EHA-TSH Hematology Tutorial on Lymphoma

Tutored Clinical Case 1

Speaker: Pervin Topcuoglu

[Ankara University]

İzmir, Turkey

April 6-7, 2019

Clinical history

‒ A 39-year-old man has painless progressive swelling on the right neck about one month.

‒ No significant medical history

‒ No B symptoms

‒ His occupation: Mechanic in automobile industry.

Physical Examination

‒ ECOG performance status: 0

‒ Vital sign is normal

‒ Palpable LAP at right anterior cervical (2,5x2 cm)

‒ No other peripheral lymphadenopathy

‒ No hepatosplenomegaly

Initial Examination

‒ WBC: 6.6x109/L (Normal range: 4.5-11x109/L)

‒ Leukocyte differentiation:

• Neutrophil: 3.98x109/L (1.8-7.7x109/L)

• Lymphocyte: 1.76x109/L (1.5-4x109/L)

• Monocyte: 0.64x109/L (0.2-0.95x109/L)

• Eosinophil: 0.21x109/L (0-0.7x109/L)

• Basophil: 0.7x109/L (0.0-0.15x109/L)

Initial Examination

‒ Albumin: 4.55x109/L (3.5-5.2x109/L)

‒ LDH: 205 U/L (<248 U/L)

‒ Alkaline phosphatase: 85 U/L (30-120 U/L)

‒ Renal and liver function tests were normal

‒ Sedimentation Rate: 3 mm/h

‒ Viral serology for hepatitis and HIV negative

Excisional biopsy

Neck Ultrasonography: anterior right cervical LAP (3x2 cm)

FNB: Atypical lymphoid proliferation

Excisional biopsy of cervical LN

Reed-Sternberg Cells

IHC:CD30+, CD15+, EBV-LMP-1+, PAX5 focal +

Reactivelymphoid cells:

CD3+ and CD20+

Luca DC. Weil Cornell Medicine. Pathology&Laboratory Medicine. 2002-2017, PathologyOutlines.com, Inc

MC-

cHL

PET/CT Scan

SUV Max: 20.1

Ann-Arbor Staging with Cotswolds-Modification

Stage I Involvement of a single lymphatic site or

localized involvement of a single extranodal (EN) organ or site (IE)

Stage II Involvement of two or more lymph node regions on the same side of the

diaphragm or

localized involvement of a single EN organ or site in association with regional

lymph node involvement on the same side of the diaphragm (IIE)

Stage III Involvement of two or more lymph node regions or of EN organs on both sides of

the diaphragm

Stage IV Non-localized, diffuse or disseminated involvement of one or more EN organs,

with or without associated lymph node involvement

Addendum A B symptoms are absent.

Addendum B B symptoms are present: fever (temperature >38ºC), drenching night sweats,

and/or unexplained loss of >10% of body weight within the preceding 6 months.

Addendum X Bulky disease present (nodal mass >1/3 of intrathoracic diameter or 10 cm in

dimension)

Lugano Classification (Derived from Ann-Arbor Staging with Cotswolds- Modification)

Stage I Involvement of a single lymph node ((LN) region (eg, cervical, axillary, inguinal,

mediastinal) or lymphoid structure such as the spleen, thymus, or Waldeyer's ring.

Stage II Involvement of two or more LN regions or LN structures on the same side of the

diaphragm. Hilar nodes should be considered to be "lateralized" and when involved on

both sides, constitute stage II disease.

For the purpose of defining the number of anatomic regions, all nodal disease within

the mediastinum is considered to be a single LN region, and hilar involvement

constitutes an additional site of involvement. The number of anatomic regions should

be indicated by a subscript (eg, II-3).

Stage III Involvement of LN regions or lymphoid structures on both sides of the diaphragm. This

may be subdivided stage III-1 or III-2: stage III-1 is used for patients with involvement of

the spleen or splenic hilar, celiac, or portal nodes; and stage III-2 is used for patients

with involvement of the paraaortic, iliac, inguinal, or mesenteric nodes.

Stage IV Diffuse or disseminated involvement of one or more extranodal organs or tissue beyond

that designated E, with or without associated lymph node involvement.

Cheson BD, et al. J Clin Oncol 2014; 32: 3059-3068

Stage II Involvement of two or more lymph node regions on the

same side of the diaphragm or

localized involvement of a single EN organ or site in

association with regional lymph node involvement on the

same side of the diaphragm

Addendum A B symptoms are absent.

Treatment

Early stage HL-favorable (No risk factor)

‒ 2xABVD

‒ Interim PET/CT

‒ Complete Metabolic Response

‒ 20 Gy ISRT

‒ Today, he is complete remission in 18th months.

Discussion‒ Early stage is clinical stage I or II.

‒ Subsequent stratification is favorable and unfavorable

prognosis.

Bröckelmann PJ, et al. Blood 2018; 131(15):1666-1678

Discussion

H10F trial in early-stage favorable HL with 754 patients randomized

RFs: • age ≥50 ys, • large mediastinal

mass, ESR>30mm/h with B-symptoms (BS),

• ESR without BS >50mm/h,

• ≥3 nodal• areas

André MPA, et al. J Clin Oncol 35:1786-1794.

Discussion

‒ iPET (-) patients

André MPA, et al. J Clin Oncol 35:1786-1794.

Favorable Unfavorable

Discussion

‒ iPET (+) patients

André MPA, et al. J Clin Oncol 35:1786-1794.

Discussion

‒ Long-term follow-up data of the four randomized trials (HD7, HD8, HD10 and HD11) largely support the current risk-adapted therapeutic strategies in early-stage HL.

‒ They confirmed excellent efficacy of two cycles of ABVD followed by 20 Gy IFRT in early favorable HL.

Sase S, et al. J Clin Oncol 2017;35:1999-2007.

Discussion

‒ Favorable early stage HL

HD16 trial in early-stage favorable HL with 1150 patients randomized

RFs: age ≥50 ys, large mediastinal mass, ESR>30mm/h with BS, ESR without BS >50mm/h, ≥3 nodalareas

Fuchs M, et al. ASH 2018 Oral presentation

Discussion‒ Favorable early stage HL

HD16 trial in early-stage favorable HL with 1150 patients randomized

Fuchs M, et al. ASH 2018 Oral presentation

PET - patients