High-Dose Methotrexate Usage Without Drug-Level Monitoring in Advanced Pediatric Mature B-Cell Non-Hodgkin Lymphoma in a Resource-Limited Setting in Malawi
PURPOSEExcellent survival for advanced (stages II with high lactate dehydrogenase, III, and IV) pediatric mature B-cell non-Hodgkin lymphoma (MB-NHL) has been achieved with intensive regimens, but adoption in sub-Saharan Africa is limited by inadequate supportive care. We provide real-world data on...
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American Society of Clinical Oncology
2025-04-01
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| Series: | JCO Global Oncology |
| Online Access: | https://ascopubs.org/doi/10.1200/GO-24-00591 |
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| author | Rizine R. Mzikamanda Loviisa Mulanje Casey L. McAtee Apatsa Matatiyo Zoe Mwale Grace Chirwa Watipaso Wanda Atupele Miranda Mpasa Stella Wachepa Minke H.W. Huibers Steve Martin Tamiwe Tomoka Maurice Mulenga Yuri Fedoriw Gugulethu Mapurisa Julie M. Gastier Foster Nader El-Mallawany Katherine D. Westmoreland Peter Wasswa Carl E. Allen Nmazuo Ozuah |
| author_facet | Rizine R. Mzikamanda Loviisa Mulanje Casey L. McAtee Apatsa Matatiyo Zoe Mwale Grace Chirwa Watipaso Wanda Atupele Miranda Mpasa Stella Wachepa Minke H.W. Huibers Steve Martin Tamiwe Tomoka Maurice Mulenga Yuri Fedoriw Gugulethu Mapurisa Julie M. Gastier Foster Nader El-Mallawany Katherine D. Westmoreland Peter Wasswa Carl E. Allen Nmazuo Ozuah |
| author_sort | Rizine R. Mzikamanda |
| collection | DOAJ |
| description | PURPOSEExcellent survival for advanced (stages II with high lactate dehydrogenase, III, and IV) pediatric mature B-cell non-Hodgkin lymphoma (MB-NHL) has been achieved with intensive regimens, but adoption in sub-Saharan Africa is limited by inadequate supportive care. We provide real-world data on treating advanced MB-NHL with high-dose methotrexate (HD-MTX; ≥1,000 mg/m2/cycle) where real-time serum MTX monitoring is unavailable.METHODSWe identified two cohorts—a retrospective (January 2017-December 2020) cohort treated with 1,000 or 3,000 mg/m2/cycle of HD-MTX and a prospective (July 2022-July 2023) cohort—with a modified LMB96 protocol containing 3,000 mg/m2/cycle of HD-MTX. All doses of HD-MTX were given over 3 hours. Estimates of 12-month event-free survival (EFS) and overall survival (OS) were calculated with abandonment as an event. Clinical toxicity data were available for the prospective cohort.RESULTSThe retrospective cohort had 108 patients who received HD-MTX 1,000 mg/m2 (n = 98, 91%) or 3,000 mg/m2 per cycle. The 12-month EFS and OS were 39% (95% CI, 30 to 50) and 54% (95% CI, 44 to 64), respectively. HD-MTX at 3,000 mg/m2 had superior EFS: 69% (95% CI, 49 to 96) versus 33% (95% CI, 24 to 46), P = .004. The prospective cohort had 38 patients. Two ≥grade 3 mucositis, one acute kidney injury, and three treatment-related deaths (8%) occurred. Seven (18%) abandoned treatment. With a median follow-up of 14.5 months, 12-month EFS and OS were 45% (95% CI, 32 to 65) and 59% (95% CI, 45 to 79), respectively. Most relapses were stage IV: EFS 20% versus 51% (non–stage IV; P = .057). Severe malnutrition was associated with OS of 33% versus 58% (normal) or 76% (moderate; P = .055).CONCLUSIONHD-MTX dosed at 3,000 mg/m2/cycle is feasible in low-resource settings where routine MTX monitoring is unavailable. Stage IV disease and severe malnutrition may contribute to poorer outcomes. |
| format | Article |
| id | doaj-art-d92a81218229461bb6f235f4e327b019 |
| institution | DOAJ |
| issn | 2687-8941 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | American Society of Clinical Oncology |
| record_format | Article |
| series | JCO Global Oncology |
| spelling | doaj-art-d92a81218229461bb6f235f4e327b0192025-08-20T03:06:09ZengAmerican Society of Clinical OncologyJCO Global Oncology2687-89412025-04-011110.1200/GO-24-00591High-Dose Methotrexate Usage Without Drug-Level Monitoring in Advanced Pediatric Mature B-Cell Non-Hodgkin Lymphoma in a Resource-Limited Setting in MalawiRizine R. Mzikamanda0Loviisa Mulanje1Casey L. McAtee2Apatsa Matatiyo3Zoe Mwale4Grace Chirwa5Watipaso Wanda6Atupele Miranda Mpasa7Stella Wachepa8Minke H.W. Huibers9Steve Martin10Tamiwe Tomoka11Maurice Mulenga12Yuri Fedoriw13Gugulethu Mapurisa14Julie M. Gastier Foster15Nader El-Mallawany16Katherine D. Westmoreland17Peter Wasswa18Carl E. Allen19Nmazuo Ozuah20Pediatric Hematology-Oncology, Kamuzu Central Hospital, Lilongwe, MalawiDepartment of Epidemiological Methods and Etiological Research, Leibniz Institute of Prevention Research and Epidemiology, Bremen, GermanyDepartment of Pediatrics, Baylor College of Medicine, Houston, TXUniversity of North Carolina Project Malawi, Lilongwe, MalawiBaylor College of Medicine Children's Foundation—Malawi, Lilongwe, MalawiPediatric Hematology-Oncology, Kamuzu Central Hospital, Lilongwe, MalawiPediatric Hematology-Oncology, Kamuzu Central Hospital, Lilongwe, MalawiPediatric Hematology-Oncology, Kamuzu Central Hospital, Lilongwe, MalawiPediatric Hematology-Oncology, Kamuzu Central Hospital, Lilongwe, MalawiPrinces' Maxima Center Pediatric Oncology, Utrecht, the NetherlandsDepartment of Pediatrics, University of South Carolina School of Medicine, Greenville, SCUniversity of North Carolina Project Malawi, Lilongwe, MalawiUniversity of North Carolina Project Malawi, Lilongwe, MalawiUniversity of North Carolina Project Malawi, Lilongwe, MalawiUniversity of North Carolina Project Malawi, Lilongwe, MalawiDepartment of Pediatrics, Baylor College of Medicine, Houston, TXDepartment of Pediatrics, Baylor College of Medicine, Houston, TXUniversity of North Carolina Project Malawi, Lilongwe, MalawiDepartment of Pediatrics, Baylor College of Medicine, Houston, TXDepartment of Pediatrics, Baylor College of Medicine, Houston, TXDepartment of Pediatrics, Baylor College of Medicine, Houston, TXPURPOSEExcellent survival for advanced (stages II with high lactate dehydrogenase, III, and IV) pediatric mature B-cell non-Hodgkin lymphoma (MB-NHL) has been achieved with intensive regimens, but adoption in sub-Saharan Africa is limited by inadequate supportive care. We provide real-world data on treating advanced MB-NHL with high-dose methotrexate (HD-MTX; ≥1,000 mg/m2/cycle) where real-time serum MTX monitoring is unavailable.METHODSWe identified two cohorts—a retrospective (January 2017-December 2020) cohort treated with 1,000 or 3,000 mg/m2/cycle of HD-MTX and a prospective (July 2022-July 2023) cohort—with a modified LMB96 protocol containing 3,000 mg/m2/cycle of HD-MTX. All doses of HD-MTX were given over 3 hours. Estimates of 12-month event-free survival (EFS) and overall survival (OS) were calculated with abandonment as an event. Clinical toxicity data were available for the prospective cohort.RESULTSThe retrospective cohort had 108 patients who received HD-MTX 1,000 mg/m2 (n = 98, 91%) or 3,000 mg/m2 per cycle. The 12-month EFS and OS were 39% (95% CI, 30 to 50) and 54% (95% CI, 44 to 64), respectively. HD-MTX at 3,000 mg/m2 had superior EFS: 69% (95% CI, 49 to 96) versus 33% (95% CI, 24 to 46), P = .004. The prospective cohort had 38 patients. Two ≥grade 3 mucositis, one acute kidney injury, and three treatment-related deaths (8%) occurred. Seven (18%) abandoned treatment. With a median follow-up of 14.5 months, 12-month EFS and OS were 45% (95% CI, 32 to 65) and 59% (95% CI, 45 to 79), respectively. Most relapses were stage IV: EFS 20% versus 51% (non–stage IV; P = .057). Severe malnutrition was associated with OS of 33% versus 58% (normal) or 76% (moderate; P = .055).CONCLUSIONHD-MTX dosed at 3,000 mg/m2/cycle is feasible in low-resource settings where routine MTX monitoring is unavailable. Stage IV disease and severe malnutrition may contribute to poorer outcomes.https://ascopubs.org/doi/10.1200/GO-24-00591 |
| spellingShingle | Rizine R. Mzikamanda Loviisa Mulanje Casey L. McAtee Apatsa Matatiyo Zoe Mwale Grace Chirwa Watipaso Wanda Atupele Miranda Mpasa Stella Wachepa Minke H.W. Huibers Steve Martin Tamiwe Tomoka Maurice Mulenga Yuri Fedoriw Gugulethu Mapurisa Julie M. Gastier Foster Nader El-Mallawany Katherine D. Westmoreland Peter Wasswa Carl E. Allen Nmazuo Ozuah High-Dose Methotrexate Usage Without Drug-Level Monitoring in Advanced Pediatric Mature B-Cell Non-Hodgkin Lymphoma in a Resource-Limited Setting in Malawi JCO Global Oncology |
| title | High-Dose Methotrexate Usage Without Drug-Level Monitoring in Advanced Pediatric Mature B-Cell Non-Hodgkin Lymphoma in a Resource-Limited Setting in Malawi |
| title_full | High-Dose Methotrexate Usage Without Drug-Level Monitoring in Advanced Pediatric Mature B-Cell Non-Hodgkin Lymphoma in a Resource-Limited Setting in Malawi |
| title_fullStr | High-Dose Methotrexate Usage Without Drug-Level Monitoring in Advanced Pediatric Mature B-Cell Non-Hodgkin Lymphoma in a Resource-Limited Setting in Malawi |
| title_full_unstemmed | High-Dose Methotrexate Usage Without Drug-Level Monitoring in Advanced Pediatric Mature B-Cell Non-Hodgkin Lymphoma in a Resource-Limited Setting in Malawi |
| title_short | High-Dose Methotrexate Usage Without Drug-Level Monitoring in Advanced Pediatric Mature B-Cell Non-Hodgkin Lymphoma in a Resource-Limited Setting in Malawi |
| title_sort | high dose methotrexate usage without drug level monitoring in advanced pediatric mature b cell non hodgkin lymphoma in a resource limited setting in malawi |
| url | https://ascopubs.org/doi/10.1200/GO-24-00591 |
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