Enterotoxins A and B produced by Staphylococcus aureus increase cell proliferation, invasion and cytarabine resistance in acute myeloid leukemia cell lines.

As in the case of cancer, the risk of infection increases when the host's immune system is not working properly. It has been shown that toxins produced by the bacteria responsible for bacterial infections can alter the properties of cancer cells as well as their sensitivity to chemotherapy agents. Staphylococcus aureus (S. aureus) is one of the most prevalent pathogens in acute myeloid leukemia (AML) patients and it produces several virulence factors, including Staphylococcal enterotoxin A (SEA) and Staphylococcal enterotoxin B (SEB). Cytotoxicity, transwell migration, invasion assays, and various transcriptomic and gene set enrichment (GSE) analyses were used to determine how SEA and SEB alter cell proliferation, migration, invasion, and Cytarabine (Cyt) resistance in AML cell lines. The treatment of AML cell lines with SEA/SEB caused an increase in cell proliferation and Cyt resistance. Toxins enhanced the proclivity of cells to migrate and invade, with around 50% of cells in the presence of SEA and SEB. Transcriptomic and gene set enrichment analyses, and subsequent PCR validations showed dysregulation of immune related genes and genesets. Apparently, this allows AML cells to escape and survive the undesirable environment created by toxins, possibly via the ER stress signaling pathway. Therefore, SEA and SEB can significantly alter the characteristics of AML cancer cells and evaluation of alterations in responsible immune genes and pathways may be crucial for controlling the progression of cancer. In addition, our results suggest that there may be a strong interaction between the immune related pathways and the ER signaling pathway.

Hypophosphatemia related to the use of ibrutinib.

INTRODUCTION: Tyrosine kinase inhibitors (TKis) and Bruton's TKi (BTKis) constitute broadly used antitumor drug groups with almost completely tolerable and manageable side-effect profiles. Mainly side effects are cardiovascular and gastrointestinal for the TKi group. Hypophosphatemia is documented frequently in many studies with TKis but rarely mentioned with ibrutinib use up to the present. CASE REPORT: A 61-year-old patient with the diagnosis of chronic lymphocytic leukemia had hypophosphatemia-related complaints and symptoms when ibrutinib use was preferred for his second relapse of the disease. After drug discontinuation, we started ibrutinib again with an alternating dose. We managed to control hypophosphatemia, and the patient has been following up for 2 years in remission status without any support or a second drug need. MANAGEMENT AND OUTCOME: We have presented here a chronic lymphocytic leukemia case that developed mild-severe hypophosphatemia associated with ibrutinib use. By using an alternating dose of ibrutinib, we managed to control the disease and drug side effects. DISCUSSION: TKis and BTKis are widely in use for different indications. Hypophosphatemia is rare but it can cause drug discontinuation or change if it is not manageable. It is mentioned that hypophosphatemia can be seen due to a common group effect with the mechanism of causing secondary hyperparathyroidism and renal tubulopathy. In our case, we could explain the side effect of hypophosphatemia with secondary hyperparathyroidism and renal tubulopathy. Prospective, large-group studies are needed to explain the hypophosphatemia and other side effects of ibrutinib and new BTKis in detail.

Comment on Zamfir et al. Hematologic Malignancies Diagnosed in the Context of the mRNA COVID-19 Vaccination Campaign: A Report of Two Cases. Medicina 2022, 58, 874.

The SARS-CoV-2 spike protein mRNA-based vaccines have prevented countless mortality and morbidity, and have an excellent risk/benefit ratio. However, various adverse events may rarely occur after the BNT162b2 vaccine, like any other medical intervention. The COVID-19 itself and the spike protein produced endogenously by mRNA vaccines may have immunological, microenvironmental, prothrombotic, and neoplastic effects. As a contribution to the published report, we would like to share our experience regarding four cases in which myeloid neoplasms emerged following the vaccination. Conclusions: There is no doubt that vaccination could continue along the lines of established universal recommendations. Meanwhile, all hematological adverse events must be closely monitored and reported. Further efforts should be focused on the probable pathobiological mechanisms and causalities of spike protein-related toxicity and clonal myeloid disorders.

Efficacy of eltrombopag in thrombocytopenia after hematopoietic stem celltransplantation.

BACKGROUND: Thrombocytopenia is a common complication following hematopoietic stem cell transplantation (HSCT). Eltrombopag has been used in thrombocytopenia treatment after HSCT in recent years. Herein, we present our experience of 25 patients treated with eltrombopag for post-HSCT thrombocytopenia. METHODS: Fifteen autologous hematopoietic stem cell transplantation (AHSCT) and 10 allogenic hematopoietic stem cell transplantation (allo-HSCT) recipients treated with eltrombopag for treatment of prolonged isolated thrombocytopenia (PIT) or secondary failure of platelet recovery (SFPR) in the stem cell transplantation unit of Hacettepe University Hematology Department between 2017 and 2021 were included in the study. The primary endpoint of this study is eltrombopag response in patients diagnosed with PIT or SFPR. Platelet count above 50,000/mm3 for five consecutive days without platelet transfusion was considered as eltrombopag response. Overall survival (OS) analyses were calculated based on the time between HSCT and death from any cause. The patients who were alive at the last follow-up were censored at this time for calculation of OS analyses. RESULTS: AHSCT (66.7% (10/15)) and allo-HSCT (50% (5/10)) recipients responded to eltrombopag for the treatment of post-HSCT thrombocytopenia. There was no excess toxicity related to the eltrombopag use. The median response duration of allo-HSCT recipients and AHSCT recipients were 41 (13-104) days and 50 (7-342) days, respectively. There was a statistically significant OS duration difference between the responders and nonresponders in allo-HSCT and AHSCT recipients with p values of 0.005 and 0.02, respectively. DISCUSSION: Eltrombopag is promising for the treatment of thrombocytopenia after AHSCT and allo-HSCT in terms of efficacy and safety.

Prophylactic Central Nervous System Irradiation Is Not Indispensable in Adult Patients with Acute Lymphoblastic Leukemia: A Multicenter Retrospective Cohort Study

Objective: Studies comparing the efficacy and safety of prophylactic regimens for central nervous system (CNS) involvement in acute lymphoblastic leukemia (ALL) are scarce in adults. This multicenter retrospective study aimed to compare the efficacy of prophylactic regimens with and without CNS irradiation on the development of CNS relapse during follow-up. Materials and Methods: This was a multicenter comparative cohort study. A total of 203 patients were included from four tertiary care centers in Turkey. Patients were divided into two groups according to whether they received CNS irradiation or not. The groups were analyzed retrospectively regarding patient and disease characteristics, with the main focus being CNS relapse. Results: While 105 patients received chemotherapy-based prophylaxis, 98 patients received additional CNS irradiation. These groups were statistically comparable in terms of demographic characteristics and risk factors for CNS involvement. In the irradiation group, patients were younger and had more stem cell transplants. In a median of 23.8 (11.1-62.4) months, there was no difference between the two groups regarding CNS relapse-free survival (log-rank p=0.787). Conclusion: Craniospinal irradiation may not be indispensable for every adult patient with ALL, similarly to pediatric patients. It is crucial to avoid the long-term toxicities of radiation, especially in patients with long life expectancy. Craniospinal irradiation may be reserved for therapeutic use in cases of CNS relapse and prophylaxis for some high-risk patients.

Central nervous system involvement in patients with acute myeloid leukemia

Background/aim: To evaluate the incidence, clinical features, risk factors, and prognosis of central nervous system (CNS) involvement in patients with acute myeloid leukemia (AML). Materials and methods: All AML patients who were admitted to Hacettepe University hospital between 2000 and 2021 were evaluated. The medical records of 548 AML cases were retrospectively analyzed. Results: The frequency of CNS involvement was 2.4% (n = 13) at diagnosis and 4.6% (n = 25) at diagnosis or during follow-up. Parenchymal involvement was seen in 5 patients, leptomeningeal involvement was seen in 11 patients. Three patients had both leptomeningeal and parenchymal involvements, and 6 patients had optic nerve or ocular involvement. In univariate analysis, younger age and extramedullary involvement at diagnosis were associated with CNS disease at diagnosis, and extramedullary involvement at diagnosis was associated with CNS disease during follow-up. In multivariate analysis; younger age and extramedullary involvement at diagnosis were associated with CNS disease at diagnosis and during follow-up respectively. Median overall survival was 5.4 months in patients with CNS disease at diagnosis and 16.9 months in patients with CNS disease during follow-up and 16.2 months in patients with no CNS disease. Conclusion: CNS disease is a rare complication of AML. Younger age and extramedullary involvement at diagnosis are risk factors for CNS involvement.

The clinical course of COVID-19 in hematopoietic stem cell transplantation (HSCT) recipients

Background/aim: The disease caused by SARS-CoV-2 was named as COVID-19. There is as yet insufficient information about the effects of HSCT on the clinical course of COVID-19. In the present study, we aimed to investigate the clinical course of COVID-19 in patients who had undergone HSCT. Materials and methods: We analyzed baseline characteristics, clinical course and findings of COVID-19, hospitalization and death rates, overall survival, and case fatality rates of HSCT recipients diagnosed with COVID-19 retrospectively. Results: 57.6% of the patients underwent AHSCT, and 42.4% underwent allo-HSCT. 60.6%, 27.3%, and 12.1% of the patients had mild, moderate, and severe COVID-19 or critical illness, respectively. Overall, 45.5% were hospitalized, 12.1% required intensive care, and 9.1% necessitated invasive mechanical ventilation. The total CFR was 9.1% in HSCT recipients, 22.2% in patients with active hematologic malignancy, and 4.2% in patients without active hematologic malignancy. Conclusion: It can be concluded that mortality of HSCT recipients is lower in patients whose primary disease is in remission compared to ones that are not in remission. Further studies with larger group patients are needed in order to delineate the effects of COVID-19 on HSCT patients.

Perspectives for immune plasma treatment of COVID-19

Background/aim: The SARS-CoV-2 infection was declared as a pandemic by the World Health Organization (WHO) on March 11, 2020, and the death toll from COVID-19, which is the disease caused by SARS-CoV-2, has already surpassed that of many previous epidemics. A wide variety of treatment options are being considered for COVID-19, but there is still no definitive treatment or vaccine. This study aims to explain the background of convalescent plasma (CP) treatment and its relations with COVID-19 immunity, to define ideal treatment procedures, and to reveal present and future perspectives in the light of the rapidly growing data. Immunological basis of COVID-19-associated immune response and convalescent plasma as a treatment option: Since it has been shown that the impaired immune response of the host is one of the most important factors that increase the severity of the infection, treatment strategies to suppress aberrant immune activation are currently being considered. CP, which is derived from recently recovered patients and contains neutralizing antibodies and many other immune- modulatory substances, seems to be the most convenient strategy to restore normal immune function considering the fast spreading nature of the ongoing pandemic. Conclusion: Even though mechanisms of action of plasma therapy are not fully delineated, it was shown that it could lead to a reduction in mortality since other alternatives such as monoclonal antibodies or SARS-CoV-2 hyperimmunoglobulin require much more time and effort to be developed.

Prolonged viral shedding in a lymphoma patient with COVID-19 infection receiving convalescent plasma.

Acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first identified in Wuhan, China; and spread all over the world. Reverse-transcription polymerase chain reaction (RT-PCR) test for SARS-CoV-2 usually returns to negative in 20 days post-infection, but prolonged positivity has been reported up to 63 days. A case whose viral shedding lasted 60 days is reported from China. Herein we report a patient with a history of autologous stem cell transplantation (ASCT) for lymphoma whose RT-PCR test remained positive for SARS-CoV-2 for 74 days. The prolonged RT-PCR positivity, despite convalescent plasma infusion, may suggest that the given antibodies may be ineffective in terms of viral clearance. In patients with hematological malignancies or immunosuppression, such as ASCT, may lead to prolonged viral shedding, and strict isolation is warranted for long-term SARS-CoV-2 infection control.

Convalescent (immune) plasma treatment in a myelodysplastic COVID-19 patient with disseminated tuberculosis.

During the ongoing COVID-19 pandemic due to the SARS-CoV-2 virus of which evidence-based medical paradigms cannot be easily applied; difficult clinical decisions shall be required particularly in the 'difficult-to-treat' cases of high risk group with associated comorbidities. Convalescent immune plasma therapy is a promising option as a sort of 'rescue' treatment in COVID-19 immune syndrome, where miraculous antiviral drugs are not available yet. In this report, we aim to convey our experience of multi-task treatment approach with convalescent immune plasma and anti-cytokine drug combination in a COVID-19 patient with extremely challenging comorbidities including active myeloid malignancy, disseminated tuberculosis and kidney failure.