Prediction of CD34+ hematopoietic stem cells in healthy allogeneic stem cell donors on the Optia cell separator based on CE2: Which formula is more correlated with actual CD34+?

BACKGROUND: Peripheral blood-derived hematopoietic stem cells (HSCs) are widely used for various adult stem cell transplants. To obtain sufficient HSCs from healthy volunteer donors during the apheresis process and ensure that the donors are exposed to fewer apheresis-related side effects, calculation methods have been developed for the prediction of processed blood volume or CD34+ count. However, there is no consensus on a formula to predict the volume of blood to be processed or the number of stem cells to be obtained. OBJECTIVE: This study aimed to estimate the predicted blood volume and CD34+ cell counts using collection efficiency (CE)-based formulas and evaluate their accuracy compared to the actual CD34+ cell counts. It also seeks to identify the factors that affect CE. METHODS: Data from 397 healthy, unrelated stem cell donors were retrospectively analyzed. An algorithm using four different CE2 metrics (1st quartile, mean, 3rd quartile, and median) was developed to predict the volume of blood to be processed using the Spectra Optia continuous mononuclear cell collection procedure. RESULTS: When employing the mean CE2 algorithm, the results revealed a strong correlation (r = .894, p < .001) between predicted and actual CD34+ values. The study also identified strong associations between pre-apheresis CD34+, pre-apheresis leukocyte count, the use of two doses of G-CSF, and low CE2. CONCLUSION: These findings suggest that the mean CE2 algorithm could be a potent, straightforward, and accurate tool for predicting CD34+ stem cell counts in healthy allogeneic stem cell donors and potentially optimizing stem cell collection procedures.

Hepatic veno-occlusive disease (sinusoidal obstruction syndrome) after hematopoietic stem cell transplantation in adult patients: Diagnosis, incidence, prophylaxis, and treatment.

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) affecting the liver is a rare, possibly life-threatening complication of hematopoietic stem cell transplantation (HSCT). Sinusoidal endothelial cell (SEC) damage triggered by various factors (especially conditioning regimen) results in post sinusoidal portal hypertension due to obstruction of the hepatic vein. Diagnosis is guided by traditional clinical diagnostic criteria; the modified Seattle criteria, the Baltimore and revised European Group for Blood and Marrow Transplantation (EBMT), specifically. While there are promising results of imaging techniques studies in the diagnosis of VOD/SOS, none of those imaging techniques are routinely utilized in diagnosis yet. However, risk stratification is essential; conflicting results have been shown in studies aiming to define risk factors for development of VOD/SOS conducted to date. The only approved drug for the treatment of VOD/SOS yet is defibrotide, with early treatment offering higher chances of survival. In this review, we will focus on pathogenesis, clinical presentation and diagnostic criteria, risk factors, prophylaxis, and treatment of the VOD/SOS occurring post-HSCT.

Transient elastography of liver: Could it be a guide for diagnosis and management strategy in hepatic veno-occlusive disease (sinusoidal obstruction syndrome)?

Hepatic veno-occlusive disease (VOD), also termed sinusoidal obstruction syndrome (SOS), is a rare and life threatening complication of hematopoetic stem cell transplantation (HSCT). Many conditions can mimic the clinical signs of VOD/SOS. Differential diagnosis and diagnosis of the disease at an early stage is important, since the severe form of the disease has higher mortality rates and early-initiated specific treatment has better response rates. A sensitive and specific non-invasive imaging technique that can diagnose the disease at an early stage is still an unmet need today. We aimed to determine the role of liver stiffness measurement (LSM) with transient elastograph (TE) for the diagnosis of VOD/SOS after allogeneic HSCT. Between January 2019 and October 2021, a total of 49 patients underwent allogeneic HSCT and were retrospectively analyzed. Thirty-one adult patients who had a two or more LSM value were included in the study. Revised European Society for Blood and Marrow Transplantation (EBMT) was the criteria used for the diagnosis of VOD/SOS. Two of 31 patients developed VOD/SOS (6.4 %). Very high LSM values were detected in all patients who developed VOD/SOS. Early and specific VOD/SOS treatment resulted in improvement of LSM values together with other related features. However, LSM values did not increase significantly in patients with high a bilirubin level (≥2 mg/dl) without VOD/SOS. This study demonstrates that TE might be a promising non-invasive imaging method for diagnosis, follow-up and differential diagnosis of this dismal complication of HSCT. Yet, these results need to be supported by prospective studies.

Extracorporeal photopheresis in the treatment of acute and chronic graft-versus-host disease: A position statement from the Turkish Society of Apheresis (TSA).

Graft versus host disease (GVHD) is still the most important cause of mortality and morbidity after allogeneic stem cell transplantation. Though perfect response rates are not achieved, steroids are still the first-line treatment. In the face of the presence of the drugs approved by FDA in recent years for acute and chronic GVHD as second-line therapy in the steroid-refractory group, there exists no standard approach. Extracorporeal photopheresis (ECP) with an immunomodulatory effect, is favored in the treatment of both acute and chronic steroid refractory GVHD as it does not increase the risk of relapses or infections. Having a low profile of side effects, ECP is also generally well-tolerated by patients. Being a time requiring procedure, the fact is that it is not able to be practiced in all health centers and requires central venous catheters in patients unfit for venous access may be enumerated among its shortcomings. No complete standard is available with respect to ECP application frequency-time; it varies from one center to another. The Turkish Society of Apheresis established the Turkish ECP (TECP) group and sought some answers to the questions regarding the use of ECP in the treatment of GVHD, and issued a position statement.

Current practice of autologous hematopoietic progenitor cell mobilization in adult patients with multiple myeloma and lymphoma: The results of a survey from Turkish hematology research and education group (ThREG).

Autologous hematopoietic cell transplantation (AHCT) is an established treatment option for adult patients presenting with multiple myeloma (MM), Hodgkin lymphoma (HL) and various subtypes of non-Hodgkin lymphoma (NHL) in upfront and/or relapsed/refractory disease settings. Although there are recently published consensus guidelines addressing critical issues regarding autologous hematopoietic progenitor cell mobilization (HPCM), mobilization strategies of transplant centers show high variability in terms of routine practice. In order to understand the current institutional policies regarding HPCM in Turkey and to obtain the required basic data for preparation of a national positional statement on this issue, Turkish Hematology Research and Education Group (ThREG) conducted a web-based HPCM survey. The survey was designed to include multiple-choice questions regarding institutional practice of HPCM in adults presenting MM, HL, and NHL. The representatives of 27 adult HCT centers participated to the study. Here we report the results of this survey shedding light on the real-world experience in Turkey in terms of autologous HPCM mobilization strategies in patients presenting with MM and lymphoma.

Revisiting post-gastrectomy anemia with a brief survey among a group of Turkish medical oncologists.

PURPOSE: Total or subtotal gastrectomy are performed as curative or palliative treatment in patients with gastric cancer. Anemia is a frequent complication of gastrectomy. Patients undergoing total or subtotal gastrectomy should be carefully monitored for the development of anemia and be given appropriate treatment when indicated. This survey-based study aimed to determine the level of knowledge about post-gastrectomy anemia in Turkish medical oncologists. METHODS: The study included 110 Turkish medical oncologists that agreed voluntarily to participate in the survey and answer an 8-item questionnaire. The survey was distributed as a questionnaire during the 5th Turkish Medical Oncology Congress in March 2014. RESULTS: All participants completed the questionnaire. Most of the participants would not recommend oral iron or cobalamin replacement after gastrectomy. CONCLUSION: The results of the survey indicate that Turkish medical oncologists have some knowledge about post-gastrectomy anemia, but need to learn more about appropriate follow-up and replacement therapies for post-gastrectomy anemia.

Chemomobilization with high-dose etoposide and G-CSF results in effective and safe stem cell collection in heavily pretreated lymphoma patients: report from a single institution study and review.

The optimal mobilization strategy prior to autologous stem cell transplantation (auto-SCT) for patients with lymphoma is yet to be determined. We reviewed our institutional experience using chemomobilization with high-dose (HD) etoposide (1.6 g/m(2) ) and G-CSF (300 µg/day) in 79 patients with lymphoma. The majority (76%) had received at least two prior regimens of chemotherapy, and 12 (15.2%) patients had previously failed to mobilize following HD cyclophosphamide or DHAP or ICE with G-CSF. HD etoposide and G-CSF chemomobilization resulted in successful collection (>2 × 10(6) CD34+ cells/kg) in 82.3% of patients within a median 2 (1-6) apheresis days. Patients had stem cells collected between days +8 and +15, with a median +12 day. Median total CD34+ cells/kg collected was 5.95 × 10(6) (0.1-36.8). Seventy-one percent of patients yielded >2 × 10(6) CD34+ cells/kg in ≤2 d of apheresis and were defined as good mobilizers. While median CD34+ cells/kg collected for good mobilizers was 7.6 × 10(6) , it was 2.6 × 10(6) for poor mobilizers (P < 0.001). This regimen was safe with a low rate of febrile neutropenia (7.6%) and acceptable rates of RBC (40.5%) and platelet transfusions (22.8%). Hematopoietic recovery after auto-SCT was achieved on expected time. Therapy-related myelodysplastic syndrome/acute myeloid leukemia occurred in only one patient (1.3%) with in a median follow-up of 16 months after chemomobilization. We conclude that HD etoposide and G-CSF chemomobilization appear to result in effective, tolerable, and safe stem cell collection in the majority of heavily pretreated lymphoma patients.

Assessment and comparison of acute cardiac toxicity during high-dose cyclophosphamide and high-dose etoposide stem cell mobilization regimens with N-terminal pro-B-type natriuretic peptide.

This study was undertaken to prospectively evaluate and compare the acute effect of high-dose (HD), cyclophosphamide (CY) and HD etoposide (ET) on cardiac function assessed by plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients undergoing stem-cell mobilization. NT-proBNP was measured at baseline and 6h after completion of mobilization chemotherapy (MC) in 58 patients. Of 58 patients, 33 received HD CY, and 25 received HD ET. The mean baseline NT-proBNP values were similar between the CY and ET group (119.5 vs 149, respectively, p>0.05). NT-proBNP levels were increased in almost all patients, except 2 from CY group. A significant difference between NT-proBNP concentrations at baseline and 6h after completion of MC was observed in both groups (p<0.001). The value of changes in NT-proBNP was more significant in the ET group. The changes in NT-proBNP according to the MC regimens were analyzed and a cut-off value of 422pg/ml was determined. Based on this cut-off value, only the type of MC was significantly correlated with the chances in NT-proBNP concentrations. Receiving HD ET as a MC was found to be 5.25 times more cardiotoxic compared to the HD CY. Congestive heart failure was seen in 3 (5.2%) patients. Our results suggest that stem cell mobilization with HD CY and HD ET cause acute cardiac toxicity mediated by neurohumoral activation, which was detected by the increases in cardiac biomarker NT-proBNP, and as a matter of fact cardiotoxicity of HD ET seems to be more potent than those exhibited by HD CY.

Granulocyte Transfusions in Neutropenic Infections: Insights From a Single-Center Study.

Introduction Despite the development of modern antibiotic and antifungal therapies, neutropenic infections remain life-threatening. Granulocyte transfusion (GTX) is a less frequently used treatment modality in patients with refractory neutropenic infections. The role of donor GTX remains controversial, partly because of the lack of proper clinical trials. This study aimed to contribute to the literature by evaluating the efficacy and side effects of granulocyte transfusions in our center. Methods Eight febrile neutropenic patients with confirmed infections received granulocyte transfusions from ABO-compatible related and unrelated donors. Donors received filgrastim and dexamethasone stimulation, and granulocyte suspensions were irradiated and administered within six hours. Monitoring, antibiotic therapy, and granulocyte colony-stimulating factor (G-CSF) support were maintained. Results Our study observed a 28-day survival rate of 25%, which was lower than that reported in previous literature. The median number of transfusions was 3, with an average eight-day duration post-infection diagnosis, and no side effects were observed. Conclusion While some patients benefited from GTX, overall survival rates remained modest, indicating the need for further research. Prospective, well-powered randomized controlled trials are essential to address patient selection, dosing, and duration to determine the clinical utility of GTX. This study underscores the complexity of GTX in real-world clinical practice and provides insight into the ongoing debate regarding its efficacy in treating severe neutropenic infections.

Turkish Hematologists' Preferences for Related Donor Selection: Results of a Multicenter Survey

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a widely utilized treatment for various hematological diseases. While selection criteria for unrelated donors are well established, there is a lack of consistency and standardization in the selection of related donors. This study investigated the current approach of hematologists to the selection of related donors at Turkish HSCT centers. The study employed a cross-sectional survey design, distributing a self-administered questionnaire to 95 adult and pediatric transplantation centers in Türkiye to investigate their approaches to related donor selection for allo-HSCT. The questionnaire collected data on various topics including the center's experience in performing allo-HSCT, patient groups treated, number of allo-HSCT procedures conducted between 2015 and 2021, preferences for related donors, considerations in related donor selection (such as sex and past pregnancies), guidelines utilized for related donor selection, upper age limit for related donors, and the use of specialized advanced analyses for elderly donors. The response rate to the survey was 38.9%. Variability was observed across centers in terms of sex consideration and the impact of past pregnancies on related female donor rejection. Different guidelines were employed for related donor selection, with the European Bone Marrow Transplantation guidelines being the most commonly used. Regarding the upper age limit for related donors, 8.1% of centers accepted an upper age limit of 55 years, 48.7% preferred an upper age limit of 65 years, and 43.2% selected related donors aged 65 and above. The lack of standardized guidelines for related donor selection in HSCT centers leads to variability in criteria and potential risks. Collaboration among centers is essential to establish consensus and develop standardized protocols.

Results of Levofloxacin Prophylaxis Timing in Autologous and Allogeneic Stem Cell Transplantation: A Retrospective Cohort Study.

Background Despite preventive measures and varying antibiotic recommendations, bacterial infections continue to pose a significant threat to individuals undergoing hematopoietic stem cell transplantation (HSCT). Levofloxacin prophylaxis is commonly used, but the optimal timing for initiation is debated. This study aims to assess infection outcomes based on timing of levofloxacin prophylaxis (initiation at the first day of conditioning vs. after infusion of stem cells) in autologous and allogeneic HSCT patients. Methods We compared infectious episodes, responsible pathogens, and clinical outcomes based on the implementation of levofloxacin prophylaxis in patients receiving autologous or allogeneic HSCT procedures. This retrospective single-center study involved a review of the medical records of autologous and allogeneic HSCT patients treated at our adult stem cell transplantation unit between 2018 and 2020. The study included 23 patients who underwent autologous HSCT and 12 patients who underwent allogeneic HSCT. We compared the demographic data, febrile neutropenia, proven bacterial infections, and 30-day survival among the autologous and allogeneic transplant groups, including those who received oral levofloxacin 500 mg/day prophylaxis. Results Positive blood cultures (26.1% vs. 75%; p = 0.011), mean neutrophil engraftment (10.6±1.2 vs. 14.8±1.3; p<0.001), and mean platelet engraftment (11.2±1.1 vs. 15.4±3.2; p = 0.004) were all lower in autologous transplant patients versus their allogeneic counterparts. When each type of HSCT was evaluated within the same type, there were no observed differences in infection frequency, infection type, or 30-day mortality between the patient groups with different levofloxacin initiation times. Conclusion Healthcare professionals should choose the most appropriate timing for initiating levofloxacin prophylaxis based on individual patient factors and clinical circumstances while considering the cost-effectiveness implications. Further research with a larger sample size and prospective design is needed to support our findings.

Bidirectional ABO Mismatch Is Associated With Elevated Mortality in Hematopoietic Stem Cell Transplantation: Insights From a Single-Center Experience.

Background Hematopoietic stem cell transplantation (HSCT) is a promising therapy for various disorders and provides new opportunities for patients. ABO incompatibility in allogeneic HSCT (allo-HSCT) remains a topic of debate because of its potential impact on clinical outcomes. This study aimed to analyze the survival outcomes of patients who underwent ABO-incompatible HSCT and evaluate the occurrence of pure red cell aplasia. Methods This retrospective study included 20 patients who underwent ABO-incompatible HSCT. Data on patient characteristics, transplant details, and follow-ups were collected. Conditioning regimens and graft-versus-host disease (GVHD) prophylaxis strategies were employed. Results Neutrophil and platelet engraftment durations did not differ significantly between major and bidirectional mismatches. Pure red cell aplasia occurred in 4 patients (20%) with major mismatches, all of whom responded well to bortezomib treatment. Patients with a bidirectional mismatch exhibited a 3.57-fold increase (hazard ratio [HR]: 0.28; p<0.05) in the risk of mortality compared to those in the major mismatch group. Conclusion The results indicate that ABO mismatch, whether bidirectional or major, does not significantly affect neutrophil and platelet engraftment duration, suggesting that ABO incompatibility may not be a major factor influencing hematological recovery in allo-HSCT. Interestingly, patients with bidirectional mismatch exhibited a significantly higher mortality rate than those with major mismatch. This finding suggests that a bidirectional ABO mismatch may have an unfavorable prognosis in terms of overall survival in allo-HSCT patients.

Daily vs every other day administration of G-CSF following autologous peripheral stem cell transplantation: a prospective randomized study.

The purpose of the study was to evaluate whether every other day administration of G-CSF was as safe and efficient as daily administration of G-CSF on neutrophil engraftment following autologous peripheral stem cell transplantation (APSCT). Duration of G-CSF administration, incidence of blood stream infections, duration of febrile neutropenia, duration of non-prophylactic antibiotic therapy, transfusion requirements, duration of hospitalization and G-CSF costs were also studied. Forty-seven patients with diagnosis of lymphoma and multiple myeloma undergoing APSCT were randomized to receive post-transplant daily or every other day G-CSF therapy both beginning on day +1. Both groups were comparable with regard to patient characteristics. There was no significant difference in time to neutrophil engraftment (p=0.31). The duration of G-CSF administration was significantly less in the every other day group (p<0.001). There were no detectable differences seen in the number of febrile days, duration of non-prophylactic antibiotics, the incidence of blood stream infections, transfusion requirements and the duration of hospitalization. There was a trend towards a faster platelet recovery in the every other day group, although the difference was not statistically significant (p=0.059). The number of doses of G-CSF used per transplant is significantly reduced, resulting in a significant reduction in drug costs.

A Multi-Center Study on the Efficacy of Eltrombopag in Management of Refractory Chronic Immune Thrombocytopenia: A Real-Life Experience

Objective: The aim of the present study was to evaluate the efficacy and safety of eltrombopag, an oral thrombopoietin receptor agonist, in patients with chronic immune thrombocytopenia (ITP). Materials and Methods: A total of 285 chronic ITP patients (187 women, 65.6%; 98 men, 34.4%) followed in 55 centers were enrolled in this retrospective cohort. Response to treatment was assessed according to platelet count (/mm3) and defined as complete (platelet count of >100,000/mm3), partial (30,000-100,000/mm3 or doubling of platelet count after treatment), or unresponsive (<30,000/mm3). Clinical findings, descriptive features, response to treatment, and side effects were recorded. Correlations between descriptive, clinical, and hematological parameters were analyzed. Results: The median age at diagnosis was 43.9±20.6 (range: 3-95) years and the duration of follow-up was 18.0±6.4 (range: 6-28.2) months. Overall response rate was 86.7% (n=247). Complete and partial responses were observed in 182 (63.8%) and 65 (22.8%) patients, respectively. Thirty-eight patients (13.4%) did not respond to eltrombopag treatment. For patients above 60 years old (n=68), overall response rate was 89.7% (n=61), and for those above 80 years old (n=12), overall response rate was 83% (n=10). Considering thrombocyte count before treatment, eltrombopag significantly increased platelet count at the 1st, 2nd, 3rd, 4th, and 8th weeks of treatment. As the time required for partial or complete response increased, response to treatment was significantly reduced. The time to reach the maximum platelet levels after treatment was quite variable (1-202 weeks). Notably, the higher the maximum platelet count after eltrombopag treatment, the more likely that side effects would occur. The most common side effects were headache (21.6%), weakness (13.7%), hepatotoxicity (11.8%), and thrombosis (5.9%). Conclusion: Results of the current study imply that eltrombopag is an effective therapeutic option even in elderly patients with chronic ITP. However, patients must be closely monitored for response and side effects during treatment. Since both response and side effects may be variable throughout the follow-up period, patients should be evaluated dynamically, especially in terms of thrombotic risk factors.

Coincidence of follicular lymphoma and hurtle cell thyroid carcinoma in a patient at presentation: which one is the source of bone metastasis? Case report and review of the literature.

Thyroid incidentaloma is defined as a new identified thyroid lesion occasionally detected during imaging studies. Incidence of thyroid incidentalomas is relatively rare in patients with lymphoma. Because of high rate of malignancy, these lesions with high intensity focal 18 FDG uptake detected on positron emission tomography with computed tomography (PET/CT) should undergo to biopsy regardless of size.

Serum galactomannan levels in the diagnosis of invasive aspergillosis.

BACKGROUND/AIMS: In this study, the sensitivity-specificity of galactomannan-enzyme immunoassay (GM-EIA) with a cut-off value of 0.5 for a single, two, or three consecutive positivity in the diagnosis of invasive pulmonary aspergillosis (IPA) in neutropenic patients with hematological malignancy was investigated. METHODS: IPA was classified as "proven," "probable," or "possible" as described in the guidelines prepared by the European Organization for Research and Treatment of Cancer and Mycoses Study Group." Serum samples were collected from the patients twice a week throughout their hospitalization. A total of 1,385 serum samples, with an average of 8.3 samples per episode, were examined. RESULTS: Based on the 165 febrile episodes in 106 patients, 80 (48.5%) were classified as IPA (4 proven, 11 probable, 65 possible) and 85 (51.5%) as non-IPA. The sensitivity/ specificity was 100%/27.1% for a single proven/probable IPA with the cut of value of GM-EIA ≥ 0.5, 86.7%/71.8% for two consecutive positive results, and 73.3%/85.9% for three consecutive positive results. CONCLUSIONS: With the galactomannan levels measured twice a week, consecutive sensitivity decreased and specificity increased. Therefore, an increase may be obtained in sensitivity-specificity by more frequent monitoring of GM-EIA starting from the first day of positivity is detected.