Assessing the Relationship between Chronic Lymphoid Leukemia Mortality Rates and Human Development Index: A 26-Year Trend Analysis Using Location-Scale Mixed Effects Model

Background: Chronic lymphoid leukemia (CLL) is one of the most prevalent types of leukemia, which is responsible for a remarkable mortality rate in the world. This study aimed to investigate the global trend of this cancer from 1990 to 2015 and to determine the relationship between trend of CLL mortality rate and Human Development Index (HDI) throughout the world. Methods: The age-standardized mortality rate data of all countries of the world (per 100,000) were extracted from the GBD database. In addition, the HDI values for the studied countries in different years were obtained from the UNDP database. The statistical analysis was performed using the mixed-effects location-scale model in the SAS software, version 9.4. Results: The findings of the statistical modeling showed a downward slope for CLL Age Standardized Mortality Rate (ASMR) for total world countries ( ˆ   0.002 ). We also find a significant association between CLL ASMR and HDI. Countries with higher HDI had higher level of CLL ASMR in years 1990 to 2015 with a negative slope. Furthermore, countries with lower HDI had Lower level of CLL ASMR with rather fixed rates in this period. Conclusion: These findings showed a decreasing trend of global CLL ASMR in the previous decades, although, the fixed trend of CLL ASMR in countries with low HDI is worrisome. The health policymakers should make more efforts to decrease the mortality due to this cancer in these countries.

Epileptic Seizure Provoked by Bone Metastasis of Chronic Lymphoid Leukemia and Merkel Cell Carcinoma

Background. Merkel cell carcinoma (MCC) is a rare primary neuroendocrine cutaneous tumor, rarely metastasizing to the brain. Chronic lymphoid leukemia (CLL) is a disease predisposing to MCC. According to previous reports, headache and focal neurological deficits suggest disease progression to the brain. We present a patient with MCC whose seizure was not elicited by a cerebral metastasis, but by bone metastases compressing the brain. Case Presentation. A 62-year-old female patient had a history of CLL. A lesion with the appearance of an atheroma was removed from the right upper arm. Histology confirmed the diagnosis of MCC. She was admitted to the neurology department with her first GM seizure. The cranial MRI/MRA showed bone metastases in the right parietal and both frontal areas, compressing the brain. Flow cytometry of CSF did not reveal metastasis of MCC. Conclusions. The case history of the patient was unique even among the rare cases of MCC with neurological involvement. The seizure was not elicited by a cerebral metastasis, but by bone metastases compressing the brain. In addition to patient history, clinical presentation and radiological findings enabled a suspected diagnosis of skull metastasis of MCC compressing the brain, causing symptomatic epileptic seizures.

Relevance and management of secondary hypogammaglobulinema in clinical practice

Advance protocols for the treatment most of oncology, hematology and some inherited disorders may lead to development severe secondary hypogammaglobulinaemia. Particularly, it is often caused by therapy with monoclonal antibodies binding B-cells (such as rituximab, belimumab, inotuzumab), therapy with inhibitors of tyrosine-kinase (imatinib, desatinib), as well as applying a variety of immunosuppressive and chemotherapy agents (steroids, azathioprine, cyclophosphamide etc.). It should be note, that chronic lymphoid leukemia and multiple myeloma could be complicated with hypogammaglobulinaemia, not only because of specific therapy, but also as features of the diseases. Hematopoietic stems cells transplantation can also lead to development severe and prolonged hypogammaglobulinaemia. This is associated with intensive immune/myeloablative therapy, as well as with immunologic reconstitution after transplantation. Modern intravenous immunoglobulins (IVIG) have a wide repertoire of pathogen-specific activity with high safety profile and constitute essential part of therapy patients with secondary hypogammaglobulinaemia. The paper presents literature review of IVIG usage in various clinical situations, as well as several clinical examples of personal experience.