Difference between revisions of "Classical Hodgkin lymphoma, pediatric"

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{{#lst:Section editor transclusions|peds}}
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<span id="BackToTop"></span>
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<big>''This page contains studies that were specific to pediatric populations. For the more general Hodgkin lymphoma page, follow [[Hodgkin lymphoma|this link]].</big><br><br>
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<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">
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''Are you looking for a regimen but can't find it here? It is possible that we've moved it to the [[Hodgkin_lymphoma_-_historical|historical regimens page]]. For placebo or observational studies in this condition, please visit [[Hodgkin lymphoma - null regimens|this page]]. If you still can't find it, please let us know so we can add it.''<br>
+
[[#top|Back to Top]]
−
 
+
</div>
 +
{{#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>
 
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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>
 
<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>
 
|}
 
|}
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{{TOC limit|limit=3}}
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{{TOC limit|limit=4}}
 
=Guidelines=
 
=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=
+
=Upfront therapy, high-risk=
−
==OEPA {{#subobject:0e614f|Regimen=1}}==
+
==ABVE-PC {{#subobject:67406e|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">
 +
===Regimen {{#subobject:9134b2|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 +
!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/PMC9945772/ Castellino et al. 2022 (COG AHOD1331)]
 +
|2015-2019
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Bv-AVEPC|Bv-AVEPC]]
 +
| style="background-color:#d73027" |Inferior EFS
 
|-
 
|-
−
|[[#top|back to top]]
 
 
|}
 
|}
−
OEPA: '''<u>O</u>'''ncovin (Vincristine), '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>A</u>'''driamycin (Doxorubicin)
+
''Note: response evaluation occurs after the first 2 cycles.''
−
 
+
<div class="toccolours" style="background-color:#b3e2cd">
−
===Regimen {{#subobject:25c262|Variant=1}}===
+
====Chemotherapy====
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
+
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV push or intermittent infusion once per day on days 1 & 2
−
!style="width: 33%"|Study
+
**Concentration not to exceed 2 mg/mL
−
!style="width: 33%"|Years of enrollment
+
**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
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
*[[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
 +
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1 & 8
 +
*[[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>
 +
*[[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===
 +
# '''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]
 +
==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
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:1nc4b2|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 +
!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://doi.org/10.1200/jco.2009.26.9381 Mauz-Körholz et al. 2010 (GPOH-HD-2002)]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9945772/ Castellino et al. 2022 (COG AHOD1331)]
−
|2002-2005
+
|2015-2019
−
| style="background-color:#91cf61" |Phase II
+
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc)
 +
|[[#ABVE-PC|ABVE-PC]]
 +
| 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)
 
|-
 
|-
 
|}
 
|}
−
''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.''
+
''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====
 
====Chemotherapy====
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
+
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV push or intermittent infusion once per day on days 1 & 2
−
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV once per day on days 2 to 6
+
**Concentration not to exceed 2 mg/mL
−
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 15
+
**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
−
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 15
+
*[[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 2 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
−
====Subsequent treatment====
+
====Glucocorticoid therapy====
−
*Treatment group 2: [[#COPDAC|COPDAC]] x 2
+
*[[Prednisone (Sterapred)]] 20 mg/m<sup>2</sup> PO twice per day on days 1 to 7
−
*Treatment group 3: [[#COPDAC|COPDAC]] x 4
+
====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===
 
===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 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]
−
 
 
−
 
 
−
 
 
−
 
 
  
−
 
+
=Upfront therapy, intermediate-risk=
−
=Untreated, intermediate risk=
+
==ABVE-PC {{#subobject:918uu2|Regimen=1}}==
−
==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
 
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: 40%; text-align:center;"  
+
===Regimen {{#subobject:941bb2|Variant=1}}===
−
!style="width: 25%"|Study
+
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 33%"|Study
 +
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT  
+
|2002-2009
 +
| style="background-color:#91cf61" |Non-randomized part 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.''
+
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====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 over 10 to 30 minutes 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
+
*[[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
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV 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 1, 8
−
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4
+
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 2, 3
−
*[[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 over 60 minutes once on day 1
−
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0
+
====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
 
'''21-day cycle for 2 cycles'''
 
'''21-day cycle for 2 cycles'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 
====Subsequent treatment====
 
====Subsequent treatment====
−
*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]]
+
*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]]
−
*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
+
*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
−
===Regimen variant #2, 3 cycles with response adaptation {{#subobject:14cd95|Variant=1}}===
+
</div></div>
−
{| class="wikitable" style="width: 40%; text-align:center;"
+
===References===
−
!style="width: 25%"|Study
+
# '''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]
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
==DECA {{#subobject:jqqcu2|Regimen=1}}==
−
|-
+
DECA: '''<u>D</u>'''examethasone, '''<u>E</u>'''toposide, '''<u>C</u>'''isplatin, '''<u>A</u>'''ra-C (Cytarabine)
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]
+
<div class="toccolours" style="background-color:#eeeeee">
−
| style="background-color:#91cf61" |Phase II
+
===Regimen {{#subobject:94172v|Variant=1}}===
−
|-
+
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
−
|}
+
!style="width: 33%"|Study
−
''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.''
+
!style="width: 33%"|Dates of enrollment
−
====Chemotherapy====
+
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
*[[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: 40%; 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)]
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT  
+
|2002-2009
 +
| style="background-color:#91cf61" |Non-randomized part 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.''
+
''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====
 
====Preceding treatment====
−
*[[#ABVE-PC|ABVE-PC]] 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====
 
====Chemotherapy====
−
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1
+
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 3 hours 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
+
**Mix with cytarabine in D5W at an etoposide concentration of at most 0.4 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
+
*[[Cisplatin (Platinol)]] 90 mg/m<sup>2</sup> IV over 6 hours once on day 1
−
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4
+
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours on days 1, 2
−
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7
+
'''21-day cycle for 2 cycles'''
−
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0
+
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
  
−
'''21-day cycle for 4 cycles, including the first 2 cycles'''
 
 
====Subsequent treatment====
 
====Subsequent treatment====
−
*Rapid early responders with CR: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy versus [[Hodgkin_lymphoma_-_null_regimens#Observation|no further treatment]]
+
*[[#ABVE-PC_2|ABVE-PC]] continuation x 2, then [[#Radiation_therapy|IFRT]] consolidation
−
*Rapid early responders with less than CR: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy
+
</div></div>
−
*Slow early responders: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy
+
===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]
−
===Regimen variant #4, 5 cycles {{#subobject:7e95ea|Variant=1}}===
+
=Upfront therapy, low-risk=
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
==OEPA {{#subobject:0e614f|Regimen=1}}==
−
!style="width: 25%"|Study
+
OEPA: '''<u>O</u>'''ncovin (Vincristine), '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>A</u>'''driamycin (Doxorubicin)
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:25c262|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]
+
|[https://doi.org/10.1200/jco.2009.26.9381 Mauz-Körholz et al. 2010 (GPOH-HD-2002)]
−
| style="background-color:#91cf61" |Phase II
+
|2002-2005
 +
| style="background-color:#91cf61" |Phase 2
 
|-
 
|-
 
|}
 
|}
−
''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.''
+
''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.''
−
====Preceding treatment====
+
<div class="toccolours" style="background-color:#b3e2cd">
−
*[[#ABVE-PC|ABVE-PC]] x 3, with slow early response
 
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1
+
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
−
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7
+
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV once per day on days 2 to 6
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7
+
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 15
−
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4
+
====Glucocorticoid therapy====
−
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7
+
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 15
−
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0
+
'''28-day cycle for 2 cycles'''
−
====Supportive medications====
+
</div>
−
*[[Dexrazoxane (Zinecard)]] 300 mg/m<sup>2</sup> IV once per day on days 0, 1, 7 (this was a randomization)
+
<div class="toccolours" style="background-color:#cbd5e7">
−
*[[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====
 
====Subsequent treatment====
−
*[[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy
+
*GPOH-HD-2002, treatment group 2: [[#COPDAC|COPDAC]] consolidation x 2
 +
*GPOH-HD-2002, treatment group 3: [[#COPDAC|COPDAC]] consolidation x 4
 +
</div></div>
 
===References===
 
===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
+
# '''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]
−
# '''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
 
−
 
 
−
 
 
  
−
=Radiation therapy {{#subobject:b169ea|Regimen=1}}=
+
=Consolidation after upfront therapy=
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
==Radiation therapy {{#subobject:b169ea|Regimen=1}}==
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
 
RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 
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%"|Study
−
!style="width: 20%"|Years of enrollment
+
!style="width: 20%"|Dates of enrollment
 
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 20%"|Comparator
 
!style="width: 20%"|Comparator
Line 183: Line 215:
 
|1995-1998
 
|1995-1998
 
| style="background-color:#1a9851" |Phase 3 (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
 
| style="background-color:#1a9850" |Superior EFS
 
|-
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]
 
|1997-2001
 
|1997-2001
−
| style="background-color:#91cf61" |Phase II
+
| style="background-color:#91cf61" |Phase 2
 
| style="background-color:#d3d3d3" |
 
| style="background-color:#d3d3d3" |
 
| style="background-color:#d3d3d3" |
 
| style="background-color:#d3d3d3" |
Line 195: Line 227:
 
|2002-2009
 
|2002-2009
 
| style="background-color:#1a9851" |Phase 3 (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
 
| 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====
 
====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====
 
====Radiotherapy====
−
*[[External beam radiotherapy]] 21 Gy in 12 to 14 fractions of 1.5 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===
 
===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 [http://www.bloodjournal.org/content/114/10/2051.long 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:Disease-specific pages]]
 
[[Category:Aggressive lymphomas]]
 
[[Category:Aggressive lymphomas]]
 
[[Category:Pediatric hematologic neoplasms]]
 
[[Category:Pediatric hematologic neoplasms]]

Latest revision as of 11:32, 13 May 2024

Back to Top

Section editor
Noyd.png
 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

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

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

21-day cycle for 5 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 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

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

21-day cycle for 5 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 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

Glucocorticoid therapy

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

  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 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

Chemotherapy

21-day cycle for 2 cycles

Subsequent treatment

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

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

Glucocorticoid therapy

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

  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 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

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
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