bluuebunny/crossref_metadata_2025_split huggingface dataset:
Innovative Treatment for Post-COVID Syndrome: A Clinical Breakthrough
Authors: Chen Ying Chieh , Rosenthal Joseph , Su Gili , Lau Ernest , Chen Chinhhsin , Martinez Aristides Canalejo , Wang Jonas , Lee Tong Young 
Published: December 2024

As of July 2024, over 775 million people worldwide have confirmed cases of COVID-19, according to the World Health Organization. While the majority recover fully, studies reveal that 10 to 20% of these individuals experience persistent symptoms, known as post-COVID syndrome (long COVID). This condition affects multiple organ systems, with fatigue being the most frequently reported and burdensome symptom by 87% of patients. Post-COVID syndrome significantly impairs daily functioning and quality of life, highlighting the urgent need for effective treatments.
RegeneCyte® (HPC, cord blood, hUCB), developed by StemCyte Inc., is a pioneering regenerative medicine therapy (RMT). It is rich in monocytes, lymphocytes, stem cells (CD34+ cells), and progenitor cells. The safe and effective use of hUCB transplantation in treating various conditions, from hematological malignancies to neurological disorders, positions it as a promising candidate for addressing post-COVID syndrome, particularly in alleviating fatigue.
Our phase IIa clinical trial (NCT#05682560) investigates the safety, tolerability, and efficacy of RegeneCyte® for post-COVID syndrome. The randomized, single-blind, placebo-controlled study involves 30 subjects aged 18 to 65 years, with persistent post-COVID symptoms for over 6 months but not exceeding 18 months. Subjects are randomized in a 2:1 ratio between the treatment and placebo arms. Fatigue severity is assessed using the Chalder Fatigue Scale (CFQ-11) as the effectiveness endpoint. Twenty subjects in the treatment arm receive three intravenous doses of RegeneCyte® every three weeks, with follow-up over 20 weeks. Each dose contains at least 1 × 10^7 total nucleated cells (TNC)/kg, with a cumulative dose of at least 3 × 10^7 TNC/kg per subject. This is the first clinical trial which use three units of HPC in one subject in the past decades.
Preliminary data from the first 15 subjects show no trends in the changes of clinical safety laboratory parameters between the RegeneCyte® and placebo groups. Efficacy results at week 12 reveal that 90% of RegeneCyte®-treated subjects are classified as “non-fatigue” cases, compared to 100% in the placebo group remaining “fatigue” cases. Furthermore, 80% of RegeneCyte®-treated subjects show improvement to a “normal” level of physical fatigue, whereas all placebo recipients remain at the “fatigue” level. These findings demonstrate that RegeneCyte® is safe, well-tolerated, and significantly improves fatigue symptoms in post-COVID syndrome patients.
In conclusion, RegeneCyte®, a first-in-class regenerative medicine therapy, shows significant potential in treating post-COVID syndrome. The clinical evidence of profound fatigue reduction and a high safety profile underscores its therapeutic promise. RegeneCyte® infusion presents a viable treatment option for post-COVID syndrome, addressing unmet medical needs and expanding the scope of RegeneCyte® applications.
Allogeneic Hematopoietic Progenitor Cell from Peripheral Whole Blood in Acute Myeloid Leukemia
Authors: Amaru Ricardo , Mamani Reyna , Velarde Jeaneth , Carrasco Mireya , Quispe Soto Edgar Teddy , Mancilla Silvia , Valencia Juan Carlos , Paton Daniela , Amaru Ariel 
Published: December 2024

Acute Myeloid Leukemia (AML) standard treatment involves initial induction therapy administrating two cycles of the 3+7 protocol (3 days anthracycline + 7 days cytarabine), and post-remission therapy of 3 cycles of high-dose cytarabine. The 5-year overall survival is 20 % (PMID: 33734442). During prolonged aplasia, infections and hemorrhages can cause treatment failure and death (PMID: 32236160). That is why transfusions of allogeneic hematopoietic progenitor cells (Allo-HPC) from whole peripheral blood to reduce the time of aplasia and complications were of interest.
We studied 6 patients (3 males, 3 females) with AML (M1, M2), average age 35 years (18-60 years), who received Allo-HPC from whole peripheral blood during aplasia after each 3+7 regimen. The transfusion was performed at day 14 (day 12-16) post-regimen, when patients had neutrophils &lt;100/ul (0-100/ul). Regarding donors, one corresponded to HLA identical sibling, and 5 to haploidentical (2 fathers, 2 mothers and 1 brother), they received G-CSF 300 μg subcutaneously every 12 hours over 3 days, then 450 ml phlebotomy was performed. Phlebotomy displayed median WBC 27,310/ul, neutrophils 21,830/ul, CD34+ cells 9/ul, hemoglobin 14.8 g/dl, and platelets 218,000/ul. Thus, whole peripheral blood obtained was transfused through patients' CVC after premedication with dexamethasone 8 mg and metamizole 1 g. FISH (Y chromosome, Vysis CEP-Y DYZ1) and RT-PCR (HUMARA gene) studies were performed for chimerism analysis.
Recovery of neutrophils &gt;500/ul was observed at day 9 and platelets &gt;20,000/ul at day 6. One case of cutaneous rush was observed as an adverse event. MRD after each cycle reflected 0.01% average. Three patients remain alive with follow-up of 4 years, 5 years and 1 year respectively. Two patients relapsed and died during 1year follow-up. One patient developed optic neuritis and did not receive high-dose cytarabine therapy, relapsed and died after 6 months. None of the patients presented acute or chronic GVHD. Regarding the results of chimerism, one male patient (1year follow-up) showed mixed chimera by FISH (Y=95%) and by RT-PCR (HUMARA gene), such studies were still in progress in the other two women patients.
Contrasting patients who received Allo-HPC from the ones who do not, statistically differences were found in neutrophils recovery and hospital staying, the former displayed 9 + 3 days vs 14 + 4 days (p=0.008) and 19 +5 days vs 25 + 4 days (p=0.009) respectively, infections also decreased from 83% to 25%.
Transfusion of Allogeneic Hematopoietic Progenitor Cell from Peripheral whole blood reduces the duration of aplasia, infections, inpatient stays, and increases survival.
Incidence of Engraftment Syndrome with and without Budesonide Prophylaxis in Patient with Multiple Myeloma Undergoing Autologous Stem Cell Transplant
Authors: Daniels Stephanie , Gloe Lucy , Kota Vamsi K. , Rakestraw Alexandria , Clemmons Amber 
Published: December 2024

Engraftment syndrome (ES), a rare post-transplant complication, has been defined differently across the existing literature. This study aims to determine if budesonide prophylaxis reduces the incidence of ES after autologous hematopoietic cell (auto-HCT) for patients with multiple myeloma (MM), as defined by three separate published criteria - Spitzer1, Maiolino2, and Dhakal3, respectively.
A single-center, IRB-approved, retrospective review was conducted on adult patients who received auto-HCT for the treatment of MM between January 2017-October 2023. Based on results of the Dhakal study reporting the benefit of budesonide to prevent ES, our local institution made a practice change in October 2021 to prescribe budesonide 3mg by mouth three times a day, beginning on day +5 until discharge, for ES prophylaxis in all patients with a diagnosis of MM undergoing auto-HCT. Patients were divided into those who did not receive budesonide prophylaxis (n=169) and those who did receive budesonide prophylaxis (n=144). Primary endpoint was incidence of ES by each criteria. Secondary endpoints included receipt of steroids to treat ES, time to engraftment, and 30- and 100-day mortality rates. Exploratory endpoints were new start antibiotics in the peri-engraftment period and number of doses of anti-diarrheal and anti-emetic agents.
Overall, most patients were Caucasian or African-American, male, and the median age was 66 years. No difference existed between groups for any demographic factor including dose of melphalan, receipt of plerixafor, or median number of CD34 cells infused (all p&gt;0.05). No difference existed between the two groups with respect to the primary outcome of incidence of ES by Spitzer, Maiolino, or Dhakal criteria or by provider documented ES (all p&gt;0.05). Further, no difference existed between the groups with respect to the secondary or exploratory outcomes (all p&gt;0.05); however, those who received budesonide were less likely to receive new treatment with an antibiotics within 3 days before or 10 days after neutrophil engraftment (20.9% vs 47.5%, p&lt;0.001).
Our findings show budesonide does not appear to reduce the incidence of ES when utilizing Spitzer or Mailoino criteria. The low overall rates of ES by Spitzer, Mailoloino, and provider documentation in this study suggest a preventative strategy may not be warranted. However, reduction in incidence of new onset febrile neutropenia in the peri-engraftment period warrants further study.
Efficacy and Safety Profile of Busulfan Plus Low Dose Melphalan (BUMEL) Versus High Dose Melphalan (HDMEL) As a Conditioning Regimen for Autologous Hematopoietic Stem Cells Transplantation (Auto-SCT) in Multiple Myeloma Patients: A Systematic Review and Meta-Analysis
Authors: Kakar Imran , Maqbool Shahzaib , Rehman Abdur , Faraz Fatima , Shahzad Moazzam 
Published: December 2024

Introduction:
Multiple myeloma (MM) is a hematological malignancy characterized by the abnormal proliferation of monoclonal plasma cells in the bone marrow, leading to symptoms such as bone pain, hypercalcemia, and renal dysfunction. A significant advancement in the treatment of MM is autologous hematopoietic stem cell transplantation, which has been effectively utilized to improve patient outcomes. This meta-analysis aims to explore the comparative efficacy and safety profile of Busulfan plus low dose Melphalan (BUMEL) versus High dose Melphalan (HDMEL) as a conditioning regimen for Autologous Hematopoietic stem cells transplantation in patients of Multiple Myeloma.
Methods:
A comprehensive literature review including 13 final studies was conducted using PubMed, Cochrane, and Embase. We included randomized controlled trials focused on patients with multiple myeloma treated with Busulfan plus low-dose Melphalan and high-dose Melphalan. A hazard ratio (HR) corresponding to a 95% confidence Interval (CI) was adopted to assess OS and PFS. The DerSimonian and Laird random effects model was used to pool Hazard ratios (HR) and dichotomous outcomes were pooled using risk ratio while continuously using Mean difference. The random effects model was used using the inverse variance method. a p-value of &lt;0.5 was considered statistically significant.
Results:
The BUMEL-based conditioning regimen was found to be more favorable regarding progression-free survival (PFS) compared to the HDMEL regimen (HR 0.89; 95% CI 0.77-0.97, P = 0.006). However, overall survival (OS) was comparable between the two therapeutic groups, with no statistically significant difference observed (HR 1.12; 95% CI 0.82-1.43, P = 0.76). Regarding the safety profile, gastrointestinal side effects were less common with the BUMEL regimen (OR 0.81; 95% CI 0.57-0.90, P &lt; 0.004) compared to HDMEL. Conversely, other side effects such as mucositis, infections, and hepatic toxicity were more prevalent with BUMEL-based therapy.
Conclusion:
In our meta-analysis, the BUMEL-based regimen demonstrated higher effectiveness in terms of progression-free survival (PFS), with this comparison being statistically significant. Although overall survival (OS) also favored the BUMEL-based therapy, there was no statistically significant difference between the two groups. The overall toxicity profile was higher in the BUMEL group, except gastrointestinal toxicity, which was less common, thus balancing the efficacy and safety profiles between the BUMEL and HDMEL regimens.
Keywords: Autologous Hematopoietic stem cell transplantation, BUMEL, HDMEL, Multiple Myeloma.
Lived Experiences and Coping Strategies of Adults with Sickle Cell Disease in Uganda: Implications for Improving Health and Well-Being
Authors: Ahebwe Shivan , Rujumba Joseph , Green Nancy S. S. , Idro Richard 
Published: December 2024

Introduction: Sickle cell disease (SCD) is a significant contributor to childhood morbidity and mortality in Uganda and sub-Saharan Africa. However, with improvements in clinical care, many children have reached adulthood. However, there is a paucity of data on their experiences despite the importance of patient-reported perspectives to inform interventions for improving their quality of life. We explored the lived experiences and coping strategies of adults living with SCD in Kampala, Uganda.
Methods: We conducted a qualitative study at the oldest and largest sickle cell clinic in Uganda located at Mulago National Referral Hospital in Kampala between March and July 2022. Data were collected through in-depth interviews with 15 adults aged 25 to 40 years living with SCD attending the clinic, as well as five key informant interviews with healthcare workers at the sickle cell clinic, the Ministry of Health and a non-government organization providing support to people living with SCD. All interviews were audio recorded, transcribed verbatim and analyzed using a content thematic approach.
Results: The adults living with SCD described facing significant physical, social and emotional challenges such as stigma and discrimination at family, community and institutional levels in the context characterized by inadequate support. Furthermore, adults with SCD encountered difficulties in attaining education, securing employment and accessing health care services, each of which they perceive as having negatively affected their quality of life. The major coping strategies adopted were drawing on religious beliefs, striving to attain adherence to medical treatment and seeking support from their networks, especially their families.
Conclusions: The voices of adults living with SCD in this study depict the intersecting social, economic and psychological challenges and vulnerabilities that negatively affect the quality of life of affected adults. Stigma, challenges from health care, educational and vocational systems, as well as a general lack of formal support, dominate the everyday experiences of adults living with SCD in Uganda. Affected adults draw on religion, adherence to medical treatment and support, especially from their families, as major coping strategies. There is a need to strengthen support from health care, social, religious and vocational support for patients with SCD beyond childhood. Addressing this gap in support will require more investment from public and private sectors with local, national and global resources to optimize the health and well-being of young adults living with SCD.
Echinocandin-Resistant Candidemia, the Next Upcoming Threat in the Era of Echinocandin Prophylaxis Among Pediatric Hematological Malignancies in Limited Resources Countries
Authors: Madney Youssef , Khedr Reham , Hafiz Hanfy , Shalby Lobna , Gaber Mervat , ELsheshtawy Khaled , Adel Naglaa , Alhaddad Alaa 
Published: December 2024

Background: Hematological cancer patients are at risk for developing candidemia, and echinocandins are commonly employed for prophylaxis in those patients. The rising resistance of Candida spp. to echinocandins poses an emerging threat. Our study aims to identify echinocandin-resistant Candida patterns and their impact on clinical outcomes among pediatric hematological malignancies in limited-resource countries.
Patients and Methods:From 2014 to 2020, Echinocandins were the primary antifungal prophylaxis for children with acute and relapsing leukemias. We conducted a retrospective analysis of patients with candidemia at the Children's Cancer Hospital Egypt (CCHE). The analysis included patterns of resistant Candida species and their outcomes. Breakthrough candidemia was defined as candidemia occurring during antifungal agent administration. Identification of Candida spp. was performed using the Vitek and Vitek2 systems.
Results: Three hundred fifty (350) pediatric cancer patients with candidemia were included in the study, with a median age of 4 years (range: 4 months to 18 years). The main underlying diseases were hematological malignancies (70%) with acute lymphoblastic leukemia being the most prevalent, followed by acute myeloid leukemia. Non-Albicans candida species constituted the majority (73%) of isolates compared to Candida Albicans (27%). The most frequently isolated species included: C. Albicans (27%), C.Tropicalis(29%), C.parapsilosis (21%), C. krusei (7%), C.glabrata(3%), C. famata (2%) and C. guilliermondii (1.5%). Resistant candida was reported among 74 (21%) patients. Echinocandin-resistant candida strains reported in 17(5%) patients: C. parasitosis (7), C. albicans (4), C. tropicalis (2), C. krusei (3) and C. lipolytica (1). Breakthrough candidemia occurred in 62 (17%) patients receiving echinocandin prophylaxis, with C. parapsilosis being the most common isolated pathogen (31 cases, 50%). Unfortunately, ten patients (16%) with breakthrough candidemia died secondary to candida sepsis syndrome. The overall 30 -day mortality rate was 24% (85/350 patients). Patients with Echinocandin-resistant candida were associated with high-risk mortality (20%).
Conclusion: Echinocandin-resistant Candida is a major threat in high-risk hematological pediatric cancer patients with a high mortality rate. Therefore, clinicians should pay attention to resistance and Breakthrough Candida even in patients under echinocandin prophylaxis. Antifungal stewardship may be helpful.
Relative Efficacy of Systemic Treatments for Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia: A Network Meta-Analysis According to 17p Deletion/TP53 Mutations
Authors: Kim Jinchul , Cho Jinhyun , Lim Joo Han , Lee Moon Hee , Lee Myung-Won 
Published: December 2024

Introduction: The treatment landscape forrelapsed/refractory chronic lymphocytic leukemia (R/R CLL) has significantly advanced with the introduction of novel targeted therapies. Although these treatments have shown improved outcomes for R/R CLL patients, no single standard of care has been established. This network meta-analysis aims to evaluate the relative efficacy of systemic treatments for R/R CLL, focusing on key genetic mutations, specifically 17p deletion and TP53 mutations.
Methods: We conducted a systematic literature review to identify all publicly available randomized controlled trials (RCTs) using PubMed, EMBASE, the Cochrane database, and several meeting abstracts through February 2024. A Bayesian network meta-analysis with fixed-effects models was employed to estimate hazard ratios (HRs) for progression-free survival (PFS) with 95% credible intervals (CIs) across all treatment options and to determine the ranking of the included regimens. Ibrutinib was used as reference treatment.
Results: Twelve trials involving 4,437 patients and 13 treatment options were included in the meta-analysis: three Bruton tyrosine kinase (BTK) inhibitors (ibrutinib, acalabrutinib, and zanubrutinib), two BTK inhibitors combined with other treatments (ibrutinib plus rituximab plus bendamustine [RB] and ibrutinib plus rituximab), two phosphoinositide 3-kinase (PI3K) inhibitors (idelalisib and duvelisib), three PI3K inhibitors combined with other treatments (idelalisib plus ofatumumab, idelalisib plus RB, idelalisib plus rituximab), three anti-CD20-based treatment (RB, ofatumumab, and rituximab), and one BCL-2 inhibitor (venetoclax plus rituximab). Venetoclax plus rituximab and zanubrutinib emerged as the most effective treatments for the overall R/R CLL population, showing the lowest hazard ratios (HR 0.62, 95% CI 0.32-1.20 and HR 0.65, 95% CI 0.49-0.86, respectively) versus ibrutinib, and were ranked as the best agents (surface under the cumulative ranking curve [SUCRA] value of 90% for both) among the included drugs. In the 17p deletion/TP53 mutation subgroup, zanubrutinib demonstrated the most favorable efficacy (HR 0.52, 95% CI 0.31-0.88 versus ibrutinib) with the highest SUCRA value (97%). For patients without these mutations, venetoclax plus rituximab was the most effective (HR 0.49, 95% CI 0.26-0.94 versus ibrutinib) with a SUCRA value of 94%.
Conclusions: Our findings highlight the superior efficacy of venetoclax plus rituximab and zanubrutinib for treating R/R CLL and confirm that the role of each regimen may vary depending on clinically significant mutations.
A Phase II Investigator-Initiated Trial of Epcoritamab with Gemcitabine, Dexamethasone, and Cisplatin (GDP) Salvage Chemotherapy in Relapsed Refractory Large B-Cell Lymphoma
Authors: Modi Dipenkumar , Kim Seongho , Domagalski Mary , Mittal Varun 
Published: December 2024

Background and Significance: Approximately 30% of patients with large B cell lymphoma (LBCL) relapse after receiving rituximab-containing chemoimmunotherapy. Patients with rapidly progressing and symptomatic disease often require effective bridging therapy while awaiting CAR T-cell therapy. In addition, a salvage chemotherapy, which offers high response rates, is warranted to improve long-term outcomes. Epcoritamab is a CD3xCD20 bispecific antibody approved for relapsed refractory (RR) DLBCL after ≥2 prior lines of therapy. We hypothesized that the combination of epcoritamab, and gemcitabine, dexamethasone, and cisplatin (GDP) salvage chemotherapy could be effective for RR LBCL patients eligible for CAR T-cell therapy or stem cell transplant.
Study Design and Methods: This is a phase II investigator-initiated multicenter trial evaluating safety and efficacy of epcoritamab with GDP salvage chemotherapy in RR LBCL. Key eligibility criteria will include patients ≥18 years of age with CD20 positive RR LBCL with an eligible subtype, ³1 prior line of therapy, and eligible for CAR T-cell therapy or stem cell transplant (SCT), ECOG PS 0-2, and FDG avid and measurable disease by PET. All patients will receive 3 cycles of epcoritamab and GDP in the outpatient setting. No hospitalization for CRS monitoring is mandated. Epcoritamab will be administered subcutaneously during cycle 1 as weekly step-up doses (0.16/0.8/48 mg) and then weekly from cycle 2 day 1(cycle 2-3). GDP consists of gemcitabine 1000 mg/m2 IV on days 1 and 8, cisplatin 75 mg/m2 IV on day 1, and dexamethasone 40 mg orally days 1 through 4. Patients can proceed to CAR T-cell therapy or SCT upon completion of cycle 3 per investigator discretion. Patients who do not undergo CAR T-cell therapy or SCT may remain in the study and receive epcoritamab monotherapy for 6 cycles (cycle 4 through cycle 9, each cycle= 28 days), or until unacceptable toxicity, or disease progression per the Lugano Criteria.
The primary end point is complete remission (CR) rate per the Lugano criteria. Secondary end points include overall response rate, duration of response, progression-free survival, overall survival, safety and tolerability of epcoritamab and GDP, and feasibility of peripheral blood T-lymphocytes collection or stem cell mobilization. The sample size is justified using Simon's two-stage minimax design for the alternative CR rate of 65% against the null CR rate of 40%. In the first stage, 14 patients will be accrued. If there are 5 or less CR in these patients, the study will be stopped. Otherwise, 18 additional patients will be accrued for a total of 32. This design will yield a 1-sided type I error rate of 2.5% and power of 80% when the true CR rate is 65%. The study is currently enrolling. The clinicalTrials.gov ID is NCT05852717.