Erdheim-Chester disease of brain parenchyma without any systemic involvement: A case report and review of literature.

Erdheim-Chester disease is a non-Langerhans cell histiocytosis syndrome characterised by histiocytic infiltration of different organs and systems in the body. Erdheim-Chester disease with isolated central nervous system (CNS) involvement causes diagnostic difficulties due to the absence of systemic findings and may result in misdiagnosis and inaccurate treatment choices. The case discussed in this report exemplifies how challenging it is to diagnose Erdheim-Chester disease with isolated CNS involvement. This case, which presented with progressive pyramidocerebellar syndrome, was clinically and radiologically resistant to all immunosuppressive and immunomodulatory treatments administered. The presence of false negative results in repeated histopathological investigations and the absence of evidence for systemic disease hindered the diagnosis and treatment work-up. In this study, we reviewed and discussed the prominent features of the presented case in light of the relevant literature.

Tocilizumab in COVID-19: The Cerrahpasa-PREDICT score.

BACKGROUND: Cytokine release syndrome (CRS), characterized by overproduction of proinflammatory cytokines in the course of severe coronavirus disease 2019 (COVID-19), has been suggested as the major cause of mortality. Tocilizumab, a recombinant humanized monoclonal antibody against human IL-6 receptor, poses a therapeutic option for the treatment of CRS leading to severe acute respiratory syndrome in coronavirus-2 (SARS-CoV-2) infection. METHODS: We performed a single-center retrospective study to reveal the outcome of COVID-19 patients on tocilizumab and proposed "the Cerrahpasa-PREDICT score", a new clinical scoring system using clinical and laboratory parameters that would help predicting the 28-day mortality of COVID-19 patients receiving tocilizumab. RESULTS: Eighty-seven patients (median age: 59 years) were included of whom 75.8% were male. Tocilizumab use significantly improved clinical and laboratory parameters. The 28-day mortality rate on tocilizumab was 16.1%. The Cerrahpasa-PREDICT score, consisting of platelet counts, procalcitonin, D-dimer levels, SO2R and the time from symptom onset to tocilizumab administration had a positive predictive value of 94.5% and negative predictive value of 92.9% for anticipating 28-day mortality. CONCLUSIONS: Severe COVID-19 should closely be monitored for the signs of hyperinflammation. We showed that administration of tocilizumab early in the course of the disease (prior to ICU admission) resulted in a favorable outcome. Close monitoring usually aids identifying patients who would benefit from tocilizumab. In this regard, the Cerrahpasa-PREDICT score might serve as a practical tool for estimating the 28-day mortality in COVID-19 patients who received tocilizumab and would facilitate timely recognition of fatal cases to be evaluated for other therapeutic options.

The prognostic value of serum levels of a proliferation-inducing ligand (APRIL) in treatment-naïve patients with chronic lymphocytic leukemia

Background/aim: A proliferation-inducing ligand (APRIL) has been investigated as a prognostic marker in chronic lymphocytic leukemia (CLL) patients. However, there is no cut-off level for serum APRIL (sAPRIL) levels that predict time to treatment in CLL patients. Materials and methods: Between May and December 2012, 94 consecutive CLL patients and 25 healthy controls were assessed. sAPRIL levels were measured by ELISA. Demographic data and prognostic markers were obtained from the patients' files. Treatment-naïve patients were followed up for 6.5 years for any treatment need. Results: Patients were divided into 3 groups: Treatment-naïve (n = 47), chemotherapy receiving (n = 25), and those who had received chemotherapy previously (n = 22). There was no difference in median sAPRIL levels of patients who were receiving chemotherapy at the sampling time and the healthy controls, which indicates that sAPRIL levels might be influenced by treatment. For treatment-naïve patients, the best cut-off in predicting time to treatment was found at the sAPRIL level of 2.04 ng/mL, with 78% sensitivity and 63% specificity. Time to treatment was significantly earlier in the APRIL high group (n = 27) than in the APRIL low group (n = 20) (P = 0.010, log-rank test). Conclusion: sAPRIL, a simple, promising blood test which can be measured by ELISA, will likely obtain a place in the wide range of prognostic markers in CLL. Prospective large-scale studies are required to validate and confirm the feasibility of the proposed cut-off level of 2.04 ng/mL as a predictor of time to treatment in treatment-naïve CLL patients.

Hepatitis B reactivation in hematopoietic stem cell transplanted patients: 20 years of experience of a single center from a middle endemic country.

Hematopoietic stem cell transplantation (HSCT) is a risk factor for viral hepatitis reactivations because it affects lymphocyte number and functions. Latent hepatitis B virus (HBV) may stay in dormant form in hepatocytes and may be reactivated in prolonged immunosuppression. This study analyzes the incidence of reactivation of HBV infections in HSCT patients in a middle endemic country like Turkey. Five hundred and sixty-one HSCT patients from 1994 to 2015 were retrospectively evaluated. Sixty-six patients had a serologic feature of HBV infection. Fifteen patients were hepatitis B surface antigen (HBsAg)-positive patients (3 allogeneic and 12 autologous) while 51 of them were anti-hepatitis B core IgG (anti-HBc IgG)-positive patients (22 allogeneic and 29 autologous). Although under lamivudine prophylaxis, reactivation was seen in three of 12 (25%) chronic HBV (HBsAg positive) patients who received autologous HSCT and in two of the three HBsAg-positive patients who received allogeneic HSCT. Rate of reactivation in the whole HBsAg-positive group was 33%. Reactivation occurred on median 270th day (range: 60-730). Reverse seroconversion incidence was 10% on 133th day for HBsAg negative, but anti-HBc IgG-positive patients, which increased to 17% on 360th and to 23% on 1500th day. Cumulative incidence increased to 41% on 2280th day for isolated anti-HBc IgG-positive patients. Hepatitis B surface antibodies (anti-HBs) were found to be protective as reactivation did not exceed 11% on 5050th day when anti-HBs was positive. When anti-HBc IgG-positive cases were analyzed according to their transplantation types, allogeneic HSCT was found to have higher cumulative incidence (45% on 3258th day) for HBV reactivation than autologous HSCT (7% on 5050th day). Besides, HBV reactivation in anti-HBc IgG-positive patients who received allogeneic transplantation was related to mortality. Findings of this study suggest that HBV prophylaxis extending over 1 year should be prescribed for HBsAg-positive patients independent of the transplantation type. Prophylaxis should also be given to anti-HBc IgG-positive patients if an allogeneic HSCT is to be performed.

Follicular lymphoma generating in a patient with non-small cell lung cancer following nivolumab discontinuation.

INTRODUCTION: Immune checkpoint inhibitors have demonstrated the benefit for many cancer types, melanoma, non-small cell lung cancer, urothelial cancer, renal cell cancer, etc. Especially in advanced non-small cell lung cancer, significant improvement in survival results has been shown. CASE REPORT: Here, we report a 66-year-old man with lung adenocarcinoma who received nivolumab for 80 cycles.Management and Outcome: Two months after discontinuing nivolumab, he developed follicular lymphoma. Pneumonitis was also accompanied, which was treated with metilprednisolon, but he died due to progressive respiratory failure. DISCUSSION: Our clinical knowledge with checkpoint inhibitors is increasing day by day, and to the best of our knowledge, this paper presents the first case in the English literature who developed follicular lymphoma after discontinuing nivolumab in non-small cell lung cancer patient.

New drugs approved for acute myeloid leukaemia in 2018.

Acute myeloid leukaemia (AML) is a haematopoietic stem cell disorder, that is characterized by the clonal expansion of myeloid blasts and suppression of normal haematopoiesis. The 3 + 7 regimen is the backbone of standard first-line induction therapy among young/fit patients. However, in elderly and/or unfit patients with newly diagnosed AML, who cannot receive intensive chemotherapy, low-dose cytarabine or hypomethylating agents (azacitidine or decitabine) are the treatment options, which generally cannot induce durable responses. Among young/fit patients, for high-risk disease in first remission, or in cases with relapsed/refractory AML, allogeneic stem cell transplantation should be performed when complete remission is achieved. However, since AML is primarily a disease of the elderly, neither intensive chemotherapy nor allogeneic stem cell transplantation can be generally tolerated in most cases. There is clearly a need for new treatment options in elderly and young/unfit patients who cannot receive intensive chemotherapy. The discovery of novel molecular genetic markers (e.g. FMS-like tyrosine kinase 3, isocitrate dehydrogenase 1 and 2) resulted in the development of new therapeutic options in AML. This review mainly focuses on 4 targeted therapy agents; glasdegib and venetoclax used in combination treatment with low-dose cytarabine or hypomethylating agents among newly diagnosed cases with AML; and ivosidenib and gilteritinib as monotherapy in the treatment of relapsed/refractory AML, which were all approved by the US Food and Drug Administration in 2018.

Coexistence of Hermansky-Pudlak syndrome and JAK2V617F-positive essential thrombocythemia.

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder consisting of oculocutaneous albinism, platelet storage pool deficiency, and lysosomal accumulation of ceroid lipofuscin. The storage pool deficiency of HPS is associated with the lack of dense bodies in the platelets, resulting in impaired response in the secondary phase of aggregation. Patients with HPS have normal coagulation tests; however, their bleeding time is usually prolonged despite normal or increased platelet counts. Essential thrombocythemia (ET) is an uncommon condition, with an incidence of approximately 1.1 per 100,000/year, and it is the most common cause of primary thrombocytosis. JAK2V617F positivity can be observed in approximately half of the patients with ET. Bleeding events in ET have usually been associated with acquired von Willebrand syndrome paradoxically occurring when the platelet counts are extremely high. We, herein, present a case with bleeding diathesis diagnosed as having both HPS and JAK2V617F-positive ET.

Dasatinib-induced pulmonary arterial hypertension.

Drug-induced (group 1) pulmonary hypertension (PH) is an important subgroup of PH involving dasatinib as a likely related agent, which is a second-generation tyrosine kinase inhibitor (TKI) used in the treatment of chronic myeloid leukaemia (CML). The mechanism of dasatinib-induced pulmonary arterial hypertension (PAH) is unclear. However, the occurrence of PAH with late onset in CML patients suggests a chronic pathological mechanism with an insidious onset rather than an acute inflammatory or cardiac aetiology. Dasatinib has a broader effect than other TKIs; the major known difference between dasatinib and other TKIs is the additional inhibition of Src family kinases. Therefore, Src inhibition was thought to play a role in the development of dasatinib-induced PAH. However, recently, it was also speculated that chronic dasatinib therapy may cause pulmonary endothelial damage, attenuate hypoxic pulmonary vasoconstriction responses and increase susceptibility to PAH independently of the Src family kinase-induced mechanism. Dasatinib-induced PAH usually seems to be reversible with the cessation of the drug, and sometimes with PAH-specific treatment strategies. Transthoracic echocardiography can be recommended as a routine screening prior to dasatinib initiation, and this non-invasive procedure can be utilized in patients having signs and symptoms attributable to PAH during dasatinib treatment.

Cytopenia in adult brucellosis patients.

BACKGROUND & OBJECTIVES: Brucellosis can lead to haematological abnormalities including cytopenia confusing with haematological malignancies. The aim of this study was to compare the main characteristics of brucellosis patients without cytopenia (Group 1) and with cytopenia (Group 2). METHODS: This five-year period study which was performed in two referral hospitals in Turkey, included all adult brucellosis patients. Abnormally, low counts of leucocyte or haemoglobin or platelets in a patient were considered as cytopenia. The demographics, clinical, laboratory, treatment and outcome data were analyzed. RESULTS: A total of 484 brucellosis patients were enrolled. Among the cases, 162 (33.5%) of them had cytopenia. One hundred and four (21.5%) had anaemia, 88 (18.8%) had thrombocytopenia, 71 (14.6%) had leucopenia and 28 (5.8%) had pancytopenia. The mean age of group 2 was 35.01±16.05 yr and it was 33.31±14.39 yr in group 1. While there was no difference between the groups in terms of duration of treatment, the median length of hospital stay (LOS) was significantly longer in group 2 (9 vs 10 days; P<0.001). The most frequently applied combination therapy consisted of doxycycline plus rifampicin and doxycycline plus streptomycin regimens. No significant difference was observed in terms of duration of treatment, LOS and restoration time of cytopenia between the patients who received either of these combinations. INTERPRETATION & CONCLUSIONS: Our findings suggested that the patients with cytopenia should be investigated for brucellosis, especially if living in, or with a history of travel to, endemic areas, in view of the increase in world travel.