{"title":"Non-linear relationship between soluble interleukin-2 receptor and prognosis of diffuse large B-cell lymphoma.","authors":"Hikaru Tsukasaki, Kei Fujita, Shin Lee, Tetsuji Morishita, Kana Oiwa, Eiju Negoro, Takeshi Hara, Hisashi Tsurumi, Takanori Ueda, Takahiro Yamauchi","doi":"10.1007/s00277-024-06064-5","DOIUrl":"https://doi.org/10.1007/s00277-024-06064-5","url":null,"abstract":"<p><p>Despite an emphasis on the prognostic impact of serum soluble interleukin-2 receptor (sIL-2R) at diagnosis in patients with diffuse large B-cell lymphoma (DLBCL), whether the prognostic impact of elevated sIL-2R is linear remains unclear. To verify the presence of a non-linear association between sIL-2R level at diagnosis and overall survival (OS) in patients with newly diagnosed DLBCL, we conducted a multi-center, observational retrospective study. Among 488 analyzable patients, Cox proportional hazards modeling identified serum sIL-2R level at diagnosis as an independent predictor of OS. Multivariate Cox hazard modeling with restricted cubic spline model demonstrated that the relationship between serum sIL-2R level and OS was clearly non-linear (P for effect of sIL-2R = 0.002; P for non-linearity = 0.015). Mortality risk increased gradually as sIL-2R levels increased and plateaued at approximately 5,000 U/mL. Segmented regression analysis revealed that the trend in negative prognostic impact from a gradual increase in serum sIL-2R level changed significantly, with a breakpoint at approximately 2,000 U/mL. Multivariate receiver operating characteristic curves showed a significant improvement in prediction ability when serum sIL-2R level was added to the International Prognostic Index (IPI). Serum sIL-2R level at diagnosis was not only a prognostic factor, but also improved predictive accuracy for OS when incorporated with the IPI. However, the negative correlation between increasing sIL-2R and prognosis was non-linear.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493498","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}
Christian J Puzo, Karl M Hager, Henry M Rinder, Olga K Weinberg, Alexa J Siddon
{"title":"Overall survival in TP53-mutated AML and MDS.","authors":"Christian J Puzo, Karl M Hager, Henry M Rinder, Olga K Weinberg, Alexa J Siddon","doi":"10.1007/s00277-024-06054-7","DOIUrl":"https://doi.org/10.1007/s00277-024-06054-7","url":null,"abstract":"<p><p>TP53 mutations in patients with AML and MDS frequently portend a poor prognosis, related to both p53 allele status and blast count. In 2022, the ICC and WHO released updated guidelines for classifying p53-mutated AML/MDS. The characteristics of p53 mutations, their associated co-mutations, and their effects on overall survival (OS) are not known in the context of these new guidelines. A retrospective chart review was undertaken for all patients with AML or MDS and at least one TP53 mutation detected on next generation sequencing (NGS) at Yale New Haven Hospital from 2015 to 2023. All patients (N = 210) met criteria for one of the 5 diagnostic classes based on WHO and ICC guidelines. Kaplan-Meier curves with associated log-rank testing and Cox proportional hazards model quantified the effects of clinical and molecular data on survival. Multi-hit pathogenic mutations were related to poorer OS in MDS but not AML using either the WHO (p = .02) or the ICC (p = .01) diagnostic criteria. The most significant predictors of OS in the sample overall were platelet count < 50 K (HR: 2.01, 95% CI [1.47, 2.75], p < .001) and TP53 VAF ≤ 40% (HR: 0.68, 95% CI[0.50, 0.91], p = .01). Blast count ranges, complex karyotype, and p53 mutation type or location, showed no association with OS. In our cohort defined by the 2022 ICC and WHO criteria, VAF and thrombocytopenia, rather than blast count or p53 mutation features, significantly predicted OS. These results speak to each criteria's ability to identify cases of similarly aggressive disease biology and prognosis.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493499","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}
Fabio Efficace, Francesco Sparano, Massimo Breccia, Corinna Greco, Paola Carluccio, Erika Borlenghi, Prassede Salutari, Luciano Levato, Thomas Baldi, Valentina Mancini, Olimpia Finizio, Francesco Autore, Paola Fazi, Uwe Platzbecker, Marco Vignetti, Maria Teresa Voso
{"title":"Health-related quality of life benefits of arsenic trioxide in patients with non-high-risk acute promyelocytic leukemia are sustained over time: long-term results of the GIMEMA APL0406 trial.","authors":"Fabio Efficace, Francesco Sparano, Massimo Breccia, Corinna Greco, Paola Carluccio, Erika Borlenghi, Prassede Salutari, Luciano Levato, Thomas Baldi, Valentina Mancini, Olimpia Finizio, Francesco Autore, Paola Fazi, Uwe Platzbecker, Marco Vignetti, Maria Teresa Voso","doi":"10.1007/s00277-024-06038-7","DOIUrl":"https://doi.org/10.1007/s00277-024-06038-7","url":null,"abstract":"<p><p>Very limited evidence is available on the long-term health-related quality of life (HRQoL) of patients with acute promyelocytic leukemia (APL) treated with arsenic trioxide (ATO). We performed an extended follow-up of the APL0406 randomized controlled trial to investigate HRQoL of patients treated with either ATO or chemotherapy. A secondary objective was to describe the prevalence of clinically important problems and symptoms of these patients by type of treatment. Overall, 117 patients were included in this analysis after a median follow-up of 10 years (IQR 8-11) since diagnosis. Of these, 60 (51.3%) were treated with ATO, and 57 (48.7%) with chemotherapy. A statistically significant and clinically relevant difference, favoring patients treated with ATO, was found in 2 of the 3 main prespecified EORTC QLQ-C30 scales, that is, cognitive functioning (∆ = 7.7; 95% CI 0.5 to 14.9; p = 0.036) and fatigue (∆ = -9.4; 95% CI -17.9 to -0.8; p = 0.031). The prevalence of clinically important problems and symptoms tended to be slightly higher in patients treated with chemotherapy. These findings suggest that previously observed HRQoL advantages of ATO therapy of patients included in the APL0406 trial are sustained over the long-term period. This study was registered at ClinicalTrials.gov (NCT03096496).</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493493","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}
Sunil Lakhwani, María Victoria Mateos, Joaquín Martínez-López, Bruno Paiva, Laura Rosiñol Dachs, Rafael Martínez, Albert Oriol, Joan Bargay, Yolanda González-Montes, Mercedes Gironella, Cristina Encinas, Jesús Martín, Isidro Jarque, Miquel Granell, Eugenia Abella, Aránzazu García-Mateo, José Ángel Hernández-Rivas, Elena Ramila, Isabel Krsnik, Luis Felipe Casado Montero, Felipe De Arriba, Luis Palomera, Antonia Sampol, José María Moraleda, María Casanova, Pilar Delgado, Ana Lafuente, Elena Amutio, Aurelio López-Martínez, Albert Altés, M Ángeles Ruíz, Adrián Alegre, Lucia Lopez-Anglada, Javier De La Cruz, Rafael Alonso Fernández, Joan Bladé Creixenti, Juan-José Lahuerta, Jesús San-Miguel, Miguel-Teodoro Hernández
{"title":"Immunoparesis recovery in newly diagnosed transplant ineligible multiple myeloma patients, an independent prognostic factor that complements minimal residual disease.","authors":"Sunil Lakhwani, María Victoria Mateos, Joaquín Martínez-López, Bruno Paiva, Laura Rosiñol Dachs, Rafael Martínez, Albert Oriol, Joan Bargay, Yolanda González-Montes, Mercedes Gironella, Cristina Encinas, Jesús Martín, Isidro Jarque, Miquel Granell, Eugenia Abella, Aránzazu García-Mateo, José Ángel Hernández-Rivas, Elena Ramila, Isabel Krsnik, Luis Felipe Casado Montero, Felipe De Arriba, Luis Palomera, Antonia Sampol, José María Moraleda, María Casanova, Pilar Delgado, Ana Lafuente, Elena Amutio, Aurelio López-Martínez, Albert Altés, M Ángeles Ruíz, Adrián Alegre, Lucia Lopez-Anglada, Javier De La Cruz, Rafael Alonso Fernández, Joan Bladé Creixenti, Juan-José Lahuerta, Jesús San-Miguel, Miguel-Teodoro Hernández","doi":"10.1007/s00277-024-06031-0","DOIUrl":"https://doi.org/10.1007/s00277-024-06031-0","url":null,"abstract":"<p><p>Information on the prognostic value of immunoparesis (IP) recovery in multiple myeloma (MM) patients has been only generated in some observational and retrospective studies. We have evaluated the prognostic impact of IP recovery and its association with minimal residual disease (MRD) in a series of 113 newly diagnosed transplant-ineligible (NDTI) patients, that received fix duration treatment (18 cycles of VMP/lenalidomide-dexamethasone) within the PETHEMA/GEM2010MAS65 trial and who achieved CR or VGPR. Immunoglobulin levels were measured at diagnosis, at the end of treatment (after cycle 18th) and during subsequent follow up whereas MRD was analyzed only at the end of the treatment (after cycle 18th). We found that patients who had IP at diagnosis and recovered it during or after treatment had longer progression free survival (PFS) [p < 0.001; HR 0.32 (0.19-0.52)] and longer overall survival (OS) [p = 0.007; HR 0.40 (0.20-0.80)] compared to those who failed to recover it. When we analyzed IP recovery in MRD negative patients, we found that those cases with IP recovery had longer PFS [p = 0.007; HR 0.31 (0.13-0.76)] and longer OS [p = 0.012; HR 0.21 (0.06-0.80)] as compared to MRD negative patients but without IP recovery. In conclusion, IP recovery confers better prognosis in NDTI-MM patients with fixed duration treatment who achieve CR or VGPR and the prognostic value of MRD can be complemented when combined with IP recovery.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493494","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}
Benjamin J Lee, Shawn P Griffin, Jean Doh, Stefan O Ciurea, Deepa Jeyakumar, Piyanuch Kongtim, Kiran Naqvi
{"title":"Intensification of upfront chemotherapy for patients with myeloid blast phase CML: a single center experience.","authors":"Benjamin J Lee, Shawn P Griffin, Jean Doh, Stefan O Ciurea, Deepa Jeyakumar, Piyanuch Kongtim, Kiran Naqvi","doi":"10.1007/s00277-024-06045-8","DOIUrl":"https://doi.org/10.1007/s00277-024-06045-8","url":null,"abstract":"<p><p>Outcomes for patients with myeloid blast phase chronic myeloid leukemia (CML-MBP) are dismal, and no preferred chemotherapy regimen has been identified. Recent studies have suggested a higher response rate with administration of timed-sequenced regimens (TSR) (purine analog, high-dose cytarabine, anthracycline) in high-risk acute myeloid leukemia patients. We retrospectively evaluated outcomes of newly diagnosed CML-MBP patients consecutively treated at our institution with a TSR or standard-dose cytarabine and an anthracycline (\"7 + 3\") combined with a tyrosine-kinase inhibitor (TKI) between 2011 and 2023. Endpoints of interest included hematologic response, clinically significant cytogenetic response (CSCR) defined as achieving at least a minor cytogenetic response (Ph + metaphases 0%-≤65%) after induction therapy, event-free survival (EFS), and overall survival (OS). A total of 18 patients with CML-MBP were included of whom 9 (50%) received a TSR and 9 (50%) received \"7 + 3\". Hematologic response (55.6% vs. 55.6%) and CSCR (25% vs. 37.5%) were similar between TSR- and \"7 + 3\" treated patients. Twelve patients (66.7%) experienced at least one grade ≥ 3 non-hematologic, end-organ toxicity with 33.3% and 11.1% of TSR- and 7 + 3-treated patients, respectively, experiencing at least two. Our data suggests that intensification of upfront chemotherapy does not appear to improve treatment outcomes in CML-MBP patients however, further studies are warranted to confirm these findings involving a larger cohort.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493496","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":"Aplastic Anemia in the light of the COVID-19 pandemic: infection, vaccination, and pathophysiologic mechanisms.","authors":"Nelson Luis Cahuapaza-Gutierrez","doi":"10.1007/s00277-024-06052-9","DOIUrl":"https://doi.org/10.1007/s00277-024-06052-9","url":null,"abstract":"<p><p>Patients infected with SARS-CoV-2 and vaccinated against COVID-19 could develop aplastic anemia (AA). Comprehensive review and analysis were conducted through a selective literature search in PubMed, Scopus, EMBASE, and Web of Science. For this analysis, 26 studies were included, comprising 16 case reports, 7 case series, and 3 observational studies, totaling 53 patients. The causes of acquired or idiopathic AA are diverse; this review presents recent findings, including possible new etiologies such as SARS-CoV-2 infection and COVID-19 vaccines. This possible association is explored, addressing the existing gap, and aiming to improve daily medical practice. This article reviews the relationship between AA and SARS-CoV-2 infection, as well as COVID-19 vaccines, analyzing cases of de novo occurrence and relapses of AA. Although a definitive mechanistic link has not yet been established, possible underlying pathophysiological mechanisms are explored.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493489","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}
Si Li, Rui Gao, Xu Han, Kai Wang, Bingyu Kang, Xiaolu Ma
{"title":"MALAT1/miR-582-5p/GALNT1/MUC1 axis modulates progression of AML leukemia stem cells by regulating JAK2/STAT3 pathway.","authors":"Si Li, Rui Gao, Xu Han, Kai Wang, Bingyu Kang, Xiaolu Ma","doi":"10.1007/s00277-024-06043-w","DOIUrl":"https://doi.org/10.1007/s00277-024-06043-w","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is characterized by uncontrolled clonal expansion and differentiation block of immature myeloid cells. Some studies have shown that leukemia stem cells (LSC) are thought to be responsible for the initiation and development of leukemia. Moreover, abnormal O-glycosylation is a key modification in the process of cancer malignancy. In this study, GALNT1 expression was significantly upregulated in LSCs, while knockdown of GALNT1 inhibited cell viability and promoted apoptosis. Importantly, GALNT1 was the direct target of miR-582-5P, and MALAT1 directly interacted with miR-582-5P. In addition, Our investigation corroborated that MALAT1 functioned as an endogenous sponge of miR-582-5P to regulate mucin1 (MUC1) expression, catalyzed by GALNT1, which modulated the activity of JAK2/STAT3 pathway. MALAT1 and MUC1 were targets of transcription factor STAT3 and were regulated by STAT3. In general, these new findings indicated that MALAT1/miR-582-5P/GALNT1 axis is involved in the progression of LSCs, illuminating the possible mechanism mediated by O-glycosylated MUC1 via JAK2/STAT3 pathway.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456650","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}
Beatriz Cáceres-Nazario, Joshua Rivenbark, Manish K Saha, Stephanie Mathews, Samuel M Rubinstein
{"title":"Novel use of Siltuximab in a patient with VEXAS Syndrome.","authors":"Beatriz Cáceres-Nazario, Joshua Rivenbark, Manish K Saha, Stephanie Mathews, Samuel M Rubinstein","doi":"10.1007/s00277-024-06037-8","DOIUrl":"https://doi.org/10.1007/s00277-024-06037-8","url":null,"abstract":"<p><p>VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is an increasingly recognized disorder that occurs due to somatic mutations of a ubiquitin-activating enzyme encoded by ubiquitin-like modifier activating enzyme 1 gene, UBA1. Clinical findings associated with VEXAS syndrome include recurrent fevers, polychondritis, periorbital edema, pleural effusions, myocarditis and/or pericarditis, hepatosplenomegaly, myelodysplastic syndrome, cytopenias, inflammatory arthritis, neutrophilic dermatosis, and deep venous thrombosis. Novel renal manifestations like interstitial nephritis are infrequent, and to our knowledge, acute renal failure due to C3 glomerulonephritis (C3GN) has not yet been reported. Overwhelming systemic inflammation can result in morbid end-organ damage and death. While there is no formal guideline or established protocol for its management, treatment of VEXAS syndrome with tocilizumab, an interleukin-6 (IL-6)-directed therapy, has been described in the literature. Here, we report a case of a 71-year-old male patient presenting with C3GN as an initial manifestation of VEXAS syndrome and explore the rationale for our approach to treatment with IL-6 blockade. Our patient was initially treated with two inpatient doses of tocilizumab with successful transition to siltuximab in the outpatient setting. He continues to benefit from ongoing siltuximab treatment for more than one year to date without any safety issues or relapse of VEXAS syndrome.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456651","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":"A girl with a novel nonsense mutation in Chediak-Higashi syndrome was relieved successfully by treatment with HCST and UCBT: a case report.","authors":"CanLiu, Aijun Zou, Xianyu Wang, Qiang Yu","doi":"10.1007/s00277-024-06039-6","DOIUrl":"https://doi.org/10.1007/s00277-024-06039-6","url":null,"abstract":"<p><p>Chediak-Higashi syndrome (CHS) is a life-threatening autosomal recessive immunodeficiency disease presenting with recurrent infections, hypopigmentation, progressive neurodegeneration, and hemophagocytic lymphohistiocytosis (HLH), known as the accelerated stage. Two-thirds of patients experience a fatal accelerated phase. CHS is caused by lysosomal transport regulator (LYST) gene mutations. We report the case of CHS, who was born with pale skin and silver hair. Bone marrow aspirate revealed large inclusions in granulocytes, monocytes, and lymphocytes. Genetic analysis revealed a new nonsense mutation in the LYST gene: c.8186G > A (W2729Ter). The child presented with fever, hepatosplenomegaly, and lymphadenectasis. Laboratory tests showed pancytopenia, hypofibrinogenemia, and high serum ferritin, indicating an accelerated phase of CHS. She underwent allogeneic hematopoietic stem cell transplantation (HCST) combined with umbilical cord blood transplantation (UCBT) after HLH-related chemotherapy. The patient has been alive for nine months without recurrence. We have identified a novel nonsense mutation in the LYST gene that correlates with a severe phenotype, and HSCT combined with UCBT is an effective treatment.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456644","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}