1. Abstract ID:  #427
Case Report: A Challenging Case of Managing Relapsed & Refractory Hodgkin's Lymphoma
Prashanth Hari Dass, Michael B. Jameson, and Elliot M. Epner
Waikato Hospital, Hamilton, New Zealand
Correspondence:
Introduction
Relapse 34 months later…
Follow up
She represented with right chest wall pain & nocturnal wheeze.
Relapse confirmed on CT (Image 3) & biopsy.
3 cycles of IGEV (Ifosfamide, Gemcitabine & Vinorelbine) chemotherapy followed by successful harvest of peripheral blood haemopoietic stem cells.
PET-CT scan showed HL progression (Image 4).
CT 3 months post-autograft showed resolution of lymphadenopathy, minor residual lung consolidation & pleural thickening (Image 7).
CXR 15 months post autograft was unremarkable.
Hodgkin's Lymphoma (HL) :
An uncommon malignant disease originating predominantly from B lymphocytes
More common in western countries compared to Asia. 1
Although largely curable, 33% of patients subsequently relapse. Half of these patients are refractory to salvage treatment.2
Image 3 PET CT: Relapse at
34 months
Image 4 PET CT: Progression post-IGEV
Case Report
History & Examination
19 year-old HIV-negative female
4 month history of enlarging cervical lymphadenopathy, night sweats & weight loss
Investigations
CT scan: large anterior mediastinal mass & bilateral supraclavicular lymphadenopathy (Image 1) – unfavourable Stage IIB.
Histology: Grade 2 nodular sclerosing HL syncytial variant. Reed-Sternberg cells stained positive to CD30, Fascin, CD15, EBER & CD20(focally). PAX-5 was negative.
International Prognostic Score 0.
Treatment
6 cycles of ABVD chemotherapy (Doxorubicin, Vinblastine, Dacarbazine & Bleomycin) with Filgrastim.
PET-CT scan after 2 cycles ABVD showed complete metabolic response (Image 2).
She then received involved nodal radiation, 30.6Gy in 17 Fractions.
Image 7 CT scan 3 months post-autograft – complete remission
Discussion
Brentuximab vedotin x 2 cycles failed to induce remission in our patient. The addition of epigenetic therapy to a third cycle produced a dramatic response.
Cladribine, an adenosine deaminase inhibitor is efficacious in many haematological malignancies. 3
The addition of Valproate (Histone Deacytelase inhibitor) to Cladribine is synergistic.4
Managing Refractory HL
Image 5 CXR after 1 cycle of ESHAP: No response
Image 6 CXR - dramatic reduction of hilar mass from 11cm to 6.5cm post Brentuximab, Cladribine & Valproate
1 cycle of ESHAP (Etoposide, Methylprednisolone, Cytarabine & Cisplatin) given while awaiting funding for Brentuximab Vedontin, but no response on CXR (Image 5).
She then received 2 cycles of Brentuximab vedotin (1.8mg/kg).
PET-CT scan showed stable pulmonary mass; FDG uptake reduced but still moderate.
In view of refractory disease, cycle 3 Brentuximab given with IV Cladribine 5mg/m2 Day 1 & Sodium Valproate 500mg orally three times per day.
This was well tolerated.
CXR after this cycle showed dramatic reduction of the hilar mass (Image 6).
This was followed by high-dose BEAM chemotherapy & autologous peripheral blood stem cell transplant.
Conclusions
This is a fascinating case of refractory HL that achieved complete response with the addition of epigenetic therapy to brentuximab vedotin.
We propose a prospective trial to evaluate its efficacy and safety in larger subsets of patients.
Image 1 CT at diagnosis
Image 2 PET-CT post 2 cycles ABVD
References
Z Mozaheb. Epidemiology of Hodgkin’s Lymphoma. Health 5 (2013)
F. Montanari. & C. Diefenbach. Relapsed Hodgkin Lymphoma: Management StrategiesCurr Hematol Malig Rep September ; 9(3): 284–293. doi: /s
S. Spurgeon, M. Yu, J. D. Phillips, E. M. Epner. CLADRIBINE: NOT JUST ANOTHER PURINE ANALOGUE? Expert Opin Investig Drugs 2009 Aug;18(8):
A. B. Bouzar, M. Boxus, J Defoiche et al. Valproate synergizes with purine nucleoside analogues to induce apoptosis of B-chronic lymphocytic leukaemia cells. British Journal of Haematology