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NCCN Flash Update: NCCN Guidelines Updated for Pediatric Hodgkin Lymphoma

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®), the NCCN Drugs & Biologics Compendium (NCCN Compendium^®), the NCCN Radiation Therapy Compendium™, and the NCCN Imaging Appropriate Use Criteria (NCCN Imaging AUC™) for Pediatric Hodgkin Lymphoma. These NCCN Guidelines^® are currently available as Version 1.2025.

Link directly to the Updates section of the NCCN Guidelines: Pediatric Hodgkin Lymphoma

Global Changes

References updated throughout the Guideline.

PHL-1

Footnote a modified: Core needle biopsy may be adequate if it is diagnostic. Fine-needle aspiration (FNA) is ~~discouraged in establishing a diagnosis~~ not an appropriate diagnostic test. See Principles of Pathology (PHL-B).
Footnote i added: Per WHO 2022, NLPHL remains under the family of HL, while in the ICC 2022 update, the term NLPHL was replaced with new terminology, nodular lymphocyte predominant B-cell lymphoma (NLPBL) (Alaggio R, et al. Leukemia 2022;36:1720-1748; Campo E, et al. Blood 2022;140:1229-1253). Recommendations for management of NLPHL remain in the pediatric HL guidelines as treatment regimens are typically guided by HL experience in clinical practice.

PHL-2

Page has been significantly revised.

PHL-3

Clinical Stage modified: ~~Low risk~~ Stage I–II CHL without risk factors
Footnote t added: For growth factor recommendations, see Select Principles of Supportive Care (PHL-G). (Also for PHL-4 B and PHL-5B)
Footnote v added: See PHL-2 for risk factors as defined by EuroNET-PHL and COG. (Also for PHL-4 B)

PHL-4

Page has been significantly revised

PHL-4 A

New page added

PHL-4 B

Footnote z added: RER = rapid early response; SER = slow early response; LMA = large mediastinal adenopathy; RRL = rapidly responding lesions; SRL = slow responding lesions. (Also for PHL-5 B)

PHL-5

Page has been significantly revised

PHL-5 A

New page added

PHL-5 B

Footnote m added: ISRT can safely replace IFRT (PHL-F).
Footnote bb added: Nivolumab is dosed per kg in patients <18 years of age. See Principles of Systemic Therapy (PHL-E).
Footnote cc added: False-positive findings may be observed on FDG-PET/CT or FDG-PET/MRI after treatment with a regimen that includes a CPI. Repeat imaging at short intervals (per LYRIC recommendations) may be considered prior to obtaining a biopsy. Cheson BD, et al. Blood 2016;128:2489-2496. (Also for PHL-9)
Footnote dd added: BrECADD regimen: brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone.
Footnote removed: Cyclophosphamide dosing in AHOD0031 differs from AHOD1331. Castellino SM, et al. N Engl J Med 2022;387:1649-1660. See Principles of Systemic Therapy (PHL-E).
Footnote removed: Metzger ML, et al. J Clin Oncol 2021;39:2276-2283.
Footnote removed: BEACOPP has been studied in pediatric trials (ie, CCG-59704). Consider only for select patients with extensive disease given concerns for acute and long-term toxicity risk. See NCCN Guidelines for Hodgkin Lymphoma where regimens with reduced number of cycles of BEACOPP have been developed.

PHL-6

Stage IA (complete resection) confirmed by FDG-PET/CT, observe, bullet 1 modified: Clinical exam ± ultrasound of primary site every 3–4 mo for the first 2 y; additional imaging as indicated if concern for relapse
Footnote ee added: The following risk factors may also inform decisions about primary treatment of NLPHL: age ≥45 years, hemoglobin <10.5 g/dL, and splenic involvement. Binkley MS, et al. J Clin Oncol 2024;42:2271-2280. (Also for PHL-7)

PHL-7

Footnote removed: An FDA-approved biosimilar is an acceptable substitute for rituximab.

PHL-8

Disease Surveillance/Follow-up After Completion of Treatment
- Imaging, sub-bullet 5, sub-sub-bullet 2 modified: Surveillance FDG-PET is ~~not recommended~~ discouraged due to risk for false positives.

PHL-9

Biopsy site of concern, positive
- Re-induction therapy, Deauville 4-5 added: Subsequent therapy (see additional therapy options on PHL-E, 3 of 4) or High-dose therapy and autologous stem cell rescue (HDT/ASCR) +/- ISRT
- Re-induction therapy, Deauville 1-3 modified: ~~If metabolic CR (Deauville ≤3) proceed to~~ HDT/ASCR ± ISRT ± maintenance chemotherapy
Footnote jj added: Consider consultation with radiation oncology depending on level of clinical suspicion.

PHL-A (1 of 3)

Column removed: HL Type (Also for PHL-A 2 of 3)
Column removed: Risk Group/Stage (Also for PHL-A 2 of 3)
OEPA/OEPA-COPDAC, criteria for RT
- Bullet 1 modified: < CR on imaging after 2 cycles of OEPA (applies to patients ~~with low-risk [LR] disease~~ in TG1 [stage IA, IB, and IIA without E] on GPOH HD-2002)
- Bullet 2 modified: All patients ~~with intermediate-/high-risk (IR/HR) disease~~ in TG2 (stage IA/B + E, IIA + E, IIB, and IIIA) and TG3 (stage IIB + E, IIIA+ E, IIIB, and IVA/B ± E) on HD-2002 received RT
- Bullet 3 modified: Patients ~~with LR/IR/HR disease~~ in all TGs on C1 received RT only if FDG-PET positive (Deauville 3–5) or not in at least partial response (PR) after 2 cycles of OEPA
Footnote removed: Stage IVA was included in the intermediate-risk group in the trial, although is not recommended for standard care. (Also for PHL-A 2 of 3)

PHL-A (2 of 3)

Regimen added: Nivolumab-AVD (S1826)
Regimen added: Bv-AVD (S1826)
Footnote b added: Patients with ≥3 Deauville 4-5 lesions and/or a lesion that that did not achieve ≥30% reduction in transverse diameter
were considered to have refractory disease.

PHL-B (1 of 5)

Histologic Classification
- Bullet 2, sub-bullet added: Per WHO 2022, NLPHL remains under the family of HL, while ICC 2022 replaces the term NLPHL with nodular lymphocyte-predominant B-cell lymphoma (NLPBL).
- Bullet 2, sub-bullet added: Both classifications recognize the clinical and biologic similarities of NLPHL to an indolent B-cell lymphoma and NLPBL is an acceptable term per WHO 2022.
Footnote removed: Per WHO 2022, NLPHL remains under the family of HL, while ICC 2022 replaces the term NLPHL with nodular lymphocyte-predominant B-cell lymphoma (NLPBL). Both classifications recognize the clinical and biologic similarities of NLPHL to an indolent B-cell lymphoma and NLPBL is an acceptable term per WHO 2022 (Alaggio R, et al. Leukemia 2022;36:1720-1748; Campo E, et al. Blood 2022;140:1229-1253).

PHL-B (2 of 5)

Tissue Adequacy for Diagnosis
- Bullet 1 modified: An excisional or incisional biopsy where possible is recommended. ~~A core biopsy may be appropriate in some settings.~~ Fine-needle aspiration (FNA) is ~~discouraged in establishing a diagnosis~~ not an appropriate diagnostic test.
- Bullet 2 modified: For CHL, ample tissue may be necessary to exclude other entities in the differential diagnosis and for specific morphologic subtyping.A core biopsy may be appropriate in some settings.

PHL-B (3 of 5)

Immunohistochemical Considerations and Ancillary Testing
- Bullet 3, sub-bullet 1 modified: "CHL: Neoplastic Hodgkin/Reed-Sternberg (HRS) cells are PAX5+ (weaker expression than background B lymphocytes), CD30+, CD15+, CD45-, or CD3-~~, or CD20- (majority)~~. CD20 may be variably expressed in 20%–40% of cases and, when present, is typically expressed by a subset of HRS cells..."

PHL-C (1 of 3)

Footnote e added: Special attention should be given to end-of-therapy scans when utilizing CPIs given their potential for delayed response or pseudo-progression. Cheson BD, et al. Blood 2016;128:2489-2496.

PHL-D (1 of 3)

Liver, FDG-PET/CT or FDG-PET/MRI, protocol modified: ~~Focal FDG-PET–positive lesions~~ Liver involvement is defined as any hepatic lesion on CT or MRI that correlates with 18 F-FDG uptake greater than background liver.

PHL-D (3 of 3)

Footnote f modified: E-lesions are defined by the HD10 study as localized involvement of extralymphatic tissue (by contiguous growth from an involved lymph node or in close anatomic relation) that is treatable by irradiation (Engert A, et al. N Engl J Med 2010;363:640-652; Lister TA, et al. J Clin Oncol 1989;7:1630-1636; Spijkers S, et al. Pediatr Radiol 2019;49:266-276). An E-lesion is defined as a contiguous infiltration of a lymph node mass into extralymphatic structures or organs (eg, lung or bone). Pleural and pericardial involvement should be considered E-lesions, but a pleural or pericardial effusion alone is not considered an E-lesion. Disease that extends beyond the lymphatic system without adjacent lymphatic involvement is considered stage IV; liver or bone marrow involvement is always considered stage IV disease (Zijtregtop EAM, et al. Blood Adv 2023;7:6303-6319). CNS disease is considered extra-axial.

PHL-E (1 of 5)

Risk classifications removed from regimens for consistency with algorithm
ABVE-PC note removed: Cyclophosphamide dosing in AHOD0031 differs from AHOD1331.
Regimen and dosing added: Bv-AVD (S1826)
Regimen and dosing added: Nivolumab-AVD (S1826)
Footnote a added: An FDA-approved biosimilar is an appropriate substitute for any recommended systemic biologic therapy in the NCCN Guidelines. (Also for PHL-E 2)
Footnote b added: For growth factor recommendations, see Select Principles of Supportive Care (PHL-G). (Also for PHL-E 2)

PHL-E (2 of 5)

OEPA (GPOH-HD-2002), Etoposide dose modified: 125 mg/m² IV daily on Days ~~2–6~~1–5 (Also for OEPA-COPDAC [GPOH-HD-2002; EuroNET-PHL-C1])
Footnote removed: An FDA-approved biosimilar is an acceptable substitute for rituximab.

PHL-E (3 of 5)

Page has been significantly revised.

PHL-F (1 of 4)

Bullet 5, sub-bullet 1 modified: Initial diagnostic imaging with contrast-enhanced CT, MRI, FDG-PET/CT or FDG-PET/MRI, ultrasound, and other imaging modalities facilitate target definition.

PHL-F (2 of 4)

Bullet 2 modified: Planning for ISRT requires CT-based simulation and treatment planning capabilities. Incorporating other modern imaging such as FDG-PET/CT ~~and~~ or FDG-PET/MRI often enhances treatment volume determination.

PHL-F (3 of 4)

RT fields, bullet 4 added: Some protocols, such as HLHR13, incorporate RNRT, in which individually involved nodes are assessed for response to determine need for RT to each node. If this approach is selected, particular attention to detail is required in response assessment and radiation contouring.
Stage modified: ~~Low/Intermediate Risk~~ Stage I–II With or Without Risk Factors
Stage modified: ~~High Risk~~ Stage III–IV

PHL-G (1 of 3)

New section added: Select Principles of Supportive Care

For the complete updated versions of the NCCN Guidelines, NCCN Guidelines with NCCN Evidence Blocks™, the NCCN Drugs & Biologics Compendium (NCCN Compendium^®), the NCCN Biomarkers Compendium^®, the NCCN Chemotherapy Order Templates (NCCN Templates^®), the NCCN Radiation Therapy Compendium™, and the NCCN Imaging Appropriate Use Criteria (NCCN Imaging AUC™), please visit NCCN.org.

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