Spinal cord metastasis in a patient treated with bevacizumab for glioblastoma

Spinal metastases from glioblastoma are extremely rare and may be misdiagnosed leading to a delay in investigation and treatment. Patient outcomes are poor with a high morbidity and mortality. Metastases are seen in the context of increasing survival due to improvements in glioblastoma therapies. We report a case of a patient developing a thoracic spinal cord metastasis while receiving anti-angiogenesis therapy with bevacizumab

Molecular Mechanisms of Disease Progression in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type during Ibrutinib Therapy

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is one of the well-recognized extranodal lymphomas commonly addicted to the B-cell receptor-MYD88 superpathway. We aimed to describe the genomic changes in a patient who progressed through treatment with ibrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor. An 80-year-old woman presented with multiply relapsed PCDLBCL-LT after multiple lines of chemoimmunotherapy and radiotherapy. Pre-treatment testing of the localized cutaneous tumor lesion on a lymphoid amplicon panel demonstrated an MYD88 p.L265P mutation. Ibrutinib therapy was subsequently commenced, resulting in complete resolution of the skin disease. Despite an ongoing skin response, the patient developed progressive nodal disease at two months. Genomic analysis of the cutaneous tumor sample at baseline was compared to that of the inguinal lymph node upon progression, and revealed the acquisition of multiple genomic changes. These included several aberrations expected to bypass BTK inhibition, including two CARD11-activating mutations, and a deleterious mutation in the nuclear factor kappa B (NF-κB) negative regulator, NFKBIE. In addition, an IgH-IRF8 translocation was detected (which brings the IRF8 transcription factor under control of the immunoglobulin heavy chain locus), representing a third plausible mechanism contributing to ibrutinib resistance. Several copy-number changes occurred in both samples, including an amplification of 18q, which encodes the anti-apoptotic protein BCL2. We describe the first case of novel genomic changes of PCDLBCL-LT that occurred while on ibrutinib, providing important mechanistic insights into both pathogenesis and drug resistance

Role of Haematopoietic Stem Cell Transplantation in Peripheral T-Cell Lymphoma

Peripheral T-cell lymphomas (PTCLs) are distinct pathological entities with clinical advancements lagging behind their B-cell lymphoma counterpart. Frequently aggressive in their clinical behaviour, clinicians are constantly challenged with low complete remission rates, early relapses and failure to achieve long-term responses despite aggressive first-line chemotherapy, resulting in poor overall survival in the majority of patients. There is currently no consensus regarding the optimal therapy for PTCL and treatment approaches are mainly derived from prospective phase II studies, registry data and retrospective studies. Despite its biological heterogeneity, a less than satisfactory "one-size-fits-all" approach has been adopted to date. Although its role remains controversial, for many years, haematopoietic stem cell transplantation has been adopted by clinicians with the aim of overcoming poor outcomes by consolidating responses. In this review, we aim to define the role of both autologous and allogeneic stem cell transplantation in PTCL in both frontline and salvage settings, especially in the context of recent advancements in this field