Annals of Hematology最新文献

{"title":"Understanding gut Microbiome changes in Korean children, adolescents, and young adults with hematologic malignancies.","authors":"Meerim Park, Jongheon Jung, Jun Ah Lee, Eunyoung Lee, Hyewon Lee, Hyeon Seok Eom, Hyeon Jin Park","doi":"10.1007/s00277-025-06293-2","DOIUrl":"https://doi.org/10.1007/s00277-025-06293-2","url":null,"abstract":"<p><p>We investigated whether changes in the gut microbiome composition are associated with infections and immunologic complications during the treatment of Korean children, adolescents, and young adults (AYAs) with hematologic malignancies. We analyzed stool samples from 26 patients and 10 healthy siblings using 16 S rRNA gene sequencing. At diagnosis, patients exhibited a lower abundance of Lachnospiraceae and a higher abundance of Enterococcaceae than their healthy siblings. Both the Chao1 and Shannon diversity indices declined from diagnosis to the end of induction chemotherapy. Patients with fever during induction had a lower baseline microbial diversity and higher Ruminococcus g4 abundance than those without fever. The use of either meropenem or piperacillin/tazobactam during induction was correlated with reduced richness and altered composition of the gut microbiome after induction. The Chao index and beta diversity of stool samples significantly differed before conditioning when compared with those of healthy siblings. During allogeneic hematopoietic stem cell transplantation, both the Chao1 and Shannon diversity indices significantly decreased on day 14 but recovered by day 60. Our study highlights the role of gut microbiome diversity and compositional structure in influencing treatment outcomes in children and AYA with hematologic malignancies, providing the information required to improve the gut microbiome configuration and treatment outcomes.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment patterns and healthcare resource utilization in ruxolitinib-treated patients with myelofibrosis with and without anemia: a real-world analysis","authors":"Tom Liu,&nbsp;Mirko Fillbrunn,&nbsp;Shiyuan Zhang,&nbsp;Jingyi Chen,&nbsp;Weilong Li,&nbsp;Julia Platt,&nbsp;Nicole Niehoff,&nbsp;Gautam Sajeev,&nbsp;James Signorovitch","doi":"10.1007/s00277-025-06279-0","DOIUrl":"10.1007/s00277-025-06279-0","url":null,"abstract":"<div><p>Anemia affects many patients with myelofibrosis and is associated with poor prognosis. The Janus kinase inhibitor ruxolitinib is often used in myelofibrosis but may cause or worsen anemia. Using healthcare claims data from the IQVIA PharMetrics Plus database, this retrospective analysis evaluated healthcare resource utilization (HCRU), healthcare costs, and treatment patterns in ruxolitinib-treated patients with myelofibrosis stratified by anemia diagnosis prior to ruxolitinib initiation. Of 11,499 patients diagnosed with myelofibrosis between January 2011 and December 2022, 481 had ≥ 1 ruxolitinib claim on or after the myelofibrosis diagnosis date and were included in this analysis. Mean follow-up was 2.0 years. At baseline, anemic patients (<i>n</i> = 257) were older (mean age, 60.2 vs. 56.8 years; <i>P</i> &lt; 0.001) and had a higher mean Charlson Comorbidity Index (1.0 vs. 0.5; <i>P</i> &lt; 0.001) than nonanemic patients (<i>n</i> = 224). During follow-up, anemic patients exhibited higher median annual all-cause HCRU (inpatient admissions, 0.3 vs. 0.0 [<i>P</i> &lt; 0.001]; outpatient visits, 40.0 vs. 20.0 [<i>P</i> &lt; 0.001]; emergency department visits, 0.4 vs. 0.0 [<i>P</i> &lt; 0.010]) and also had numerically higher median annual all-cause total healthcare costs ($198,491 vs. $170,419; <i>P</i> = 0.549) and medical costs ($44,830 vs. $12,017; <i>P</i> = 0.638) but significantly lower median annual total pharmacy costs ($129,381 vs. $136,686; <i>P</i> &lt; 0.050), compared with nonanemic patients. Ruxolitinib discontinuation rates were higher and median time to discontinuation was approximately 1 year earlier in anemic patients (14.1 vs. 23.8 months; <i>P</i> &lt; 0.010). In conclusion, patients with myelofibrosis and baseline anemia who are treated with ruxolitinib may be an HCRU-intensive population, suggesting a potential need for alternative treatments that reduce their medical resource burden.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"104 3","pages":"1605 - 1616"},"PeriodicalIF":3.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-025-06279-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The validation of advanced-stage Hodgkin lymphoma international prognostic index (A-HIPI) in Turkish patients with classical Hodgkin lymphoma","authors":"Oguzhan Koca,&nbsp;Berk Ozyurt,&nbsp;Aysenur Umar,&nbsp;Deniz Ozmen,&nbsp;Tugrul Elverdi,&nbsp;Ayse Salihoglu,&nbsp;Muhlis Cem Ar,&nbsp;Zafer Baslar,&nbsp;Ahmet Emre Eskazan","doi":"10.1007/s00277-025-06292-3","DOIUrl":"10.1007/s00277-025-06292-3","url":null,"abstract":"<div><p>In advanced-stage classical Hodgkin lymphoma (cHL), the prognosis has improved due to combination chemotherapy and PET/CT-guided treatment modification, resulting in a decreased prognostic capacity of IPS models. A novel model, A-HIPI, was found to be superior to IPS in predicting prognosis. In this study, we aimed to validate the A-HIPI model among Turkish cHL patients and compare its performance with other clinical prediction models. We retrospectively evaluated patients diagnosed with advanced-stage cHL between 2005 and 2018 at Istanbul University-Cerrahpaşa. We used IPS-7, IPS-3, and A-HIPI scores to calculate the C-index (Harrell’s Concordance Index) for discrimination; calibration intercept, and calibration slope for calibration. The models were compared using Akaike’s Information Criterion (AIC). Two hundred and seven patients were enrolled with a median follow-up of 75 months, 37 patients (17.9%) died. The 5-year PFS and OS were 66.6% and 84.9%, respectively. All three models were found to be prognostic for PFS and OS. The A-HIPI model was well-calibrated for PFS and OS in patients aged ≤65 years, but not calibrated for patients aged &gt; 65 years. With A-HIPI, the respective C-index for PFS and OS was 0.605 and 0.740; whereas, for IPS-7 it was 0.598 and 0.684, and for IPS-3 it was 0.624 and 0.705. The lowest AIC value for OS was observed with the A-HIPI. The lowest AIC value for PFS was observed with IPS-3. This study validated the A-HIPI model in a homogeneous patient group for treatment protocol, with all follow-ups performed at a single center after the early 2000s in Turkey. The A-HIPI model demonstrated better performance than other models, except for patients aged &gt; 65 years. A new clinical prediction model is needed for patients &gt; 65 years, as IPS models are out of date and A-HIPI has not been validated for this group.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"104 3","pages":"1765 - 1775"},"PeriodicalIF":3.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-025-06292-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-CD20 maintenance strategies to face the challenge of COVID-19 pandemic in follicular lymphoma: results from the R-FolSTOP multicentre Italian study","authors":"Alessia Castellino,&nbsp;Lorenzo Comba,&nbsp;Laura Bertolotti,&nbsp;Carola Boccomini,&nbsp;Michele Clerico,&nbsp;Paolo Nicoli,&nbsp;Anna Vanazzi,&nbsp;Fulvia Fanelli,&nbsp;Tommasina Perrone,&nbsp;Francesco Marchesi,&nbsp;Federica Cocito,&nbsp;Michele Merli,&nbsp;Sara Bigliardi,&nbsp;Bianca Mecacci,&nbsp;Valentina Bozzoli,&nbsp;Gloria Margiotta-Casaluci,&nbsp;Erika Meli,&nbsp;Antonella Anastasia,&nbsp;Lucia Farina,&nbsp;Ombretta Annibali,&nbsp;Annarita Conconi,&nbsp;Sara Rattotti,&nbsp;Sara Galimberti,&nbsp;Claudia Castellino,&nbsp;Massimo Massaia","doi":"10.1007/s00277-025-06295-0","DOIUrl":"10.1007/s00277-025-06295-0","url":null,"abstract":"<div><p>The SARS-CoV2 pandemic has posed unprecedented challenges between temporary or permanent discontinuation of immunosuppressive treatment to protect patients, or disease control prioritization by not interrupting treatment. Maintenance treatment with anti-CD20 monoclonal antibodies (MoAbs) improves progression-free survival (PFS) in follicular lymphoma (FL), but also impairs anti-SARS-CoV2 immune response. This challenge has been addressed in Italy by temporary, definitive or no discontinuation of anti-CD20 treatment. We report the outcome of 539 FL patients receiving anti-CD20 MoAbs (rituximab in 431, obinutuzumab in 108), which were temporarily discontinued in 150 patients (group A), definitively discontinued in 166 (group B), or uninterrupted in 223 (group C). In the overall cohort, the 3-year progression-free survival (3y PFS) and 3-year overall survival (3y OS) rates were 80% and 88%. PFS and OS were significantly better in group A compared to group B and C (<i>p</i> = 0.01). Induction chemoimmunotherapy significantly influenced OS: the 3y OS was 91% vs 85% in CHOP vs bendamustine treated patients (<i>p</i> = 0.04), while the 3y OS was 90% vs 77% in rituximab vs obinutuzumab treated patients (<i>p</i> = 0.002). SARS-Cov2 infection was the main cause of death (67% of cases). Vaccination with multiple doses demonstrated to be clinically helpful, with impact on OS.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"104 3","pages":"1655 - 1667"},"PeriodicalIF":3.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-025-06295-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MYC networks associate with decreased CD8 T-cell presence in diffuse large B-cell lymphoma and may be addressed by the synergistic combination of AZD4573 and Selinexor - a preliminary analysis.","authors":"Alison C Rutz, Kennedee S Weber, Aidan L Forberg, Adam Nik, Jordan Unrau, Ainslee J Hemmen, Michael Minicozzi, Keenan T Hartert","doi":"10.1007/s00277-025-06298-x","DOIUrl":"https://doi.org/10.1007/s00277-025-06298-x","url":null,"abstract":"<p><p>Diffuse Large B-cell Lymphoma (DLBCL) is a genomically-heterogenous disease affecting over 70,000 patients per year that presents a clinical challenge despite the success of frontline regimens and second-line Chimeric Antigen receptor T-cell (CAR-T) therapy. Recently, genomic alterations and tumor microenvironment features associated with poor CAR-T response have been identified, with MYC amplification emerging in new analyses. This retrospective analysis aimed to integrate various data to identify genomic partnerships capable of providing added clarity and actionable treatment targets within this population. Publicly-available data were analyzed for differential expression based on MYC, 24-month event-free survival (EFS24) status, and CAR-T response. Notable T-cell partner genes such as IL7R (FDR = 0.00150) and CD58 (FDR = 5.375E-06) and cell death mediators such as PDCD1LG2 (FDR = 4.061E-06) were significantly lost in patients with High/Altered MYC that also failed EFS24. CD8 T-cell presence was also significantly lower in High/Altered MYC de-novo patients (p = 0.00112) and CAR-T non-responders (p = 0.00835). De-novo patients with both High/Altered MYC and CD8 T-cell absence faced a significantly inferior survival compared to counterparts with only one factor or neither (p = 0.0226). rrDLBCL patients reflected similar oncogenic pathways associated with greater scRNA MYC expression. In vitro application of the CDK9 inhibitor AZD4573 and XPO1 inhibitor Selinexor significantly reduced DLBCL cell line viability as single agents and produced synergistic results when applied in combination. Our analysis presents key associations between the MYC oncogene and depleted TME presence capable of providing clarity within the evolving precision CAR-T treatment landscape.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TP53 deletion is associated with poor survival of adult ALK-positive ALCL patients receiving CHOP-based chemotherapy","authors":"Seiichiro Katagiri,&nbsp;Daigo Akahane,&nbsp;Kunihiko Takeyama,&nbsp;Norihide Sato,&nbsp;Nobuyuki Takayama,&nbsp;Jun Ando,&nbsp;Hideaki Nitta,&nbsp;Masaaki Noguchi,&nbsp;Ken Naganuma,&nbsp;Shuji Momose,&nbsp;Takayuki Tabayashi,&nbsp;Masahiro Kizaki,&nbsp;Hiroshi Kawada,&nbsp;Yara Yukie Kikuti,&nbsp;Joaquim Carreras,&nbsp;Naoya Nakamura,&nbsp;Akihiko Gotoh","doi":"10.1007/s00277-025-06297-y","DOIUrl":"10.1007/s00277-025-06297-y","url":null,"abstract":"<div><p>In most cases of anaplastic lymphoma kinase–positive anaplastic large cell lymphoma (ALK + ALCL), long-term survival is achieved using CHOP therapy. However, some cases have a poor prognosis. Here, we investigated the clinical impact of <i>TP53</i> deletion on adult ALK + ALCL patients via a multicenter, retrospective analysis. <i>TP53</i> deletion was evaluated by fluorescence in situ hybridization (FISH) using paraffin sections of lymphoma samples. To re-evaluate the FISH results, whole genome copy number changes were analyzed in DNA extracted from paraffin sections using OncoScan analysis. Fourteen patients treated with first-line chemotherapy enrolled at six centers were analyzed. All patients received CHOP-based therapy as initial therapy. The 5-year progression-free survival (PFS) and overall survival (OS) of the 14 patients were 28.6% (median 7 months) and 57.1% (median 99 months), respectively. FISH analysis revealed 6 (43%) patients were positive for <i>TP53</i> deletion (deletion group) and 8 (57%) were negative (non-deletion group). All six patients in the deletion group were diagnosed at an advanced stage; five were refractory to initial treatment, one relapsed after treatment, and all patients died of ALK + ALCL. The median PFS was 3.5 months in the deletion group and 76 months in the non-deletion group. The median OS was 7 months in the deletion group and has yet to be confirmed in the non-deletion group. OncoScan analysis showed <i>TP53</i> copy number reduction in the deletion group and no <i>TP53</i> copy number abnormalities in the non-deletion group. This study suggests that <i>TP53</i> deletion is a poor prognostic factor in ALK + ALCL treated with CHOP-based therapy.\u0000</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"104 3","pages":"1801 - 1806"},"PeriodicalIF":3.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-025-06297-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gilteritinib versus salvage chemotherapy in predominantly Asian patients with relapsed/refractory FLT3-mutated acute myeloid leukemia: a regional analysis of COMMODORE in China, South-East Asia, and Russia","authors":"Bin Jiang,&nbsp;Jian Li,&nbsp;Ligen Liu,&nbsp;Xin Du,&nbsp;Hao Jiang,&nbsp;Jianda Hu,&nbsp;Xiaoxi Zeng,&nbsp;Taishi Sakatani,&nbsp;Masanori Kosako,&nbsp;Yaru Deng,&nbsp;Larisa Girshova,&nbsp;Sergey Bondarenko,&nbsp;Lily Wong Lee Lee,&nbsp;Archrob Khuhapinant,&nbsp;Elena Martynova,&nbsp;Nahla Hasabou,&nbsp;Jianxiang Wang","doi":"10.1007/s00277-025-06235-y","DOIUrl":"10.1007/s00277-025-06235-y","url":null,"abstract":"<div><p>\u0000 The COMMODORE study demonstrated the efficacy and safety of gilteritinib versus salvage chemotherapy (SC) treatment in a predominantly Asian population with relapsed/refractory (R/R) <i>FMS</i>-like tyrosine kinase 3 (<i>FLT3</i>)-mutated(^mut+) acute myeloid leukemia (AML); here we present an exploratory analysis of the study stratified by region (China, South-East Asia and Russia). COMMODORE was a Phase 3, open-label, randomized (1:1), multicenter trial. There were 151, 50, and 33 patients in the China, South-East Asia, and Russia cohorts, respectively. Patients treated with gilteritinib had prolonged median overall survival (OS) versus SC-treated patients in all regions (China: 10.0 vs. 5.7 months, HR [95% CI]: 0.614 [0.385, 0.981]; South-East Asia: 7.8 vs. 4.7 months, HR [95% CI]: 0.887 [0.427, 1.843]; Russia: 8.8 vs. 2.6 months, HR [95% CI]: 0.271 [0.111, 0.662]). Improvements in event-free survival (EFS) were observed in the gilteritinib versus SC arms across all cohorts (China: 2.1 vs. 0.8 months; HR [95% CI]: 0.645 [0.427, 0.974]; South-East Asia 2.4 vs. &lt; 0.1 months; HR [95% CI]: 0.415 [0.208, 0.830]; Russia: 6.2 vs. 0.6 months; HR [95% CI]: 0.221 [0.080, 0.614]). Complete remission rates were numerically higher in the gilteritinib versus SC arm across all three regions. Gilteritinib compared with SC treatment improved OS and EFS with no new safety signals, reinforcing the known efficacy and safety profile of gilteritinib in patients with R/R <i>FLT3</i>^mut+ AML, and affirming the clinical benefit of gilteritinib in three different patient populations. ClinicalTrials.gov identifier: NCT03182244.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"104 3","pages":"1563 - 1575"},"PeriodicalIF":3.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-025-06235-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sickle cell disease and opioid overdose outcomes in the United States: a nationwide analysis","authors":"Anna L. Bode,&nbsp;Oscar F. Borja-Montes,&nbsp;Mohammed A. Quazi,&nbsp;Aqsa Mumtaz,&nbsp;Amir H. Sohail,&nbsp;Christopher R. Smith,&nbsp;Muhammad Rizwan Khawaja,&nbsp;Abu Baker Sheikh","doi":"10.1007/s00277-025-06236-x","DOIUrl":"10.1007/s00277-025-06236-x","url":null,"abstract":"<div><p>Sickle cell disease (SCD) predominantly affects individuals of African descent and is characterized by frequent painful vaso-occlusive crises, often requiring opioid management. With the opioid epidemic raising concerns about opioid overdose, this study examines in-hospital outcomes among SCD and non-SCD patients hospitalized for opioid overdose. Using the National Inpatient Sample (NIS) from 2016 to 2021, we analyzed 479,175 opioid overdose hospitalizations, including 1,315 (0.3%) with a concomitant diagnosis of SCD. Propensity score matching was used to balance demographics, comorbidities, and hospital characteristics. SCD patients were younger (45.3% aged 30–49 vs. 33.1%, <i>p</i> &lt; 0.001), predominantly of African descent (92.1% vs. 14.1%, <i>p</i> &lt; 0.001), and more often from lower-income households (58.4% vs. 35.2%, <i>p</i> &lt; 0.001). SCD patients had lower rates of mechanical ventilation (aOR: 0.7, 95% CI: 0.6–0.9) and anoxic brain injury (aOR: 0.5, 95% CI: 0.4–0.8) but experienced longer hospital stays and higher costs. No significant differences in in-hospital mortality were observed (aOR: 0.89, 95% CI: 0.7–1.1, <i>p</i> = 0.34). These findings emphasize the need for a nuanced approach to managing SCD patients during opioid overdose hospitalizations, focusing on mitigating complications, addressing prolonged hospital stays and higher costs, and reducing healthcare disparities through tailored strategies informed by the unique needs of this population.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"104 3","pages":"1551 - 1561"},"PeriodicalIF":3.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-025-06236-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Twin pregnancy during treatment with asciminib for chronic myeloid leukemia - a case report.","authors":"Géssika B G M Gutierrez de Moraes Pereira, Victor A Rocha, Paulo Victor R Barbosa, Christopher Cralcev, Alice V de Jesus, Mariana B Spadoni, Teresa Vilela V Pereira, João Paulo C Magalhães, Gislaine O Duarte, Guilherme Duffles, Felipe S Maia, Fernanda Surita, José Paulo S Guida, Carmino Antonio de Souza, Maria Laura Costa, Katia B B Pagnano","doi":"10.1007/s00277-025-06238-9","DOIUrl":"https://doi.org/10.1007/s00277-025-06238-9","url":null,"abstract":"<p><p>Managing chronic myeloid leukemia during pregnancy presents significant challenges, with limited treatment options available depending on the stage of pregnancy. All existing tyrosine kinase inhibitors are considered teratogenic, especially during the first trimester and should be avoided. In this case report, we detail the successful, unplanned dichorionic diamniotic twin pregnancy of a patient with chronic-phase myeloid leukemia previously resistant to imatinib and dasatinib who was exposed to the allosteric tyrosine kinase inhibitor asciminib during the early weeks of gestation. Upon confirmation of the pregnancy, asciminib was discontinued, and the patient was treated with pegylated interferon. The patient developed preeclampsia, and the twins were delivered prematurely via cesarean section. No other abnormalities were observed in the newborns. During her pregnancy, the patient experienced a loss of the major molecular response; however, she regained it within two months of resuming asciminib after giving birth. To our knowledge, this case represents the first report of a twin pregnancy during asciminib treatment.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic variants in NHEJ1 and related DNA repair disorders: insights into phenotypic heterogeneity and links to hypoplastic myelodysplastic syndromes and familial hematological malignancies susceptibility","authors":"Mahmoud I. Elbadry,&nbsp;Elsayed Abdelkreem,&nbsp;Ahmed Tawfeek,&nbsp;Go Hun Seo,&nbsp;Shereen Philip Aziz","doi":"10.1007/s00277-025-06257-6","DOIUrl":"10.1007/s00277-025-06257-6","url":null,"abstract":"<div><p>This study investigates the burden, phenotypes, progression, and outcomes of familial hematological malignancies (FHM) through clinical evaluation, gene panel testing, and whole exome sequencing, highlighting the significance of identifying genetic causes for personalized treatment. Over six years, 357 patients initially diagnosed with bone marrow failure (BMF) were evaluated, with 152 patients lacking identifiable causes undergoing further analysis. Among these, 53 (34.9%) exhibited features of inherited BMF syndromes, and 13 (24.5%) developed FHM. In a separate cohort of 27 patients with inherited immunodeficiency disorders, 8 (29.6%) developed FHM associated with <i>NHEJ1</i> or <i>LYST</i> variants, underscoring the familial clustering of hematologic disorders. Notably, 6 of 7 patients from the same family (family-1) with homozygous <i>NHEJ1</i> variants progressed to secondary myelodysplastic syndrome (sMDS), acute myeloid leukemia (AML), or lymphoma. Among 780 patients diagnosed with hematological malignancies during the study period, 45 (5.8%) were confirmed to have FHM, with 33 patients enrolled for detailed analysis. Of these, 16 (48.5%) had DNA-repair deficiencies (DNA-RD), including eight with Fanconi anemia, six with <i>NHEJ1</i> variants, and two with <i>BRCA2</i> mutations. The remaining 17 patients presented conditions such as familial myeloproliferative neoplasms, dyskeratosis congenita (DC) [<i>TERT</i>, <i>DKC1</i> variants], and Chediak-Higashi syndrome. Two siblings (family-3) with a rare <i>TERT</i> variant and a unique DC phenotype developed sMDS after prolonged BMF. Patients with DNA-RD were younger and exhibited higher rates of growth failure, recurrent infections, and endocrinopathies. These cases frequently progressed to sMDS or AML. A comparative analysis of 319 individuals with DNA double-strand break repair deficiencies revealed a 45% frequency of hematological malignancies. Lymphoma was most common in Nijmegen breakage syndrome (79.4%) while MDS/AML was prevalent in Cernunnos deficiency (66.6%). The findings emphasize the importance of early diagnosis, genetic testing, and personalized management, including timely transplantation, to improve outcomes in FHM. This research underscores the need for clinical awareness and surveillance to facilitate timely interventions and mitigate disease progression.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"104 3","pages":"1633 - 1653"},"PeriodicalIF":3.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-025-06257-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}