Occult recurrence of monomorphic epitheliotropic intestinal T-cell lymphoma and the role of MATK gene expression in diagnosis.

Monomorphic epitheliotropic intestinal T-cell lymphomas (MEITL), formerly Type II enteropathy-associated T-cell lymphomas (EATL), are rare peripheral T-cell lymphomas. They are associated with poor survival outcomes, in part because of their late diagnosis. Although MEITLs may be reliably diagnosed based on histological and immunophenotypic findings, overlaps with other NK/T and T-cell lymphomas may confound the diagnosis. The distinctive high-level nuclear staining of the novel marker Megakaryocyte-associated tyrosine kinase (MATK) in MEITLs is an invaluable tool in distinguishing MEITL from classical EATL and other NK/T or T-cell lymphomas. 18-Fluorine-2-fluorodeoxyglucose positron emission tomography (18 F-FDG PET) has been shown to be a useful tool in the staging and follow-up of aggressive lymphomas. Herein, we describe an unusual case of occult hepatic recurrence of MEITL that was non-avid on 18 F-FDG PET, in which diagnosis was confirmed based on the expression of MATK in tumour cells. Copyright © 2016 John Wiley & Sons, Ltd.

Multiple Myeloma of Testes and Spermatic Cord on 18F-FDG PET/CT.

Extramedullary multiple myeloma (EM) has negative prognostic implications on the overall survival as well as progression-free survival. Testis is a rare site of EM, which can be a part of diffuse involvement in multiple myeloma or a site of recurrence in patients with remission. We present a case of EM of testes and left spermatic cord in an 80-year-old man who presented with painless progressive enlargement of the scrotum. F-FDG PET/CT revealed tracer avidity of both testes and left spermatic cord. Bilateral radical orchidectomy was subsequently performed, and the diagnosis of multiple myeloma was confirmed on histopathology.

Pomalidomide and dexamethasone combination with additional cyclophosphamide in relapsed/refractory multiple myeloma (AMN001)-a trial by the Asian Myeloma Network.

Pomalidomide is a third generation immunomodulatory drug which in combination with dexamethasone, has been shown to be active in relapsed/refractory multiple myeloma. However, the data in Asian patients remain limited. We conducted a prospective phase two clinical trial in major cancer centers in Singapore, South Korea, Taiwan, Japan and Hong Kong to assess the efficacy and safety of pomalidomide and dexamethasone combination (PomDex) +/- cyclophosphamide in Asian patients with relapsed/refractory multiple myeloma who failed lenalidomide and bortezomib. Patients were treated with pomalidomide (4 mg daily for 21 days every 4 weeks) and dexamethasone (40 mg weekly). If there is less than a minimal response after three cycles of PomDex, cyclophosphamide 300 mg/m2 can be added (PomCyDex). A total of 136 patients were enrolled. The median PFS was 9 and 10.8 months for the PomDex and PomCyDex group, respectively. The median OS was 16.3 months. This regimen appears to be active across age groups and prior lines of treatment. This combination was overall well tolerated with grade 3 and 4 adverse events of mainly cytopenias. PomDex is highly active and well-tolerated in Asian patients. The addition of cyclophosphamide can improve the response and outcomes further in patients with suboptimal response to PomDex.

Role of Conventional Karyotyping in Multiple Myeloma in the Era of Modern Treatment and FISH Analysis.

BACKGROUND: The Revised International Staging System (R-ISS) has been widely adopted to prognosticate multiple myeloma. As a result, the continued utility of conventional metaphase karyotyping has been called into question. PATIENTS AND METHODS: A multi-center study for newly diagnosed patients with multiple myeloma who received novel agent(s) at induction was conducted. Conventional metaphase karyotype information was categorized based on ploidy. We evaluated the impact of ploidy on overall survival (OS) including multivariate analysis, taking into account the R-ISS stages, transplant status, age, and novel agent(s) used at induction. We also evaluated if it is possible to identify high-risk (HR) patients with conventional karyotyping when a fluorescence in situ hybridization analysis is not available. Results were validated in an independent cohort. RESULTS: There were 308 patients evaluable. Ploidy significantly affected the OS of patients with R-ISS stage II, with non-hyperdiploid patients doing the worst. In the multivariate analysis, ploidy was significantly associated with OS. R-ISS stage II patients with or without non-hyperdiploid karyotype had significantly different survival. We replaced HR fluorescence in situ hybridization abnormalities with HR metaphase karyotypic abnormalities (non-hyperdiploid karyotype). When compared with R-ISS, there was a high level of concordance in HR patients identified using HR karyotypic abnormalities. These results were validated with an independent cohort of 375 patients. CONCLUSION: Conventional metaphase karyotyping is an independent prognostic factor even in the setting of R-ISS.

Pegylated Filgrastim Versus Filgrastim for Stem Cell Mobilization in Multiple Myeloma After Novel Agent Induction.

BACKGROUND: The current standard of care for transplant-eligible myeloma patients is novel agent-based induction, followed by high-dose chemotherapy and autologous stem cell rescue. Chemo-mobilization of peripheral blood CD34+ stem cells (PBSCs) with pegylated filgrastim (pegfilgrastim), a sustained-duration formulation of filgrastim, has been used as an alternative to filgrastim in several studies involving heterogeneous cohorts of lymphoma and multiple myeloma (MM) patients and shown to be equivalent in PBSC yield and cost-effectiveness. The present study focused on the efficacy of pegfilgrastim in PBSC mobilization compared with filgrastim exclusively after novel agent-based induction in a homogeneous group of MM patients. PATIENTS AND METHODS: We analyzed the data from 89 patients with MM treated at 2 transplant centers in Singapore who had received novel agent-based induction chemotherapy, PBSC mobilization with vinorelbine/cyclophosphamide, high-dose melphalan conditioning, and autologous stem cell rescue. Of the 89 patients, 61 were included in the pegfilgrastim group and 28 in the filgrastim group, with a similar median age and disease characteristics. PBSC harvesting was performed at a similar median time of 9.51 ± 0.84 days for both, and the peak peripheral blood CD34+ stem cell count was 19.90 × 106/kg for pegfilgrastim and 32.50 × 106/kg for filgrastim (95% confidence interval, -4.36 to 0.70 × 106/kg). RESULTS: No significant difference was found in the median PBSC collection between the 2 groups (pegfilgrastim, 7.90 × 106/kg vs. filgrastim, 10.10 × 106/kg; P = .16). CONCLUSION: The present study has demonstrated that a single dose of pegfilgrastim is comparable to filgrastim in terms of the timing and efficacy of PBSC harvest and could potentially spare the patient 6 days of filgrastim injections. In addition, ours is the first study to compare these growth factors using vinorelbine/cyclophosphamide as mobilization chemotherapy.

The Singapore Myeloma Study Group Consensus Guidelines for the management of patients with multiple myeloma.

Multiple myeloma (MM) is an incurable plasma cell neoplasm with an incidence of 100 patients per year in Singapore. Major advances have been made in the diagnosis, risk stratification and treatment of MM in the recent past. The reclassification of a subset of patients with smouldering MM, based on high-risk biomarkers, and the development of the revised international staging system are among the key new developments in diagnosis and staging. The use of novel agent-based treatment has resulted in significant improvements in the survival and quality of life of many patients with MM. Determining the optimal use of proteasome inhibitors, immunomodulators and, more recently, monoclonal antibodies is an area of ongoing investigation. In this guideline, we aim to provide an overview of the management of MM, incorporating the latest developments in diagnosis and treatment.