely to develop anemia and leucopenia.

scholarly journals Pretreatment Plasma Folate Modulates the Pharmacodynamic Effect of High-Dose Methotrexate in Children with Acute Lymphoblastic Leukemia and Non-Hodgkin Lymphoma: “Folate Overrescue” Concept Revisited

2006 ◽  
Vol 52 (4) ◽  
pp. 692-700 ◽  
Author(s):  
Jaroslav Sterba ◽  
Ladislav Dusek ◽  
Regina Demlova ◽  
Dalibor Valik
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Hodgkin Lymphoma ◽  
Lymphoblastic Leukemia ◽  
Plasma Homocysteine ◽  
Whole Body ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Plasma Folate ◽  
Non Hodgkin Lymphoma ◽  
Dose Methotrexate

Abstract Background: To evaluate the influence of pretreatment plasma folate concentrations on methotrexate exposure in children with acute lymphoblastic leukemia/non-Hodgkin lymphoma treated with high-dose methotrexate, we assessed time profiles of plasma homocysteine, folate, and vitamin B12 concentrations in children treated with high-dose methotrexate with leucovorin rescue. Methods: We analyzed 98 treatment courses. The study endpoints were to determine how methotrexate exposure is related to homocysteine accumulation and whether it is influenced by pretreatment plasma folate. Results: Peak concentrations of homocysteine increased from the start of the intravenous infusion through cessation of methotrexate therapy up to time point t42, when this trend was reversed by administration of folinic acid. The area under the curve (AUC) for plasma homocysteine showed decreasing course-to-course tendencies with a statistically significant decrease only between courses 1 and 2 (P ≤0.05), indicating decreased whole-body homocysteine accumulation in response to administration of consecutive methotrexate courses. Therapeutic courses with low initial folate concentrations (≤10 nmol/L) gave significantly higher responses in homocysteine accumulation expressed both as hcysAUC0–66 h and the peak t42 homocysteine concentrations than did courses with initial folate >10 nmol/L. Correspondingly, in the courses with low initial folate, peak plasma concentrations of methotrexate were significantly higher than in courses with high precourse concentrations of plasma folate. Conclusion: Endogenous pretreatment plasma folate modulates the magnitude of the methotrexate effect, providing support for a “folate overrescue” concept.

scholarly journals Impact of High-Dose Methotrexate on the Outcome of Patients with Diffuse Large B-Cell Lymphoma and Skeletal Involvement

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2945
Author(s):  
Mélanie Mercier ◽  
Corentin Orvain ◽  
Laurianne Drieu La Rochelle ◽  
Tony Marchand ◽  
Christopher Nunes Gomes ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Skeletal Involvement ◽  
Large B Cell Lymphoma ◽  
Dose Methotrexate ◽  
The Impact ◽  
Large B Cell

Diffuse large B-cell lymphoma (DLBCL) with extra nodal skeletal involvement is rare. It is currently unclear whether these lymphomas should be treated in the same manner as those without skeletal involvement. We retrospectively analyzed the impact of combining high-dose methotrexate (HD-MTX) with an anthracycline-based regimen and rituximab as first-line treatment in a cohort of 93 patients with DLBCL and skeletal involvement with long follow-up. Fifty patients (54%) received upfront HD-MTX for prophylaxis of CNS recurrence (high IPI score and/or epidural involvement) or because of skeletal involvement. After adjusting for age, ECOG, high LDH levels, and type of skeletal involvement, HD-MTX was associated with an improved PFS and OS (HR: 0.2, 95% CI: 0.1–0.3, p < 0.001 and HR: 0.1, 95% CI: 0.04–0.3, p < 0.001, respectively). Patients who received HD-MTX had significantly better 5-year PFS and OS (77% vs. 39%, p <0.001 and 83 vs. 58%, p < 0.001). Radiotherapy was associated with an improved 5-year PFS (74 vs. 48%, p = 0.02), whereas 5-year OS was not significantly different (79% vs. 66%, p = 0.09). A landmark analysis showed that autologous stem cell transplantation was not associated with improved PFS or OS. The combination of high-dose methotrexate and an anthracycline-based immunochemotherapy is associated with an improved outcome in patients with DLBCL and skeletal involvement and should be confirmed in prospective trials.

A single-center qualitative study evaluating the safety and efficacy of a pharmacist-driven protocol for high-dose methotrexate management

2020 ◽  
pp. 107815522092745
Author(s):  
Stephanie F Matta ◽  
Leslie A Gieselman ◽  
Robert S Mancini
Keyword(s):  
Length Of Stay ◽  
Kidney Injury ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Improvement Project ◽  
Treatment Delays ◽  
Dose Methotrexate ◽  
Significant Difference ◽  
The Impact ◽  
Inpatient Length Of Stay

Introduction Delayed methotrexate clearance in several patients admitted to the oncology unit at a regional medical center necessitated the development of a pharmacist-driven protocol for supportive therapy with high-dose methotrexate. This performance improvement project evaluated the impact of the protocol on inpatient length of stay, patient safety, and clinical outcomes. Methods Retrospective data were collected over 14 months pre-implementation and prospective data were collected over 19 months post-implementation. Primary outcomes included mean length of stay and incidence of kidney injury. Secondary outcomes included myelosuppression, treatment delays, mucositis, protocol adherence, and pharmacist interventions. Chi-squared and unpaired two sample t-test were used for data analysis. Intervention A literature review of consensus recommendations for supportive care post high-dose methotrexate administration was conducted to develop the protocol. Education on implementation was provided to involved disciplines. Results One-hundred ten high-dose methotrexate admissions for 23 patients were analyzed: 24 pre-protocol and 86 post-protocol. Mean length of stay was 5.17 nights pre-protocol and 3.91 nights post-protocol ( p = 0.026). Incidence of kidney injury significantly decreased (16.7% pre-protocol versus 3.5% post-protocol; p = 0.0394). Lower incidences of all-grade anemia (83.3% versus 58.1%), neutropenia (62.5% versus 29.1%), and thrombocytopenia (58.3% versus 33.7%) as well as treatment delays (29.2% versus 11.6%; p = 0.036) were reported post protocol. No statistically significant difference in mucositis was detected. Pharmacist adherence to protocol was ≥80% resulting in 348 interventions with 99.4% provider acceptance. Conclusion The implementation of a pharmacist-driven high-dose methotrexate management protocol resulted in a statistically significant decrease in inpatient length of stay and kidney injury. Further studies are needed to assess the impact on additional outcomes.

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