Real-world data on the effectiveness and safety of Ixazomib-Lenalidomide-Dexamethasone therapy in relapsed/refractory multiple myeloma patients: a multicenter experience in Turkey.

A multicenter, retrospective, observational study was conducted to explore effectiveness and safety of ixazomib plus lenalidomide with dexamethasone (IRd) in relapsed/refractory multiple myeloma (RRMM) patients following at least ≥ two lines of therapy. Patients' treatment responses, overall response rate, progression-free survival rate, and adverse events were recorded. Mean age of 54 patients was 66.5 ± 9.1 years. There were 20 patients (37.0%) with progression. Median progression-free survival was 13 months in patients who received a median of three therapy lines in a 7.5-month follow-up period. Overall response rate was 38.5%. Of 54 patients, 19 (40.4%) had at least one adverse event, and nine (19.1%) had an adverse event of at least grade 3 or more. Of 72 adverse events observed in 47 patients, 68% were grade 1 or 2. Treatment was not stopped in any patient due to adverse events. IRd combination therapy was effective and safe in heavily treated RRMM patients.

The Clinical Efficacy of Epoetin Alfa and Darbepoetin Alfa in Patients with Low-Risk or Intermediate-1-Risk Myelodysplastic Syndrome: Retrospective Multi-center Real-Life Study.

This study aimed to evaluate the clinical efficacy of epoetin alfa and darbepoetin alfa in patients with myelodysplastic syndromes (MDS) in the real-life setting. A total of 204 patients with low-risk or intermediate-1-risk MDS who received epoetin alfa or darbepoetin alfa were included. Hemoglobin levels and transfusion need were recorded before and during 12-month treatment. Hemoglobin levels were significantly higher at each follow up visit when compared to baseline levels in both epoetin alfa (mean ± SD 8.68 ± 1.0 g/dL at baseline vs. 9.83 ± 1.45, 9.99 ± 1.55, 10.24 ± 1.77 and 10.2 ± 1.5 g/dL, respectively) and darbepoetin alfa (8.83 ± 1.09 g/dL at baseline vs. 9.62 ± 1.37, 9.78 ± 1.49, 9.9 ± 1.39 and 10.1 ± 1.5 g/dL, respectively) groups (p < 0.001 for each). Transfusion need significantly decreased from baseline at each study visit in the epoetin alfa group (p < 0.001) and only at the 12th month visit (p < 0.001) in the darbepoetin alfa group. Hemoglobin levels or transfusion need was similar between treatment groups. Overall, 12-month response rate was 58.1% for epoetin alfa and 41.9% for darbepoetin alfa, with no significant difference between treatment groups, whereas higher response rate was noted within the first three months (62.7%) compared to next 9 months (ranged 44.4-60%) of treatment in the epoetin alfa group (p ranged 0.002 to < 0.001). This real-life retrospective study revealed similar efficacy of epoetin alfa and darbepoetin alfa among low risk or intermediate-1 risk MDS patients with no difference in treatment response between treatment groups, whereas a likelihood of earlier treatment response in the epoetin alfa group. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-021-01458-1.

The evaluation of patients with essential thrombocythemia in terms of risk of thrombosis.

OBJECTIVE: The aim of this study was to compare the incidence of factors associated with an increased risk of thrombosis in patients with essential thrombocythemia. METHODS: A total of 200 patients followed-up in our unit with a diagnosis of essential thrombocythemia in 13 years were analyzed retrospectively. RESULTS: Of the study participants, 60.5% were females and 39.5% were males, with an overall mean (±SD) age of 54.93 (±14.21) years. In 119 patients, Janus Kinase 2 was positive with 56.3% of cases. When two patient categories were defined as those with or without history of thrombosis, no significant differences were found in terms of Janus Kinase 2 positivity, mean age, as well as white blood cells and platelet counts (p>0.05). Also, no significant differences in thrombotic event incidence were found between patient categories defined on the basis of cut-off values for white blood cells (cut-off values of 15×103/mm3 and 8.7×103/mm3) and platelets (cut-off values of 1500×103/mm3) (p>0.05). CONCLUSION: Although our results are generally in line with the published data, some divergence from previous results has been observed with respect to risk factors for thrombotic events. Absence of a correlation between leukocytosis and thrombosis may be related with the significant decline in white blood cells after treatment. Also, a significant reduction in platelet counts occurring in association with treatment is linked with a lowered incidence of thrombosis. Janus Kinase 2-positive patients had a similar thrombosis frequency with that reported in the literature.

Efficacy and safety of plasmapheresis in symptomatic hyperviscosity and cast nephropathy: A Multicenter Experience in Turkey.

BACKGROUND AND OBJECTIVES: Cast nephropathy (CN) and hyperviscosity (HV), which we encounter in plasma cell diseases, are serious clinical manifestations that increase mortality and morbidity if not managed well in the early period. Therapeutic plasma exchange (TPE) procedures based on the removal of patient plasma is a frequently preferred treatment modality. TPE is recommended at varying levels of evidence for the treatment of CN and HV in plasma cell disorders. MATERIAL AND METHODS: A total of 61 patients, 50 with multipl myeloma (MM) and 10 with Waldenström macroglobulinemia (WM), who underwent TPE for CN and HV, were included in our multicenter, and retrospective study. RESULTS: A statistically significant decrease was found in all disease-related biochemical markers, which were measured 1 week after the application of TPE added to standard medical treatment (IgG; p < 0.001, IgM; p = 0.004, IgA; p = 0.14, kappa light chain; p < 0.001, lambda light chain; p < 0.001, ß-2 microglobulin; p < 0.001, total protein; p < 0.001, albumin; p < 0.001, LDH; p = 0.02, creatine; p < 0.001, hemoglobin; p = 0.010). Clinically, all 11 patients who underwent TPE for HV responded. While a partial response (PR: 80 %) was obtained in 40 of 50 MM patients with CN, no response was obtained in 10 patients (non-response: 20 %). CONCLUSION: In conclusion, it was observed that TPE reduced all biochemical markers related to HV and CN, while making a significant contribution to clinical improvement. We believe that adding TPE to the standard treatment in this patient group will reduce mortality and morbidity in the early period and have a positive effect on survival in the long term.

Effects on mortality of early vs late administration of convalescent plasma in the treatment of Covid-19.

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first seen in the city of Wuhan, China, in December 2019 and then spread worldwide. On 24 March 2020, the U.S. Food and Drug Administration reported that the use of convalescent plasma (CP) containing antibodies against COVID-19 could be effective against infection. The aim of this study is to retrospectively investigate whether early CP transfusion treatment has an effect on recovery of clinical and laboratory parameters in patients diagnosed with severe COVID-19 who were admitted to the intensive care unit (ICU). The study included 141 consecutive patients who had laboratory confirmation of COVID-19 and were admitted to the ICU between 1 May and 30 September 2020. Of the 141 patients, 84 received CP in the first five days of hospitalization in the ICU (early group), and 57 received CP after the fifth day of hospitalization in the ICU (late group). There were no significant differences between the two groups in terms of age, gender, comorbidities and the severity of the disease (according to the evaluation of lung tomography). There was no difference between the two groups in terms of mechanical ventilator needed, inotrope support, and tracheostomy procedure during the ICU admission (p = 0.962, p = 0.680, and p = 0.927, respectively). Despite these limitations, the overriding result of our study is that it suggests that administration of CP either early or late in the treatment of COVID-19, had no effect on mortality.

Efficacy of convalescent plasma according to blood groups in COVID-19 patients

Background/aim: In this study, we aim to investigate the efficacy of convalescent plasma (CP) according to blood groups (BGs) in the treatment of critically ill patients diagnosed with COVID-19. Materials and methods: Twenty-eight critically ill and laboratory-confirmed COVID-19 patients who were admitted to the intensive care unit (ICU) of Sakarya University, Medical Faculty were included in the study. Patients were divided into 2 groups: patients who received anti-A antibody (Ab) containing CP (BG O and B) and those who did not receive CP containing anti-A Ab (BG A and AB). Results: Among the 28 patients, 13 patients received anti-A Ab containing CP (BG; B: 6, O: 7) and 15 patients did not receive anti-A Ab CP (BG; A: 13, AB: 2). Duration in ICU, the rates of mechanical ventilation (MV) support and vasopressor support, the case fatality rate, and the discharge rate were lower in patients who received CP containing anti-A Ab than not containing anti-A Ab CP. However, only the difference in the rate of MV support achieved statistically significance (P = 0.04) Conclusion: In our study, it was observed that the efficiency of CP without anti-A antibody was lower than that of plasma containing anti-A antibody, although it was not statistically significant. This result is thought to be due to the anti-A antibody's ability to block the ACE2 receptor. We believe that this hypothesis should be investigated in controlled studies with higher patient numbers.

Comparative evaluation of memory T cells in COVID-19 patients and the predictive role of CD4+CD8+ double positive T lymphocytes as a new marker.

BACKGROUND: The COVID-19 pandemic has affected the entire world, posing a serious threat to human health. T cells play a critical role in the cellular immune response against viral infections. We aimed to reveal the relationship between T cell subsets and disease severity. METHODS: 40 COVID-19 patients were randomly recruited in this cross-sectional study. All cases were confirmed by quantitative RT-PCR. Patients were divided into two equivalent groups, one severe and one nonsevere. Clinical, laboratory and flow cytometric data were obtained from both clinical groups and compared. RESULTS: Lymphocyte subsets, CD4+ and CD8+ T cells, memory CD4+ T cells, memory CD8+ T cells, naive CD4+ T cells, effector memory CD4+ T cells, central memory CD4+ T cells, and CD3+CD4+ CD25+ T cells were significantly lower in severe patients. The naive T cell/CD4 + EM T cell ratio, which is an indicator of the differentiation from naive T cells to memory cells, was relatively reduced in severe disease. Peripheral CD4+CD8+ double-positive T cells were notably lower in severe presentations of the disease (median DP T cells 11.12 µL vs 1.95 µL; p< 0.001). CONCLUSIONS: As disease severity increases in COVID-19 infection, the number of T cell subsets decreases significantly. Suppression of differentiation from naive T cells to effector memory T cells is the result of severe impairment in adaptive immune functions. Peripheral CD4+CD8+ double-positive T cells were significantly reduced in severe disease presentations and may be a useful marker to predict disease severity.

Comparative evaluation of memory T cells in COVID-19 patients and the predictive role of CD4+CD8+ double positive T lymphocytes as a new marker

SUMMARY BACKGROUND: The COVID-19 pandemic has affected the entire world, posing a serious threat to human health. T cells play a critical role in the cellular immune response against viral infections. We aimed to reveal the relationship between T cell subsets and disease severity. METHODS: 40 COVID-19 patients were randomly recruited in this cross-sectional study. All cases were confirmed by quantitative RT-PCR. Patients were divided into two equivalent groups, one severe and one nonsevere. Clinical, laboratory and flow cytometric data were obtained from both clinical groups and compared. RESULTS: Lymphocyte subsets, CD4+ and CD8+ T cells, memory CD4+ T cells, memory CD8+ T cells, naive CD4+ T cells, effector memory CD4+ T cells, central memory CD4+ T cells, and CD3+CD4+ CD25+ T cells were significantly lower in severe patients. The naive T cell/CD4 + EM T cell ratio, which is an indicator of the differentiation from naive T cells to memory cells, was relatively reduced in severe disease. Peripheral CD4+CD8+ double-positive T cells were notably lower in severe presentations of the disease (median DP T cells 11.12 µL vs 1.95 µL; p< 0.001). CONCLUSIONS: As disease severity increases in COVID-19 infection, the number of T cell subsets decreases significantly. Suppression of differentiation from naive T cells to effector memory T cells is the result of severe impairment in adaptive immune functions. Peripheral CD4+CD8+ double-positive T cells were significantly reduced in severe disease presentations and may be a useful marker to predict disease severity.

RESUMO OBJETIVO: A pandemia de COVID-19 tem afetado o mundo todo, constituindo uma ameaça grave para a saúde humana. As células T desempenham um papel crítico na imunidade celular contra infecções virais. Procuramos desvendar a relação entre sub grupos de células T e a severidade da doença. MÉTODOS: Um total de 40 pacientes com COVID-19 foram aleatoriamente recrutados para o presente estudo transversal. Todos os casos foram confirmados por RT-PCR quantitativo. Os pacientes foram divididos em dois grupos equivalentes, um grave e um não-grave. Os dados da avaliação clínica, laboratorial e da citometria de fluxo foram obtidos para ambos os grupos e comparados. RESULTADOS: Os subconjuntos de linfócitos, células T CD4+ e CD8+, células T de memória CD4+, células T de memória CD8+, células T CD4+ virgens, células T efetoras CD4+, células T de memória central CD4+ e células T CD3+ CD4+ CD25+ estavam significativamente mais baixas nos pacientes graves. A razão células T virgens/células T efetoras TCD4+, que é um indicador da diferenciação entre células T virgens e células de memória, estava relativamente reduzida em casos graves da doença. As células T duplo-positivas CD4+CD8+ periféricas estavam notavelmente mais baixas em casos graves da doença (mediana das células T DP: 11,12 µL vs. 1,95 µL; p< 0,001). CONCLUSÃO: Conforme aumenta a gravidade da doença nos casos de COVID-19, o número de subconjuntos de células T diminui significativamente. A supressão da diferenciação de células T virgens para células T efetoras é o resultado do comprometimento grave das funções imunológicas adaptativas. As células T duplo-positivas CD4+CD8+ periféricas estavam notavelmente mais baixas em casos graves da doença e podem ser um marcador útil para predizer a severidade da doença.

Sclerosing angiomatoid nodular transformation presenting with thrombocytopenia after laparoscopic splenectomy - Case report and systematic review of 230 patients.

BACKGROUND: Sclerosing angiomatoid vascular transformation (SANT) is a rare vascular disease of the spleen, which is difficult to diagnose due to its pre-intervention appearance of malignancy. Case Report: An 85-year-old male was transferred to our clinic for thrombocytopenia and splenic mass. A contrast enhanced abdominal CT and MRI showed nodular lesions, the largest 50mm in diameter, and several areas of heterogeneous contrast field involvement in the spleen parenchyma. Laparoscopic splenectomy was performed with normal range of platelet level. The patient's postoperative course was uneventful and he was discharged on the 6th postoperative day. Histopathology revealed SANT. The patient is now in the 18 th month of remission with platelet levels within normal range and with no recurrence. RESULTS: Between 2004 and April 2020, a total of 230 SANT patients who underwent laparoscopic or open splenectomy or biopsy were reported in the literature. Most patients were female (52.1%), and the median age was 46 years (9 weeks-85 years). Most patients were asymptomatic (56%). Open splenectomy was performed on 166 patients (72.1%),laparoscopic splenectomy on 35 patients (15.2%) and laparoscopic partial splenectomy on 15 patients (6.5%). The median operation time and spleen weight were 143 minutes (88-213) and 260gr (68-2,720), respectively. Median follow-up time was 12 months (0-166). No recurrence was seen in patients undergoing total splenectomy. CONCLUSION: SANT is an unusual disease of the spleen. In the light of this systematic review, a minimally invasive method for total or partial splenectomy,specifically laparoscopy, can be preferred as the treatment of choice.

The Role of CD200 and CD43 Expression in Differential Diagnosis between Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma.

OBJECTIVE: Atypical chronic lymphocytic leukemia (CLL) is most frequently confused with mantle cell lymphoma (MCL). Several markers may contribute to the diagnosis of CLL. However, there is no consensus on which markers are needed to be used in flow cytometry for the diagnosis of CLL. The aim of the present study was to investigate the role of CD43 and CD200 markers in the differential diagnosis between CLL and MCL. MATERIALS AND METHODS: To address this issue, 339 consecutive patients with CLL and MCL were included in the flow cytometry lymphoproliferative disease panel for evaluation of CD43 and CD200 expressions, but not in the Matutes scoring system. RESULTS: CD200 was expressed in 97.3% of atypical CLL cases, whereas it was dimly expressed in only 6.1% of MCL cases. CD43 expression was 95.7% in atypical CLL cases. In the MCL cases, its expression rate was 39.4%. CONCLUSION: CD43 and CD200 were found to be more valuable markers than CD22, CD79b, and FMC7. CD43 and CD200 could also be considered as definitive markers in atypical CLL patients, for whom the Matutes scoring system remains ineffective.

Management of neurobrucellosis: an assessment of 11 cases.

OBJECTIVE: The central nervous system involvement of Brucellosis causes a hard to treat infection with multiple sequelae. The aim of this paper is to discuss the course of neurobrucellosis in response to therapy. PATIENTS AND METHODS: Patients with neurobrucellosis were evaluated. The diagnosis was established by the isolation of bacteria, abnormal CSF findings and positive serology. Ceftriaxone, rifampicin, doxycycline and trimethoprim sulfamethoxazole were the antibiotic choices for these cases. RESULTS: We present 11 cases with neurobrucellosis. None of our patients died, albeit one case has a critical situation due to subarachnoid hemorrhage and its' concordant sequelae. Only one of four patients with walking difficulty and two with hearing loss were normalized with therapy. Imaging techniques did not provide any specific contribution regarding the Brucella infection. CONCLUSIONS: Parenteral ceftriaxone should be used as an initial alternative in the management of neurobrucellosis. Although the therapy should be individualized, the duration of therapy should be a minimum of six months with suitable antibiotics.