Development of Drug-Induced Cutaneous Vasculitis in a Patient with Relapsed Angioimmunoblastic T-cell Lymphoma Treated with Novel Bortezomib and Panobinostat Combination: A Possible Surrogate Marker of Response

Abstract

enlargement and cervical lymphadenopathy of 1 month duration. A lymph node biopsy done revealed the presence of a neoplastic T-lymphocytic infiltrate which stained positively for CD3, CD2 and CD7, but weakly for CD5. The association with proliferation of high endothelial venules, eosinophilia and CD21 marking the expanded but disrupted follicular dendritic cell meshwork confirmed the diagnosis AITL. A staging positron emission tomography (PET) scan and bone marrow trephine biopsy demonstrated extensive FDG avid lymphadenopathy above and below the diaphragm, and the absence of marrow involvement by lymphoma respectively. He was commenced on 21-day CHOP (cyclophosphamide, adriamycin, vincristine, prednisolone) chemotherapy for treatment of the stage IIIB AITL. He attained a PET complete response after 4 cycles of CHOP chemotherapy. The response was consolidated with 2 cycles and ICE (ifosfamide, cyclophosphamide and etoposide) regimen, followed by high dose therapy (HDT) with BEAM (carmustine, etoposide, cytarabine and melphalan) conditioning and autologous stem cell support. His response was however, short-lived and 6 months post-HDT, he had a biopsy-proven relapse with involvement of supra and infradiaphramatic lymph nodes, including the cervical and inguinal regions (Figures 1a and 2a). This was also accompanied by bone marrow disease and peripheral blood hypereosinophilia. He was subsequently enrolled into clinical trial NCT00901147 which explores the combination of bortezomib (1.3 mg/m 2 on days 1, 4, 8, 11) and panobinostat 20mg (3 times per week for 2 weeks) given in a 21-day cycle in relapsed/refractory T-cell lymphoma. Upon completion of the second cycle of the study combination, he developed scattered erythematous papular rash localised to the neck, upper trunk and forearms which were mildly pruritic (Figure 3).He did not have fever, prurisy and autoimmune manifestation. A skin biopsy performed on the lesion over his right forearm demonstrated perivascular lymphoid infiltrates with dyskeratosis of overlying epidermal keratinocytes, consistent