EJHaem最新文献

{"title":"Concurrent hyperdiploid acute myeloid leukemia and trisomy 12+ chronic lymphocytic leukemia","authors":"Tulasi Geevar, Yasmeen Abulkhair, Cuihong Wei, Hong Chang","doi":"10.1002/jha2.1009","DOIUrl":"https://doi.org/10.1002/jha2.1009","url":null,"abstract":"<p>A 75-year-old man presented with weakness and night sweats of 2 weeks duration. He had anemia (75 g/L), and thrombocytopenia (22 × 10<sup>9</sup>/L) with a white blood cell count of 10.6 × 10<sup>9</sup>/L. Peripheral smear (Figure 1, panel A, 10x objective) showed lymphocytosis (7.6 × 10<sup>9</sup>/L) and 8% promonocytes/blasts. Bone marrow aspirate showed 60% blasts/promonocytes and lymphocytosis (panel B, 63x objective). Biopsy (panel C, 20x objective) showed small lymphoid aggregates, positive for CD5/CD20 (panels D&E, 10x objective), and sheets of MPO+/CD117+ blasts (panels F and G, 20x objectives). Flow cytometry (panels I–M) demonstrated ∼40% atypical monocytic cells (green) and ∼25% blasts (red) which were positive for MPO/HLA-DR/CD64/CD117 and negative for CD34/CD14. There were ∼45% lambda restricted B-cells (pink), positive for CD5/CD19/CD20 (dim)/CD23/CD43/CD200. Karyotyping showed 50, XY with trisomy for chromosomes 2, 8, 19, 21, and without structural abnormalities. Next Generation Sequencing showed NRAS mutation with a variant allele frequency of 17%. Fluorescent in situ hybridization (FISH) in addition showed trisomy 12. A diagnosis of concomitant hyperdiploid acute myeloid leukemia (H-AML) and B-chronic lymphocytic leukemia (B-CLL) with trisomy 12 was rendered.</p><p>A custom interphase FISH was performed using probes for chromosomes 8 and 12 (panel H) which showed trisomy 8 (green signals) in larger nuclei and trisomy 12 (red signals) in smaller nuclei. Both abnormalities were not detected within the same nuclei, indicating the different clonal origin of blasts and CLL cells.</p><p>The patient was treated with an induction regimen consisting of 7 days of cytarabin and 3 days of daunorubicin. He entered a hematologic remission for AML, also with a marked reduction in CLL clones in the bone marrow. He completed two cycles of consolidation therapy but relapsed 14 months after treatment, with 25% blasts in the bone marrow. He was started on venetoclax and azacytidine. His disease progressed, and he succumbed to his illness 2 years after the initial diagnosis.</p><p>Hyperdiploidy (≥3 trisomies without structural abnormalities) is a rare event in AML, reported in < 2% of cases, and confers an intermediate prognosis [<span>1</span>]. It is important to distinguish H-AML from AML with complex karyotype (≥3 unrelated chromosome abnormalities in the absence of other recurring genetic abnormalities and excluding hyperdiploidy) as the latter entity has a poor prognosis as per the 2022 ELN recommendations [<span>2, 3</span>]. Trisomy 12 occurs in ∼20% of CLL, associated with intermediate prognosis [<span>4</span>]. The rare concurrence of H-AML and trisomy 12 B-CLL in this case may represent two separate disease processes.</p><p>Tulasi Geevar, Yasmeen Abulkhair, and Cuihong Wei collected data; Tulasi Geevar and Hong Chang wrote the paper; Hong Chang supervised the study.</p><p>The authors declare no conflict of interest.</p><p>The ","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"1082-1083"},"PeriodicalIF":0.0,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.1009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438980","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":"Single-centre experience of implementing physiotherapist-led prehabilitation for chimeric antigen receptor T cell therapy","authors":"Orla McCourt,&nbsp;Paul Maciocia,&nbsp;Claire Roddie,&nbsp;Angela Hwang,&nbsp;Leigh Wood,&nbsp;Aikaterini Panopoulou,&nbsp;Deborah Ann Springell,&nbsp;Maise Al Bakir,&nbsp;Maeve O'Reilly","doi":"10.1002/jha2.1006","DOIUrl":"https://doi.org/10.1002/jha2.1006","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>This report outlines the evaluation of physiotherapist-led prehabilitation/rehabilitation for recipients of chimeric antigen receptor T (CAR-T) cell therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A hybrid approach was used, incorporating in-person assessment of quality of life and functional capacity (6-min walk test and timed sit-to-stand test), and a personalised home exercise programme with remotely delivered physiotherapist support pre/post-admission.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Functional deficits were prevalent at referral for CAR-T. Prehabilitation and rehabilitation were highly acceptable to patients, and improvements in functional capacity were documented pre-admission.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This data highlights the importance of pre-CAR-T functional assessment and prehabilitation to optimise preparation and recovery.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"1033-1037"},"PeriodicalIF":0.0,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.1006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439017","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":"Certainty in uncertainty: Determining the rate and reasons for reclassification of variants of uncertain significance in haematological malignancies","authors":"Anoop K. Enjeti,&nbsp;Natasha Walker,&nbsp;Oliver Fahey,&nbsp;Elizabeth Johnston,&nbsp;Hannah Legge-Wilkinson,&nbsp;Nateika Ramsurrun,&nbsp;Jonathan Sillar,&nbsp;Lisa F. Lincz,&nbsp;Andrew Ziolkowski,&nbsp;David Mossman","doi":"10.1002/jha2.1002","DOIUrl":"https://doi.org/10.1002/jha2.1002","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Variants of uncertain significance (VUS) are commonly reported in cancer with the widespread adoption of diagnostic massive parallel sequencing. The rate of reclassification of VUS in patients with haematological malignancy is not known and we evaluated this retrospectively. We also investigated whether re-evaluating VUS in 12–24 months or greater than 24 months post-initial classification was significant.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>A retrospective audit of patients with haematological malignancies referred to the Molecular Medicine Department at the John Hunter Hospital in Newcastle, Australia between September 2018 and December 2021. Data was analysed for VUS, which was then re-analysed in standard software using current somatic variant guidelines. Proportions of VUS at baseline were compared to post-re-analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The most common diagnoses in the patient cohort (<i>n</i> = 944) were acute myelogenous leukaemia (41%), myelodysplastic syndrome (31%), and chronic myelomonocytic leukaemia (7%). A total of 210 VUS were re-analysed. The most common VUS were in the TET2 (20%), RUNX1 (10%) and DNMT3A (9%) genes. A total of 103 were re-analysed at 24–39 months post-initial classification and 107 variants were re-analysed between 12 and 24 months post-initial classification. Of these, 33 (16%) of VUS were re-classified at 24–39 months and 12 (11%) were re-classified at 12–24 months post-initial classification. The most common variants that were re-classified in both groups were CSF3R (32%), TET2 (29%), ASXL1 (11%) and ZRSR2 (11%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study on reclassification of VUS in blood cancers demonstrated that one in seven VUS were re-classified 12 months post initial classification. This can inform practice guidelines and potentially impact the prognosis, diagnosis and treatment of haematological malignancies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"957-963"},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.1002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438900","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":"Mixed autoimmune hemolytic anemia as the initial presentation of systemic lupus erythematosus: A case report and review","authors":"Brian P. Edwards,&nbsp;Sidhartha Gautam Senapati,&nbsp;Mariia Kasianchyk,&nbsp;Joel Shah,&nbsp;Fatih Ayvali,&nbsp;Satish Maharaj","doi":"10.1002/jha2.1008","DOIUrl":"https://doi.org/10.1002/jha2.1008","url":null,"abstract":"<p>Autoimmune hemolytic anemia (AIHA) is an acquired condition caused by autoantibody mediated destruction of erythrocytes. AIHA is classified as warm or cold depending on whether the autoantibodies involved react optimally at or below body temperature (37°C), respectively. Mixed AIHA, with features of both, is rare and clinically more severe. We report a case of mixed AIHA that was found to be the presentation of systemic lupus erythematosus (SLE). Treatment with rituximab and prednisone resulted in good response. Although more commonly associated with warm AIHA, SLE can present with mixed AIHA.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"1053-1056"},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.1008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438917","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 diagnosis of non-neuronopathic and late-onset acid sphingomyelinase deficiency (Niemann-Pick disease A/B) following bone marrow biopsy showing foamy histiocytosis","authors":"Ivo N. SahBandar,&nbsp;Gustavo H. B. Maegawa,&nbsp;Danielle Brandman,&nbsp;Jacob H. Rand,&nbsp;Hana I. Lim,&nbsp;Julia T. Geyer","doi":"10.1002/jha2.1003","DOIUrl":"https://doi.org/10.1002/jha2.1003","url":null,"abstract":"&lt;p&gt;The patient was a 44-year-old East-Asian descent male presenting with longstanding splenomegaly, thrombocytopenia, easy bruising since childhood, and cryptogenic cirrhosis with a history of recurrent variceal bleeding, currently being evaluated for a liver transplant. Pertinent laboratory findings include low serum albumin (3.6, &lt;i&gt;N&lt;/i&gt; = 3.9–5.2 g/dL), increased total (4.8, &lt;i&gt;N&lt;/i&gt; = 0.3–1.2 mg/dL), direct (1.3, &lt;i&gt;N&lt;/i&gt; = ≤ 0.3 mg/dL), and indirect bilirubin (3.5, &lt;i&gt;N&lt;/i&gt; = 0.1–0.8 mg/dL), mild AST elevation (53, &lt;i&gt;N&lt;/i&gt; = ≤ 34 U/L), mild normocytic anemia (Hgb 119, &lt;i&gt;N&lt;/i&gt; = 126–170 g/L, MCV 85.9, &lt;i&gt;N&lt;/i&gt; = 78.6–94.2 fL), and thrombocytopenia (22 × 10e9, &lt;i&gt;N&lt;/i&gt; = 156–325 × 10e9/L).&lt;/p&gt;&lt;p&gt;The bone marrow biopsy and clot section showed erythroid hyperplasia, decreased granulopoiesis with complete maturation for both lineages, and reduced megakaryocytes (Figure 1, panel A, H&amp;E, 40X original magnification). A significant number of foamy histiocytes were identified, some of which contained cytoplasmic red blood cells (erythrophagocytosis, panel A). While most macrophages were negative for Periodic acid–Schiff (PAS) special stain, rare PAS-positive macrophages were seen (black arrow; Figure 1, panel B, PAS special stain, 40X original magnification). The described findings ruled out the presence of glycogen storage or Whipple disease. Representative macrophages (Figure 1, panels C–E, Wright-Giemsa, 100X original magnification) show typical features of acid sphingomyelinase deficiency (ASMD, aka Niemann-Pick disease types A/B) with low nuclear to cytoplasmic ratio and ample uniformly finely vacuolated cytoplasm, some contained red blood cells and debris (panel D), and sea blue histiocytes with deeply basophilic cytoplasm were noted (panel E). No organisms were identified by Grocott-Gomori methenamine silver (GMS) staining, and immunohistochemistry studies showed foamy histocytes non-reactivity to S100, langerin, and BRAF (figures not shown).&lt;/p&gt;&lt;p&gt;The clinical history and bone marrow biopsy findings were suspicious for lysosomal storage disease, and subsequent sphingomyelinase enzymatic activity (dried-blot spot, DBS) showed decreased residual activity (0.4 nmol/L, N ≥ 2.5 nmol/L) consistent with the late-onset non-neuronopathic form of ASMD, which is characterized by the development of hepatosplenomegaly and associated thrombocytopenia. In addition, the oxysterol, cholestane-3beta,5alpha- 6beta-triol (1.0 nmol/mL, &lt;i&gt;N&lt;/i&gt; ≤ 0.8), and lyso-sphingomyelin (0.582 nmol/mL &lt;i&gt;N&lt;/i&gt; ≤ 0.100) were elevated in DBS. Interestingly, chitotriosidase (492 nmols/h/mL, &lt;i&gt;N&lt;/i&gt; 4–120) and angiotensin-converting enzyme (114 IU/L, &lt;i&gt;N&lt;/i&gt; 16–85) were also elevated, reflecting the expanded reticulum endothelial system. Other lysosomal enzymes were at normal levels, as well as other sphingolipids, including lyso-glucosylphingosine. The case illustrates the importance of identifying bone marrow lipid-laden foam cells, triggering investigations for ASMD, ","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"1078-1079"},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.1003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438918","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":"Neoplastic plasma cells with concomitant azurophilic crystalline inclusions and Snapper-Schneid bodies","authors":"Radu Chiriac,&nbsp;Luc-Marie Gerland,&nbsp;Lucile Baseggio","doi":"10.1002/jha2.1004","DOIUrl":"https://doi.org/10.1002/jha2.1004","url":null,"abstract":"<p>A 66-year-old woman was being monitored for severe osteoporosis. Laboratory studies showed a 6 g/dL M spike and immunoglobulin M kappa paraprotein. Also, CRAB criteria were met.</p><p>The bone marrow (BM) aspirate revealed the presence of 30% atypical plasma cells (PC), which contained numerous large cytoplasmic azurophilic granules that appeared as dots resembling intracellular microorganisms. Concurrently, these cells were reminiscent of the “storage-type” histiocytes reported in lysosomal storage diseases (Figure 1, Panels A and B; May-Grunwald Giemsa stain [MGG], x100 objective). However, a subset of PC displayed coarse azurophilic granules, morphologically consistent with Snapper-Schneid bodies (Figure 1, Panels A and B [arrows]; MGG stain, x100 objective). Flow cytometry of the BM aspirate revealed a monotypic CD38+/CD138+ PC population with an aberrant profile characterized by the loss of CD45 and CD19. These PC were also CD56-, CD200+, CD20+, CD117+, and CD27- (Figure 1, Panel C), and expressed kappa immunoglobulin light chain, consistent with the observed paraprotein.</p><p>Various types of cytoplasmic inclusions have been documented in plasma cell neoplasms, including Russell bodies, crystals, and Auer rod-like inclusions, while azurophilic granules and Snapper-Schneid bodies remain uncommon. This myeloma case is particularly noteworthy as it demonstrates the presence of both azurophilic granules and Snapper-Schneid bodies in an untreated patient with a rare paraprotein: immunoglobulin M kappa. Previous case reports have documented this phenomenon in pretreated patients, including those involving diamidine treatment [<span>1</span>].</p><p>The presence of PC with atypical granules and an aberrant immunophenotype underscores diagnostic complexity, requiring thorough morphological and immunological examination. Careful distinction of these features from those of microbial infections or lysosomal storage diseases is essential to ensure appropriate clinical management.</p><p>Radu Chiriac wrote the manuscript; Lucile Baseggio and Luc-Marie Gerland conducted the cytological and flow cytometric studies. All authors contributed to the final manuscript.</p><p>The authors declare no conflict of interest.</p><p>The authors received no specific funding for this work.</p><p>This manuscript respects the ethical policy of Hospices Civils de Lyon for the treatment of human research participants.</p><p>No patient-identifying data were used. The authors did not obtain written informed consent from the patient but the patient did not object to his data being used for research purposes (as required by the ethics policy of Hospices Civils de Lyon).</p><p>The authors have confirmed clinical trial registration is not needed for this submission.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"1076-1077"},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.1004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439028","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 treatment of large B-cell lymphoma with chimeric antigen receptor T-cell therapy after loncastuximab tesirine","authors":"Mehdi Hamadani,&nbsp;Melanie Lucero,&nbsp;Jakob D DeVos,&nbsp;Lei Chen","doi":"10.1002/jha2.993","DOIUrl":"https://doi.org/10.1002/jha2.993","url":null,"abstract":"<p> \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"1110-1113"},"PeriodicalIF":0.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.993","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438891","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, description, and timing of serious and opportunistic infections in patients with hairy cell leukemia","authors":"Nilesh Kapoor,&nbsp;Qiuhong Zhao,&nbsp;Andrew Stiff,&nbsp;Seema A. Bhat,&nbsp;Mirela I. Anghelina,&nbsp;Leslie A. Andritsos,&nbsp;James S. Blachly,&nbsp;Narendranath Epperla,&nbsp;Zeinab El Boghdadly,&nbsp;Michael R. Grever,&nbsp;Kerry A. Rogers","doi":"10.1002/jha2.982","DOIUrl":"https://doi.org/10.1002/jha2.982","url":null,"abstract":"<p>Hairy cell leukemia is an uncommon B-cell malignancy with excellent response to purine analogs and to targeted therapies such as ibrutinib and vemurafenib. However, purine analogs are known to be highly immunosuppressive and the infection burden in this patient population with current therapies is unknown. We therefore conducted a retrospective cohort study following 149 patients. Median follow-up time was 6.9 years. Thirty-six percent developed an opportunistic or serious infection requiring hospitalization. Most cases were bacterial and most coincided with neutropenia and/or CD4 T-lymphopenia. No single treatment agent was significantly associated with increased or decreased incidence of infection. Reassuringly, the cumulative incidence of infections plateaued 2 months after initial treatment suggesting clinically significant immune recovery. Only one patient in our cohort passed away due to infection. Estimated 10-year overall survival was 99% suggesting that infections may not cause as much mortality as was seen prior to current therapies.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"1005-1009"},"PeriodicalIF":0.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.982","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439128","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":"Benefits of serum protein electrophoresis as part of hematopoietic stem cell donor clearance","authors":"Laura Kilinc,&nbsp;Burkhardt Schleipen,&nbsp;Karen Ende,&nbsp;Deborah Buk,&nbsp;Alexander H. Schmidt,&nbsp;Isabel Auer,&nbsp;Thilo Mengling","doi":"10.1002/jha2.997","DOIUrl":"https://doi.org/10.1002/jha2.997","url":null,"abstract":"&lt;p&gt;To be cleared for hematopoietic stem cell (HSC) donation, potential donors must undergo a physical examination including blood testing to test their health status and eligibility to donate, ensuring safety for the donor and limiting the risk of transmitting infectious, genetic, or neoplastic diseases from the donated HSC product to the recipient. In Germany, the applicable national standards [&lt;span&gt;1&lt;/span&gt;] require additional donor blood testing with serum protein electrophoresis (SPEP), to exclude the presence of monoclonal gammopathy of undetermined significance (MGUS) as part of this physical examination.&lt;/p&gt;&lt;p&gt;MGUS is a premalignant plasma cell disorder in which plasma cells produce incomplete or non-functional monoclonal antibodies (paraproteins). Patients with MGUS have a life-long risk of developing multiple myeloma (MM), smoldering myeloma (SMM), or a related malignant disorder. The condition is usually discovered by the presence of serum monoclonal protein (M protein) that forms a peak (M gradient), usually in the gamma-globulin fraction, in SPEP [&lt;span&gt;2&lt;/span&gt;]. MGUS is found in more than 3% of the population aged 50 years and older, its prevalence increases with age, and it is more often found in men than in women [&lt;span&gt;3, 4&lt;/span&gt;]. The risk for MGUS patients to develop MM, SMM or a related malignant disorder is about 1% per consecutive year [&lt;span&gt;4, 5&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Even if large quantities of plasma cells should not be transferred during HSC transplantation, a transfer of premalignant clonal cell populations to the recipient cannot be excluded. Transmission of MGUS has already been shown in solid organ transplantations [&lt;span&gt;6&lt;/span&gt;]. In addition, blood-borne malignancies have been transferred by HSC transplantation [&lt;span&gt;7, 8&lt;/span&gt;]. Therefore, registered donors with MGUS are ineligible for HSC donation and need to be identified and excluded during the physical examination with SPEP prior to donor clearance for HSC donation. However, in many countries, donor testing for MGUS is not carried out prior to HSC donation. Our findings highlight the need to include MGUS testing with SPEP for potential HSC donors prior to HSC collection as a standard to ensure both donor and specifically patient safety.&lt;/p&gt;&lt;p&gt;In this work, we present data from DKMS Germany within a time period of 13 years (2009–2022) in which potential HSC donors were screened for MGUS during the physical examination prior to HSC collection. Based on these data, we analyzed the effect of MGUS testing with SPEP at this process step and discuss implications for HSC donation.&lt;/p&gt;&lt;p&gt;Since 2009 (observation period: January 2009 until December 2022), DKMS Germany has had all potential HSC donors who were requested for donation tested for MGUS as part of the physical examination, taking place within 30 days prior to the planned collection date at the collection center. The method used to detect MGUS was SPEP. Immunofixation electrophoresis (IFE) was used to further dif","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"1107-1109"},"PeriodicalIF":0.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.997","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439124","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":"Changes in indicators of cerebral metabolic stress following treatment with voxelotor in children and adolescents with sickle cell anemia","authors":"Andrew M. Heitzer,&nbsp;Ping Zou,&nbsp;Jason Hodges,&nbsp;Clark Brown,&nbsp;Mark Davis,&nbsp;Sandy Dixon,&nbsp;Robert J. Ogg,&nbsp;Jeremie Estepp,&nbsp;Jane S Hankins,&nbsp;Ranganatha Sitaram,&nbsp;Clifford M. Takemoto","doi":"10.1002/jha2.1001","DOIUrl":"https://doi.org/10.1002/jha2.1001","url":null,"abstract":"<p>Voxelotor is a small molecule that reduces the polymerization of sickle hemoglobin by increasing its affinity for oxygen. In patients with sickle cell anemia, it has been postulated that increasing hemoglobin-oxygen affinity could limit oxygen offloading from hemoglobin, causing an increase in cerebral metabolic stress. To investigate this hypothetical concern, we used multimodal brain imaging to define the effects of voxelotor on cerebral blood flow and oxygen extraction. We followed four patients for 2–5 months during and/or after voxelotor therapy. This study showed no observable increase in cerebral blood flow or oxygen extraction fraction during treatment.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"976-980"},"PeriodicalIF":0.0,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.1001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439123","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}