血清蛋白电泳作为造血干细胞捐献者清理工作一部分的益处

EJHaem Pub Date : 2024-08-29 DOI:10.1002/jha2.997
Laura Kilinc, Burkhardt Schleipen, Karen Ende, Deborah Buk, Alexander H. Schmidt, Isabel Auer, Thilo Mengling
{"title":"血清蛋白电泳作为造血干细胞捐献者清理工作一部分的益处","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":null,"url":null,"abstract":"<p>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 [<span>1</span>] 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.</p><p>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 [<span>2</span>]. 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 [<span>3, 4</span>]. The risk for MGUS patients to develop MM, SMM or a related malignant disorder is about 1% per consecutive year [<span>4, 5</span>].</p><p>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 [<span>6</span>]. In addition, blood-borne malignancies have been transferred by HSC transplantation [<span>7, 8</span>]. 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.</p><p>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.</p><p>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 differentiate the paraproteins. The total serum protein content was also determined on a routine basis. Furthermore, abnormal SPEP curves can further reveal other diseases such as antibody deficiencies.</p><p>During the physical examination, no cases of MM or SMM were detected, but donors presenting abnormal SPEP curves (M gradient) indicating MGUS (defined as M protein concentration &lt; 3 g/dL and absence of end-organ damage characterized by CRAB criteria (hypercalcemia, renal insufficiency, anemia, bone lesions)) [<span>4, 9</span>] were not cleared to proceed for donation. Cases were retested for MGUS via their general practitioner to either confirm or refute the original diagnosis. All deferred cases between 2009 and 2017 were included in a follow-up study and were routinely followed up for ten years (as are all actual stem cell donors) but the proportion of deferred donors which did not respond was high (around 40% of deferred cases and 57% of MGUS cases did not respond).</p><p>In the period from January 2009 to December 2022, 4344 of 97,938 requested donors (4.4%; 1511/29,003 female, 2833/68,935 male), were not cleared to proceed to HSC donation. Besides the main reasons such as poor vein status or an enlarged spleen, another common reason for donor deferral was the diagnosis of potential MGUS: In 143 potential donors (0.15%; 38 females and 105 males) abnormal paraprotein was detected, corresponding to 3.3% of all non-clearances. In three cases (one MM and two SMM) disease progression was confirmed diagnostically within 1 year. Regardless of donor sex, 52% of all MGUS cases were identified in 40- to 49-year-old donors (Figure 1). The median age at donor request creation of the MGUS cases was 43 years (age range: 21–60 years). In comparison, the median age of all requested donors in the observed period was 28 years.</p><p>Of the 143 donors who were not cleared due to an MGUS diagnosis, only four cases were detected with total serum protein above the reference range (≥ 84 g/L). Therefore, according to our data, testing of total protein alone was not suited to exclude monoclonal gammopathy in HSC donors since more than 97% of MGUS cases would have remained undetected if total serum protein concentration without SPEP had been used as a diagnostic measure. Monoclonal IgG kappa or lambda gammopathies were by far the most frequently diagnosed (76%, 109 cases), whereas IgM (11%, 16 cases) and IgA gammopathies (9%, 13 cases) were diagnosed less frequently. The rarest subclass was a biclonal gradient (IgG and IgA), which was detected only in two donors. In three cases no specific information was provided.</p><p>In the further course, normal SPEP/IFE results were documented in 17 donors (12%) several months after abnormal paraprotein detection during the physical examination. Forty-five donors (31%) confirmed the MGUS diagnosis after consulting another doctor, whereas 81 donors (57%) did not disclose information about their MGUS status afterward.</p><p>In addition, electrophoresis revealed 23 cases of antibody deficiency (0.5% of donor non-clearances). These cases would have remained undiagnosed otherwise and could have posed an additional risk for the HSC donor and recipient.</p><p>Overall, our data revealed 0.15% MGUS cases in our study population which is consistent with data from other population cohorts, ranging from 0.05% to 6.1% depending on age, ethnicity, and geographic area [<span>10</span>]. Individuals requested for HSC donation are generally a positively selected population group that is younger and healthier compared to the general population, which explains why the incidence of MGUS that we observed is at the lower end of the reported range.</p><p>According to our analysis, the vast majority of MGUS cases (139/143; 97.2%) would not have been detected without SPEP/IFE, and the affected donors would most likely have donated HSC. As a transmission risk of donor MGUS cannot be excluded, this is a strong argument in favor of routine testing for MGUS in the physical examination of potential HSC donors, especially as the costs and efforts of the corresponding tests (SPEP/IFE) are low.</p><p>A specific donation risk for clinically asymptomatic donors with MGUS remains unknown, thus the execution of SPEP/IFE does not have a direct positive effect on donor safety. Nevertheless, it is beneficial for the donor to be aware of the presence of MGUS to establish routine disease monitoring and prevent associated complications or consequential organ damage.</p><p>Taken together, the analysis of SPEP/IFE improves the quality and safety profile in HSC donor clearance during the physical examination and should become a standard diagnostic for potential HSC donors prior to donation wherever the medical infrastructure allows, specifically for older donors (&gt; 40 years).</p><p>Laura Kilinc and Thilo Mengling conceptualized and wrote the paper. Burkhardt Schleipen, Deborah Buk, Isabel Auer, and Thilo Mengling collected data. Laura Kilinc, Burkhardt Schleipen, Karen Ende, and Thilo Mengling analyzed data. Karen Ende and Alexander H. Schmidt contributed to the writing of the manuscript. All authors reviewed and approved 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>The authors have confirmed ethical approval statement is not needed for this submission.</p><p>The authors have confirmed patient consent statement is not needed for this submission.</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":"1107-1109"},"PeriodicalIF":0.0000,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.997","citationCount":"0","resultStr":"{\"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\":null,\"url\":null,\"abstract\":\"<p>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 [<span>1</span>] 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.</p><p>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 [<span>2</span>]. 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 [<span>3, 4</span>]. The risk for MGUS patients to develop MM, SMM or a related malignant disorder is about 1% per consecutive year [<span>4, 5</span>].</p><p>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 [<span>6</span>]. In addition, blood-borne malignancies have been transferred by HSC transplantation [<span>7, 8</span>]. 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.</p><p>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.</p><p>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 differentiate the paraproteins. The total serum protein content was also determined on a routine basis. Furthermore, abnormal SPEP curves can further reveal other diseases such as antibody deficiencies.</p><p>During the physical examination, no cases of MM or SMM were detected, but donors presenting abnormal SPEP curves (M gradient) indicating MGUS (defined as M protein concentration &lt; 3 g/dL and absence of end-organ damage characterized by CRAB criteria (hypercalcemia, renal insufficiency, anemia, bone lesions)) [<span>4, 9</span>] were not cleared to proceed for donation. Cases were retested for MGUS via their general practitioner to either confirm or refute the original diagnosis. All deferred cases between 2009 and 2017 were included in a follow-up study and were routinely followed up for ten years (as are all actual stem cell donors) but the proportion of deferred donors which did not respond was high (around 40% of deferred cases and 57% of MGUS cases did not respond).</p><p>In the period from January 2009 to December 2022, 4344 of 97,938 requested donors (4.4%; 1511/29,003 female, 2833/68,935 male), were not cleared to proceed to HSC donation. Besides the main reasons such as poor vein status or an enlarged spleen, another common reason for donor deferral was the diagnosis of potential MGUS: In 143 potential donors (0.15%; 38 females and 105 males) abnormal paraprotein was detected, corresponding to 3.3% of all non-clearances. In three cases (one MM and two SMM) disease progression was confirmed diagnostically within 1 year. Regardless of donor sex, 52% of all MGUS cases were identified in 40- to 49-year-old donors (Figure 1). The median age at donor request creation of the MGUS cases was 43 years (age range: 21–60 years). In comparison, the median age of all requested donors in the observed period was 28 years.</p><p>Of the 143 donors who were not cleared due to an MGUS diagnosis, only four cases were detected with total serum protein above the reference range (≥ 84 g/L). Therefore, according to our data, testing of total protein alone was not suited to exclude monoclonal gammopathy in HSC donors since more than 97% of MGUS cases would have remained undetected if total serum protein concentration without SPEP had been used as a diagnostic measure. Monoclonal IgG kappa or lambda gammopathies were by far the most frequently diagnosed (76%, 109 cases), whereas IgM (11%, 16 cases) and IgA gammopathies (9%, 13 cases) were diagnosed less frequently. The rarest subclass was a biclonal gradient (IgG and IgA), which was detected only in two donors. In three cases no specific information was provided.</p><p>In the further course, normal SPEP/IFE results were documented in 17 donors (12%) several months after abnormal paraprotein detection during the physical examination. Forty-five donors (31%) confirmed the MGUS diagnosis after consulting another doctor, whereas 81 donors (57%) did not disclose information about their MGUS status afterward.</p><p>In addition, electrophoresis revealed 23 cases of antibody deficiency (0.5% of donor non-clearances). These cases would have remained undiagnosed otherwise and could have posed an additional risk for the HSC donor and recipient.</p><p>Overall, our data revealed 0.15% MGUS cases in our study population which is consistent with data from other population cohorts, ranging from 0.05% to 6.1% depending on age, ethnicity, and geographic area [<span>10</span>]. Individuals requested for HSC donation are generally a positively selected population group that is younger and healthier compared to the general population, which explains why the incidence of MGUS that we observed is at the lower end of the reported range.</p><p>According to our analysis, the vast majority of MGUS cases (139/143; 97.2%) would not have been detected without SPEP/IFE, and the affected donors would most likely have donated HSC. As a transmission risk of donor MGUS cannot be excluded, this is a strong argument in favor of routine testing for MGUS in the physical examination of potential HSC donors, especially as the costs and efforts of the corresponding tests (SPEP/IFE) are low.</p><p>A specific donation risk for clinically asymptomatic donors with MGUS remains unknown, thus the execution of SPEP/IFE does not have a direct positive effect on donor safety. Nevertheless, it is beneficial for the donor to be aware of the presence of MGUS to establish routine disease monitoring and prevent associated complications or consequential organ damage.</p><p>Taken together, the analysis of SPEP/IFE improves the quality and safety profile in HSC donor clearance during the physical examination and should become a standard diagnostic for potential HSC donors prior to donation wherever the medical infrastructure allows, specifically for older donors (&gt; 40 years).</p><p>Laura Kilinc and Thilo Mengling conceptualized and wrote the paper. Burkhardt Schleipen, Deborah Buk, Isabel Auer, and Thilo Mengling collected data. Laura Kilinc, Burkhardt Schleipen, Karen Ende, and Thilo Mengling analyzed data. Karen Ende and Alexander H. Schmidt contributed to the writing of the manuscript. All authors reviewed and approved 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>The authors have confirmed ethical approval statement is not needed for this submission.</p><p>The authors have confirmed patient consent statement is not needed for this submission.</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\":\"1107-1109\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-08-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.997\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"EJHaem\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/jha2.997\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"EJHaem","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jha2.997","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

摘要

要获得造血干细胞(HSC)捐献许可,潜在捐献者必须接受包括血液检测在内的身体检查,以检测其健康状况和捐献资格,确保捐献者的安全,并限制捐献的造血干细胞产品向受者传播传染性、遗传性或肿瘤性疾病的风险。在德国,适用的国家标准[1]要求对捐献者的血液进行额外的血清蛋白电泳(SPEP)检测,以排除是否存在意义未定的单克隆抗体病(MGUS),并将其作为体检的一部分。MGUS 是一种恶性浆细胞病,浆细胞会产生不完全或无功能的单克隆抗体(副蛋白)。MGUS患者终生都有可能患上多发性骨髓瘤(MM)、烟雾型骨髓瘤(SMM)或相关的恶性疾病。发现这种疾病通常是因为在 SPEP 中出现了血清单克隆蛋白(M 蛋白),这种蛋白会形成一个峰值(M 梯度),通常出现在γ-球蛋白部分[2]。在 50 岁及以上的人群中,MGUS 的发病率超过 3%,发病率随年龄增长而增加,男性多于女性 [3,4]。MGUS 患者发展为 MM、SMM 或相关恶性疾病的风险约为连续每年 1%[4,5]。即使在造血干细胞移植过程中不会转移大量浆细胞,也不能排除将恶性前克隆细胞群转移给受者的可能性。在实体器官移植中已经出现了 MGUS 的传播[6]。此外,造血干细胞移植也会转移血液传播的恶性肿瘤 [7,8]。因此,患有 MGUS 的登记捐献者不符合捐献造血干细胞的资格,需要在进行 SPEP 体检时加以识别和排除,然后才能批准捐献造血干细胞。然而,在许多国家,造血干细胞捐献前并未对捐献者进行 MGUS 检测。我们的研究结果强调,有必要在采集造血干细胞前对潜在的造血干细胞捐献者进行 SPEP 下的 MGUS 检测,并将其作为一项标准,以确保捐献者和患者的安全。在这项研究中,我们展示了德国 DKMS 在 13 年内(2009-2022 年)的数据,在这些数据中,潜在的造血干细胞捐献者在采集造血干细胞前的体检中接受了 MGUS 筛查。自 2009 年以来(观察期:2009 年 1 月至 2022 年 12 月),德国 DKMS 对所有申请捐献造血干细胞的潜在造血干细胞捐献者进行了 MGUS 检测,作为身体检查的一部分,检测时间为造血干细胞采集中心计划采集日期前 30 天内。用于检测 MGUS 的方法是 SPEP。免疫固定电泳(IFE)用于进一步区分副蛋白。血清总蛋白含量也是常规检测项目。此外,异常的 SPEP 曲线可进一步揭示其他疾病,如抗体缺乏。在体检过程中,未发现 MM 或 SMM 病例,但如果捐献者的 SPEP 曲线(M 梯度)异常,表明存在 MGUS(定义为 M 蛋白浓度为 3 g/dL,且不存在 CRAB 标准(高钙血症、肾功能不全、贫血、骨病变)[4, 9]所描述的内脏损害),则不允许继续捐献。病例通过其全科医生重新进行了 MGUS 检测,以确诊或反驳最初的诊断。2009年1月至2022年12月期间,97938名申请捐献者中有4344人(4.4%;女性1511/29003人,男性2833/68935人)未通过造血干细胞捐献审批。除了静脉状态不佳或脾脏肿大等主要原因外,另一个导致捐献者被推迟的常见原因是被诊断出可能患有间变性肌营养不良症:143 名潜在捐献者(0.15%;38 名女性和 105 名男性)被检测出副蛋白异常,占所有未获批准捐献者的 3.3%。有三个病例(一个 MM 和两个 SMM)在一年内经诊断确诊为疾病进展。无论捐献者性别如何,52%的 MGUS 病例是在 40 至 49 岁的捐献者中发现的(图 1)。MGUS 病例申请供体时的中位年龄为 43 岁(年龄范围:21-60 岁)。在 143 例因确诊为 MGUS 而未被清除的供体中,只有 4 例被检测出血清总蛋白超过参考范围(≥ 84 g/L)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Benefits of serum protein electrophoresis as part of hematopoietic stem cell donor clearance

Benefits of serum protein electrophoresis as part of hematopoietic stem cell donor clearance

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 [1] 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.

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 [2]. 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 [3, 4]. The risk for MGUS patients to develop MM, SMM or a related malignant disorder is about 1% per consecutive year [4, 5].

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 [6]. In addition, blood-borne malignancies have been transferred by HSC transplantation [7, 8]. 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.

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.

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 differentiate the paraproteins. The total serum protein content was also determined on a routine basis. Furthermore, abnormal SPEP curves can further reveal other diseases such as antibody deficiencies.

During the physical examination, no cases of MM or SMM were detected, but donors presenting abnormal SPEP curves (M gradient) indicating MGUS (defined as M protein concentration < 3 g/dL and absence of end-organ damage characterized by CRAB criteria (hypercalcemia, renal insufficiency, anemia, bone lesions)) [4, 9] were not cleared to proceed for donation. Cases were retested for MGUS via their general practitioner to either confirm or refute the original diagnosis. All deferred cases between 2009 and 2017 were included in a follow-up study and were routinely followed up for ten years (as are all actual stem cell donors) but the proportion of deferred donors which did not respond was high (around 40% of deferred cases and 57% of MGUS cases did not respond).

In the period from January 2009 to December 2022, 4344 of 97,938 requested donors (4.4%; 1511/29,003 female, 2833/68,935 male), were not cleared to proceed to HSC donation. Besides the main reasons such as poor vein status or an enlarged spleen, another common reason for donor deferral was the diagnosis of potential MGUS: In 143 potential donors (0.15%; 38 females and 105 males) abnormal paraprotein was detected, corresponding to 3.3% of all non-clearances. In three cases (one MM and two SMM) disease progression was confirmed diagnostically within 1 year. Regardless of donor sex, 52% of all MGUS cases were identified in 40- to 49-year-old donors (Figure 1). The median age at donor request creation of the MGUS cases was 43 years (age range: 21–60 years). In comparison, the median age of all requested donors in the observed period was 28 years.

Of the 143 donors who were not cleared due to an MGUS diagnosis, only four cases were detected with total serum protein above the reference range (≥ 84 g/L). Therefore, according to our data, testing of total protein alone was not suited to exclude monoclonal gammopathy in HSC donors since more than 97% of MGUS cases would have remained undetected if total serum protein concentration without SPEP had been used as a diagnostic measure. Monoclonal IgG kappa or lambda gammopathies were by far the most frequently diagnosed (76%, 109 cases), whereas IgM (11%, 16 cases) and IgA gammopathies (9%, 13 cases) were diagnosed less frequently. The rarest subclass was a biclonal gradient (IgG and IgA), which was detected only in two donors. In three cases no specific information was provided.

In the further course, normal SPEP/IFE results were documented in 17 donors (12%) several months after abnormal paraprotein detection during the physical examination. Forty-five donors (31%) confirmed the MGUS diagnosis after consulting another doctor, whereas 81 donors (57%) did not disclose information about their MGUS status afterward.

In addition, electrophoresis revealed 23 cases of antibody deficiency (0.5% of donor non-clearances). These cases would have remained undiagnosed otherwise and could have posed an additional risk for the HSC donor and recipient.

Overall, our data revealed 0.15% MGUS cases in our study population which is consistent with data from other population cohorts, ranging from 0.05% to 6.1% depending on age, ethnicity, and geographic area [10]. Individuals requested for HSC donation are generally a positively selected population group that is younger and healthier compared to the general population, which explains why the incidence of MGUS that we observed is at the lower end of the reported range.

According to our analysis, the vast majority of MGUS cases (139/143; 97.2%) would not have been detected without SPEP/IFE, and the affected donors would most likely have donated HSC. As a transmission risk of donor MGUS cannot be excluded, this is a strong argument in favor of routine testing for MGUS in the physical examination of potential HSC donors, especially as the costs and efforts of the corresponding tests (SPEP/IFE) are low.

A specific donation risk for clinically asymptomatic donors with MGUS remains unknown, thus the execution of SPEP/IFE does not have a direct positive effect on donor safety. Nevertheless, it is beneficial for the donor to be aware of the presence of MGUS to establish routine disease monitoring and prevent associated complications or consequential organ damage.

Taken together, the analysis of SPEP/IFE improves the quality and safety profile in HSC donor clearance during the physical examination and should become a standard diagnostic for potential HSC donors prior to donation wherever the medical infrastructure allows, specifically for older donors (> 40 years).

Laura Kilinc and Thilo Mengling conceptualized and wrote the paper. Burkhardt Schleipen, Deborah Buk, Isabel Auer, and Thilo Mengling collected data. Laura Kilinc, Burkhardt Schleipen, Karen Ende, and Thilo Mengling analyzed data. Karen Ende and Alexander H. Schmidt contributed to the writing of the manuscript. All authors reviewed and approved the final manuscript.

The authors declare no conflict of interest.

The authors received no specific funding for this work.

The authors have confirmed ethical approval statement is not needed for this submission.

The authors have confirmed patient consent statement is not needed for this submission.

The authors have confirmed clinical trial registration is not needed for this submission.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信