Classical Hodgkin lymphoma, pediatric

Section editor transclusions This page contains studies that were specific to pediatric populations. For the more general Hodgkin lymphoma page, follow this link.

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6 regimens on this page 6 variants on this page

Guidelines

NCCN

• NCCN Guidelines - Hodgkin Lymphoma (Pediatric and AYA)

Upfront Therapy, High Risk

ABVE-PC

ABVE-PC: Adriamycin (Doxorubicin), Bleomycin, Vincristine, Etoposide, Prednisone, Cyclophosphamide

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Castellino et al. 2022 (COG AHOD1331)	2015-2019	Phase 3 (C)	Bv-AVEPC	Inferior EFS

Chemotherapy

• Doxorubicin (Adriamycin) 25 mg/m² IV push or intermittent infusion once per day on days 1 & 2
  • Concentration not to exceed 2 mg/mL
  • IV push over 1 to 5 minutes or by intermittent infusion over 1 to 15 minutes; may prolong to 60 minutes if institutional policies mandate
• Bleomycin (Blenoxane) 5 units/m² IV over 10 to 20 minutes or SC once on day 1, then 10 units/m² IV over 10 to 20 minutes or SC once on day 8
• Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2.8 mg) IV once per day on days 1 & 8
• Etoposide (Vepesid) 125 mg/m² IV over 60 to 120 minutes once per day on days 1 to 3
  • Rate should not exceed 300 mg/m²
• Cyclophosphamide (Cytoxan) 600 mg/m² IV over 30 to 60 minutes once per day on days 1 & 2

Glucocorticoid therapy

• Prednisone (Sterapred) 20 mg/m² PO twice per day on days 1 to 7

Supportive therapy

• Filgrastim (Neupogen) 5 mcg/kg SC (preferred) or IV once per day beginning on day 4, 5, 6, 7, 8, or 9, per institutional policy and continuing until ANC greater than 1000/uL
  • Alternative: Pegfilgrastim (Neulasta) 100 mcg/kg (Maximum dose of 6 mg) SC once on day 4, 5, or 6

21-day cycle for 2 cycles, then response evaluation, then 21-day cycle for 3 cycles

References

1. COG AHOD1331: Castellino SM, Pei Q, Parsons SK, Hodgson D, McCarten K, Horton T, Cho S, Wu Y, Punnett A, Dave H, Henderson TO, Hoppe BS, Charpentier AM, Keller FG, Kelly KM. Brentuximab Vedotin with Chemotherapy in Pediatric High-Risk Hodgkin's Lymphoma. N Engl J Med. 2022 Nov 3;387(18):1649-1660. link to original article PubMed NCT02166463

Bv-AVEPC

Bv-AVEPC: Brentuximab vedotin, Adriamycin (Doxorubicin), Vincristine, Etoposide, Prednisone, Cyclophosphamide

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Castellino et al. 2022 (COG AHOD1331)	2015-2019	Phase 3 (E-switch-ooc)	ABVE-PC	Superior EFS EFS36: 92.1% vs 82.5% (HR 0.41, 95% CI 0.25-0.67)

Antibody-drug conjugate therapy

• Brentuximab vedotin (Adcetris) 1.8 mg/kg (maximum dose of 180 mg) IV over 30 minutes once on day 1, given prior to chemotherapy
  • Do NOT use In Line Filters

Chemotherapy

• Doxorubicin (Adriamycin) 25 mg/m² IV push or intermittent infusion once per day on days 1 & 2
  • Concentration not to exceed 2 mg/mL
  • IV push over 1 to 5 minutes or by intermittent infusion over 1 to 15 minutes; may prolong to 60 minutes if institutional policies mandate
• Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2.8 mg) IV once on day 8
• Etoposide (Vepesid) 125 mg/m² IV over 60 to 120 minutes once per day on days 1 to 3
  • Rate should not exceed 300 mg/m²
• Cyclophosphamide (Cytoxan) 600 mg/m² IV over 30 to 60 minutes once per day on days 1 & 2

Glucocorticoid therapy

• Prednisone (Sterapred) 20 mg/m² PO twice per day on days 1 to 7

Supportive therapy

• Filgrastim (Neupogen) 5 mcg/kg SC (preferred) or IV once per day beginning on day 4, 5, 6, 7, 8, or 9, per institutional policy and continuing until ANC greater than 1000/uL
  • Alternative: Pegfilgrastim (Neulasta) 100 mcg/kg (Maximum dose of 6 mg) SC once on day 4, 5, or 6

21-day cycle for 2 cycles, then response evaluation, then 21-day cycle for 3 cycles

References

1. COG AHOD1331: Castellino SM, Pei Q, Parsons SK, Hodgson D, McCarten K, Horton T, Cho S, Wu Y, Punnett A, Dave H, Henderson TO, Hoppe BS, Charpentier AM, Keller FG, Kelly KM. Brentuximab Vedotin with Chemotherapy in Pediatric High-Risk Hodgkin's Lymphoma. N Engl J Med. 2022 Nov 3;387(18):1649-1660. link to original article PubMed NCT02166463

Upfront Therapy, Intermediate Risk

ABVE-PC

ABVE-PC: Adriamycin (Doxorubicin), Bleomycin, Vincristine, Etoposide, Prednisone, Cyclophosphamide

Regimen

Study	Years of enrollment	Evidence
Friedman et al. 2014 (COG AHOD0031)	2002-2009	Non-randomized portion of phase 3 RCT

Chemotherapy

• Doxorubicin (Adriamycin) 25 mg/m² IV over 10 to 30 minutes once per day on days 1, 2
• Bleomycin (Blenoxane) 5 units/m² IV over 10 to 20 minutes or SC once on day 1, then 10 units/m² IV over 10 to 20 minutes or SC once on day 8
• Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2.8 mg) IV once per day on days 1, 8
• Etoposide (Vepesid) 125 mg/m² IV over 60 minutes once per day on days 1, 2, 3
• Cyclophosphamide (Cytoxan) 800 mg/m² IV over 60 minutes once on day 1

Glucocorticoid therapy

• Prednisone (Sterapred) 40 mg/m²/day PO divided twice per day or three times per day on days 1 to 7

21-day cycle for 2 cycles

Subsequent treatment

• COG AHOD0031, rapid early responders with CR: ABVE-PC x 2, then IFRT versus no further treatment
• COG AHOD0031, rapid early responders with less than CR: ABVE-PC x 2, then IFRT
• COG AHOD0031, slow early responders: ABVE-PC x 2, then IFRT versus DECA x 2, then ABVE-PC x 2, then IFRT

References

1. COG AHOD0031: Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. link to original article does not contain dosing details link to PMC article PubMed NCT00025259

DECA

DECA: Dexamethasone, Etoposide, Cisplatin, Ara-C (Cytarabine)

Regimen

Study	Years of enrollment	Evidence
Friedman et al. 2014 (COG AHOD0031)	2002-2009	Non-randomized portion of phase 3 RCT

Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.

Preceding treatment

• ABVE-PC x 2, with slow early response

Glucocorticoid therapy

• Dexamethasone (Decadron) 10 mg/m² IV over 15 minutes on days 1, 2, given prior to etoposide/cytarabine

Chemotherapy

• Etoposide (Vepesid) 100 mg/m² IV over 3 hours once per day on days 1, 2
  • Mix Etoposide (Vepesid) with Cytarabine (Ara-C) in D5W at an Etoposide (Vepesid) concentration of ≤ 0.4 mg/mL
• Cisplatin (Platinol) 90 mg/m² IV over 6 hours once on day 1
• Cytarabine (Ara-C) 3000 mg/m² IV over 3 hours on days 1, 2
  • Mix Etoposide (Vepesid) with Cytarabine (Ara-C) in D5W at an Etoposide (Vepesid) concentration of ≤ 0.4 mg/mL

21-day cycle for 2 cycles

Subsequent treatment

• ABVE-PC x 2, then IFRT

References

1. COG AHOD0031: Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. link to original article does not contain dosing details link to PMC article PubMed NCT00025259

Upfront Therapy, Low Risk

OEPA (GPOD-HD-2002)

OEPA: Oncovin (Vincristine), Etoposide, Prednisone, Adriamycin (Doxorubicin)

Regimen

Study	Years of enrollment	Evidence
Mauz-Körholz et al. 2010 (GPOH-HD-2002)	2002-2005	Phase 2

Note: This regimen is meant for boys as it is potentially less gonadotoxic. The original protocol used three doses of dacarbazine per cycle but this was increased to four after a mid-protocol amendment. Patients with early-stage disease only received the OEPA portion, see text for details.

Chemotherapy

• Vincristine (Oncovin) 1.5 mg/m² IV once per day on days 1, 8, 15
• Etoposide (Vepesid) 125 mg/m² IV once per day on days 2 to 6
• Doxorubicin (Adriamycin) 40 mg/m² IV once per day on days 1 & 15

Glucocorticoid therapy

• Prednisone (Sterapred) 60 mg/m² PO once per day on days 1 to 15

28-day cycle for 2 cycles

Subsequent treatment

• Treatment group 2: COPDAC x 2
• Treatment group 3: COPDAC x 4

References

1. GPOH-HD-2002: Mauz-Körholz C, Hasenclever D, Dörffel W, Ruschke K, Pelz T, Voigt A, Stiefel M, Winkler M, Vilser C, Dieckmann K, Karlén J, Bergsträsser E, Fosså A, Mann G, Hummel M, Klapper W, Stein H, Vordermark D, Kluge R, Körholz D. Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study. J Clin Oncol. 2010 Aug 10;28(23):3680-6. Epub 2010 Jul 12. link to original article contains dosing details in manuscript PubMed NCT00416832

Consolidation therapy

Radiation therapy

RT: Radiation Therapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Nachman et al. 2002 (CCG 5942)	1995-1998	Phase 3 (C)	Observation	Superior EFS
Schwartz et al. 2009 (POG P9425)	1997-2001	Phase 2
Friedman et al. 2014 (COG AHOD0031)	2002-2009	Phase 3 (C)	Observation	Did not meet primary endpoint of EFS48

Note: This regimen is intended for pediatric patients, younger than 22 years old.

Preceding treatment

• CCG 5942: COPP-ABV hybrid x 4 or 6 or multi-drug therapy, depending on risk stratification
• POG P9425: ABVE-PC x 3 to 5
• COG AHOD0031 RERs: ABVE-PC x 4
• COG AHOD0031 SERs: ABVE-PC x 4 versus ABVE-PC x 2, then DECA x 2, then ABVE-PC x 2

Radiotherapy

• External beam radiotherapy 21 Gy in 12 to 14 fractions of 1.5 to 1.75 Gy per fraction

References

1. CCG 5942: Nachman JB, Sposto R, Herzog P, Gilchrist GS, Wolden SL, Thomson J, Kadin ME, Pattengale P, Davis PC, Hutchinson RJ, White K; Children's Cancer Group. Randomized comparison of low-dose involved-field radiotherapy and no radiotherapy for children with Hodgkin's disease who achieve a complete response to chemotherapy. J Clin Oncol. 2002 Sep 15;20(18):3765-71. link to original article contains dosing details in manuscript PubMed NCT00592111
   1. Update: Wolden SL, Chen L, Kelly KM, Herzog P, Gilchrist GS, Thomson J, Sposto R, Kadin ME, Hutchinson RJ, Nachman J. Long-term results of CCG 5942: a randomized comparison of chemotherapy with and without radiotherapy for children with Hodgkin's lymphoma--a report from the Children's Oncology Group. J Clin Oncol. 2012 Sep 10;30(26):3174-80. Epub 2012 May 29. link to original article link to PMC article PubMed
2. POG P9425: Schwartz CL, Constine LS, Villaluna D, London WB, Hutchison RE, Sposto R, Lipshultz SE, Turner CS, deAlarcon PA, Chauvenet A. A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425. Blood. 2009 Sep 3;114(10):2051-9. Epub 2009 Jul 7. Erratum: in Blood 2016 128:605 link to original article contains dosing details in manuscript link to PMC article PubMed NCT00005578
3. COG AHOD0031: Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. link to original article does not contain dosing details link to PMC article PubMed NCT00025259