Classic Hodgkin lymphoma (cHL): Treatment of unfavorable prognosis early (stage I-II) cHL in adults

INTRODUCTION — Classic Hodgkin lymphoma (cHL) is a lymphoma in which malignant Hodgkin/Reed-Sternberg (HRS) cells are embedded in a polymorphous infiltrate that includes reactive (ie, nonmalignant) lymphocytes, eosinophils, fibroblasts, and other inflammatory cell types. HRS cells are derived from transformed B lymphocytes. Prototypical HRS cells have a characteristic morphology with prominent nucleoli in separate nuclear lobes ("owl's eyes") (picture 1), but mononuclear and other HRS variants are common.

The management of cHL is stratified by disease stage and prognostic features:

●Advanced stage – Stage III or stage IV. (See "Initial treatment of advanced (stage III-IV) classic Hodgkin lymphoma".)

●Limited stage – Stage I or stage II. The management of limited-stage cHL is further stratified according to the presence of adverse prognostic features:

•Unfavorable prognosis – The presence of a large mediastinal mass; bulky nodal disease; >3 sites of involvement; systemic systems ("B" symptoms of fever, drenching sweats, weight loss); erythrocyte sedimentation rate (ESR) >50 mm/hour or >30 mm/hour if B symptoms are present.

•Favorable prognosis – None of the negative prognostic features. (See "Treatment of favorable prognosis early (stage I-II) classic Hodgkin lymphoma".)

There are four histologic subtypes of cHL (nodular sclerosis cHL, lymphocyte predominant cHL, mixed cellularity cHL, lymphocyte depleted cHL) that have different demographic features and prognoses, but management is not guided by the cHL histologic subtype.

The treatment of unfavorable prognosis early-stage cHL is discussed in this topic.

The evaluation, diagnosis, and staging of cHL are discussed separately. (See "Clinical presentation and diagnosis of classic Hodgkin lymphoma in adults" and "Pretreatment evaluation, staging, and treatment stratification of classic Hodgkin lymphoma".)

Nodular lymphocyte predominant B cell lymphoma (also called nodular lymphocyte predominant Hodgkin lymphoma) is not a subtype of cHL and is discussed separately. (See "Nodular lymphocyte-predominant Hodgkin lymphoma: Clinical manifestations, diagnosis, and staging".)

EVALUATION — The disease stage, prognostic category, and medical fitness of a patient with cHL must be established prior to treatment.

The clinical presentation, initial evaluation, pathologic features, diagnostic criteria, and differential diagnosis of cHL are presented separately. (See "Clinical presentation and diagnosis of classic Hodgkin lymphoma in adults".)

Clinical and laboratory

●History – Constitutional "B" symptoms (unexplained fever >38^°C, drenching night sweats, weight loss >10 percent), location and duration of lymphadenopathy and/or organomegaly, and comorbid illnesses.

●Examination – Physical examination may reveal lymphadenopathy and findings associated with comorbid conditions (eg, heart or lung disease).

●Laboratory

•Hematology

-Complete blood count and differential count

-Erythrocyte sedimentation rate (ESR)

•Chemistries – Complete metabolic panel, including kidney and liver function tests, and lactate dehydrogenase.

•Infectious – Human immunodeficiency virus (HIV), hepatitis B, and hepatitis C.

Imaging

●Positron emission tomography (PET)/computed tomography (CT)

●Chest radiograph – A chest radiograph is optional. It is used to define bulk disease in the EORTC (European Organisation for Research and Treatment of Cancer) risk stratification system. Definitions of an unfavorable prognosis are described below. (See 'Unfavorable prognosis' below.)

Chest radiography can also be used as a convenient, inexpensive, and low-radiation method for monitoring the response of a mediastinal mass to treatment.

●Other – Contrast-enhanced CT and/or magnetic resonance imaging (MRI), if needed to evaluate suspected extranodal sites of disease.

Other

●Heart

•Electrocardiogram.

•Echocardiogram or radionuclide ventriculography for cardiac ejection fraction.

•Some experts prescribe a statin to reduce cardiac dysfunction in patients who will receive an anthracycline. A phase 3 trial that randomly assigned atorvastatin versus placebo to 300 patients who were scheduled to receive anthracycline-based chemotherapy demonstrated less decline in ejection fraction among those who received atorvastatin, but there was no difference in heart failure rate [1], as discussed separately. (See "Risk and prevention of anthracycline cardiotoxicity", section on 'Primary prevention with cardiovascular drugs'.)

●Lungs – Pulmonary function tests, including diffusing capacity for carbon monoxide (DLCO); DLCO ≥60 percent is generally required for treatment with bleomycin.

●Bone marrow examination – A bone marrow examination is not generally required.

A bone marrow examination should be performed if there is thrombocytopenia and/or neutropenia without multiple (eg, ≥3) sites of marrow involvement by PET. Note that a homogeneous pattern of marrow uptake (which is thought to be caused by cytokine release) is not considered evidence of marrow involvement.

●Fertility

•Pregnancy test, if appropriate.

•Fertility preservation, if appropriate.

STAGING AND PROGNOSIS — Treatment decisions are guided by the disease stage and prognostic category.

Stage — Staging is based on positron emission tomography (PET)/CT, interpreted using the five-point (Deauville) scoring system (table 1), and according to the Lugano classification (table 2) [2]. (See "Pretreatment evaluation, staging, and treatment stratification of classic Hodgkin lymphoma".)

●Early-stage cHL – Defined as stage I or II disease:

•Stage I – Involvement of a single lymph node region (I) or of a single extralymphatic organ or site (IE).

•Stage II – Involvement of two or more lymph node regions on the same side of the diaphragm alone (II) or with involvement of limited contiguous extralymphatic organ or tissue (IIE).

●Advanced-stage cHL – Defined as stage III or IV:

•Stage III – Involvement of lymph node regions or lymphoid structures on both sides of the diaphragm.

•Stage IV – Additional noncontiguous extralymphatic involvement, with or without associated lymphatic involvement.

Unfavorable prognosis — The management of early-stage cHL is stratified according to prognostic category (ie, favorable versus unfavorable prognosis), but criteria vary among research groups.

The preferred method for assessing a prognosis varies among practitioners, but the choice of prognostic scoring system should adhere to what was used in the chosen treatment protocol.

●GHSG (German Hodgkin Study Group)

•Mediastinal mass – >0.33 mediastinal mass ratio (MMR; maximum width of mass/maximum intrathoracic diameter).

•Number of nodal sites – >2 (note that GHSG includes the infraclavicular/subpectoral area with the cervical area and considers involvement of the mediastinum plus hila a single region).

•B symptoms or erythrocyte sedimentation rate (ESR) – ESR >50 if no B symptoms; ESR >30 if B symptoms present.

•Extranodal disease – Any extranodal disease.

●EORTC (European Organisation for Research and Treatment of Cancer)

•Age – ≥50 years.

•Mediastinal mass – >0.35 mediastinal thoracic ratio (MTR; maximum width of mediastinal mass/intrathoracic diameter at T5-6).

•B symptoms or ESR – ESR >50 if no B symptoms; ESR >30 if B symptoms present.

•Number of nodal sites – >3 (note that EORTC includes the infraclavicular/subpectoral area with the axillary area and considers involvement of the mediastinum plus hila a single region).

●NCCN (National Comprehensive Cancer Network) – At least one of the following:

•Mediastinal mass – >0.33 MMR

•Bulky disease – >10 cm mass

•B symptoms or ESR – Any B symptoms or ESR ≥50

•Number of nodal sites – >3

MANAGEMENT

Response-guided therapy — For unfavorable prognosis early-stage cHL, we use positron emission tomography (PET) response-guided therapy rather than a predetermined course of treatment. This strategy permits the individualization of treatment based on the PET response to initial systemic treatment. As a result, patients with a robust response to initial therapy are spared unnecessary treatment and attendant toxicity, while those with less responsive disease can receive treatment modified according to the nature and degree of response.

Response-guided therapy involves:

●Two initial cycles of systemic chemotherapy (see 'Initial systemic therapy' below)

●Interim restaging with PET after two treatment cycles (PET2) (see 'PET2 interim response' below)

●Further therapy guided by PET2 response (see 'Further treatment' below)

There is no evidence that overall survival (OS) differs with the routine use of combined modality therapy (CMT; ie, chemotherapy followed by radiation therapy [RT]) compared with response-guided therapy. Routine CMT is associated with fewer relapses but more late treatment-related adverse effects (AEs). Because there are effective salvage therapies for relapsed/refractory cHL, a higher rate of relapses does not necessarily translate into inferior OS. Short-term AEs are similar with both approaches, but the incidence of late AEs is not well defined using contemporary chemotherapy and RT.

Initial systemic therapy — For patients with unfavorable prognosis early-stage cHL, we recommend initial treatment with two cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) rather than other chemotherapy regimens, based on the more favorable balance of outcomes and toxicity with ABVD.

After treatment with two cycles of ABVD, further therapy is guided by the PET2 response, as described below. (See 'Further treatment' below.)

●Administration – ABVD includes each of the following drugs given on days 1 and 15 of each 28-day cycle (table 3); two treatments are considered one 28-day treatment cycle.

•Doxorubicin 25 mg/m² intravenously

•Bleomycin 10 units/m² intravenously

•Vinblastine 6 mg/m² intravenously

•Dacarbazine 375 mg/m² intravenously

ABVD is given without regard for the absolute neutrophil count (ANC), with no dose reductions, treatment delays, or growth factor (eg, filgrastim) support. Dose intensity >99 percent can be achieved without filgrastim support [3].

●Toxicity – The main grade ≥3 acute AEs are leukopenia (24 percent), alopecia (24 percent), and nausea/vomiting (14 percent) [4]. Long-term toxicities include cardiopulmonary toxicity, neuropathy, and second malignancies. (See "Approach to the adult survivor of classic Hodgkin lymphoma".)

●Outcomes – No chemotherapy regimen has been shown to offer a more favorable balance of efficacy and toxicity for early-stage cHL than ABVD.

•In two randomized trials of unfavorable prognosis early-stage cHL, BEACOPP-based (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) (table 4) CMT was more toxic than ABVD-based CMT, but it did not achieve better survival. Neither GHSG (German Hodgkin Study Group) HD11 nor EORTC (European Organisation for Research and Treatment of Cancer) H9U demonstrated a difference in OS or freedom from progression between BEACOPP and ABVD, but BEACOPP caused more grade ≥3 AEs (74 versus 52 percent) [5,6].

•In the phase 3 HD14 trial, CMT using hybrid BEACOPP/ABVD chemotherapy (two cycles of escalated BEACOPP followed by two cycles of ABVD) was associated with a similar OS but more toxicity than CMT using four cycles of ABVD [4,7]. A systematic review of five trials (3427 patients) reported that BEACOPP was associated with better OS (hazard ratio [HR] 0.74 [95% CI 0.57-0.97]) but more grade ≥3 AEs (relative risk [RR] 3.73 [95% CI 2.58-5.38]) [8]. Despite limited long-term follow-up for AEs, BEACOPP was associated with more acute myeloid leukemia and myelodysplastic syndromes/neoplasms (RR 3.90 [95% CI 1.36-11.21]).

Long-term outcomes with BV+AVD (brentuximab vedotin, doxorubicin, vinblastine, dacarbazine) for the treatment of early-stage cHL are not yet available. The phase 2 BREACH study randomly assigned (2:1) 170 patients with unfavorable prognosis early-stage cHL to BV+AVD or ABVD; both chemotherapy regimens were followed by 30 gray (Gy) involved node RT (INRT) [9]. BV+AVD achieved an 88 percent complete response (CR) compared with a 77 percent CR with ABVD, but there was no difference in progression-free survival (PFS). There was more grade ≥3 neutropenia and febrile neutropenia with BV+AVD, but they had similar rates of infections. In a small study, the treatment of unfavorable prognosis early-stage cHL using four cycles of BV+AVD (without RT) was associated with a 99 percent two-year OS and 94 percent two-year PFS [10].

Treatment with BV+AVD for advanced-stage cHL is discussed separately. (See "Initial treatment of advanced (stage III-IV) classic Hodgkin lymphoma", section on 'Initial treatment'.)

PET2 interim response — PET2 (ie, PET after two cycles of ABVD) is performed to assess the response to initial systemic therapy.

Response is judged using the five-point (Deauville) scoring system (table 1) according to the Lugano classification (table 2):

●CR – Deauville score 1 to 3

●Less than CR – Deauville score 4 to 5

Further treatment — Further management is guided by the PET2 response, as discussed below. (See 'Complete response' below and 'Deauville 4' below and 'Deauville 5' below.)

For patients with CR (Deauville score 1 to 3) or Deauville score 4 on PET2, the choice of CMT (ie, additional chemotherapy plus RT) versus chemotherapy only (ie, no RT) is informed by toxicity, comorbidities, risk factors for AEs, and personal preference.

We consider the following when selecting an approach:

●Higher risk with RT – Chemotherapy only may be preferred for patients in whom RT presents a higher risk of short-term and/or long-term AEs. As examples:

•A young woman with nonbulky bilateral axillary and mediastinal disease might favor chemotherapy alone and accept a slightly higher risk of recurrence in exchange for a reduced long-term risk of breast cancer.

•A patient with a higher risk for lung cancer (eg, substantial smoking history, industrial exposures) might consider that RT would add excessive risk.

•Patients with underlying cardiac disease or cardiac risk factor(s) with an estimated mean heart dose >8 Gy based on disease distribution.

●Higher risk with chemotherapy alone – CMT may be preferred for patients with a higher risk for cardiac toxicity or other chemotherapy-related AEs.

As an example:

•Older patients and those with heart disease or significant cardiovascular risk factors may favor CMT to limit the cumulative exposure to doxorubicin.

Complete response — For patients with CR on PET2, CMT or chemotherapy only are appropriate options. Both approaches are associated with similar long-term survival, but toxicity and risks for relapse differ. Relapse may be more common with chemotherapy only, but effective treatments are available for relapsed cHL. CMT has been associated with more second cancers, but the risk has declined with contemporary chemotherapy and RT.

The selection of CMT versus chemotherapy should be individualized, with consideration of the sites/volume of disease (which may affect RT fields), comorbidities, risk factors for late AEs (eg, cardiac risk factors, age, female sex, smoking history, family history), and patient preference. Examples of clinical scenarios that might influence the choice of CMT versus chemotherapy only are discussed above. (See 'Further treatment' above.)

Trials that inform treatment choices for patients with CR on PET2 include:

●CMT versus chemotherapy only – There was no difference in survival for patients with early-stage cHL who received CMT versus chemotherapy only after CR on PET2 in EORTC H10 [11]. Patients with CR on PET2 were randomly assigned to four additional cycles of ABVD (six cycles total) versus CMT (two additional cycles of ABVD followed by 30 to 36 Gy INRT). Trial enrollment was terminated when a planned interim analysis of the combined favorable and unfavorable arms reported that ABVD only was associated with inferior PFS compared with CMT; however, there was no difference in PFS between trial arms for the subgroup of patients with unfavorable prognosis disease. With longer follow-up, there was no difference in OS or PFS for the entire trial population [12].

●Chemotherapy only

•Treatment with four cycles of AVD (doxorubicin, vinblastine, dacarbazine; ie, no further bleomycin) after achieving CR on PET2 was associated with excellent outcomes in the phase 3 RATHL (Response-Adapted Therapy in Advanced Hodgkin Lymphoma) trial; nearly one-half of the enrolled patients had unfavorable prognosis early-stage cHL [13]. Patients with CR on PET did not receive RT; instead, they were randomly assigned to four additional cycles of AVD versus four additional cycles of ABVD. The chemotherapy regimens had similar efficacy, but AVD was associated with less toxicity.

•In the GHSG HD17 trial, there was no loss of efficacy when RT was omitted in patients who achieved CR with four cycles of chemotherapy [14]. Patients with unfavorable prognosis early-stage cHL received initial treatment with two cycles of escalated BEACOPP followed by two cycles of ABVD; those who achieved CR were then randomly assigned to standard CMT (30 Gy INRT) versus response-guided therapy (ie, RT for patients with positive PET4 [PET after four treatment cycles]; no RT for patients with CR). Compared with standard CMT, there was no difference in the five-year PFS for patients with CR after chemotherapy who did not receive RT. Cytopenias were similar with both approaches, but 6 percent of patients treated with CMT experienced dysphagia and/or mucositis.

●Second cancers

•Long-term follow-up of GHSG HD11 reported that CMT using ABVD with RT was associated with 5 percent cumulative incidence of second cancers after 10 years; this corresponds to a 1.4-fold increase in second cancers compared with the age- and sex-matched general population [15]. Risks of second cancers and other late AEs after RT are discussed separately. (See "Second malignancies after treatment of classic Hodgkin lymphoma" and "Approach to the adult survivor of classic Hodgkin lymphoma", section on 'Late complications'.)

•There was no difference in late AEs between patients who received RT and those who did not receive RT in the GHSG HD17 trial after nearly four years of follow-up [14].

•In the RATHL trial, with a 41-month median follow-up, second cancers were reported in 2.4 percent of patients who were treated with chemotherapy (either ABVD or AVD) only (no RT) [13].

Monitoring for relapse and for treatment-related AEs is described below. (See 'Monitoring' below.)

Combined modality therapy — For patients with CR on PET2 who choose CMT, we suggest two additional cycles of ABVD (four cycles total) followed by 30 Gy involved site RT (ISRT) or INRT.

Patients who might favor CMT rather than chemotherapy only are discussed above. (See 'Further treatment' above.)

CMT using four cycles of ABVD plus RT is supported by the following studies:

●EORTC H9U included patients with unfavorable prognosis early-stage cHL who were randomly assigned to 30 Gy involved field RT (IFRT) following either six cycles of ABVD or four cycles of ABVD [6]. The five-year OS and event-free survival were similar in both trial arms, indicating that four cycles of ABVD are sufficient in this setting.

●For patients with unfavorable prognosis early-stage cHL, four cycles of ABVD plus 30 Gy RT in GHSG HD11 were associated with a 94 percent five-year OS and 87 percent five-year PFS [5].

A phase 3 trial (EORTC H10) that compared CMT versus chemotherapy only for patients with CR on PET2 is presented above. (See 'Complete response' above.)

Chemotherapy only — For patients with CR on PET2 who choose chemotherapy only, we suggest four cycles of AVD rather than further treatment with ABVD, based on the more favorable balance of outcomes and toxicity with AVD.

Patients who might favor chemotherapy only (ie, no RT) are discussed above. (See 'Complete response' above.)

The administration of AVD is like that of ABVD, but bleomycin is omitted. (See 'Initial systemic therapy' above.)

●Outcomes

•Treatment using four additional cycles of AVD achieved similar outcomes but less toxicity compared with four additional cycles of ABVD in the RATHL trial; 42 percent of the 1214 enrolled patients had unfavorable prognosis early-stage cHL [13]. Among patients with CR on PET2 who were randomly assigned to four cycles of either ABVD or AVD, there was no difference in the three-year OS (97.2 versus 97.6 percent, respectively) or three-year PFS (85.7 versus 84.4 percent). Compared with AVD, treatment with ABVD was associated with more clinical AEs of any grade (31 versus 21 percent) and more grade ≥3 pulmonary/upper respiratory AEs (3 versus 1 percent), dyspnea (2 versus <0.5 percent), and neutropenic fever (5 versus 2 percent).

•In CALGB 50801, patients with unfavorable prognosis early-stage cHL with bulky disease who achieved CR on PET2 received four additional cycles of ABVD [16]. The three-year OS was 98.6 percent and three-year PFS was 93.1 percent. Grade ≥3 AEs included 8 percent febrile neutropenia.

•In H10U, patients with unfavorable prognosis early-stage cHL who were treated with four additional cycles of ABVD (six cycles total; no RT) after achieving CR on PET2 had an 89.6 percent five-year PFS, which was not different from the outcomes of patients treated with CMT (two additional cycles of ABVD plus RT) [17].

A phase 3 trial (EORTC H10U) that compared CMT versus chemotherapy only for patients with CR on PET2 is discussed above. (See 'Complete response' above.)

Deauville 4 — For patients with extensive or multiple sites of Deauville 4 on PET2, we suggest CMT (further chemotherapy plus RT) rather than chemotherapy alone.

●CMT for patients with Deauville score 4 is described below. (See 'Combined modality therapy' below.)

●Some experts consider intensified response-guided chemotherapy alone to be an acceptable alternative, especially for patients who may have less tolerance for RT based on comorbidities or distribution of disease. Intensified response-guided chemotherapy is discussed below. (See 'Chemotherapy' below.)

For patients with a single site of Deauville score 4, treatment is individualized. Acceptable options include treatment like that for Deauville score 4 or treatment like that for CR on PET2, as described above. (See 'Complete response' above.)

No randomized trials have directly compared CMT versus intensified chemotherapy only in this setting. In general, outcomes are similar with both approaches, but it is difficult to compare results across studies because of different patient populations, study criteria, and treatment regimens.

●CMT – The chemotherapy component of CMT has varied among studies.

•In the EORTC H10 trial, patients with unfavorable prognosis early-stage cHL who had Deauville score 4 or 5 on PET2 were randomly assigned to CMT using two additional cycles of ABVD versus two cycles of escalated BEACOPP; all these patients received 30 Gy INRT after completing chemotherapy [17]. There was no difference in the 10-year OS (89.3 percent with ABVD versus 96.0 percent with escalated BEACOPP) or PFS between the two CMT regimens [12]. BEACOPP was associated with more grade ≥3 toxicity, including febrile neutropenia (24 versus 1 percent), neutropenia (54 versus 30 percent), and thrombocytopenia (20 versus 0 percent), while ABVD was associated with more disease progression/relapse (11 versus 3 percent).

•In CALGB 50801, patients with unfavorable prognosis early-stage cHL with bulky disease who had less than CR were treated with four cycles of escalated BEACOPP followed by 30.6 Gy IFRT [16]. The three-year OS was 94.4 percent, and the three-year PFS was 89.7 percent [16].

●Intensified chemotherapy

•In the RATHL trial, the three-year OS was 87.8 percent for patients treated with three or four cycles of BEACOPP for positive PET2; few patients went on to receive consolidation RT [13].

Combined modality therapy — The preferred chemotherapy component of CMT in this setting varies among study groups.

The chemotherapy component of CMT is individualized according to fitness, age, volume of disease, and patient preference. We consider the following when selecting a chemotherapy component of CMT in this setting:

●We avoid further treatment with a bleomycin-containing regimen in patients >60 years or those with lung disease or creatinine clearance below 25 to 35 mL/min.

●For patients >60 years or with lung comorbidities, CMT using AVD is acceptable.

●For patients who presented with bulky disease, some experts favor four cycles of escalated BEACOPP followed by 30.6 Gy RT, as per CALGB 50801 [16].

Outcomes with CMT for less than CR on PET2 are presented above. (See 'Deauville 4' above.)

Chemotherapy — There is no consensus for patients who will be treated with chemotherapy only for Deauville score 4 on PET2.

Options include:

●ABVD – Two cycles of ABVD followed by PET restaging. Patients who achieve CR (Deauville score 1 to 3) can receive one or two additional cycles of ABVD or AVD, or consolidative RT. Patients with less than CR should be managed as refractory cHL, as discussed separately. (See "Treatment of relapsed or refractory classic Hodgkin lymphoma".)

●Intensified chemotherapy – Some experts favor treatment escalation using two or three cycles of either escalated BEACOPP or BrECADD (brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone) followed by PET restaging. For CR on restaging, patients can receive one or two cycles of further chemotherapy, with or without RT. Patients with less than CR should be managed as refractory cHL, as discussed separately. (See "Treatment of relapsed or refractory classic Hodgkin lymphoma".)

Deauville 5 — We biopsy the site of persistent activity to exclude an alternative diagnosis (eg, infection, another malignancy).

Management is guided by the biopsy findings:

●No viable cHL – Treat like Deauville score 4. (See 'Deauville 4' above.)

●Persistent cHL – Treat for refractory cHL, as described separately. (See "Treatment of relapsed or refractory classic Hodgkin lymphoma".)

If a biopsy is not performed, we treat as described for Deauville score 4. (See 'Deauville 4' above.)

MONITORING — After completing planned therapy, the patient is monitored for relapse and adverse effects of treatment. Imaging should be limited to avoid unnecessary radiation exposure.

●Frequency of visits – The patient should be seen every three months in the first year, every four to six months in the second year, and then annually.

●Evaluation – Interim history, physical examination, and laboratory studies, including:

•Hematology

-Complete blood count and differential count

-Erythrocyte sedimentation rate should be performed if it was elevated at diagnosis

•Chemistries – Complete metabolic panel, including kidney and liver function tests, and lactate dehydrogenase.

•Imaging – Imaging is performed as clinically indicated, but routine surveillance imaging is generally not performed.

If clinically indicated, CT can be obtained up to every six months for the first two years (ie, ≤4 CTs total) or if relapse is suspected.

To reduce radiation exposure and avoid false-positive results, positron emission tomography should be performed only for a suspected relapse.

CLINICAL TRIALS — Often there is no better therapy to offer a patient than enrollment onto a well-designed, scientifically valid, peer-reviewed clinical trial. Additional information and instructions for referring a patient to an appropriate research center can be obtained from the United States National Institutes of Health (www.clinicaltrials.gov).

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Management of Hodgkin lymphoma".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Beyond the Basics topics (see "Patient education: Hodgkin lymphoma in adults (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Description – The management of cHL is guided by disease stage and prognostic category.

Unfavorable prognosis early-stage cHL refers to:

•Stage I or stage II – ≥1 site of nodal disease on one side of the diaphragm, with or without limited extralymphatic disease. (See 'Stage' above.)

plus

•Unfavorable prognosis – Criteria for unfavorable prognosis vary among research groups. (See 'Unfavorable prognosis' above.)

●Initial therapy – We suggest two initial cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) rather than other regimens (Grade 2C). (See 'Initial systemic therapy' above.)

●Interim response assessment – Positron emission tomography (PET) is repeated after two treatment cycles (PET2), using the five-point PET (Deauville) score (table 1), as defined by Lugano criteria (see 'PET2 interim response' above):

●Complete response (CR) on PET2 – For Deauville score 1 to 3, treatment is individualized by toxicity, comorbidities, and patient preference, as discussed above (see 'Complete response' above):

Either of the following approaches is acceptable for CR on PET2:

•Combined modality therapy (CMT) – For CMT, we suggest two additional cycles of ABVD (four cycles total) (table 3) followed by radiation therapy (RT) rather than four additional cycles of ABVD (six cycles total) followed by RT (Grade 2B). (See 'Combined modality therapy' above.)

•Chemotherapy only – For chemotherapy only, we suggest four cycles of AVD (doxorubicin, vinblastine, dacarbazine; ie, no bleomycin) rather than additional ABVD (Grade 2B). (See 'Chemotherapy only' above.)

●Less than CR on

•Deauville score 4 – For extensive or multiple sites of Deauville score 4, we suggest CMT rather than chemotherapy alone (Grade 2C). (See 'Deauville 4' above.)

Some experts consider chemotherapy alone (no RT) acceptable; the treatment may be individualized according to comorbidities and patient preference.

Either of the following approaches is acceptable:

-CMT – Further chemotherapy followed by RT. There is no consensus chemotherapy component of CMT; acceptable options include two to four cycles of ABVD and escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) (table 4). (See 'Combined modality therapy' above.)

-Intensified chemotherapy – Two or three cycles of ABVD, escalated BEACOPP, or BrECADD (brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone) followed by PET restaging. Patients who achieve CR can receive further chemotherapy, with or without consolidative RT. Patients with less than CR are managed as refractory cHL. (See "Treatment of relapsed or refractory classic Hodgkin lymphoma".)

For a single site of Deauville 4, acceptable options include treatments like that for Deauville score 4 or like CR on PET2. (See 'Complete response' above.)

•Deauville score 5 – Biopsy the site of PET activity.

-If no biopsy is obtained, or if there is no viable cHL, treat like Deauville 4. (See 'Deauville 4' above.)

Treat biopsy-proven persistent cHL like refractory cHL. (See "Treatment of relapsed or refractory classic Hodgkin lymphoma".)

●Monitoring – Monitor for relapse and treatment-related adverse effects. Imaging is limited or avoided, except for suspected relapse. (See 'Monitoring' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate acknowledges Peter M Mauch, MD, who contributed to earlier versions of this topic review.