Sickle cell disease (SCD) is characterized by acute episodes called vaso-occlusive crises (VOC). VOC is marked by severe pain due to blocked blood vessels by sickled cells. Ketamine has been reported to be effective and safe in managing VOC in SCD patients.
Objectives/methods
This review aims to determine ketamine's safety and efficacy through analysis of clinical trials and observational studies.
Methods
Adhering to PRISMA guidelines, this systematic review and meta-analysis systematically searched seven databases on May 20, 2024 for randomized control trials (RCT), cohorts, and case–control studies.
Results
Five studies with 689 participants met the inclusion criteria. A meta-analysis of two studies (518 observations) for the Numerical Rating Scale (NRS) pain score showed no significant difference, with a standardized mean difference (MD) of 0.23 (95% CI: −0.13 to 0.59, p = 0.21, I2 = 0%). For morphine milligram equivalent (MME), a meta-analysis of two studies (344 observations) resulted in an MD of −0.03 (95% CI: −0.09 to 0.04, p = 0.45, I2 = 97%). However, the side effects analysis from four studies (608 observations) showed a significantly higher relative risk (RR) of 5.74 (95% CI: 2.80–11.79, p < 0.0001, I2 = 0%) for mild side effects, including nausea, vomiting, and dizziness.
Conclusion
Ketamine qualitative synthesis shows potential for improving pain management in SCD patients during VOC, but without statistically significant differences in pain reduction. It is associated with increased mild side effects, though no severe adverse events were reported. Further research is needed to increase the sample size and power of the analysis to clarify optimal dosing and administration protocols for ketamine in this context.
{"title":"Safety and efficacy of ketamine use in patients with vaso-occlusive crisis: A systematic review and meta-analysis","authors":"Ernesto Calderon Martinez, Stephin Zachariah Saji, Thomas Campos Carmona, Vaidarshi Abbagoni, Mohammad Salman, Mishell Estefanía Llerena Vargas, Suchita Mylavarapu, Druvini Fernando, Lakshmi Sheethal Arvapalli, Nathalia Schettino Samad, Nithin Karnan, Camila Sanchez Cruz","doi":"10.1002/jha2.1050","DOIUrl":"10.1002/jha2.1050","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Sickle cell disease (SCD) is characterized by acute episodes called vaso-occlusive crises (VOC). VOC is marked by severe pain due to blocked blood vessels by sickled cells. Ketamine has been reported to be effective and safe in managing VOC in SCD patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives/methods</h3>\u0000 \u0000 <p>This review aims to determine ketamine's safety and efficacy through analysis of clinical trials and observational studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Adhering to PRISMA guidelines, this systematic review and meta-analysis systematically searched seven databases on May 20, 2024 for randomized control trials (RCT), cohorts, and case–control studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Five studies with 689 participants met the inclusion criteria. A meta-analysis of two studies (518 observations) for the Numerical Rating Scale (NRS) pain score showed no significant difference, with a standardized mean difference (MD) of 0.23 (95% CI: −0.13 to 0.59, <i>p</i> = 0.21, <i>I</i><sup>2</sup> = 0%). For morphine milligram equivalent (MME), a meta-analysis of two studies (344 observations) resulted in an MD of −0.03 (95% CI: −0.09 to 0.04, <i>p</i> = 0.45, <i>I</i><sup>2</sup> = 97%). However, the side effects analysis from four studies (608 observations) showed a significantly higher relative risk (RR) of 5.74 (95% CI: 2.80–11.79, <i>p</i> < 0.0001, <i>I</i><sup>2</sup> = 0%) for mild side effects, including nausea, vomiting, and dizziness.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Ketamine qualitative synthesis shows potential for improving pain management in SCD patients during VOC, but without statistically significant differences in pain reduction. It is associated with increased mild side effects, though no severe adverse events were reported. Further research is needed to increase the sample size and power of the analysis to clarify optimal dosing and administration protocols for ketamine in this context.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1312-1321"},"PeriodicalIF":0.0,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848097","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}
Monica Messina, Alfonso Piciocchi, Leonardo M. Siena, Stefano Soddu, Francesco Buccisano, Cristina Mecucci, Giovanni Martinelli, Antonio Curti, Roberto Cairoli, Paola Fazi, Marco Vignetti, Maria Teresa Voso, Adriano Venditti, Anna Candoni
Given the limited data on the real-life therapeutic use of feline McDonough sarcoma (FMS)-like tyrosine kinase 3 (FLT3) inhibitors in Italy, we surveyed investigators at 59 Italian hematology centers to gain insight into the proportion of acute myeloid leukemia (AML) patients receiving FLT3 inhibitors and we collected data on the efficacy and safety of these agents. The survey results showed that in the real-life setting the response rate of the 3/7 + midostaurin regimen in newly diagnosed FLT3-mutated AML and of gilteritinib in the relapsed/refractory AML were comparable to that reported in the registrative clinical trials. The 3/7 + midostaurin treatment resulted in a 63% of complete remission (CR) rates and gilteritinib in a 44% of CR rates. The discontinuation rate of gilteritinib for intolerance or toxicity was low (accounting for 4% of treated cases).
{"title":"A GIMEMA survey on therapeutic use and response rates of FLT3 inhibitors in acute myeloid leukemia: Insights from Italian real-world practice","authors":"Monica Messina, Alfonso Piciocchi, Leonardo M. Siena, Stefano Soddu, Francesco Buccisano, Cristina Mecucci, Giovanni Martinelli, Antonio Curti, Roberto Cairoli, Paola Fazi, Marco Vignetti, Maria Teresa Voso, Adriano Venditti, Anna Candoni","doi":"10.1002/jha2.1045","DOIUrl":"10.1002/jha2.1045","url":null,"abstract":"<p>Given the limited data on the real-life therapeutic use of feline McDonough sarcoma (FMS)-like tyrosine kinase 3 (FLT3) inhibitors in Italy, we surveyed investigators at 59 Italian hematology centers to gain insight into the proportion of acute myeloid leukemia (AML) patients receiving FLT3 inhibitors and we collected data on the efficacy and safety of these agents. The survey results showed that in the real-life setting the response rate of the 3/7 + midostaurin regimen in newly diagnosed FLT3-mutated AML and of gilteritinib in the relapsed/refractory AML were comparable to that reported in the registrative clinical trials. The 3/7 + midostaurin treatment resulted in a 63% of complete remission (CR) rates and gilteritinib in a 44% of CR rates. The discontinuation rate of gilteritinib for intolerance or toxicity was low (accounting for 4% of treated cases).</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1274-1277"},"PeriodicalIF":0.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848496","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}
Davidson Zhao, Musani Rumina, Mojgan Zarif, Cuihong Wei, Hong Chang
<p>To the Editor,</p><p>Secondary-type mutations (STM: <i>ASXL1</i>, <i>BCOR</i>, <i>EZH2</i>, <i>SF3B1</i>, <i>SRSF2</i>, <i>STAG2</i>, <i>U2AF1</i>, and <i>ZRSR2</i>) in acute myeloid leukemia (AML) were reported to be highly specific for secondary disease and associated with inferior event-free survival (EFS) [<span>1, 2</span>]. In light of these findings, the newly-revised 5th edition of the WHO Classification of Haematolymphoid Tumours (WHO-HAEM5) includes STM in the criteria defining AML, myelodysplasia-related (AML-MR) [<span>3</span>]. In the newly-published International Consensus of Classification of myeloid neoplasms and acute leukemia (ICC), <i>RUNX1</i> mutation together with STM as described by WHO-HAEM5 define the entity of AML with myelodysplasia-related gene mutations [<span>4</span>]. To date, several studies have examined the impact of STM in other molecularly defined entities of AML such as <i>NPM1</i>+ AML [<span>5-9</span>]. However, the impact of STM in AML with <i>CEBPA</i> mutation has not been studied extensively and remains unclear. Thus, we sought to investigate the clinical impact of STM in AML with <i>CEBPA</i> mutation.</p><p>We conducted a retrospective analysis with a single center cohort of 38 cases of AML with <i>CEBPA</i> mutation diagnosed at our institution from 2015 to 2024. Patients were included if they met WHO-HAEM5 criteria of blasts ≥ 20% and either biallelic <i>CEBPA</i> mutation or single <i>CEBPA</i> mutation in the basic leucine zipper (bZIP) domain. Cytogenetic testing, molecular genetic testing, and variant calling in next-generation sequencing were performed according to previously described procedures [<span>10</span>]. Gene panel for targeted sequencing and exon coverage for hotspot genes are listed in Tables S1 and S2.</p><p>The baseline clinicopathological characteristics and co-mutation landscape of the study cohort are summarized in Table 1 and Figure 1A. Of the 38 patients with AML with <i>CEBPA</i> mutation, 11 (29%) had STM. <i>SRSF2</i> and <i>STAG2</i> were the most common STMs (both 8/38, 21%), followed by <i>ASXL1</i> (6/38, 16%), <i>BCOR</i> (2/38, 5%), and <i>U2AF1</i> (1/38, 3%). <i>RUNX1</i> mutations were found in two (5%) patients, both of whom had concurrent WHO-HAEM5-defined STMs. <i>EZH2</i>, <i>ZRSR2</i>, and <i>SF3B1</i> mutations were not detected. The most common recurrent (>10%) co-mutated genes in the cohort were <i>TET2</i> (10/38; 26%), <i>GATA2</i> (9/38, 24%), <i>WT1</i> (8/38, 21%), <i>NRAS</i> (6/38, 16%) and <i>FLT3</i>-ITD (4/38, 11%). Compared to patients without STM, patients with STM were older, had less proliferative disease, had lower hemoglobin levels, and had significantly lower variant allele frequency of mutant <i>CEBPA</i> and infrequent in-frame bZIP <i>CEBPA</i> mutation.</p><p>Consistent with the older age of the STM+ group, only five (46%) patients received intensive chemotherapy compared to all 27 (100%) patients in the STM-ve group. Of note,
{"title":"Impact of secondary-type mutations in acute myeloid leukemia with CEBPA mutation","authors":"Davidson Zhao, Musani Rumina, Mojgan Zarif, Cuihong Wei, Hong Chang","doi":"10.1002/jha2.1055","DOIUrl":"10.1002/jha2.1055","url":null,"abstract":"<p>To the Editor,</p><p>Secondary-type mutations (STM: <i>ASXL1</i>, <i>BCOR</i>, <i>EZH2</i>, <i>SF3B1</i>, <i>SRSF2</i>, <i>STAG2</i>, <i>U2AF1</i>, and <i>ZRSR2</i>) in acute myeloid leukemia (AML) were reported to be highly specific for secondary disease and associated with inferior event-free survival (EFS) [<span>1, 2</span>]. In light of these findings, the newly-revised 5th edition of the WHO Classification of Haematolymphoid Tumours (WHO-HAEM5) includes STM in the criteria defining AML, myelodysplasia-related (AML-MR) [<span>3</span>]. In the newly-published International Consensus of Classification of myeloid neoplasms and acute leukemia (ICC), <i>RUNX1</i> mutation together with STM as described by WHO-HAEM5 define the entity of AML with myelodysplasia-related gene mutations [<span>4</span>]. To date, several studies have examined the impact of STM in other molecularly defined entities of AML such as <i>NPM1</i>+ AML [<span>5-9</span>]. However, the impact of STM in AML with <i>CEBPA</i> mutation has not been studied extensively and remains unclear. Thus, we sought to investigate the clinical impact of STM in AML with <i>CEBPA</i> mutation.</p><p>We conducted a retrospective analysis with a single center cohort of 38 cases of AML with <i>CEBPA</i> mutation diagnosed at our institution from 2015 to 2024. Patients were included if they met WHO-HAEM5 criteria of blasts ≥ 20% and either biallelic <i>CEBPA</i> mutation or single <i>CEBPA</i> mutation in the basic leucine zipper (bZIP) domain. Cytogenetic testing, molecular genetic testing, and variant calling in next-generation sequencing were performed according to previously described procedures [<span>10</span>]. Gene panel for targeted sequencing and exon coverage for hotspot genes are listed in Tables S1 and S2.</p><p>The baseline clinicopathological characteristics and co-mutation landscape of the study cohort are summarized in Table 1 and Figure 1A. Of the 38 patients with AML with <i>CEBPA</i> mutation, 11 (29%) had STM. <i>SRSF2</i> and <i>STAG2</i> were the most common STMs (both 8/38, 21%), followed by <i>ASXL1</i> (6/38, 16%), <i>BCOR</i> (2/38, 5%), and <i>U2AF1</i> (1/38, 3%). <i>RUNX1</i> mutations were found in two (5%) patients, both of whom had concurrent WHO-HAEM5-defined STMs. <i>EZH2</i>, <i>ZRSR2</i>, and <i>SF3B1</i> mutations were not detected. The most common recurrent (>10%) co-mutated genes in the cohort were <i>TET2</i> (10/38; 26%), <i>GATA2</i> (9/38, 24%), <i>WT1</i> (8/38, 21%), <i>NRAS</i> (6/38, 16%) and <i>FLT3</i>-ITD (4/38, 11%). Compared to patients without STM, patients with STM were older, had less proliferative disease, had lower hemoglobin levels, and had significantly lower variant allele frequency of mutant <i>CEBPA</i> and infrequent in-frame bZIP <i>CEBPA</i> mutation.</p><p>Consistent with the older age of the STM+ group, only five (46%) patients received intensive chemotherapy compared to all 27 (100%) patients in the STM-ve group. Of note,","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1370-1372"},"PeriodicalIF":0.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848583","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}
Kerrie Sweeney, Aaron Niblock, Diana Greenfield, John Snowden
Advances in myeloma have resulted in improved prognosis for patients. However complications of the disease and treatment, pose a risk of specific long-term consequences. An audit tool was adapted to assess adherence to the British Society for Haematology guidelines for screening and management of long-term myeloma consequences. Thereafter a screening checklist was developed to prompt the implementation of guideline recommendations, followed by a re-audit evaluating the effectiveness of the checklist.
Good baseline practice was identified relating to vaccinations, herpes prophylaxis, dental assessment, bisphosphonates, calcium/ vitamin D supplementation and holistic needs assessments. However gaps in practice included monitoring of lipids, HBA1C, NT-pro-BNP/ BNP, BMI, calcium/ vitamin D and parathyroid hormone in kidney disease, endocrine screening and geriatric assessments. Re-audit demonstrated that geriatric assessment remains a gap in practice, however other standards now scored between 80 to 100% compliance, highlighting the benefits of a screening checklist, to increase adherence to recommendations.
{"title":"Immediate improvement in patient care: Auditing adherence to the British Society for Haematology guidelines on screening and management of the long-term consequences of multiple myeloma and treatment","authors":"Kerrie Sweeney, Aaron Niblock, Diana Greenfield, John Snowden","doi":"10.1002/jha2.999","DOIUrl":"10.1002/jha2.999","url":null,"abstract":"<p>Advances in myeloma have resulted in improved prognosis for patients. However complications of the disease and treatment, pose a risk of specific long-term consequences. An audit tool was adapted to assess adherence to the British Society for Haematology guidelines for screening and management of long-term myeloma consequences. Thereafter a screening checklist was developed to prompt the implementation of guideline recommendations, followed by a re-audit evaluating the effectiveness of the checklist.</p><p>Good baseline practice was identified relating to vaccinations, herpes prophylaxis, dental assessment, bisphosphonates, calcium/ vitamin D supplementation and holistic needs assessments. However gaps in practice included monitoring of lipids, HBA1C, NT-pro-BNP/ BNP, BMI, calcium/ vitamin D and parathyroid hormone in kidney disease, endocrine screening and geriatric assessments. Re-audit demonstrated that geriatric assessment remains a gap in practice, however other standards now scored between 80 to 100% compliance, highlighting the benefits of a screening checklist, to increase adherence to recommendations.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1359-1362"},"PeriodicalIF":0.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848579","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}
Primary central nervous system lymphoma (PCNSL) is a rare lymphoid malignancy. Systemic profiling of the PCNSL tumor microenvironment (TME) was previously conducted through gene expression analysis. We investigated the prognostic impact of TME on survival to establish novel prognostic biomarkers in PCNSL patients.
Methods
We analyzed expression levels of 770 neuroinflammation-related (NFR) genes via NanoString nCounter technology in tumor samples from 30 PCNSL patients. Genes related to the “recurrence group (RG)” or “non-recurrence group (NRG)” were identified and validated using whole transcriptomic analysis of an independent PCNSL cohort (n = 30).
Results
Forty-five of 770 NFR genes were highly expressed in the RG (3-year overall survival (OS, 22.2%), compared with the NRG group (3-year OS 66.7%). Signatures related to glial cells were enriched in the RG-associated gene set. Multivariate analysis revealed that high expressions of TUBB4A (p = 0.028, HR: 3.88), S100B (p = 0.046, HR: 3.093), and SLC6A1 (p = 0.034, HR: 3.765) were significantly related to death. Expression levels of these three genes were also significantly associated with poor OS in the validation cohort. Immunohistochemical staining against TUBB4A, S100B, and proteins specific to glial cells (GFAP, OLIG2, and CD68) revealed significantly higher positivity in RG glial cells.
Conclusion
These data suggest that TME-related genes play a crucial role in the pathogenesis of PCNSL, complementing the well-known involvement of the NF-kB signaling pathway. TME targeting, especially glial cell-specific proteins, may thus open new and complementary avenues of therapy for all stages of PCNSL.
{"title":"Association between microenvironment-related genes and prognosis of primary central nervous system lymphoma","authors":"Keiichiro Hattori, Kenichi Makishima, Sakurako Suma, Yoshiaki Abe, Yasuhito Suehara, Tatsuhiro Sakamoto, Naoki Kurita, Ryota Ishii, Ryota Matsuoka, Masahide Matsuda, Takao Tsurubuchi, Ryo Nishikawa, Shota Tanaka, Akitake Mukasa, Yoshitaka Narita, Koichi Ichimura, Motoo Nagane, Shingo Takano, Bryan J. Mathis, Eiichi Ishikawa, Daisuke Matsubara, Shigeru Chiba, Mamiko Sakata-Yanagimoto","doi":"10.1002/jha2.1046","DOIUrl":"10.1002/jha2.1046","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Primary central nervous system lymphoma (PCNSL) is a rare lymphoid malignancy. Systemic profiling of the PCNSL tumor microenvironment (TME) was previously conducted through gene expression analysis. We investigated the prognostic impact of TME on survival to establish novel prognostic biomarkers in PCNSL patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed expression levels of 770 neuroinflammation-related (NFR) genes via NanoString nCounter technology in tumor samples from 30 PCNSL patients. Genes related to the “recurrence group (RG)” or “non-recurrence group (NRG)” were identified and validated using whole transcriptomic analysis of an independent PCNSL cohort (<i>n</i> = 30).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Forty-five of 770 NFR genes were highly expressed in the RG (3-year overall survival (OS, 22.2%), compared with the NRG group (3-year OS 66.7%). Signatures related to glial cells were enriched in the RG-associated gene set. Multivariate analysis revealed that high expressions of <i>TUBB4A</i> (<i>p</i> = 0.028, HR: 3.88), <i>S100B</i> (<i>p</i> = 0.046, HR: 3.093), and <i>SLC6A1</i> (<i>p</i> = 0.034, HR: 3.765) were significantly related to death. Expression levels of these three genes were also significantly associated with poor OS in the validation cohort. Immunohistochemical staining against TUBB4A, S100B, and proteins specific to glial cells (GFAP, OLIG2, and CD68) revealed significantly higher positivity in RG glial cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These data suggest that TME-related genes play a crucial role in the pathogenesis of PCNSL, complementing the well-known involvement of the NF-kB signaling pathway. TME targeting, especially glial cell-specific proteins, may thus open new and complementary avenues of therapy for all stages of PCNSL.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1201-1214"},"PeriodicalIF":0.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848509","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}
Joachim Baech, Tarec Christoffer El-Galaly, Joshua P. Entrop, Ingrid Glimelius, Daniel Molin, Sissel Johanne Godtfredsen, Michael J. Crowther, Karin E. Smedby, Sandra Eloranta, Caroline E. Dietrich
Introduction
Congestive heart failure (CHF) is a known complication after anthracyclines and radiotherapy for classical Hodgkin lymphoma (cHL). Contemporary cHL treatment may be associated with less risk because radiotherapy use and techniques have changed substantially over time.
Methods
In this study, Swedish cHL patients diagnosed in 2000–2018, and treated with adriamycin [doxorubicin], bleomycin, vinblastine, and dacarbazine (ABVD) or bleomycin, etoposide, Adriamycin [doxorubicin], cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), were matched 1:10 to the general population on birth year and sex to investigate relative rates and cumulative risks of CHF.
Results
A total of 1994 cHL patients were included, with a median age of 34 years. The median follow-up was 8.1 years. The CHF rate was higher for patients versus comparators (adjusted hazard ratio [HR] = 3.02, 95% confidence interval [CI]: 2.26–4.02). Patients treated with ≤200 mg/m2 of anthracyclines had HR of 2.89 (95% CI: 1.51–3.47) versus 3.91 (95% CI: 2.72–5.60) for >200 mg/m2. Treatment with ABVD was associated with a significantly higher CHF rate (adjusted HR = 3.25, 95% CI: 2.31–4.23), while BEACOPP was not (adjusted HR = 1.95, 95% CI: 0.91–4.16). The increase in relative rates translated to the absolute scale, with an increased risk persisting up to 18 years for low cumulative doses.
Conclusion
These findings highlight that cHL survivors still face a substantial excess risk of CHF in the modern treatment era and that focus on cardiovascular health remains relevant.
{"title":"Congestive heart failure after anthracycline-containing treatment for Hodgkin lymphoma: A Swedish matched cohort study","authors":"Joachim Baech, Tarec Christoffer El-Galaly, Joshua P. Entrop, Ingrid Glimelius, Daniel Molin, Sissel Johanne Godtfredsen, Michael J. Crowther, Karin E. Smedby, Sandra Eloranta, Caroline E. Dietrich","doi":"10.1002/jha2.1048","DOIUrl":"10.1002/jha2.1048","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Congestive heart failure (CHF) is a known complication after anthracyclines and radiotherapy for classical Hodgkin lymphoma (cHL). Contemporary cHL treatment may be associated with less risk because radiotherapy use and techniques have changed substantially over time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, Swedish cHL patients diagnosed in 2000–2018, and treated with adriamycin [doxorubicin], bleomycin, vinblastine, and dacarbazine (ABVD) or bleomycin, etoposide, Adriamycin [doxorubicin], cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), were matched 1:10 to the general population on birth year and sex to investigate relative rates and cumulative risks of CHF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 1994 cHL patients were included, with a median age of 34 years. The median follow-up was 8.1 years. The CHF rate was higher for patients versus comparators (adjusted hazard ratio [HR] = 3.02, 95% confidence interval [CI]: 2.26–4.02). Patients treated with ≤200 mg/m<sup>2</sup> of anthracyclines had HR of 2.89 (95% CI: 1.51–3.47) versus 3.91 (95% CI: 2.72–5.60) for >200 mg/m<sup>2</sup>. Treatment with ABVD was associated with a significantly higher CHF rate (adjusted HR = 3.25, 95% CI: 2.31–4.23), while BEACOPP was not (adjusted HR = 1.95, 95% CI: 0.91–4.16). The increase in relative rates translated to the absolute scale, with an increased risk persisting up to 18 years for low cumulative doses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings highlight that cHL survivors still face a substantial excess risk of CHF in the modern treatment era and that focus on cardiovascular health remains relevant.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1190-1200"},"PeriodicalIF":0.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848539","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}
Red blood cell (RBC) enucleation is a crucial step in the process of erythropoiesis. By removing the nucleus, RBCs gain greater flexibility, enabling them to traverse narrow capillaries with ease, thereby enhancing the efficiency of oxygen and carbon dioxide transport. This transformation underscores the intricate balance between cellular structure and function essential for maintaining homeostasis.
Topic
This review delves into the multifaceted enucleation process, outlining its complex steps that encompass protein sorting, vesicle trafficking, cytoskeletal remodeling, and apoptosis regulation, while also exploring the potential of enhancing the enucleation rate of RBCs in vitro. We emphasize the intricate regulation of this process, which is orchestrated by multiple factors. This includes transcription factors that meticulously guide protein synthesis and sorting through the modulation of gene expression, as well as non-coding RNAs that play a pivotal role in post-transcriptional regulation during various stages of RBC enucleation. Additionally, macrophages participate in the enucleation process by engulfing and clearing the extruded nuclei, further ensuring the proper development of RBCs. Although many studies have deeply explored the molecular mechanisms of enucleation, the roles of apoptosis and anti-apoptotic processes in RBC enucleation remain incompletely understood.
Implication
In this review, we aim to comprehensively summarize the RBC enucleation process and explore the progress made in ex vivo RBC generation. In the future, a deeper understanding of the enucleation process could provide significant benefits to patients suffering from anemia and other related conditions.
{"title":"New insights into the mechanisms of red blood cell enucleation: From basics to clinical applications","authors":"Qianli Zhuo, Zhaojun Zhang, Xiangdong Fang","doi":"10.1002/jha2.1051","DOIUrl":"10.1002/jha2.1051","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Red blood cell (RBC) enucleation is a crucial step in the process of erythropoiesis. By removing the nucleus, RBCs gain greater flexibility, enabling them to traverse narrow capillaries with ease, thereby enhancing the efficiency of oxygen and carbon dioxide transport. This transformation underscores the intricate balance between cellular structure and function essential for maintaining homeostasis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Topic</h3>\u0000 \u0000 <p>This review delves into the multifaceted enucleation process, outlining its complex steps that encompass protein sorting, vesicle trafficking, cytoskeletal remodeling, and apoptosis regulation, while also exploring the potential of enhancing the enucleation rate of RBCs in vitro. We emphasize the intricate regulation of this process, which is orchestrated by multiple factors. This includes transcription factors that meticulously guide protein synthesis and sorting through the modulation of gene expression, as well as non-coding RNAs that play a pivotal role in post-transcriptional regulation during various stages of RBC enucleation. Additionally, macrophages participate in the enucleation process by engulfing and clearing the extruded nuclei, further ensuring the proper development of RBCs. Although many studies have deeply explored the molecular mechanisms of enucleation, the roles of apoptosis and anti-apoptotic processes in RBC enucleation remain incompletely understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Implication</h3>\u0000 \u0000 <p>In this review, we aim to comprehensively summarize the RBC enucleation process and explore the progress made in ex vivo RBC generation. In the future, a deeper understanding of the enucleation process could provide significant benefits to patients suffering from anemia and other related conditions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1301-1311"},"PeriodicalIF":0.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848604","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}
Giulia Freddi, Enea Parimbelli, Federico Vai, Silvana Quaglini, Valeria Bozzi, Serena Barozzi, Fausta Beneventi, Irene De Maggio, Chiara Cavagnoli, Antonio Di Sabatino, Patrizia Noris, Federica Melazzini
Thrombocytopenia during pregnancy is often thought to be associated with severe bleeding manifestations. Three are the main disorders associated with this condition: gestational thrombocytopenia (GT), immune thrombocytopenia (ITP), and inherited thrombocytopenias (ITs). Reaching the correct diagnosis of this condition has relevant therapeutic and outcome implications. We performed a retrospective, observational, monocentric study enrolling 59 consecutive women with isolated thrombocytopenia, attended to our referral center in the last 3 years. Together with personal and family history, platelet (PLT) count trend and mean platelet volume (MPV) in pregnancy are helpful for the diagnosis, with the highest PLT count in GT and lowest in ITs, with different timing of count decrease. MPV is significantly increased in both ITs and ITP. Misdiagnosis with ITP was responsible for unnecessary and unsuccessful therapy in some GT or ITs pregnant women, determining relevant side effects. Excluding inherited platelet function disorders (IPFDs), the bleeding risk for mother with thrombocytopenia and their newborns is similar to the general population. Vaginal delivery is associated with a lower risk of bleeding than cesarean section and therefore is preferable whenever obstetrical–gynecological conditions permit.
{"title":"Isolated thrombocytopenia in pregnancy: A monocentric retrospective study of 63 pregnancies in 59 women","authors":"Giulia Freddi, Enea Parimbelli, Federico Vai, Silvana Quaglini, Valeria Bozzi, Serena Barozzi, Fausta Beneventi, Irene De Maggio, Chiara Cavagnoli, Antonio Di Sabatino, Patrizia Noris, Federica Melazzini","doi":"10.1002/jha2.957","DOIUrl":"10.1002/jha2.957","url":null,"abstract":"<p>Thrombocytopenia during pregnancy is often thought to be associated with severe bleeding manifestations. Three are the main disorders associated with this condition: gestational thrombocytopenia (GT), immune thrombocytopenia (ITP), and inherited thrombocytopenias (ITs). Reaching the correct diagnosis of this condition has relevant therapeutic and outcome implications. We performed a retrospective, observational, monocentric study enrolling 59 consecutive women with isolated thrombocytopenia, attended to our referral center in the last 3 years. Together with personal and family history, platelet (PLT) count trend and mean platelet volume (MPV) in pregnancy are helpful for the diagnosis, with the highest PLT count in GT and lowest in ITs, with different timing of count decrease. MPV is significantly increased in both ITs and ITP. Misdiagnosis with ITP was responsible for unnecessary and unsuccessful therapy in some GT or ITs pregnant women, determining relevant side effects. Excluding inherited platelet function disorders (IPFDs), the bleeding risk for mother with thrombocytopenia and their newborns is similar to the general population. Vaginal delivery is associated with a lower risk of bleeding than cesarean section and therefore is preferable whenever obstetrical–gynecological conditions permit.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1125-1132"},"PeriodicalIF":0.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848600","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}
The authors regret that the Acknowledgments section contains a mistake in the reference to the funding by the “Instituto de Salud Carlos III (ISCIII)” in the published article.
The correct reference is “This work was supported by Instituto de Salud Carlos III (ISCIII), projects PI19/00083 and PI22/00556 (co-funded by the European Union)”.
The authors would like to apologize for any inconvenience caused.
[这更正了文章DOI: 10.1002/jha2.826.]。
{"title":"Correction to: Circulating tumor DNA for monitoring classic Hodgkin lymphoma patients: Correlation with FDG-PET/CT","authors":"","doi":"10.1002/jha2.1044","DOIUrl":"10.1002/jha2.1044","url":null,"abstract":"<p>EJHaem. 2024 Feb; 5(1): 70–75.</p><p>The authors regret that the Acknowledgments section contains a mistake in the reference to the funding by the “Instituto de Salud Carlos III (ISCIII)” in the published article.</p><p>The correct reference is “This work was supported by Instituto de Salud Carlos III (ISCIII), projects PI19/00083 and PI22/00556 (co-funded by the European Union)”.</p><p>The authors would like to apologize for any inconvenience caused.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1373"},"PeriodicalIF":0.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848543","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}
Patients undergoing chimeric antigen receptor (CAR) T-cell therapy face prolonged treatment timelines and are prone to cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) after infusion. Disabilities in physical function and the importance of rehabilitation during CAR-T-cell therapy to maintain physical function have been poorly documented.
Method
We performed a retrospective cohort study to assess changes in exercise tolerance via differences in a 6-min-walking distance (Δ6MWD) and factors influencing it.
Results
A total of 77 patients who underwent rehabilitation during CAR-T-cell therapy were enrolled, and their 6MWD was 450 m (median, range 180–705 m) before and 450.5 m (107.0–735.0 m) 30 days after CAR-T treatment. No significant alteration in Δ6MWD was observed overall (11.0 m, 95% confidence interval, −56.1 to 88.2 m). Multiple regression analyses indicated that age (over vs. under 65 years) revealed no notable differences in Δ6MWD (20 vs. 10 m), while ΔHb (β = 0.24, p = 0.03), moderate/severe CRS (grade 1 with continuous fever or grade ≥2; β = −0.25, p = 0.03), and ICANS (any grade; β = −0.22, p = 0.04) were significantly associated with lower Δ6MWD.
Conclusion
This real-world study indicated that CAR-T-cell therapy is less likely to reduce physical function even in older patients if rehabilitation is properly performed, whereas CRS and ICANS can be risk factors to deprive exercise tolerance.
导语：接受CAR - t细胞治疗的患者面临治疗时间延长，输注后容易发生细胞因子释放综合征（CRS）和免疫效应细胞相关神经毒性综合征（ICANS）。身体功能障碍和car - t细胞治疗期间康复对维持身体功能的重要性文献很少。方法：我们进行了一项回顾性队列研究，通过6分钟步行距离（Δ6MWD）的差异评估运动耐量的变化及其影响因素。结果：共纳入77例CAR-T细胞治疗期间康复的患者，其6MWD在CAR-T治疗前为450 m（中位数，180-705 m），在CAR-T治疗后30天为450.5 m （107.0-735.0 m）。总体上Δ6MWD无显著变化（11.0 m， 95%可信区间，-56.1 ~ 88.2 m）。多元回归分析显示年龄（65岁以上vs. 65岁以下）Δ6MWD无显著差异（20 vs. 10 m），而ΔHb (β = 0.24, p = 0.03)，中/重度CRS(1级持续发烧或≥2级；β = -0.25, p = 0.03)， ICANS(任何分级；β = -0.22, p = 0.04)与较低的Δ6MWD显著相关。结论：这项现实世界的研究表明，如果康复治疗得当，即使在老年患者中，car - t细胞治疗也不太可能降低身体功能，而CRS和ICANS可能是剥夺运动耐量的危险因素。
{"title":"Fluctuation of physical function during chimeric antigen receptor T-cell therapy during rehabilitation intervention: Real-world data and risk factor analyses","authors":"Ryota Hamada, Yasuyuki Arai, Toshio Kitawaki, Naokazu Nakamura, Masanobu Murao, Michiko Matsushita, Junsuke Miyasaka, Tsugumi Asano, Tomoyasu Jo, Momoko Nishikori, Junya Kanda, Chisaki Mizumoto, Kouhei Yamashita, Ryosuke Ikeguchi, Akifumi Takaori-Kondo","doi":"10.1002/jha2.1043","DOIUrl":"10.1002/jha2.1043","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Patients undergoing chimeric antigen receptor (CAR) T-cell therapy face prolonged treatment timelines and are prone to cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) after infusion. Disabilities in physical function and the importance of rehabilitation during CAR-T-cell therapy to maintain physical function have been poorly documented.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>We performed a retrospective cohort study to assess changes in exercise tolerance via differences in a 6-min-walking distance (Δ6MWD) and factors influencing it.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 77 patients who underwent rehabilitation during CAR-T-cell therapy were enrolled, and their 6MWD was 450 m (median, range 180–705 m) before and 450.5 m (107.0–735.0 m) 30 days after CAR-T treatment. No significant alteration in Δ6MWD was observed overall (11.0 m, 95% confidence interval, −56.1 to 88.2 m). Multiple regression analyses indicated that age (over vs. under 65 years) revealed no notable differences in Δ6MWD (20 vs. 10 m), while ΔHb (<i>β</i> = 0.24, <i>p</i> = 0.03), moderate/severe CRS (grade 1 with continuous fever or grade ≥2; <i>β</i> = −0.25, <i>p</i> = 0.03), and ICANS (any grade; <i>β</i> = −0.22, <i>p</i> = 0.04) were significantly associated with lower Δ6MWD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This real-world study indicated that CAR-T-cell therapy is less likely to reduce physical function even in older patients if rehabilitation is properly performed, whereas CRS and ICANS can be risk factors to deprive exercise tolerance.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1252-1259"},"PeriodicalIF":0.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848567","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