Overview of recent trends in diagnosis and management of leptomeningeal multiple myeloma.

Neurological complications related to multiple myeloma (MM) are not uncommon; however, direct involvement of the central nervous system (CNS) is extremely rare and represents a diagnostic and therapeutic challenge. Significant survival difference has been noted with the introduction of novel therapy in patients with MM, but their effect on the incidence and their use for management of leptomeningeal myeloma (LMM) is uncertain. Analysis of published data demonstrates its recent increased incidence, median time to CNS presentation, and slight improvement in median survival after diagnosis of LMM. Less common MM isotypes have been overrepresented in LMM. CNS relapse occurred mostly in patients with Durie-Salmon stage III MM. Despite treatments, standard or experimental, the survival rates of LMM remain dismal. Monitoring high risk patients closely, even after achieving complete remission, may be useful in early detection of LMM. As we gain better understanding of LMM, we recommend that future research and clinical care focus on earlier diagnosis and development of more efficient CNS-directed therapy to improve survival in this patient population.

CML in pregnancy: A case report using leukapheresis and literature review.

Chronic myelogenous leukemia (CML) complicating pregnancy is uncommon. Literature search demonstrates only a few case reports and some case series but large studies are lacking due to its uncommon presentation. Management of these patients is particularly challenging due to limited available options as several chemotherapy drugs could potentially lead to adverse outcomes and fetal malformations. Leukapheresis has been used in these situations; however paucity of data exists regarding the outcome and complications associated with the procedure. Using leukapheresis alone for extended period to manage CML during pregnancy is also rare. Here we report a case of CML complicating pregnancy which was successfully managed utilizing leukapheresis, followed by a review of literature addressing this controversial issue.

Profile of pembrolizumab in the treatment of head and neck squamous cell carcinoma: design development and place in therapy.

Head and neck squamous cell cancer (HNSCC) is the sixth most common malignancy worldwide, and despite advances in cytotoxic, surgical and radiation techniques, outcomes are still poor in those with both locally advanced and metastatic diseases. The need for development of better therapeutics along with a greater understanding of the relationship between the immune system and malignancies has led to a new therapeutic modality, immune modulators, particularly checkpoint inhibitors in HNSCC. It is now well recognized that HNSCC circumvents crucial pathways utilized by the immune system to escape surveillance. These hijacked pathways include impairing tumor antigen presentation machinery and co-opting checkpoint receptors. This understanding has led to the development of monoclonal antibodies targeting checkpoint receptors and has resulted in promising outcomes in HNSCC. This article describes the mechanisms that HNSCC utilizes to escape immune surveillance, clinical impact of checkpoint inhibitors (with a focus on pembrolizumab), ongoing studies, and future directions.

Simultaneous presentation of pancreatic cancer in a genetically unrelated couple.

Patients with pancreatic cancer tend to have a poor prognosis despite aggressive treatment, and their 5-year overall survival rate remains dismal. Several risk factors could potentially trigger the development of pancreatic cancer but many of them identified so far have been only weakly linked. Occurrence of pancreatic cancer in a husband and wife around the same time in the same household even when exposed to similar environmental factors is rare. Although familial pancreatic cancer is a known entity, pancreatic cancer in genetically unrelated married couples has not been studied. Here we present such a scenario involving one couple. In this case report, we discuss the chronological events leading to pancreatic cancer in a genetically unrelated married couple and the risk factors that may have led to cancer, in addition to exploring the possible links.

Overview of Recent Trends in the Management of Metastatic Anal Cancer.

Anal cancer is a relatively rare gastrointestinal tumor with roughly 7,000 new cases per year. Metastatic anal cancer as an initial presentation occurs in 10-20% of the patients. Treatment for localized disease is well established with concurrent chemoradiation (CCR) therapy as the standard of care; however, metastatic anal cancer remains a therapeutic challenge. National Comprehensive Cancer Network (NCCN) guidelines recommend systemic chemotherapy as the initial choice of treatment for metastatic anal disease. NCCN also recognizes the fact that there are limited data to influence the management of metastatic anal cancer but that some evidence suggests flouropyrimidine and cisplatin as the initial choice of treatment outside the setting of clinical trial. If the patient fails this regimen, options become limited with no strong level I evidence available to guide the treatment. We present two cases of metastatic anal cancer and discuss the potential treatment strategies after failing the initial systemic chemotherapy.

Influence of Rituximab on Central Nervous System Relapse in Diffuse Large B-Cell Lymphoma and Role of Prophylaxis--A Systematic Review of Prospective Studies.

Despite the improvement in overall survival in patients with diffuse large B-cell lymphoma (DLBCL) in the rituximab era, the occurrence of central nervous system (CNS) relapse heralds a very poor prognosis. The evidence is conflicting on the incidence and pattern of CNS relapse in the rituximab era compared with before the rituximab era and on the role of CNS prophylaxis. We conducted a systematic analysis of the data from 7 prospective studies, studying the incidence and type of CNS relapse, the role of prophylaxis, and survival after CNS relapse, with and without rituximab-based chemotherapy. No statistically significant difference was found in the incidence of CNS relapse with the use of rituximab-based chemotherapy compared with CHOP (cyclophosphamide, doxorubicin, vincristine [Oncovin], prednisone) chemotherapy. Leptomeningeal disease was more common and the survival after CNS disease was better in the rituximab era. No difference was found in the incidence of isolated CNS relapse. Chemoprophylaxis significantly decreased the incidence of CNS recurrence. The use of rituximab has not influenced the incidence of CNS relapse compared with the use of CHOP. Chemoprophylaxis plays a significant role in high-risk patients with DLBCL in decreasing CNS recurrence. Large randomized clinical trials are warranted to differentiate between intrathecal and systemic chemoprophylaxis.

Low-dose ruxolitinib for improving leukopaenia and reducing recurrent infections associated with myelofibrosis.

Myelofibrosis, either primary or resulting from essential thrombocythemia or polycythemia vera, may present with highly variable white blood cell counts, including progressive leukopaenia with its associated risk of infections. Medications have been developed to reduce splenomegaly and other symptoms, but there are no reports of improved white blood cell counts. We report a case of primary myelofibrosis with marked improvement in leukopaenia and reduced recurrent infections, in addition to reduction in spleen size and improvement in disease-associated symptoms, within 20 weeks after using low-dose ruxolitinib. Although reduction of splenomegaly in myelofibrosis patients is the anticipated benefit of ruxolitinib, the drug may also have the potential to improve leukopaenia if used at a low dose.