Christin B. DeStefano, Nicholas Burwick, Drew A. Helmer
{"title":"Are veterans at increased risk of myeloproliferative neoplasms?","authors":"Christin B. DeStefano, Nicholas Burwick, Drew A. Helmer","doi":"10.1002/ajh.27453","DOIUrl":"10.1002/ajh.27453","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"99 10","pages":"1852-1854"},"PeriodicalIF":10.1,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27453","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905553","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}
<p>The economic inequality of healthcare has been well documented. Out-of-pocket costs, which include laboratory costs, contribute to the financial burden that patients must bear for healthcare. This is particularly true for those patients living with a condition that requires frequent laboratory monitoring. Such is the case for those suffering from iron deficiency and iron deficiency anemia. Anemia accounts for 68.4 million years of life lived with a disability.<span><sup>1</sup></span> Data from Scripps-Kaiser and the National Health and Nutrition Examination Survey highlights the prevalence of anemia in the United States to be highest in Black women (or those who menstruate).<span><sup>2</sup></span> Recent data from Canada showed the correlation between anemia and socioeconomic status with lower household income associated with the greatest odds of anemia.<span><sup>3</sup></span> Various factors contribute to the burden of anemia in women of color, including disproportionately higher rates of heavy menstrual bleeding (HMB) from fibroids.<span><sup>4</sup></span> HMB, defined as greater than 80 mL blood loss per month or excessive menstrual blood loss that interferes with a woman's physical, emotional, social, and material quality of life, depletes iron stores leading to iron deficiency.<span><sup>5</sup></span> HMB has been reported to affect between 10% and 30% of reproductive age women in the United States, with a symptom duration of years commonly reported.<span><sup>6</sup></span> These numbers are even higher in persons with a bleeding disorder or on anticoagulation.<span><sup>7</sup></span> Iron deficiency leads to fatigue, impaired cognitive function, and decreased mood, leading to loss of quality of life and personal productivity.<span><sup>8</sup></span></p><p>HMB and resultant iron deficiency require frequent healthcare visits and laboratory monitoring. The correlation between race, income, and healthcare spending are profound. One study found Black insured participants were more likely to reduce spending on basic needs, leisure activities, and skip medications to cover the cost of medical care compared to non-Black participants.<span><sup>9</sup></span></p><p>To address disparities in healthcare access and affordability, it is necessary to understand the financial implications of obtaining necessary testing. Federal regulations require hospitals to post charges for procedures and laboratory tests. Charge data are available as master files or as on-line calculators for a limited number of tests. Price estimates can also be directly requested from financial service offices. Price estimates may include a discount for self-pay. We set out to determine the self-pay charges for iron deficiency and anemia testing including a complete blood cell count (CBC) and a serum/plasma ferritin at major medical centers in Boston, Connecticut, and two national laboratories.</p><p>In this cross-sectional study, we manually collected laboratory charge
{"title":"Self-pay laboratory charges for iron deficiency diagnosis in the Boston and New Haven metropolitan areas","authors":"Layla Van Doren, Carlo Brugnara","doi":"10.1002/ajh.27457","DOIUrl":"10.1002/ajh.27457","url":null,"abstract":"<p>The economic inequality of healthcare has been well documented. Out-of-pocket costs, which include laboratory costs, contribute to the financial burden that patients must bear for healthcare. This is particularly true for those patients living with a condition that requires frequent laboratory monitoring. Such is the case for those suffering from iron deficiency and iron deficiency anemia. Anemia accounts for 68.4 million years of life lived with a disability.<span><sup>1</sup></span> Data from Scripps-Kaiser and the National Health and Nutrition Examination Survey highlights the prevalence of anemia in the United States to be highest in Black women (or those who menstruate).<span><sup>2</sup></span> Recent data from Canada showed the correlation between anemia and socioeconomic status with lower household income associated with the greatest odds of anemia.<span><sup>3</sup></span> Various factors contribute to the burden of anemia in women of color, including disproportionately higher rates of heavy menstrual bleeding (HMB) from fibroids.<span><sup>4</sup></span> HMB, defined as greater than 80 mL blood loss per month or excessive menstrual blood loss that interferes with a woman's physical, emotional, social, and material quality of life, depletes iron stores leading to iron deficiency.<span><sup>5</sup></span> HMB has been reported to affect between 10% and 30% of reproductive age women in the United States, with a symptom duration of years commonly reported.<span><sup>6</sup></span> These numbers are even higher in persons with a bleeding disorder or on anticoagulation.<span><sup>7</sup></span> Iron deficiency leads to fatigue, impaired cognitive function, and decreased mood, leading to loss of quality of life and personal productivity.<span><sup>8</sup></span></p><p>HMB and resultant iron deficiency require frequent healthcare visits and laboratory monitoring. The correlation between race, income, and healthcare spending are profound. One study found Black insured participants were more likely to reduce spending on basic needs, leisure activities, and skip medications to cover the cost of medical care compared to non-Black participants.<span><sup>9</sup></span></p><p>To address disparities in healthcare access and affordability, it is necessary to understand the financial implications of obtaining necessary testing. Federal regulations require hospitals to post charges for procedures and laboratory tests. Charge data are available as master files or as on-line calculators for a limited number of tests. Price estimates can also be directly requested from financial service offices. Price estimates may include a discount for self-pay. We set out to determine the self-pay charges for iron deficiency and anemia testing including a complete blood cell count (CBC) and a serum/plasma ferritin at major medical centers in Boston, Connecticut, and two national laboratories.</p><p>In this cross-sectional study, we manually collected laboratory charge","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"99 11","pages":"2233-2235"},"PeriodicalIF":10.1,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27457","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905554","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}
Samer Al Hadidi, Obada Ababneh, Carolina Schinke, Sharmilan Thanendrarajan, Clyde Bailey, Guido Tricot, John Shaughnessy Jr, Fenghuang Zhan, Jeffrey Sawyer, Eric R. Siegel, Maurizio Zangari, Bart Barlogie, Frits van Rhee
<p>Autologous hematopoietic stem cell transplantation (HSCT) is a standard treatment for eligible multiple myeloma (MM) patients.<span><sup>1</sup></span> Before high-dose chemotherapy and autologous HSCT, patients typically receive induction therapy with a proteasome inhibitor and an immunomodulatory (IMiD) agent. This approach, along with posttransplant maintenance therapies, has improved survival, with some patients achieving a median overall survival (OS) of over 10 years.<span><sup>1</sup></span></p><p>While late mortality rates have decreased over the past three decades, the incidence of second primary malignancies (SPM) has not.<span><sup>2</sup></span> Given improved survival rates, understanding long-term complications like SPM is crucial, particularly as most phase III MM trials lack extended follow-up.<span><sup>3</sup></span></p><p>Autologous HSCT enhances long-term disease control and survival in newly diagnosed MM patients but increases the risk of SPM, including second hematologic malignancies (SHM). A Swedish study found that higher cumulative doses of melphalan were linked to a 2.8-fold increased risk of therapy-related myeloid neoplasms.<span><sup>4</sup></span> In a study of 3948 MM patients, 4% developed SPM, with 64% being solid tumors, 20% myeloid, 14% SHM, and 2% lymphoid malignancies. This study included only single autologous HSCT patients and had a median follow-up of 37 months, limiting the assessment of late SPM development.<span><sup>5</sup></span></p><p>The principal objective of this study was to examine the occurrence and attributes of SPM and their subsequent effects on OS. Additionally, we sought to investigate whether the utilization of tandem autologous HSCT was associated with an elevated risk of SPM in comparison with single autologous HSCT. Secondary aims included the classification of various SPM types that emerged following autologous HSCT. Methods are detailed in supplementary.</p><p>A total of 1379 patients with newly diagnosed MM enrolled on four TT trials. An overview of the patients' characteristics can be found in [Table S1]. The median follow-up durations varied across different treatment groups: 25.3 years for TT I, 20.4 years for TT II (Arm A), 19.8 years for TT II (Arm B), 17.1 years for TT IIIA, and 15.4 years for TT IIIB. When considering the entire cohort of 1379 patients in the study, the median follow-up period was 16.6 years, with an interquartile range (IQR) spanning from 13.5 to 20 years. A total of 2640 transplants were performed on patients in our study cohort, with most of the transplants as first autologous HSCT (<i>n</i> = 1267) and second autologous HSCT (<i>n</i> = 1034) [Table S2]. Patients' baseline characteristics according to the type of transplant are summarized in [Table S3]. Overall, among the total of 1379 enrolled patients in the study, 974 patients (71%) underwent tandem autologous HSCT, with an average time interval of approximately 3.2 months between the first and secon
74岁），P值为0.001。虽然串联方法没有增加恶性肿瘤的发生率，但我们强调需要对老年 MM 患者进行严格筛查，并根据既定指南提出监测血液学异常和常见实体瘤（如乳腺癌、前列腺癌、结直肠癌和黑色素瘤）的具体建议。纳入的患者未接受抗CD38单克隆抗体、双特异性抗体或嵌合抗原受体T细胞（CAR T）等新型药物的前期治疗，而这些药物已显著改变了治疗格局。总之，我们的研究全面考察了在各种早期 TT 方案下接受自体造血干细胞移植治疗的 MM 患者的 SPM。在早期TT方案下接受串联自体造血干细胞移植治疗并随访中位数超过15年的患者中，SHM和继发性实体恶性肿瘤的发生率相对较低。自体造血干细胞移植治疗MM，尤其是我们试验中的串联自体造血干细胞移植，可显著改善OS，应尽早向符合条件的患者提供：SAH、CS、GT、IERS、BB、FVR。执行并协助分析：SAH、OA和E.RS。撰写论文原稿：SAH：SAH。审阅并编辑论文：所有作者。SAH 报告称从 Jansen、辉瑞和赛诺菲获得咨询费。
{"title":"Second primary malignancies after tandem autologous hematopoietic stem cell transplantation for multiple myeloma","authors":"Samer Al Hadidi, Obada Ababneh, Carolina Schinke, Sharmilan Thanendrarajan, Clyde Bailey, Guido Tricot, John Shaughnessy Jr, Fenghuang Zhan, Jeffrey Sawyer, Eric R. Siegel, Maurizio Zangari, Bart Barlogie, Frits van Rhee","doi":"10.1002/ajh.27452","DOIUrl":"10.1002/ajh.27452","url":null,"abstract":"<p>Autologous hematopoietic stem cell transplantation (HSCT) is a standard treatment for eligible multiple myeloma (MM) patients.<span><sup>1</sup></span> Before high-dose chemotherapy and autologous HSCT, patients typically receive induction therapy with a proteasome inhibitor and an immunomodulatory (IMiD) agent. This approach, along with posttransplant maintenance therapies, has improved survival, with some patients achieving a median overall survival (OS) of over 10 years.<span><sup>1</sup></span></p><p>While late mortality rates have decreased over the past three decades, the incidence of second primary malignancies (SPM) has not.<span><sup>2</sup></span> Given improved survival rates, understanding long-term complications like SPM is crucial, particularly as most phase III MM trials lack extended follow-up.<span><sup>3</sup></span></p><p>Autologous HSCT enhances long-term disease control and survival in newly diagnosed MM patients but increases the risk of SPM, including second hematologic malignancies (SHM). A Swedish study found that higher cumulative doses of melphalan were linked to a 2.8-fold increased risk of therapy-related myeloid neoplasms.<span><sup>4</sup></span> In a study of 3948 MM patients, 4% developed SPM, with 64% being solid tumors, 20% myeloid, 14% SHM, and 2% lymphoid malignancies. This study included only single autologous HSCT patients and had a median follow-up of 37 months, limiting the assessment of late SPM development.<span><sup>5</sup></span></p><p>The principal objective of this study was to examine the occurrence and attributes of SPM and their subsequent effects on OS. Additionally, we sought to investigate whether the utilization of tandem autologous HSCT was associated with an elevated risk of SPM in comparison with single autologous HSCT. Secondary aims included the classification of various SPM types that emerged following autologous HSCT. Methods are detailed in supplementary.</p><p>A total of 1379 patients with newly diagnosed MM enrolled on four TT trials. An overview of the patients' characteristics can be found in [Table S1]. The median follow-up durations varied across different treatment groups: 25.3 years for TT I, 20.4 years for TT II (Arm A), 19.8 years for TT II (Arm B), 17.1 years for TT IIIA, and 15.4 years for TT IIIB. When considering the entire cohort of 1379 patients in the study, the median follow-up period was 16.6 years, with an interquartile range (IQR) spanning from 13.5 to 20 years. A total of 2640 transplants were performed on patients in our study cohort, with most of the transplants as first autologous HSCT (<i>n</i> = 1267) and second autologous HSCT (<i>n</i> = 1034) [Table S2]. Patients' baseline characteristics according to the type of transplant are summarized in [Table S3]. Overall, among the total of 1379 enrolled patients in the study, 974 patients (71%) underwent tandem autologous HSCT, with an average time interval of approximately 3.2 months between the first and secon","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"99 11","pages":"2222-2224"},"PeriodicalIF":10.1,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27452","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896493","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}
Although the development and regulatory approval of the thrombopoietin receptor agonists revolutionized aspects of the immune thrombocytopenia (ITP) treatment landscape over the past two decades, there remain many areas of high unmet need. Therefore, a number of investigational and repurposed agents are currently undergoing clinical development in ITP. In a departure from historical trials, which largely focused on the indefinite treatment of persistent or chronic ITP, ongoing trials run the gamut of disease phases, and include novel agents being evaluated in early phases of the disease to attempt to modify the disease course. Many agents in development target disease pathophysiologic mechanisms not previously targeted by agents in current use, including platelet autoantibody recycling, B-cell maturation and differentiation, long-lived plasma cells, and the complement system, among others. These agents represent promising treatment options for patients with otherwise refractory disease or who are intolerant of currently available therapies. Additionally, with our increasing understanding of the diverse immune mechanisms at play in ITP, the expansion of the therapeutic armamentarium to include agents targeting diverse pathophysiologic mechanisms may allow a more personalized therapeutic selection in the future. This manuscript provides an up-to-date, in-depth overview of recently completed and ongoing clinical trials in ITP.
{"title":"2025 update on clinical trials in immune thrombocytopenia","authors":"Hanny Al-Samkari","doi":"10.1002/ajh.27448","DOIUrl":"10.1002/ajh.27448","url":null,"abstract":"<p>Although the development and regulatory approval of the thrombopoietin receptor agonists revolutionized aspects of the immune thrombocytopenia (ITP) treatment landscape over the past two decades, there remain many areas of high unmet need. Therefore, a number of investigational and repurposed agents are currently undergoing clinical development in ITP. In a departure from historical trials, which largely focused on the indefinite treatment of persistent or chronic ITP, ongoing trials run the gamut of disease phases, and include novel agents being evaluated in early phases of the disease to attempt to modify the disease course. Many agents in development target disease pathophysiologic mechanisms not previously targeted by agents in current use, including platelet autoantibody recycling, B-cell maturation and differentiation, long-lived plasma cells, and the complement system, among others. These agents represent promising treatment options for patients with otherwise refractory disease or who are intolerant of currently available therapies. Additionally, with our increasing understanding of the diverse immune mechanisms at play in ITP, the expansion of the therapeutic armamentarium to include agents targeting diverse pathophysiologic mechanisms may allow a more personalized therapeutic selection in the future. This manuscript provides an up-to-date, in-depth overview of recently completed and ongoing clinical trials in ITP.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"99 11","pages":"2178-2190"},"PeriodicalIF":10.1,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27448","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892703","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}
Robert T. Means Jr, Caixia Bi, Edward C. C. Wong, Lance A. Bare, Michael J. McPhaul
<p>Iron deficiency anemia is recognized as one of the most important contributors to the worldwide burden of illness. It has a particularly high incidence in children and females of childbearing years in both the developed and less-developed world. It is generally recognized that serum ferritin concentration is the single most useful laboratory test in the diagnosis of iron deficiency.<span><sup>1</sup></span> However, it has significant limitations. Ferritin is an acute phase reactant and can be increased out of proportion to iron stores when inflammation is present and even without inflammation the specific ferritin concentration that represents iron deficiency is not clearly established, particularly in females.<span><sup>1, 2</sup></span></p><p>The authors reviewed anonymized data from 28,134 Quest Diagnostics employees participating in the Quest Blueprint For Wellness (BFW) screening program to evaluate age-specific ferritin reference intervals in a population of adults aged 18–80 years without anemia or other red cell abnormalities. In addition, changes in red cell indices in relation to serum ferritin concentrations (mean corpuscular volume (MCV); mean corpuscular hemoglobin (MCH); mean corpuscular hemoglobin concentration (MCHC); and the coefficient of variation of the red blood cell distribution width (RDW)) as well as the hemoglobin concentration, red blood cell concentration (RBC), and the hematocrit were analyzed in order to identify a more physiologic ferritin cutoff at which changes suggestive of iron deficiency may begin to appear. Individuals with values outside the Quest reference intervals for hemoglobin concentration, hematocrit, RBC, MCV, MCH, MCHC, and RDW (reference values shown in Table S2); serum total iron binding capacity (TIBC) saturation <20%; or an International Classification of Diseases-10 (ICD 10) code indicating an anemia diagnosis or a self-reported history of anemia on their BFW health questionnaire were excluded. To exclude individuals whose serum ferritin concentrations might be elevated out of proportion to iron stores by inflammation, individuals with high sensitivity C-reactive protein (hsCRP) >3 mg/L were excluded. Data from the remaining 24 812 individuals (55% female) were analyzed as presented below. Specific details of the study population including racial/ethnic and geographic demographics are shown in Table S1 and Figure S1.</p><p>The statistical technique multimodal decomposition was utilized to determine the reference ranges for serum ferritin concentrations in the final study population. Results were expressed by age deciles, with the lower limit representing the 2.5% confidence interval of population distribution for the individuals studied. A detailed description of methodology is provided in Supplemental Methods.</p><p>The ferritin reference interval lower limits for females 50 years of age or younger ranged between 11 and 13 ng/mL and were substantially lower than the lower limits for ma
{"title":"Ferritin reference intervals in a population of working-age adults without anemia","authors":"Robert T. Means Jr, Caixia Bi, Edward C. C. Wong, Lance A. Bare, Michael J. McPhaul","doi":"10.1002/ajh.27444","DOIUrl":"10.1002/ajh.27444","url":null,"abstract":"<p>Iron deficiency anemia is recognized as one of the most important contributors to the worldwide burden of illness. It has a particularly high incidence in children and females of childbearing years in both the developed and less-developed world. It is generally recognized that serum ferritin concentration is the single most useful laboratory test in the diagnosis of iron deficiency.<span><sup>1</sup></span> However, it has significant limitations. Ferritin is an acute phase reactant and can be increased out of proportion to iron stores when inflammation is present and even without inflammation the specific ferritin concentration that represents iron deficiency is not clearly established, particularly in females.<span><sup>1, 2</sup></span></p><p>The authors reviewed anonymized data from 28,134 Quest Diagnostics employees participating in the Quest Blueprint For Wellness (BFW) screening program to evaluate age-specific ferritin reference intervals in a population of adults aged 18–80 years without anemia or other red cell abnormalities. In addition, changes in red cell indices in relation to serum ferritin concentrations (mean corpuscular volume (MCV); mean corpuscular hemoglobin (MCH); mean corpuscular hemoglobin concentration (MCHC); and the coefficient of variation of the red blood cell distribution width (RDW)) as well as the hemoglobin concentration, red blood cell concentration (RBC), and the hematocrit were analyzed in order to identify a more physiologic ferritin cutoff at which changes suggestive of iron deficiency may begin to appear. Individuals with values outside the Quest reference intervals for hemoglobin concentration, hematocrit, RBC, MCV, MCH, MCHC, and RDW (reference values shown in Table S2); serum total iron binding capacity (TIBC) saturation <20%; or an International Classification of Diseases-10 (ICD 10) code indicating an anemia diagnosis or a self-reported history of anemia on their BFW health questionnaire were excluded. To exclude individuals whose serum ferritin concentrations might be elevated out of proportion to iron stores by inflammation, individuals with high sensitivity C-reactive protein (hsCRP) >3 mg/L were excluded. Data from the remaining 24 812 individuals (55% female) were analyzed as presented below. Specific details of the study population including racial/ethnic and geographic demographics are shown in Table S1 and Figure S1.</p><p>The statistical technique multimodal decomposition was utilized to determine the reference ranges for serum ferritin concentrations in the final study population. Results were expressed by age deciles, with the lower limit representing the 2.5% confidence interval of population distribution for the individuals studied. A detailed description of methodology is provided in Supplemental Methods.</p><p>The ferritin reference interval lower limits for females 50 years of age or younger ranged between 11 and 13 ng/mL and were substantially lower than the lower limits for ma","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"99 10","pages":"2047-2049"},"PeriodicalIF":10.1,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27444","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888268","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}
Abdul-Hamid Bazarbachi, Divaya Bhutani, Jai Radhakrishnan, Markus Mapara, Mathew S. Maurer, Suzanne Lentzsch, Rajshekhar Chakraborty
<p>The therapeutic goal in immunoglobulin light-chain amyloidosis (AL) is to eradicate the plasma cell (PC) clone producing misfolded amyloid fibrils. Therapies for AL often draw inspiration from successful treatments in multiple myeloma (MM). However, the field faced a challenge when second-generation proteasome inhibitors and immunomodulatory drugs (IMiDs) used for MM proved poorly tolerated by AL patients, creating a significant treatment gap between the two diseases. The ANDROMEDA trial marked a turning point by combining daratumumab, a CD38-directed monoclonal antibody, with the previous standard of care—bortezomib, cyclophosphamide, and dexamethasone (VCd). This combination dramatically improved response rates, with approximately 80% of patients achieving a “≥” very good partial response (VGPR), compared to 50% with VCd alone.<span><sup>1</sup></span></p><p>Before the ANDROMEDA trial, approximately one-third of AL patients eventually required a second line of treatment (2nd LoT), often due to an unsatisfactory hematologic response (less than partial response [PR]), hematologic progression/relapse, and lack of organ response.<span><sup>2</sup></span> The landscape of 2nd LoT in the daratumumab era and the outcomes of such treatments are poorly characterized. Our study addresses this knowledge gap by examining the real-world outcomes of 100 consecutive patients with newly diagnosed AL who received upfront daratumumab-based therapy between January 2018 and December 2023.</p><p>The median age was 67.6 years [39.6–91.1]; 60% of patients were male; and the majority were White (67.3%) (Table S1). NYHA Class was III/IV in 44.3% at diagnosis. Most had lambda light chain involvement (76%), and median dFLC was 229 mg/L [2–9069]. Median NT-proBNP was 3317 ng/L [22–70 000], 26.9% ≥8500 ng/L. Median HS troponin-T was 64 ng/L [10–405]. Median BMPC percentage was 15% [2–70]. Regarding cytogenetics, 46% had <i>t</i>(11;14), 39.4% had del(13q), 40% had 1q gain/amplification, 28.6% had hyperdiploidy, and 13.4% had high-risk myeloma abnormalities. Most patients had modified Mayo 2004 stage IIIA (39.2%) or IIIB (24.7%) and renal stage II (46.3%). The most common frontline regimen was Dara-VCd (91%), followed by Dara-Vd/Dara-ixazomib-d (4%), Dara-d (4%), and Dara-Cd (1%), and 13% underwent ASCT consolidation. Comparing baseline characteristics between patients who received 2nd LoT versus those who did not, significant differences were noted in dFLC and %BMPC, with dFLC >180 mg/L in 78.8% versus 51.5% respectively (<i>p</i> = .005) and BMPC >15% in 67.6% versus 40.7% respectively (<i>p</i> = .02).</p><p>Median follow-up after 1st LoT was 22.3 months [2–69.7], with hematologic response evaluable for 84/100 patients. Most achieved either CR (46.4%), low-dFLC-PR (3.6%), or VGPR (21.4%) (Table S2). Twenty-three patients had either a PR (13.1%) or no response (NR) (15.5%) and received 2nd LoT. Overall, 34% required a 2nd LoT. Three patients who did not respond t
开始第 2 次 LoT 治疗后的生存率与一线治疗观察到的生存率相当，这表明患者仍可通过后续治疗获救。Ravichandran 等人在达拉单抗之前的时代也报道了类似的研究结果，尽管患者在第 4 线之前多次复发，但持久的治疗反应和反应深度是预测各治疗线疗效的关键因素。7 影响 OS 而不影响 TTNT 的因素有几个，包括基线表现状态差、疾病晚期和器官受累程度，这凸显了尽管有血液学反应，但纤维沉积造成的器官损伤是无法挽救的。新的纤维定向疗法，如与淀粉样蛋白纤维结合并促进其吸收的安赛拉单抗和比他单抗，提供了很有前景的途径，目前正在开发中8-10。第 2 次 LoT 的非随机分配限制了对不同疗法疗效的明确结论，由于缺乏启动第 2 次 LoT 的标准化标准，各机构的做法各不相同，这对我们的研究结果在不同中心的推广性和可重复性提出了挑战。A.H.B. 和 R.C. 设计/实施了研究、收集了数据、分析/解释了数据、进行了统计分析并撰写了手稿。D.B.、J.R.、M.M.、M.M.、S.L.和R.C.校对了手稿并提供了专家意见。
{"title":"Timing and outcomes of second-line therapy in the era of daratumumab-based frontline therapy in AL amyloidosis","authors":"Abdul-Hamid Bazarbachi, Divaya Bhutani, Jai Radhakrishnan, Markus Mapara, Mathew S. Maurer, Suzanne Lentzsch, Rajshekhar Chakraborty","doi":"10.1002/ajh.27450","DOIUrl":"10.1002/ajh.27450","url":null,"abstract":"<p>The therapeutic goal in immunoglobulin light-chain amyloidosis (AL) is to eradicate the plasma cell (PC) clone producing misfolded amyloid fibrils. Therapies for AL often draw inspiration from successful treatments in multiple myeloma (MM). However, the field faced a challenge when second-generation proteasome inhibitors and immunomodulatory drugs (IMiDs) used for MM proved poorly tolerated by AL patients, creating a significant treatment gap between the two diseases. The ANDROMEDA trial marked a turning point by combining daratumumab, a CD38-directed monoclonal antibody, with the previous standard of care—bortezomib, cyclophosphamide, and dexamethasone (VCd). This combination dramatically improved response rates, with approximately 80% of patients achieving a “≥” very good partial response (VGPR), compared to 50% with VCd alone.<span><sup>1</sup></span></p><p>Before the ANDROMEDA trial, approximately one-third of AL patients eventually required a second line of treatment (2nd LoT), often due to an unsatisfactory hematologic response (less than partial response [PR]), hematologic progression/relapse, and lack of organ response.<span><sup>2</sup></span> The landscape of 2nd LoT in the daratumumab era and the outcomes of such treatments are poorly characterized. Our study addresses this knowledge gap by examining the real-world outcomes of 100 consecutive patients with newly diagnosed AL who received upfront daratumumab-based therapy between January 2018 and December 2023.</p><p>The median age was 67.6 years [39.6–91.1]; 60% of patients were male; and the majority were White (67.3%) (Table S1). NYHA Class was III/IV in 44.3% at diagnosis. Most had lambda light chain involvement (76%), and median dFLC was 229 mg/L [2–9069]. Median NT-proBNP was 3317 ng/L [22–70 000], 26.9% ≥8500 ng/L. Median HS troponin-T was 64 ng/L [10–405]. Median BMPC percentage was 15% [2–70]. Regarding cytogenetics, 46% had <i>t</i>(11;14), 39.4% had del(13q), 40% had 1q gain/amplification, 28.6% had hyperdiploidy, and 13.4% had high-risk myeloma abnormalities. Most patients had modified Mayo 2004 stage IIIA (39.2%) or IIIB (24.7%) and renal stage II (46.3%). The most common frontline regimen was Dara-VCd (91%), followed by Dara-Vd/Dara-ixazomib-d (4%), Dara-d (4%), and Dara-Cd (1%), and 13% underwent ASCT consolidation. Comparing baseline characteristics between patients who received 2nd LoT versus those who did not, significant differences were noted in dFLC and %BMPC, with dFLC >180 mg/L in 78.8% versus 51.5% respectively (<i>p</i> = .005) and BMPC >15% in 67.6% versus 40.7% respectively (<i>p</i> = .02).</p><p>Median follow-up after 1st LoT was 22.3 months [2–69.7], with hematologic response evaluable for 84/100 patients. Most achieved either CR (46.4%), low-dFLC-PR (3.6%), or VGPR (21.4%) (Table S2). Twenty-three patients had either a PR (13.1%) or no response (NR) (15.5%) and received 2nd LoT. Overall, 34% required a 2nd LoT. Three patients who did not respond t","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"99 11","pages":"2225-2228"},"PeriodicalIF":10.1,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27450","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878174","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}
Mitapivat has been shown in a randomized clinical trial to significantly improve hemoglobin levels and reduce transfusion requirements,3 offering an improved quality of life, whilst also reducing the compounded risks associated with chronic transfusion in a young population.
{"title":"Echinocytes in pyruvate kinase deficiency, post-splenectomy","authors":"Sarah A. Bassiony, Asad Luqmani, Barbara J. Bain","doi":"10.1002/ajh.27449","DOIUrl":"10.1002/ajh.27449","url":null,"abstract":"<p>Mitapivat has been shown in a randomized clinical trial to significantly improve hemoglobin levels and reduce transfusion requirements,<span><sup>3</sup></span> offering an improved quality of life, whilst also reducing the compounded risks associated with chronic transfusion in a young population.</p><p>The authors declare no conflict of interest.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"99 12","pages":"2379-2380"},"PeriodicalIF":10.1,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27449","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141873971","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}
<div> <section> <h3> Disease overview</h3> <p>Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm with an annual incidence of two cases/100 000. It accounts for approximately 15% of newly diagnosed cases of leukemia in adults.</p> </section> <section> <h3> Diagnosis</h3> <p>CML is characterized by a balanced genetic translocation, t(9;22) (q34;q11.2), involving a fusion of the Abelson murine leukemia (<i>ABL1</i>) gene from chromosome 9q34 with the breakpoint cluster region (<i>BCR</i>) gene on chromosome 22q11.2. This rearrangement is known as the Philadelphia chromosome. The molecular consequence of this translocation is the generation of a <i>BCR::ABL1</i> fusion oncogene, which in turn translates into a BCR::ABL1 oncoprotein.</p> </section> <section> <h3> Frontline therapy</h3> <p>Four tyrosine kinase inhibitors (TKIs), imatinib, dasatinib, bosutinib, and nilotinib, are approved by the United States Food and Drug Administration (FDA) for first-line treatment of newly diagnosed CML in the chronic phase (CML-CP). Clinical trials with second and third-generation TKIs in frontline CML-CP therapy reported significantly deeper and faster responses but had no impact on survival prolongation, likely because of their potent efficacy and the availability of effective TKIs salvage therapies for patients who have a cytogenetic relapse with frontline TKI therapy. All four TKIs are equivalent if the aim of therapy is to improve survival. In younger patients with high-risk disease and in whom the aim of therapy is to induce a treatment-free remission status, second-generation TKIs may be favored.</p> </section> <section> <h3> Salvage therapy</h3> <p>For CML post-failure on frontline therapy, second-line options include second and third-generation TKIs. Although potent and selective, these TKIs exhibit unique pharmacological profiles and response patterns relative to different patient and disease characteristics, such as patients' comorbidities and financial status, disease stage, and <i>BCR::ABL1</i> mutational status. Patients who develop the T315I “gatekeeper” mutation display resistance to all currently available TKIs except ponatinib, asciminib, and olverembatinib. Allogeneic stem cell transplantation remains an important therapeutic option for patients with CML-CP and failure (due to resistance) of at least two TKIs and for all patients in advanced-phase disease. Older patients who have a cytogenetic relapse post-failure on all TKIs can maintain long-term survival if they continue a daily most effective/least toxic TKI, with or without the ad
{"title":"Chronic myeloid leukemia: 2025 update on diagnosis, therapy, and monitoring","authors":"Elias Jabbour, Hagop Kantarjian","doi":"10.1002/ajh.27443","DOIUrl":"10.1002/ajh.27443","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Disease overview</h3>\u0000 \u0000 <p>Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm with an annual incidence of two cases/100 000. It accounts for approximately 15% of newly diagnosed cases of leukemia in adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Diagnosis</h3>\u0000 \u0000 <p>CML is characterized by a balanced genetic translocation, t(9;22) (q34;q11.2), involving a fusion of the Abelson murine leukemia (<i>ABL1</i>) gene from chromosome 9q34 with the breakpoint cluster region (<i>BCR</i>) gene on chromosome 22q11.2. This rearrangement is known as the Philadelphia chromosome. The molecular consequence of this translocation is the generation of a <i>BCR::ABL1</i> fusion oncogene, which in turn translates into a BCR::ABL1 oncoprotein.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Frontline therapy</h3>\u0000 \u0000 <p>Four tyrosine kinase inhibitors (TKIs), imatinib, dasatinib, bosutinib, and nilotinib, are approved by the United States Food and Drug Administration (FDA) for first-line treatment of newly diagnosed CML in the chronic phase (CML-CP). Clinical trials with second and third-generation TKIs in frontline CML-CP therapy reported significantly deeper and faster responses but had no impact on survival prolongation, likely because of their potent efficacy and the availability of effective TKIs salvage therapies for patients who have a cytogenetic relapse with frontline TKI therapy. All four TKIs are equivalent if the aim of therapy is to improve survival. In younger patients with high-risk disease and in whom the aim of therapy is to induce a treatment-free remission status, second-generation TKIs may be favored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Salvage therapy</h3>\u0000 \u0000 <p>For CML post-failure on frontline therapy, second-line options include second and third-generation TKIs. Although potent and selective, these TKIs exhibit unique pharmacological profiles and response patterns relative to different patient and disease characteristics, such as patients' comorbidities and financial status, disease stage, and <i>BCR::ABL1</i> mutational status. Patients who develop the T315I “gatekeeper” mutation display resistance to all currently available TKIs except ponatinib, asciminib, and olverembatinib. Allogeneic stem cell transplantation remains an important therapeutic option for patients with CML-CP and failure (due to resistance) of at least two TKIs and for all patients in advanced-phase disease. Older patients who have a cytogenetic relapse post-failure on all TKIs can maintain long-term survival if they continue a daily most effective/least toxic TKI, with or without the ad","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"99 11","pages":"2191-2212"},"PeriodicalIF":10.1,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27443","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141873970","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}
Hagop M. Kantarjian, Kebede Begna, Elias J. Jabbour, Shilpa Paul, Mary Alma Welch, Ayalew Tefferi
{"title":"Optimal frontline therapy of chronic myeloid leukemia today, and related musings","authors":"Hagop M. Kantarjian, Kebede Begna, Elias J. Jabbour, Shilpa Paul, Mary Alma Welch, Ayalew Tefferi","doi":"10.1002/ajh.27445","DOIUrl":"10.1002/ajh.27445","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"99 10","pages":"1855-1861"},"PeriodicalIF":10.1,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27445","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141873972","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}
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