Mahender Yellu

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.

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.

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. Copyright

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.

Pancreatic Cancer Epidemiology and Environmental Risk Factors

Pancreatic cancer is one of the leading causes of cancer death worldwide. It is currently the fourth leading cause of cancer-related deaths in both men and women in the United States and has a less than 10% 5-year survival rate for all stages combined.

Influence of rituximab and central nervous system directed prophylactic therapy on central nervous system relapse in high-risk diffuse large B-cell lymphoma

Background: Central nervous system (CNS) relapse in patients with diffuse large B-cell lymphoma (DLBCL) although rare, can be devastating. Conflicting reports have been published regarding the protective effect of systemic rituximab therapy and likely reduction in incidence of CNS relapse in post-rituximab era. Methods: We retrospectively identified all the DLBCL patients at our institute between 2004 and 2014 who received systemic rituximab-based chemo-therapy at initial presentation. Patients were categorized into two groups, “standard risk” with no risk factors and “high risk” with one or more of the following risk factors, elevated lactate dehydrogenase (LDH) (above the institute normal), international prognostic index (IPI) ≥3, involvement of testis, breast, bone, kidneys, adrenal gland, retroperitoneal lymph nodes, para-meninges, and bone marrow. Descriptive statistics were used to analyze inci-dence of CNS relapse, patient and disease characteristics. Historically reported incidence rates were used for comparison. Results: A total of 122 patients received rituximab-based therapy at the initial diagnosis; 73 patients (60%) qualified for standard risk; 49 patients (40%) met the criteria for “high risk” based on the above definition. Standard risk group received no CNS directed prophylaxis and none of these patients had CNS relapse. Thirty-one of 49 (63%) “high risk” patients received CNS prophylaxis, mainly intrathecal (IT) methotrexate. Five patients (4.0%) developed CNS relapse in the entire study population. Percentage of patients developed CNS relapse in high-risk patients was 10.2% (5/49). Median time to relapse was 8.76 months and median survival after CNS relapse was 9.16 months. Four out of five patients who developed CNS relapse received prophylaxis with IT. Conclusions: CNS relapse continued to be a rare but devas-tating complication in post rituximab era, however our study confirms that majority of the DLBCL patients do not need CNS directed therapy. Current CNS directed therapies are probably inadequate to prevent CNS relapse in high risk DLBCL patients, therefore further research to develop better agents is needed in this area.

Retracted: Overview of recent trends in diagnosis and management of leptomeningeal multiple myeloma: Diagnosis/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. Copyright

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.

Retracted: 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. Copyright

Lymphoma Presenting as Secondary HLH: A Review With a Tale of Two Cases

Lymphoma-associated hemophagocytic syndrome is a disease with an extremely poor prognosis and can be easily missed at diagnosis. Identifying and treating the underlying lymphoma early is of utmost importance because that directly affects outcome. Thorough and repeated testing for the underlying cause is imperative. Further studies are necessary to better understand the most appropriate front-line therapy. Allogeneic bone marrow transplant has shown promising results in children and needs to be studied further in adults.