Non-Hodgkin lymphoma, pediatric

Section editor
	David Noyd, MD, MPH University of Washington Seattle, WA, USA LinkedIn

This page contains studies that were specific to pediatric populations, who are generally treated based on risk-stratification, not on the underlying histology. See individual trials for inclusion criteria.

3 regimens on this page 3 variants on this page

Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

NCCN

• NCCN Guidelines - Pediatric Aggressive Mature B-Cell Lymphomas

Untreated, pre-phase

CVP

CVP: Cyclophosphamide, Vincristine, Prednisone
COP: Cyclophosphamide, Oncovin (Vincristine), Prednisone

Regimen

Study	Dates of enrollment	Evidence
Patte et al. 2007 (FAB/LMB96)	1996-2001	Non-randomized part of phase 3 RCT

Chemotherapy

• Cyclophosphamide (Cytoxan) 300 mg/m² IV once on day 1
• Vincristine (Oncovin) 1 mg/m² IV once on day 1

Glucocorticoid therapy

• Prednisone (Sterapred) 60 mg/m²/day IV or PO on days 1 to 7

CNS therapy, prophylaxis

• Methotrexate (MTX) (dose not specified) IT once on day 1

7-day course

Subsequent treatment

• COPADM induction

References

1. FAB/LMB96: Patte C, Auperin A, Gerrard M, Michon J, Pinkerton R, Sposto R, Weston C, Raphael M, Perkins SL, McCarthy K, Cairo MS; FAB/LMB96 International Study Committee. Results of the randomized international FAB/LMB96 trial for intermediate risk B-cell non-Hodgkin lymphoma in children and adolescents: it is possible to reduce treatment for the early responding patients. Blood. 2007 Apr 1;109(7):2773-80. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00002757

Untreated, induction

COPADM

COPADM: Cyclophosphamide, Oncovin (Vincristine), Prednisone, ADriamycin (Doxorubicin), Methotrexate

Regimen variant #1

Study	Dates of enrollment	Evidence
Patte et al. 2007 (FAB/LMB96)	1996-2001	Non-randomized part of phase 3 RCT

Note: It is not clear from Patte et al. 2007 whether the cyclophosphamide was fractionated.

Preceding treatment

• COP pre-phase

Chemotherapy

• Cyclophosphamide (Cytoxan) 250 mg/m² IV twice per day on days 2 to 4 (total dose: 1500 mg/m²)
• Vincristine (Oncovin) 2 mg/m² IV once on day 1
• Doxorubicin (Adriamycin) 60 mg/m² IV once on day 2
• Methotrexate (MTX) 3000 mg/m² IV over 3 hours once on day 1

Glucocorticoid therapy

• Prednisone (Sterapred) 60 mg/m²/day IV or PO on days 1 to 7

Supportive therapy

• Leucovorin (Folinic acid)

CNS therapy, prophylaxis

• Methotrexate (MTX) (dose not specified) IT once per day on days 2 & 6

One course

Subsequent treatment

• COPADM re-induction; reduced-dose versus COPADM re-induction; standard-dose

Regimen variant #2

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Minard-Colin et al. 2020 (Inter-B-NHL Ritux 2010)	2011-2015	Phase 3 (C)	R-COPADM	Inferior OS

Note: Cycle 2 should start as soon as peripheral blood counts have recovered (ANC approximately 1000/uL and platelets approximately 100 x 10⁹/L), which is usually days 18 to 21. The main difference between this and the above variant is the capped vincristine and the tapering of the steroids.

Preceding treatment

• Inter-B-NHL Ritux 2010, high-risk: COP pre-phase

Chemotherapy

• Cyclophosphamide (Cytoxan) 250 mg/m² IV over 15 minutes every 12 hours on days 2 to 4 (total dose: 1500 mg/m²)
• Vincristine (Oncovin) 2 mg/m² (maximum dose of 2 mg) IV once on day 1
• Doxorubicin (Adriamycin) 60 mg/m² IV over 60 minutes once on day 2
• Methotrexate (MTX) 3000 mg/m² IV over 3 hours once on day 1

Glucocorticoid therapy

• Prednisone (Sterapred) 30 mg/m² PO twice per day on days 1 to 5, then tapered over 3 days

Supportive therapy

• Leucovorin (Folinic acid) 15 mg/m² PO every 6 hours until MTX level less than 0.15, beginning 24 hours after the start of the HD-MTX infusion

CNS therapy, prophylaxis

• Methotrexate (MTX) 8 to 15 mg (dose varies with age) IT once per day on days 2 & 6
• Hydrocortisone (Cortef) 8 to 15 mg (dose varies with age) IT once per day on days 2 & 6

16- to 21-day cycle for 2 cycles (see note)

References

1. FAB/LMB96: Patte C, Auperin A, Gerrard M, Michon J, Pinkerton R, Sposto R, Weston C, Raphael M, Perkins SL, McCarthy K, Cairo MS; FAB/LMB96 International Study Committee. Results of the randomized international FAB/LMB96 trial for intermediate risk B-cell non-Hodgkin lymphoma in children and adolescents: it is possible to reduce treatment for the early responding patients. Blood. 2007 Apr 1;109(7):2773-80. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00002757
2. Inter-B-NHL Ritux 2010: Minard-Colin V, Aupérin A, Pillon M, Burke GAA, Barkauskas DA, Wheatley K, Delgado RF, Alexander S, Uyttebroeck A, Bollard CM, Zsiros J, Csoka M, Kazanowska B, Chiang AK, Miles RR, Wotherspoon A, Adamson PC, Vassal G, Patte C, Gross TG; European Intergroup for Childhood Non-Hodgkin Lymphoma; Children’s Oncology Group. Rituximab for High-Risk, Mature B-Cell Non-Hodgkin's Lymphoma in Children. N Engl J Med. 2020 Jun 4;382(23):2207-2219. link to original article link to PMC article dosing details in supplement have been reviewed by our editors PubMed NCT01516580

R-COPADM

R-COPADM: Rituximab, Cyclophosphamide, Oncovin (Vincristine), Prednisone, ADriamycin (Doxorubicin), Methotrexate

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Minard-Colin et al. 2020 (Inter-B-NHL Ritux 2010)	2011-2015	Phase 3 (E-RT-esc)	COPADM	Superior OS (secondary endpoint) OS36: 95.1% vs 87.3% (HR 0.36, 95% CI 0.16-0.82) Superior EFS (primary endpoint) EFS36: 93.9% vs 82.3% (HR 0.32, 95% CI 0.15-0.66)

Note: Cycle 2 should start as soon as peripheral blood counts have recovered (ANC approximately 1000/uL and platelets approximately 100 x 10⁹/L), which is usually days 18 to 21.

Preceding treatment

• Inter-B-NHL Ritux 2010, high-risk: COP pre-phase

Targeted therapy

• Rituximab (Rituxan) 375 mg/m² IV once per day on days -2 & 1

Chemotherapy

• Cyclophosphamide (Cytoxan) 250 mg/m² IV over 15 minutes every 12 hours on days 2 to 4 (total dose: 1500 mg/m²)
• Vincristine (Oncovin) 2 mg/m² (maximum dose of 2 mg) IV once on day 1
• Doxorubicin (Adriamycin) 60 mg/m² IV over 60 minutes once on day 2
• Methotrexate (MTX) 3000 mg/m² IV over 3 hours once on day 1

Glucocorticoid therapy

• Prednisone (Sterapred) 30 mg/m² PO twice per day on days 1 to 5, then tapered over 3 days

Supportive therapy

• Leucovorin (Folinic acid) 15 mg/m² PO every 6 hours until MTX level less than 0.15, beginning 24 hours after the start of the HD-MTX infusion

CNS therapy, prophylaxis

• Methotrexate (MTX) 8 to 15 mg (dose varies with age) IT once per day on days 2 & 6
• Hydrocortisone (Cortef) 8 to 15 mg (dose varies with age) IT once per day on days 2 & 6

16- to 21-day cycle for 2 cycles (see note)

References

1. Inter-B-NHL Ritux 2010: Minard-Colin V, Aupérin A, Pillon M, Burke GAA, Barkauskas DA, Wheatley K, Delgado RF, Alexander S, Uyttebroeck A, Bollard CM, Zsiros J, Csoka M, Kazanowska B, Chiang AK, Miles RR, Wotherspoon A, Adamson PC, Vassal G, Patte C, Gross TG; European Intergroup for Childhood Non-Hodgkin Lymphoma; Children’s Oncology Group. Rituximab for High-Risk, Mature B-Cell Non-Hodgkin's Lymphoma in Children. N Engl J Med. 2020 Jun 4;382(23):2207-2219. link to original article link to PMC article dosing details in supplement have been reviewed by our editors PubMed NCT01516580