Hematology-Oncology & Internal Medicine & Family Medicine
Lymphome de Hodgkin: symptômes et traitement | Clinique Omicron
Hodgkin's lymphoma (HL) is a lymphoid neoplasia characterized by the presence of pathognomonic tumor cells - Reed-Sternberg (RS) cells - within a rich reactive inflammatory infiltrate. These binucleated or multinucleated giant cells, derived from germinal center B lymphocytes, express CD30 and CD15, and are surrounded by an immunosuppressive microenvironment that today constitutes a major therapeutic target. LH accounts for around 10-15 % of all lymphomas, and preferentially affects young adults (bimodal peak: 15-35 years and >55 years), with a slight male predominance. Incidence in Canada is around 3,000 new cases per year. With an overall cure rate of over 85 % thanks to modern chemoradiotherapy protocols adapted to PET-CT, HL is one of the most curable hematological cancers - even in advanced stages. The discovery of painless cervical adenopathy in a young adult, often associated with B-symptoms (fever, night sweats, weight loss) and unexplained pruritus, should raise the diagnosis in the first instance. Recent advances - brentuximab vedotin (anti-CD30), nivolumab, pembrolizumab - have transformed the management of refractory and recurrent forms, paving the way for strategies without radiotherapy in young subjects.
Classification, tumor biology, and staging
- WHO 2022 Histological Classification: HL is divided into two biologically and clinically distinct entities; classical Hodgkin's lymphoma (CHL) - 95 % of HLs: Reed-Sternberg (RS) cells + variants (lacunar cells in nodular sclerosis + mummified cells + lymphocytic variants) → phenotype: CD30+ + CD15+ + PAX5 (weak) + CD45- + CD20- (or weakly positive) + variable BCL6 → EBV (Epstein-Barr virus): associated in 30-40 % of LHCs (variable proportion depending on subtype and geographic region) → histological subtypes of LHC: nodular sclerosis (NS): 70-75 % → bands of fibrosis dividing the lymph node into nodules + lacunar cells (variant of RS) + CD30++ → female predominance + young adult + mediastinum ++ + mixed cellularity (MC): 15-20 % → abundant classical RS cells + EBV + (80 %) → middle-aged adult + advanced stages + developing countries + rich in lymphocytes (RL): 5 % → rare RS + numerous lymphocytes + favorable prognosis + lymphocyte deletion (DL): <1 % → rarest form + most abundant RS + HIV+ + advanced stages + least favorable prognosis; nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) — 5 % of HL: tumor cells «popcorn» (LP cells — lymphocyte predominant) → phenotype: CD20+ + CD45+ + BCL6+ + CD30− + CD15− → indolent evolution + frequent late local relapses + risk of transformation into diffuse large B-cell lymphoma (DLBCL) → distinct management from classical HL (rituximab active on CD20+)
- Ann Arbor Staging modified Lugano 2014 and prognostic factors: Ann Arbor staging (revised - Lugano classification 2014 - Cheson et al. - JCO 2014): stage I: involvement of a single lymph node region or extraganglionic site + stage II: involvement of ≥2 lymph node regions on the same side of the diaphragm ± direct extension to an adjacent organ (IIE) + stage III: lymph node involvement on both sides of the diaphragm ± splenic involvement (IIIS) + stage IV: diffuse extraganglionic involvement (bone marrow + liver + lungs + bone - not contiguous) + suffix A/B: A = absence of symptoms B + B = presence of at least 1 symptom B: unexplained fever >38°C + profuse night sweats + weight loss >10 % in 6 months; poor prognostic factors - limited unfavorable stages (EORTC + GHSG): GHSG (German Hodgkin Study Group) - unfavorable factors (stages I-II): bulky mediastinal mass (ratio of mediastinal mass to thoracic diameter >0.33) + extraganglionic involvement + SV >50 mm/h (without B symptoms) or >30 mm/h (with B symptoms) + ≥3 lymph node areas involved + EORTC: similar factors + age >50 years → defines groups: favorable (0 factors) + intermediate (1-2 factors) + unfavorable (>2 factors); international prognostic score (IPS) - advanced stages (III-IV - Hasenclever 1998 - NEJM): 7 poor prognostic factors (1 point each): albumin <40 gl + hb <105 sexemasculin stade iv âge ≥45 ans leucocytes>15 × 10⁹/L + lymphocytes 6e9/L or <8 % leukocytes → PS 0–1: 5-year progression-free survival (PFS): 77–84 % + PS ≥4: 5-year PFS: 42–47 %
- Initial diagnostic assessment and role of PET-CT: suggestive clinical presentation: painless cervical (70 % of cases) + mediastinal (60 % of LHC-SN cases) + axillary + inguinal adenopathy → firm consistency + non-painful + non-inflammatory + unexplained generalized pruritus (mediators released by eosinophils + basophils from the microenvironment) + alcohol-bread : intense pain in adenopathies triggered by alcohol consumption → pathognomonic for LH (10-15 % of cases) + B symptoms: fever (often undulating - Pel-Ebstein fever: cycles of high fever + apyrexia) + profuse night sweats + weight loss >10 %; initial diagnostic workup: lymph node biopsy complete excision (no fine-needle puncture-aspiration - insufficient for architecture) → immunohistochemistry: CD30 + CD15 + CD20 + CD45 + EBV-EBER + ALK + thoraco-abdomino-pelvic + cervical CT with injection + ¹⁸F-FDG PET-CT (reference standard for staging - Cheson 2014): lymph node + extraganglion hypermetabolism → initial staging + assessment of response during treatment (interim PET-CT - Deauville score) + osteo-medullary biopsy: replaced by PET-CT (superior sensitivity for detecting spinal cord involvement) → still indicated if PET not available or clinico-radiological discordance + biological workup: CBC + ESR + LDH + albumin + beta-2 microglobulin + liver workup + creatinine + HIV + HBV + HCV serologies (before immunosuppression) + pregnancy test if woman of childbearing age + fertility workup (sperm or oocyte cryopreservation depending on treatment envisaged); Deauville score (5-point scale - PET-CT evaluation during treatment): 1: no fixation + 2: fixation ≤mediastinum + 3: fixation >mediastinum but ≤liver + 4: fixation moderately superior to liver + 5: fixation markedly superior to liver or new lesion → PET-CT interim negative (score 1-3): complete metabolic response → therapeutic deescalation possible → PET positive (score 4-5): evolving residue → therapeutic escalation.
Treatment, monitoring, and long-term sequelae
| Clinical situation | Therapeutic strategy | Surveillance and complications |
|---|---|---|
| Classical LH limited stages (I–IIA) favorable and unfavorable ABVD × 2–4 — ISRT radiotherapy — PET-adaptive |
Limited stages (I-IIA) are treated with a combined chemo-radiotherapy approach adapted to interim PET-CT, with the aim of therapeutic de-escalation to reduce long-term sequelae; 1st-line chemotherapy - ABVD (doxorubicin-Adriamycin + bleomycin + vinblastine + dacarbazine): historical standard regimen (DeVita 1970 + Bonadonna 1975) → 28-day cycles (D1 + D15) → well tolerated + proven efficacy over 40 years of data; protocols according to risk group: limited favorable stages (GHSG: 0 unfavorable factors): ABVD × 2 cycles + ISRT (Involved-Site Radiation Therapy - 20 Gy) → GHSG HD10 trial (Engert 2010 - NEJM): ABVD × 2 + 20 Gy = equivalent to × 4 + 30 Gy → 5-year control rate: 93-97 % + limited unfavorable stages (GHSG: ≥1 unfavorable factor): ABVD × 4 cycles + ISRT 30 Gy → GHSG HD11 trial (Ruhl 2006 - JCO) → stages II with bulky mass (bulky): ABVD × 4-6 + ISRT 30-36 Gy; PET-adapted approach (de-escalation): PET-CT after cycle 2 (interim PET) → if Deauville score 1-3 (complete response) → possible omission of radiotherapy or dose reduction → RAPID trial (Radford 2015 - NEJM): stage IA-IIA patients + negative PET-CT after 3 ABVD cycles → no significant difference in progression-free survival between radiotherapy and no radiotherapy → progression to omission of RT in good responders + H10 trial (Raemaekers 2014 - JCO): less favorable results without RT → benefit/risk balance to be discussed individually; brentuximab vedotin (BV) in limited stages: BREACH trial (phase 2) + AVD + BV protocols under evaluation in unfavorable limited stages → not yet standard in 2025 | ISRT (Involved-Site Radiation Therapy) - modern technique: ISRT replaces EFRT (Extended Field RT) and IFRT (Involved Field RT) of the 1990s-2000 → target volumes reduced to the initially affected site only (based on pre-treatment PET-CT imaging) → major dose reduction to organs at risk (lungs + heart + breasts + thyroid + spinal cord) → doses: 20 Gy for favorable stages + 30-36 Gy for unfavorable or bulky → technique: IMRT (intensity-modulated radiotherapy) or proton therapy (if available - cardiac and pulmonary dose reduction) → proton therapy in Canada: CHUM proton therapy center (Montreal) → under development 2024-2025; post-treatment monitoring limited stages: end-of-treatment PET-CT (Deauville score) → complete remission (CR) if score 1-3 → follow-up: clinical + CT every 6 months × 2 years then annually × 3 years + CBC + VS + biological workup every 3-6 months → no systematic surveillance PET-CT in CR (NCCN + ESMO 2023 - risk of false positives + cost) → specific monitoring of sequelae: annual TSH if cervical irradiation + cardiovascular workup (risk factors + ECG + cardiac ultrasound depending on cardiac dose received) + annual mammography from 8-10 years post-radiation thoracic if breast irradiation in women <30 years → increased risk of secondary breast cancer ×5 in this context → EFR if mediastinal irradiation + bleomycin (synergistic pulmonary toxicity) |
| LH classic advanced stages (IIB–IV) ABVD — BV-AVD — BEACOPP escalated — PET-adaptive |
Advanced stages require 6 cycles of chemotherapy with or without consolidation by radiotherapy depending on PET-CT response - the approach is increasingly individualized; chemotherapy regimens for advanced stages: ABVD × 6 cycles : standard reference regimen → complete response rate: 70-80 % → 5-year overall survival (OS): 85-90 % for all advanced stages + escalated BEACOPP (bleomycin + etoposide + doxorubicin + cyclophosphamide + vincristine + procarbazine + prednisone): intensified → GHSG HD12-HD15: superior to ABVD for progression-free survival in stages III-IV with IPS ≥3 → but: major hematological toxicity (frequent febrile neutropenia) + infertility + secondary myelodysplasia → reserved for patients <60 years with high IPS (≥3-4) + BV-AVD (brentuximab vedotin + doxorubicin + vinblastine + dacarbazine): ECHELON-1 trial (Connors 2018 - NEJM): BV-AVD vs ABVD stages III-IV → reduced risk of progression or death by 23 % → 2-year PFS rate: 82 % vs 77 % → toxicity: peripheral neuropathy ++ (34 % grade 3-4) → FDA approved 2018 + Health Canada 2019 + reimbursed INESSS Quebec for stages III-IV → becomes standard of care in 1st line for advanced stages in Canada + BV-AVD preferred to ABVD as no bleomycin (avoids pulmonary toxicity); PET-CT interim and therapeutic adaptation - advanced stages: PET-CT after cycle 2 (ABVD): Deauville score 1-3 (PET-) → continue ABVD → PET after cycle 2 + score 4-5 (PET+) → escalation: switch to escalated BEACOPP (RATHL trial - Johnson 2016 - NEJM + HD0801 trial) → improved PFS vs. continued ABVD + in case of BV-AVD: interim PET-CT not yet formally guided by data - evolving practice | Consolidation by radiotherapy in advanced stages: indications in 2025: only if PET-positive residue at end of chemotherapy (Deauville score 4-5) → ISRT 30-36 Gy on residue + initial bulky mass (>10 cm): consolidation ISRT discussed even in case of PET RC → tends to be avoided in young people if complete PET negative → HD15 trial (Engert 2012 - NEJM): among BEACOPP + PET-CT end-of-treatment negative patients: no benefit to RT consolidation → confirms PET-guided approach; end-of-treatment PET response: CR (Deauville 1-3) → monitoring → 5-year overall survival: 90-95 % for stages III-IV in CR + partial response or positive residue (Deauville 4-5) → biopsy of residue if accessible → if viable: 2nd-line treatment + autograft; monitoring of advanced stages: same as limited stages + monitoring of sequelae of polychemotherapy: cardiotoxicity (anthracyclines - doxorubicin cumulative dose + bleomycin → synergistic with RT) → baseline echocardiography + follow-up at 1 year + 5 years + pulmonary toxicity (bleomycin → interstitial lung disease + fibrosis - increased risk if O₂ per-operative or per-anesthetic + mediastinal irradiation) → baseline EFR + at 1 year → report to any anesthetist → risk of O₂ toxicity even years after bleomycin + peripheral neuropathy (BV): clinical monitoring + EMG if symptoms + gonadotoxicity (infertility): variable depending on protocol → BEACOPP + alkylants: high risk → spermatocryoconservation and oocyte cryoconservation before any treatment → oncofertility (CHU de Québec + CHUM) |
| Refractory and recurrent LH ICE — DHAP — autologous transplant — brentuximab vedotin — nivolumab — pembrolizumab |
Approx. 10-15 % of HL are refractory to 1st-line or relapse after initial response - their treatment has been transformed by new targeted therapies; definition: primary refractory: lack of CR after 1st-line chemotherapy (PET-positive residue at end of treatment) + early relapse: relapse within 12 months of end of 1st-line treatment → poor prognosis + late relapse: relapse >12 months → more favorable prognosis → can be reprocessed by same regimen in some cases; salvage chemotherapies (2nd line): objective: obtain sufficient CR (PET-negative) to go to autograft → regimens: ICE (ifosfamide + carboplatin + etoposide): most widely used protocol in Canada + in daily practice + DHAP (dexamethasone + cisplatin + high-dose cytarabine) + IGEV (ifosfamide + gemcitabine + etoposide + vinorelbine) + GVD (gemcitabine + vinorelbine + liposomal doxorubicin) + brentuximab vedotin (BV) in 2nd line (if CD30+): SG35-0003 trial (Younes 2012 - JCO): 102 relapsed/refractory LH patients → objective response rate 75 % + CR rate 34 % → FDA 2011 + Health Canada 2013 approved + BV + nivolumab combination (CheckMate 205 - Herrera 2018 - Lancet Oncology): objective response rate 85 % → options awaiting autograft. | Hematopoietic stem cell autotransplantation (ASCT) - standard 2nd line: ASCT = reference treatment for refractory/recurrent HL in RC2 (2nd complete remission) → high-dose conditioning: BEAM (carmustine + etoposide + cytarabine + melphalan) → reinfusion of autologous HSC → 5-year overall survival rate after 2nd-line ASCT: 50-60 % + post-ASCT consolidation with vedotin brentuximab: AETHERA trial (Moskowitz 2015 - Lancet): BV × 16 cycles post-ASCT vs placebo → improved PFS (42 months vs 24 months) → FDA 2015 + Health Canada approval + reimbursed INESSS for patients at high risk of post-ASCT relapse (early relapse + primary refractory + ≥2 risk factors); immune checkpoint inhibitors (anti-PD-1) - refractory/recurrent HL: mechanism: RS cells overexpress PD-L1 and PD-L2 (amplification 9p24.1 - JAK2 locus + PD-L1/PD-L2) → inhibition of cytotoxic T lymphocytes → anti-PD-1 restores anti-tumor immunity → nivolumab (Opdivo): CheckMate 205 trial (Armand 2016 - JCO): 243 LH-r/r patients → objective response rate 69 % + CR 16 % + 2-year OS 86 % → FDA 2016 + Health Canada 2017 approval + pembrolizumab (Keytruda): KEYNOTE-087 trial (Chen 2017 - JCO): response rate 69 % → FDA approved 2017 + Health Canada 2019 → INESSS Quebec reimbursement conditional on criteria + HSC allograft: indication: relapse after ASCT + eligible patient + compatible donor → potentially curative treatment of multi-refractory forms → 5-year survival rate: 40-50 % → GVH toxicity + procedure-related mortality 5-15 % |
| Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) and late sequelae Rituximab — late surveillance — secondary cancers — heart |
LPLN is distinguished from LHC by its biology (CD20+) and evolution - its management is individualized according to stage and risk factors for transformation; particular features of LPLN: indolent evolution + frequent late local relapses (10-15 years) with no impact on overall survival + risk of transformation into LBDGC: 2-7 % of cases → biopsy of any rapidly progressive adenopathy to rule out transformation → treatment of LPLN: stage IA with no unfavorable factors: ISRT radiotherapy alone (30 Gy) → watchful waiting option in very limited forms of incidental discovery → advanced stages: rituximab (anti-CD20) alone × 4-6 cycles → response rate 94 % (Ekstrand 2003 - Annals of Oncology) → or ABVD if rituximab insufficient or transformation suspected + relapse: rituximab + chemotherapy according to catch-up regimen + ASCT if transformation + rituximab in maintenance after relapse: reduced risk of subsequent relapse; late sequelae of LH treatment - most important : secondary cancers (main issue in 2025): risk × 2-5 vs general population → breast cancers (mediastinal irradiation in women 250-300 mg/m²) → dilated cardiomyopathy + coronary artery disease accelerated by mediastinal irradiation → ESC 2022 recommendations (cardio-oncology): baseline echocardiography before treatment + at 1 year + at 5 years + then every 5 years depending on cardiac dose received → screening for modifiable cardiovascular risk factors (hypertension + diabetes + dyslipidemia + smoking) → strict LDL targets if mediastinal RT (<1.8 mmol/L) | Long-term monitoring of LH survivors: monitoring program according to the International Lymphoma Radiation Oncology Group (ILROG) + ESMO 2023 + NCCN 2024: biology + clinical every 3-6 months × 2 years → then annually × 3 years → then every 2-3 years for life (late risks); screening for secondary cancers: breast cancer: annual breast MRI from 8-10 years post thoracic RT in women irradiated before age 30 → mammography in alternation → SOGC + ASCO formal recommendation + colorectal cancer: colonoscopy at 10 years post subdiaphragmatic RT or at 40 years (whichever comes first) + annual TSH: if cervical or high mediastinal irradiation → hypothyroidism in 30-40 % at 10 years + thyroid cancer: palpation + cervical ultrasound every 2-3 years if cervical irradiation + annual CBC for life: screen for secondary myelodysplasia + LDH: relapse of LH possible up to 10-15 years post-treatment (rare but documented); fertility and pregnancy post-LH: BEACOPP + alkylating agents → high risk of premature ovarian failure + azoospermia → spermatocryoconservation + oocyte/embryonic cryopreservation BEFORE any cytotoxic treatment → ABVD: gonadotoxicity less but not zero + pregnancy after treated LH is not contraindicated → recommended time frame: 1-2 years after the end of treatment (maximum risk of relapse in this period) → specialized obstetrical follow-up if pelvic or cardiac irradiation + long-term quality of life: chronic fatigue (40-60 % of survivors at 5 years) + anxiety + depression + post-treatment syndrome + multidisciplinary oncology management: psycho-oncology consultation + physical medicine + rehabilitation |
ℹ️
Sign of alcohol-bread: pathognomonic but rare: Intense and immediate pain in lymph nodes triggered by alcohol consumption—'alcohol-pruritus«—is a pathognomonic clinical sign of Hodgkin's lymphoma, present in 10–15 % of cases. Its mechanism is not fully elucidated (vasodilation + adenopathy edema). Its presence in a patient presenting with lymphadenopathy should immediately guide the workup toward a lymph node biopsy—the absence of this sign does not rule out the diagnosis.
Situations requiring urgent medical assessment
Enlarged cervical or mediastinal lymphadenopathy + superior vena cava syndrome (Stokes' collar edema + collateral venous circulation + dyspnea + facial cyanosis) → Mediastinal compression by Hodgkin's mass → Oncological emergency → Emergency thoracic CT scan + biopsy as soon as possible → Corticosteroid therapy pending diagnosis if respiratory distress → Urgent oncology/hematology consultation.
Unexplained fever >38°C persistent + weight loss >10 % + profuse night sweats + firm cervical or axillary adenopathy in a 20-35 year old adult → Hodgkin lymphoma as a first differential diagnosis → CBC + ESR + LDH + whole-body CT scan + excisional lymph node biopsy → do not delay investigation beyond 2 weeks.
Fever + neutropenia (ANC <0.5 × 10⁹/L) in a patient undergoing BEACOPP or BV-AVD chemotherapy → Febrile neutropenia → Infectious emergency → Blood cultures + abdomino-thoracic CT scan + broad-spectrum antibiotics (piperacillin-tazobactam or cefepime) within 60 minutes → G-CSF according to protocol → hospitalization.
Progressive dyspnea + dry cough + low-grade fever in a patient treated with bleomycin or post-mediastinal radiotherapy Bleomycin-induced pneumonopathy or radiation pneumonopathy → Thoracic high-resolution CT (HRCT) → Pulmonary function tests (PFTs) → Immediate discontinuation of bleomycin if confirmed → Corticosteroid therapy → Avoid high-concentration O₂ (synergistic with bleomycin toxicity).
Consult at Clinique Omicron
Clinique Omicron physicians can initiate workup for suspected lymphadenopathy—particularly in young adults with B symptoms, unexplained pruritus, or mediastinal mass—including laboratory tests (CBC, LDH, ESR, CRP, serologies), imaging (chest X-ray, CT scan), and referral to a surgeon for diagnostic lymph node biopsy. Long-term follow-up for Hodgkin lymphoma survivors—monitoring for relapse, screening for secondary cancers, cardiovascular assessment—can be coordinated at several service points in Quebec, in collaboration with the hematology-oncology teams at tertiary centers. To book an appointment, visit cliniqueomicron.ca.
The content of this page is for informational purposes only and does not replace the advice of a physician or a hematologist-oncologist. The diagnosis and treatment of Hodgkin lymphoma should be carried out in a specialized hematology-oncology center with access to PET-CT, hematological pathology, and new targeted therapies.
Omicron Clinic
Need to consult a doctor?
Treatment within 24-48 hours. In-clinic or telemedicine, anywhere in Quebec.
Insurance receipts. 7j/7. No family doctor required.