Pocket Oncology (Pocket Notebook Series), 1st Ed.

HODGKIN LYMPHOMA

Zachary H. Word and Craig Moskowitz

Epidemiology

• Represents ∼12% of lymphomas

• ∼8–9K cases annually in US, resulting in ∼1300 death

• Typically affects younger pts (20s–30s) but can also affect older adults

Biology/Pathology

• 2 major types:

Classical HL

NLPHL

• Classical HL characterized pathologically by the Reed–Sternberg Cell, a large, bilobed, or multinucleated cell that classically has an “owl’s eyes” appearance & stains (+) for CD15 & CD30

• Subtypes of Classical HL include: Nodular sclerosis (most common), lymphocyte rich, mixed cellularity, & lymphocyte depleted. Tx does not differ among these subtypes

• NLPHL is a more indolent disease characterized by the Lymphocytic & Histiocytic cell, a Reed–Sternberg variant that stains negative for CD15 & CD30, but (+) for CD20

Workup

• Excisional bx preferred for initial dx; core-needle bx may be adequate, FNA typically inadequate

• Cross-sectional imaging w/PET/CT

• BM bx required for complete staging

• Echo if anthracycline to be used, PFTs if bleomycin to be used

Staging

• Cotswolds modification of the Ann Arbor Staging System (Lister TA, et al. J Clin Oncol 1989;7:1630)

Risk Factors

• The IPS includes 7 RFs for adverse outcome (N Engl J Med 1998; 339:1506):

Serum albumin <4 g/dL

WBC ≥15K

Male sex

Hb <10.5 g/dL

Age ≥45

Stage IV

Lymphocyte count <600/mm3 or <8% of WBC

• Other RFs include: B-sx, elevated ESR, bulky disease, mixed-cellularity or lymphocyte depleted histology, abdominal or pulmonary hilar involvement & increasing number of nodal sites

Management: Early Stage Disease

• Includes Stages I–IIA, nonbulky

• Standard combined modality Rx w/2–4 cycles of ABVD & 20–30 Gy ISRT results in PFS ∼85% & OS >90% (J Clin Oncol 2003;21:3601; N Engl J Med 2012;366:399).

• ABVD = doxorubicin, bleomycin, vinblastine, & dacarbazine

• Additional RT (10 Gy) is given to sites of bulky disease

• 2 cycles of ABVD & 20 Gy of IFRT equally effective in a select group of early stage pts (“early favorable”) who have no clinical RFs (N Engl J Med 2010;363:640)

• Repeat PET post-tx for response assessment

Management: Advanced Stage Disease

• “Adv Stage” includes stages III–IV. Some groups include bulky disease of any stage and/or Stage IIB w/unfavorable factors

• ABVD chemotherapy for 6 cycles is standard in North America. Pts w/bulky disease receive ISRT of 30–36 Gy

• Escalated BEACOPP improves FFTF & possibly OS in pts w/unfavorable RFs (eg, IPS ≥4), but is more toxic than ABVD (N Engl J Med 2003;348:2386)

• Limited data for benefit of consolidative RT (J Clin Oncol 2004;22:62) but typically reserved for bulky disease in current era of improved salvage Rx

• Post-tx PET for response assessment. Interim PET (after cycle 2) predicts outcome, but still considered investigational (J Clin Oncol 2007;25:3746)

Toxicity

• BPT results in cough, shortness of breath, PFT (↓ DLCO) & imaging abnormalities

• Monitoring includes clinical surveillance ± routine PFTs

• RFs for BPT (J Clin Oncol 2005;23:7614):

ABVD chemotherapy

↑ Age

Use of granulocyte growth factors (G-CSF)

• Risk of infxn low even in neutropenic pts not receiving G-CSF tx delays should be avoided whenever possible. Neutropenia does not necessitate a dose delay or reduction

Management: Relapsed Classical Hodgkin Lymphoma

• Most pts should receive salvage chemotherapy such as ICE or DHAP ± accelerated TLI/STLI w/boost (J Clin Oncol 1993;11:1062) followed by consolidative autologous stem cell transplant if responsive

• RFs for adverse outcome post relapse (Blood 2001;97:616):

Remission duration <12 mos

B-sx

Extranodal disease

• Role of allogeneic transplant is unclear

• Brentuximab vedotin has 75% RR in post-ASCT setting

• Multiple combination chemotherapy regimens have reported activity in multiply relapsed pts

Nodular Lymphocyte Predominant Hodgkin Lymphoma

• Indolent, relapsing neoplasm w/different natural hx & tx paradigm than classical HL

• Most commonly early stage; better prognosis than classical HL

• RT alone, or in combination w/chemotherapy effective in early stage disease

• Rituximab containing chemotherapy (eg, R-CHOP) effective in adv stage

Survivorship

• 2º Malignancies overtake HL as the greatest risk of mortality in about 20 y post tx

• Annual breast screening should begin 8–10 y after RT that included some of the breast (no later than age 40) in women who receive it. MRI together w/mammography for women that receive RT between ages 10 & 30 is the standard screening for women at high risk for breast CA

• Annual chest imaging recommended for pts at increased risk of lung CA due to tobacco use, receipt of alkylating agents, or chest RT

• Cardiovascular RFs should be screened for & modified

• TSH annually in pts who received RT to the neck