Pub Date : 2024-06-10DOI: 10.1016/j.bneo.2024.100025
Abstract
CD38 is a surface ectoenzyme expressed at high levels on myeloma plasma cells and is the target for the monoclonal antibodies (mAbs) daratumumab and isatuximab. Pretreatment CD38 density on tumor cells is an important determinant of mAb efficacy. Several small molecules have been found to increase tumor surface CD38, with the goal of boosting mAb efficacy in a cotreatment strategy. Numerous other CD38-targeting therapeutics are currently in preclinical or clinical development. Here, we sought to extend our currently limited insight into CD38 surface expression by using a multiomics approach. Genome-wide CRISPR interference screens integrated with patient–centered epigenetic analysis confirmed known regulators of CD38, such as RARA, while revealing XBP1 and SPI1 as other key transcription factors governing surface CD38 levels. CD38 knockdown followed by cell surface proteomics demonstrated no significant remodeling of the myeloma “surfaceome” after genetically induced loss of this antigen. Integrated transcriptome and surface proteome data confirmed high specificity of all-trans retinoic acid in upregulating CD38, in contrast to the broader effects of azacytidine and panobinostat. Finally, unbiased phosphoproteomics identified inhibition of MAP kinase pathway signaling in tumor cells after daratumumab treatment. Our work provides a resource to design strategies to enhance efficacy of CD38-targeting immunotherapies in myeloma.
{"title":"Functional multiomics reveals genetic and pharmacologic regulation of surface CD38 in multiple myeloma","authors":"","doi":"10.1016/j.bneo.2024.100025","DOIUrl":"10.1016/j.bneo.2024.100025","url":null,"abstract":"<div><h3>Abstract</h3><p>CD38 is a surface ectoenzyme expressed at high levels on myeloma plasma cells and is the target for the monoclonal antibodies (mAbs) daratumumab and isatuximab. Pretreatment CD38 density on tumor cells is an important determinant of mAb efficacy. Several small molecules have been found to increase tumor surface CD38, with the goal of boosting mAb efficacy in a cotreatment strategy. Numerous other CD38-targeting therapeutics are currently in preclinical or clinical development. Here, we sought to extend our currently limited insight into CD38 surface expression by using a multiomics approach. Genome-wide CRISPR interference screens integrated with patient–centered epigenetic analysis confirmed known regulators of <em>CD38</em>, such as RARA, while revealing XBP1 and SPI1 as other key transcription factors governing surface CD38 levels. <em>CD38</em> knockdown followed by cell surface proteomics demonstrated no significant remodeling of the myeloma “surfaceome” after genetically induced loss of this antigen. Integrated transcriptome and surface proteome data confirmed high specificity of all-trans retinoic acid in upregulating CD38, in contrast to the broader effects of azacytidine and panobinostat. Finally, unbiased phosphoproteomics identified inhibition of MAP kinase pathway signaling in tumor cells after daratumumab treatment. Our work provides a resource to design strategies to enhance efficacy of CD38-targeting immunotherapies in myeloma.</p></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950328024000256/pdfft?md5=a27e6b08696b724b63d2d012e38a44b2&pid=1-s2.0-S2950328024000256-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141638776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-10DOI: 10.1016/j.bneo.2024.100023
Abstract
Histiocytic disorders are rare hematologic neoplasms characterized by a notable dependence on mitogen-activated protein kinase signaling. Targeted therapy is an emerging treatment option, yet the number of reported patients remains limited. Here, we describe 40 patients with histiocytic neoplasms who were treated with targeted therapy in 7 tertiary referral hospitals from the Netherlands and Belgium. The cohort comprised of 6 (15%) children and 34 (85%) adults with diverse histiocytoses, including Langerhans cell histiocytosis (LCH; n = 12), Erdheim–Chester disease (n = 14), central nervous system xanthogranuloma (n = 2), Rosai–Dorfman disease (n = 3), histiocytic sarcoma (n = 2), ALK–positive histiocytosis (n = 1), and mixed/unclassifiable histiocytosis (n = 6). Five patients were included in a clinical trial; 35 (88%) received BRAF/MEK inhibitors outside of trials. Among these 35 patients with available follow-up data, median time on targeted treatment was 1.9 years (range, 0.04-5.8 years). Complete or partial responses were observed in 25 of 27 (93%) patients treated for multisystemic and/or solid lesions and 2 of 8 (25%) patients treated for neurodegenerative LCH. Responses were generally durable, although 10 patients lost response after dose reduction or therapy interruption. Responses were recaptured in 9 of 10 cases. Two patients developed new or progressive neurodegenerative lesions: 1 during and 1 after vemurafenib therapy. At last follow-up, 8 adults had stopped targeted therapy because of toxicity. This study corroborates the favorable outcomes of BRAF/MEK inhibition in patients with histiocytosis described previously. However, it also highlights limitations and calls for prospective studies.
{"title":"Real-world experience with targeted therapy in patients with histiocytic neoplasms in the Netherlands and in Belgium","authors":"","doi":"10.1016/j.bneo.2024.100023","DOIUrl":"10.1016/j.bneo.2024.100023","url":null,"abstract":"<div><h3>Abstract</h3><p>Histiocytic disorders are rare hematologic neoplasms characterized by a notable dependence on mitogen-activated protein kinase signaling. Targeted therapy is an emerging treatment option, yet the number of reported patients remains limited. Here, we describe 40 patients with histiocytic neoplasms who were treated with targeted therapy in 7 tertiary referral hospitals from the Netherlands and Belgium. The cohort comprised of 6 (15%) children and 34 (85%) adults with diverse histiocytoses, including Langerhans cell histiocytosis (LCH; n = 12), Erdheim–Chester disease (n = 14), central nervous system xanthogranuloma (n = 2), Rosai–Dorfman disease (n = 3), histiocytic sarcoma (n = 2), ALK–positive histiocytosis (n = 1), and mixed/unclassifiable histiocytosis (n = 6). Five patients were included in a clinical trial; 35 (88%) received BRAF/MEK inhibitors outside of trials. Among these 35 patients with available follow-up data, median time on targeted treatment was 1.9 years (range, 0.04-5.8 years). Complete or partial responses were observed in 25 of 27 (93%) patients treated for multisystemic and/or solid lesions and 2 of 8 (25%) patients treated for neurodegenerative LCH. Responses were generally durable, although 10 patients lost response after dose reduction or therapy interruption. Responses were recaptured in 9 of 10 cases. Two patients developed new or progressive neurodegenerative lesions: 1 during and 1 after vemurafenib therapy. At last follow-up, 8 adults had stopped targeted therapy because of toxicity. This study corroborates the favorable outcomes of BRAF/MEK inhibition in patients with histiocytosis described previously. However, it also highlights limitations and calls for prospective studies.</p></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950328024000232/pdfft?md5=d4a89468e3562c13ebf6916d17549241&pid=1-s2.0-S2950328024000232-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141403218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1016/j.bneo.2024.100016
Ellen Madarang , Jillian Lykon , Wei Zhao , Mikkael A. Sekeres , Terrence Bradley , Namrata S. Chandhok , Justin Taylor , Sangeetha Venugopal , Tulay Koru-Sengul , Sunil Girish Iyer , Jason S. Gilbert , Ryan M. Miller , Jacopo Nanni , Irene Zacheo , Agnese Mattei , Najla Al Ali , Ashwin Kishtagari , Giovanni Marconi , David A. Sallman , Daniel A. Pollyea , Justin Watts
Abstract
Venetoclax (VEN) plus a hypomethylating agent (HMA) regimen is the standard of care for older adults with acute myeloid leukemia (AML); however, it is associated with significant myelosuppression and complications, potentially limiting its use in those who are very old. We performed a multicenter retrospective analysis of VEN-HMA treatment in octogenarians and nonagenarians to further understand the tolerability, feasibility, dosing considerations, and clinical efficacy in this unique group. Patients with AML aged ≥80 years who received VEN-HMA between March 2015 and April 2022 were reviewed. VEN-HMA dosing was determined by treating physician, accounting for CYP3A4 drug interaction dose adjustments. In total, 154 patients were included, with a median age of 82 years (range, 80-92), who received treatment with VEN-HMA (83% with azacitidine and 17% with decitabine). Most patients (53%) had European LeukemiaNet 2017 adverse risk AML, 33% had intermediate, 8% had favorable, and 6% were unknown. With a median follow-up of 7.7 months, 36 patients (23%) remained in remission, with 31 (20%) still on VEN-HMA. The 30-day and 60-day mortality rates were 8.5% and 17%, respectively. The composite complete remission (CRc) rate for patients with newly diagnosed AML without prior myelodysplastic syndrome was 73% (48 of 66). Median overall survival (OS) was 8.1 months, and in patients who achieved a response (CRc), median OS was 13.2 months. Landmark analysis from the time CRc was first achieved showed that patients receiving VEN for ≤14 days had improved OS; median, 24.0 months. Patients who are very old can be treated safely with combination VEN-HMA with expectations of dose reductions and cycle extensions to ensure tolerability over the long term.
{"title":"Venetoclax and hypomethylating agents in octogenarians and nonagenarians with acute myeloid leukemia","authors":"Ellen Madarang , Jillian Lykon , Wei Zhao , Mikkael A. Sekeres , Terrence Bradley , Namrata S. Chandhok , Justin Taylor , Sangeetha Venugopal , Tulay Koru-Sengul , Sunil Girish Iyer , Jason S. Gilbert , Ryan M. Miller , Jacopo Nanni , Irene Zacheo , Agnese Mattei , Najla Al Ali , Ashwin Kishtagari , Giovanni Marconi , David A. Sallman , Daniel A. Pollyea , Justin Watts","doi":"10.1016/j.bneo.2024.100016","DOIUrl":"10.1016/j.bneo.2024.100016","url":null,"abstract":"<div><h3>Abstract</h3><p>Venetoclax (VEN) plus a hypomethylating agent (HMA) regimen is the standard of care for older adults with acute myeloid leukemia (AML); however, it is associated with significant myelosuppression and complications, potentially limiting its use in those who are very old. We performed a multicenter retrospective analysis of VEN-HMA treatment in octogenarians and nonagenarians to further understand the tolerability, feasibility, dosing considerations, and clinical efficacy in this unique group. Patients with AML aged ≥80 years who received VEN-HMA between March 2015 and April 2022 were reviewed. VEN-HMA dosing was determined by treating physician, accounting for CYP3A4 drug interaction dose adjustments. In total, 154 patients were included, with a median age of 82 years (range, 80-92), who received treatment with VEN-HMA (83% with azacitidine and 17% with decitabine). Most patients (53%) had European LeukemiaNet 2017 adverse risk AML, 33% had intermediate, 8% had favorable, and 6% were unknown. With a median follow-up of 7.7 months, 36 patients (23%) remained in remission, with 31 (20%) still on VEN-HMA. The 30-day and 60-day mortality rates were 8.5% and 17%, respectively. The composite complete remission (CRc) rate for patients with newly diagnosed AML without prior myelodysplastic syndrome was 73% (48 of 66). Median overall survival (OS) was 8.1 months, and in patients who achieved a response (CRc), median OS was 13.2 months. Landmark analysis from the time CRc was first achieved showed that patients receiving VEN for ≤14 days had improved OS; median, 24.0 months. Patients who are very old can be treated safely with combination VEN-HMA with expectations of dose reductions and cycle extensions to ensure tolerability over the long term.</p></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950328024000165/pdfft?md5=d6c6fab40ecf4f727e977362cb0cfbff&pid=1-s2.0-S2950328024000165-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141058132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1016/j.bneo.2024.100013
Alexander Pemov , Jung Kim , Wen Luo , Jia Liu , Cole Graham , Kristine Jones , Delphine DeMangel , Neal D. Freedman , Charles Dumontet , Bin Zhu , Mary L. McMaster , Douglas R. Stewart
Abstract
Waldenström macroglobulinemia (WM) is a rare hematological malignancy. Risk for WM is elevated 20-fold among first-degree relatives of patients with WM. However, the list of variants and genes that cause WM remains incomplete. In this study we analyzed exomes from 64 WM pedigrees for evidence of genetic susceptibility for this malignancy. We determined the frequency of pathogenic (P) or likely pathogenic (LP) variants among patients with WM; performed variant- and gene-level association analyses with the set of 166 WM cases and 681 unaffected controls; and examined the segregation pattern of deleterious variants among affected members in each pedigree. We identified P/LP variants in TREX1 and SAMHD1 (genes that function at the interface between innate immune response, genotoxic surveillance, and DNA repair) segregating in patients with WM from 2 pedigrees. There were additional P/LP variants in cancer-predisposing genes (eg, POT1, RECQL4, PTPN11, PMS2). In variant- and gene-level analyses, no associations were statistically significant after multiple testing correction. On a pathway level, we observed involvement of genes that play a role in telomere maintenance (q-value = 0.02), regulation of innate immune response (q-value = 0.05), and DNA repair (q-value = 0.08). Affected members of each pedigree shared multiple deleterious variants (median, n = 18), but the overlap between the families was modest. In summary, P/LP variants in highly penetrant genes constitute a modest proportion of the deleterious variants; each pedigree is largely unique in its genetic architecture, and multiple genes are likely involved in the etiology of WM.
{"title":"The landscape of rare genetic variants in familial Waldenström macroglobulinemia","authors":"Alexander Pemov , Jung Kim , Wen Luo , Jia Liu , Cole Graham , Kristine Jones , Delphine DeMangel , Neal D. Freedman , Charles Dumontet , Bin Zhu , Mary L. McMaster , Douglas R. Stewart","doi":"10.1016/j.bneo.2024.100013","DOIUrl":"10.1016/j.bneo.2024.100013","url":null,"abstract":"<div><h3>Abstract</h3><p>Waldenström macroglobulinemia (WM) is a rare hematological malignancy. Risk for WM is elevated 20-fold among first-degree relatives of patients with WM. However, the list of variants and genes that cause WM remains incomplete. In this study we analyzed exomes from 64 WM pedigrees for evidence of genetic susceptibility for this malignancy. We determined the frequency of pathogenic (P) or likely pathogenic (LP) variants among patients with WM; performed variant- and gene-level association analyses with the set of 166 WM cases and 681 unaffected controls; and examined the segregation pattern of deleterious variants among affected members in each pedigree. We identified P/LP variants in <em>TREX1</em> and <em>SAMHD1</em> (genes that function at the interface between innate immune response, genotoxic surveillance, and DNA repair) segregating in patients with WM from 2 pedigrees. There were additional P/LP variants in cancer-predisposing genes (eg, <em>POT1, RECQL4, PTPN11, PMS2</em>). In variant- and gene-level analyses, no associations were statistically significant after multiple testing correction. On a pathway level, we observed involvement of genes that play a role in telomere maintenance (q-value = 0.02), regulation of innate immune response (q-value = 0.05), and DNA repair (q-value = 0.08). Affected members of each pedigree shared multiple deleterious variants (median, n = 18), but the overlap between the families was modest. In summary, P/LP variants in highly penetrant genes constitute a modest proportion of the deleterious variants; each pedigree is largely unique in its genetic architecture, and multiple genes are likely involved in the etiology of WM.</p></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S295032802400013X/pdfft?md5=7d264d4490d9a6245a10e30efcc10a9c&pid=1-s2.0-S295032802400013X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140784350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1016/j.bneo.2024.100014
Chung Hoow Kok , Yazad Irani , Jade Clarson , Verity Saunders , Phuong Dang , Naranie Shanmuganathan , Susan Branford , David Yeung , Agnes S. M. Yong , Timothy P. Hughes
Abstract
Achieving a deep molecular response (DMR) is a prerequisite for treatment-free remission in chronic myeloid leukemia (CML) and a key milestone for patients with CML. This study identified patients unlikely to achieve a 5-year DMR through differential expression of cluster of differentiation (CD) genes, and clinical variables at diagnosis. Peripheral blood samples (n = 131) from patients treated with imatinib or nilotinib underwent transcriptomic microarray profiling. The decision-tree analysis delineated 2 distinct poor-risk (PR) cohorts, distinguished by high 3-month BCR::ABL1% (PR-1), or high CD302 expression (PR-2). The 5-years DMR achievement rate was significantly lower in both PR groups than in the good-risk (GR) group in patients treated frontline with imatinib (0% vs 27% vs 83%; P < .0001) or nilotinib (PR-2 vs GR, 17% vs 83%; P = .02). Gene-set enrichment analysis revealed reduced expression of cell cycle–related genes in PR-2, as well as increased metabolism and STAT3 pathway genes, which has previously been linked to leukemic cell persistence and resistance to tyrosine kinase inhibitors. Moreover, PR-2 had a higher frequency of CD34+CD302+ and CD14+CD302+ cells than GR samples. Strategies aimed at targeting STAT3 and/or metabolic pathways associated with high CD302 may provide novel therapeutic approaches that could help improve treatment outcomes and eradicate residual disease.
摘要获得深度分子反应（DMR）是慢性粒细胞白血病（CML）无治疗缓解的先决条件，也是CML患者的一个重要里程碑。本研究通过分化簇（CD）基因的差异表达和诊断时的临床变量来确定不太可能实现5年DMR的患者。对接受伊马替尼或尼洛替尼治疗的患者的外周血样本（n = 131）进行了转录组芯片分析。决策树分析划分出了2个不同的低风险（PR）队列，分别是3个月BCR::ABL1%高表达（PR-1）或CD302高表达（PR-2）。在接受伊马替尼（0% vs 27% vs 83%; P <.0001）或尼洛替尼（PR-2 vs GR, 17% vs 83%; P = .02）一线治疗的患者中，两个PR组的5年DMR达标率均显著低于良险（GR）组。基因集富集分析显示，PR-2 中细胞周期相关基因的表达减少，代谢和 STAT3 通路基因的表达增加，而 STAT3 通路基因以前曾与白血病细胞的持久性和对酪氨酸激酶抑制剂的耐药性有关。此外，与GR样本相比，PR-2样本中CD34+CD302+和CD14+CD302+细胞的频率更高。针对STAT3和/或与高CD302相关的代谢途径的策略可能会提供新的治疗方法，有助于改善治疗效果和根除残留疾病。
{"title":"CD302 predicts achievement of deep molecular response in patients with chronic myeloid leukemia treated with imatinib","authors":"Chung Hoow Kok , Yazad Irani , Jade Clarson , Verity Saunders , Phuong Dang , Naranie Shanmuganathan , Susan Branford , David Yeung , Agnes S. M. Yong , Timothy P. Hughes","doi":"10.1016/j.bneo.2024.100014","DOIUrl":"https://doi.org/10.1016/j.bneo.2024.100014","url":null,"abstract":"<div><h3>Abstract</h3><p>Achieving a deep molecular response (DMR) is a prerequisite for treatment-free remission in chronic myeloid leukemia (CML) and a key milestone for patients with CML. This study identified patients unlikely to achieve a 5-year DMR through differential expression of cluster of differentiation (CD) genes, and clinical variables at diagnosis. Peripheral blood samples (n = 131) from patients treated with imatinib or nilotinib underwent transcriptomic microarray profiling. The decision-tree analysis delineated 2 distinct poor-risk (PR) cohorts, distinguished by high 3-month <em>BCR</em>::<em>ABL1</em>% (PR-1), or high <em>CD302</em> expression (PR-2). The 5-years DMR achievement rate was significantly lower in both PR groups than in the good-risk (GR) group in patients treated frontline with imatinib (0% vs 27% vs 83%; <em>P</em> < .0001) or nilotinib (PR-2 vs GR, 17% vs 83%; <em>P</em> = .02). Gene-set enrichment analysis revealed reduced expression of cell cycle–related genes in PR-2, as well as increased metabolism and STAT3 pathway genes, which has previously been linked to leukemic cell persistence and resistance to tyrosine kinase inhibitors. Moreover, PR-2 had a higher frequency of CD34<sup>+</sup>CD302<sup>+</sup> and CD14<sup>+</sup>CD302<sup>+</sup> cells than GR samples. Strategies aimed at targeting STAT3 and/or metabolic pathways associated with high CD302 may provide novel therapeutic approaches that could help improve treatment outcomes and eradicate residual disease.</p></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950328024000141/pdfft?md5=203d3abae466c2edbbfccec17f07d8a0&pid=1-s2.0-S2950328024000141-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141240049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-23DOI: 10.1016/j.bneo.2024.100017
Jad Othman , Ho Pui Jeff Lam , Sarah Leong , Faisal Basheer , Islam Abdallah , Kathryn Fleming , Priyanka Mehta , Heba Yassin , John Laurie , Michael Austin , Paolo Gallipoli , Tom Taylor , Mike Dennis , Johnathon Elliot , Georgina Clarke , Raymond Dang , Jennifer Vidler , Pramila Krishnamurthy , Anne-Louise Latif , Pallavi Kalkur , Richard Dillon
Abstract
Venetoclax with azacitidine is the standard of care for patients with acute myeloid leukemia (AML) who are unfit for intensive chemotherapy; however, uncertainties remain regarding the treatment schedule, accurate prognostication, and outcomes for patients treated outside clinical trials. The option of venetoclax with low-dose cytarabine (LDAC) is also available; however, it is not clear for which patients it may be a useful alternative. Here, we report a large real-world cohort of 654 patients treated in 53 UK hospitals with either venetoclax and azacitidine (n = 587) or LDAC (n = 67). The median age was 73 years, and 59% had de novo AML. Most patients received 100 mg of venetoclax with an azole antifungal. In cycle 1, patients spent a median of 14 days in the hospital, and 85% required red cell transfusion, 59% platelet transfusion, and 63% required IV antibiotics. Supportive care requirements significantly reduced after the first cycle. Patients receiving venetoclax-azacitidine had a complete remission (CR)/CR with incomplete hematological recovery rate of 67%, day 30 and day 60 mortality of 5% and 8%, respectively, and median overall survival of 13.6 months. Mutations in NPM1, RUNX1, STAG2, and IDH2 were associated with improved survival, whereas age, secondary and therapy-related AML, +8, MECOM rearrangements, complex karyotype, ASXL1, and KIT mutations were associated with poorer survival. Prognostic systems derived specifically for patients treated with venetoclax-azacitidine performed better than the European LeukemiaNet and Medical Research Council classifications; however, improved risk classifications are still required. In the 149 patients with NPM1 mutated AML, outcomes were similar for those treated with venetoclax-azacitidine and venetoclax-LDAC.
{"title":"Real-world outcomes of newly diagnosed AML treated with venetoclax and azacitidine or low-dose cytarabine in the UK NHS","authors":"Jad Othman , Ho Pui Jeff Lam , Sarah Leong , Faisal Basheer , Islam Abdallah , Kathryn Fleming , Priyanka Mehta , Heba Yassin , John Laurie , Michael Austin , Paolo Gallipoli , Tom Taylor , Mike Dennis , Johnathon Elliot , Georgina Clarke , Raymond Dang , Jennifer Vidler , Pramila Krishnamurthy , Anne-Louise Latif , Pallavi Kalkur , Richard Dillon","doi":"10.1016/j.bneo.2024.100017","DOIUrl":"10.1016/j.bneo.2024.100017","url":null,"abstract":"<div><h3>Abstract</h3><p>Venetoclax with azacitidine is the standard of care for patients with acute myeloid leukemia (AML) who are unfit for intensive chemotherapy; however, uncertainties remain regarding the treatment schedule, accurate prognostication, and outcomes for patients treated outside clinical trials. The option of venetoclax with low-dose cytarabine (LDAC) is also available; however, it is not clear for which patients it may be a useful alternative. Here, we report a large real-world cohort of 654 patients treated in 53 UK hospitals with either venetoclax and azacitidine (n = 587) or LDAC (n = 67). The median age was 73 years, and 59% had de novo AML. Most patients received 100 mg of venetoclax with an azole antifungal. In cycle 1, patients spent a median of 14 days in the hospital, and 85% required red cell transfusion, 59% platelet transfusion, and 63% required IV antibiotics. Supportive care requirements significantly reduced after the first cycle. Patients receiving venetoclax-azacitidine had a complete remission (CR)/CR with incomplete hematological recovery rate of 67%, day 30 and day 60 mortality of 5% and 8%, respectively, and median overall survival of 13.6 months. Mutations in <em>NPM1</em>, <em>RUNX1</em>, <em>STAG2</em>, and <em>IDH2</em> were associated with improved survival, whereas age, secondary and therapy-related AML, +8, <em>MECOM</em> rearrangements, complex karyotype, <em>ASXL1</em>, and <em>KIT</em> mutations were associated with poorer survival. Prognostic systems derived specifically for patients treated with venetoclax-azacitidine performed better than the European LeukemiaNet and Medical Research Council classifications; however, improved risk classifications are still required. In the 149 patients with <em>NPM1</em> mutated AML, outcomes were similar for those treated with venetoclax-azacitidine and venetoclax-LDAC.</p></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950328024000177/pdfft?md5=1de290f83adace13a5f6e05842b39ad6&pid=1-s2.0-S2950328024000177-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141136394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-21DOI: 10.1016/j.bneo.2024.100021
Johann-Christoph Jann ∗ , Nanni Schmitt ∗ , Alexander Streuer , Qingyu Xu , Vladimir Riabov , Eva Altrock , Nadine Weimer , Verena Nowak , Julia Obländer , Iris Palme , Melda Göl , Marie Demmerle , Felicitas Rapp , Fabian Siegel , Laurenz Steiner , Mahmoud Ghazal , Angelika Duda , Verena Haselmann , Ali Darwich , Ahmed Jawhar , Daniel Nowak
Abstract
Myelodysplastic neoplasms (MDS) are hypothesized to remodel their bone marrow (BM) microenvironment to reinforce conditions for their propagation. In this study, we investigated interactions between MDS cells and the BM niche at single-cell level. In a patient-derived xenograft (PDX) model, we analyzed 13 000 cells from different murine niche cell populations after long-term (>24 weeks) exposure to MDS vs healthy human grafts. Subsequently, we analyzed over 24 000 primary human BM cells enriched for the nonhematopoietic compartment by using whole bone fragments from n = 8 patients with MDS and n = 7 healthy, age-matched donors. In PDX who received MDS transplantation, mesenchymal cell (MSC) subpopulations were forced to overexpress hematopoietic factors such as Cxcl12 and Il7 upon contact with hematopoietic MDS cells as compared with healthy grafts. Single-cell analyses of primary in situ BM cells from patients with MDS showed highly heterogeneous MSC subpopulations on a patient-individual level. We identified inflammatory gene expression profiles as well as overexpression of C-X-C Motif Chemokine Ligand 12, KIT ligand, and Interleukin 7 in MDS MSCs and endothelial cells. In conclusion, we demonstrate reprogramming of the BM microenvironment by MDS cells, pointing to altered MSC subpopulations with increased growth factor expression profiles in a subgroup of patients with MDS.
{"title":"Instructive interaction between myelodysplastic hematopoiesis and the bone marrow microenvironment at the single-cell level","authors":"Johann-Christoph Jann ∗ , Nanni Schmitt ∗ , Alexander Streuer , Qingyu Xu , Vladimir Riabov , Eva Altrock , Nadine Weimer , Verena Nowak , Julia Obländer , Iris Palme , Melda Göl , Marie Demmerle , Felicitas Rapp , Fabian Siegel , Laurenz Steiner , Mahmoud Ghazal , Angelika Duda , Verena Haselmann , Ali Darwich , Ahmed Jawhar , Daniel Nowak","doi":"10.1016/j.bneo.2024.100021","DOIUrl":"10.1016/j.bneo.2024.100021","url":null,"abstract":"<div><h3>Abstract</h3><p>Myelodysplastic neoplasms (MDS) are hypothesized to remodel their bone marrow (BM) microenvironment to reinforce conditions for their propagation. In this study, we investigated interactions between MDS cells and the BM niche at single-cell level. In a patient-derived xenograft (PDX) model, we analyzed 13 000 cells from different murine niche cell populations after long-term (>24 weeks) exposure to MDS vs healthy human grafts. Subsequently, we analyzed over 24 000 primary human BM cells enriched for the nonhematopoietic compartment by using whole bone fragments from n = 8 patients with MDS and n = 7 healthy, age-matched donors. In PDX who received MDS transplantation, mesenchymal cell (MSC) subpopulations were forced to overexpress hematopoietic factors such as Cxcl12 and Il7 upon contact with hematopoietic MDS cells as compared with healthy grafts. Single-cell analyses of primary in situ BM cells from patients with MDS showed highly heterogeneous MSC subpopulations on a patient-individual level. We identified inflammatory gene expression profiles as well as overexpression of C-X-C Motif Chemokine Ligand 12, KIT ligand, and Interleukin 7 in MDS MSCs and endothelial cells. In conclusion, we demonstrate reprogramming of the BM microenvironment by MDS cells, pointing to altered MSC subpopulations with increased growth factor expression profiles in a subgroup of patients with MDS.</p></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950328024000219/pdfft?md5=7e40a71e101380a24de189eb79bb44c9&pid=1-s2.0-S2950328024000219-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141131243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-21DOI: 10.1016/j.bneo.2024.100018
Ulrich Dührsen , Andreas Bockisch , Bernd Hertenstein , Imke E. Karsten , Frank Kroschinsky , Michael Heuser , Andreas Hochhaus , Heinz-Gert Höffkes , Dirk Behringer , Gabriele Prange-Krex , Mareike Tometten , Martin Grieshammer , Götz U. Grigoleit , Oliver Schmalz , Karin Jordan , Helga Bernhard , Tobias Gaska , Aristoteles Giagounidis , Roland Schroers , Uwe M. Martens , M. Neuhäuser
Abstract
The PETAL (Positron Emission Tomography–Guided Therapy of Aggressive Non-Hodgkin Lymphomas) trial investigated whether treatment intensification after 2 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP; plus rituximab [R] for CD20+ lymphomas) improved survival in aggressive non-Hodgkin lymphoma. A total of 754 patients (87.5%) had a negative and 108 (12.5%) had a positive interim positron emission tomography (iPET) scan. iPET-positive patients were randomly assigned to receive another 6 (R-)CHOP cycles or 6 blocks of a more intensive protocol. Interim PET-negative patients received another 4 cycles of R-CHOP with or without 2 additional doses of R. After a median follow-up of 4 years, treatment intensification had not improved outcome. These results were confirmed after 10.3 years of follow-up. The present analysis also describes the management of relapse that was part of the study. Among 240 relapsing patients, 94 of 133 autologous transplantation–eligible patients (70.7%) and 16 of 107 ineligible patients (15.0%) received the salvage treatments recommended in the study protocol. Adherence to recommendations had no impact on outcome. Best results were seen after allogeneic transplantation, followed by autologous transplantation and treatment without transplantation (5-year overall survival rate, 64.3% vs 45.5% vs 22.6%), but patients undergoing allogeneic transplantation were significantly younger and their disease was well controlled at the time of transplantation. Early outcome prediction by iPET, alone or in combination with other methods, is a powerful tool to investigate the value of immunological treatment options for patients with a poor response to chemotherapy. This trial was registered at ClinicalTrials.gov as #NCT00554164.
摘要PETAL（正电子发射断层扫描引导的侵袭性非霍奇金淋巴瘤治疗）试验研究了在环磷酰胺、多柔比星、长春新碱和泼尼松（CHOP；CD20+淋巴瘤加利妥昔单抗[R]）治疗2个周期后加强治疗是否能提高侵袭性非霍奇金淋巴瘤患者的生存率。共有 754 名患者（87.5%）的中期正电子发射断层扫描（iPET）结果为阴性，108 名患者（12.5%）的中期正电子发射断层扫描（iPET）结果为阳性。中位随访 4 年后，强化治疗并未改善疗效。这些结果在随访 10.3 年后得到了证实。本分析报告还介绍了作为研究一部分的复发治疗情况。在240名复发患者中，133名符合自体移植条件的患者中有94名（70.7%）和107名不符合条件的患者中有16名（15.0%）接受了研究方案中建议的挽救治疗。遵守建议对结果没有影响。接受同种异体移植的疗效最好，其次是自体移植和不进行移植的治疗（5年总生存率分别为64.3% vs 45.5% vs 22.6%），但接受同种异体移植的患者明显更年轻，而且移植时病情控制良好。通过iPET单独或结合其他方法进行早期结果预测，是研究化疗反应不佳患者免疫治疗方案价值的有力工具。该试验已在 ClinicalTrials.gov 注册，编号为 #NCT00554164。
{"title":"Response-guided first-line therapy and treatment of relapse in aggressive lymphoma: 10-year follow-up of the PETAL trial","authors":"Ulrich Dührsen , Andreas Bockisch , Bernd Hertenstein , Imke E. Karsten , Frank Kroschinsky , Michael Heuser , Andreas Hochhaus , Heinz-Gert Höffkes , Dirk Behringer , Gabriele Prange-Krex , Mareike Tometten , Martin Grieshammer , Götz U. Grigoleit , Oliver Schmalz , Karin Jordan , Helga Bernhard , Tobias Gaska , Aristoteles Giagounidis , Roland Schroers , Uwe M. Martens , M. Neuhäuser","doi":"10.1016/j.bneo.2024.100018","DOIUrl":"10.1016/j.bneo.2024.100018","url":null,"abstract":"<div><h3>Abstract</h3><p>The PETAL (Positron Emission Tomography–Guided Therapy of Aggressive Non-Hodgkin Lymphomas) trial investigated whether treatment intensification after 2 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP; plus rituximab [R] for CD20<sup>+</sup> lymphomas) improved survival in aggressive non-Hodgkin lymphoma. A total of 754 patients (87.5%) had a negative and 108 (12.5%) had a positive interim positron emission tomography (iPET) scan. iPET-positive patients were randomly assigned to receive another 6 (R-)CHOP cycles or 6 blocks of a more intensive protocol. Interim PET-negative patients received another 4 cycles of R-CHOP with or without 2 additional doses of R. After a median follow-up of 4 years, treatment intensification had not improved outcome. These results were confirmed after 10.3 years of follow-up. The present analysis also describes the management of relapse that was part of the study. Among 240 relapsing patients, 94 of 133 autologous transplantation–eligible patients (70.7%) and 16 of 107 ineligible patients (15.0%) received the salvage treatments recommended in the study protocol. Adherence to recommendations had no impact on outcome. Best results were seen after allogeneic transplantation, followed by autologous transplantation and treatment without transplantation (5-year overall survival rate, 64.3% vs 45.5% vs 22.6%), but patients undergoing allogeneic transplantation were significantly younger and their disease was well controlled at the time of transplantation. Early outcome prediction by iPET, alone or in combination with other methods, is a powerful tool to investigate the value of immunological treatment options for patients with a poor response to chemotherapy. This trial was registered at <span>ClinicalTrials.gov</span><svg><path></path></svg> as #NCT00554164.</p></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950328024000189/pdfft?md5=0e7371b07f0b752e8ed5c88b58052061&pid=1-s2.0-S2950328024000189-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141145706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-20DOI: 10.1016/j.bneo.2024.100019
Christopher S. Strouse , Vanessa E. Siebert , Bradley T. Loeffler , Bradley D. McDowell , Brian J. Smith , Brian K. Link
Abstract
Bendamustine is among the most commonly used chemoimmunotherapies for patients with follicular lymphoma (FL). It is typically delivered with a goal regimen consisting of 6 cycles, but it is possible that treatment goals could be achieved with fewer cycles, particularly in older patients. We used data from the National Cancer Institute (NCI) linkage between Surveillance, Epidemiology, and End Results program and Medicare claims to evaluate the overall survival of patients with FL receiving 3 to 4 vs 5 to 6 cycles of bendamustine. Patients receiving 1 to 2 cycles of bendamustine chemotherapy were not included. Patients receiving 5 to 6 cycles of bendamustine were significantly younger (mean age, 75.0 vs 76.2 years; P < .01) and had fewer comorbidities by the NCI comorbidity index (mean score, 1.7 vs 2.0; P = .05) than those receiving 3 to 4 cycles of bendamustine, and on univariate analysis exhibited significantly lower risk of death (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.57-0.98; P = .04). However, multivariate analysis controlling for age and comorbidity did not reveal a significant association between overall survival and number of cycles of bendamustine (HR, 0.87; 95% CI, 0.66-1.15; P = .33). Limitations inherent to use of data such as these for causal inference are acknowledged. Nonetheless, these analyses suggest some older patients with FL achieve satisfactory survival outcomes even with lesser bendamustine exposure, and future efforts to prospectively identify such patients are warranted.
{"title":"Optimal number of cycles of bendamustine as initial chemoimmunotherapy for older patients with follicular lymphoma","authors":"Christopher S. Strouse , Vanessa E. Siebert , Bradley T. Loeffler , Bradley D. McDowell , Brian J. Smith , Brian K. Link","doi":"10.1016/j.bneo.2024.100019","DOIUrl":"10.1016/j.bneo.2024.100019","url":null,"abstract":"<div><h3>Abstract</h3><p>Bendamustine is among the most commonly used chemoimmunotherapies for patients with follicular lymphoma (FL). It is typically delivered with a goal regimen consisting of 6 cycles, but it is possible that treatment goals could be achieved with fewer cycles, particularly in older patients. We used data from the National Cancer Institute (NCI) linkage between Surveillance, Epidemiology, and End Results program and Medicare claims to evaluate the overall survival of patients with FL receiving 3 to 4 vs 5 to 6 cycles of bendamustine. Patients receiving 1 to 2 cycles of bendamustine chemotherapy were not included. Patients receiving 5 to 6 cycles of bendamustine were significantly younger (mean age, 75.0 vs 76.2 years; <em>P</em> < .01) and had fewer comorbidities by the NCI comorbidity index (mean score, 1.7 vs 2.0; <em>P</em> = .05) than those receiving 3 to 4 cycles of bendamustine, and on univariate analysis exhibited significantly lower risk of death (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.57-0.98; <em>P</em> = .04). However, multivariate analysis controlling for age and comorbidity did not reveal a significant association between overall survival and number of cycles of bendamustine (HR, 0.87; 95% CI, 0.66-1.15; <em>P</em> = .33). Limitations inherent to use of data such as these for causal inference are acknowledged. Nonetheless, these analyses suggest some older patients with FL achieve satisfactory survival outcomes even with lesser bendamustine exposure, and future efforts to prospectively identify such patients are warranted.</p></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950328024000190/pdfft?md5=39bb4295030312550b540bb0e3d862e2&pid=1-s2.0-S2950328024000190-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141136987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-20DOI: 10.1016/j.bneo.2024.100020
Jun Y. Jiang , Chijioke Nze , Danielle Guffey , Rockbum Kim , Abiodun O. Oluyomi , Omar Rosales , Raka Bandyo , Courtney N. Miller-Chism , Mark M. Udden , Martha P. Mims , Hilary Ma , Gustavo A. Rivero , Akiva Diamond , Purnima S. Teegavarapu , Ang Li ∗ , Christopher R. Flowers ∗
Abstract
Real-world outcome data for patients with large B-cell lymphomas (LBCLs) who are uninsured or have socioeconomic barriers to care are limited. We performed a retrospective cohort study of patients with newly diagnosed LBCL treated in a large safety-net hospital system. Between January 2011 and June 2022, 496 patients aged >18 years were diagnosed with LBCL at Harris Health System, Houston, Texas. The median age was 53 years, 75% were uninsured, and 81% were in the most disadvantaged Area Deprivation Index national quartiles. Most (69%) had stage III/IV disease, 44% had poor-risk disease by the Revised International Prognostic Index (R-IPI), and 17% had a history of HIV infection. The median diagnosis-to-treatment interval was 17 days. The median follow-up time was 53.5 months. Among 464 evaluable patients, 66% achieved a complete response, and 11% had a partial response. Of 48 patients, 26 (54%) eligible for cell therapies received them. At 5 years, event-free and overall survival (OS) rates were 57% and 68%, respectively. Factors that affected OS included Hispanic ethnicity (hazard ratio [HR], 0.70; P = .027), R-IPI (HR, 4.67 for poor vs very good risk; P < .001), National Cancer Institute Comorbidity Index (HR, 1.53 per unit increment; P = .003), hemoglobin (HR, 0.89 per unit increment; P = .002), and International Normalized Ratio (HR, 2.17 per unit increment; P = .007). Insurance status was not associated with differences in OS. In our safety-net health system with robust financial assistance programs and limited access to cell therapies, uninsured status was not associated with inferior outcomes. Addressing barriers to care may improve outcomes in other settings.
{"title":"Clinical outcomes of patients with newly diagnosed large B-cell lymphoma in a safety-net hospital system","authors":"Jun Y. Jiang , Chijioke Nze , Danielle Guffey , Rockbum Kim , Abiodun O. Oluyomi , Omar Rosales , Raka Bandyo , Courtney N. Miller-Chism , Mark M. Udden , Martha P. Mims , Hilary Ma , Gustavo A. Rivero , Akiva Diamond , Purnima S. Teegavarapu , Ang Li ∗ , Christopher R. Flowers ∗","doi":"10.1016/j.bneo.2024.100020","DOIUrl":"10.1016/j.bneo.2024.100020","url":null,"abstract":"<div><h3>Abstract</h3><p>Real-world outcome data for patients with large B-cell lymphomas (LBCLs) who are uninsured or have socioeconomic barriers to care are limited. We performed a retrospective cohort study of patients with newly diagnosed LBCL treated in a large safety-net hospital system. Between January 2011 and June 2022, 496 patients aged >18 years were diagnosed with LBCL at Harris Health System, Houston, Texas. The median age was 53 years, 75% were uninsured, and 81% were in the most disadvantaged Area Deprivation Index national quartiles. Most (69%) had stage III/IV disease, 44% had poor-risk disease by the Revised International Prognostic Index (R-IPI), and 17% had a history of HIV infection. The median diagnosis-to-treatment interval was 17 days. The median follow-up time was 53.5 months. Among 464 evaluable patients, 66% achieved a complete response, and 11% had a partial response. Of 48 patients, 26 (54%) eligible for cell therapies received them. At 5 years, event-free and overall survival (OS) rates were 57% and 68%, respectively. Factors that affected OS included Hispanic ethnicity (hazard ratio [HR], 0.70; <em>P</em> = .027), R-IPI (HR, 4.67 for poor vs very good risk; <em>P</em> < .001), National Cancer Institute Comorbidity Index (HR, 1.53 per unit increment; <em>P</em> = .003), hemoglobin (HR, 0.89 per unit increment; <em>P</em> = .002), and International Normalized Ratio (HR, 2.17 per unit increment; <em>P</em> = .007). Insurance status was not associated with differences in OS. In our safety-net health system with robust financial assistance programs and limited access to cell therapies, uninsured status was not associated with inferior outcomes. Addressing barriers to care may improve outcomes in other settings.</p></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950328024000207/pdfft?md5=e382f0d8e27c903ab9a7be1a0e9c73ff&pid=1-s2.0-S2950328024000207-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141144995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号