Can high-dose methotrexate be safely administered to outpatients?

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 34-34
Author(s):  
Briana Genge ◽  
Tricia Carasco ◽  
Leslie Young ◽  
Leigha Laporte ◽  
Tara D. Baetz
Keyword(s):  
Cohort Analysis ◽  
B Cell Lymphoma ◽  
Control Group ◽  
High Dose ◽  
Inpatient Setting ◽  
High Dose Methotrexate ◽  
Cns Prophylaxis ◽  
Dose Methotrexate ◽  
Significant Toxicity ◽  
Significant Difference

34 Background: High-dose methotrexate (HD-MTX) is administered as prophylaxis for central nervous system (CNS) relapse in Diffuse Large B Cell Lymphoma (DLBCL). It is traditionally administered in an inpatient setting due to its complex supportive care regimen. We developed an outpatient protocol and evaluated the safety of this approach. Methods: In 2019 a multidisciplinary team at Kingston Health Sciences Centre developed an outpatient HD-MTX protocol for CNS prophylaxis in DLBCL. Select eligible patients received their HD-MTX infusion in the day unit and returned daily for bloodwork and monitoring. Leucovorin and continuous intravenous hydration were administered via ambulatory infusion pumps. A single centre retrospective cohort analysis was conducted on all patients who received outpatient HD-MTX. These patients were compared to a historical control group who underwent inpatient HD-MTX and who would have met outpatient eligibility criteria. To evaluate the safety of the outpatient protocol we compared the risk of significant toxicity, defined as an elevation in serum creatinine or oral mucositis of grade III or higher, or development of febrile neutropenia. We also evaluated the time to MTX serum clearance, patient admissions and delays of subsequent chemotherapy cycles. Results: From June 2017 to March 2021, 6 outpatients undergoing 14 HD-MTX cycles and 13 inpatients undergoing 28 cycles were evaluated. Significant toxicity occurred in one outpatient cycle compared to five inpatient cycles (7.1% vs 17.9%, p = 0.79). Average time to MTX clearance was 4.1 days for outpatients and 3.5 days for inpatients (p = 0.013). Only one outpatient was admitted to hospital, resulting in an average length of hospital stay of 0.5 days for outpatients compared to 4.96 days for inpatients. There was no significant difference in the need to delay a subsequent cycle of chemotherapy. Conclusions: Outpatient administration of HD-MTX can be administered safely and effectively as CNS prophylaxis in select patients with DLBCL.[Table: see text]

Timing of high dose methotrexate CNS prophylaxis in DLBCL: a multicenter international analysis of 1,384 patients

Blood ◽  
2022 ◽  
Author(s):  
Matthew R. Wilson ◽  
Toby Andrew Eyre ◽  
Amy A Kirkwood ◽  
Nicole Wong Doo ◽  
Carole Soussain ◽  
...  
Keyword(s):  
High Risk ◽  
International Prognostic Index ◽  
Multivariable Analysis ◽  
B Cell Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Cns Prophylaxis ◽  
Dose Methotrexate ◽  
Cns Relapse ◽  
Increased Risk

Prophylactic high-dose methotrexate (HD-MTX) is often used for diffuse large B-cell lymphoma (DLBCL) patients at high risk of central nervous system (CNS) relapse, despite limited evidence demonstrating efficacy or the optimal delivery method. We conducted a retrospective, international analysis of 1,384 patients receiving HD-MTX CNS prophylaxis either intercalated (i-HD-MTX) (n=749) or at the end (n=635) of R-CHOP/R-CHOP-like therapy (EOT). There were 78 CNS relapses (3-year rate 5.7%), with no difference between i-HD-MTX and EOT; 5.7% vs 5.8%, p=0.98, 3-year difference: 0.04% (-2.0% to 3.1%). Conclusions were unchanged on adjusting for baseline prognostic factors or on 6-month landmark analysis (n=1,253). In patients with high CNS international prognostic index (n=600), 3-year CNS relapse rate was 9.1% with no difference between i-HD-MTX and EOT. On multivariable analysis, increasing age and renal/adrenal involvement were the only independent risk factors for CNS relapse. Concurrent intrathecal prophylaxis was not associated with reduction in CNS relapse. R-CHOP delays of ≥7 days were significantly increased with i-HD-MTX versus EOT, with 308/1573 (19.6%) i-HD-MTX treatments resulting in delay to subsequent R-CHOP (median 8 days). Increased risk of delay occurred in older patients when delivery was later than day 10 in the R-CHOP cycle. In summary, we found no evidence that EOT delivery increases CNS relapse risk versus i-HD-MTX. Findings in high-risk subgroups were unchanged. Rates of CNS relapse in this HD-MTX-treated cohort were similar to comparable cohorts receiving infrequent CNS prophylaxis. If HD-MTX is still considered for certain high-risk patients, delivery could be deferred until R-CHOP completion.

scholarly journals Timing of high-dose methotrexate CNS prophylaxis in DLBCL: an analysis of toxicity and impact on R-CHOP delivery

2020 ◽  
Vol 4 (15) ◽  
pp. 3586-3593
Author(s):  
Matthew R. Wilson ◽  
Toby A. Eyre ◽  
Nicolas Martinez-Calle ◽  
Matthew Ahearne ◽  
Katrina E. Parsons ◽  
...  
Keyword(s):  
International Prognostic Index ◽  
Multivariable Analysis ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
End Points ◽  
Cns Prophylaxis ◽  
Dose Methotrexate ◽  
Cns Relapse

Abstract High-dose methotrexate (HD-MTX) is increasingly used as prophylaxis for patients with diffuse large B-cell lymphoma (DLBCL) at high risk of central nervous system (CNS) relapse. However, there is limited evidence to guide whether to intercalate HD-MTX (i-HD-MTX) between R-CHOP-21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone given at 21-day intervals) or to give it at the end of treatment (EOT) with R-CHOP-21. We conducted a retrospective, multicenter analysis of 334 patients with DLBCL who received CNS prophylaxis with i-HD-MTX (n = 204) or EOT HD-MTX (n = 130). Primary end points were R-CHOP delay rates and HD-MTX toxicity. Secondary end points were CNS relapse rate, progression-free survival, and overall survival. The EOT group had more patients with a high CNS international prognostic index (58% vs 39%; P < .001) and more concurrent intrathecal prophylaxis (56% vs 34%; P < .001). Of the 409 cycles of i-HD-MTX given, 82 (20%) were associated with a delay of next R-CHOP (median, 7 days). Delays were significantly increased when i-HD-MTX was given after day 9 post–R-CHOP (26% vs 16%; P = .01). On multivariable analysis, i-HD-MTX was independently associated with increased R-CHOP delays. Increased mucositis, febrile neutropenia, and longer median inpatient stay were recorded with i-HD-MTX delivery. Three-year cumulative CNS relapse incidence was 5.9%, with no differences between groups. There was no difference in survival between groups. We report increased toxicity and R-CHOP delay with i-HD-MTX compared with EOT delivery but no difference in CNS relapse or survival. Decisions on HD-MTX timing should be individualized and, where i-HD-MTX is favored, we recommend scheduling before day 10 of R-CHOP cycles.

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.

scholarly journals P0008CASE REPORT: METABOLIC ALKALOSIS RESULTING IN RESPIRATORY COMPROMISE IN A PATIENT UNDERGOING HIGH DOSE METHOTREXATE THERAPY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Darragh O'Donoghue ◽  
Heather Truong ◽  
Heidi Finnes ◽  
Jennifer McDonald ◽  
Nelson Leung
Keyword(s):  
Metabolic Alkalosis ◽  
B Cell Lymphoma ◽  
Methotrexate Therapy ◽  
High Dose ◽  
Close Monitoring ◽  
High Dose Methotrexate ◽  
Respiratory Compromise ◽  
Dose Methotrexate ◽  
Adequate Hydration ◽  
Bicarbonate Infusion

Abstract Background and Aims High dose Methotrexate (HDMTX) is an important component of several modern oncological/haematological treatment protocols due to its central nervous system penetrance. Nephrotoxicity represents a significant adverse effect and can limit therapeutic options. Therefore, strategies to prevent this are paramount. Urinary alkalinisation and large volume resuscitation to maintain adequate hydration and urine output are the typical strategies. Urinary alkalinisation prevents tubular precipitation of methotrexate and therefore, a strict urinary pH target of 7 is maintained via a continuous bicarbonate infusion. Method We describe a case report, of Iatrogenic metabolic alkalosis leading to respiratory compromise in a patient receiving HDMTX from Mayo Clinic, Rochester. Results We present the case of a 76-year-old woman with a Diffuse Large B-Cell Lymphoma with CNS involvement who presented for elective admission for her 1st cycle of HDMTX. She received 7g of Methotrexate at dosing of 8 g/m2. She received the standard urinary alkalinisation with pre- and post-hydration. Her baseline HCO3- was 28 mEq/L. Her 48 hour MTX level was elevated at 1.2 so the urinary alkalinisation protocol was continued until &lt;0.1 mcmol/L. On day 4, she developed frequent episodes of apnoea. Her ABG demonstrated a metabolic alkalaemia pH 7.54, pCO 53, pO2 91, HCO3 45. She was transferred to the ICU for close monitoring. Her bicarbonate infusion was discontinued and she received acetazolamide. Her bicarbonate improved to 31 after 12 hours. She had a significant improvement in her respiratory status with no further episodes of apnoea. Her bicarbonate infusion was restarted due to elevated MTX levels. She was discharged home with no further complications. Conclusion Iatrogenic Metabolic alkalosis leading to respiratory compromise represents a rare but important complication of urinary alkalinsation protocols for High-dose Methotrexate therapy.

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.

Osteogenic sarcoma: alterations in the pattern of pulmonary metastases with adjuvant chemotherapy.

1983 ◽  
Vol 1 (4) ◽  
pp. 251-254 ◽  
Author(s):  
N Jaffe ◽  
E Smith ◽  
H T Abelson ◽  
E Frei
Keyword(s):  
Adjuvant Chemotherapy ◽  
Median Time ◽  
Pulmonary Metastases ◽  
Osteogenic Sarcoma ◽  
Median Number ◽  
Control Group ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Age And Sex

The number and time to appearance of pulmonary metastases were evaluated in 15 patients with osteogenic sarcoma receiving adjuvant chemotherapy with high-dose methotrexate and doxorubicin (adjuvant group). The results were compared to 33 age- and sex-matched controls (control group). The adjuvant group demonstrated a reduction in the number and a delay in the appearance of the metastases. The median time to development of metastases was 17 mo in the adjuvant group and 7 mo in the control group, and the median number of metastases was 2 and 12, respectively.

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