The effect of leucovorin rescue therapy on methotrexate-induced oral mucositis in the treatment of paediatric ALL: A systematic review

Beek, Justine N. van der; Oosterom, Natanja; Pieters, Rob; Jonge, Robert de; Heuvel‐Eibrink, MM van den; Heil, SG

doi:10.1016/j.critrevonc.2019.07.003

Cited by 27 publications

(23 citation statements)

References 38 publications

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“…In addition to nephrotoxicity, neurotoxicity, and hepatotoxicity, OM has been the focus of many studies due to morbidity association with secondary infections, induction of parenteral nutrition, interference with planned doses, prolongation of hospitalisation, and worsening quality of life 6,9,14 . However, few studies have evaluated these aspects in the paediatric population 9,13,17‐22 . Here, we evaluated in a paediatric population the association between MTX excretion and hepatic and kidney function changes, in order to better understand factors that may be predictive of the onset of OM.…”

Section: Discussionmentioning

confidence: 99%

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

Valer

Curra

Gabriel

et al. 2020

Int J Paed Dentistry

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Background Oral mucositis (OM) is one of the main adverse effects of the chemotherapeutic agent methotrexate (MTX). Aim To evaluate the relationship of OM with MTX metabolism time and other toxicities in childhood, cancer patients receiving high‐dose of methotrexate (HD‐MTX). Design Seventy‐seven childhood patients receiving HD‐MTX for treatment of leukaemia, osteosarcoma or lymphoma were evaluated. MTX serum level, hepatic and renal function parameters, and presence and intensity of OM were analysed. Results The patients were submitted to 255 cycles of chemotherapy. OM was diagnosed in 191 (74.9%) cycles. Of these, 119 (46.6%) presented ulcerative lesions. Lymphoma was associated with severe OM (P = .01). OM was associated with higher serum levels of aspartate aminotransferase (P = .006), alanine aminotransferase (P = .04) and creatinine (P = .008). Increase of one unit of total bilirubin and indirect bilirubin associated, respectively, with 11% and 39% higher prevalence of OM. For each increase of one unit of creatinine serum level, it was observed a 37% higher prevalence of OM in patients with lymphoma. No association was found between delayed excretion of MTX and OM development. Conclusions OM is a prevalent complication of childhood cancer patients receiving HD‐MTX. Renal and hepatic toxicity could be considered risk factors for OM, especially in patients with lymphoma.

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Section: Discussionmentioning

confidence: 99%

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

Valer

Curra

Gabriel

et al. 2020

Int J Paed Dentistry

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“…We performed measurements in red blood cells, which are expected to reflect RBC folate and MTX-PG levels in other cells. However, red blood cells do not have a nucleus nor mitochondria and therefore no active formation of DNA-or RNA structures [42]. In future studies, it would be of scientific value to determine folate-and MTX-PG levels in leukemic blasts or other nuclear blood cells such as leucocytes.…”

Section: Discussionmentioning

confidence: 99%

The evaluation of red blood cell folate and methotrexate levels during protocol M in childhood acute lymphoblastic leukemia

et al. 2020

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Background After High-Dose Methotrexate (HD-MTX), folinic acid rescue therapy (Leucovorin) is administered to reduce side effects in pediatric acute lymphoblastic leukemia (ALL) patients. Leucovorin and MTX are structural analogues, possibly competing for cellular transport and intracellular metabolism. We hypothesize that Leucovorin accumulates during consecutive courses, which might result in a lower MTX uptake. Methods We prospectively measured red blood cell (RBC) folate and MTX levels during four HD-MTX and Leucovorin courses in 43 patients treated according the DCOG ALL-11 protocol with 2-weekly HD-MTX (5 g/m2/dose) and Leucovorin (15 mg/m2/dose) using LC-MS/MS. We estimated a linear mixed model to assess the relationship between these variables over time. Results Both RBC MTX-PG and folate levels increased significantly during protocol M. MTX-PG2–5 levels increased most substantially after the first two HD-MTX courses (until median 113.0 nmol/L, IQR 76.8–165.2) after which levels plateaued during the 3d and 4th course (until median 141.3 nmol/L, IQR 100.2–190.2). In parallel, folate levels increased most substantially after the first two HD-MTX courses (until median 401.6 nmol/L, IQR 163.3–594.2) after which levels plateaued during the 3d and 4th course (until median 411.5 nmol/L, IQR 240.3–665.6). The ratio folate/MTX-PG decreased significantly over time, which was mostly due to the relatively higher increase (delta) of MTX-PG. Conclusion These results suggest that the increase in RBC folate levels does not seem to have a large effect on RBC MTX levels. Future studies, assessing competition of Leucovorin and MTX on other cellular mechanisms which might negatively affect treatment efficacy, are necessary.

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“…Numerous previous studies have shown that pre-transplantation pretreatment with high-dose methotrexate (HD-MTX) is the main reason for the high incidence of oral mucositis. Therefore, folinic acid diluent is used in different ways to prevent toxicity [9]. Although the use of folinic acid diluent for prophylactic toxicity antagonism has achieved some efficacy, the incidence of OM remains high.…”

Section: Discussionmentioning

confidence: 99%

“…Although the use of folinic acid diluent for prophylactic toxicity antagonism has achieved some efficacy, the incidence of OM remains high. [9] In addition, acute and chronic mucosa-associated GVHD caused by allogeneic graft re-infusion is another important cause of OM [10]. Transfusion of HLA matched or partially matched hematopoietic stem cell results in the short-term release of enormous amounts of interleukin family inflammatory factors and complements a large number of inflammatory mediators' further damage the mucosa, and the numerous side effects of glucocorticoids limit their use in the treatment of OM 15.…”

Section: Discussionmentioning

confidence: 99%

Effect of Recombinant Human Interleukin-11 on Oral Mucositis Associated with Allogeneic Hematopoietic Stem Cell Transplantation

Chen¹,

Ding²,

Luo³

et al. 2020

AJNS

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Background: Hematopoietic stem cell transplantation gives new life to malignant hematologic patient. However, oral mucositis caused by graft-versus-host disease affects the quality of life of patients. Objective: To observe the efficacy of recombinant human interleuko-11 in the treatment of allogeneic hematopoietic stem cell transplantation associated with oral mucositis. Methods: 54 patients requires an allogeneic hematopoietic stem cell transplantation in patients with hematological clinical observation research, the control group was 0.05% acetic acid chloride solution is folinic acid joint and diluent containing wash, the experimental group on the basis of the join recombinant human interleukin-11 atomization and contain gargle, comparing curative effect, the ulcer healing time and pain, anxiety and depression scores, as well as oral infections. Results: the efficacy of recombinant human interleukin-11 treatment group was better than that of control group (X 2 =4.43; P = 0.035); Nebulized inhalation and gargle containing recombinant human interleuk-11 significantly reduced the mean healing days of oral ulcers (Experimenta group A vs. control group C, P=0.05, P=0.004, P=0.000). Experimental group B vs. control group C, P=0.045, P=0.005, P=0.000) and can reduce the occurrence of pain and bad mood. Conclusion: recombinant human interleukin-11 is effective in the treatment of oral mucositis associated with allogeneic hematopoietic stem cell transplantation. It can effectively shorten the course of disease and reduce the incidence of oral infection, anxiety and depression while reducing the pain of patients.

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The effect of leucovorin rescue therapy on methotrexate-induced oral mucositis in the treatment of paediatric ALL: A systematic review

Cited by 27 publications

References 38 publications

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

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

The evaluation of red blood cell folate and methotrexate levels during protocol M in childhood acute lymphoblastic leukemia

Effect of Recombinant Human Interleukin-11 on Oral Mucositis Associated with Allogeneic Hematopoietic Stem Cell Transplantation

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