Classical Hodgkin lymphoma, pediatric
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Section editor | |
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David Noyd, MD, MPH University of Washington Seattle, WA, USA |
Last updated on 2024-07-23: 6 regimens on this page
6 variants on this page
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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.
Upfront therapy, high-risk
ABVE-PC
ABVE-PC: Adriamycin (Doxorubicin), Bleomycin, Vincristine, Etoposide, Prednisone, Cyclophosphamide
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Castellino et al. 2022 (COG AHOD1331) | 2015-2019 | Phase 3 (C) | Bv-AVEPC | Inferior EFS |
Note: response evaluation occurs after the first 2 cycles.
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/μL
- Alternative: Pegfilgrastim (Neulasta) 100 mcg/kg (Maximum dose of 6 mg) SC once on day 4, 5, or 6
21-day cycle for 5 cycles
References
- 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 link to PMC article PubMed NCT02166463
Bv-AVEPC
Bv-AVEPC: Brentuximab vedotin, Adriamycin (Doxorubicin), Vincristine, Etoposide, Prednisone, Cyclophosphamide
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Castellino et al. 2022 (COG AHOD1331) | 2015-2019 | Phase 3 (E-RT-switch-ooc) | ABVE-PC | Superior EFS (primary endpoint) EFS36: 92.1% vs 82.5% (HR 0.41, 95% CI 0.25-0.67) |
Note: response evaluation occurs after the first 2 cycles.
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/μL
- Alternative: Pegfilgrastim (Neulasta) 100 mcg/kg (Maximum dose of 6 mg) SC once on day 4, 5, or 6
21-day cycle for 5 cycles
References
- 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 link to PMC article PubMed NCT02166463
Upfront therapy, intermediate-risk
ABVE-PC
ABVE-PC: Adriamycin (Doxorubicin), Bleomycin, Vincristine, Etoposide, Prednisone, Cyclophosphamide
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Friedman et al. 2014 (COG AHOD0031) | 2002-2009 | Non-randomized part 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 continuation x 2, then IFRT consolidation versus no further treatment
- COG AHOD0031, rapid early responders with less than CR: ABVE-PC continuation x 2, then IFRT consolidation
- COG AHOD0031, slow early responders: ABVE-PC continuation x 2 followed by IFRT consolidation versus DECA salvage x 2 followed by ABVE-PC continuation x 2 followed by IFRT consolidation
References
- 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 | Dates of enrollment | Evidence |
---|---|---|
Friedman et al. 2014 (COG AHOD0031) | 2002-2009 | Non-randomized part 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
- Induction 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 with cytarabine in D5W at an etoposide concentration of at most 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
21-day cycle for 2 cycles
References
- 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
OEPA: Oncovin (Vincristine), Etoposide, Prednisone, Adriamycin (Doxorubicin)
Regimen
Study | Dates 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
References
- 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 dosing details in manuscript have been reviewed by our editors PubMed NCT00416832
Consolidation after upfront therapy
Radiation therapy
RT: Radiation Therapy
Regimen
Study | Dates 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: Induction COPP-ABV hybrid x 4 or 6 or multi-drug therapy, depending on risk stratification
- POG P9425: Induction ABVE-PC x 3 to 5
- COG AHOD0031, rapid early responders: Induction ABVE-PC x 4
- COG AHOD0031, slow early responders: Induction ABVE-PC x 4 versus induction ABVE-PC x 2 followed by salvage DECA x 2 followed by ABVE-PC continuation x 2
Radiotherapy
- External beam radiotherapy 2100 cGy in 12 to 14 fractions of 150 to 175 cGy per fraction
References
- 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 dosing details in manuscript have been reviewed by our editors PubMed NCT00592111
- 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
- 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 dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00005578
- 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