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

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

Are you looking for a regimen but can't find it here? It is possible that we've moved it to the historical regimens page. For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it.

6 regimens on this page 6 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 Hodgkin Lymphoma

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

Subsequent treatment

ABVE-PC continuation x 2, then 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

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

Subsequent treatment

GPOH-HD-2002, treatment group 2: COPDAC consolidation x 2
GPOH-HD-2002, treatment group 3: COPDAC consolidation x 4

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 contains dosing details in manuscript 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 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
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
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

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+<span id="BackToTop"></span>
-!colspan="2" align="center" style="color:white; font-size:125%; background-color:#4a1486"|'''Section editor'''
+<div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px">
-|-
+[[#top|Back to Top]]
-|style="background-color:#F0F0F0"|[[File:Liang.jpg|frameless|upright=0.3|center]]
+</div>
-|<big>[[User:Wayneliang|Wayne H. Liang, MD, MS, FAMIA]]<br>UAB<br>Birmingham, AL</big><br>[https://www.linkedin.com/in/wayneliang/ LinkedIn]<br>[[File:Social-twitter-icon.png|frameless|upright=0.1]] [https://twitter.com/WayneLiangMD WayneLiangMD]
+{{#lst:Editorial board transclusions|peds}}
-|-
+<big>''This page contains studies that were specific to pediatric populations. For the more general Hodgkin lymphoma page, follow [[Classical Hodgkin lymphoma|this link]].</big><br><br>
-|}
+''Are you looking for a regimen but can't find it here? It is possible that we've moved it to the [[Classical Hodgkin lymphoma, pediatric - historical|historical regimens page]]. For placebo or observational studies in this condition, please visit [[Classical Hodgkin lymphoma - null regimens|this page]]. If you still can't find it, please let us know so we can add it.''<br>
-<big>''This page contains studies that were specific to pediatric populations. For the more general Hodgkin lymphoma page, follow [[Hodgkin lymphoma|this link]].</big>
 {| class="wikitable" style="float:right; margin-right: 5px;"
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 <div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 |}
-{{TOC limit|limit=3}}
+{{TOC limit|limit=4}}
 =Guidelines=
-==[https://www.nccn.org/ NCCN]==
+'''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.'''
-*[https://www.nccn.org/professionals/physician_gls/pdf/ped_hodgkin.pdf NCCN Guidelines - Hodgkin Lymphoma (Pediatric and AYA)]
+==NCCN==
+*[https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1498 NCCN Guidelines - Pediatric Hodgkin Lymphoma]
-=Untreated, induction=
-==OEPA {{#subobject:0e614f|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-OEPA: '''<u>O</u>'''ncovin (Vincristine), '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>A</u>'''driamycin (Doxorubicin)
-===Regimen {{#subobject:25c262|Variant=1}}===
-{| class="wikitable sortable" style="width: 75%; text-align:center;"
-!style="width: 33%"|Study
-!style="width: 33%"|Years of enrollment
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://doi.org/10.1200/jco.2009.26.9381 Mauz-Körholz et al. 2010 (GPOH-HD-2002)]
-|2002-2005
-| style="background-color:#91cf61" |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/m<sup>2</sup> IV once per day on days 1, 8, 15
-*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV once per day on days 2 to 6
-*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 15
-*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 15
-'''28-day cycle for 2 cycles'''
-====Subsequent treatment====
-*Treatment group 2: [[#COPDAC|COPDAC]] x 2
-*Treatment group 3: [[#COPDAC|COPDAC]] x 4
-===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. [https://doi.org/10.1200/jco.2009.26.9381 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/20625128 PubMed] NCT00416832
-==OPPA {{#subobject:6418c0|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-OPPA: '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone, '''<u>A</u>'''driamycin (Doxorubicin)
-===Regimen {{#subobject:e17569|Variant=1}}===
-{| class="wikitable sortable" style="width: 75%; text-align:center;"
-!style="width: 33%"|Study
-!style="width: 33%"|Years of enrollment
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://doi.org/10.1200/jco.2009.26.9381 Mauz-Körholz et al. 2010 (GPOH-HD-2002)]
-|2002-2005
-| style="background-color:#91cf61" |Phase II
-|-
-|}
-''This regimen is meant for girls. Patients with early-stage disease only received the OPPA portion, see text for details.''
-====Chemotherapy====
-*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
-*[[Procarbazine (Matulane)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 15
-*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 15
-*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 15
-'''28-day cycle for 2 cycles'''
-====Subsequent treatment====
-*Treatment group 2: [[#C-MOPP|COPP]] x 2
-*Treatment group 3: [[#C-MOPP|COPP]] x 4
-===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. [https://doi.org/10.1200/jco.2009.26.9381 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/20625128 PubMed] NCT00416832
-=Untreated, early-stage favorable (ESF)=
-==VAMP (Methotrexate) {{#subobject:4d666a|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-VAMP: '''<u>V</u>'''inblastine, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>M</u>'''ethrotrexate,  '''<u>P</u>'''rednisone
-===Regimen {{#subobject:6f694d|Variant=1}}===
-{| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526806/ Metzger et al. 2012 (HOD99)]
-| style="background-color:#91cf61" |Non-randomized portion of RCT
-|-
-|}
-''To be completed? This is to be distinguished from the VAMP protocols used in AML and multiple myeloma.''
-====Chemotherapy====
-*[[Vinblastine (Velban)]]
-*[[Doxorubicin (Adriamycin)]]
-*[[Methotrexate (MTX)]]
-*[[Prednisone (Sterapred)]]
-'''4 cycles'''
+=Upfront therapy, high-risk=
-====Subsequent treatment====
+==ABVE-PC {{#subobject:67406e|Regimen=1}}==
-*Early responders: [[Hodgkin_lymphoma_-_null_regimens#Observation|Observation]] versus [[#Radiation_therapy_2|RT]]
-===References===
-# '''HOD99:''' Metzger ML, Weinstein HJ, Hudson MM, Billett AL, Larsen EC, Friedmann A, Howard SC, Donaldson SS, Krasin MJ, Kun LE, Marcus KJ, Yock TI, Tarbell N, Billups CA, Wu J, Link MP. Association between radiotherapy vs no radiotherapy based on early response to VAMP chemotherapy and survival among children with favorable-risk Hodgkin lymphoma. JAMA. 2012 Jun 27;307(24):2609-16. [https://jamanetwork.com/journals/jama/fullarticle/1199151 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526806/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22735430 PubMed]
-=Untreated, intermediate risk=
-==ABVE-PC {{#subobject:c24d93|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide
-===Regimen variant #1, 2 cycles with response adaptation {{#subobject:7fa6ea|Variant=1}}===
+<div class="toccolours" style="background-color:#eeeeee">
-{| class="wikitable" style="width: 50%; text-align:center;"
+===Regimen {{#subobject:9134b2|Variant=1}}===
-!style="width: 25%"|Study
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9945772/ Castellino et al. 2022 (COG AHOD1331)]
-| style="background-color:#91cf61" |Non-randomized portion of RCT
+|2015-2019
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Bv-AVEPC|Bv-AVEPC]]
+| style="background-color:#d73027" |Inferior EFS
 |-
 |}
-''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.''
+''Note: response evaluation occurs after the first 2 cycles.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1
+*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV push or intermittent infusion once per day on days 1 & 2
-*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7
+**Concentration not to exceed 2 mg/mL
-*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7
+**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
-*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4
+*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SC once on day 1, then 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SC once on day 8
-*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7
+*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1 & 8
-*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0
+*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 3
+**Rate should not exceed 300 mg/m<sup>2</sup>
-'''21-day cycle for 2 cycles'''
+*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV over 30 to 60 minutes once per day on days 1 & 2
-====Subsequent treatment====
+====Glucocorticoid therapy====
-*Rapid early responders: [[#ABVE-PC|ABVE-PC]] x 2 (4 cycles total), then [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy versus [[Hodgkin_lymphoma_-_null_regimens#Observation|no further treatment]]
+*[[Prednisone (Sterapred)]] 20 mg/m<sup>2</sup> PO twice per day on days 1 to 7
-*Slow early responders: [[#ABVE-PC|ABVE-PC]] x 2 (4 cycles total) versus DECA x 2, then [[#ABVE-PC|ABVE-PC]] x 2; then [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy
+====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
-===Regimen variant #2, 3 cycles with response adaptation {{#subobject:14cd95|Variant=1}}===
+**Alternative: [[Pegfilgrastim (Neulasta)]] 100 mcg/kg (Maximum dose of 6 mg) SC once on day 4, 5, or 6
-{| class="wikitable" style="width: 50%; text-align:center;"
+'''21-day cycle for 5 cycles'''
-!style="width: 25%"|Study
+</div></div>
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]
-| style="background-color:#91cf61" |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/m<sup>2</sup> IV once per day on days 0 & 1
-*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7
-*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7
-*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4
-*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7
-*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0
-====Supportive medications====
-*[[Dexrazoxane (Zinecard)]] 300 mg/m<sup>2</sup> 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: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy
-*Slow early responders: [[#ABVE-PC|ABVE-PC]] x 2 (5 cycles total), then [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy
-===Regimen variant #3, 4 cycles with response adaptation {{#subobject:17a940|Variant=1}}===
-{| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]
-| style="background-color:#91cf61" |Non-randomized portion of 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|ABVE-PC]] x 2
-====Chemotherapy====
-*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1
-*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7
-*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7
-*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4
-*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7
-*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0
-'''21-day cycle for 4 cycles, including the first 2 cycles'''
-====Subsequent treatment====
-*Rapid early responders with CR: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy versus [[Hodgkin_lymphoma_-_null_regimens#Observation|no further treatment]]
-*Rapid early responders with less than CR: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy
-*Slow early responders: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy
-===Regimen variant #4, 5 cycles {{#subobject:7e95ea|Variant=1}}===
-{| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]
-| style="background-color:#91cf61" |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|ABVE-PC]] x 3, with slow early response
-====Chemotherapy====
-*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1
-*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7
-*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7
-*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4
-*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7
-*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0
-====Supportive medications====
-*[[Dexrazoxane (Zinecard)]] 300 mg/m<sup>2</sup> 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====
-*[[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy
 ===References===
-# '''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 [http://www.bloodjournal.org/content/114/10/2051.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19584400 PubMed] NCT00005578
+# '''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. [https://doi.org/10.1056/nejmoa2206660 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9945772/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/36322844/ PubMed] [https://clinicaltrials.gov/study/NCT02166463 NCT02166463]
-# '''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. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259
+==Bv-AVEPC {{#subobject:67y7uj|Regimen=1}}==
+Bv-AVEPC: '''<u>B</u>'''rentuximab '''<u>v</u>'''edotin, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide
-=Untreated, advanced stage=
+<div class="toccolours" style="background-color:#eeeeee">
-==MOPP {{#subobject:bcde0|Regimen=1}}==
+===Regimen {{#subobject:1nc4b2|Variant=1}}===
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-MOPP: '''<u>M</u>'''echlorethamine, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone
-===Regimen variant #3, uncapped vincristine {{#subobject:ff7478|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[http://www.bloodjournal.org/content/42/2/163.long Young et al. 1973a]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9945772/ Castellino et al. 2022 (COG AHOD1331)]
-|1964-NR
+|2015-2019
-| style="background-color:#91cf61" |Non-randomized (RT)
+| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc)
-| style="background-color:#d3d3d3" |
+|[[#ABVE-PC|ABVE-PC]]
-| style="background-color:#d3d3d3" |
+| style="background-color:#1a9850" |Superior EFS (primary endpoint)<br>EFS36: 92.1% vs 82.5%<br>(HR 0.41, 95% CI 0.25-0.67)
-|-
-|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197610)38:4%3C1494::AID-CNCR2820380408%3E3.0.CO;2-E Kolygin 1976]
-|1970-1975
-| style="background-color:#91cf61" |Non-randomized (RT)
-| style="background-color:#d3d3d3" |
-| style="background-color:#d3d3d3" |
 |-
 |}
+''Note: response evaluation occurs after the first 2 cycles.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====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====
-*[[Mechlorethamine (Mustargen)]] 6 mg/m<sup>2</sup> IV once per day on days 1 & 8
+*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV push or intermittent infusion once per day on days 1 & 2
-*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once per day on days 1 & 8
+**Concentration not to exceed 2 mg/mL
-*[[Procarbazine (Matulane)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 14
+**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
-*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 14
+*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once on day 8
+*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 3
-'''28-day cycle for 6 to 8 cycles'''
+**Rate should not exceed 300 mg/m<sup>2</sup>
+*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV over 30 to 60 minutes once per day on days 1 & 2
+====Glucocorticoid therapy====
+*[[Prednisone (Sterapred)]] 20 mg/m<sup>2</sup> 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'''
+</div></div>
 ===References===
-# Young RC, DeVita VT, Johnson RE. Hodgkin's disease in childhood. Blood. 1973 Aug;42(2):163-74. [http://www.bloodjournal.org/content/42/2/163.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/4793108 PubMed]
+# '''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. [https://doi.org/10.1056/nejmoa2206660 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9945772/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/36322844/ PubMed] [https://clinicaltrials.gov/study/NCT02166463 NCT02166463]
-# Kolygin BA. Combination chemotherapy of Hodgkin's disease in children. Cancer. 1976 Oct;38(4):1494-7. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197610)38:4%3C1494::AID-CNCR2820380408%3E3.0.CO;2-E link to original article] [https://pubmed.ncbi.nlm.nih.gov/991072 PubMed]
-=Consolidation after upfront therapy=
+=Upfront therapy, intermediate-risk=
-==C-MOPP {{#subobject:034931|Regimen=1}}==
+==ABVE-PC {{#subobject:918uu2|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide
-|-
+<div class="toccolours" style="background-color:#eeeeee">
-|[[#top|back to top]]
+===Regimen {{#subobject:941bb2|Variant=1}}===
-|}
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-C-MOPP: '''<u>C</u>'''yclophospha'''<u>M</u>'''ide, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone
-<br>COPP: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone
-===Regimen variant #1, 2 cycles {{#subobject:cfcc4b|Variant=1}}===
-{| class="wikitable sortable" style="width: 75%; text-align:center;"
 !style="width: 33%"|Study
-!style="width: 33%"|Years of enrollment
+!style="width: 33%"|Dates of enrollment
 !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://doi.org/10.1200/jco.2009.26.9381 Mauz-Körholz et al. 2010 (GPOH-HD-2002)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]
-|2002-2005
+|2002-2009
-| style="background-color:#91cf61" |Phase II
+| style="background-color:#91cf61" |Non-randomized part of phase 3 RCT
 |-
 |}
-====Preceding treatment====
+<div class="toccolours" style="background-color:#b3e2cd">
-*[[#OPPA|OPPA]] x 2
 ====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8
+*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2
-*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1 & 8
+*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SC once on day 1, then 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SC once on day 8
-*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 15
+*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8
-*[[Procarbazine (Matulane)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 15
+*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 2, 3
+*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 60 minutes once on day 1
-'''28-day cycle for 2 cycles'''
+====Glucocorticoid therapy====
+*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided twice per day or three times per day on days 1 to 7
-===Regimen variant #2, 4 cycles {{#subobject:228db9|Variant=1}}===
+'''21-day cycle for 2 cycles'''
-{| class="wikitable sortable" style="width: 75%; text-align:center;"
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
+====Subsequent treatment====
+*COG AHOD0031, rapid early responders with CR: [[#ABVE-PC|ABVE-PC]] continuation x 2, then [[#Radiation_therapy|IFRT]] consolidation versus [[#Observation_888|no further treatment]]
+*COG AHOD0031, rapid early responders with less than CR: [[#ABVE-PC|ABVE-PC]] continuation x 2, then [[#Radiation_therapy|IFRT]] consolidation
+*COG AHOD0031, slow early responders: [[#ABVE-PC|ABVE-PC]] continuation x 2 followed by [[#Radiation_therapy|IFRT]] consolidation versus [[#DECA|DECA]] salvage x 2 followed by [[#ABVE-PC|ABVE-PC]] continuation x 2 followed by [[#Radiation_therapy|IFRT]] consolidation
+</div></div>
+===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. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain dosing details''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218/ PubMed] [https://clinicaltrials.gov/study/NCT00025259 NCT00025259]
+==DECA {{#subobject:jqqcu2|Regimen=1}}==
+DECA: '''<u>D</u>'''examethasone, '''<u>E</u>'''toposide, '''<u>C</u>'''isplatin, '''<u>A</u>'''ra-C (Cytarabine)
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:94172v|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
 !style="width: 33%"|Study
-!style="width: 33%"|Years of enrollment
+!style="width: 33%"|Dates of enrollment
 !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://doi.org/10.1200/jco.2009.26.9381 Mauz-Körholz et al. 2010 (GPOH-HD-2002)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]
-|2002-2005
+|2002-2009
-| style="background-color:#91cf61" |Phase II
+| style="background-color:#91cf61" |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.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
-*[[#OPPA|OPPA]] x 2
+*Induction [[#ABVE-PC_2|ABVE-PC]] x 2, with slow early response
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Glucocorticoid therapy====
+*[[Dexamethasone (Decadron)]] 10 mg/m<sup>2</sup> IV over 15 minutes on days 1, 2, '''given prior to etoposide/cytarabine'''
 ====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8
+*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 3 hours once per day on days 1, 2
-*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1 & 8
+**Mix with cytarabine in D5W at an etoposide concentration of at most 0.4 mg/mL
-*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 15
+*[[Cisplatin (Platinol)]] 90 mg/m<sup>2</sup> IV over 6 hours once on day 1
-*[[Procarbazine (Matulane)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 15
+*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours on days 1, 2
+'''21-day cycle for 2 cycles'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
-'''28-day cycle for 4 cycles'''
+====Subsequent treatment====
+*[[#ABVE-PC_2|ABVE-PC]] continuation x 2, then [[#Radiation_therapy|IFRT]] consolidation
+</div></div>
 ===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. [https://doi.org/10.1200/jco.2009.26.9381 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/20625128 PubMed] NCT00416832
+# '''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. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain dosing details''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218/ PubMed] [https://clinicaltrials.gov/study/NCT00025259 NCT00025259]
+=Upfront therapy, low-risk=
-==COPDAC {{#subobject:195ad7|Regimen=1}}==
+==OEPA {{#subobject:0e614f|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+OEPA: '''<u>O</u>'''ncovin (Vincristine), '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>A</u>'''driamycin (Doxorubicin)
-|-
+<div class="toccolours" style="background-color:#eeeeee">
-|[[#top|back to top]]
+===Regimen {{#subobject:25c262|Variant=1}}===
-|}
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-COPDAC: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone, '''<u>DAC</u>'''arbazine
-===Regimen variant #1, 2 cycles {{#subobject:e9d06d|Variant=1}}===
-{| class="wikitable sortable" style="width: 75%; text-align:center;"
 !style="width: 33%"|Study
-!style="width: 33%"|Years of enrollment
+!style="width: 33%"|Dates of enrollment
 !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://doi.org/10.1200/jco.2009.26.9381 Mauz-Körholz et al. 2010 (GPOH-HD-2002)]
 |2002-2005
-| style="background-color:#91cf61" |Phase II
+| style="background-color:#91cf61" |Phase 2
 |-
 |}
-====Preceding treatment====
+''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.''
-*[[#OEPA|OEPA]] x 2
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8
+*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
-*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1 & 8
+*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV once per day on days 2 to 6
-*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 15
+*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 15
-*[[Dacarbazine (DTIC)]] 250 mg/m<sup>2</sup> IV once per day on days 1 to 4
+====Glucocorticoid therapy====
+*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 15
 '''28-day cycle for 2 cycles'''
+</div>
-===Regimen variant #2, 4 cycles {{#subobject:515d30|Variant=1}}===
+<div class="toccolours" style="background-color:#cbd5e7">
-{| class="wikitable sortable" style="width: 75%; text-align:center;"
+====Subsequent treatment====
-!style="width: 33%"|Study
+*GPOH-HD-2002, treatment group 2: [[#COPDAC|COPDAC]] consolidation x 2
-!style="width: 33%"|Years of enrollment
+*GPOH-HD-2002, treatment group 3: [[#COPDAC|COPDAC]] consolidation x 4
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+</div></div>
-|-
-|[https://doi.org/10.1200/jco.2009.26.9381 Mauz-Körholz et al. 2010 (GPOH-HD-2002)]
-|2002-2005
-| style="background-color:#91cf61" |Phase II
-|-
-|}
-====Preceding treatment====
-*[[#OEPA|OEPA]] x 2
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8
-*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1 & 8
-*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 15
-*[[Dacarbazine (DTIC)]] 250 mg/m<sup>2</sup> IV once per day on days 1 to 4
-'''28-day cycle for 4 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. [https://doi.org/10.1200/jco.2009.26.9381 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/20625128 PubMed] NCT00416832
+# '''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. [https://doi.org/10.1200/jco.2009.26.9381 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20625128/ PubMed] [https://clinicaltrials.gov/study/NCT00416832 NCT00416832]
+=Consolidation after upfront therapy=
 ==Radiation therapy {{#subobject:b169ea|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
-===Regimen variant #2, 21 Gy of IFRT {{#subobject:dfa48c|Variant=1}}===
+<div class="toccolours" style="background-color:#eeeeee">
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
+===Regimen {{#subobject:dfa48c|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 383: / Line 214: @@
 |[https://doi.org/10.1200/JCO.2002.12.007 Nachman et al. 2002 (CCG 5942)]
 |1995-1998
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[Hodgkin_lymphoma_-_null_regimens#Observation|Observation]]
+|[[Classical_Hodgkin_lymphoma_-_null_regimens#Observation|Observation]]
 | style="background-color:#1a9850" |Superior EFS
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]
 |1997-2001
-| style="background-color:#91cf61" |Phase II
+| style="background-color:#91cf61" |Phase 2
 | style="background-color:#d3d3d3" |
 | style="background-color:#d3d3d3" |
@@ Line 395: / Line 226: @@
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]
 |2002-2009
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[Hodgkin_lymphoma_-_null_regimens#Observation|Observation]]
+|[[Classical_Hodgkin_lymphoma_-_null_regimens#Observation|Observation]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of EFS48
 |-
 |}
-''This regimen is intended for pediatric patients, younger than 22 years old.''
+''Note: This regimen is intended for pediatric patients, younger than 22 years old.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
-*CCG 5942: [[#C-MOPP.2FABV|COPP-ABV hybrid]] x 4 or 6 or multi-drug therapy, depending on risk stratification
+*CCG 5942: Induction [[#C-MOPP.2FABV|COPP-ABV hybrid]] x 4 or 6 or multi-drug therapy, depending on risk stratification
-*POG P9425: [[#ABVE-PC|ABVE-PC]] x 3 to 5
+*POG P9425: Induction [[#ABVE-PC|ABVE-PC]] x 3 to 5
-*COG AHOD0031 RERs: [[#ABVE-PC|ABVE-PC]] x 4
+*COG AHOD0031, rapid early responders: Induction [[#ABVE-PC|ABVE-PC]] x 4
-*COG AHOD0031 SERs: [[#ABVE-PC|ABVE-PC]] x 4 versus [[#ABVE-PC|ABVE-PC]] x 2, then DECA x 2, then [[#ABVE-PC|ABVE-PC]] x 2
+*COG AHOD0031, slow early responders: Induction [[#ABVE-PC|ABVE-PC]] x 4 versus induction [[#ABVE-PC|ABVE-PC]] x 2 followed by salvage [[#DECA|DECA]] x 2 followed by [[#ABVE-PC|ABVE-PC]] continuation x 2
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Radiotherapy====
-*[[External beam radiotherapy]] 21 Gy in 12 to 14 fractions of 1.50 to 1.75 Gy per fraction
+*[[External beam radiotherapy]] 2100 cGy in 12 to 14 fractions of 150 to 175 cGy per fraction
+</div></div>
 ===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. [https://doi.org/10.1200/JCO.2002.12.007 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/12228196 PubMed] NCT00592111
+# '''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. [https://doi.org/10.1200/JCO.2002.12.007 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12228196/ PubMed] [https://clinicaltrials.gov/study/NCT00592111 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. [https://doi.org/10.1200/JCO.2011.41.1819 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3434976/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22649136 PubMed]
+## '''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. [https://doi.org/10.1200/JCO.2011.41.1819 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3434976/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22649136/ 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 [http://www.bloodjournal.org/content/114/10/2051.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19584400 PubMed] NCT00005578
+# '''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 [https://doi.org/10.1182/blood-2008-10-184143 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19584400/ PubMed] [https://clinicaltrials.gov/study/NCT00005578 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. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259
+# '''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. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain dosing details''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218/ PubMed] [https://clinicaltrials.gov/study/NCT00025259 NCT00025259]
+[[Category:Classical Hodgkin lymphoma regimens]]
-[[Category:Hodgkin lymphoma regimens]]
 [[Category:Disease-specific pages]]
 [[Category:Aggressive lymphomas]]
-[[Category:Pediatric cancers]]
+[[Category:Pediatric hematologic neoplasms]]

Difference between revisions of "Classical Hodgkin lymphoma, pediatric"

Latest revision as of 00:41, 27 June 2024

Guidelines

NCCN

Upfront therapy, high-risk

ABVE-PC

Regimen

Chemotherapy

Glucocorticoid therapy

Supportive therapy

References

Bv-AVEPC

Regimen

Antibody-drug conjugate therapy

Chemotherapy

Glucocorticoid therapy

Supportive therapy

References

Upfront therapy, intermediate-risk

ABVE-PC

Regimen

Chemotherapy

Glucocorticoid therapy

Subsequent treatment

References

DECA

Regimen

Preceding treatment

Glucocorticoid therapy

Chemotherapy

Subsequent treatment

References

Upfront therapy, low-risk

OEPA

Regimen

Chemotherapy

Glucocorticoid therapy

Subsequent treatment

References

Consolidation after upfront therapy

Radiation therapy

Regimen

Preceding treatment

Radiotherapy

References

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