bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Single-Center Study of Long-Term Efficacy and Discontinuation Patterns of Thrombopoietin Receptor Agonists in Chronic Immune Thrombocytopenia
Authors: Stafylidis Christos , Diamantopoulos Panagiotis T , Vlachopoulou Dimitra , Antoniadou Vasiliki , Syriopoulou Stavroula , Patsialos Iraklis , Mantzourani Marina 
Published: December 2024

Introduction
Thrombopoietin receptor agonists (TPO-RAs) have shown promising efficacy in the management of persistent or chronic immune thrombocytopenia (ITP), as second-line treatment, whereas sustained responses after TPO-RA discontinuation have also been reported. We present real-world data of TPO-RA-treated chronic ITP patients in a single center.
Methods
This retrospective study was conducted at the Hematology Unit of the First Department of Internal Medicine of the National and Kapodistrian University of Athens, Laikon General Hospital in Athens, Greece. Data were obtained from consecutive adult patients with chronic/refractory primary ITP treated with TPO-RAs from January 2010 to June 2024. Complete response (CR), defined as platelet count ≥ 100 × 109/L and absence of bleeding as well as durable response, defined as platelet count ≥ 30 x 109/L and at least doubling of the baseline count, were evaluated in these patients after initiation of TPO-RA treatment.
Results
A total of 52 patients were included. The median age was 52 (19-72) years and 70% were female. Patients had been previously treated with corticosteroids (100%), intravenous immunoglobulin (54%), immunosuppressants (21%), rituximab (8%), or splenectomy (17%). The majority of the patients (65%) received eltrombopag as initial TPO-RA treatment, while 35% were treated with romiplostim. The median time from diagnosis to TPO-RA treatment initiation was four years. The median duration of TPO-RA treatment was 48 months. CR was achieved in 52% of patients with TPO-RA treatment, whereas 23% of patients yielded durable responses. The median time to CR was 24 months. Ten patients (19%) who did not initially respond to eltrombopag, switched to another TPO-RA (90% avatrombopag), with 70% of them achieving CR and 20% yielding a durable response. The median time to CR after switching to a different TPO-RA was 16 months. Among all patients who achieved durable responses, a reduction in TPO-RA dose was achieved in 71%. Treatment discontinuation was observed in 58% of patients, due to either CR (90%) or poor response (10%). The median treatment-free period was 11 months, while treatment reinitiation due to loss of CR was noted in 11%.
Conclusion
TPO-RAs are highly effective in treating chronic ITP patients who are refractory to or relapse after first-line treatments. Furthermore, these agents can lead to sustained responses, thus allowing for treatment discontinuation and ultimately contributing to life quality improvement. Finally, switching to another TPO-RA may be beneficial for patients who do not initially respond.
Clinical Outcomes for Black Patients Following Hematopoietic Stem Cell Transplant: An Analysis of the National Inpatient Sample
Authors: Thor Danielle C , Elias Tony , Polineni Vineet , Brik Ben 
Published: December 2024

Background: As hematopoietic stem cell transplant (HSCT) grows in accessibility and utility, it remains imperative to understand outcomes for its recipients. Limited data is available on the race-based correlations for this steadily increasing patient population. We sought to examine the National Inpatient Sample (NIS) database to describe in-hospital outcomes among the black population who have received a HSCT.
Methods: Data were extracted from the NIS Database from 2019 and 2020. The NIS was searched for hospitalizations of all patients greater than 18 years old who had previously received a HSCT and were hospitalized thereafter. We then analyzed the outcomes of patients who were identified as black. Multivariate logistic regression analysis was used to adjust for confounders; SPSS software was used for statistical analysis. The primary outcome was inpatient mortality and secondary outcomes are listed below.
Results: This study included 8,302 patients who had received a HSCT, of which 1070 (12.9%) were identified as black. Black recipients of a HSCT had a higher prevalence of obesity (8.6% versus 7.0%, p&lt;0.001), hypertension (32.4% versus 23.7%, p&lt;0.001), and chronic kidney disease (28.1% versus 21.3%, p&lt;0.001), as well as a lower prevalence of smoking (17.1% versus 20.5%, p&lt;0.001). Multivariate regression demonstrated that black recipients of a HSCT had higher inpatient mortality (OR 1.130, CI 1.087-1.174, p&lt;0.001). On secondary analysis, black HSCT recipients were found to be more likely to have non-alcoholic fatty liver disease (OR 1.092, CI 1.039-1.147, p&lt;0.001), thrombocytopenia (OR 1.133, CI 1.112-1.155, p&lt;0.001), peripheral artery disease (OR 1.113, CI 1.067-1.161, p&lt;0.001), hypertension (OR 1.215, CI 1.190-1.240, p&lt;0.001), acute kidney failure (OR 1.162, CI 1.141-1.183, p&lt;0.001), all-cause arrhythmias (OR 1.152, CI 1.120-1.186, p&lt;0.001), all-cause shock (OR 1.173, CI 1.104-1.246, p&lt;0.001), all-cause heart block (OR 1.089, CI 1.048-1.132, p&lt;0.001), pericarditis (OR 1.186, CI 1.119-1.258, p&lt;0.001), sepsis (OR 1.136, CI 1.119-1.153, p&lt;0.001), hematuria (OR 1.128, CI 1.078-1.180, p&lt;0.001), esophagitis (OR 1.138, CI 1.119-1.157, p&lt;0.001), coagulopathies (OR 1.150, CI 1.108-1.193, p&lt;0.001), chronic pulmonary disease (OR 1.120, CI 1.094-1.146, p&lt;0.001), pulmonary hypertension (OR 1.178, CI 1.118-1.240, p&lt;0.001), severe liver disease (OR 1.096, CI 1.061-1.132), acute heart failure (OR 1.188, CI 1.161-1.216, p&lt;0.001), and myocardial infarction (OR 1.113, CI 1.081-1.147, p&lt;0.001).
Conclusion: In this nationally-representative, population-based retrospective cohort study, black patients who have received a HSCT and were subsequently hospitalized were associated with higher mortality and worse outcomes.
Developing Novel Nanobodies Against the 5-Methylcytosine Dioxygenases TET2
Authors: Cai Xiaoli , Liu Xiaoxuan , He Lian , Liu Siyao , Fang Shaohai , Ma Guolin , Wang Rui , Zhou Yubin , Huang Yun Nancy 
Published: December 2024

The Ten-eleven Translocation (TET) family of dioxygenases mediate DNA demethylation by oxidating 5-methylcytosine in the mammalian genome. Among the three TET family members, TET2 is frequently mutated in hematological disorders, including age-related clonal hematopoiesis and hematological malignancies. Previous reports suggest that loss-of-function mutations of TET2 lead to increased self-renewal and myeloid bias of hematopoietic stem and progenitor cells (HSPCs) in both mouse and human studies, suggesting its tumor-suppressive role. On the other hand, TET2 depletion in myeloid or lymphoid cells enhances their immune function in the tumor microenvironment and remarkably augments the efficacy of anti-tumor immunotherapy. Indeed, loss of TET2 enables antigen-independent CAR-T cell clonal expansion and improves tumor infiltration. Therefore, there remains a clinical need to harness TET2 in the hematopoietic system in a tunable manner to enhance anti-cancer immunity and suppress tumor cell growth while limiting the risk of uncontrolled proliferation.
Developing nanobodies as therapeutics has emerged as a promising avenue, offering minimal toxicity and facile delivery. A nanobody is about one-tenth of the size of a full-size antibody (~15 kDa), ranking it among the smallest known antigen-binding modules. The unique structures of complementarity determining regions (CDRs), along with their smaller molecular size, allow nanobodies to penetrate deeper and more rapidly into target cells or tissues. Additionally, the high homology of nanobodies to the human family III heavy chain domain results in low immunogenicity and high tolerance, making them ideal candidates for translational therapeutic development.
In this study, we developed a set of nanobodies against human TET2. We validate the specific recognition of nanobodies to human TET2 based on cell-based imaging and biochemical immunoprecipitation approaches. Randomized mutagenesis was performed in CDRs to further improve the binding affinity between nanobodies and TET2. The specific recognition between optimized nanobodies and TET2 were further evaluated using GST-tagged recombinant protein. We then further fused the nanobodies with modular domains derived from the proteasomal degradation machinery to enable specific degradation of TET2 protein in both HEK293T and Jurkat T cell lines. We will apply this nanobody-based degradation tool in human CD19 CAR-T cells to explore its potential to increase CAR-T efficacy and enhance tumor killing. In summary, the development of nanobodies against TET2 provides a novel approach to modulate endogenous TET2 protein level and activity, setting the stage for precise epigenetic regulation in both HSPCs and immune cells to benefit cell-based therapies.
Epidemiological Analysis and Overall Survival of Leukemia in the Pediatric Population in a Developing Middle Eastern Country over 18 Years
Authors: Abdulelah Ahmed A , Abdulelah Zaid A , Al-Bitar Farah , AlQirem Lina , Al-Husni Dua' , Alhajahjeh Abdulrahman , Abdel-Razeq Hikmat , Haddadin Michael 
Published: December 2024

Introduction: Leukemia in the pediatric age group is widely regarded as the third most common malignancy and contributes to significant burden due to the resultant morbidity and mortality. Accordingly, it is undoubtedly warranted to thoroughly evaluate and consequently establish the epidemiological characteristics in developing middle eastern countries with scarce resources, such as Jordan, to achieve effective risk stratification and introduction of appropriate measures.
Methods: Extensive and comprehensive data on a cohort consisting of 2038 pediatric males and females of different nationalities residing in Jordan who were diagnosed with leukemia during the timespan of 2000-2018 was obtained from the official cancer reporting body in Jordan, the Jordan Cancer Registry. Epidemiological features and characteristics, including overall survival and crude incidence, of leukemia in the pediatric age group were evaluated through statistical analysis.
Results: A total of 2038 pediatric patient with a mean age of 7.86 ± 5.36 years old and a male predominance of 59.2% were included in the analysis. Acute lymphocytic leukemia was the most commonly encountered malignancy as reported in 68.2% of the study population, followed by acute myeloid leukemia which was reported in 21.6%. The overall survival was 94.7%, 92.5%, 92.2%, 92.1%, and 92.0% at 1-year, 2-year, 3-year, 4-year, and 5-year interval, respectively. Furthermore, a statistically significant decline in the crude incidence of pediatric leukemia in Jordan over 18 years was identified with a crude incidence estimated effect of -0.059.
Conclusion: Over a span of 18 years, leukemia in the pediatric age group in Jordan demonstrated a significant decline of approximately 5.9% in the crude incidence along with a generally comparable overall survival to the witnessed rates in the international reports.
Retrospective Study Evaluating Outcomes of Patients Treated with HIDAC123 Regimen with No Growth Factor Support Post Remission AML Treatment
Authors: Kamau James , Dadeboyina Chandrakala , Ghafari Ghazal , Straining Rachael , Hua Gwen 
Published: December 2024

Introduction: High-dose cytarabine (HiDAC) is a widely used post-remission consolidation therapy for patients with acute myeloid leukemia (AML). However, the optimal regimen for HiDAC administration remains unclear, with studies on the use of granulocyte colony-stimulating factor (G-CSF) yielding mixed results. This study aims to evaluate the safety and efficacy of the HiDAC-123 regimen without routine G-CSF support in patients who achieved first complete remission (CR) after a single cycle of induction chemotherapy.
Methods: This retrospective analysis included adult patients (≥18 years) diagnosed with AML between June 1, 2013, and June 1, 2023. All patients achieved CR or CR with incomplete hematological recovery (CRi) after one cycle of intensive induction chemotherapy. The standard HiDAC dosing was 3 g/m², with dose adjustments based on age and renal function. A total of 24 patients received 48 cycles of HiDAC-123 with G-CSF, while 51 patients received 110 cycles of HiDAC-123 without G-CSF. Primary endpoints were relapse and overall survival rates. Secondary endpoints included time to marrow recovery, incidence of documented infections, and need for platelet transfusions within the 28-day consolidation cycle.
Results: The mean age was 57.9 years in the HiDAC-123 with G-CSF group and 51.7 years in the HiDAC-123 without G-CSF group (p=0.0285). The relapse incidence was higher in the G-CSF group 54.2% versus 41.2% (p=0.292), with the average time to disease recurrence of 240 versus 343 days (p=0.0730). Overall survival rates were 41.7% versus 54.9%, respectively (p=0.285). Time to marrow recovery (WBC &gt; 1.0 and ANC &gt; 500) was faster in patients receiving G-CSF (4.00 days versus 6.85 days, p=0.000667). The incidence of infections was lower in the G-CSF group (22.9% versus 26.4%, p=0.372). The average number of platelet transfusions required was similar between the two cohorts (1.56 versus 1.6, p=0.855).
Conclusions: The HiDAC-123 regimen with G-CSF support resulted in faster marrow recovery and fewer infections but did not significantly impact relapse or overall survival rates. The study's limitations include its small sample size and retrospective design. Further prospective trials are necessary to evaluate the effects of G-CSF on the safety and efficacy of the HiDAC-123 regimen.
High-Risk TP53-Mutated Acute Myeloid Leukemia in Puerto Rico: Elevated Variant Allele Frequency and Clinical Implications
Authors: Crespo Orta Ian , Marrero Leon William , Cintron-Colon Hector R , Sanchez Paredes Dominic , Rodriguez-Arocho Cristian I. , Caceres William , Cruz-Chacon Alexis M. 
Published: December 2024

Background: Acute myeloid leukemia (AML) is a heterogeneous and aggressive hematologic malignancy with poor prognosis, particularly in patients with TP53 mutations. TP53 mutations disrupt tumor suppressor gene function, causing genomic instability, chemoresistance, and adverse clinical outcomes. Variant allele frequency (VAF) of TP53 mutations carries prognostic significance, with higher VAF (&gt;40%) being linked to worse outcomes. Despite extensive research on TP53 mutations in AML, there is a lack of knowledge regarding their prevalence and specific characteristics in the Puerto Rican community.
Methods: This is a retrospective study of newly diagnosed AML patients with TP53 mutations detected via next-generation sequencing (NGS) at San Juan City Hospital, a primary referral center for AML in Puerto Rico. We analyzed patient demographics, cytogenetics, molecular markers, and VAF of TP53 mutations. This study is compliant with the Declaration of Helsinki for Studies.
Results: Among the 184 newly diagnosed AML patients identified during the study period (2020-2024), 14% (N = 25) exhibited TP53 mutations. Within this subset, 64% were male, with a median age of 66 years. The average TP53 VAF was 47%, higher than reported in previous studies, with 65% of cases exhibiting a VAF &gt;40%. We identified complex cytogenetics in 72% of cases, with 36% having co-occurring RUNX1 mutations and 40% having 5q deletions. Additionally, 57% of the cohort had biallelic TP53 mutations. Outcome data showed only 4 patients surviving, with 2 having undergone allogeneic stem cell transplant and the other 2 currently receiving treatment.
Conclusion: This study is the first to describe TP53 mutated AML in patients from Puerto Rico. There is an elevated prevalence of TP53 VAF, biallelic mutations, and concurrent RUNX1 and 5q deletions compared to the general population. These findings suggest that Puerto Rican patients with TP53 mutated AML form a high-risk subgroup burdened by TP53 mutations. Further investigations are required to understand the reasons behind the elevated VAF in this community, considering the unique sociostructural factors influencing health on the island and existing health inequalities. Additionally, our findings highlight the necessity for targeted treatments and personalized therapeutic strategies for this high-risk group due to their connection with chemoresistance and poor prognosis. Tackling these challenges through appropriate and fair healthcare interventions is essential for improving outcomes for this vulnerable population.
Trends in Mortality Due to Hematologic Malignancies Among Patients Aged 25 and Older in the United States: Racial and Ethnic Disparities, Insights from the CDC Wonder Database
Authors: Durugu Satya R , Ahmed Faizan , Ali Hassan , Sinha Shrishti , Iqbal Sabah , Rojulpote Krishna V , Abboud Brian , Thirumaran Rajesh 
Published: December 2024

Introduction
Hematologic malignancies significantly impact mortality among adults aged 25 and older in the United States. This study investigates racial and ethnic disparities in mortality rates from 1999 to 2020.
Methods
Data from the CDC WONDER database (1999-2020) were retrospectively analyzed to calculate age-adjusted mortality rates (AAMRs) per 100,000 persons. Trends were assessed using Average Annual Percentage Change (AAPC) and Annual Percent Change (APC), stratified by race/ethnicity.
Results
Between 1999 and 2020, hematologic malignancies caused 1,463,046 deaths among adults aged 25 and older. White and Black populations had the highest AAMRs, followed by Hispanics, American Indians and Alaska Natives, as well as Asian, Asian American and Pacific Islanders. White populations saw a significant decrease in AAMR from 1999 to 2018 (APC: -1.5114; 95% CI: -1.6751 to -1.3964; p &lt; 0.001), followed by a slight non-significant increase from 2018 to 2020 (APC: 1.3750; 95% CI: -0.9371 to 2.3460; p = 0.1382). Similarly, Black populations experienced a significant decline in AAMR from 1999 to 2018 (APC: -1.5083; 95% CI: -1.7281 to -1.3535; p &lt; 0.001), with a non-significant increase from 2018 to 2020 (APC: 2.5566; 95% CI: -0.3603 to 4.1183; p = 0.0853). Hispanics saw a significant decrease in AAMR from 1999 to 2018 (APC -1.33; 95% CI: -3.46 to 2.68; P= 0.080), followed by slight non-significant increase in AAMR from 2018-2020 (APC 2.18; 95% CI: -1.38 TO 4.50; P=0.560). American Indian or Alaska Native saw decline in AAMR from 1999 - 2020 (APC -1.17; 95% CI -1.91 to -0.29; P=0.0099) while Asian or Pacific Islanders saw significant decline in AAMR from 1999-2020 (AAPC -1.52; 95% CI -1.69 to -1.24); P&lt;0.001.
Conclusion
This study highlights significant racial and ethnic disparities in mortality rates due to hematologic malignancies among adults aged 25 and older in the U.S. Despite overall declines, there remains a persistently higher mortality rate among White and Black populations compared to Hispanic, American Indian and Alaska Native, as well as Asian, Asian American, and Pacific Islander populations. These findings indicate that race and ethnicity impact survival across multiple hematologic malignancies, necessitating further investigation into the factors driving these differences. The relationship between environmental exposures and disparities in incidence and clinical presentation should be explored in future studies to develop multilevel explanatory models, investigate interventional trials, and create preventive strategies.
Clinical Analysis and Gene Mapping of 12 Children with Therapy-Related Myelodysplastic Syndrome/Acute Leukemia
Authors: Chen Xia , Zhu Xiaofan 
Published: December 2024

Objective Retrospectively analyze the clinical characteristics, regimen, prognosis and genetic profiles of the largest single-center therapy-related myelodysplastic syndrome/acute leukemia (t-MDS/AL) in China.
Methods clinical data of all pediatric patients diagnosed with t-MDS/AL since January 1,2018, were retrospectively collected and analyzed.
Results
(1) 12 pediatric t-MDS/AL patients were involved including 5 boys and 7 girls. The median age of primary and secondary tumors were 8 years old (range: 1-13 years) and 11 years old (range: 4-15 years). All patients received chemotherapy/radiotherapy after primary tumor diagnosis, and developed hematologic malignancies 6-71 months later, including 5 cases of t-MDS, 6 cases of t-AML and 1 case of t-ALL among them. Then 3 in 5 cases of t-MDS developed AML in late stage.
(2) All patients fellow up to July 1,2024. one patient received partial remission (PR) after EA induction regimen, but relapsed soon later, then gave up. 2 cases were treated with decitabine chemotherapy all with non-remission (NR). One case was treated with HAD induction regimen and NR. One case was treated with HAG regimen, NR. One case was treated with Decitabine + CAG regimen, NR. One case was treated with HAG + cladribine regimen and achieved complete remission (CR). 1 case was treated with VIA protocol, CR. One case of t-ALL was treated with induction chemotherapy (NR) in CCCG-ALL-2015 regimen. In the transplantation group, there were 6 cases, including 2 cases of direct transplantation without treatment, 3 cases of rescue transplantation with NR status and 1 case of transplantation with CR status, one patient relapsed 6 months after transplantation, and one patient relapsed 2 months after transplantation. In the non-transplantation group, there were 4 cases, 1 case of disease-free survival, 1 case of persistent NR status and 2 cases of death.
(3) The fusion gene of acute leukemia was detected in 10 patients. There were WT1 gene in 6 cases, P2RY8-CRLF2 fusion gene in 1 case, AML1-ETO fusion gene in 2 cases, MLL-AF9 fusion gene in 1 case, FLT3-ITD in 1 case and FLT3-TKD in 1 case.
(4) In the cytogenetics, only 2 cases had normal karyotype, 1 case had complex karyotype with recurrent genetic abnormalities such as t(8; 21), t(9; 11) and other chromosomal abnormalities such as 45, x,-y, etc. Another common abnormal karyotype was -17.
(5) the second-generation sequencing showed that there were 2 mutations in TP53, 2 mutations in KMT2D, 2 mutations in RUNX1,2 mutations in NRAS and 2 mutations in FLT3.
Conclusion Therapy-related hematologic malignancy is a rare disease which is caused by lots of factors. The remission rate of traditional chemotherapy is low and the mortality is high. Reducing the overlap of chemotherapy drugs, choosing new drugs, or performing transplantation directly and as soon as possible may improve the prognosis.