EJHaem最新文献

{"title":"Terminal deoxynucleotidyl transferase-positive high-grade B-cell lymphoma with MYC and BCL2 rearrangements transformed from follicular lymphoma","authors":"Radu Chiriac, Lucile Baseggio, Marie Donzel","doi":"10.1002/jha2.1060","DOIUrl":"10.1002/jha2.1060","url":null,"abstract":"<p>A 48-year-old man with a 2-year history of classical follicular lymphoma (according to the 5th WHO classification) [<span>1</span>] involving the axillary lymph nodes achieved complete remission after six cycles of obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. By the end of the third cycle of maintenance therapy with obinutuzumab, the patient presented with epigastric and left hypochondrial pain while in complete remission for 8 months.</p><p>Laboratory studies revealed a lactate dehydrogenase level of 2000 U/L (reference range: 135–235 U/L) and mild anemia (90 g/L). However, the peripheral blood smear showed 10% atypical intermediate-sized lymphomatous cells, characterized by nuclei with oval to irregular contours, finely stippled chromatin, variable nucleoli, and intensely basophilic cytoplasm with numerous vacuoles (Figure 1A). Staging bone marrow was negative. Peripheral blood flow cytometry showed a kappa-restricted population of mature B-cells that were CD45+, CD19+, CD10+, CD5-, and CD20- (Figure 1B). To evaluate the abdominal pain, <sup>18</sup>F-fluorodeoxyglucose (<sup>18</sup>F-FDG) positron emission tomography/computed tomography revealed a left retroperitoneal solid mass with increased <sup>18</sup>F-FDG uptake, an SUVmax of 20, and measuring 6 × 16 cm (Figure 1C).</p><p>Mass biopsy revealed a predominance of monomorphic medium-sized blastoid cells with scant basophilic cytoplasm, round nuclei, and conspicuous nucleoli. Mitotic figures were easily observed (Figure 1D). The neoplastic cells were positive for B-cell markers, including PAX5 and CD19, but negative for CD20. They exhibited a germinal center phenotype (CD10+, BCL6-, and MUM1+) and overexpressed both c-MYC and BCL2. Diffuse terminal deoxynucleotidyl transferase (TdT) expression and monotypic surface immunoglobulin light chain expression were also observed. CD5, CD34, P53, and Epstein–Barr virus-encoded RNA in situ hybridization were negative. The Ki-67 proliferation index was 70%. Fluorescence in-situ hybridization performed with break-apart probes on tissue samples showed <i>MYC</i> (80%) and <i>BCL2</i> (90%) rearrangements, with no <i>BCL6</i> rearrangement (Figure 1D, insets).</p><p>Ifosfamide and etoposide-based chemotherapy were initiated, followed by anti-CD19 chimeric antigen receptor T-cell infusion, which was initially well-tolerated; however, a recurrence developed 3 months later. He was switched to dexamethasone, high-dose cytarabine, and oxaliplatin but developed tumor lysis syndrome with renal failure despite prophylaxis. He experienced progressive disease involving the kidney, lower retroperitoneum, extraperitoneal space, and testis, ultimately dying 7 months after diagnosis.</p><p>This case describes a complex example of an aggressive TdT-positive high-grade B-cell lymphoma (HGBCL), with <i>MYC</i> and <i>BCL2</i> rearrangements transformed from follicular lymphoma marked by significant tissue involvement and a concurrent l","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1351-1353"},"PeriodicalIF":0.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848238","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}

{"title":"Low-dose nivolumab for extranodal natural killer/T-cell lymphoma, nasal type","authors":"Satish Maharaj, Simone Chang","doi":"10.1002/jha2.1059","DOIUrl":"10.1002/jha2.1059","url":null,"abstract":"<p>Natural killer (NK)/T-cell lymphoma is a rare subtype of non-Hodgkin lymphoma that is associated with poor outcomes. Efforts to improve treatment are urgently needed and immune checkpoint inhibitor therapies have shown promise in a series of relapsed/refractory diseases. A 59-year-old Hispanic male presented with near-total obstruction of his left nasal airway. Computed tomography imaging showed left greater than right sinusitis with near-total airway obstruction on the left side. Magnetic resonance imaging (MRI) and positron emission tomography (PET) scan showed a hypermetabolic primary mass in the left nasal cavity measuring 3.5 cm in length by 1.7 cm in width, SUV max 10.99. Nasal endoscopy showed a highly vascular exophytic tumor filling the nasal airway and sinuses; debulking and surgical biopsy were performed.</p><p>Pathology from this showed extranodal NK/T-cell lymphoma, nasal-type (ENKTL). Tumor cells were positive for LCA, CD2, CD3 and CD56 immunostains; negative for CD5, CD4, CD8, CD10, CD20, MUM1, CD21, BCL2, BCL6, CD79A, Cyclin D1, CD30, ALK1, Pan-keratin, HV8, CD57, and c-Myc immunostains. Karyotyping was normal, 46, XY[20], and bone marrow biopsy showed normocellular bone marrow without involvement and active maturing trilinear hematopoiesis. Flow cytometry analysis of the nasal mass demonstrated relatively increased natural killer cells, 66% of lymphocytes CD3-/CD56+ with normal expression of CD16 and no immunophenotypic aberrancies without diminished or loss of CD2, CD7, and/or CD57, or abnormal uniform expression of CD8. Epstein-Barr virus (EBV) was positive by RNA in situ hybridization (EBER Positive). Peripheral blood also was positive with EBV DNA Quantitative polymerase chain reaction level 705 copies/mL.</p><p>Using these evaluations, the patient was determined to have Stage II disease using the Chinese Southwest Oncology Group and Asia Lymphoma Study Group (CA) staging system (CASS) established in 2020 [<span>1</span>]. CASS Stage II is defined as a primary tumor localized to the nasal cavity or nasopharynx involving local structures, without regional lymph node involvement. Research has shown that the Ann Arbor staging system (AASS), established for Hodgkin Lymphoma, has limited predictive ability and poor prognostication for ENKTL with CASS better in discriminating survival than AASS [<span>2, 3</span>]. Unlike most other lymphomas, ENKTL is primarily extranodal, and therefore using the AASS, the majority of ENKTL (70%–90%) appears early (stage I/II) leading to unbalanced distribution and poor predictive accuracy.</p><p>Another model developed for patients treated with non-anthracycline-containing regimens is the prognostic index for NK/T-cell lymphomas (PINK-E) (negative scoring parameters: age  >60 years, stage III/IV disease, distant lymph node involvement, non-nasal subtype, and detectable presentation EBV DNA) [<span>4</span>]. Using PINK-E, this patient would be classified as low-risk. Using the PINK-E model,","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1363-1365"},"PeriodicalIF":0.0,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848601","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}

{"title":"Enteropathy-associated T-cell lymphoma: A population-based cohort study on incidence, treatment, and outcome in the Netherlands","authors":"Frederik O. Meeuwes,&nbsp;Mirian Brink,&nbsp;Wouter J. Plattel,&nbsp;Joost S. P. Vermaat,&nbsp;Marie José Kersten,&nbsp;Mariëlle Wondergem,&nbsp;Otto Visser,&nbsp;Marjolein W. M. van der Poel,&nbsp;Rimke Oostvogels,&nbsp;F. J. Sherida H. Woei-A-Jin,&nbsp;Lara Böhmer,&nbsp;Tjeerd J. F. Snijders,&nbsp;Gerwin A. Huls,&nbsp;Marcel Nijland","doi":"10.1002/jha2.1049","DOIUrl":"10.1002/jha2.1049","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Enteropathy-associated T-cell lymphoma (EATL) is a peripheral T-cell lymphoma (PTCL) with a poor prognosis. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without etoposide consolidated by autologous stem cell transplantation (ASCT) are recommended for fit PTCL patients. The role of etoposide and ASCT in EATL is unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study reports the incidence, treatment, and outcome of EATL patients using the Netherlands Cancer Registry, with nationwide coverage of &gt;95%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All patients diagnosed in 1989–2021 (<i>n</i> = 351, 77% treated) were identified (median age 67 years, 56% male, 50% limited stage). Time period analysis assessed trends in primary therapy and overall survival (OS). Treatment included chemotherapy (CT) (34%), surgery (18%), surgery and CT (19%) or CT followed by ASCT (7%). The 5-year OS for treated patients with limited versus advanced stage was 19% and 9% respectively. The 2-year OS improved over time (21%–33%, <i>p = </i>0.06). Surgery only (hazard ratio [HR] 2.16; 95% confidence interval [CI] 1.55–3.01, <i>p &lt;</i> 0.01) and advanced-stage disease (HR 1.67; 95% CI 1.25–2.23, <i>p =</i> 0.01) were predictors of poor prognosis. ASCT (HR 0.31; 95% CI 0.18–0.56) was associated with improved OS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>There was no statistical difference in OS between patients treated with or without etoposide. Current first-line treatment is ineffective.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1215-1222"},"PeriodicalIF":0.0,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848557","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}

{"title":"IFN-α treatment may enable discontinuation of TKIs in NK cell-licensed patients with CML-CP","authors":"Hiroshi Ureshino,&nbsp;Kazuharu Kamachi,&nbsp;Keisuke Kidoguchi,&nbsp;Shinya Kimura","doi":"10.1002/jha2.1053","DOIUrl":"10.1002/jha2.1053","url":null,"abstract":"<p>The magnitude of the natural killer (NK) cell response contributes to the achievement of treatment-free remission (TFR) in patients with chronic myeloid leukemia (CML) and is regulated by the interaction between killer immunoglobulin-like receptors (KIRs) on NK cells and human leukocyte antigen (HLA) class I molecules on target cells. The abundant combination between <i>KIR</i> and <i>HLA</i> through genetic polymorphisms determines the functional diversity of NK cells. We previously reported that <i>KIR3DL1-HLA-Bw</i> status is associated with achievement of TFR by reflecting NK cell potential. Patients with strong interaction between <i>KIR3DL1/HLA-Bw</i> were identified as having a higher molecular relapse risk, based on the “missing self” hypothesis which suggests that the lack of cognate ligands for KIRs may induce target cell lysis. However, all the patients with strong interaction between <i>KIR3DL1/HLA-Bw</i> who received prior IFN-α therapy achieved TFR (<i>p</i> = 0.007), explained by the “NK cell licensing” concept, whereby NK cells become more functional through the recognition “self” HLA class I molecules by KIRs. NK cell licensing may contribute to the potential efficacy of IFN-α treatment in patients with CML. We defined high-risk molecular relapse patients and suggest that <i>KIR3DL1/HLA-Bw</i> status may help detect patients who could benefit from IFN-α for maintaining TFR.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1278-1282"},"PeriodicalIF":0.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848576","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}

{"title":"Incidence and risk factors of graft failure in allogeneic hematopoietic stem cell transplantation for mucopolysaccharidosis in a nationwide pediatric cohort. A study on behalf of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy","authors":"Laura Danhardt,&nbsp;Arnaud Wiedemann,&nbsp;Gerard Michel,&nbsp;Jean-Hugues Dalle,&nbsp;Fanny Rialland,&nbsp;Cécile Renard,&nbsp;Charlotte Jubert,&nbsp;Johan Maertens,&nbsp;Anne Sirvent,&nbsp;Nimrod Buchbinder,&nbsp;Christine Devalck,&nbsp;Bénédicte Brichard,&nbsp;Catherine Paillard,&nbsp;Stephanie Nguyen,&nbsp;Angelo Paci,&nbsp;David Combarel,&nbsp;Martin Castelle,&nbsp;Simona Pagliuca,&nbsp;Cecile Pochon","doi":"10.1002/jha2.1056","DOIUrl":"10.1002/jha2.1056","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Context</h3>\u0000 \u0000 <p>Mucopolysaccharidosis (MPS) requires urgent treatment to prevent neurological damage. While gene therapy holds promise for effectively treating these diseases with minimal toxicity, access remains limited for most patients. Consequently, advancing allogeneic hematopoietic stem cell transplantation (HSCT) for young children is crucial. Since the 2010s, cord blood (CB) transplants with reduced-toxicity conditioning (RTC) have become the standard of care.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Patients and methods</h3>\u0000 \u0000 <p>Recent reports in France indicate a significant incidence of graft failures (GF), prompting a large-scale retrospective study from the French-speaking bone marrow transplantation society's registry, to understand GF risks, guide clinicians in selecting transplant platforms, and describe outcomes of second HSCT in young patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This report analyses 93 children who underwent HSCT for MPS between 2000 and 2020. The GF rate was notably high (22.6% at day 100), primarily associated with the donor's HLA compatibility and the recipient's age. Well-matched CB and RTC were not found to be risk factors for GF. This study also details the procedures for second and third transplants in patients who rejected their first HSCT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In the era of RTC, CB remains a viable and expedient option for MPS transplantation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1295-1300"},"PeriodicalIF":0.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848595","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}

{"title":"Real-world practitioner perceptions of CARTITUDE-4 results for patients with previously treated multiple myeloma","authors":"Alexandrina Balanean,&nbsp;Samuel Baird,&nbsp;Brooke Dulka,&nbsp;Luke Jennings-Zhang,&nbsp;Robert N. Bone,&nbsp;Yolaine Jeune-Smith,&nbsp;Bruce Feinberg,&nbsp;Muhamed Baljevic","doi":"10.1002/jha2.1047","DOIUrl":"10.1002/jha2.1047","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Initially approved for the fifth-line or later therapeutic setting, the chimeric antigen receptor (CAR) T-cell regimen ciltacabtagene autoleucel (cilta-cel) was recently approved for second-line (2L) treatment in relapsed/refractory multiple myeloma (RRMM). Oncology practitioners use clinical trials to inform treatment, but real-world impressions and impact on practice are lacking. We aimed to determine whether presenting CARTITUDE-4 clinical trial data would impact real-world preferences/perceptions around CAR T-cell therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Recruiting from the Cardinal Health Oncology Provider Extended Network (OPEN), we surveyed hematologists/oncologists to investigate fourth-line (4L) preferences in a hypothetical patient with triple-class–refractory MM. We posed the same questions and answers before and after the trial presentation and compared pre-/post-preferences toward cilta-cel and sequencing relative to bispecific antibodies (BsAbs). Using the same methodology as described above, we also performed a secondary analysis comparing pre-/post-perceptions on the use of CAR T-cell therapy in earlier lines for patients with triple-class–refractory MM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 50 respondents, decision-making factors before the trial presentation included CAR T-cell center availability (58%), comorbidities (52%), and center locations (34%). Additionally, 48% of 46 respondents chose 4L cilta-cel. Among 47, 40% wanted more real-world/long-term CAR T-cell therapy outcomes in any line, 38% wanted more 2L data, and 34% favored 2L/third-line (3L) use. After the presentation, the preference for cilta-cel doubled from 48% to 88% (<i>p </i>&lt; 0.001) among 50 respondents and rose from 34% to 55% (<i>p </i>= 0.001) for earlier-line CAR T-cell therapy among 49. Moreover, 55% of 49 respondents preferred CAR T-cell therapy prior to BsAbs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>We have shown that making oncology practitioners aware of trials precipitated decision-making factors and led to notable, significant shifts in future intended practice patterns. Being aware of trial data enables practitioners to make more informed decisions, tailor therapies to individual patients, and ultimately improve outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1154-1164"},"PeriodicalIF":0.0,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848079","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}

{"title":"Successful treatment of low-risk myelodysplastic syndrome-related anemia in patients with chronic kidney disease with daprodustat: A report of two cases","authors":"Hiroyoshi Kunimoto,&nbsp;Takayuki Sakuma,&nbsp;Takuma Ohashi,&nbsp;Mayoko Shirafuta,&nbsp;Hiroshi Teranaka,&nbsp;Hideaki Nakajima","doi":"10.1002/jha2.1057","DOIUrl":"10.1002/jha2.1057","url":null,"abstract":"<p>Anemia is a major clinical manifestation seen in myelodysplastic syndromes (MDS). Treatment options for anemia in low-risk MDS are limited. Especially, oral medication which is uniformly effective for anemia in low-risk MDS is required. Hypoxia-inducible factor (HIF) prolyl hydroxylase (HIF-PH) inhibitors, such as daprodustat, are oral tablets effective for renal anemia. Pharmacological restoration of HIF activity by HIF-PH inhibitors may be beneficial for MDS-related anemia as well. Yet, their efficacy and safety against low-risk MDS are unclear. Here, we report two cases of low-risk MDS complicated with chronic kidney disease whose anemia responded to daprodustat treatment.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1335-1339"},"PeriodicalIF":0.0,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848233","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}

{"title":"Safety and efficacy of ketamine use in patients with vaso-occlusive crisis: A systematic review and meta-analysis","authors":"Ernesto Calderon Martinez,&nbsp;Stephin Zachariah Saji,&nbsp;Thomas Campos Carmona,&nbsp;Vaidarshi Abbagoni,&nbsp;Mohammad Salman,&nbsp;Mishell Estefanía Llerena Vargas,&nbsp;Suchita Mylavarapu,&nbsp;Druvini Fernando,&nbsp;Lakshmi Sheethal Arvapalli,&nbsp;Nathalia Schettino Samad,&nbsp;Nithin Karnan,&nbsp;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>² = 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>² = 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> &lt; 0.0001, <i>I</i>² = 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}

{"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,&nbsp;Alfonso Piciocchi,&nbsp;Leonardo M. Siena,&nbsp;Stefano Soddu,&nbsp;Francesco Buccisano,&nbsp;Cristina Mecucci,&nbsp;Giovanni Martinelli,&nbsp;Antonio Curti,&nbsp;Roberto Cairoli,&nbsp;Paola Fazi,&nbsp;Marco Vignetti,&nbsp;Maria Teresa Voso,&nbsp;Adriano Venditti,&nbsp;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}

{"title":"Impact of secondary-type mutations in acute myeloid leukemia with CEBPA mutation","authors":"Davidson Zhao,&nbsp;Musani Rumina,&nbsp;Mojgan Zarif,&nbsp;Cuihong Wei,&nbsp;Hong Chang","doi":"10.1002/jha2.1055","DOIUrl":"10.1002/jha2.1055","url":null,"abstract":"&lt;p&gt;To the Editor,&lt;/p&gt;&lt;p&gt;Secondary-type mutations (STM: &lt;i&gt;ASXL1&lt;/i&gt;, &lt;i&gt;BCOR&lt;/i&gt;, &lt;i&gt;EZH2&lt;/i&gt;, &lt;i&gt;SF3B1&lt;/i&gt;, &lt;i&gt;SRSF2&lt;/i&gt;, &lt;i&gt;STAG2&lt;/i&gt;, &lt;i&gt;U2AF1&lt;/i&gt;, and &lt;i&gt;ZRSR2&lt;/i&gt;) in acute myeloid leukemia (AML) were reported to be highly specific for secondary disease and associated with inferior event-free survival (EFS) [&lt;span&gt;1, 2&lt;/span&gt;]. 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) [&lt;span&gt;3&lt;/span&gt;]. In the newly-published International Consensus of Classification of myeloid neoplasms and acute leukemia (ICC), &lt;i&gt;RUNX1&lt;/i&gt; mutation together with STM as described by WHO-HAEM5 define the entity of AML with myelodysplasia-related gene mutations [&lt;span&gt;4&lt;/span&gt;]. To date, several studies have examined the impact of STM in other molecularly defined entities of AML such as &lt;i&gt;NPM1&lt;/i&gt;+ AML [&lt;span&gt;5-9&lt;/span&gt;]. However, the impact of STM in AML with &lt;i&gt;CEBPA&lt;/i&gt; mutation has not been studied extensively and remains unclear. Thus, we sought to investigate the clinical impact of STM in AML with &lt;i&gt;CEBPA&lt;/i&gt; mutation.&lt;/p&gt;&lt;p&gt;We conducted a retrospective analysis with a single center cohort of 38 cases of AML with &lt;i&gt;CEBPA&lt;/i&gt; mutation diagnosed at our institution from 2015 to 2024. Patients were included if they met WHO-HAEM5 criteria of blasts ≥ 20% and either biallelic &lt;i&gt;CEBPA&lt;/i&gt; mutation or single &lt;i&gt;CEBPA&lt;/i&gt; 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 [&lt;span&gt;10&lt;/span&gt;]. Gene panel for targeted sequencing and exon coverage for hotspot genes are listed in Tables S1 and S2.&lt;/p&gt;&lt;p&gt;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 &lt;i&gt;CEBPA&lt;/i&gt; mutation, 11 (29%) had STM. &lt;i&gt;SRSF2&lt;/i&gt; and &lt;i&gt;STAG2&lt;/i&gt; were the most common STMs (both 8/38, 21%), followed by &lt;i&gt;ASXL1&lt;/i&gt; (6/38, 16%), &lt;i&gt;BCOR&lt;/i&gt; (2/38, 5%), and &lt;i&gt;U2AF1&lt;/i&gt; (1/38, 3%). &lt;i&gt;RUNX1&lt;/i&gt; mutations were found in two (5%) patients, both of whom had concurrent WHO-HAEM5-defined STMs. &lt;i&gt;EZH2&lt;/i&gt;, &lt;i&gt;ZRSR2&lt;/i&gt;, and &lt;i&gt;SF3B1&lt;/i&gt; mutations were not detected. The most common recurrent (&gt;10%) co-mutated genes in the cohort were &lt;i&gt;TET2&lt;/i&gt; (10/38; 26%), &lt;i&gt;GATA2&lt;/i&gt; (9/38, 24%), &lt;i&gt;WT1&lt;/i&gt; (8/38, 21%), &lt;i&gt;NRAS&lt;/i&gt; (6/38, 16%) and &lt;i&gt;FLT3&lt;/i&gt;-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 &lt;i&gt;CEBPA&lt;/i&gt; and infrequent in-frame bZIP &lt;i&gt;CEBPA&lt;/i&gt; mutation.&lt;/p&gt;&lt;p&gt;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}