Leukocytoclastic vasculitis due to ruxolitinib treatment: A rare adverse effect.

WHAT IS KNOWN AND OBJECTIVE: Primary myelofibrosis (PMF) is characterized by myeloid cell proliferation and prominent bone marrow fibrosis. Ruxolitinib, a selective inhibitor of JAK 1 and 2, significantly reduces constitutional symptoms and spleen size compared with placebo, and has significant clinical benefits in patients with myelofibrosis. The most common haematological side effects are thrombocytopenia and anaemia, and the most common non-haematological side effects are grade 1-2 diarrhoea and pyrexia. Leukocytoclastic vasculitis is small vessel vasculitis, characterized histopathologically by immune complex-mediated vasculitis of the dermal capillaries and venules in the lower extremities, which can be seen as palpable purpura. Although the cause is 50% idiopathic, the aetiology of leukocytoclastic vasculitis can be collected under many headings. CASE SUMMARY: The case is here presented of a patient with PMF who developed leukocytoclastic vasculitis after ruxolitinib treatment. Ruxolitinib was discontinued as the lesions were thought to be drug-related and all skin lesions disappeared approximately 2 months after termination of the drug. When the ruxolitinib treatment was restarted at the same dose (2 × 15 mg), the skin lesions recurred. The drug dose was reduced to 1 × 15 mg, and the rashes disappeared. Currently, the patient has no active complaints and is being followed up with ruxolitinib 1 × 15 mg without any complications. WHAT IS NEW AND CONCLUSION: To the best of our knowledge, leukocytoclastic vasculitis due to ruxolitinib is extremely uncommon. This case report can be considered to contribute to the literature of this rare event.

A rare case of diffuse large B-cell lymphoma-associated hemophagocytic lymphohistiocytosis.

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is an aggressive and life-threatening syndrome of excessive immune activation. Herein, we aimed to report a diffuse large B-cell lymphoma (DLBCL) case that was presented as HLH. CASE REPORT: A 32-year-old man presented to a hospital with complaints of vomiting, nausea and diarrhea in October 2019. Fever and hepatosplenomegaly was detected in physical investigation. Bone marrow aspiration investigation revealed the hemaphagocytosis. HLH-2004 protocol was started for hemophagocytosis. Whole body magnetic resonance imaging (MR) revealed no lymphadenopathy. Bone marrow biopsy revealed high-grade B-cell lymphoma, favoring DLBCL. There were no pathologic cells in lumber puncture investigation. MANAGEMENT AND OUTCOME: He was diagnosed with secondary hemaphagocytic syndrome due to DLBCL, and chemotherapy was switched to rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (R-EPOCH) regimen. After three cycles of R-EPOCH chemotherapy regimen, complete remission was confirmed with positron emission tomography-computerised tomography (PET-CT) scan. DISCUSSION: Our patients' findings are suitable for six out of eight criteria of hemaphagocytic syndrome. The H-score of our patient was more than 250, reflecting the >99% probability of HLH syndrome. Compatible with literature knowledge, our patient had responded very well to etoposide-containing regimens. In our patient, no lymphadenopathy was detected by physical examination or MR scan, and the diagnosis of DLBCL was only made by the result of bone marrow investigation. In conclusion, herein, we have reported a DLBCL case that had presented with HLH, and clinicians should be aware that B-cell lymphomas may be the underlying cause of HLH.

Thrombocytopenia due to rivaroxaban: A rare adverse effect.

INTRODUCTION: Rivaroxaban is a novel, oral direct acting anticoagulant (DOAC) that is used for both treatment and prevention of thromboembolic diseases. Due to mechanism of action; most common side effect may be seen with hemorrhage. Here in we reported that a patient with chronic atrial fibrillation presented with thrombocytopenia while taking rivaroxaban. CASE REPORT: A 76-year-old female patient with atrial fibrillation was given rivaroxaban, after lack of dose administration of warfarin and gastrointestinal bleeding. In 12th dayweek of treatment, the patient was admitted to emergency department (ED) with oral mucosal bleeding and petechial spots.The patient diagnosed as Drug-induced Thrombocytopenia (DITP)due to rivaroxaban use, after ruled out most possibilities ofITP (immune thrombocytopenic purpura). After rivaroxaban is discontinued, the patient's bleeding complaints regressed,symptoms were completely resolved, and platelet count rapidly increased towards physiological level in days. The patient is currently in the 6th month of follow-up and is has no bleeding. CONCLUSION: To the best of our knowledge there are only two cases about rivaroxaban induced thrombocytopenia (RIT). In addition to the well-known side effects ofrivaroxaban treatment, it should be kept in mind that thrombocytopenia may also develop.Naranjo adverse drug reaction probability scale calculated as 7 points.(probable cause for the patient's thrombocytopenia).

Q fever as a rare cause of hemophagocytic lymphohistiocytosis: Case report.

Hemophagocytic Lymphohistiocytosis (HLH) is a reactive disorder of the mononuclear phagocytic system characterized by increased histiocytic proliferation, activation and hemaphagocytosis. The underlying etiology may be genetic (primary) or acquired (secondary). Secondary causes include drugs, autoimmune diseases, malignancies and infections of which EBV is the most common. A 28-year old male patient who was a shepherd with no known concomitant comorbid disease was admitted to the Emergency Department with the complaints of abdominal pain, fever, severe fatigue. Physical examination revealed high fever, hepatosplenomegaly and laboratory examination revealed pancytopenia, hyperferritinemia and hypertriglyceridemia. Hemophagocytes were observed in the bone marrow biopsy and the patient was diagnosed as HLH. The patient was treated with cyclosporine A, dexamethasone, intravenous immunoglobulin (IvIg) and etoposide according to the HLH 2004 protocol. Coxiella burnetii was detected in the serological evaluation of the etiology and doxycycline was added to the current treatment. Fever was controlled in the second week of the treatment and the patient was discharged after complete recovery of the cytopenia in the fourth week. In the outpatient setting, treatment was completed in 8 weeks and follow-up of the patient is still ongoing without medication. To the best of our knowledge, this is the first case from Turkey of HLH secondary to Q-fever which was treated and managed successfully. Since the mortality of HLH is quite high, the etiology should be determined as soon as possible to be able to provide appropriate treatment.

Ibrutinib-induced polyneuropathy: A case report.

INTRODUCTION: Ibrutinib is an oral irreversible inhibitor of Bruton's tyrosine kinase signaling. It is a well-tolerated agent with some side-effects, the most common of which are atrial fibrillation, diarrhea, upper respiratory tract infection, fatigue, nausea, rash and cytopenias. Most of these toxicities are mild, although some have a severe clinical course. CASE REPORT: The case is here reported of a chronic lymphocytic leukemia patient with ibrutinib-induced polyneuropathy. A 63-year-old male patient with chronic lymphocytic leukemia was given ibrutinib as a third line treatment regimen. After the 10th month of therapy he had progressive complaints of numbness and tingling in his legs. The patient was diagnosed as grade 3 sensorineural polyneuropathy with electromyography.Management and outcome: Considering that ibrutinib treatment may cause neuropathy, the ibrutinib was discontinued, after which the neuropathic complaints improved. However, the neck and axillary lymph nodes were enlarged and treatment had to be re-started therefore ibrutinib was started at a low dose and gradually increased. The patient is currently in the 14th month of treatment and still using ibrutinib without any severe side-effects. DISCUSSION: To the best of our knowledge, polyneuropathy as a unique side-effect of ibrutinib has not been previously reported. In addition to the well-known side effects of ibrutinib treatment, it should be kept in mind that polyneuropathy may also develop.

The incidence and risk factors of thrombosis and the need for thromboprophylaxis in lymphoma and leukemia patients: A 9-year single-center experience.

BACKGROUND: Patients with cancer are at increased risk of thromboembolic complications. There is no evidence-based guideline on the use of routine prophylaxis in hematological malignancies except in patients with multiple myeloma. The purpose of this study was to determine the incidence and risk factors of thrombosis and suggest a rationale for primary thromboprophylaxis in acute leukemia and lymphoma patients. PATIENTS AND METHODS: A retrospective study was conducted on newly-diagnosed acute leukemia and lymphoma patients who presented at our institution from November 2009 to March 2018. The study included a total of 157 patients with acute leukemia and 238 patients with lymphoma. The groups were analyzed to determine the incidence and risk factors of thromboembolic complications. RESULTS: The incidence of all thrombotic complications was 10.12% (40/395) including 11.4% (18/157) in patients with acute leukemia and 9.2% (22/238) in patients with lymphoma. The majority of events occurred in the first 6 months. Acute leukemia patients with thrombosis had a higher number of comorbidities than those without thrombosis (p < 0.05). Lymphoma patients with thrombotic complications had significantly higher beta-2-microglobulin and lactate dehydrogenase levels compared to those without thrombosis (p < 0.05). Major bleeding events developed in five (3.1%) acute leukemia patients and two (0.8%) lymphoma patients. All the major bleeding events occurred when the patients were thrombocytopenic (platelet < 50,000/mm3). CONCLUSIONS: Acute leukemia patients with any comorbidity and lymphoma patients with higher lactate dehydrogenase and beta-2-microglobulin are at high risk of developing thromboembolic complications. The prophylactic use of anticoagulant should be considered for those patients especially in the first 6 months.

Is urine immunofixation electrophoresis necessary for monitoring myeloma patients who have undergone hematopoietic stem cell transplantation?

INTRODUCTION: To investigate the role of urine immunofixation electrophoresis in detecting relapse in patients with myeloma who have undergone autologous and allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: The study included a total of 78 patients, comprising 49 males and 29 females, with progressive disease or relapse after HSCT. Serum protein electrophoresis (sPE), serum immunofixation electrophoresis (sIFE) and serum free light chain κ/λ ratio in addition to urine immunofixation (uIFE) were studied. RESULTS: sPE, sIFE and κ/λ ratio demonstrated relapse in 65.3%, 88.3% and 58.9% of the cases by theirselves respectively. The combination panel of sPE and sIFE demonstrated relapse in 88.3% of patients whereas sPE, sIFE and κ/λ ratio all together demonstrated relapse in 95.8% of the patients. In relapsed patients, urine immunofixation was found to be positive in 16.2% of the patients. No patients with relapsed disease were missed by omitting uIFE from serum studies (sPE, sIFE and sFLC). CONCLUSION: For evaluation of relapse in MM patients after HSCT, uIFE had no additional diagnostic capability compared to serum studies (sPE, sIFE, and sFLC). Therefore, urine studies should be performed more selectively.

The efficacy of double filtration plasmapheresis in the treatment of homozygous familial hypercholesterolemia: A single-center experience.

INTRODUCTION: Different modalities of low-density lipoprotein (LDL) apheresis are used to treat patients with familial hypercholesterolemia (FH). The aim of this study was to describe the efficacy of the Double Filtration Plasmapheresis (DFPP) method for FH cases in our hands and to compare with other LDL apheresis techniques. MATERIALS AND METHODS: This retrospective study was conducted between January 2016 and January 2018 in the University of Health Sciences, Diskapi Yildirim Beyazit Training and Research Hospital, Adult Hematology Clinic and Therapeutic Apheresis Unit. The study included 5 patients with a diagnosis of homozygous FH. A total of 288 DFFP procedures were performed twice a month (every 15 days) for 2 years. RESULTS: The percentage reductions in Lipoprotein A, total cholesterol, Low Density Lipoprotein-C, High Density Lipoprotein-C and triglyceride levels were found to be 84%, 69.2%, 69.8%, 58.8% and 50.1% respectively (5 cases, n = 288). No cardiac event occurred after the initiation of LA with DFPP. CONCLUSION: DFPP is an effective and safe LA method that can be used in the treatment of homozygous FH patients who do not respond to diet and statin therapy.

Refractory Thrombotic Thrombocytopenic Purpura in a patient with Kaposi sarcoma.

The case is here presented of a 70-year old male patient with rare coexistence of Kaposi Sarcoma and resistant Thrombotic Thrombocytopenic Purpura (TTP). The Kaposi lesions were determined before the diagnosis of TTP and were exacerbated after receiving TTP-associated immunosuppressive therapy, in particular associated with rituximab. TTP in this case was resistant to conventional therapies such as steroid and plasma exchange and current immunosuppressive (rituximab, cyclophosphamide, vincristin) treatments. Novel treatment agents consisting of bortezomib and eculizumab given to the patient were also ineffective. To the best of our knowledge, this case presents the first case of coexistence of TTP and Kaposi sarcoma from Turkey and the challenge of refractory TTP management.

An acute transverse myelitis attack after autologous stem cell transplantation: A rare case.

Transverse myelitis is a quite rare complication of hematopoietic stem cell transplantation. The case is here reported of a 49 year old male with diffuse large B cell lymphoma in complete remission who developed transverse myelitis after autologous stem cell transplantation. The patient presented with numbness and sensory loss of the bilateral lower extremities and difficulty in urinating on the 20th day after cell transplantation. Millimetric hyperintensity was detected in the C5-C6 and T2-T5 segments of the spinal cord on cervical and thoracic vertebral magnetic resonance imaging. Treatment was initiated of pulse steroid and intravenous immunoglubulin followed by plasmapheresis and cyclophosphamide due to inadequate response. The patient then started a rehabilitation program and was discharged in the 9th month after stem cell transplantation when most of the symptoms were relieved. To the best of our knowledge, this is the first case reported in literature of TM development after autologous stem cell transplantation.

CD81 Expression in the Differential Diagnosis of Chronic Lymphocytic Leukemia.

BACKGROUND: Immunophenotyping has a central role in CLL. However, CLL is a very heterogenous disease, both morphologically and immunophenotypically; thus, its diagnosis may prove a challenge. We investigated CD81 ex-pression in the differential diagnosis of CLL and MCL. METHODS: We retrospectively examined CD81 expression with 8 color Multiparameter Flow cytometry devices in 101 CLL and 19 MCL cases. RESULTS: We found negative CD81 expression in CLL cases whereas it was positive in MCL cases. CONCLUSIONS: Our results suggest that CD81 may be a valuable marker for the differential diagnosis of CLL. We are of the opinion that it should be definitely included in the diagnostic algorithm for CLL.

A first time report on the coocurrence of sarcoidosis and ALK(-) CD30(+) anaplastic large cell lymphoma that is highly responsive to brentuximab vedotin treatment.

Sarcoidosis is known to be associated with higher incidence of solid tumors and hematological malignancies. ALK(-) CD30(+) anaplastic large cell lymphoma is a type of non-Hodgkin lymphoma showing poor prognosis, and seldom co-occurs with sarcoidosis. As this rare and highly mortal disease did not respond to classical chemotherapies and showed remission with brentuxumab vedontin treatment, we are presenting our first case reported from Turkey hoping to contribute to the literature.

Is antimicrobial prophylaxis necessary for lymphoma patients? A single centre, real-life experience.

BACKGROUND: Prophylaxis is strongly recommended in patients with hematological malignancy who are usually at higher risk for infection and neutropenic fever. It is still unclear whether or not there is a definite need for antimicrobial prophylaxis in intermediate-risk hematology patients such as those with lymphoma. METHODS: A retrospective analysis was made of patients admitted from January 2009 to December 2017 to the Hematology Department of Diskapi Yildirim Beyazit Training and Research Hospital, a tertiary referral hospital in Ankara, Turkey. The study included patients who were diagnosed with any type of lymphoma and given chemotherapy. Routine antimicrobial prophylaxis was administered to 127 lymphoma patients, and not to 65 lymphoma patients. These two groups were compared in respect of the incidence of total infection episodes (IE), febrile neutropenia episodes, and nonneutropenic clinically documented infection episodes. RESULTS: For all patients with lymphoma and subtypes of non-Hodgkin lymphoma or Hodgkin lymphoma, no significant difference was determined between the groups in respect of the total incidence of IE, febrile neutropenia and nonneutropenic clinically documented infection both during the first-line chemotherapy and throughout the total follow-up period (p > 0.05). Patients with prophylaxis had a higher incidence of IE, which was treated with parenteral antibiotics both during the first-line chemotherapy and throughout the total follow-up period (p < 0.05). CONCLUSION: Antimicrobial prophylaxis was seen to have no effect on the total incidence of infection episode and febrile neutropenia. Therefore, the routine use of antimicrobial prophylaxis should not be recommended for patients with lymphoma.

The rare coexistence of high titer inhibitor development and gastrointestinal stromal tumor in a patient with severe hemophilia: A case report.

Hemophilia is a hereditary disease with impaired blood coagulation due to a genetic deficiency of blood coagulation factors. The development of inhibitors further complicates the course of the disease and management. The case is here reported of a haemophilia patient who presented with coexisting development of high titer inhibitor with Gastrointestinal Stromal Tumor (GIST) diagnosis and was admitted with upper gastrointestinal system bleeding. The patient had no prior history of inhibitor presence. During all procedures including surgery, excellent hemostasis was achieved with rFVIIa treatment and no hemorrhagic complication was observed. To the best of our knowledge, this constitutes the first reported case of GIST associated with inhibitor development in a hemophilia A patient.

Dimethyl Sulfoxide-Induced Tonic-Clonic Seizure and Cardiac Arrest During Infusion of Autologous Peripheral Blood Stem Cells.

Various side effects associated with dimethyl sulfoxide (DMSO) which is used for cryopreservation of bone marrow or peripheral blood progenitor cells (PBPCs) have been reported. Among the central nervous system side effects the epileptic seizures, stroke, transient and temporary leucoencephalopathy, and global amnesia are well known. Herein we report a 52-year-old man who experienced tonic-clonic seizure within minutes after the initiation of DMSO cryopreserved autologous PBPC infusion. Unfortunately, he also developed cardiac arrest and required intubation for ventilation after the seizure. Pathophysiology of acute neurological and cardiac toxicity is unclear, but may also be idiosyncratic. Clinicians should be aware of the toxicity of cryoprotectant agents during PBSC infusion. Determining the risk factors associated with increased DMSO toxicity and taking preventive actions is utmost important.

Platelet Inventory and Using Out-of-group Platelet Suspension: A Cost-Effective Strategy for a Blood Transfusion Service.

BACKGROUND: Platelet (PLT) transfusions are essential for advanced hospitals, especially those with onco-hematology departments. However, platelet concentrates (PCs) have supply limitations and a shorter shelf life, which create difficulties for blood transfusion services (TSs). MATERIALS AND METHODS: This retrospective study was conducted over a 4-year period between January 2017 and January 2021 in a tertiary referral hospital. From the beginning of 2020, as a new strategy of our TS, a PLT inventory was produced and ABO-identical transfusions were prioritized when the inventory allowed; when this was not possible, ABO and Rh incompatible transfusion was employed. The numbers of transfused and discarded PCs were compared for each year. RESULTS: In 2017, a total of 799 PPCs were used and 70 PPCs were discarded with the expiration ratio (ER) of 8.0%. In 2018, 1124 PPCs were used and 99 PPCs were discarded with the ER of 7.4%. In 2019, 726 PPCs were used and 91 PPCs were discarded with the ER of 11.1%. In 2020, 1100 PPCs were used for 569 patients, of which 251 PPCs were ABO and Rh incompatible without any severe transfusion reaction. A total of 56 PPCs were discarded with the ER of 4.8%. CONCLUSION: The results of the current study suggested that with the determination of the platelet stock level and the use of out-of-group PCs, the rate of discarded PLT could be reduced. Nevertheless, based on current literature and experience, each TSs should make their own strategies and policies to provide an adequate supply of PCs.

Long-term Results of Imatinib Discontinuation in Patients with Chronic-phase Chronic Myeloid Leukemia: A National Multicenter Prospective Study

Objective: The discovery of imatinib was a milestone for chronic myeloid leukemia (CML). As the life expectancy of CML patients has approached that of the general population, research has shifted towards improving quality of life and economic considerations. After 2010, it was shown that some patients could maintain molecular response even after discontinuing imatinib. This national multicenter prospective cohort study aimed to observe the long-term consequences of discontinuing imatinib therapy in adult chronic-phase CML patients. Materials and Methods: We enrolled 41 CML patients from 4 different centers in this non-randomized single-arm trial. Molecular responses of all patients were re-evaluated using real-time polymerase chain reaction at a single center. The median follow-up time after imatinib discontinuation was 48 months (minimum-maximum: 6-81 months). Results: The rate of molecular relapse-free survival at 48 months was 33.2% (confidence interval: 48.2-18.2). Twenty-seven of 41 patients lost their major molecular response, treatment was started again, and deep molecular response was re-achieved with imatinib in all cases. There was no significant relationship between molecular relapse and clinical factors such as duration of treatment or molecular response status. Discontinuing imatinib resulted in savings of approximately 4,392,000 Turkish lira or 245,150 US dollars. Conclusion: Tyrosine kinase inhibitor discontinuation with close molecular monitoring is a safe option and provides important national economic benefits for chronic phase CML patients. This approach should be considered for all eligible patients. This is the first tyrosine kinase inhibitor discontinuation study from Türkiye.

α-Amylase monitoring by a novel amperometric biosensor based on Au electrode: its optimization, characterization, and application.

A low-cost and sensitive amperometric biosensor was developed for the determination of α-amylase activity. The biosensor was constructed by immobilizing glucose oxidase-gelatin via glutaraldehyde on the Au electrode surface. Measurements were carried out chronoamperometrically at -0.7 V. Several parameters such as glucose oxidase activity, gelatin amount, and glutaraldehyde percentage for cross-linking were optimized. Optimum pH, optimum temperature, repeatability, and storage stabilities of the biosensor were identified. Under the optimum experimental conditions, a linear calibration curve was obtained for α-amylase between 0.819 and 13.110 U/ml. Sample analyses were carried out by detecting α-amylase activities in baker's yeast samples.

Association of Thrombin-Activatable Fibrinolysis Inhibitor with Acute Pulmonary Embolism.

BACKGROUND: Thrombin-activatable fibrinolysis inhibitor (TAFI) inhibits fibrinolysis and high levels may have an association with thrombosis. The aim of the current study was to investigate the association of TAFI antigen levels with pulmonary thromboembolism (PTE). PATIENTS AND METHODS: A case-control study was conducted with 29 patients with PTE and 17 age- and gender-matched control individuals. Plasma levels of TAFI were measured at the time of diagnosis, then at 3 and 6 months after the event. RESULTS: Initial TAFI levels (%) were higher in patients with PTE than in the control group (190,0 [65,0-250,0] vs 133,0 [83,0-153,0]; p = 0.003). TAFI levels significantly decreased at the third and sixth months after initial diagnosis (p < 0.05). The percentage reductions in TAFI levels were 12 and 36.8% at 3 and 6 months, respectively. The Odss ratio (OR) of TAFI level for PTE was found to be 1.024 (95% CI: 1.007-1.040; p = 0.005). There was no significant correlation of initial TAFI levels with age, gender, smoking status, history of thrombosis, pulmonary artery pressure, and D-dimer levels (p > 0.05). In the sixth month of treatment, patients with residual thrombosis were seen to have similar baseline levels and reductions of TAFI as patients without residual thrombosis (p > 0.05). CONCLUSION: The result of this study suggests that high TAFI levels may have a role in the occurrence of PTE without impact on treatment outcome.