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.

A single-center experience of haploidentical stem cell transplantation in hematological malignancies.

BACKGROUND: Since well-designed prospective comparative trials are lacking, haploidentical hematopoietic stem cell transplantations approach should be based on the expertise of a particular center. In this study, we aimed to report the results and outcomes of patients who underwent haploidentical hematopoietic stem cell transplantation. METHODS: : Thirty-nine patients who underwent transplantation in our clinic between 2015 and 2022 were retrospectively analyzed. Primary end point of this study is to find out the survival rates of the patients. RESULTS: The overall survival of patients was 29.9 ± 4.9 months. The disease-free survival of the patients was 37.8 ± 5.7 months. The 3-year overall survival rate of the patients was %50 and the 3-year disease-free survival rate of the patients was %53. Nineteen patients were nonsurvivors among a total of 39 patients. Busulfan-fludarabine-thiotepa was the most frequently used conditioning regimen for transplantation. Busulfan-fludarabin-antithymocyte globulin regimen is the second preferred conditioning regimen. Cyclosporine- cyclophosphamide-mycophenolate mofetil was the most widely used graft-versus-host disease prophylaxis regimen. Sixteen patients had graft-versus-host disease, 28% of the patients had acute graft-versus-host disease, and 13% had chronic graft-versus-host disease. Gastrointestinal system consists of the most involved organs in graft-versus-host disease since 15% of the patients had gastrointestinal graft-versus-host disease. First-degree relatives (parent/child) were the most frequent donor source for haploidentical hematopoietic stem cell transplantation. Sepsis was the most frequent reason of death among transplant patients. DISCUSSION: In our center, we prefer to use high dose posttransplantation cyclophosphamide after haploidentical hematopoietic stem cell transplantation for graft-versus-host disease prophylaxis. With this approach, our center's overall survival and disease-free survival rates are comparable and compatible with the literature findings.

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.

Long-term results of allogeneic peripheral blood hematopoietic stem cell transplantation for severe aplastic anemia.

OBJECTIVE: Aplastic anemia (AA) is a life-threatening disorder and may be associated with significant morbidity and mortality Currently, the first treatment option is allogeneic hematopoietic stem cell transplant (allo-HSCT) for patients younger than 40 years. Bone marrow is recommended as the stem cell source due to less graft versus host disease (GVHD) risk and better outcomes than peripheral blood (PB)-derived stem cell. The aim of this study is to share the data of AA patients who have underwent PB-derived allo-HSCT in our bone marrow transplantation center. METHODS: Twenty-seven patients who underwent PB-derived allo-HSCT from human leukocyte antigen matched sibling donors were analyzed retrospectively. RESULTS: The median follow-up time was 95.2 months (range, 4.8-235 months). The 10-year survival was 89 %. The median neutrophil and platelet engraftment time was 11 days (range, 9-16 days) and 13 days (range, 11-29 days), respectively. Primary platelet engraftment failure was observed in 1 patient (3.7 %). Acute and chronic GVHD observed in 2 (7.4 %) and 3 (11.1 %) patients, respectively. Neutropenic fever was observed in 13 (44.8 %) of patients until the engraftment after allo-HSCT. One patient died due to CMV infections, two died due to septic shock secondary to fungal infection. CONCLUSION: Although there is no prospective data directly comparing BM with PB as stem cell source in AA, observational studies indicates better OS with BM. PB can be used in certain situations such as higher risk for graft failure and donor preference. This study demonstrated that PB-derived stem cell seems to be a reasonable alternative to BM.

Platelet-rich plasma treatment improves postoperative recovery in patients with pilonidal sinus disease: a randomized controlled clinical trial.

BACKGROUND: Pilonidal sinus is a common health problem. The current study aimed to compare the impact of autologous platelet-rich plasma (PRP) with that of minimally invasive techniques in terms of pain reduction, return to daily activities, quality of life, and duration of wound healing after open excision and secondary closure. METHODS: Patients who were over 18 years old and had chronic PS disease between March 2018 and January 2019 were enrolled and randomly divided into three groups. Open surgery and moist dressings were applied to patients in group A. Open surgery followed by PRP application was performed on patients in group B. Group C underwent curettage of the sinus cavity followed by application of PRP. In this prospective randomized controlled study, patients completed questionnaires (including the Nottingham Health Profile (NHP), Short Form-36 (SF-36) and clinical information) before and after surgery. Demographics, preoperative characteristics, healing parameters, and quality-of-life scores were evaluated and calculated before and after surgery. RESULTS AND CONCLUSION: The cavity volume and wound-healing time were compared among the groups on postoperative days 0, 2, 3, 4, and 21. Each patient was followed up throughout the process of wound healing, and follow-up was continued afterward to monitor the patients for recurrence. Due to the nature of the treatment that group C received, this group achieved shorter healing times and smaller cavity volume than the other groups. In contrast, the recovery time per unit of cavity volume was significantly faster in group B than in the other groups. Overall postoperative pain scores were significantly lower for both PRP groups (open surgery, group B; minimally invasive surgery, group C) than for group A (p < 0.001) and showed different time courses among the groups. In the treatment of PS disease, PRP application improves postoperative recovery in that it speeds patients' return to daily activities, reduces their pain scores and increases their quality of life. Trial registration The current study is registered on the public website ClinicalTrials.gov (ClinicalTrials.gov identifier number: NCT04697082; date: 05/01/2021).

Regulatory consideration on preparation and clinical use of COVID-19 convalescent plasma.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease (COVID-19), spreading from Wuhan to worldwide has been emerged since December 2019. Although scientists and researchers have been racing to develop specific therapeutic agents or vaccines against SARS-CoV-2 since the identification of the agent, either a drug or a vaccine has not been approved to treat or to prevent COVID-19 up to date. On the base of historical experiences, Convalescent Plasma (CP), a passive antibody therapy, has been evaluated as a hopeful and potential therapeutic option since the beginning of the COVID-19 outbreak. Immune plasma had been used previously for the treatment of H1N1 influenza virus, SARS-CoV-1 and MERS-CoV epidemics successfully. In this scope competent authorities are responsible to set up certain principles and criteria for the collection and clinical use of COVID-19 Convalescent Plasma (CCP). This document has been prepared to aid both for the convalescent plasma suppliers and the clinicians. The first part encompasses the supply of CCP and the second part lead the clinical use of CCP for the treatment of patients with severe COVID-19 infection. Turkish Ministry of Health developed a guide on collection and clinical use of CCP and created a web-based monitoring system to follow-up the patients treated with convalescent plasma in universal. This follow-up process is thought to be crucial for the creation and development of current and future treatment modalities. This guide would be a pathfinder for clinicians and/or institutions those eager to conduct CCP treatment more effectively.

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.

CD34+ hematopoietic progenitor cell dose as a predictor of engraftment and survival in multiple myeloma patients undergoing autologous stem cell transplantation

Background/aim: High-dose melphalan and autologous hematopoietic stem cell transplantation (AHSCT) is the standard treatment strategy for multiple myeloma (MM) patients who are eligible for it. The recommended dose of CD34+ hematopoietic progenitor cells (HPCs) for adequate engraftment is above 2 × 106/kg. The aim of this study was to evaluate the relationship between the dose of CD34+HPCs and survival in MM patients who underwent AHSCT at a tertiary care center. Materials and methods: Enrolled in this study were 271 MM patients who underwent AHSCT between 2003 and 2019. Clinical characteristics of the patients, disease status pre-AHSCT, reinfused CD34+ cell doses, and neutrophil and platelet engraftment days were recorded, retrospectively. The patients were divided into 2 groups according to whether the dose of reinfused CD 34+ HPCs was <5 × 106/kg or ≥5 × 106/kg. The groups were compared in terms of engraftment and overall survival (OS) times. Results: The median age of the patients was 54.8 (33­76) years. The median dose of infused CD34+ HPCs was 5.94 × 106/kg (1.47­59.5 × 106/kg). The median follow-up period was 54 months (4­211). The median OS of the patients was 103 months (11­144). The median neutrophil and platelet engraftment time was 10 (8­24) and 11 (7­40) days. Doses of <5 × 106/kg and ≥5 × 106/kg CD34+ HPC were reinfused in 38.1% and 61.9% of the patients, respectively. There was a negative significant correlation between the reinfused CD34+cell level and neutrophil/platelet engraftment times (r = ­0.32, P < 0.001; r = ­0.27, P < 0.001, respectively). The median OS times were observed as 103 months (11­144) and 145 months (123­166) for patients who had been administered <5 × 106/kg and ≥5 × 106/kg of CD34+ HPCs, respectively (P = 0.009). Conclusion: The increased amount of CD34+ autologous hematopoietic stem cell dose after high dose melphalan chemotherapy in MM patients shortened the platelet and neutrophil engraftment time and increased OS. Early platelet engraftment and administration of a CD34+ HPC count that is ≥5 × 106/kg can be considered as predictors of better survival in patients.

The effects of blood group types on the risk of COVID-19 infection and its clinical outcome

Background/aim: COVID-19 (Coronavirus disease of 2019) is an infectious disease outbreak later on declared as a pandemic, caused by the SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2). It spreads very rapidly and can result in severe acute respiratory failure. The clinical studies have shown that advanced age and chronic diseases increase the risk of infection. However, influence of the blood groups on COVID-19 infection and its outcome remains to be confirmed. The aim of this study is to investigate whether there exists a relationship between the blood groups of the patients and risk of SARS-CoV-2 infection and the clinical outcomes in COVID-19 patients Material and method: 186 patients with PCR confirmed diagnosis of COVID-19 were included in this study. Age, sex, blood groups, comorbidities, need for intubation and intensive care unit follow up and mortalities of the patients were analyzed retrospectively. 1881 healthy individuals, who presented to the Hacettepe University Blood Bank served as the controls. Results: The most frequently detected blood group was blood group A (57%) amongst the COVID-19 patients. This was followed by blood group O (24.8%). The blood group types did not affect the clinical outcomes. The blood group A was statistically significantly more frequent among those infected with COVID-19 compared to controls (57% vs. 38%, P < 0.001; OR: 2.1). On the other hand, the frequency of blood group O was significantly lower in the COVID-19 patients, compared to the control group (24.8% vs. 37.2%, P: 0.001; OR: 1.8). Conclusions: The results of the present study suggest that while the blood group A might have a role in increased susceptibility to the COVID-19 infection, the blood group O might be somewhat protective. However, once infected, blood group type does not seem to influence clinical outcome.

The Turkish experience with therapeutic plasma exchange: A national survey.

Therapeutic plasma exchange (TPE) is used to treat more than 60 diseases worldwide and has drawn growing interest. Little is known about the current situation of TPE activity in Turkey, so we developed a survey to obtain information about this timely topic. We collected data on TPE from 28 apheresis units throughout Turkey. We performed a total of 24,912 TPE procedures with 3203 patients over the past decade. Twenty years ago, the majority of procedures were performed for neurological and hematological disorders, and today, most TPE procedures are done for the same reasons. The only historical change has been an increase in TPE procedures in renal conditions. Currently, renal conditions were more frequently an indication for TPE than rheumatic conditions. Fresh frozen plasma was the most frequently used replacement fluid, followed by 5% albumin, used in 57.9% and 34.6% of procedures, respectively. The most frequently used anticoagulants in TPE were ACD-A and heparin/ACD-A, used with 1671 (52.2%) and 1164 (36.4%) patients, respectively. The frequency of adverse events (AEs) was 12.6%. The most common AEs were hypocalcemia-related symptoms, hypotension, and urticaria. We encountered no severe AEs that led to severe morbidity and mortality. Overall, more than two thirds of the patients showed improvement in the underlying disease. Here, we report on a nationwide survey on TPE activity in Turkey. We conclude that there has been a great increase in apheresis science, and the number of TPE procedures conducted in Turkey has increased steadily over time. Finally, we would like to point out that our past experiences and published international guidelines were the most important tools in gaining expertise regarding TPE.

Unclassifiable non-CML classical myeloproliferative diseases with microcytosis: findings indicating diagnosis of polycythemia vera masked by iron deficiency

Background/aim: Polycythemia Vera (PV) is a myeloproliferative disorder characterized by overproduction of morphologically normal red blood cells (RBCs), granulocytes, and platelets, a phenotype that is caused by a mutation (V617F) in Janus kinase 2 (JAK2). However, JAK2 V617F is also found in approximately 50% of patients with essential thrombocytosis and primary myelofibrosis, rendering its presence nonspecific as a diagnostic test. An increased red cell mass is a major criterion for the diagnosis of PV according to World Health Organization (WHO) 2016 criteria. High hemoglobin (Hgb) or Hematocrit (Hct) are universally used as indicators of an increased red cell mass for the diagnosis of PV. However, conditions such as iron deficiency (ID) with decreased mean cell volume may mask the diagnosis due to nonelevated Hct level. The aim of this study was to investigate the clinical characteristics of the patients with unclassifiable non-CML classical myeloproliferative disease with microcytosis (MPD/M) and nonelevated Hgb and Hct levels at diagnosis and to determine if some of these cases could be real PV cases masked due to ID-related microcytosis. Materials and methods: There were 23 MPD/M cases among 208 non-CML classical MPD cases (11%). Among 22 patients who had adequate test results related to the cause of microcytosis, ID and beta-thalassemia trait (TT) were the apparent causes of microcytosis in 15 and 1 cases, respectively. Results: Clinicopathological correlations revealed consistently positive JAK2 V617F mutation status (20/20, 100%), frequently elevated RBC count (17/23, 73.9%), and PV-compatible bone marrow findings (10/12, 83.3%). These findings are compatible with PV instead of essential thrombocytopenia or primary myelofibrosis. In spite of frequent cytoreductive treatment, 3 patients developed increased Hgb/Htc levels during median 58.2 (279­63) months' follow-up. Conclusion: These data show that the majority of MPD/M cases are PV patients masked due to ID-related microcytosis.

Mitoxantrone-melphalan conditioning regimen for autologous stem cell transplantation in relapsed/refractory lymphoma

Background/aim: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has become the standard approach for patients with relapsed/refractory Hodgkin's lymphoma (HL) or non-Hodgkin's lymphoma (NHL). In this study, we report the outcome of the mitoxantrone-melphalan conditioning regimen for lymphoma. Materials and methods: The study group included 53 patients who were relapsed/refractory HL (n = 14) and NHL (n = 39) and received mitoxantrone and melphalan followed by ASCT. The transplant regimen consisted of mitoxantrone (60 mg/m2) and melphalan (180 mg/m2) followed by peripheral blood stem cell infusion (PBSC). Results: Prior to high-dose chemotherapy, 37.7% of the patients were in complete remission (CR) and 45.3% were in partial remission (PR), and 17% had stable or progressive disease. After high-dose chemotherapy and PBSC, 44 out of 51 patients achieved CR (86.2%). CR was achieved in 24 out of 33 patients (72.7%) who were transplanted in a marginally active phase of the disease. At a median followup of 25.4 months (1.8­131.3 months) after ASCT, 13 patients relapsed/ progressed and 8 patients died. The estimated 2-year overall survival (OS) was 81.9%, and event-free survival (EFS) was 59.3%. Conclusion: High-dose chemotherapy followed by ASCT is an effective conditioning regimen in relapsed/refractory lymphoma patients who are undergoing ASCT.

A multicenter experience of thrombotic microangiopathies in Turkey: The Turkish Hematology Research and Education Group (ThREG)-TMA01 study.

Thrombotic microangiopathies (TMAs) are rare, but life-threatening disorders characterized by microangiopathic hemolytic anemia and thrombocytopenia (MAHAT) associated with multiorgan dysfunction as a result of microvascular thrombosis and tissue ischemia. The differentiation of the etiology is of utmost importance as the pathophysiological basis will dictate the choice of appropriate treatment. We retrospectively evaluated 154 (99 females and 55 males) patients who received therapeutic plasma exchange (TPE) due to a presumptive diagnosis of TMA, who had serum ADAMTS13 activity/anti-ADAMTS13 antibody analysis at the time of hospital admission. The median age of the study cohort was 36 (14-84). 67 (43.5%), 32 (20.8%), 27 (17.5%) and 28 (18.2%) patients were diagnosed as thrombotic thrombocytopenic purpura (TTP), infection/complement-associated hemolytic uremic syndrome (IA/CA-HUS), secondary TMA and TMA-not otherwise specified (TMA-NOS), respectively. Patients received a median of 18 (1-75) plasma volume exchanges for 14 (153) days. 81 (52.6%) patients received concomitant steroid therapy with TPE. Treatment responses could be evaluated in 137 patients. 90 patients (65.7%) achieved clinical remission following TPE, while 47 (34.3%) patients had non-responsive disease. 25 (18.2%) non-responsive patients died during follow-up. Our study present real-life data on the distribution and follow-up of patients with TMAs who were referred to therapeutic apheresis centers for the application of TPE.

Leukapheresis do not improve early death rates in acute myeloid leukemia patients with hyperleukocytosis.

Hyperleukocytosis (HL) is defined as the clinical condition when the white blood cell (WBC) count is above 100,000/mm3 in peripheral blood. It has been already shown in the literature that leukapheresis, a conventional technique to decrease the serum WBC level, is ineffective for long-term survival in cases of hyperleukocytotic acute myeloid leukemia (AML) with leukostasis. However, the effect of leukapheresis on early mortality is still unclear. In this study, we aimed to evaluate the effect of leukapheresis on early mortality of patients with AML who have HL. Twenty-eight de novo patients with AML, diagnosed with HL between 2002 and 2015 at the Hacettepe Hematology Department, were analyzed retrospectively. Leukapheresis was performed in 10 patients, and the mean WBC decrease with leukapheresis was 57.4×103/µl which accounts for 31% of the initial WBC count. The indications for leukapheresis were hyperviscosity and prophylaxis in four and six patients, respectively. In the group of patients who received leukapheresis, three of four patients who had hyperviscosity symptoms died, and three of six patients died who did not have symptoms. In our study, we observed that the leukapheresis procedure is highly effective in reducing plasma WBC levels. However, although it is statistically insignificant, our findings also revealed that there is a much higher rate of death in patients who were treated with leukapheresis. Therefore we conclude that leukapheresis does not lower rates of early death; nevertheless, this finding should be confirmed by prospective studies with larger cohorts.

Rebound Thrombocytosis following Induction Chemotherapy is an Independent Predictor of a Good Prognosis in Acute Myeloid Leukemia Patients Attaining First Complete Remission.

There are very few data about the relationship between acute myeloid leukemia (AML) prognosis and bone marrow recovery kinetics following chemotherapy. In this study, we aimed to assess the prognostic importance and clinical associations of neutrophil and platelet recovery rates and rebound thrombocytosis (RT) or neutrophilia (RN) in the postchemotherapy period for newly diagnosed AML patients. De novo AML patients diagnosed between October 2002 and December 2013 were evaluated retrospectively. One hundred patients were suitable for inclusion. Cox regression analysis using need for reinduction chemotherapy as a stratification parameter revealed RT as the only parameter predictive of OS, with borderline statistical significance (p = 0.06, OR = 7; 95% CI 0.92-53), and it was the only parameter predictive of DFS (p = 0.024, OR = 10; 95% CI 1.3-75). In order to understand whether RT or RN was related to a better marrow capacity or late consolidation, we considered neutrophil recovery time and platelet recovery time and nadir-first consolidation durations in all patients in the cohort. Both the marrow recovery duration and the time between marrow aplasia and first consolidation were shorter in RT and RN patients. To our knowledge, this is the first study to report a correlation between RT/RN and prognosis in AML.

Examination of drug removal profiles in patients undergoing therapeutic plasma exchange: A retrospective study.

INTRODUCTION: Therapeutic plasma exchange (TPE) eliminates disease-contributing substances but may also affect drug concentrations. This study aimed to assess the prevalence of prescription drugs removable via TPE by reviewing patient medication histories. METHODS: A retrospective, single-center study was conducted from January 1, 2021 to December 31, 2022. The study included 244 patients undergoing 1087 TPE sessions. Drugs prescribed to patients on TPE days were categorized as "yes" (probably removable), "maybe" (possibly removable), and "no" (unlikely removable) regarding their removability via TPE. RESULTS: Among 3966 prescriptions, 556 (14.0%) were analyzed, with 21.8%, 36.5%, and 41.7% falling into the "yes," "maybe," and "no" categories for removability. Although only 14.0% were categorized, 83.6% of patients received at least one analyzable drug. Among them, 83.8% had at least one potentially removable drug. CONCLUSION: Real-world data highlights the need for caution in drug treatments during TPE to ensure optimal therapeutic outcomes, particularly for specific drugs.

Antimicrobial management in patients undergoing therapeutic plasma exchange: A Cross-Sectional Nationwide Survey.

There is little evidence of antimicrobial elimination via therapeutic plasma exchange (TPE) and no guidelines for antimicrobial optimal dosing in patients undergoing TPE. We aimed to assess current practices and knowledge regarding antimicrobial management during TPE. A structured online survey was conducted from May to November 2023, and physicians were invited to participate through national scientific platforms and professional societies. One hundred five participants completed the survey, of whom 61% were infectious disease physicians, with 68.6% having more than 10 years of experience. That the TPE procedure could significantly affect plasma concentrations of antimicrobial agents was reported by 74.3% of the respondents. Among the physicians, 42.9% suggest antimicrobial dose adjustment, and 38.1% recommend temporarily discontinuing antimicrobial drug administration during TPE. Therapeutic drug monitoring was recommended by 33.3% of the respondents for certain antimicrobials, mainly glycopeptides and aminoglycosides, in patients undergoing concurrent TPE. Furthermore, 59.3% of physicians sometimes consult with another healthcare professional for treatment management, most commonly a pharmacist or a clinical pharmacist and an infectious diseases specialist. The core questions regarding potential drug-, procedure-, and patient-related antimicrobial elimination factors via TPE were responded to accurately by less than half of the physicians. It was clear that they had a lack of clinical practices and knowledge regarding antimicrobial management during TPE. To ensure the therapeutic efficacy of antimicrobials and avoid treatment failure, physicians should improve their practice strategies and consider antimicrobial elimination factors with TPE in this data-poor setting.

Hemoglobin cast nephropathy: a rare but serious complication of hemolysis in a pediatric patient.

BACKGROUND: Intravascular hemolysis is a serious and rare condition in children and causes the release of hemoglobin and heme into circulation, which have proinflammatory properties. These substances lead to inflammation, oxidative stress, apoptosis, and organelle dysfunction that lead to acute kidney injury (AKI). We report a pediatric case diagnosed with hemolysis-associated hemoglobin cast nephropathy due to autoimmune hemolytic anemia. CASE: A 4-year-old boy, who was admitted to another hospital with complaints of fever and dark urine for one day, developed anemia and kidney failure in the follow-up, was referred to our hospital. In physical examination, pallor and icterus on the sclera were noted. The patient had low hemoglobin and haptoglobin levels concomitant with high levels of serum lactate dehydrogenase, urea and creatinine. A peripheral blood smear showed marked spherocytes without schistocytes. A kidney biopsy was performed due to ongoing overt hemolysis and dialysis requirement, which showed findings consistent with hemoglobin cast nephropathy. Although the initial polyspecific direct antiglobulin test (DAT) was negative, due to persistent intravascular hemolysis DAT was studied monospecifically and showed IgM antibody positivity. Therefore, a diagnosis of autoimmune hemolytic anemia was made, and corticosteroid treatment was started. Hemolysis immediately ceased and the need for erythrocyte transfusion and dialysis disappeared. CONCLUSIONS: Acute kidney injury associated with hemoglobin cast nephropathy is an extremely rare condition in childhood. Although the initial course is severe and potentially life-threatening, the prognosis is favorable with the treatment of the underlying cause and management of AKI. Therefore, pediatricians should be aware of this rare clinical entity during clinical practice.

How do we collect better granulocyte?

We studied retrospectively the factors affecting the product quality in 459 donor granulocyte apheresis procedures from 420 donors for 71 neutropenic patients from 2004 to 2010 in a single center. The counts of the granulocyte and platelet collected were measured to evaluate the product quality. The data was analyzed to determine a possible relationship between product quality and several parameters including gender, preleukapheresis neutrophil count, type of anticoagulation and separator type and mode of the apheresis system. We found that collection of better granulocyte is possible from a donor in a single procedure by changing anticoagulation type and separator mode during apheresis.