Shaji Kumar, Joshua Richter, Saad Z. Usmani, Yael C. Cohen, Jing Christine Ye, María-Victoria Mateos, Vania Hungria, Elena Zamagni
Despite advances in therapy, extramedullary disease (EMD) remains an aggressive form of multiple myeloma associated with poor outcomes. Patients with true EMD, in which plasmacytomas have become completely independent of bone, have a particularly poor prognosis. The pathogenesis of EMD is driven by complex mechanisms involving loss of adhesion molecules, heterogeneous genetic and epigenetic changes, and a solid tumor-like architecture within the microenvironment. Although the introduction of advanced imaging techniques and immunotherapy has led to improved detection and more promising outcomes and regimens, respectively, more prospective studies dedicated to true EMD are needed.
{"title":"Extramedullary Disease—Achilles Heel in Myeloma?","authors":"Shaji Kumar, Joshua Richter, Saad Z. Usmani, Yael C. Cohen, Jing Christine Ye, María-Victoria Mateos, Vania Hungria, Elena Zamagni","doi":"10.1002/ajh.70138","DOIUrl":"10.1002/ajh.70138","url":null,"abstract":"<p>Despite advances in therapy, extramedullary disease (EMD) remains an aggressive form of multiple myeloma associated with poor outcomes. Patients with true EMD, in which plasmacytomas have become completely independent of bone, have a particularly poor prognosis. The pathogenesis of EMD is driven by complex mechanisms involving loss of adhesion molecules, heterogeneous genetic and epigenetic changes, and a solid tumor-like architecture within the microenvironment. Although the introduction of advanced imaging techniques and immunotherapy has led to improved detection and more promising outcomes and regimens, respectively, more prospective studies dedicated to true EMD are needed.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 3","pages":"521-536"},"PeriodicalIF":9.9,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12869003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145852931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marie-Hélène Odièvre, Noémie de Cacqueray, Ilhem Rahal, Alizée Soulié, Mélanie Migaud, Martina Bevacqua, Martin Castelle, Pablo Bartolucci, Slimane Allali, Claire Heilbronner
<p>Heme detoxification through therapeutic plasma exchange (TPE) in sickle cell disease (SCD) has shown benefits in patients with severe intravascular hemolysis complicated by acute multiple organ failure (MOF) syndrome [<span>1, 2</span>]. A favorable outcome was reported after eculizumab (ECZ) treatment of a red blood cell (RBC) transfusion-related hyper-hemolysis in a patient with SCD and parvovirus B19-induced (PVB19) aplastic crisis [<span>3</span>]. These observations, together with our positive experience with anti-C5 antibody treatment for delayed hemolytic transfusion reactions in SCD patients [<span>4</span>], led us to perform rescue TPE followed by ECZ administration in a girl with SCD who developed major intravascular hemolysis with macrophage activation, fat embolism syndrome (FES), and MOF related to severe PVB19 infection.</p><p>This 13-year-old girl with homozygous SCD had no prior history of acute chest syndrome (ACS), cerebral vasculopathy, or chronic organ dysfunction. Her basal hemoglobin (Hb) was 9 g/dL. She was not treated with hydroxyurea and had never been transfused. In November 2023, she presented to our SCD reference center with complaints of headache and asthenia for one week. Physical examination revealed conjunctival pallor without jaundice, a weight of 82 kg, no fever, and no hepatosplenomegaly. Laboratory testing (Table 1) revealed an Hb of 6.3 g/dL with an extremely low reticulocyte count of 3.6 × 10<sup>9</sup>/L suggestive of acute PVB19 infection. She was transfused with two packed RBC units. During the transfusion, she developed anxiety, lower back and chest pain, and dark-colored urine was noted, with no associated hemodynamic disturbances. Eighteen hours after the end of the transfusion, Hb was 8.3 g/dL and HbA 21.8% as expected. No alloantibodies were found and direct antiglobulin test was negative. On day 2, she developed a severe ACS with shortness of breath, high respiratory rate, oxygen requirements up to 7 L/min, bilateral lung consolidation (mostly in the lower pulmonary fields) confirmed on chest X-ray and required admission to the intensive care unit (ICU) for non-invasive ventilation (NIV). IgG and IgM titers and blood polymerase chain reaction (PCR) confirmed acute PVB19 infection. On day 3, she received four more packed RBC units due to Hb values having decreased to 5.6 g/dL. During the transfusion, her respiratory status deteriorated rapidly, with increasing oxygen requirements from the baseline value of 7 L/min on the NIV machine up to 12 L/min. Pulmonary embolism was ruled out. A transthoracic echocardiography found myocardial edema consistent with macrophage activation. Clinical conditions became critical at the end of day 3 with fever up to 40°C, acute respiratory distress syndrome, shock, anuric acute kidney failure, impaired consciousness, and major hepatosplenomegaly. Blood analysis revealed pancytopenia, elevated inflammatory and hemolytic markers, disseminated intravascular coagulation
{"title":"Plasma Exchange and Eculizumab Treatment of a Child With Sickle Cell Disease, Severe Intravascular Hemolysis, Macrophage Activation, and Multiple Organ Failure","authors":"Marie-Hélène Odièvre, Noémie de Cacqueray, Ilhem Rahal, Alizée Soulié, Mélanie Migaud, Martina Bevacqua, Martin Castelle, Pablo Bartolucci, Slimane Allali, Claire Heilbronner","doi":"10.1002/ajh.70174","DOIUrl":"10.1002/ajh.70174","url":null,"abstract":"<p>Heme detoxification through therapeutic plasma exchange (TPE) in sickle cell disease (SCD) has shown benefits in patients with severe intravascular hemolysis complicated by acute multiple organ failure (MOF) syndrome [<span>1, 2</span>]. A favorable outcome was reported after eculizumab (ECZ) treatment of a red blood cell (RBC) transfusion-related hyper-hemolysis in a patient with SCD and parvovirus B19-induced (PVB19) aplastic crisis [<span>3</span>]. These observations, together with our positive experience with anti-C5 antibody treatment for delayed hemolytic transfusion reactions in SCD patients [<span>4</span>], led us to perform rescue TPE followed by ECZ administration in a girl with SCD who developed major intravascular hemolysis with macrophage activation, fat embolism syndrome (FES), and MOF related to severe PVB19 infection.</p><p>This 13-year-old girl with homozygous SCD had no prior history of acute chest syndrome (ACS), cerebral vasculopathy, or chronic organ dysfunction. Her basal hemoglobin (Hb) was 9 g/dL. She was not treated with hydroxyurea and had never been transfused. In November 2023, she presented to our SCD reference center with complaints of headache and asthenia for one week. Physical examination revealed conjunctival pallor without jaundice, a weight of 82 kg, no fever, and no hepatosplenomegaly. Laboratory testing (Table 1) revealed an Hb of 6.3 g/dL with an extremely low reticulocyte count of 3.6 × 10<sup>9</sup>/L suggestive of acute PVB19 infection. She was transfused with two packed RBC units. During the transfusion, she developed anxiety, lower back and chest pain, and dark-colored urine was noted, with no associated hemodynamic disturbances. Eighteen hours after the end of the transfusion, Hb was 8.3 g/dL and HbA 21.8% as expected. No alloantibodies were found and direct antiglobulin test was negative. On day 2, she developed a severe ACS with shortness of breath, high respiratory rate, oxygen requirements up to 7 L/min, bilateral lung consolidation (mostly in the lower pulmonary fields) confirmed on chest X-ray and required admission to the intensive care unit (ICU) for non-invasive ventilation (NIV). IgG and IgM titers and blood polymerase chain reaction (PCR) confirmed acute PVB19 infection. On day 3, she received four more packed RBC units due to Hb values having decreased to 5.6 g/dL. During the transfusion, her respiratory status deteriorated rapidly, with increasing oxygen requirements from the baseline value of 7 L/min on the NIV machine up to 12 L/min. Pulmonary embolism was ruled out. A transthoracic echocardiography found myocardial edema consistent with macrophage activation. Clinical conditions became critical at the end of day 3 with fever up to 40°C, acute respiratory distress syndrome, shock, anuric acute kidney failure, impaired consciousness, and major hepatosplenomegaly. Blood analysis revealed pancytopenia, elevated inflammatory and hemolytic markers, disseminated intravascular coagulation","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 3","pages":"581-585"},"PeriodicalIF":9.9,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70174","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145852901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ahmed Alnughmush, Suheil Albert Atallah-Yunes, Tamer Hellou, Thomas M. Habermann, Yucai Wang, Javier Munoz, Madiha Iqbal, Rebecca L. King, William G. Breen, Jose C. Villasboas, Thomas E. Witzig, Stephen M. Ansell, Grzegorz S. Nowakowski
<p>Extranodal marginal zone lymphoma (EMZL) of mucosa-associated lymphoid tissue (MALT) constitutes approximately 70% of all marginal zone lymphoma (MZL) cases, with the gastric subtype representing the most prevalent anatomical site of origin [<span>1</span>]. Although MALT lymphomas have been described across a broad spectrum of extranodal sites, data specifically addressing primary breast involvement remains limited, largely derived from small case series and population-based analyses, such as those using the SEER database [<span>2-5</span>]. This knowledge gap is particularly relevant in light of epidemiologic trends indicating a decline in the incidence of gastric MALT lymphoma, accompanied by a rising incidence of non-gastric subtypes, including primary breast MALT lymphoma [<span>6, 7</span>].</p><p>Primary breast lymphoma accounts for less than 1% of all non-Hodgkin lymphomas and approximately 3% of extranodal cases. Among these, diffuse large B-cell lymphoma represents the predominant histologic subtype, whereas primary breast MALT lymphoma comprises an estimated 20%–25% of cases [<span>7-9</span>].</p><p>In light of these observations, we sought to provide a comprehensive evaluation of this rare entity, detailing its clinical characteristics, treatment patterns, and outcomes. To our knowledge, this represents the largest single-institution cohort reported to date, with the goal of improving the delineation of clinical features and guiding contemporary management practices.</p><p>Following institutional review board approval, we conducted a retrospective analysis of 38 patients diagnosed with primary breast MALT lymphoma at Mayo Clinic between 1993 and 2024, identified through Epic electronic medical records. Patients were excluded if they had a prior history of MALT lymphoma or if breast involvement occurred as part of disseminated systemic disease. Clinical, pathological, and treatment-related data were abstracted through manual review of the electronic medical records. Statistical analyses were performed using JMP Pro version 17.0.0 (SAS Institute, Cary, NC, USA), with two-sided <i>p</i> values < 0.05 considered statistically significant.</p><p>Event-free survival (EFS) was defined as the interval from diagnosis to disease progression, initiation of subsequent unplanned therapy, or death from any cause and was censored at the date of last follow-up. Overall survival (OS) was defined as the time from diagnosis to death from any cause, with censoring at last known follow-up.</p><p>A total of 38 patients were identified with unilateral or bilateral primary breast MALT lymphoma. The median age at diagnosis was 65.5 years (IQR, 61–74), and the vast majority were female (97.4%). Patient and disease characteristics are summarized in Table 1. Most cases (<i>n</i> = 30, 78.9%) were diagnosed incidentally, with 29 (96.7%) detected on routine screening mammography and one (3.3%) identified via chest CT performed for surveillance of a prior ma
{"title":"Primary Breast MALT Lymphoma: Clinical Features and Outcomes From a Single-Institution Experience at Mayo Clinic","authors":"Ahmed Alnughmush, Suheil Albert Atallah-Yunes, Tamer Hellou, Thomas M. Habermann, Yucai Wang, Javier Munoz, Madiha Iqbal, Rebecca L. King, William G. Breen, Jose C. Villasboas, Thomas E. Witzig, Stephen M. Ansell, Grzegorz S. Nowakowski","doi":"10.1002/ajh.70178","DOIUrl":"10.1002/ajh.70178","url":null,"abstract":"<p>Extranodal marginal zone lymphoma (EMZL) of mucosa-associated lymphoid tissue (MALT) constitutes approximately 70% of all marginal zone lymphoma (MZL) cases, with the gastric subtype representing the most prevalent anatomical site of origin [<span>1</span>]. Although MALT lymphomas have been described across a broad spectrum of extranodal sites, data specifically addressing primary breast involvement remains limited, largely derived from small case series and population-based analyses, such as those using the SEER database [<span>2-5</span>]. This knowledge gap is particularly relevant in light of epidemiologic trends indicating a decline in the incidence of gastric MALT lymphoma, accompanied by a rising incidence of non-gastric subtypes, including primary breast MALT lymphoma [<span>6, 7</span>].</p><p>Primary breast lymphoma accounts for less than 1% of all non-Hodgkin lymphomas and approximately 3% of extranodal cases. Among these, diffuse large B-cell lymphoma represents the predominant histologic subtype, whereas primary breast MALT lymphoma comprises an estimated 20%–25% of cases [<span>7-9</span>].</p><p>In light of these observations, we sought to provide a comprehensive evaluation of this rare entity, detailing its clinical characteristics, treatment patterns, and outcomes. To our knowledge, this represents the largest single-institution cohort reported to date, with the goal of improving the delineation of clinical features and guiding contemporary management practices.</p><p>Following institutional review board approval, we conducted a retrospective analysis of 38 patients diagnosed with primary breast MALT lymphoma at Mayo Clinic between 1993 and 2024, identified through Epic electronic medical records. Patients were excluded if they had a prior history of MALT lymphoma or if breast involvement occurred as part of disseminated systemic disease. Clinical, pathological, and treatment-related data were abstracted through manual review of the electronic medical records. Statistical analyses were performed using JMP Pro version 17.0.0 (SAS Institute, Cary, NC, USA), with two-sided <i>p</i> values < 0.05 considered statistically significant.</p><p>Event-free survival (EFS) was defined as the interval from diagnosis to disease progression, initiation of subsequent unplanned therapy, or death from any cause and was censored at the date of last follow-up. Overall survival (OS) was defined as the time from diagnosis to death from any cause, with censoring at last known follow-up.</p><p>A total of 38 patients were identified with unilateral or bilateral primary breast MALT lymphoma. The median age at diagnosis was 65.5 years (IQR, 61–74), and the vast majority were female (97.4%). Patient and disease characteristics are summarized in Table 1. Most cases (<i>n</i> = 30, 78.9%) were diagnosed incidentally, with 29 (96.7%) detected on routine screening mammography and one (3.3%) identified via chest CT performed for surveillance of a prior ma","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 3","pages":"639-643"},"PeriodicalIF":9.9,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70178","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145852894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to “Budesonide, Added to PTCy ‐Based Regimen, for Prevention of Acute GI GVHD After Allogeneic Stem Cell Transplantation”","authors":"","doi":"10.1002/ajh.70179","DOIUrl":"https://doi.org/10.1002/ajh.70179","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"12 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145844740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}