EHA-TSH Haematology Tutorial on Lymphoma

Tutored Clinical Case 1

DLBCL and Double Hit Lymphoma: Diagnosis and Treatment (First Line and Relapsed Disease)

Speaker: Burhan Ferhanoğlu, MD

Koç University School of Medicineİzmir, Turkey

April 6-7, 2019

• Clinical summary:

• December 2015:• 27 yr old lady• 32 wk pregnancy, uncomplicated• Cervical enlarged lymph node

• Lymph nodes detected in the imaging studies:• Cervical US/MRI: 19x22 mm, 20x35 mm • Abdominal MRI:para-aortic, aorto-caval 2 cm• Iliac, obturator and inguinal 2.5 cm

• Pregnancy outcome- labour induced• A healthy girl born

• Lymph node biopsy ordered

• Additional work-up:• WBC:12 x 109/L, Neu 80% Ly 15% • Hb:107 g/L MCV:89 fL• Plt:145 x 109/L• LDH:133 U/L (<250)• Liver/kidney function tests were normal

-Neoplastic infiltration of high grade round cells was detected. Lymphoproliferative disorders were in the differential diagnosis.

-Tdt (-), PAX-5 (+), CD20 (+), CD10 (+), MUM-1 (-), CD5 (-), Bcl-1 (-), Bcl-2 (+), C-myc (+) in more than 70% of cells, CD2 (-), CD3 (-), MPO (-), Ki-67 index was 80%

-These features point us to Burkitt or Burkitt like B cell lymphomas-Bcl2 positive and relatively low Ki-67 index for Burkitt-The diagnosis is

D i f f u s e L a r g e B C e l l L y m p h o m a , N o t O t h e r w i s eS p e c i f i e d

MUM1-,TdT-,CD43 + (mild)

• December 25, 2015• Admitted to our clinic for continuation of

chemotherapy

• 1 cycle of R-CHOP previously administered in another center• FISH analysis ordered

• Bone marrow biopsy applied

• IPI:1• Age<60, LDH:normal, stage:III bulky

disease

Bone Marrow Evaluation

- Bone marrow was not infiltrated-Cytogenetic analysis: 46,XX- Flow cytometric analysis of the bone marrow aspirate did not reveal any infltration

- BCL2 translocation was detected

- BCL6, C-MYC and C-MYC/IGHtranslocations were not detected

Lymph node evaluation

• Following the initial R-CHOP cycle, significantprogression of the disease was observed withinthe 3 weeks.

• Second cycle administered as GMALL (Burkitt) block 1A• t(8,14) result was pending

• December 30, 2015• Atypical epileptical seizure observed• MR: left precentral leptomeningeal/pial abnormality-

suspected lymphoma involvement• Anti-epileptics initiated

• December 31, 2016

• Cytology for CSF repeated

• No atypical cells observed

• We could not find evidence of CNS involvement. Thus, we administered:

• DA-EPOCH-R

• HD-MTX ( after each treatment, on D15)

• 50 Gy (2 Gy/fr/day) IFRT to the neck and leftaxillary region

And we performed interim PET after 4 cycles

• February 26, 2016:

• Interim PET Residual malignancy in theleft supraclavicular lymph node.

• almost complete response in the leftcervical axillary and supradiaphragmaticfoci.

• Mild heterogeneity in the long bones andin the pelvic bones (this may be due to G-CSF effect).

• Regression of the infra-diaphragmaticlymph nodes.

• March 28-April 05 2016

• Boost RT

• April 20, 2016

• Last cycle of chemo

• Cranial MRI did not show any lymphoma involvement

• LP performed, no infiltration was seen in cytopathological and flow cytometric analysis

• May 10, 2016:

• PET-CT end of treatment pet.

• Right inguinal and external iliachypermetabolic lymph node

• Lymph node biopsy: B cell lymphoma, HighGrade, Germinal Center B cell origin; FISH results were same as the initial report

• Bone marrow biopsy: No lymphomainfiltration

• Flow cytometry did not reveal any infiltration

• autoSCT planned

• 3xR-DHAP initiated as salvage regimen

• 2 cycles administered

• June 2016• PET Amorphous consolidation in the left upper

pulmonary lobe (SUV max 4.25; infection? inflammation?), diffuse Fdg uptake in the spleen(SUV max 3.43), progression of the masses of 4x15 cm adjacent to abdominal wall muscles (SUV max9.5), of theintraabdominal soft tissue masses (SUV max 8.6 & 12.7). Progression of the FDG uptake in the uterine fundus (SUV maax 9.7). Progression of the right external iliac LAP (5.5x2 cm; SUV max11.57) and stable right inguinal mass (SUV max13). Increased uptake in the skeletal system.

• GDPx1

• July 2016• autoSCT administered

• Early PET/CT right inguinal FDG-avidlesion of 2x3 cm• 20 fr/IFRT applied

• September 21, 2016

• PET on day 60 Disease progressionexhibited as breast, skin, bone marrowand left axillary involvement.

• Facial hypo-aesthesia was evaluated as possible presentation of CNS involvement.

• October 2016

• Mass on breast and ulcerated lesion on abdominal skin

• WBC:3.2 x 109/L

• Hb:10 g/dL

• Plt:10 x 109/L

• Leukoerytroblastosis was detected on theperipheral blood smear

• Biopsies performed for skin/breast/bone marrowdisease

• Skin biopsy: DLBCL, Germinal Center B-cell origin

• Breast biopsy: DLBCL

• Bone marrow was also infiltrated with theoriginal B-cell lymphoid neoplasia

• Cytogenetic evaluation revealed complexkaryotype

• October to November 2016

• R-HyperCVAD administered

• alloSCT planned

• Patient symptoms and cytopenias did not improve

• New skin lesions appeared

• Breast lesions progressed

• Axillary lymph nodes enlarged

• «best supportive care vs Nivolumab»

• November 28, 2016

• The patient died.

Jun 16Following

salvage

May 16End of

treatment

Feb 16iPET after

DA-EPOCH-R, HD-MTX &

RTDec 15

Diagnosis

Sep 162months

after auto-SCT

EHA-TSH Haematology Tutorial on Lymphoma

Tutored Clinical Case 1

DLBCL and Double Hit Lymphoma: Diagnosis and Treatment (First Line and Relapsed Disease)

Speaker: Burhan Ferhanoğlu, MD

Koç University School of Medicineİzmir, Turkey

April 6-7, 2019