Prognostic significance of bone marrow fibrosis in diffuse large B-cell lymphoma.

INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphomas. The aim of this study is to determine the relationship between the increase in the degree of fibrosis in the bone marrow and prognosis and mortality in newly diagnosed DLBCL. METHODS: Bone marrow biopsy of 153 newly diagnosed DLBCL patients was determined by staining with reticulin, Masson's trichrome histochemical stain, and the degree of fibrosis was determined. RESULTS: In the bone marrow biopsy performed at the time of diagnosis, bone marrow fibrosis (BMF) was observed in 70 patients. While BMF-1 was detected in 42 patients (60%), BMF-2 was detected in 25 patients (35%) and BMF-3 was detected in 3 patients (4%). As the degree of BMF increased, the median overall survival and median progression-free survival times were significantly shorter (p: 0.008), (p < 0.001). In patients with an increased degree of BMF, a significant decrease in leukocyte and neutrophil counts was observed after chemotherapy (p: 0.004). According to the results of the multivariate Cox regression model, it was determined that high NCCN-IPI risk (HR: 8.25; %95 CI: 1.09-62.52; p = 0.041) and being BMF ≥ 2 (HR: 3.75; %95 CI: 1.65-8.51; p = 0.002), increased the risk of death (p = 0.002, -2 loglikelihood = 392,553). CONCLUSION: When the literature was reviewed, it was seen that this study was the first to define that bone marrow fibrosis grade 2 and above in DLBCL is a prognostic marker associated with worse survival. In the bone marrow pathology, which is examined to detect advanced disease in DLBCL, besides lymphomatous involvement, the detection of fibrosis grade is very important.

Progressive Multifocal Leukoencephalopathy Among Ibrutinib Treatment In Chronic Lymphocytic Leukemia.

INTRODUCTION: Both chronic lymphocytic leukemia (CLL) itself and the drugs used for its treatment, pose a risk for progressive multifocal leukoencephalopathy (PML). Although the relationship between Rituximab and PML is well known, case reports that have been recently published, suggest that ibrutinib; which is used in the treatment of CLL, may increase the risk of PML. CASE REPORT: Here, we report a case of 64 year-old female patient with CLL who was previously treated with rituximab, fludarabine and bendamustin but developed PML after receiving monotherapy with ibrutinib. According to Naranjo's algorithm, the causality relationship with the drug is possible with a score of 3. The patient initially exhibited neurological symptoms. Magnetic resonance of the brain revealed a bilateral asymmetric hyperintensity in the white matter involving the parietal and occipital lobules, and there was no mass effect, edema, hemorrhagic or iscemic lesions. No enhancement of contrast media was observed. The findings were consistent with demyelination and suggestive of PML. MANAGEMENT AND OUTCOME: Mirtazapine treatment was initiated. However, neurological sympthoms continuously progressed over the following weeks and the patient, aged 64, died six weeks after diagnosis of PML. DISCUSSION: PML is a rare and often fatal demyelinating disease of the central nervous system (CNS) that is exclusively seen in immunocompromised patients and there is no specific agent to treat PML. The case discussed here, highlights that the use of ibrutinib in chronic lymphocytic leukemia (CLL) therapy may result in PML.

Isolated Richter's transformation in central nervous system in a patient with refractory chronic lymphocytic leukemia.

A 67-year-old woman was diagnosed with Chronic Lymphocytic Leukemia (CLL) and chemotherapy was started. Due to epileptic seizure and left hemiplegia that developed on the twenty first day of the treatment, cranial magnetic resonance imaging was performed and a markedly increased mass of a diameter of 5 cm in the right frontal lobe was seen. Diffuse large B-cell non-Hodgkin lymphoma was concluded at diagnostic brain biopsy. Repeated bone marrow biopsy implemented simultaneously, was reported as CLL. Based on the diagnosis of isolated Richter transformation in the CNS secondary to CLL, R-IDARAM (Rituximab, idarubicin, dexamethasone,cytrabine, methotrexate) treatment was initiated. The patient died on the eighteenth day of treatment due to neutropenic fever and septicemia caused by pulmonary infection.

Determination of the relationship between mortality and SOFA, qSOFA, MASCC scores in febrile neutropenic patients monitored in the intensive care unit.

PURPOSE: Febrile neutropenia (FN) is a hematological emergency. It is challenging and confusing for the clinicians to make the decision of the febrile neutropenic patients under chemotherapy to be monitored at intensive care unit (ICU). The aim of this study was to define the factors supporting decision-making for the critical patients with febrile neutropenia. METHODS: The data of 60 patients, who were taken to the ICU while they were under treatment in the Hematology Clinic with a diagnosis of febrile neutropenia, were analyzed retrospectively, in order to identify clinically useful prognostic parameters. RESULTS: The ICU mortality rate was 80%. Mortality was significantly associated with higher sequential organ failure assessment score (SOFA), quick sequential organ failure assessment score (qSOFA), and hematological SOFA (SOFAhem) scores on admission. All cases having SOFA score 10 and above and qSOFA score 2 and above died. In multivariate analysis, qSOFA score was found to be statistically significant in predicting mortality in regard to ICU admission (p = 0.004). CONCLUSION: Mortality of febrile neutropenic patients admitted to ICU is high. It would be appropriate to determine the extent of organ dysfunction instead of underlying disease, for making the decision of ICU admission. It should be noticed that the risk mortality is high for the FN cases with SOFA score 10 or above, qSOFA score 2 or above, and in need of mechanical ventilation and positive inotropic support; hence, early intervention is recommended. In our study, the most significant parameter in predicting ICU mortality was found to be qSOFA.

An adult case of atypical hemolytic uremic syndrome presented with posterior reversible encephalopathy syndrome: Successful response to late-onset eculizumab treatment.

Atypical hemolytic uremic syndrome is a rare and progressive disease caused by uncontrolled alternative complement activation. Dysregulation of the complement activation results in thrombotic microangiopathy and multiorgan damage. A 29-yearold woman who was admitted with complaints of vomiting and headache was detected to have acute renal failure with microangiopathic hemolytic anemia (MAHA). After the diagnosis of atypical hemolytic uremic syndrome (aHUS), she was treated with plasma exchange (PE) and hemodialysis (HD). She has experienced hypertensionrelated posterior reversible encephalopathy syndrome (PRES) at the second plasma exchange. She was initiated on eculizumab therapy because of no response to PE on the 34th days. Her renal functions progressively improved with eculizumab treatment. Dependence on dialysis was over by the 4th month. Dialysis free-serum Creatinine level was 2.2 mg/dL [glomerular filtration rate (e-GFR): 30 mL/min/1.73 m2] after 24 months. Neurological involvement (PRES, etc.) is the most common extrarenal complication and a major cause of mortality and morbidity from aHUS. More importantly, we showed that renal recovery may be obtained following late-onset eculizumab treatment in patient with aHUS after a long dependence on hemodialysis.

The relationship between mortality and microbiological parameters in febrile neutropenic patients with hematological malignancies.

OBJECTIVES: To determine effective risk factors on mortality in febrile neutropenic cases with hematologic malignancy. Patients with hematologic diseases are more prone to infections and those are frequent causes of mortality. METHODS: This retrospective study was performed using data of 164 febrile neutropenic cases with hematologic malignancies who were followed up in a hematology clinic of a tertiary health care center between 2011-2015. The relationship between descriptive and clinical parameters rates and rates of mortality on the 7th and the 21st days were investigated. RESULTS: Patients with absolute neutrophil count less than 100/mm3, duration of neutropenia longer than 7 days, pneumonia or gastrointestinal foci of infection, central catheterization (p=0.025), isolation of Gram (-) bacteria in culture, carbapenem resistance, septic shock, and bacterial growth during intravenous administration of antibiotic treatment were under more risk for mortality on both the 7th and the 21st days. The final multivariate logistic regression results showed that pneumonia (p less than 0.0001), septic shock (p=0.004) and isolation of Gram-negative bacteria (p=0.032) were statistically significant risk factors. CONCLUSION: Early diagnosis and appropriate treatment of serious infections, which are important causes of morbidity and mortality, are crucial in patients with febrile neutropenia. Thus, each center should closely follow up causes of infection and establish their empirical antibiotherapy protocols to accomplish better results in the management of febrile neutropenia.