ALK negative anaplastic large cell lymphoma with CNS involvement needs more than just brentuximab vedotin
Dear Editor, A 60 year old Chinese female, who had relapsed anaplastic large cell lymphoma (ALCL) anaplastic lymphoma kinase (ALK) negative, was referred to our transplant service, following initial treatment with CHEOP (cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisolone) chemotherapy. She attained a second complete remission following salvage therapy with ICE (ifosfamide, etoposide, and carboplatin) and subsequently underwent an autologous transplantation (ASCT) using BEAM (carmustine, etoposide, cytarabine, and melphalan) conditioning regimen. She relapsed 6 months after ASCT with disease above and below the diaphragm and cutaneous involvement. She was treated with brentuximab vedotin and attained a third complete remission on positron emission tomography computed tomography scan (PET CT) after the fourth cycle. After completing eight cycles of brentuximab vedotin, she presented with a gradual functional decline, increased drowsiness and confusion. Magnetic resonance imaging (MRI) of the brain revealed moderately extensive patchy enhancement in the periventricular location, third and fourth ventricles, and bilateral lateral ventricles. The MRI also showed a concurrent involvement of adjacent corpus callosum and caudate nucleus, parts of the cortex, and subcortical white matter (Fig. 1) Lumbar puncture showed an elevated total cell count (139 cells/microL) with large neoplastic lymphoid cells seen in cerebrospinal fluid (CSF) cytology (Fig. 2a) Immunohistochemical stains were performed on cytospin prepared smears. The neoplastic lymphoid cells were positive for CD2, CD3, and CD30 consistent with the involvement of the CSF by ALCL and ALK (Fig. 2b) CSF studies for infective etiology, including JC virus PCR, were negative. Repeat PET CT done 2 weeks prior to her admission, after 8 cycles of brentuximab vedotin, showed disease in persistent complete remission. While maintaining a complete remission systemically, she was diagnosed with an isolated central nervous system (CNS) relapse of ALCL and ALK. ALK negative ALCL carry worse overall survival (OS) rates than most other T cell mature lymphoproliferative counterparts [1, 2] Prognosis remains dismal for relapsed/refractory disease. Single agent brentuximab vedotin has been shown to have excellent treatment efficacy in relapsed ALCL with overall response rates of >80 and has been licensed for use in the first line salvage setting [3 5] Brentuximab vedotin is an antibody drug conjugate (ADC) composed of a chimeric monoclonal antibody (cAC10) linked to an anti tubulin agent, an anti CD30 monomethyl auristatin E (MMAE) [6] However, there has been no data in the literature on whether brentuximab vedotin can cross the blood brain barrier. Our case illustrates a patient with isolated CNS relapse despite excellent systemic response to the drug. The persistence of strong CD30 expression in malignant cells within the CSF and the isolated CNS relapse in Muhammad Bilal Abid bilal_abid@hotmail.com
Annals of Hematology