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.

scholarly journals High-dose Methotrexate and Rituximab Induction Regimen In Immunocompetent Patients With Primary CNS Lymphoma: A Retrospective Single-Center Study of Survival Predictors

2022 ◽  
Author(s):  
Andrew Burton DeAtkine ◽  
Moaaz Abdelrashid ◽  
Zach Tucker ◽  
James M. Markert ◽  
Jinsuh Kim ◽  
...  
Keyword(s):  
Survival Data ◽  
Primary Cns Lymphoma ◽  
Comprehensive Cancer Center ◽  
Survival Outcomes ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Significant Difference ◽  
The Impact ◽  
Immunocompetent Patients

Abstract Purpose:Primary Central Nervous System Lymphoma (PCNSL) is an aggressive tumor that is confined to the CNS. Although the provision of high-dose methotrexate (HD-MTX) has remarkably improved outcomes in PCNSL patients, the optimal treatment regimens and standard MTX dose have been largely controversial. Herein, we sought to explore the impact of adjuvant Rituximab and different dosages of HD-MTX on survival outcomes of immunocompetent patients with PCNSL.Methods:In this study, we examined patients with PCNSL treated at a single NCI-designated comprehensive cancer center to evaluate their survival outcomes. We conducted a retrospective analysis of 51 immunocompetent patients with PCNSL who received their induction chemotherapy at the University of Alabama at Birmingham (UAB) between 2001 and 2019. Only adult patients with a confirmed diagnosis of PCNSL who had either HD-MTX alone or in combination with Rituximab were included. Patients’ demographics, clinical characteristics, and survival data were collected and analyzed.Results:There is no significant difference in survival among patients who received MTX alone versus MTX plus Rituximab. Furthermore, lower doses of MTX were associated with worse survival outcomes; however, this difference in survival was not significant when adjusted to age.Conclusion:Our experience challenges the role of Rituximab in PCNSL during induction therapy. Our study also highlights the shorter survival in elderly patients with PCNSL which can be related, to some extent, to the relatively lower doses of HD-MTX. There is an unmet need to establish a consensus on the most effective upfront regimen in PCNSL through prospective studies.

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.

scholarly journals Oral Regimen for Urine Alkalization in Patients Receiving High Dose Methotrexate during a National Shortage of Intravenous Sodium Bicarbonate

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2309-2309 ◽  
Author(s):  
Daniel R Reed ◽  
Jeremy M Sen ◽  
Eric J Pierce ◽  
Maria C Nicolais ◽  
Michael K Keng
Keyword(s):  
Length Of Stay ◽  
Sodium Bicarbonate ◽  
Categorical Variables ◽  
Published Data ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Start Time ◽  
Urine Ph ◽  
Dose Methotrexate ◽  
The Impact

Abstract Background: High dose methotrexate (MTX) is an important agent in the prevention and treatment of cancer in the central nervous system. Administration of this drug requires alkalization of the urine, which traditionally includes the use of intravenous (IV) sodium bicarbonate (bicarb). In May 2017, IV bicarb was on national shortage; at the University of Virginia, pharmacists and physicians designed an oral (PO) regimen using bicarb and acetazolamide to ensure patients could continue receiving MTX. As there are limited published data, we aimed to assess the safety and the impact on time to start of MTX. Methods: Retrospective chart review was done 5/2016-4/2017 to establish a baseline time to methotrexate. In a prospective analysis, data was collected from May 2017 to May 2018 on all patients who received MTX. For patients receiving the PO regimen, bicarb 2,600 mg PO 6 times daily and acetazolamide 250 mg PO every 6 hours were the initial doses and titrated to maintain a urine pH greater than or equal to 7. The primary endpoint was time to MTX for patients with planned admissions who start MTX upon meeting urine pH and output parameters. Secondary endpoints included incidence of acute kidney injury (AKI) and delayed methotrexate clearance for all patient encounters. AKI was defined using Kidney Disease Improving Global Outcomes criteria. Delayed MTX clearance was defined based on failure to meet goal levels based on published chemotherapy protocols. χ2 analysis was completed on categorical variables. A statistical process control chart (p-chart) depicted time to MTX. Results: A total of 162 patient encounters were included in the analysis. The median age of patients receiving oral bicarb was 51 years (range 21-69) and was 51 years (range 21-63) for patients receiving IV bicarb. Eighty-six encounters were planned admissions that started MTX when urine parameters were met and received either IV (n=32) or PO bicarb (n=54). In these patients median time from admission to MTX was 8.4 vs 7.9 hours, respectively. Figure 1 shows consecutive patients receiving MTX prior to, during, and after resolution of the IV bicarb shortage; there is less variability and fewer outliers in the MTX start time when exclusively administering the PO regimen during the shortage. For the secondary analysis an additional 76 encounters with either unplanned admissions or predetermined MTX start time on subsequent day to admission were analyzed for safety outcomes. The rate of AKI was 14.5% vs 8.9% in the PO vs IV groups, respectively (p=0.28). There was no difference in incidence of delayed methotrexate clearance with 26.5% of patients in PO group vs 25.3% patients in IV group (p=0.87). Length of stay was slightly increased in patients who received PO vs IV alkalization (3.78 vs 3.15 days). Conclusion: Our alternative oral bicarb and acetazolamide urine alkalization regimen appears safe in patients receiving MTX and allowed for continued treatment of patients during a national IV bicarb shortage. Time to start of MTX was decreased with implementation of PO regimen, and there appeared to be a more predictable start time for MTX. While not significant, the higher incidence of AKI in PO group warrants further analysis. Future efforts include using oral outpatient alkalization prior to inpatient admission to work towards improving length of stay. Disclosures No relevant conflicts of interest to declare.

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.

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.

Early Hydration and Alkalinization-Decreased Length of Stay for High-Dose Methotrexate (HDMTX

2002 ◽  
Vol 19 (2) ◽  
pp. 55-55
Author(s):  
Teresa J. Robinson ◽  
Linda Wells ◽  
Teresa Braziel ◽  
Emily Thomas ◽  
D. Luke Holland ◽  
...  
Keyword(s):  
Length Of Stay ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Early Hydration ◽  
Dose Methotrexate

High-Dose Methotrexate and Early Intensification of Therapy Do Not Improve 3 Year EFS in Children and Adolescents with Disseminated Lymphoblastic Lymphoma. Results of the Randomized Arms of COG A5971

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3610-3610 ◽  
Author(s):  
Minnie Abromowitch ◽  
Amanda Termuhlen ◽  
Myron Chang ◽  
Sherrie L. Perkins ◽  
Thomas Gross ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lymphoblastic Leukemia ◽  
Bone Marrow Involvement ◽  
Disease Free Survival ◽  
Lymphoblastic Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Cns Disease ◽  
Dose Methotrexate ◽  
Significant Difference

Abstract The treatment of pediatric lymphoblastic lymphoma (LL) has developed in parallel with treatment strategies for childhood acute lymphoblastic leukemia using a BFM backbone. The excellent results of the NHL/BFM 90 trial prompted us to design this randomized factorial study to determine whether a regimen without high dose methotrexate (HDMTX) the CCG BFM will result in the same outcome as NHL/BFM-90 and whether intensification with anthracycline and cyclophosphamide would further improve disease free survival. From June 2000 to October 2005, 257 patients with Murphy’s Stage III and IV (excluding CNS disease) LL were randomized to one of the four regimens. All regimens used the BFM/NHL95 backbone. The CCG BFM regimen had intrathecal (IT) methotrexate throughout interim maintenance and maintenance without IV methotrexate. The NHL BFM utilized I.V. Methotrexate 5 Gms/m2 and intrathecal MTX every 2 weeks for four doses during interim maintenance without further intrathecal MTX during maintenance. One of each backbone regimens was further intensified with anthracycline and cyclophosphamide early in induction and delayed intensification. The median age was 10.3 years, 195 (76%) were males; 43 (17%) had >5% bone marrow involvement. Twelve patients with CNS disease were not randomized and received intensification and HD HDMTX with delayed CNS radiation (data not reported here). Major toxicities have been related to bone marrow suppression with 4 toxic deaths, 3 due to sepsis and 1 from cerebral hemorrhage. The frequency of grade III/IV neutropenia (alone, with fever or with infection), anemia, and thrombocytopenia were higher in the intensified arms during induction. Three of the four toxic deaths occurred on the intensified arms. The three years EFS of the HDMTX vs. none is 84.5% ± .3.5% vs. 82.7± 3.8 (ρ= 0.93) and the intensification vs. none is 83.4% ±3.7 vs 83.0% ± 3.6 (ρ= 0.66). Therefore, there was no significant difference between treatment arms. These results suggest that neither HDMTX nor early intensification improves EFS in LL. Future direction should focus on identifying biological factors early in therapy so alternative therapies may be investigated.

Combined treatment with high-dose methotrexate and whole brain radiation improves survival in primary central nervous system lymphoma (PCNSL)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18520-18520
Author(s):  
M. A. Abdelsalam ◽  
G. Hussainy ◽  
S. Akhtar ◽  
I. Maghfoor ◽  
A. Elweshi ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Prognostic Factors ◽  
Combined Treatment ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Phase Ii Trials ◽  
Whole Brain ◽  
Cox Regression Analysis ◽  
Dose Methotrexate ◽  
The Impact

18520 Background: Primary CNS lymphoma (PCNSL) is an aggressive primary brain tumor, cranial irradiation alone rarely result in long term disease control or prolonged survival. We analyzed our data for the impact of adding high dose methotrexate (HDMTX) prior to whole brain irradiation (WBI). Methods: All patients with PCNSL diagnosed and managed during 1991–2004 were identified from Oncology Data Unit. Patient’s characteristics, prognostic factors, details of treatment and outcome were reviewed. Sixty-two patients were identified, 10 were excluded (4 had WBI < 40 Gy and 6 had no treatment). Radiation alone was considered curative with a dose ≥ 40 Gy. Combined modality therapy included 3–4 cycles of HDMTX (3gm/m2) followed by WBI Results: 52 patients were analyzed for outcome. 36 had WBI, dose ≥40 Gy, 16 received 3–4 cycle of HDMTX followed by WBI (chemo-radiotherapy (CRT)). Median age was 48.2 years; 42 years in CRT group, 51 years in WBI. Patients characteristics were comparable between two groups except for higher multifocal tumor in CRT group (92% vs. x22%, p=0.029). Median follow is 12.83±6.4 months. Results are shown in Table . HR for event is 0.64 (95% CI was 0.52–0.98) and for death 0.58 (95% CI was 0.48–0.92), both in favor of CRT. Univariate regression analysis using one-way analyses of variance (ANOVA) and multivariate Cox regression analysis for prognostic factors including age (< 60 vs. ≥60), ECOG PS (0–2 vs. 3–4), extent of surgery (biopsy vs. debulking), solitary vs mutifocal tumor and dose of radiation therapy (< 50Gy vs. ≥50Gy) failed to identify any prognostic factor. Conclusions: This retrospective comparison supports other phase II trials results that high dose methotrexate followed by WBI in PCNSL improves outcome. [Table: see text] No significant financial relationships to disclose.

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