Use of Palifermin for the Prevention of High-Dose Methotrexate-Induced Oral Mucositis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4445-4445
Author(s):  
Eva Schmidt ◽  
Nils H. Thoennissen ◽  
Annika Rudat ◽  
Ralf Bieker ◽  
Christoph Schliemann ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Oral Mucositis ◽  
Wilcoxon Test ◽  
Clinical Activity ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Who Grade ◽  
Dose Methotrexate ◽  
Grade Iii

Abstract Oral mucositis is a frequent problem in high-dose methotrexate (HD-MTX) based chemotherapy, impairing the patient’s quality of life, leading to higher rates of infections and delaying subsequent chemotherapy. Numerous substances have been used to prevent or treat oral mucositis, but none of them has proven clinical benefit. Palifermin, a recombinant human keratinocyte growth factor, can lead to a prevention of oral mucositis by different effects. Clinical activity of palifermin has been proven in a controlled randomized study with patients undergoing high-dose therapy with autologous stem cell rescue. The purpose of this report is to describe the effect of palifermin in patients treated within the GMALL-B-ALL 2002 protocol containing HD-MTX who developed a severe mucositis in cycles A1 or B1. Ten patients who were treated within this protocol developed a severe WHO grade III–IV oral mucositis in cycles A1 or B1. Before and after the subsequent similar or identical cycles A2 or B2 palifermin was given to reduce the risk of mucositis. Thus, patients serve as their own control for efficacy of palifermin. All ten patients developed a grade III–IV mucositis in cycles A1 or B1 without palifermin, whereas only 2/10 developed a grade III–IV mucositis in corresponding cycles A2 or B2 with palifermin (Mann-Whitney-Wilcoxon-test p < 0.05). Five patients were treated with a lower palifermin dose than recommended. Also these patients did not develop a higher grade mucositis. Only 4/10 patients showed infections in the cycles with palifermin compared to 10/10 patients without palifermin. The duration of mucositits in patients who aquired a higher-grade (III, IV) mucositis despite treatment with palifermin could be reduced from 12.9 days (median) without to 10.4 days with palifermin. In conclusion, palifermin can significantly reduce the incidence and severeness of oral mucositis and may influence clinical sequelae such as infection and quality of life.

scholarly journals Letting Kids Be Kids: A Quality Improvement Project to Deliver Supportive Care at Home After High-Dose Methotrexate in Pediatric Patients With Acute Lymphoblastic Leukemia

2020 ◽  
Vol 37 (3) ◽  
pp. 212-220 ◽  
Author(s):  
Lori Ranney ◽  
Mary C. Hooke ◽  
Kathryn Robbins
Keyword(s):  
Quality Of Life ◽  
Quality Improvement ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Supportive Care ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate

The Children’s Oncology Group recommends children with high-risk acute lymphoblastic leukemia (ALL) receive high-dose methotrexate (HD MTX) throughout treatment. Historically, patients have been hospitalized for at least 54 hours for HD MTX. Literature supports the safety and efficacy of the transition of supportive care interventions of intravenous (IV) fluids and leucovorin to ambulatory care. The goal of this quality improvement (QI) project was to implement a system to support the safe delivery of supportive care in the home after inpatient HD MTX in children with high-risk ALL. An interdisciplinary team implemented system changes including an ambulatory supportive care protocol, standard computerized order sets, family education, and education of staff in the inpatient, outpatient, and home care setting. Measurements included laboratory results of renal function and medication clearance, length of hospitalization, and family-reported quality of life. During project implementation, 10 patients completed a total of 38 cycles. The system safely and effectively supported transition to the outpatient setting for all patients. Average length of stay was decreased by 37.8 hours per HD MTX cycle. Families reported that quality of life improved in most domains with family time and sleep having largest improvement, while level of stress remained the same. Ambulatory monitoring post-HD MTX requires a multidisciplinary approach to meet individualized patient needs. Future QI efforts should consider outpatient administration of HD MTX in addition to supportive care as a means to improved quality of life.

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.

Treatment of osteosarcoma of the extremities with the T-10 protocol, with emphasis on the effects of preoperative chemotherapy with single-agent high-dose methotrexate: a Scandinavian Sarcoma Group study.

1991 ◽  
Vol 9 (10) ◽  
pp. 1766-1775 ◽  
Author(s):  
G Saeter ◽  
T A Alvegård ◽  
I Elomaa ◽  
A E Stenwig ◽  
T Holmström ◽  
...  
Keyword(s):  
Preoperative Chemotherapy ◽  
Single Agent ◽  
High Dose ◽  
Preoperative Treatment ◽  
High Dose Methotrexate ◽  
Histologic Response ◽  
Dose Methotrexate ◽  
High Grade Osteosarcoma ◽  
The Individual ◽  
Grade Iii

From 1982 to 1989, 97 patients with extremity-localized, high-grade osteosarcoma were treated according to the T-10 protocol. Two thirds of the patients consisted of the near-complete national patient materials from Norway and Finland. Eighty patients (82%) received four courses of high-dose methotrexate (HD MTX, 8 to 12 g/m2) at weekly intervals as their only preoperative treatment, and 77 patients (79%) were assessable for histologic response grading according to Rosen et al (Cancer 49:1221-1230, 1991). Observed histologic response was no certain chemotherapy effect (grade I) in 21%, grade II effect in 62%, and grade III or IV effect in 17%. Nonresponders had significantly lower serum MTX concentrations after 24 and 48 hours than responders; the significance of the difference at 48 hours was maintained in a multivariate analysis. After a median follow-up of 45 months, projected 5-year overall and relapse-free survival for all patients were 64% and 54%, respectively. Patients with a good response to preoperative chemotherapy (grade III/IV) had a significantly better survival than grade I/II responders, despite a switch to postoperative cisplatin/doxorubicin chemotherapy in the latter group. These results were obtained in a largely nonselected group of patients. We conclude that a good initial chemotherapy effect is important for the final outcome in osteosarcoma, and that HD MTX alone is insufficient preoperative treatment for the majority of patients. The individual MTX excretion rate is of importance for tumor response, suggesting a dose-response relationship for HD MTX treatment.

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 &gt; 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 &lt; 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.

Oral mucositis in childhood cancer patients receiving high‐dose methotrexate: Prevalence, relationship with other toxicities and methotrexate elimination

2020 ◽  
Author(s):  
Jéssica Berté Valer ◽  
Marina Curra ◽  
Amanda de Farias Gabriel ◽  
Tuany Rafaeli Schmidt ◽  
Maria Beatriz Cardoso Ferreira ◽  
...  
Keyword(s):  
Childhood Cancer ◽  
Cancer Patients ◽  
Oral Mucositis ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate

scholarly journals Ambulatory high-dose methotrexate administration as central nervous system prophylaxis in patients with aggressive lymphoma

2021 ◽  
Author(s):  
S. Bernard ◽  
L. Hachon ◽  
J. F. Diasonama ◽  
C. Madaoui ◽  
L. Aguinaga ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Renal Toxicity ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Outpatient Basis ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Grade Iii

AbstractHigh-dose methotrexate (HD-MTX) at 3 g/m2 is one of the strategies for central nervous system (CNS) prophylaxis in the first-line treatment of aggressive lymphomas, especially in diffuse large B cell lymphoma patients with high-risk CNS-International Prognostic Index. The objective of our study was to retrospectively analyze the safety of 2 cycles of systemic HD-MTX administered as an ambulatory regimen. Between January 2013 and December 2016, 103 patients were carefully selected on 6 criteria, including age < 60, albumin > 34, performance status 0 or 1, normal renal and hepatic functions, good understanding of practical medical guidance, and no loss of weight. Strict procedures of HD-MTX infusion were observed including alkalinization, urine pH monitoring, and leucovorin rescue. Renal and hepatic functions were monitored at days 2 and 7. MTX clearance was not monitored. Toxicities and grades of toxicity were collected according to the NCI-CTCAE (version 4.0). Among the 103 selected patients, 92 (89%) patients successfully completed the planned 2 cycles of HD-MTX on an outpatient basis. Eleven patients completed only 1 cycle, 3 because of lymphoma progression and 8 because of toxicity including 3 grade II hepatotoxicity, 2 grade I/II renal toxicity, 1 grade III neutropenia, 1 active herpetic infection, and 1 grade III ileus reflex. Reported adverse events (AE) included 92 (84%) grade I/II and 18 (16%) grade III/IV. Grade III hepatotoxicity, mostly cytolysis, was the most frequent AE observed with 8 (8%) events. Grade III/IV hematologic toxicities concerned 9 patients with 8 grade III/IV neutropenia and 1 thrombocytopenia. Renal toxicity was rare, mild, and transient, observed with 4 (4%) grade I/II events. Ambulatory administration of HD-MTX at 3 g/m2 without MTX clearance monitoring is safe with strict medical guidance. It requires careful selection of patients before administration, and a renal and hepatic monitoring after the administration.

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