Early relapse after complete remission of primary plasma cell leukaemia manifesting clonal evolution: A case report.

INTRODUCTION: Plasma cell leukaemia (PCL) is a rare variant of multiple myeloma. We report a case of PCL to demonstrate the clonal evolution, resulting in disease relapse after achieving complete remission, and its aggressive nature of the disease, leading to poor clinical outcome. CASE REPORT: A 69-year-old man presented with a three-day-history of worsening generalized body weakness, poor oral intake, nausea, significant loss of weight and lower back pain. He was diagnosed as primary PCL, based on hypercalcaemia, renal insufficiency, anaemia, thrombocytopenia, lytic bone lesions, 24% abnormal plasma cells in peripheral blood, immunophenotype of clonal plasma cells which were positive for CD38, CD138 and CD56 markers with kappa light chain restriction, 49% abnormal plasma cells in bone marrow, monoclonal paraprotein (IgG kappa) in serum and urine, and positive IGH rearrangement (Fluorescence in-situ hybridisation, FISH). He achieved complete remission after four cycles of Bortezomib-based therapy. There was a plan for high-dose therapy plus autologous haematopoietic cell transplantation. A month later, the disease relapsed, as evidenced by 94% abnormal plasma cells in his bone marrow aspirate, complex karyotype and abnormal FISH results. He passed away a few days later, from severe septicaemia. Time-to-progression of disease was 1 month and overall survival was 5 months. DISCUSSION: This case report illustrates the clonal evolution and aggressive nature of primary PCL with older age at presentation, leading to a shorter duration of remission and overall survival.

Autologous mononuclear cells from different sources are seen to improve wound healing in patients with haematological malignancies.

INTRODUCTION: Immunosuppressive state due to haematological malignancies and chemotherapy may cause disruption to wound healing despite optimum conventional treatment and standard wound dressing. Non-healing wounds are predisposed to infection whereas chemotherapy dose reductions or interruptions are associated with poor survival. BACKGROUND: Mononuclear cells contain progenitor cells including haematopoietic and mesenchymal stem cells, endothelial progenitor cells and fibroblasts which facilitate wound healing through cytokines, growth factor secretions, cell-cell interactions and provision of extracellular matrix scaffolding. Clinical applications of autologous mononuclear cells therapy in wound healing in non-malignant patients with critical limb ischaemia have been reported with remarkable outcome. METHODS: We report three patients with haematological malignancies undergoing chemotherapy, who received autologous mononuclear cells implantation to treat non-healing wound after optimum conventional wound care. The sources of mononuclear cells (MNC) were from bone marrow (BM), peripheral blood (PB) and mobilised PB cells (mPB-MNC) using granulocyte colony stimulating factor (G-CSF). The cells were directly implanted into wound and below epidermis. Wound sizes and adverse effects from implantation were assessed at regular intervals. RESULTS: All patients achieved wound healing within three months following autologous mononuclear cells implantation. No implantation adverse effects were observed. CONCLUSIONS: Autologous mononuclear cells therapy is a feasible alternative to conventional wound care to promote complete healing in non-healing wounds compounded by morbid factors such as haematological malignancies, chemotherapy, diabetes mellitus (DM), infections and prolonged immobility.

POEMS syndrome.

POEMS syndrome is the syndrome of Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein and typical Skin changes. A 65-year-old lady presented with the 2-day-history of inability to walk, 4-month-history of progressive worsening of muscle weakness of both lower limbs and 1-year-history of progressive worsening of bilateral numbness of lower limbs. Nerve conduction study revealed generalized sensorimotor demyelinating polyneuropathy. She was initially treated as chronic inflammatory demyelinating polyradiculoneuropathy with intravenous immunoglobulin (IVIG) and high-dose prednisolone. However, she had no significant neurological improvement despite getting standard therapy. In addition to peripheral neuropathy, the presence of hepatosplenomegaly, skin changes, polycythaemia and thrombocytosis prompted for further investigations. She was diagnosed as POEMS syndrome based on the presence of two mandatory major criteria [polyneuropathy, monoclonal plasma cell proliferative disorder (lambda)], one major criterion (sclerotic bone lesions) and three minor criteria (organomegaly, skin changes and thrombocytosis/polycythaemia). She received treatment with melphalan and prednisolone. She achieved clinical improvement and partial response (haematologic and radiological) after six cycles of therapy. We highlight the awareness of this rare syndrome, for patients presenting with peripheral neuropathy and not responding to its standard therapy, by recognizing other associated clinical manifestations and proceeding further diagnostic work-up.

Diffuse large B cell lymphoma with chronic granulomatous inflammation.

Non-necrotic epithelioid granulomas have been reported in association with neoplasms including Hodgkin and non-Hodgkin lymphoma. We report a case of diffuse large B cell lymphoma with chronic granulomatous inflammation to highlight awareness of obscure tumour cells within the granuloma, to avoid delay in diagnosis and management of lymphoma. A 39-year-old Malay lady with no past medical history, presented with a 2-month history of progressive worsening of difficulty in breathing, cough, low-grade fever, loss of weight and loss of appetite. Chest X-ray showed an anterior mediastinal mass and computed tomography (CT)-guided biopsy was reported as chronic granulomatous inflammation suggestive of tuberculosis. After 2 months of anti-TB treatment, her symptoms were not relieved. The patient underwent another CT-guided biopsy of the anterior mediastinal mass in another hospital and the histopathology revealed diffuse large B cell lymphoma. The patient was referred for treatment. On histopathological review, the first sample showed noncaseating granulomas engulfing tumour cells and large abnormal lymphoid cells which were CD20 positive and with high Ki-67 proliferative index. The patient was diagnosed with diffuse large B cell lymphoma stage IV B IPSS score 3. She underwent chemotherapy (R-EPOCH) and responded well to treatment.