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)

Low Risk Pediatric Hodgkin Lymphoma

OEPA (GPOD-HD-2002)

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

Regimen

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

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
• Prednisone (Sterapred) 60 mg/m² PO once per day on days 1 to 15
• Doxorubicin (Adriamycin) 40 mg/m² IV once per day on days 1 & 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 verified protocol PubMed NCT00416832

Intermediate Risk Pediatric Hodgkin Lymphoma

ABVE-PC

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

Regimen variant #1, 2 cycles with response adaptation

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

This regimen is intended for pediatric patients, younger than 22 years old. This is the post-amendment dosing described by POG P9425; Friedman et al. 2014 does not contain dosing information.

Chemotherapy

• Doxorubicin (Adriamycin) 30 mg/m² IV once per day on days 0 & 1
• Bleomycin (Blenoxane) 10 units/m² IV or SC once per day on days 0 & 7
• Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2.8 mg) IV once per day on days 0 & 7
• Etoposide (Vepesid) 75 mg/m² IV once per day on days 0 to 4
• Prednisone (Sterapred) 40 mg/m² PO once per day on days 0 to 7
• Cyclophosphamide (Cytoxan) 800 mg/m² IV once on day 0

21-day cycle for 2 cycles

Subsequent treatment

• Rapid early responders: ABVE-PC x 2 (4 cycles total), then IFRT consolidation x 21 Gy versus no further treatment
• Slow early responders: ABVE-PC x 2 (4 cycles total) versus DECA x 2, then ABVE-PC x 2; then IFRT consolidation x 21 Gy

Regimen variant #2, 3 cycles with response adaptation

Study	Evidence
Schwartz et al. 2009 (POG P9425)	Phase II

This regimen is intended for pediatric patients, younger than 22 years old. Note that first day of chemotherapy is day 0. Bleomycin and prednisone dosing is post-amendment.

Chemotherapy

• Doxorubicin (Adriamycin) 30 mg/m² IV once per day on days 0 & 1
• Bleomycin (Blenoxane) 10 units/m² IV or SC once per day on days 0 & 7
• Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2.8 mg) IV once per day on days 0 & 7
• Etoposide (Vepesid) 75 mg/m² IV once per day on days 0 to 4
• Prednisone (Sterapred) 40 mg/m² PO once per day on days 0 to 7
• Cyclophosphamide (Cytoxan) 800 mg/m² IV once on day 0

Supportive medications

• Dexrazoxane (Zinecard) 300 mg/m² IV once per day on days 0, 1, 7 (this was a randomization)
• Filgrastim (Neupogen) 5 mcg/kg IV or SC once per day from day 5 until neutrophil recovery (held on day 7)

21-day cycle for 3 cycles

Subsequent treatment

• Rapid early responders: IFRT consolidation x 21 Gy
• Slow early responders: ABVE-PC x 2 (5 cycles total), then IFRT consolidation x 21 Gy

Regimen variant #3, 4 cycles with response adaptation

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

This regimen is intended for pediatric patients, younger than 22 years old. This is the post-amendment dosing described by POG P9425; Friedman et al. 2014 does not contain dosing information.

Preceding treatment

• ABVE-PC x 2

Chemotherapy

• Doxorubicin (Adriamycin) 30 mg/m² IV once per day on days 0 & 1
• Bleomycin (Blenoxane) 10 units/m² IV or SC once per day on days 0 & 7
• Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2.8 mg) IV once per day on days 0 & 7
• Etoposide (Vepesid) 75 mg/m² IV once per day on days 0 to 4
• Prednisone (Sterapred) 40 mg/m² PO once per day on days 0 to 7
• Cyclophosphamide (Cytoxan) 800 mg/m² IV once on day 0

21-day cycle for 4 cycles, including the first 2 cycles

Subsequent treatment

• Rapid early responders with CR: IFRT consolidation x 21 Gy versus no further treatment
• Rapid early responders with less than CR: IFRT consolidation x 21 Gy
• Slow early responders: IFRT consolidation x 21 Gy

Regimen variant #4, 5 cycles

Study	Evidence
Schwartz et al. 2009 (POG P9425)	Phase II

This regimen is intended for pediatric patients, younger than 22 years old, who are slow early responders. Note that first day of chemotherapy is day 0. Bleomycin and prednisone dosing is post-amendment.

Preceding treatment

• ABVE-PC x 3, with slow early response

Chemotherapy

• Doxorubicin (Adriamycin) 30 mg/m² IV once per day on days 0 & 1
• Bleomycin (Blenoxane) 10 units/m² IV or SC once per day on days 0 & 7
• Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2.8 mg) IV once per day on days 0 & 7
• Etoposide (Vepesid) 75 mg/m² IV once per day on days 0 to 4
• Prednisone (Sterapred) 40 mg/m² PO once per day on days 0 to 7
• Cyclophosphamide (Cytoxan) 800 mg/m² IV once on day 0

Supportive medications

• Dexrazoxane (Zinecard) 300 mg/m² IV once per day on days 0, 1, 7 (this was a randomization)
• Filgrastim (Neupogen) 5 mcg/kg IV or SC once per day from day 5 until neutrophil recovery (held on day 7)

21-day cycle for 5 cycles, including the first 3 cycles

Subsequent treatment

• IFRT consolidation x 21 Gy

References

1. 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 verified protocol link to PMC article PubMed NCT00005578
2. 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 protocol link to PMC article PubMed NCT00025259

Radiation therapy

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RT: Radiation Therapy

Regimen variant #2, 21 Gy of IFRT

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 II
Friedman et al. 2014 (COG AHOD0031)	2002-2009	Phase 3 (C)	Observation	Did not meet primary endpoint of EFS48

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 verified protocol 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 verified protocol 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 protocol link to PMC article PubMed NCT00025259