bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management of Acquired Hemophilia a in the Backdrop of Coronavirus Disease 19 and Multiple Myeloma
Authors: Cai Zhen , Dong Mengmeng , Zhang Jinna , Wang Jiasheng 
Published: December 2024

Background Acquired hemophilia A (AHA) is an autoimmune disorder characterized by unexpected bleeding that is likely caused by the development of clotting factor VIII inhibitors. Both virus infections and hematologic malignancies are among the possible underlying conditions for AHA because of their potential to cause immune dysfunction. Currently, the main treatments for AHA focus on achieving hemostasis and removing inhibitors, as well as managing the underlying pathology.
Case presentation Herein we present a patient who was diagnosed with AHA complicated with an emergency of osteofascial compartment syndrome. The patient experienced acute subcutaneous bleeding in his left calf during his recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Notably, the patient also had multiple myeloma (MM) and was undergoing maintenance treatment. Cases of coronavirus disease 19 (COVID-19) or MM-associated AHA are rare, and there have been no reported AHA cases with both underlying conditions. To determine the potential causes of AHA, a comprehensive analysis was conducted. Hemostatic and immunosuppressive treatments were administered based on the underlying etiology and relevant examination findings, ultimately resulting in a successful cure for AHA.
ConclusionThis clinical case highlights the occurrence of severe bleeding in an MM patient who was undergoing maintenance therapy and contracted SARS-CoV-2 infection. The patient was subsequently diagnosed with AHA. Given the presence of multiple immune disorder factors, clinicians should carefully analyze the potential contributing factors to guide treatment decisions and prevent future recurrences.
Combining Melphalan or Thiotepa with an Intensive Conditioning Regimen Significantly Reduces Relapse Rates in Minimal Residual Disease-Positive (MRD+) Pediatric Acute Myeloid Leukemia Patients Post Haploidentical Hematopoietic Stem Cell Transplantation
Authors: Zhu Huili , Wei Zhijie , Lu Peihua 
Published: December 2024

Introduction
Acute myeloid leukemia (AML) is the second most common hematological malignancy in children, representing 15% to 20% of childhood leukemia cases. Minimal residual disease (MRD) status before transplantation is a key prognostic factor in pediatric AML. MRD positivity (MRD+) is linked to lower survival rates and higher relapse rates.
Methods
We retrospectively analyzed 18 pediatric AML patients with MRD+ who underwent haploidentical hematopoietic stem cell transplantation (haplo-HSCT) at our hospital from January 2020 to November 2023. Among them, 8 had the RUNX1::RUNX1T1 fusion gene, 1 had KMT2A::MLLT3, 1 had KMT2A::MLLT6, and 1 had KMT2A::ENL. MRD was assessed by flow cytometry. The median age was 7.5 years (range: 2 to 17 years) with a male-to-female ratio of 11:7. The median pre-transplant MRD was 2.26% (range: 0.01% to 89.9%). There were 7 cases in first complete remission (CR1), 3 in second complete remission (CR2), 1 in partial remission (PR), and 7 with no remission (NR). All received myeloablative conditioning with melphalan or thiotepa: 14 with Busulfan/Cyclophosphamide (Bu/Cy), 3 with Busulfan/Fludarabine (Bu/Flu), 10 with melphalan, and 8 with thiotepa. Melphalan was given at 110 mg/m² and thiotepa at 5-7.5 mg/kg, both on days -3 and -2. The median follow-up was 37.11 months (range: 4.19 to 53.71 months).
Results
All patients achieved 100% white blood cell engraftment with a median time of 15 days (range: 10 to 19 days) and platelet engraftment with a median of 10 days (range: 7 to 21 days). At one month post-transplant, all had negative bone marrow MRD. No relapse occurred, but 3 patients died (2 from pneumonia and 1 from grade III acute graft-versus-host disease [aGVHD]). All 3 were in NR status pre-transplant. The estimated 4-year overall survival (OS) rate was 83.3%. Grade III-IV aGVHD occurred in 11.11% of patients, and extensive chronic graft-versus-host disease (cGVHD) in 16.67%. Mucositis was noted in 4 patients, with only 1 case being moderate to severe. Cytomegalovirus (CMV) reactivation occurred in 66.67% and Epstein-Barr virus (EBV) in 33.33% of patients, with median onset times of 28 and 32 days, respectively.
Conclusions
In pediatric AML patients with MRD+, haplo-HSCT using a conditioning regimen that includes melphalan or thiotepa resulted in 100% engraftment of white blood cells and platelets without an increased incidence of mucositis. No relapse of the primary disease was observed during the follow-up period, and the estimated 4-year OS rate was 83.3%. The rates of CMV and EBV reactivation, as well as the incidence of GVHD did not increase. These findings suggest that this regimen can effectively reduce the risk of post-transplant relapse and improve survival outcomes.
The Haploid Hematopoietic Stem Cell Transplantation Combined with Umbilical Cord Blood Transfusion in the Treatment of Hematological Malignancies - a Multicenter, Single-Arm Prospective Trial
Authors: Mei Chen , Ren Yanling , Wang Shasha , Xu Yu , Huang Xianbo , Fan Cuihua , Shao Yanping , Qian Jiejing , Tong Hongyan 
Published: December 2024

[Background] Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is increasingly utilized as a curative approach for various hematologic malignancies. However, major challenges in haplo-HSCT include a high incidence of graft-versus-host disease (GVHD), frequent occurrences of engraftment failure and transplant rejection. These issues are exacerbated by the increasing age of donors (≥ 40 years). There is an urgent need for more refined treatment strategies that mitigate the negative impact of older donors (≥ 40 years) on patient outcomes. Recent studies have demonstrated that haplo-HSCT combined with umbilical cord blood (UCB) transfusion has achieved rapid engraftment, low incidence of GVHD, and a low rate of disease recurrence in the treatment of hematological malignancies. We therefore conducted a study of haplo-HSCT combined with UCB in the treatment of hematological malignancies.
[Methods] In this multicenter, single-arm trial, patients diagnosed with hematological malignancies, who were planned to undergo haplo-HSCT with donors aged 40 years or older, from 3 different tertiary medical centers in China were included. The patients were received the infusion of UCB within 24 hours following the completion of haplo-HSCT. The UCB was HLA matched (≥ 5/10 alleles) and preference was given to blood group matching. The primary endpoint was the 100-day cumulative incidences of grade II-IV aGVHD. The secondary endpoints were the day of neutrophil and platelet engraftment. Here, we report results of the interim analysis.
[Results] As of June 2024, a total of 36 patients were enrolled, with a median age of 26 years (range, 14-65 years), 23 males and 13 females. The disease diagnoses included myeloid malignancies (20/36, 55.6%) and lymphoid malignancies (16/36 44.4%). The disease status of 3 patients were no remission, 4 patients were MRD positive and 29 patients were complete remission. The median age of donors were 50 years (range, 40-59 years). The 100-day cumulative incidences of grade II-IV aGVHD were 22.2% (8/36). The median day of neutrophil and platelet engraftment was at day 12 (range, 10-24) and day 13 (range, 10-42), respectively.
[Conclusion] This study showed that haplo-HSCT combined with UCB can effectively reduce incidence of grade II-IV aGVHD and achieve rapid engraftment in patients with hematological malignancies.
Trends in Multiple Myeloma Incidence and Mortality (1991-2021) in the United States: A Comprehensive Analysis of Gender and State-Level Disparities
Authors: Bhanushali Charmi , Mukhtiar Vaibhavi , Mehta Mansi , Bhanushali Vidhi , Cabot Clara Elizabeth Rose , Fatoki Raleigh A , Seetharaman Kala 
Published: December 2024

Introduction:
Multiple myeloma contributes to cancer-related morbidity and mortality in the United States accounting for about 2% of cancer related deaths every year. However, with the advent of targeted therapeutics, the overall survival of myeloma has increased over the years. Nevertheless, access to novel therapeutics is not uniform across different states of the nation. In this study, we aim to analyze the incidence, mortality, and trends in multiple myeloma from 1991 to 2021, with a focus on trends at both the national and state levels along with sex-based disparities.
Methods:
TheGlobal Burden of Disease database was used to extract age-standardized incidence (ASIR), age standardized mortality rates (ASMR), and disability-adjusted life years (DALYs) of multiple myeloma from 1991 to 2021 for both males and females across all states of the United States. Mortality-to-incidence indices (MIIs) were calculated using the ratio of incidence and mortality rates. Disparities related to gender, geography, and time were analyzed and trends were analyzed using joinpoint regression analysis.
Results:
The ASIR of multiple myeloma in the United States decreased by 10.33% between 1991 and 2021, with a more significant decline in females (15.95%) compared to males (8.18%). Similarly, ASMR for both sexes combined fell by 14.61%, with a more substantial decrease in females (18.52%) than in males (13.5%). Overall, the MIIs decreased by 4.78%. The DALYs for both sexes combined declined by 23.03%, with a larger reduction observed in females (26.26%) compared to males (21.79%).
There were notable variations in these trends across states over the 30-years. Changes in ASIR ranged from a 45.62% increase in Kansas to a 49.23% decrease in New Hampshire. ASMR decreased for both sexes in all states from 1991 to 2021, varying from a 1.14% decrease in Oklahoma to a 32.37% decrease in the District of Columbia. DALYs decreased in all states, ranging from a 37.54% reduction in the District of Columbia to 8.05% reduction in New Mexico.
Conclusion:
This analysis highlights gender-based and region-based disparities in the United States in multiple myeloma morbidity and mortality. While the prognosis for multiple myeloma has significantly improved over the years due to therapeutic advances, there has been a significant difference in health indices such as DALYs and ASMR across genders and regions respectively. These findings enhance our understanding of the gender and state level disparities of multiple myeloma underscoring the importance of targeted studies to explore the reasons behind these epidemiological differences.
Correlation Analysis of DNA Methylation Level and Clinical Characteristics in Pediatric MDS Patients
Authors: Yang Wenyu , Liu Chenmeng , Li Xiaolan , Wan Yang , Ren Yuanyuan , Liu Fang , Guo Ye , Zhu Xiaofan 
Published: December 2024

Objective: Pediatric myelodysplastic syndrome (MDS) has a considerably lower prevalence compared to MDS in adults, with an annual incidence rate ranging from 1 to 2 cases per million children.This study aimed to find clinical indicators that were associated with different methylation levels and prognosis.
Methods: The clinical data of 20 pediatric MDS patients with DNA samples admitted to our center from April 2017 to December 2020 were retrospectively analyzed, Quantification of DNA methylation was performed using an Illumina Infinium MethylationEPIC Beadchip platform (Illumina). Unsupervised hierarchical clustering of the most variable CpG sites across all MDS samples classified three clusters, low methylation (LM), intermediate methylation (IM), and high methylation (HM).
Results: 20 cases of pediatric MDS were admitted to our study，according to WHO 2016 myeloid tumor diagnosis criteria RCC 7 RAEB 10 and RAEB-T 3cases. The median age of onset was 7.9 years old (3.5-14.9 years) among the 20 cases, including 13 males and 7 females. At diagnosis, the median WBC count was 13.0×109/L (1.4-130.0×109/L), the median platelet count was 81.1×109/L (18.0-254.0×109/L) the median MCV was 95.5fl (79.2-124.1fl) and the median RDW-SD 56.7fl (13.7-109.6), RDW-CV 19.6 (13.7-57.2). Chromosome karyotype abnormalities were found in 80% (16/20) of patients, 9 cases(56.3%) had chromosome 7 deletion. Genomic DNA methylation levels were classified into three groups: 2 cases in the LM subgroup,9 cases IM subgroup, and 9 cases in the HM subgroup. 16 cases were given hemotopoietic stem cell transplantation(HSCT), There were significant differences in counts of white blood cell(WBC), neutrophil and platelets in different methylation subgroups (P&lt;0.05). All patients were followed up to July 2024, 2 cases lost follow-up. The median overall survival(OS) was 63.6%±11%, the median event free survival(EFS）was 64.6%±18.8%. There were no differnce in OS and EFS among different methylation groups. Compared with the LM and IM subgroup, the HM group had higher WBC (5.17 vs 2.5, 0.01) and neutrophil absolute value (3.03 vs 0.52,0.025), and lower platelet (47 vs 76, 0.067).
Conclusions: Pediatric MDS patients with HM at diagnosis had higher WBC counts and neutrophil, and with lower platelets. In our study There was no significant difference in survival among different methylation groups.
Outcomes and Prevalence of Complications in Patients with Sickle Cell Disease Receiving Blood Transfusions: Insights from the National Inpatient Database 2016-2021
Authors: Mekonen Yemesrach , Barrera Nelson , Chapiolkina Volha , Tole Camila , Guevara Nehemias , Sanchez Jorge , Sangam Sangam , Newman Azana , Bermudez Marco , Fulger Ilmana 
Published: December 2024

Introduction
Red blood cell (RBC) transfusion is frequently used in sickle cell disease (SCD) patients to help prevent and treat various acute and long-term medical issues. Since curative therapies are not a viable option for the majority of SCD patients, disease-modifying medications that can slow the progression of the disease and blood transfusion are the main focus of the current management of SCD. Although red blood cell transfusions have the potential to save lives, we are concerned about the severe side effects of transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) in this patient population. In individuals with SCD, TRALI and TACO are frequently misdiagnosed, mainly because the symptoms resemble those of acute chest syndrome. We aim to describe the outcome and prevalence of complications in hospitalized SCD patients receiving blood transfusions.
Methodology
Our study was comprehensive, utilizing the National Inpatient Sample data from 2016 to 2021 to perform a retrospective analysis. We identified and analyzed patients hospitalized with a diagnosis of sickle cell disease and those who received blood product transfusions. The primary outcome was in-hospital mortality, and secondary outcomes included length of stay (LOS), the total cost of hospitalization, and the prevalence of TRALI and TACO.
Results
There were 94,400 admissions for sickle cell disease. Among these, 19,960 patients received blood transfusions during hospitalization. The mean age in the transfusion group was 34 ± 16 years, with 57% female. TRALI was reported in only 0.13% of patients, while TACO occurred in 1.8% of patients. The odds of mortality for sickle cell patients without transfusion [aOR 1.04; 95% CI 1.03-1.05; p=0.001] and the odds of mortality in the transfusion group were similar [aOR 1.04; 95% CI 1.02-1.05; p=0.001]. The mean LOS was 4 ± 3 days for the non-transfusion group and 6 ± 3 days for the transfusion group. The total cost of hospitalization was $52,500 for the non-transfusion group versus $75,213 for the transfusion group.Conclusion
Our study on patients admitted with sickle cell disease who received blood transfusions has significant implications for patient care. We found that mortality did not differ significantly between transfused and non-transfused patients. However, patients who received transfusions had a prolonged length of stay and higher total hospitalization costs. Moreover, the prevalence of TRALI and TACO was low in transfused patients. These findings emphasize the importance of careful consideration when deciding on blood transfusions for sickle cell disease patients, urging healthcare professionals to reassess their practices and strive to provide the best care possible.
Anomalous Peaks Observed in the Mass Spectrometry of Light Chains Correlate with the Diagnosis of AL Amyloidosis
Authors: Dong Mengmeng , Xiao Xiao , Cai Zhen , Wang Jiasheng , Yang Yang , Zheng Gaofeng , Yang Li , Yan Haimeng 
Published: December 2024

Background:
Systemic light chain (AL) amyloidosis is a disease characterized by the misfolding of monoclonal immunoglobulin light chains into amyloid proteins. These misfolded proteins deposit in tissues and organs, causing structural damage and organ dysfunction. Pathological biopsy is the gold standard for diagnosing AL. Mass spectrometry, as a recently developed method for detecting light chains, is increasingly being utilized to assist in the diagnosis of plasma cell disorders.
Method:
Matrix-Assisted Laser Desorption Ionization time-of-flight (MALDI-TOF) is used to detect λ and κ light chains in the peripheral blood of patients. This method identifies λ and κ light chains based on the differences in their mass-to-charge ratios.
Result:
In patients suspected of having plasma cell disorders, we utilized MALDI-TOF to detect light chains in their peripheral blood. We observed that the presence of abnormal peaks in the mass spectrum is often associated with a diagnosis of amyloidosis. Among the 56 individuals tested, 9 exhibited abnormal peaks in the light chain profiles: 5 with amyloidosis, 3 with multiple myeloma (MM), and 1 with monoclonal gammopathy of undetermined significance (MGUS). Of these 56 individuals, 6 were diagnosed with AL based on pathological findings, and 5 of them showed abnormal peaks in peripheral blood light chain mass spectrum.
Therefore, based on our estimation with a limited sample size, using pathological diagnosis as the gold standard, the sensitivity of diagnosing amyloidosis through MALDI-TOF detection of light chain abnormal peaks is 83.3%, and the specificity is 92.2%. However, due to our limited sample size, the sensitivity and specificity values require validation through testing with a larger sample size.
The specific significance of the differential peak has not been thoroughly investigated. Based on published literature and the positions of the peaks, it is hypothesized that this may be associated with glycosylation of light chains, which could result in an abnormal protein structure. We intend to further investigate this in our future research.
Conclusion and significance:
The diagnosis of AL amyloidosis primarily depends on pathological assessment via tissue biopsy. Our research indicates that the detection of abnormal peaks in peripheral blood using MALDI-TOF for light chains demonstrates good sensitivity and accuracy for the diagnosis of AL amyloidosis. Although the sample size remains relatively small, our findings offer potential insights and approaches for developing non-invasive diagnostic methods for amyloidosis.
Daunorubicin and Cytarabine 3+5 Combined with Venetoclax in De Novo Patients with Acute Myeloid Leukemia: A Single-Center, Open-Label, Controlled Study
Authors: Huang Zhenqi , Dong Xinyi , Wu Wei , Ruan Min , Ge Jian , Long Zhangbiao 
Published: December 2024

Background: Daunorubicin and cytarabine 3+5 were the standard first-line induction chemotherapy in newly diagnosed acute myeloid leukemia currently, whereas the complete remission rate is only 70%. In order to detect a more effective and tolerated induction regime, we designed a novelty regime of daunorubicin and cytarabine 3+5 combined with venetoclax as the induction chemotherapy in de novo patients with acute myeloid leukemia, and to evaluate the efficacy and safety of this regime.
Methods: We conducted a single-institutional, non-randomized, open-label, controlled study. We enrolled patients with de novo AML aged between 18 and 60 years and ECOG score was 0-2. The test group received daunorubicin 40mg/m2/d, d1~d3; cytarabine 100mg/m2/d, d1~d5, venetoclax 100mg d1, 200mg d2, 400mg d3 ~d14, whereas the control group received daunorubicin 60mg/m2/d, d1~d3 and cytarabine 100mg/m2/d, d1~d7. The induction chemotherapy length of the two groups was 28 days per cycle, and all patients received one or two cycles of induction chemotherapy. Subsequently, these patients received sustained chemotherapy or hematopoietic stem cell transplantation. The primary endpoint was the complete remission rate after two cycles of induction therapy, the secondary endpoints were adverse events and overall survival.
Results: Between December 2021 and June 2024, forty patients with newly diagnosed acute myeloid leukemia at the first affiliated hospital of Anhui Medical University were enrolled. Twenty-one patients were in the test group and nineteen in the control group. There were 25 males and 15 females, with a median age of 46 (range 18-59) years old in both groups. The baseline characteristics were all balanced differently between the two groups. After two cycles of induction chemotherapy, the complete remission rate was 95% (20 of 21 patients) in the test group, whereas the complete remission rate was 68% (13 of 19 patients) in the control group (P＝0.0395). The most common hematological adverse events were neutropenia, thrombocytopenia, and anemia. The most frequent non-hematological adverse events include infections, vomiting, diarrhea, and hypokalemia. Infection rate was 95% in the test group and 100% in the control group. Fatal adverse events did not occur in both groups. At the median follow-up of 14 months, the median overall survival was not reached in both groups. The estimated 2-year overall survival rate was 72% in the test group and 58% in the control group, respectively.
Conclusions: Daunorubicin and cytarabine 3+5 combined with venetoclax is an effective induction therapy for de novo patients with acute myeloid leukemia, and is well tolerated for these patients in the induction chemotherapy periods.