bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Observation of Daratumumab Based Immunochemotherapy in the Treatment of Light Chain Amyloidosis
Authors: Du Jun , Gu Xiao-Ran , Liu Jia , Lu Guang , Zhong Lu 
Published: December 2024

Purpose: Systemic light chain (AL) amyloidosis arises from the aberrant folding of monoclonal immunoglobulin light chains, resulting in the formation of amyloid proteins. These proteins are subsequently deposited in various tissues and organs, instigating structural damage, organ impairment, and relentless disease progression. Daratumumab, a fully human IgG1κ monoclonal antibody engineered to target CD38, serves as both a depleting agent for plasma cells and an immunomodulator. In 2021, daratumumab in combination with cyclophosphamide, bortezomib, and dexamethasone (D-VCd regimen) became the first formally licensed treatment for AL amyloidosis. Our study, an observational investigation involving five patients diagnosed with AL amyloidosis, aims to demonstrate the efficacy and safety of daratumumab based treatment.
Methods: This clinical observation encompasses five patients, with four undergoing renal biopsies and one undergoing a fat biopsy. All patients were diagnosed with confirmed and symptomatic AL amyloidosis and received treatment with the D-VCd regimen at our institution between August 2021 and August 2023. The treatment protocol involved administering daratumumab at a dose of 16 mg/kg, bortezomib 1.3 mg/m2, cyclophosphamide 300 mg/m2 (500 mg maximum weekly dose), and dexamethasone 20 mg intravenously. Treatment was initially administered once weekly for weeks 1 to 8, followed by every 2 weeks from weeks 9 to 24 (for all patients), and subsequently extended to every 4 weeks for up to 12 months (only for Pt 3 and Pt 4).
Results: The case series comprises five male individuals with a median age of 66 years (range, 43-73 years). Among these individuals, four patients achieved a hematologic very good partial response (VGPR), two of whom achieved a complete response (CR). The mean difference of serum free light chain (dFLC) value changed from 384.2 mg/L (range, 81.1-926.1) to 95.72 mg/L (range, 0.73-447). Conversely, one patient exhibited no discernible improvement following six months of therapy, prompting the discontinuation of daratumumab. Four patients showed cardiac and renal responses after six cycles of treatment. Remarkably, after 6 cycles of treatment, according to common terminology criteria for adverse events, (CTCAE) assessment, no patients experienced adverse reactions of grade 3 or above.
Conclusions: This study presents our clinical observation of daratumumab based immunochemotherapy for AL amyloidosis, unveiling its safety and efficacy. Notably, 80% (4/5) of patients exhibited hematologic response following six cycles of treatment, devoid of any discernible side effects. Simultaneously, an equivalent proportion of patients 80% (4/5) showcased cardiac and renal responses, underscoring the treatment's effectiveness in preserving organ function and extending patient survival.
VA Combined with Mbucy Conditioning Regimen Followed By Allo-HSCT Can Improve Survival of High-Risk AML Patients: A Prospective, Single-Center, Single-Arm Clinical Trial
Authors: Cui Wei , Chen Xiaoqian , Cui Qingya , Li Zheng , Chen Sifan , Li Mengyun , Li Xuekai , Chen Juan , Yu Yan , Wu Depei , Tang Xiaowen 
Published: December 2024

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative treatment option for high-risk acute myeloid leukemia (AML). And relapse remains a leading cause of death post transplantation due to poor survival for high risk AML patients. Therefore, how to optimal conditioning regimens to reduce the relapse rate and improve overall survival(OS) post transplant are necessary.The combination of venetoclax and azacitidine(VA) disrupts energy metabolism and targets leukemia stem cells in patients with acute myeloid leukemia.Therefore, we evaluate the safety and efficacy of VA regimen followed by modified BuCy (VA-mBuCy) as conditioning regimen for high-risk AML.
Methods: This prospective, single-center, single-arm clinical trial enrolled patients diagnosed with high-risk AML (reference 2022-AML-ELN guideline) in the First Affiliated Hospital of Soochow University (NCT05823714). All patients received the VA regimen, comprising venetoclax 200mg from day 1 to day 7 and azacytidine 75mg/m2 from day 1 to 7, followed by the mBuCy conditioning regimen(Me-CCNU 250 mg/m2/d on day -10, cytarabine 2 g/m2 every 12 h on days -9 to -8, busulfan 0.8 mg/kg every 6 h on days -7 to -5, and cyclophosphamide 1.8 g/m2/d on days -4 to -3).
Result s: From Jan 2022 to Mar 2024, a total of 20 patients were enrolled, with a median age of 47 years (range: 16 to 62 years) at the time of transplantation. All patients achieved morphological complete remission(CR).16 of the 20 patients (80%) did not achieve molecular MRD-negative CR prior to transplantation, including 5 patients with KMT2A rearrangement, 2 patients with TP53 mutations, 2 patients with Mutated NPM1 with FLT3-ITD,1 patient with CBFB-MYH11 transcript,1 patient with NUP98-HOXCB transcript,1 patient with extramedullary disease. The median time for neutropenia and thrombocytopenia recovery were 12(10-15)and 13 (10-36) days. Among the 20 patients, 4 patients developes grade Ⅰ-Ⅱacute graft-versus-host disease (GVHD) and 2 patients developed mild chronic GVHD. There were no cases of veno-occlusive disease and hemorrhagic cystitis. The incidence rates for active CMV and EBV infections were 30% (6 out of 20) and 20% (4 out of 20), respectively. However, bloodstream infections (10 out of the 20 cases) occurred frequently,which responded to antibiotics soon.There were no transplantation-related mortality. The median follow-up time was 16.5 months (3-30 months). One-year overall survival (OS) rate and leukemia-free survival (LFS) rate was 94.4% and 62.6% respectively. Two-year OS rate and LFS rate was 79.3% and 46.4% respectively.
Conclusion: In conclusion, our results suggest that VA-mBuCy conditioning regimen followed by allo-HSCT represented a valid regimen, able to provide better OS of high-risk AML patients, especially with MRD-positive status.
High Efficacy of Adding G-CSF to Venetoclax Plus Azacitidine As Front-Line Treatment in Previously Untreated Acute Myeloid Leukaemia:a Pilot Study
Authors: Shi Ting , Jian Yuan , Zhang Yanru , Liu Nian , Geng Chuanying , Wang Guorong , Zhang Zhiyao , Huang Lefu , Zhang Jiajia , Zhou Yalan , Zhou Huixing , Tang Ran , Li Wenjing , Jiang Xingran , Zhao Fengyi , Gao Wen , Huang Zhongxia , Chen Wenming , Li Xin , Leng Yun , Wu Yin , Zhu Honghu 
Published: December 2024

Background: Venetoclax plus azacitidine (VA regimen) is recommended for treatment-naive patients with acute myeloid leukaemia (AML) who are unfit for intensive chemotherapy. However, the composite complete remission rate after one cycle of VA regimen is only 43.4%, which need to be improved. Regimens containing granulocyte colony-stimulating factor (G-CSF), such as FLAG,CLAG, CAG and HAG have been used in clinical practice for many years and has shown certain efficacy. We presumed that venetoclax plus azacitidine in combination with G-CSF (referred to as the VAG regimen) could have a better composite complete remission rate while maintaining an acceptable safety profile.
Methods: All patients received induction with venetoclax (100mg d1, 200mg d2, 400 mg d3-14, orally), azacitidine (100 mg/d, d1-7, subcutaneously); and G-CSF (5ug/kg/d, d1-7, subcutaneously) in 28-day cycles. The dose of venetoclax was adjusted based on concomitant moderate or strong CYP3A inhibitors. Efficacy was evaluated by bone marrow morphology and flow cytometry on day 28 of cycle 1. The primary and secondary end point were composite complete remission, MRD and safety, respectively.
Results: A total of 37 patients with AML were enrolled between January 1, 2023, and March 31, 2024, with a median age of 68 years (range, 53 to 87). Seventeen patients (46%) had adverse risk, 10 patients (27%) had intermediate risk, 9 patients (24%) had favorable risk, and 1 patient (3%) was not available. All patients completed at least 1 cycle of treatment (range: 1-8). Three patients were lost to follow-up after one cycle and two patients died during induction. The composite complete remission rate was 63% (20/32), and 14 patients (70%) were MRD negative by flow cytometry. The composite complete remission rates for the favorable-risk group, intermediate-risk group, and adverse-risk group were as follows: 89%(8/9), 33% (3/9) and 64%(9/14). Haematological adverse events of all grades occurred in most patients. The most common non-haematological adverse events of any grade included fatigue (51%, 19/37), constipation (43%, 16/37), febrile neutropenia (30%, 11/37), and pneumonia (20%, 7/37). All adverse events could be managed and improved through dose adjustments and supportive treatment.
Conclusion:The VAG regimen achieved high rates of complete remission and MRD negativity in unfit patients with newly diagnosed AML. This combined regimen has an acceptable safety profile, with low incidence of infection. A phase 2 study of VAG regimen has completed and a phase 3 trial comparing VAG vs VA regimen is undergoing currently by us.
Mondoa Promotes Resistance to Asparaginase Treatment in B-ALL By Inducing Asparagine Synthesis
Authors: Madeira Alissia Fernandes , Brückner Christian , Segner Constantin , Kolesnikova Alisa , Sipol Alexandra , Wolf Elmar , Rad Roland , Sorensen Poul H. , Hauer Julia , Ruland Jürgen Maximilian , Burdach Stefan 
Published: December 2024

Background: Cancer cells often exhibit rapid proliferation and uncontrolled division, employing adaptations to metabolic stress to maintain homeostasis and survival. MondoA (Myc-associated factor X-like protein X-interacting protein [MLXIP]), a member of the MYC interactome, is a metabolic sensor playing an important role in cancer cell adaption to stress. Our previous work demonstrated that increased MondoA expression correlates with poor outcomes in subgroups of pediatric common acute lymphoblastic leukemia (ALL; B-precursor ALL [B-ALL]) by inducing resistance to metabolic stress (Sipol et al. BLOOD 2022).
Methods: We explored the role of MondoA in resistance to L-Asparaginase (ASNase) treatment, a major non-genotoxic therapeutic principle in pediatric B-ALL, which depletes Asparagine (Asn) in the bloodstream. Utilizing CRISPR/Cas9 technology, we generated MondoA knock-out B-ALL NALM6 cell line (MKO) to study the effects on cellular metabolism and resistance mechanisms. We tested the effect of ASNase on cell viability and performed multi-omics analyses to evaluate changes in metabolic pathways and MYC binding sites in both MKO and control cells.
Results: Our study demonstrates that MondoA induces resistance to ASNase treatment in B-ALL cell lines. In our experiments, MKO cells exhibited a 92% loss of viability upon ASNase treatment, compared to an 84% loss in control cells (N = 4). Mechanistically, MondoA knock-out resulted in a redistribution of MYC binding to promoter regions, significantly affecting the epigenome, transcriptome, and proteome of the cells. Proteomic analysis revealed reduced expression of electron transport chain (ETC) complexes and key tricarboxylic acid (TCA) cycle enzymes, resulting in lower aspartate (Asp) production, a substrate for Asparagine Synthetase (ASNS). Alpha-ketoglutarate supplementation rescued MKO cells, likely by enhancing Asp production through the TCA cycle; this effect was not observed in control cells. Additionally, we discovered that ASNase resistance partially depends on sufficient glutamine (Gln) levels, another substrate for Asn de novo synthesis. Multi-omics coherence analysis of ASNS-promoter MYC binding, transcriptome, and proteome revealed downregulation of ASNS in MKO cells. These data are supported by our previous transcriptome analysis results of MondoA knock-down in other B-ALL cell lines, Reh and 697, which showed downregulation of ASNS transcripts upon silencing MondoA expression.
Conclusion: Our findings suggest a pivotal role of MondoA in ASNase therapy-resistant B-ALL and highlight its potential as a therapeutic target to improve treatment outcomes in pediatric B-ALL by enhancing sensitivity to ASNase asparaginase therapy.
Key words: B-ALL, MondoA, L-Asparaginase resistance.
Targeted Next Generation Sequencing Is Comparable with Metagenomic Next Generation Sequencing in Hematological Malignancies with Suspected Pneumonia for Pathogenic Microorganism Detection
Authors: Tang Yishu , Yulian Xiao , He Rong , Li Xin 
Published: December 2024

Pulmonary infections are commonly observed in hematologic malignancy (HM) patients.For HM patients with low immune functionality and high susceptibility to pulmonary infections, timely identification of pathogens and administration of correct medications can greatly improve patient outcomes[1, 2].The next generation sequencing can achieve an early diagnosis of respiratory infection.To date, the systematic evaluation of the clinical use of mNGS and tNGS for pneumonia in HM patients has been insufficient.
A retrospective analysis was conducted on HM patients with suspected pneumonia admitted to the Hematology Department of The Third Xiangya Hospital between April 2019 and April 2024.A total of 234 patients were identified for analysis,including 126 patients used mNGS to detect bronchoalveolar lavage fluid(BALF）and 108 patients used mNGS to detect BALF.The purpose was to compare the diagnostic efficacy of mNGS and tNGS in pulmonary infection pathogens.
The overall microbial detection rate of mNGS and tNGS were 88.9% (112/126) and 93.5% (101/108), respectively. And there was no significant difference between them ( p = 0.217).Viruses,bacteria and fungi accounted for 42.2%(117/277), 33.9% (94/277) and 23.8% (66/277) among the microorganisms detected in mNGS, respectively. Meanwhile,Viruses,bacteria and fungi accounted for 61.0%(147/241), 21.2% (51/241) and 17.8% (43/241) among the microorganisms detected in mNGS.In order to compare the diagnostic and concordance between mNGS and tNGS.We used the final clinical diagnosis as the “gold standard”.The sensitivity, specificity, positive predictive value and accuracy of mNGS were 92.7%,37.5%,91.1% and 85.7%, respectively, compared with 97.9%,45.5%,94.1% and 92.6% for tNGS.Further more,we compared the clinical impact of mNGS and tNGS on antibiotic usage.The mNGS results led to adjustments in antibiotic usage for 63 out of the 126 patients(56.3%). Following these alterations, 56 patients (88.9%) reported significant improvements.In tNGS,there are 59 out of the 108 patients(58.4%%) adjustmented in antibiotic usage and 56 patients(94.9%) reported significant improvements.The total death of mNGS and tNGS were 9.8%(11/126) and 4.0%（4/108), respectively. There were no significant differences between the two groups (P ＞0.05).Compared to the microbial range detected by tNGS, mNGS detected an additional 14 pathogenic microorganisms, in which had a very low proportion of pathogenic microorganisms (3.6%,4/112), which did not have any adverse effects on the clinical outcomes of patients.
Collectively,we found that tNGS is comparable with mNGS in HM patients with suspected pneumonia for pathogenic microorganism detection.What's more,the ability of tNGS in guiding treatment was consistent with those of mNGS.
Humanized Anti-CD25 Monoclonal Antibody for Graft-Versus-Host Disease Prophylaxis in Older Patients Receiving Haploidentical Hematopoietic Stem Cell Transplantation
Authors: Zhang Xiaoyu , Zhai Weihua , MA Qiaoling , Feng Sizhou , He Yi , Han Mingzhe , Jiang Erlie 
Published: December 2024

Introduction
Allogeneic stem cell transplantation (SCT) for elderly patients presents difficulties due to graft-versus-host disease (GVHD) and elevated non-relapse mortality (NRM). Advancing age correlates with a higher comorbidity index, diminished performance status, and an inherently increased risk of disease, all of which negatively affect survival rates. We conducted a prospective pilot study that the addition of humanized anti-CD25 monoclonal antibody as GVHD prophylaxis for older patients with hematologic malignancies undergoing haplo-identical donor transplantation.
Method
We prospectively reported and analyzed the data of 9 patients (&gt;50 years old) with hematologic malignancies who received haplo-HSCT from Augst 2023 to April 2024. The enrolled patients were administrated with a combination of cyclosporine (CsA) or tacrolimus, mycophenolate mofetil (MMF), anti-human thymocyte immunoglobulin (ATG), MTX (15mg, +1d, 10mg, +3d, +6d,+11d), and humanized anti-CD25 monoclonal antibody (Xenopax, 1mg/kg, +1d, +4d) . This study is registered with the clinicaltrial.gov (NCT05923814).
Result
All patients achieved neutrophil and platelet engraftment (neutrophil: 14 days (11-20); platelet: 19 days (11-33). Two patient developed intestine involved grade II and III aGVHD, respectively. Of note, the two aGVHD cases resolved following treatment with a median time of 21 (14 - 28) days and no recipients died of aGVHD or associated complications. No cGVHD cases were diagnosed. No severe bacterial/fungus occurred. At a median follow-up of 271 days (range, 73 - 359), only one patient died of RSV pneumonia.
Conclusions
The humanized anti-CD25 monoclonal antibody is a promising GVHD prophylaxis for older patients receiving haplo-HSCT.
The Efficacy and Safety of the Addition of Mitoxantrone Hydrochloride Liposome in Conditioning Regimen for High-Risk Acute Myeloid Leukemia: The Short-TERM Analysis
Authors: Zhang Xiaoyu , Zhai Weihua , MA Qiaoling , Han Mingzhe , Feng Sizhou , He Yi , Jiang Erlie 
Published: December 2024

Background:
Mitoxantrone, a synthetic anthracycline agent, has demonstrated superior anti-leukemic efficacy in acute myelogenous leukemia (AML). Mitoxantrone hydrochloride liposome (Lipo-MIT) represents a novel nano-drug, showcasing promising pharmacokinetics and extending survival in animal studies when compared to standard mitoxantrone. Several studies have validated the anti-tumor effects and safety of Lipo-MIT. We review our experience with Lipo-MIT as a conditioning regimen in high-risk acute myelogenous leukemia (AML) who underwent allo-HSCT.
Method
Between October 2022 and April 2024, high-risk AML patients, achieving CR1 or CR2, applied for allo-HSCT were retrospectively enrolled in this study at Institute of Hematology and Blood Diseases Hospital, CAMS and PUMC. Patients with HSCT were conditioned on the basis of Bu/Cy. Lipo-MIT was added at beginning of conditioning regimen (30mg/m2).
Result
This study included a total 17 high-risk AML patients achieving CR1 or CR2, with median age 42 years (ranged 18-60 years), received allo-HSCT (MSD-HSCT n=9, HID-HSCT n=7, MUD n=1). Five patients (5/17) had a diagnosis of extramedullary disease. Mucositis was the main reported regimen-related toxicity (10/17), most were well tolerated and only two were evaluated severe. No graft failure occurred. It is inspiring that all patients achieved hematology complete remission (CR) (100%) and 14/17 achieved MRD clearance on reconstitution day. The incidence of acute GVHD was 29.41% (5/17), and no severe aGVHD documented. With a median follow-up of 218（89-657）days, no relapse or deaths occurred among the patients.
Conclusion
The preliminary data demonstrated the efficacy and acceptable toxicity of Lipo-MIT containing regimen for high-risk AML patients.
Safety and Efficacy of R-PAD Regimen in Patients with Severe Multiple Center Idiopathic Castleman Disease: A Retrospective Case Series
Authors: Lu Yingting , Ying Chunrong , Liu Ligen , Zhao Limin , Jiang Xuewei , Zhang Tinghua , Zhang Zhizhi , Zhou Xiang , Chang Li , Zhu Xinying , Du Chao , Yang Li 
Published: December 2024

To report the efficacy and safety of R-PAD regimen in four cases of patients with idiopathic multiple center Castleman disease (iMCD).
The clinical data of the four cases of patients met the diagnostic criteria of severe iMCD were collected, the efficacy and safety of R-PAD regimen were analyzed. The detail of R-PAD regimen is as follow: Rituximab 375mg/m2 day 1; Bortezomib 1.3mg/m2 day 1, 8, 15; Liposomal adriamycin 15mg/m2 day 1; Dexamethasone 20mg day 1-4, 9-12, 17-20. Four weeks as a course, total 4-6 courses were administered. And then, thalidomide and predinisone or dexamethasone were administered as maintenance.
Total 4 cases were enrolled, 3 female and 1 male. The median age was 45 years-old. One case was with TAFRO，1 case idiopathic plasmacytic lymphadenopathy, 1 case NOS and 1 NOS with hemophagocytic lymphohistiocytosis. The complete remission rate were 100%，and no 3 grade above adverse events were found.
R-PAD regimen might be a useful protocol as an induction regimen for patients with severe iMCD.
A Systematic Review on Efficacy and Safety Profile of Blinatumomab in Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia (R/R BCP-ALL) in Children and Young Adults
Authors: Ibrahim Ahmed , Yousaf Muhammad Abdullah , Gull Nayab , Khalid Saba , Khalid Huma , Rehman Mohammad Ebad Ur , Alliende Anna Maria Akhtar , Shafqat Aiza Binte , Malik Mustafa Nadeem , Rafae Abdul 
Published: December 2024

Introduction:
Chemotherapy for relapsed or refractory B-cell precursor Acute Lymphoblastic Leukemia (R/R BCP-ALL) is associated with a high-grade toxicity profile and in a few cases subsequent relapse in children and adolescents. However, the bispecific T cell-binding antibody blinatumomab (target CD19/CD3) has been used successfully for the treatment of R/R BCP-ALL in pediatric populations with a favorable adverse effect profile and early bridging to Hematopoietic Stem Cell Transplant (HSCT). In this study, we report a systematic review of published literature on the efficacy and toxicity profile of blinatumomab in children, including data from the real world.
Materials and Methods:
Following PRISMA guidelines, an electronic search was performed on PubMed, Embase, Cochrane Library, Web of Science, and Clinicaltrials.gov, from inception to June 2024. Eligible patients were older than 28 days and younger than 18 years with an Eastern Cooperative Oncology Group score of 2 or less. Children included in this study were required to have B-cell precursor ALL, either refractory to induction or salvage chemotherapy treatments, or with relapsed disease after chemo and/ or hematopoietic stem cell transplantation. Initially, 347 articles were identified, and we finalized 12 studies with single-agent use of blinatumomab for inclusion in our review after a thorough screening. MeSH terms were “Precursor B-Cell Lymphoblastic Leukemia-Lymphoma,” “refractory”, “relapsed”, “safety”, “efficacy”, AND “blinatumomab”.
Results:
According to the reported data, the median age (mAge) was 8.6 years. Number of patients achieving Complete Remission or Complete Remission with incomplete hematologic recovery (CR/CRh) was 322 out of 555 (58%). The pooled Minimal Residual Disease (MRD) response was observed in patients 66.5% and 70.8% of patients were able to undergo HSCT. Blinatumomab treatment showed a median Overall Survival (mOS) of 10.35 months and a median Relapse-Free Survival (mRFS) of 12.7 months. The most frequently reported greater than grade 2 adverse events (AEs) were neutropenic fever (NF), cytokine release syndrome (CRS), and neurological events like headache, altered sensorium encephalopathy, etc.
Conclusion:
The current data reinforces that single-agent immunotherapy with blinatumomab is more effective in treating R/R BCP-ALL children facilitating early transplantation, and is safer, compared to standard-of-care chemotherapy. The toxicity with blinatumomab is majorly limited to cytokine release syndrome and neurologic events but is controllable and low in number. Prospective studies with longer follow-ups and bigger sample sizes, need to be conducted, to help us better understand blinatumomab.