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 "Classic Hodgkin lymphoma: Presentation, evaluation, and diagnosis 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 "Classic Hodgkin lymphoma: Presentation, evaluation, and diagnosis 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)

●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.

●Contrast-enhanced CT and/or magnetic resonance imaging (MRI) can be performed, as clinically indicated, 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

RESPONSE-GUIDED THERAPY — 

We use response-guided therapy to treat unfavorable prognosis early-stage cHL.

Positron emission tomography (PET) is used to assess response to initial systemic therapy and individualize treatment. With this approach, patients with a robust response to initial therapy are spared unnecessary treatment (eg, excessive chemotherapy or radiation therapy [RT]) 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 therapy' below)

Initial systemic therapy — For patients with unfavorable prognosis early-stage cHL, we recommend initial treatment with two cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) (algorithm 1) rather than other chemotherapy regimens based on the favorable balance of outcomes and toxicity with ABVD.

PET is performed after two cycles of ABVD (PET2). (See 'PET2 interim response' below.)

Further management is guided by the PET2 response. (See 'Further therapy' 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 offers a more favorable balance of efficacy and toxicity for early-stage cHL than ABVD.

•In two randomized trials of unfavorable prognosis early-stage cHL, combined modality therapy (CMT) using BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) (table 4) was more toxic than CMT using ABVD, 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 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".)

PET2 interim response — PET2 (ie, PET after two cycles of ABVD) is performed to assess the response to initial systemic therapy (algorithm 1).

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

●CR – Deauville score 1-3

●Partial response – Deauville score 4 or 5 and no new sites of PET activity

●Progressive disease – New sites of PET activity

Further therapy — Further management is guided by the PET2 response, as discussed in the sections that follow.

Complete response — For patients with CR (ie, Deauville score 1-3) on PET2, we consider either chemotherapy-only or CMT (chemotherapy plus RT) acceptable (algorithm 1). These approaches are associated with similar long-term survival, but adverse effects (AEs) differ.

The choice of further therapy should consider 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.

Factors that might influence the choice of CMT versus chemotherapy-only for a patient with CR on PET2 include:

●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-only 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.

●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.

Studies that inform treatment choice in this setting include:

●CMT versus chemotherapy-only

In EORTC H10, there was no difference in survival with CMT versus chemotherapy-only for patients with early-stage cHL and CR on PET2 [11]. Patients 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 entire enrolled population (ie, both favorable and unfavorable prognosis) reported that PFS was inferior for patients treated with chemotherapy-only; 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 PET2 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 after 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, no RT for patients with CR on PET4; RT for patients with positive PET4). Compared with standard CMT, there was no difference in five-year PFS for patients with CR on PET4 who did not receive RT. Cytopenias were similar with both approaches, but 6 percent of patients treated with CMT experienced dysphagia and/or mucositis.

●Treatment-related second cancers – There is no persuasive evidence that CMT and chemotherapy-only differ in their risks for second cancers in patients with cHL. Fears that RT might increase second cancers are generally extrapolated from older studies that used now-outdated RT techniques (eg, mantle fields).

Nevertheless, some patients may seek to avoid RT because of their individual risk factors (eg, risk of lung cancer in patients with a history of smoking or industrial exposures)

•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].

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

•In the RATHL trial, second cancers were reported in 2.4 percent of patients treated with chemotherapy-only (either ABVD or AVD) after median follow-up of 41 months [13].

Studies of non-Hodgkin lymphoma (NHL) may also be informative regarding treatment-related second cancers. A population-based study of 142,637 patients with NHL reported no increase in second cancers in patients who received RT [16]. Compared with a matched general population, the relative risk for second cancers in patients with NHL was 1.29, but no excess risk was associated with RT. The risk for female breast cancer in patients who received RT was not different from the endemic population. Other studies of NHL also reported no increase of second cancers in patients treated with RT [17-19].

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'.)

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 (algorithm 1).

The choice of CMT versus chemotherapy-only in this setting is discussed above. (See 'Complete response' 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 (algorithm 1) rather than further treatment with ABVD, based on the more favorable balance of outcomes and toxicity with AVD.

The choice of chemotherapy-only versus CMT in this setting is discussed above. (See 'Complete response' above.)

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 [20]. 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) [21].

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

Partial response — For partial response (PR; Deauville score 4 or 5) and no progressive disease on PET2, we suggest response-guided therapy with two additional cycles of ABVD (algorithm 1) rather than escalated BEACOPP. Outcomes are comparable with both approaches, but ABVD is less toxic.

For patients who presented with bulky disease and had PR on PET2, some experts favor four cycles of escalated BEACOPP followed by 30.6 Gy RT (per CALGB 50801 [20]), as discussed below.

For response-guided therapy, PET is repeated after two additional cycles of ABVD (PET4), and further therapy is guided by PET4 findings:

●CR – For CR on PET4 (Deauville 1-3), treat with 30 Gy RT (algorithm 1).

Some experts treat with two additional cycles of chemotherapy (AVD or ABVD) prior to RT, but no studies have compared RT-alone versus additional chemotherapy plus RT in this setting.

If treating with additional chemotherapy prior to RT, we favor AVD for patients with lung comorbidities, age >60 years, or creatinine clearance below 25 to 35 mL/min to avoid further bleomycin.

•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 [20].

●PR or progressive disease – For patients with PR or progressive disease (PD) on PET4, we biopsy a site of persistent (Deauville 4) or progressive (Deauville 5) disease (algorithm 1) and manage as discussed below. (See 'Progressive disease' below.)

Response-guided therapy using ABVD and treatment with escalated BEACOPP for PR on PET2 achieved similar outcomes, but BEACOPP is more toxic.

●In EORTC HD10, patients with unfavorable prognosis early-stage cHL who were PET positive (Deauville score 4 or 5) after two cycles of ABVD were randomly assigned to further ABVD versus BEACOPP; all received 30 Gy INRT after completing chemotherapy [21]. BEACOPP was associated with greater toxicity, but there was no difference in 10-year OS (89.3 percent with ABVD versus 96.0 percent with escalated BEACOPP) or 10-year PFS between the two regimens [12]. BEACOPP caused 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 the RATHL trial, patients with positive PET after two cycles of ABVD were treated with three or four cycles of BEACOPP [13]. Following completion of BEACOPP therapy, PET was negative in 74.4 percent; 20 patients with persistent PET activity after BEACOPP received consolidation RT. For all patients treated with BEACOPP in RATHL, three-year OS was 87.8 percent, and three-year PFS was 67.5 percent. Grade ≥3 AEs occurred in >80 percent of patients, including febrile neutropenia in 26 percent.

●In CALGB 50801, patients with bulky early-stage cHL with PR on PET2 were treated with four cycles of escalated BEACOPP followed by 30.6 Gy [20]. Treatment was associated with significant toxicity, but three-year OS was 89.7 percent.

Progressive disease — We biopsy the site of persistent PET activity to exclude an alternative diagnosis (eg, infection, inflammation, gray zone lymphoma, another cancer) (algorithm 1).

Management is guided by the biopsy findings:

●No viable cHL – For patients with little or no viable cHL on biopsy, we treat with two additional cycles of chemotherapy (either ABVD or AVD) followed by 30 Gy RT to the site of persistent PET activity.

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

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 – Management of classic Hodgkin lymphoma (cHL) is guided by disease stage and prognostic category.

Unfavorable prognosis early-stage cHL describes:

•Stage I or stage II – 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.)

●Response-guided therapy – We use positron emission tomography (PET) response-guided therapy, which enables individualized treatment. Patients with a robust response to initial treatment are spared unnecessary treatment/toxicity, while management is modified for those with less responsive disease. (See 'Response-guided therapy' above.)

●Initial therapy – We recommend two initial cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) (table 3) rather than other regimens (Grade 1B) (algorithm 1). (See 'Initial systemic therapy' above.)

●Interim response – PET is performed after ABVD x 2 (PET2) and assessed using the five-point PET (Deauville) score (table 1). (See 'PET2 interim response' above.)

●Complete response (CR) on PET2 – For CR (Deauville score 1-3) on PET2, we consider either chemotherapy-only or combined modality therapy (CMT) acceptable (algorithm 1). Selection of further therapy considers sites/volume of disease, comorbidities, risk factors for late adverse effects, and patient preference, as discussed above. (See 'Complete response' above.)

•CMT – For CMT, we suggest two additional cycles of ABVD (four cycles total) 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.)

●Partial response (PR) on PET2 – For PR (Deauville 4 or 5) and no sites of progressive disease (PD) on PET2, we suggest response-guided therapy with two additional cycles of ABVD (algorithm 1) rather than treatment escalation with BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) (table 4). (See 'Partial response' above.)

Some experts favor four cycles of BEACOPP followed by RT for patients who initially presented with bulky disease and had PR on PET2.

Response-guided therapy is guided by results of PET performed after two additional cycles of ABVD (PET4):

•CR – For Deauville 1-3 on PET4, we treat with 30 gray RT (algorithm 1); some experts treat with two additional cycles of chemotherapy prior to RT.

•PR or PD – For patients with PR or PD on PET4, we biopsy a site of persistent (Deauville 4) or progressive (Deauville 5) disease (algorithm 1).

●PD on PET2 – We biopsy the site of persistent PET activity to exclude an alternative diagnosis (algorithm 1). Further management is guided by the biopsy findings, as discussed above. (See 'Progressive disease' above.)

●Monitoring – PET is repeated after completing planned therapy. (See 'Monitoring' above.)

Clinical evaluation may be supplemented by imaging, if needed, to monitor for relapse and treatment-related adverse effects.

ACKNOWLEDGMENT — 

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