Renal function features in pediatric acute lymphoblastic leukemia during high-dose methotrexate chemotherapy

Adkhiatul Muslihatin; Mia Ratwita  Andarsini; Andi Cahyadi; Risky Vitria Prasetyo; I Dewa Gede Ugrasena; Maria Christina Shanty Larasanti

doi:10.15562/bmj.v11i3.3890

Renal function features in pediatric acute lymphoblastic leukemia during high-dose methotrexate chemotherapy

Adkhiatul Muslihatin ,

Mia Ratwita Andarsini ,

Andi Cahyadi ,

Risky Vitria Prasetyo ,

I Dewa Gede Ugrasena ,

Maria Christina Shanty Larasanti ,

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DOI: https://doi.org/10.15562/bmj.v11i3.3890 |
Published: 2022-11-18

Abstract

Introduction: High-dose Methotrexate (HD-MTX), a chemotherapy agent for acute lymphoblastic leukemia, is a cytotoxic agent for some organs, including kidneys. One of the most important toxicities due to HD-MTX is acute kidney injury due to Methotrexate crystallization in renal tubules. The prevalence of Acute kidney injury due to HD-MTX administration in pediatric ALL in dr. Soetomo General Hospital was unknown. The study aims to analyze renal function features in pediatric ALL during HD-MTX chemotherapy.

Methods: An analytical observational study with a prospective approach was conducted at Dr. Soetomo General Hospital Surabaya from December 2021 - July 2022. The subjects were ALL children aged 1-18 years who met inclusion and exclusion criteria. High-dose Methotrexate chemotherapy was given 3 times every 2 weeks during the consolidation phase. Laboratory examinations were performed before and after HD-MTX chemotherapy. Laboratory results were recorded to determine the GFR value. The difference test was performed using Wilcoxon signed rank test and the Friedman test with a significance value of p<0.05.

Results: A total of 20 subjects, the median age was 78 months old, and boys and girls were equal. Standard Risk of ALL was in 55% of subjects, and 45% were at high risk. There was no significant difference in laboratory parameters between before and after HD-MTX chemotherapy in all cycles with a p-value >0.05. The median value of GFR in each cycle is 257.5; 243.5; 228.5. Minimal GFR was 119 ml/min/1.73 m^2,and maximum GFR was 638 ml/min/1.73 m². It showed a median value of GFR in all cycles was >175 ml/min/m² (hyperfiltration).

Conclusions: We concluded there was no AKI due to HD-MTX chemotherapy in pediatric ALL. It may be caused by providing adequate hydration, urine alkalinization, and leucovorin rescue.

References

Widiaskara IM, Permono B, Ugrasena IDG, and Ratwita M. Luaran Pengobatan Fase Induksi Pasien Leukemia Limfoblastik Akut pada Anak di Rumah Sakit Umum Dr. Soetomo Surabaya, Sari Pediatri. 2017;12(2):128- 34.
Petrungaro A, Gentile M, Mazzone C, Greco R, Uccello G, Recchia AG. Ponatinib-Induced Graft-versus-Host Disease / Graft-versus-Leukemia Effect in a Patient with Philadelphia-Positive Acute Lymphoblastic Leukemia without the T315I Mutation Relapsing after Allogeneic Transplant. Chemotherapy. 2017;62. p. 353–6.
Moe PJ & Holen A. High-dose methotrexate in childhood all. Pediatric Hematology Oncology. 2000;17(8). pp. 615–22.
Pang HM, Cheng DH, Lu H, Liu T, and Zou XQ. Identification of Risk Factors in High-Dose Methotrexate-Induced Acute Kidney Injury in Childhood Acute Lymphoblastic Leukemia. Chemotherapy. 2018;63(2). pp.100-6.
Widemann BC & Adamson PC. Understanding and Managing Methotrexate Nephrotoxicity. The Oncologist. 2006;11(6). pp. 694–703.
Prasetyo RV, Saraswati PD, Kamaya IS, Sudjito SE, Kurniawan MR, Lestari DP. Incidence And Outcome of Acute Kidney Injury in Critically ill Children at Dr. Soetomo Hospital Surabaya. Bangladesh Journal of Child Health. 2015;38(3). pp. 120–3.
Widemann BC, Balis FM, Bielack BK, Pratt CB, Ferrari S. High-Dose Methotrexate-Induced Nephrotoxicity in Patients with Osteosarcoma. Cancer. 2004;100(10). pp. 2222–32.
Wang C. Monitoring and Treatment of Acute Kidney Injury in Children with Acute Lymphoblastic Leukemia After High Dose Methotrexate Chemotherapy. Iranian Journal of Pharmaceutical Research. 2016. p. 957–61.
Garcia H, Leblond V, Goldwasser F, Bouscary D, Raffoux E, Boissel N. Toxicité rénale du méthotrexate à haute dose. Néphrologie & Thérapeutique. 2018;14. p. S103–13.
Traivaree C, Likasitthananon N, Monsereenusorn C, and Rujkijyanont. The effect of intravenous hydration strategy on plasma methotrexate clearance during intravenous high-dose methotrexate administration in pediatric oncology patients. Cancer Management and Research. 2018;10. pp. 4471–8.
Van der Beek JN. The effect of leucovorin rescue therapy on methotrexate-induced oral mucositis in the treatment of pediatric ALL: A systematic review. Critical Reviews in Oncology/Hematology. 2019;142. pp. 1-8
Utomo FN, Yulistiani, Zairina N, and Permono B. Methotrexate Use Is Safe In Children with Acute Lymphoblastic Leukemia. Folia Medica Indonesiana. 2017;53. pp. 144-51
Wiczer T, Dotson E, Tuten A, Phillips G, Maddocks K. Evaluation of incidence and risk factors for high-dose methotrexate-induced nephrotoxicity. Journal of Oncology Pharmacy Practice. 2016;22(3). pp. 430–6.
Kim Y. Glomerular hyperfiltration and cancer: A nationwide population-based study. Cancer Epidemiology Biomarkers and Prevention. 2020;29(10). pp. 2070–7.
Hjorth L, Wiebe T, and Karpman D. Hyperfiltration evaluated by glomerular filtration rate at diagnosis in children with cancer. Pediatric Blood and Cancer. 2011;56(5). pp. 762–6.
Kwatra NS. Glomerular hyperfiltration in children with cancer: prevalence and a hypothesis. Pediatric Radiology. 2017;47(2). pp. 221–6.

[1] Widiaskara IM, Permono B, Ugrasena IDG, and Ratwita M. Luaran Pengobatan Fase Induksi Pasien Leukemia Limfoblastik Akut pada Anak di Rumah Sakit Umum Dr. Soetomo Surabaya, Sari Pediatri. 2017;12(2):128- 34.

[2] Petrungaro A, Gentile M, Mazzone C, Greco R, Uccello G, Recchia AG. Ponatinib-Induced Graft-versus-Host Disease / Graft-versus-Leukemia Effect in a Patient with Philadelphia-Positive Acute Lymphoblastic Leukemia without the T315I Mutation Relapsing after Allogeneic Transplant. Chemotherapy. 2017;62. p. 353–6.

[3] Moe PJ & Holen A. High-dose methotrexate in childhood all. Pediatric Hematology Oncology. 2000;17(8). pp. 615–22.

[4] Pang HM, Cheng DH, Lu H, Liu T, and Zou XQ. Identification of Risk Factors in High-Dose Methotrexate-Induced Acute Kidney Injury in Childhood Acute Lymphoblastic Leukemia. Chemotherapy. 2018;63(2). pp.100-6.

[5] Widemann BC & Adamson PC. Understanding and Managing Methotrexate Nephrotoxicity. The Oncologist. 2006;11(6). pp. 694–703.

[6] Prasetyo RV, Saraswati PD, Kamaya IS, Sudjito SE, Kurniawan MR, Lestari DP. Incidence And Outcome of Acute Kidney Injury in Critically ill Children at Dr. Soetomo Hospital Surabaya. Bangladesh Journal of Child Health. 2015;38(3). pp. 120–3.

[7] Widemann BC, Balis FM, Bielack BK, Pratt CB, Ferrari S. High-Dose Methotrexate-Induced Nephrotoxicity in Patients with Osteosarcoma. Cancer. 2004;100(10). pp. 2222–32.

[8] Wang C. Monitoring and Treatment of Acute Kidney Injury in Children with Acute Lymphoblastic Leukemia After High Dose Methotrexate Chemotherapy. Iranian Journal of Pharmaceutical Research. 2016. p. 957–61.

[9] Garcia H, Leblond V, Goldwasser F, Bouscary D, Raffoux E, Boissel N. Toxicité rénale du méthotrexate à haute dose. Néphrologie & Thérapeutique. 2018;14. p. S103–13.

[10] Traivaree C, Likasitthananon N, Monsereenusorn C, and Rujkijyanont. The effect of intravenous hydration strategy on plasma methotrexate clearance during intravenous high-dose methotrexate administration in pediatric oncology patients. Cancer Management and Research. 2018;10. pp. 4471–8.

[11] Van der Beek JN. The effect of leucovorin rescue therapy on methotrexate-induced oral mucositis in the treatment of pediatric ALL: A systematic review. Critical Reviews in Oncology/Hematology. 2019;142. pp. 1-8

[12] Utomo FN, Yulistiani, Zairina N, and Permono B. Methotrexate Use Is Safe In Children with Acute Lymphoblastic Leukemia. Folia Medica Indonesiana. 2017;53. pp. 144-51

[13] Wiczer T, Dotson E, Tuten A, Phillips G, Maddocks K. Evaluation of incidence and risk factors for high-dose methotrexate-induced nephrotoxicity. Journal of Oncology Pharmacy Practice. 2016;22(3). pp. 430–6.

[14] Kim Y. Glomerular hyperfiltration and cancer: A nationwide population-based study. Cancer Epidemiology Biomarkers and Prevention. 2020;29(10). pp. 2070–7.

[15] Hjorth L, Wiebe T, and Karpman D. Hyperfiltration evaluated by glomerular filtration rate at diagnosis in children with cancer. Pediatric Blood and Cancer. 2011;56(5). pp. 762–6.

[16] Kwatra NS. Glomerular hyperfiltration in children with cancer: prevalence and a hypothesis. Pediatric Radiology. 2017;47(2). pp. 221–6.

Renal function features in pediatric acute lymphoblastic leukemia during high-dose methotrexate chemotherapy

Abstract

References

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