scholarly journals Feasibility of High-dose Methotrexate Administered on Day 1 of (R)CHOP in aggressive non-Hodgkin Lymphomas

2021 ◽  
Author(s):  
Megan K Fleming ◽  
Ying Huang ◽  
Emily K Dotson ◽  
David A Bond ◽  
John C. Reneau ◽  
...  
Keyword(s):  
Central Nervous System Involvement ◽  
Kidney Injury ◽  
Optimal Timing ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Treatment Delays ◽  
Non Hodgkin Lymphoma ◽  
Dose Methotrexate ◽  
Grade 3 ◽  
Dose Reductions

The optimal timing for administering high-dose methotrexate (HDMTX) when combined with (R)CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone, with/without rituximab) is unclear. Recent data showed that the administration of prophylactic HDMTX before day 10 of R-CHOP may lead to fewer treatment delays. Herein, we report our experience with HDMTX administered on day 1 of (R)CHOP in patients with aggressive non-Hodgkin lymphoma. We identified 140 patients treated with ≥1 cycle of HDMTX combined with (R)CHOP for prophylaxis against (n=84) or treatment of (n=56) central nervous system involvement. Overall, (R)CHOP treatment delays ≥7 days (4% of cycles, 13% of patients), doxorubicin and/or cyclophosphamide dose reductions (1% of cycles, 6% of patients) or (R)CHOP discontinuations due to toxicity (4% of patients) were uncommon. Neutropenic fever (NF) occurred in 7% of cycles and 24% of patients and was more common during HDMTX-containing cycles. Acute kidney injury (AKI) occurred in 19% of cycles but was mostly grade ≤2. Grade ≥3 hepatotoxicity and mucositis were uncommon (each 2% of cycles). In the prophylaxis cohort, the rates of NF and grade ≥2 AKI were lower in patients who initiated HDMTX with cycle 2 or later (11% vs 30%, p=0.03 and 16% vs 39%, p=0.03, respectively). Our data show that HDMTX administration on day 1 of (R)CHOP may improve the deliverability of (R)CHOP and the overall safety of the regimen compared with historical data of HDMTX administration on day 10 or later of R-CHOP. Delaying prophylactic HDMTX beyond cycle 1 of (R)CHOP may reduce the risk of NF and AKI.

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.

Effect of single agent high-dose methotrexate-related acute kidney injury on length of hospitalization and relative dose intensity in adult patients with central nervous system lymphoma

2016 ◽  
Vol 23 (7) ◽  
pp. 496-501 ◽  
Author(s):  
Jennifer S Steward ◽  
Heather M Bullard ◽  
Timothy J O’Rourke ◽  
Alan D Campbell ◽  
Brett T Brinker ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Length Of Stay ◽  
Kidney Injury ◽  
Dose Intensity ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Chemotherapy Dose ◽  
Grade 3 ◽  
Chemotherapy Dose Intensity

Purpose Grade ≥3 adverse effects prolong hospitalization and reduce chemotherapy dose intensity. The purpose of this study was to evaluate the rate and severity of high-dose methotrexate-related acute kidney injury and analyze its effect on hospital length of stay and relative chemotherapy dose intensity. Methods This was a retrospective cohort analysis. Patients receiving ≥1 dose of high-dose methotrexate were analyzed for acute kidney injury and length of stay. Patients receiving ≥6 cycles of induction therapy were included in the analysis of relative chemotherapy dose intensity. Chi squared analysis was used to determine the differences between dichotomous data; Student’s t-test for parametric data and Mann-Whitney U test for non-parametric data for continuous variables. Statistical analyses were performed with IBM SPSS Statistics (version 21). Results Twenty-six patients and 194 treatment encounters were identified. Thirteen patients were evaluated for relative chemotherapy dose intensity. Grade ≥3 acute kidney injury occurred in four patients (15% of patients; 2% of encounters). There were no grade 5 adverse events. Mean length of stay for encounters with grade ≥3 acute kidney injury was almost three times longer than for those with ≤ grade 2 acute kidney injury (p = 0.041). Mean relative chemotherapy dose intensity was reduced approximately in half for patients experiencing grade ≥3 acute kidney injury (p < 0.01). The most common adverse events were hypokalemia and nausea. Proton pump inhibitors were the most frequently co-administered medications with the potential to affect high-dose methotrexate pharmacokinetics. Conclusion At our cancer program, the rate of grade ≥3 acute kidney injury with high-dose methotrexate is similar to that reported by others. Grade ≥3 acute kidney injury following high-dose methotrexate administration significantly prolonged length of stay and reduced relative chemotherapy dose intensity.

A retrospective safety analysis of adult patients treated with high-dose methotrexate for osteosarcoma in Stockholm, Sweden.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10083-10083 ◽  
Author(s):  
Daniel Alm ◽  
Christina Linder Stragliotto ◽  
Annika Folin ◽  
Jonas Bergh ◽  
Theodoros Foukakis
Keyword(s):  
Oral Mucositis ◽  
Blood Concentration ◽  
Renal Toxicity ◽  
Adult Patients ◽  
Bleeding Complications ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Hepatic Toxicity ◽  
Dose Methotrexate ◽  
Grade 3

10083 Background: Patients with osteosarcoma are routinely treated with pre- and post-operative chemotherapy that includes high-dose methotrexate. The treatment is associated with a risk of severe renal and hepatic toxicity. Methods: All patients with osteosarcoma that had received at least one cycle of high-dose methotrexate at the adult oncology department, Karolinska University Hospital were retrospectively identified. Treatment toxicity, including hematologic, renal, hepatic toxicity, infections and oral mucositis were registered and graded according to CTCAE v 4.0. A possible relationship between methotrexate blood concentration and toxicity was investigated. Results: Sixteen eligible patients that had received a total of 103 cycles of high-dose methotrexate were identified. Ten patients experienced a severe hepatic toxicity, (Grade 3, n=5 and Grade 4, n=5). Grade 3 renal toxicity was seen in one patient and although reversible, it led to treatment interruption. Reversible, grade 2 elavation of serum creatinine occured in 5 cases. Four grade 3 infections were seen in 2 patients and 8 patients had at least one occurrence of Grade 3 oral mucositis. Thrombocytopenia was a common event (Grade 3, n=5 and Grade 4, n=2) but no severe bleeding complications were observed. One patient died as a result of multi-organ failure two days after methotrexate administration. Methotrexate blood concentration at 24 hours from administration could predict for renal toxicity (p<0.005, by chi-square test), but not for other toxicity. Conclusions: High-dose methotrexate in adult patients with osteosarcoma was frequently associated with severe, however reversible toxicity.

Kidney Injury Molecule-1 and its association with delayed clearance and drug exposure in pediatric oncology patients treated with high dose methotrexate.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 10034-10034
Author(s):  
Andrew J. Bukowinski ◽  
Tomoyuki Mizuno ◽  
Tsuyoshi Fukuda ◽  
A.a. Vinks ◽  
Stuart Goldstein ◽  
...  
Keyword(s):  
Pediatric Oncology ◽  
Drug Exposure ◽  
Kidney Injury ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Oncology Patients ◽  
Dose Methotrexate ◽  
Kidney Injury Molecule 1

Identification of Risk Factors in High-Dose Methotrexate-Induced Acute Kidney Injury in Childhood Acute Lymphoblastic Leukemia

Chemotherapy ◽  
2018 ◽  
Vol 63 (2) ◽  
pp. 100-106 ◽  
Author(s):  
Dao-Hai Cheng ◽  
Hua Lu ◽  
Tao-Tao Liu ◽  
Xiao-Qin Zou ◽  
Hui-Mei Pang
Keyword(s):  
Risk Factors ◽  
Acute Kidney Injury ◽  
Logistic Regression ◽  
Lymphoblastic Leukemia ◽  
Kidney Injury ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Baseline Serum ◽  
Childhood All ◽  
Dose Methotrexate

Aims: Although high-dose methotrexate (HDMTX) is an effective means for the treatment of acute lymphoblastic leukemia (ALL), the development of renal dysfunction remains a significant management challenge. This study aimed to identify the key factors in HDMTX-induced acute kidney injury (AKI) in childhood ALL. Methods: We retrospectively analyzed the clinical data in 1,329 courses of HDMTX treatment in 336 Chinese ALL children at the First Affiliated Hospital of Guangxi Medical University from September 2012 to November 2016. The clinical data were compared between the groups of children with development of AKI and those without. Risk factors were identified by multiple logistic regression analysis, and the diagnostic performance of plasma MTX concentration was evaluated by receiver operating characteristic (ROC) curve analysis. Results: AKI was observed in 88 patients (26.2%) and 104 courses (7.8%). Binary logistic regression revealed that age (OR 1.349; p = 0.005), first HDMTX course (OR 1.767; p = 0.013), MTX dose per body surface area (BSA; OR 1.944; p = 0.015), and baseline serum total protein (OR 0.929; p = 0.021) significantly correlated with AKI. The area under the ROC for 48-h plasma MTX concentration was 0.890 (95% CI 0.850–0.930), and sensitivity and specificity values of the cut-off value were 78.8 and 90.4%, respectively. Conclusion: Increasing age, higher MTX dose per BSA, lower baseline serum protein, and first HDMTX course were significant risk factors for developing HDMTX-induced AKI in childhood ALL. The threshold of 48-h MTX plasma concentration is valuable for the prediction of HDMTX-induced AKI.

Risk factors for high‐dose methotrexate associated acute kidney injury in patients with hematological malignancies

2020 ◽  
Vol 38 (4) ◽  
pp. 584-588
Author(s):  
Irina Amitai ◽  
Uri Rozovski ◽  
Reem El‐Saleh ◽  
Shai Shimony ◽  
Daniel Shepshelovich ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Kidney Injury ◽  
Hematological Malignancies ◽  
Kidney Injury ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate
Sign in / Sign up

Export Citation Format

Share Document