Pub Date : 2024-05-28DOI: 10.1101/2024.05.28.24308028
Patience Kuona, Gwendoline Q Kandawasvika, Catherine Chunda-Liyoka, Ian M Ruredzo, Pauline M Sambo, Pamela Gorejena-Chidawanyika, Hamakwa M Mantina, Takudzwa J Mtisi, Cynthia Phiri, Lawson Chikara, Natasha M Kaweme, Exavior Chivige, Jombo Namushi, Tendai Maborekeke, Uma H Uthale, Collen Masimirembwa
Of the 500 000 children born with sickle cell disease annually, most cases occur in Africa, contributing to significant morbidity and mortality associated with limited sickle cell disease (SCD) health outcomes data and reduced access to therapeutic plus preventive care. We aim to develop and manage a standardized electronic SCD registry, establish consistent standards of care (SoC) for patients, improve the SCD research and biobanking capacity in Zimbabwe and Zambia. This five-year program employs mixed methods that include infrastructure and skilled manpower capacity building of SCD clinics, registry, biobanking, cohort and implementation science research studies to improve SCD treatment outcomes. We are collaborating with the SickleInAfrica consortium (Ghana, Mali, Nigeria, Tanzania, Uganda, and South Africa), the African Institute of Biomedical Sciences and Technology (AiBST) and St Jude’s Children Research Hospital. We established the SCD registry in Zimbabwe and Zambia for children and adult patients enrolling 1796/4000 (45%) participants to date. We are participating in SickleInAfrica consortium research activities, training health workers and educating SCD patient communities on SoC. This collaboration with African researchers, policymakers, health workers, and SCD patient communities will improve uptake of SCD SoC and increase our research capacity.
{"title":"Sickle hemoglobinopathy research in Zimbabwe and Zambia (SHAZ): Protocol for setting up an international Sickle Cell Disease registry","authors":"Patience Kuona, Gwendoline Q Kandawasvika, Catherine Chunda-Liyoka, Ian M Ruredzo, Pauline M Sambo, Pamela Gorejena-Chidawanyika, Hamakwa M Mantina, Takudzwa J Mtisi, Cynthia Phiri, Lawson Chikara, Natasha M Kaweme, Exavior Chivige, Jombo Namushi, Tendai Maborekeke, Uma H Uthale, Collen Masimirembwa","doi":"10.1101/2024.05.28.24308028","DOIUrl":"https://doi.org/10.1101/2024.05.28.24308028","url":null,"abstract":"Of the 500 000 children born with sickle cell disease annually, most cases occur in Africa, contributing to significant morbidity and mortality associated with limited sickle cell disease (SCD) health outcomes data and reduced access to therapeutic plus preventive care. We aim to develop and manage a standardized electronic SCD registry, establish consistent standards of care (SoC) for patients, improve the SCD research and biobanking capacity in Zimbabwe and Zambia. This five-year program employs mixed methods that include infrastructure and skilled manpower capacity building of SCD clinics, registry, biobanking, cohort and implementation science research studies to improve SCD treatment outcomes. We are collaborating with the SickleInAfrica consortium (Ghana, Mali, Nigeria, Tanzania, Uganda, and South Africa), the African Institute of Biomedical Sciences and Technology (AiBST) and St Jude’s Children Research Hospital. We established the SCD registry in Zimbabwe and Zambia for children and adult patients enrolling 1796/4000 (45%) participants to date. We are participating in SickleInAfrica consortium research activities, training health workers and educating SCD patient communities on SoC. This collaboration with African researchers, policymakers, health workers, and SCD patient communities will improve uptake of SCD SoC and increase our research capacity.","PeriodicalId":501203,"journal":{"name":"medRxiv - Hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141188048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-03DOI: 10.1101/2024.05.02.24306742
Kingsley Kamvuma, Sepiso K. Masenga, Benson M. Hamooya, Warren Chanda, Sody Munsaka
Objective Anaemia is associated with an increased risk of disease progression and all-cause mortality among HIV-infected individuals, regardless of the type of anaemia, but the magnitude of the risk is greater with more severe anaemia. Although anaemia PLWH has been extensively studied, the focus has primarily been on its prevalence and association with disease progression in untreated or poorly controlled HIV cases. This study aimed to investigate the prevalence, and factors associated with moderate-to-severe anaemia among virally suppressed HIV patients at a tertiary hospital in Zambia.
目标 贫血与艾滋病病毒感染者病情恶化和全因死亡风险增加有关，无论贫血类型如何，但贫血越严重，风险越大。尽管对 PLWH 贫血进行了广泛的研究，但研究重点主要集中在未经治疗或控制不佳的 HIV 感染者中贫血的流行率及其与疾病进展的关系。本研究旨在调查赞比亚一家三甲医院的病毒抑制型艾滋病患者中中度至重度贫血的患病率及其相关因素。
{"title":"Prevalence and Factors Associated with Moderate-to-Severe Anaemia Among Virally Suppressed People with HIV at a Tertiary Hospital in Zambia","authors":"Kingsley Kamvuma, Sepiso K. Masenga, Benson M. Hamooya, Warren Chanda, Sody Munsaka","doi":"10.1101/2024.05.02.24306742","DOIUrl":"https://doi.org/10.1101/2024.05.02.24306742","url":null,"abstract":"<strong>Objective</strong> Anaemia is associated with an increased risk of disease progression and all-cause mortality among HIV-infected individuals, regardless of the type of anaemia, but the magnitude of the risk is greater with more severe anaemia. Although anaemia PLWH has been extensively studied, the focus has primarily been on its prevalence and association with disease progression in untreated or poorly controlled HIV cases. This study aimed to investigate the prevalence, and factors associated with moderate-to-severe anaemia among virally suppressed HIV patients at a tertiary hospital in Zambia.","PeriodicalId":501203,"journal":{"name":"medRxiv - Hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140937509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-28DOI: 10.1101/2024.04.26.24306358
Aya Mudrik, Girish N Nadkarni, Orly Efros, Benjamin S Glicksberg, Eyal Klang, Shelly Soffer
Rationale and Objectives Large Language Models (LLMs) have the potential to enhance medical training, education, and diagnosis. However, since these models were not originally designed for medical purposes, there are concerns regarding their reliability and safety in clinical settings. This review systematically assesses the utility, advantages, and potential risks of employing LLMs in the field of hematology.
{"title":"Exploring the role of Large Language Models (LLMs) in hematology: a systematic review of applications, benefits, and limitations","authors":"Aya Mudrik, Girish N Nadkarni, Orly Efros, Benjamin S Glicksberg, Eyal Klang, Shelly Soffer","doi":"10.1101/2024.04.26.24306358","DOIUrl":"https://doi.org/10.1101/2024.04.26.24306358","url":null,"abstract":"<strong>Rationale and Objectives</strong> Large Language Models (LLMs) have the potential to enhance medical training, education, and diagnosis. However, since these models were not originally designed for medical purposes, there are concerns regarding their reliability and safety in clinical settings. This review systematically assesses the utility, advantages, and potential risks of employing LLMs in the field of hematology.","PeriodicalId":501203,"journal":{"name":"medRxiv - Hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140837464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-27DOI: 10.1101/2024.04.25.24306386
Josaura Fernandez-Sanchez, Rachel Rodgers, Arushana A. Maknojia, Nusrat Shaikh, Hannah Yan, Marlyd E. Mejia, Hope Hendricks, Robert R. Jenq, Pavan Reddy, Ritu Banerjee, Jeremy M. Schraw, Megan T. Baldridge, Katherine Y. King
Hematologic side effects are associated with prolonged antibiotic exposure in up to 34% of patients. Neutropenia, reported in 10-15% of patients, increases the risk of sepsis and death. Murine studies have established a link between the intestinal microbiota and normal hematopoiesis. We sought to identify predisposing factors, presence of microbiota-derived metabolites, and changes in intestinal microbiota composition in otherwise healthy pediatric patients who developed neutropenia after prolonged courses of antibiotics. In this multi-center study, patients with infections requiring anticipated antibiotic treatment of two or more weeks were enrolled. Stool samples were obtained at the start and completion of antibiotics and at the time of neutropenia. We identified 10 patients who developed neutropenia on antibiotics and 29 controls matched for age, sex, race, and ethnicity. Clinical data demonstrated no association between neutropenia and type of infection or type of antibiotic used; however intensive care unit admission and length of therapy were associated with neutropenia. Reduced intestinal microbiome richness and decreased abundance of Lachnospiraceae family members correlated with neutropenia. Untargeted stool metabolomic profiling revealed several metabolites that were depleted exclusively in patients with neutropenia, including members of the urea cycle pathway, pyrimidine metabolism and fatty acid metabolism that are known to be produced by Lachnospiraceae. Our study confirms a relationship between intestinal microbiota disruption and abnormal hematopoiesis and identifies taxa and metabolites likely to contribute to microbiota-sustained hematopoiesis. As the microbiome is a key determinant of stem cell transplant and immunotherapy outcomes, these findings are likely to be of broad significance.
{"title":"Antibiotic-associated neutropenia is marked by depletion of intestinal Lachnospiraceae in pediatric patients","authors":"Josaura Fernandez-Sanchez, Rachel Rodgers, Arushana A. Maknojia, Nusrat Shaikh, Hannah Yan, Marlyd E. Mejia, Hope Hendricks, Robert R. Jenq, Pavan Reddy, Ritu Banerjee, Jeremy M. Schraw, Megan T. Baldridge, Katherine Y. King","doi":"10.1101/2024.04.25.24306386","DOIUrl":"https://doi.org/10.1101/2024.04.25.24306386","url":null,"abstract":"Hematologic side effects are associated with prolonged antibiotic exposure in up to 34% of patients. Neutropenia, reported in 10-15% of patients, increases the risk of sepsis and death. Murine studies have established a link between the intestinal microbiota and normal hematopoiesis. We sought to identify predisposing factors, presence of microbiota-derived metabolites, and changes in intestinal microbiota composition in otherwise healthy pediatric patients who developed neutropenia after prolonged courses of antibiotics. In this multi-center study, patients with infections requiring anticipated antibiotic treatment of two or more weeks were enrolled. Stool samples were obtained at the start and completion of antibiotics and at the time of neutropenia. We identified 10 patients who developed neutropenia on antibiotics and 29 controls matched for age, sex, race, and ethnicity. Clinical data demonstrated no association between neutropenia and type of infection or type of antibiotic used; however intensive care unit admission and length of therapy were associated with neutropenia. Reduced intestinal microbiome richness and decreased abundance of <em>Lachnospiraceae</em> family members correlated with neutropenia. Untargeted stool metabolomic profiling revealed several metabolites that were depleted exclusively in patients with neutropenia, including members of the urea cycle pathway, pyrimidine metabolism and fatty acid metabolism that are known to be produced by <em>Lachnospiraceae</em>. Our study confirms a relationship between intestinal microbiota disruption and abnormal hematopoiesis and identifies taxa and metabolites likely to contribute to microbiota-sustained hematopoiesis. As the microbiome is a key determinant of stem cell transplant and immunotherapy outcomes, these findings are likely to be of broad significance.","PeriodicalId":501203,"journal":{"name":"medRxiv - Hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140837471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-12DOI: 10.1101/2024.04.11.24305663
Christian Brieghel, Mikkel Werling, Casper Møller Frederiksen, Mehdi Parviz, Caspar da Cunha-Bang, Tereza Faitova, Rebecca Svanberg Teglgaard, Noomi Vainer, Thomas Lacoppidan, Emelie Rotbain, Rudi Agius, Carsten Utoft Niemann
Lymphoid-lineage cancers (LC: lymphoma, chronic lymphocytic leukemia, multiple myeloma, and their precursors) share many epidemiological and clinical features. To develop data-driven hematology, we gathered electronic health data and created open-source data processing pipelines to create a comprehensive data resource for Danish LC Research (DALY-CARE) approved for epidemiological, molecular, and data-driven research. We included all Danish adults registered with LC diagnoses since 2002 (n=65,774) and combined 10 nationwide registers, electronic health records (EHR), and laboratory data on a high-powered cloud-computer to develop a secure research environment. We herein exemplify how DALY-CARE has been used to develop novel prognostic markers using biobank data, real-world evidence to evaluate the efficacy of care, and medical artificial intelligence algorithms deployed directly into EHR systems. The DALY-CARE data resource allows for development of both near real-time decision-support tools and extrapolation of clinical trial results to clinical practice, thereby improving care for patients with LC.
{"title":"The Danish Lymphoid Cancer Research (DALY-CARE) data resource: the basis for developing data-driven hematology","authors":"Christian Brieghel, Mikkel Werling, Casper Møller Frederiksen, Mehdi Parviz, Caspar da Cunha-Bang, Tereza Faitova, Rebecca Svanberg Teglgaard, Noomi Vainer, Thomas Lacoppidan, Emelie Rotbain, Rudi Agius, Carsten Utoft Niemann","doi":"10.1101/2024.04.11.24305663","DOIUrl":"https://doi.org/10.1101/2024.04.11.24305663","url":null,"abstract":"Lymphoid-lineage cancers (LC: lymphoma, chronic lymphocytic leukemia, multiple myeloma, and their precursors) share many epidemiological and clinical features. To develop data-driven hematology, we gathered electronic health data and created open-source data processing pipelines to create a comprehensive data resource for Danish LC Research (DALY-CARE) approved for epidemiological, molecular, and data-driven research. We included all Danish adults registered with LC diagnoses since 2002 (n=65,774) and combined 10 nationwide registers, electronic health records (EHR), and laboratory data on a high-powered cloud-computer to develop a secure research environment. We herein exemplify how DALY-CARE has been used to develop novel prognostic markers using biobank data, real-world evidence to evaluate the efficacy of care, and medical artificial intelligence algorithms deployed directly into EHR systems. The DALY-CARE data resource allows for development of both near real-time decision-support tools and extrapolation of clinical trial results to clinical practice, thereby improving care for patients with LC.","PeriodicalId":501203,"journal":{"name":"medRxiv - Hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140588037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-19DOI: 10.1101/2024.03.18.24304500
Songphol Tungjitviboonkun
Background: The goal of treatment for elderly AML patients is palliative care rather than curative chemotherapy. Advanced care planning (ACP) plays a crucial role in good death. However, the factors associated with ACP and good death have not been well described. Objective: This study aimed to characterize the association between advanced care planning and the outcome of good death in elderly AML patients. Method: AML patients aged ≥60, who received less intensive treatment from August 2020 to December 2021, were interviewed and prospectively followed. All clinical data and potential factors related to ACP and good death were collected. Results: Seventeen AML patients were included during the study period. The median age was 73 years (range 63-88). Twenty-five patients had passed away, with a median survival of 5.5 months. Thirteen patients had undergone ACP. Among them, twelve patients with ACP had passed away, and all had achieved good death, while six out of fifteen in the non-ACP group had achieved good death (p=0.003). Two-thirds of the ACP group initially expected to live for a year when undergoing ACP but later revised their expectations downward. In the non-ACP group, only two patients who achieved a good death were aware that AML would be the cause of death, whereas five out of six in the non-good death group were not aware of it. However, it was found that prognosis understanding alone did not correlate with successful end-of-life care. No other significant factors associated with patient outcomes were identified. Factors associated with the initiation of ACP discussions included decreased platelet count and increased blast count from baseline. Palliative performance status was not predictive when assessed too late. The median time from palliative consultation to death was 3.5 months, which appeared sufficient for patient preparation. Conclusion: The key factor associated with good death was the initiation of ACP discussions with the patient. Decreased platelet count and increased blast count from baseline could serve as warning signs.
{"title":"The Association of Advanced Care Planning and Good Death in Palliative Elderly Acute Myeloid Leukemia Patients in Thailand","authors":"Songphol Tungjitviboonkun","doi":"10.1101/2024.03.18.24304500","DOIUrl":"https://doi.org/10.1101/2024.03.18.24304500","url":null,"abstract":"Background: The goal of treatment for elderly AML patients is palliative care rather than curative chemotherapy. Advanced care planning (ACP) plays a crucial role in good death. However, the factors associated with ACP and good death have not been well described.\u0000Objective: This study aimed to characterize the association between advanced care planning and the outcome of good death in elderly AML patients.\u0000Method: AML patients aged ≥60, who received less intensive treatment from August 2020 to December 2021, were interviewed and prospectively followed. All clinical data and potential factors related to ACP and good death were collected.\u0000Results: Seventeen AML patients were included during the study period. The median age was 73 years (range 63-88). Twenty-five patients had passed away, with a median survival of 5.5 months. Thirteen patients had undergone ACP. Among them, twelve patients with ACP had passed away, and all had achieved good death, while six out of fifteen in the non-ACP group had achieved good death (p=0.003). Two-thirds of the ACP group initially expected to live for a year when undergoing ACP but later revised their expectations downward. In the non-ACP group, only two patients who achieved a good death were aware that AML would be the cause of death, whereas five out of six in the non-good death group were not aware of it. However, it was found that prognosis understanding alone did not correlate with successful end-of-life care. No other significant factors associated with patient outcomes were identified. Factors associated with the initiation of ACP discussions included decreased platelet count and increased blast count from baseline. Palliative performance status was not predictive when assessed too late. The median time from palliative consultation to death was 3.5 months, which appeared sufficient for patient preparation.\u0000Conclusion: The key factor associated with good death was the initiation of ACP discussions with the patient. Decreased platelet count and increased blast count from baseline could serve as warning signs.","PeriodicalId":501203,"journal":{"name":"medRxiv - Hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140166603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-16DOI: 10.1101/2024.03.15.24304360
Rachel Peck, Amber Knapp-Wilson, Kate Burley, Carolyn Doree, James Griffin, Andrew Mumford, Simon Stanworth, Kirsty Sharplin
Background: There is a large inter-individual variation in CD34+ cell yield after G-CSF mobilisation and collection from peripheral blood in healthy allogenic haematopoietic stem cell donors. Donor characteristics including gender and age, baseline and precollection blood results, mobilisation factors and collection factors have been associated with CD34+ cell concentration in the blood after G-CSF mobilisation and/or CD34+ cell yield after collection. Since the literature reporting these associations is heterogeneous, we here clarify the determinants of CD34+ cell concentration and yield through a scoping literature review. Materials and Methods: MEDLINE, Embase, PubMed and Stem Cell Evidence were searched for studies published between 2000 and 2023. The inclusion criteria were studies of allogeneic donors undergoing G-CSF mobilisation and peripheral blood stem cell collection (PBSC). Eligible studies assessed an outcome of mobilisation or collection efficacy, indicated by the blood CD34+ cell concentration after 4 or 5 days of G-CSF treatment and/or CD34+ cell yield in the first PBSC collection after mobilisation. Included studies assessed associations between these outcomes and donor factors(such as age, gender, weight, ethnicity), mobilisation factors (G-CSF scheduling or dose), collection factors (venous access, processed blood volume) and laboratory factors (such as blood cell counts at baseline and after mobilisation). Results: The 51 eligible studies evaluated between 23 and 20,884 donors. 43 studies were retrospective, 32 assessed blood CD34+ cell concentration after mobilisation and 37 assessed CD34+ cell yield. In studies that recorded both outcomes, blood CD34+ cell concentration always predicted CD34+ cell yield. The most frequently assessed factor was donor age for which most studies reported that younger donors had a higher blood CD34+ cell concentration and CD34+ cell yield. Non-European ancestry was associated with both higher blood CD34+ cell concentration and yield although this finding was inconsistent. Conclusions: There remains poor consensus about the best predictors of blood CD34+ cell concentration and yield that requires further prospective study, particularly of the role of donor ancestry. The current focus on donor gender as a major predictor may require re-evaluation
{"title":"Scoping review of factors associated with stem cell mobilisation and collection in allogeneic stem cell donors","authors":"Rachel Peck, Amber Knapp-Wilson, Kate Burley, Carolyn Doree, James Griffin, Andrew Mumford, Simon Stanworth, Kirsty Sharplin","doi":"10.1101/2024.03.15.24304360","DOIUrl":"https://doi.org/10.1101/2024.03.15.24304360","url":null,"abstract":"Background: There is a large inter-individual variation in CD34+ cell yield after G-CSF mobilisation and collection from peripheral blood in healthy allogenic haematopoietic stem cell donors. Donor characteristics including gender and age, baseline and precollection blood results, mobilisation factors and collection factors have been associated with CD34+ cell concentration in the blood after G-CSF mobilisation and/or\u0000CD34+ cell yield after collection. Since the literature reporting these associations is\u0000heterogeneous, we here clarify the determinants of CD34+ cell concentration and yield\u0000through a scoping literature review. Materials and Methods: MEDLINE, Embase, PubMed and Stem Cell Evidence were searched for studies published between 2000 and 2023. The inclusion criteria were studies of allogeneic donors undergoing G-CSF mobilisation and peripheral blood stem cell collection (PBSC). Eligible studies assessed an outcome of mobilisation or\u0000collection efficacy, indicated by the blood CD34+ cell concentration after 4 or 5 days of\u0000G-CSF treatment and/or CD34+ cell yield in the first PBSC collection after mobilisation.\u0000Included studies assessed associations between these outcomes and donor factors(such as age, gender, weight, ethnicity), mobilisation factors (G-CSF scheduling or dose), collection factors (venous access, processed blood volume) and laboratory factors (such as blood cell counts at baseline and after mobilisation). Results: The 51 eligible studies evaluated between 23 and 20,884 donors. 43 studies were retrospective, 32 assessed blood CD34+ cell concentration after mobilisation and 37 assessed CD34+ cell yield. In studies that recorded both outcomes, blood CD34+ cell concentration always predicted CD34+ cell yield. The most frequently assessed factor was donor age for which most studies reported that younger donors had a higher\u0000blood CD34+ cell concentration and CD34+ cell yield. Non-European ancestry was associated with both higher blood CD34+ cell concentration and yield although this finding was inconsistent. Conclusions: There remains poor consensus about the best predictors of blood CD34+ cell concentration and yield that requires further prospective study, particularly of the role of donor ancestry. The current focus on donor gender as a major predictor may require re-evaluation","PeriodicalId":501203,"journal":{"name":"medRxiv - Hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140156913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-16DOI: 10.1101/2024.03.14.24304155
Felix Zirngibl, Pimrapat Gebert, Bianca Materne, Michael Launspach, Annette Kuenkele, Patrick Hundsoerfer, Sandra Cyrull, Hedwig E Deubzer, Joern Sven Kuehl, Angelika Eggert, Peter Lang, Lena Oevermann, Arend von Stackelberg, Johannes H Schulte
Allogeneic hematopoietic stem cell transplantation (HSCT) serves as a therapeutic intervention for various pediatric diseases. Acute kidney injury afflicts 21-84% of pediatric HSCT cases, significantly compromising clinical outcomes. This retrospective single-institution analysis scrutinized the practice of substituting nephrotoxic ciclosporin A with the everolimus/mycophenolate mofetil combination as graft-versus-host disease (GVHD) prophylaxis in 57 patients following first allogeneic matched donor HSCT. The control cohort comprised 74 patients not receiving everolimus during the same timeframe. Study endpoints encompassed the emergence of retention parameters subsequent to the switch to everolimus, overall survival, relapse incidence of the underlying disease and acute and chronic GVHD in both treatment groups. Our findings reveal a significant improvement in renal function, evidenced by reduced creatinine and cystatin C levels 14 days after ceasing ciclosporin A and initiating everolimus treatment. Crucially, the transition to everolimus did not adversely affect overall survival post-HSCT (HR 1.4; 95% CI: 0.64 - 3.1; p=0.39). Comparable incidences of grade 2-4 and grade 3-4 acute GVHD as well as severe chronic GVHD were observed in both groups. Patients with an underlying malignant disease exhibited similar event-free survival in both treatment arms (HR 0.87, 95% CI: 0.39 - 1.9, p=0.73). This study provides compelling real-world clinical evidence supporting the feasibility of replacing CsA with everolimus and for the use of the everolimus/mycophenolate mofetil combination to manage acute kidney injury following HSCT in children.
异基因造血干细胞移植（HSCT）是治疗各种儿科疾病的干预措施。急性肾损伤占儿科造血干细胞移植病例的21%-84%，严重影响临床疗效。这项单机构回顾性分析仔细研究了57名首次接受异体匹配供体造血干细胞移植的患者用依维莫司/霉酚酸酯组合替代肾毒性环孢素A作为移植物抗宿主病（GVHD）预防药物的做法。对照组包括74名在同一时期未接受依维莫司治疗的患者。研究终点包括两组患者在改用依维莫司后的存活参数、总生存期、基础疾病复发率以及急性和慢性GVHD。我们的研究结果表明，停止环孢素 A 并开始依维莫司治疗 14 天后，患者的肌酐和胱抑素 C 水平均有所下降，这证明患者的肾功能有了明显改善。最重要的是，转用依维莫司并没有对HSCT后的总生存率产生不利影响（HR 1.4; 95% CI: 0.64 - 3.1; p=0.39）。两组患者的2-4级和3-4级急性GVHD以及严重慢性GVHD发生率相当。患有基础恶性疾病的患者在两组治疗中的无事件生存率相似（HR 0.87，95% CI：0.39 - 1.9，p=0.73）。这项研究提供了令人信服的实际临床证据，证明了用依维莫司替代CsA的可行性，以及使用依维莫司/mycophenolate mofetil组合治疗儿童造血干细胞移植后急性肾损伤的可行性。
{"title":"Everolimus and mycophenolate mofetil effectively prevent GvHD in children with severe acute kidney injury undergoing allogeneic HSCT","authors":"Felix Zirngibl, Pimrapat Gebert, Bianca Materne, Michael Launspach, Annette Kuenkele, Patrick Hundsoerfer, Sandra Cyrull, Hedwig E Deubzer, Joern Sven Kuehl, Angelika Eggert, Peter Lang, Lena Oevermann, Arend von Stackelberg, Johannes H Schulte","doi":"10.1101/2024.03.14.24304155","DOIUrl":"https://doi.org/10.1101/2024.03.14.24304155","url":null,"abstract":"Allogeneic hematopoietic stem cell transplantation (HSCT) serves as a therapeutic intervention for various pediatric diseases. Acute kidney injury afflicts 21-84% of pediatric HSCT cases, significantly compromising clinical outcomes. This retrospective single-institution analysis scrutinized the practice of substituting nephrotoxic ciclosporin A with the everolimus/mycophenolate mofetil combination as graft-versus-host disease (GVHD) prophylaxis in 57 patients following first allogeneic matched donor HSCT. The control cohort comprised 74 patients not receiving everolimus during the same timeframe. Study endpoints encompassed the emergence of retention parameters subsequent to the switch to everolimus, overall survival, relapse incidence of the underlying disease and acute and chronic GVHD in both treatment groups. Our findings reveal a significant improvement in renal function, evidenced by reduced creatinine and cystatin C levels 14 days after ceasing ciclosporin A and initiating everolimus treatment. Crucially, the transition to everolimus did not adversely affect overall survival post-HSCT (HR 1.4; 95% CI: 0.64 - 3.1; p=0.39). Comparable incidences of grade 2-4 and grade 3-4 acute GVHD as well as severe chronic GVHD were observed in both groups. Patients with an underlying malignant disease exhibited similar event-free survival in both treatment arms (HR 0.87, 95% CI: 0.39 - 1.9, p=0.73). This study provides compelling real-world clinical evidence supporting the feasibility of replacing CsA with everolimus and for the use of the everolimus/mycophenolate mofetil combination to manage acute kidney injury following HSCT in children.","PeriodicalId":501203,"journal":{"name":"medRxiv - Hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140156883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-08DOI: 10.1101/2024.03.07.24303932
Jonathan G. Martin, Alexis M. Medema, Blaire K. Rikard, Gabrielle van den Hoek, Miriam Chisholm
Introduction: Uterine fibroids are known to affect >80% of premenopausal American women of African descent, and sickle cell disease is known to disproportionately affect people of varying geographical ancestries, particularly those of sub-Saharan African descent. However, previous studies have suggested the two pathologies less frequently co-occur. This study aims to evaluate the prevalence of uterine fibroids in patients with sickle cell disease across a large metropolitan area in the United States. Methods: African American women with sickle cell disease (including HbSS, HbSC, and sickle cell trait genotypes) underwent pelvic imaging (CT/MRI/ultrasound) between February 2011 and August 2018 at two large hospital systems within a single academic institution. Based on retrospective review, the prevalence of uterine fibroids among this cohort was analyzed and compared to published data of fibroid prevalence amongst African American patients without sickle cell disease. Results: Prior data estimates that the prevalence of uterine fibroids in African American women is about 32 to 40% for those aged 32 to 35 years and up to >80% in premenopausal African American women overall. When compared to the expected prevalence in this cohort, with a median age of 31 years, women with HbSS or HbSC sickle cell disease had a significantly decreased prevalence of uterine fibroids (9.6 to 10.3%), while those with sickle cell trait reflected a prevalence (44.4%) like that of the general population. Conclusion: There was a significantly lower prevalence of uterine fibroids in premenopausal American women of African heritage with sickle cell disease in the study cohort when compared to premenopausal American women of African heritage in the general population. This suggests a higher threshold to ascribe dysfunctional uterine bleeding in premenopausal African-American women with sickle cell disease to uterine fibroids, and a lower threshold to pursue an alternative diagnosis.
{"title":"Sickle Cell Disease and Uterine Fibroids: Evaluation of the Prevalence of Fibroids across Sickle Cell Genotypes","authors":"Jonathan G. Martin, Alexis M. Medema, Blaire K. Rikard, Gabrielle van den Hoek, Miriam Chisholm","doi":"10.1101/2024.03.07.24303932","DOIUrl":"https://doi.org/10.1101/2024.03.07.24303932","url":null,"abstract":"Introduction: Uterine fibroids are known to affect >80% of premenopausal American women of African descent, and sickle cell disease is known to disproportionately affect people of varying geographical ancestries, particularly those of sub-Saharan African descent. However, previous studies have suggested the two pathologies less frequently co-occur. This study aims to evaluate the prevalence of uterine fibroids in patients with sickle cell disease across a large metropolitan area in the United States. Methods: African American women with sickle cell disease (including HbSS, HbSC, and sickle cell trait genotypes) underwent pelvic imaging (CT/MRI/ultrasound) between February 2011 and August 2018 at two large hospital systems within a single academic institution. Based on retrospective review, the prevalence of uterine fibroids among this cohort was analyzed and compared to published data of fibroid prevalence amongst African American patients without sickle cell disease. Results: Prior data estimates that the prevalence of uterine fibroids in African American women is about 32 to 40% for those aged 32 to 35 years and up to >80% in premenopausal African American women overall. When compared to the expected prevalence in this cohort, with a median age of 31 years, women with HbSS or HbSC sickle cell disease had a significantly decreased prevalence of uterine fibroids (9.6 to 10.3%), while those with sickle cell trait reflected a prevalence (44.4%) like that of the general population. Conclusion: There was a significantly lower prevalence of uterine fibroids in premenopausal American women of African heritage with sickle cell disease in the study cohort when compared to premenopausal American women of African heritage in the general population. This suggests a higher threshold to ascribe dysfunctional uterine bleeding in premenopausal African-American women with sickle cell disease to uterine fibroids, and a lower threshold to pursue an alternative diagnosis.","PeriodicalId":501203,"journal":{"name":"medRxiv - Hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140075266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-06DOI: 10.1101/2024.03.05.24303709
Tine D'aes, Katja van den Hurk, Natalie Schroyens, Susan Mikkelsen, Pieter Severijns, Emmy De Buck, Peter O'Leary, Pierre Tiberghien, Veerle Compernolle, Christian Erikstrup, Hans Van Remoortel
Most plasma used for manufacturing plasma-derived medicinal products (PDMPs) such as albumin, immunoglobulin (Ig), and clotting factors is obtained from source plasma collected via plasmapheresis, the majority of which is contributed by the United States (US). While the demand for PDMPs continues to rise, it remains unclear whether high-frequency plasmapheresis, such as the twice-weekly plasma donation allowed in the US, may have any (long-term) adverse health effects on the donor. To investigate the frequency at which plasma can be donated without harm to the donor, the current systematic review explores the impact of plasma donation frequency on cardiovascular health, protein depletion, and adverse events in healthy plasma donors. We asked the following research question: What is the impact of plasmapheresis frequency (Intervention) on the safety or health (Outcome) of healthy donors (Population)? Six databases (PubMed, Embase, Web of Science, CINAHL, the Cochrane Library, and Transfusion Evidence Library), two clinical trial registries (ICTRP and clinicaltrials.gov), and the PROSPERO database were searched. Four observational and two experimental studies were included, and one ongoing randomized controlled trial was identified. The results showed that very high-frequency donation (twice per week) may result in a clinically relevant decrease in ferritin and bring IgG levels below the EDQM-defined lower threshold of 6 g/l. However, the evidence is of low to very low certainty, and solid conclusions are hindered by the healthy donor effect and methodological limitations of the included studies. In order to determine a safe threshold donation frequency that minimizes any possible harmful effect on the donor, more high-quality prospective cohort studies and experimental studies are thus needed. In the meantime, we argue for a precautionary approach and suggest that a sustainable and stable plasma supply may better rely on a large number of voluntary donors donating at a lower frequency (up to two donations per month), rather than on a small number of donors donating at a high frequency.
{"title":"Balancing donor health and plasma collection: a systematic review of the impact of plasmapheresis frequency","authors":"Tine D'aes, Katja van den Hurk, Natalie Schroyens, Susan Mikkelsen, Pieter Severijns, Emmy De Buck, Peter O'Leary, Pierre Tiberghien, Veerle Compernolle, Christian Erikstrup, Hans Van Remoortel","doi":"10.1101/2024.03.05.24303709","DOIUrl":"https://doi.org/10.1101/2024.03.05.24303709","url":null,"abstract":"Most plasma used for manufacturing plasma-derived medicinal products (PDMPs) such as albumin, immunoglobulin (Ig), and clotting factors is obtained from source plasma collected via plasmapheresis, the majority of which is contributed by the United States (US). While the demand for PDMPs continues to rise, it remains unclear whether high-frequency plasmapheresis, such as the twice-weekly plasma donation allowed in the US, may have any (long-term) adverse health effects on the donor.\u0000To investigate the frequency at which plasma can be donated without harm to the donor, the current systematic review explores the impact of plasma donation frequency on cardiovascular health, protein depletion, and adverse events in healthy plasma donors. We asked the following research question: What is the impact of plasmapheresis frequency (Intervention) on the safety or health (Outcome) of healthy donors (Population)? Six databases (PubMed, Embase, Web of Science, CINAHL, the Cochrane Library, and Transfusion Evidence Library), two clinical trial registries (ICTRP and clinicaltrials.gov), and the PROSPERO database were searched. Four observational and two experimental studies were included, and one ongoing randomized controlled trial was identified. The results showed that very high-frequency donation (twice per week) may result in a clinically relevant decrease in ferritin and bring IgG levels below the EDQM-defined lower threshold of 6 g/l. However, the evidence is of low to very low certainty, and solid conclusions are hindered by the healthy donor effect and methodological limitations of the included studies. In order to determine a safe threshold donation frequency that minimizes any possible harmful effect on the donor, more high-quality prospective cohort studies and experimental studies are thus needed. In the meantime, we argue for a precautionary approach and suggest that a sustainable and stable plasma supply may better rely on a large number of voluntary donors donating at a lower frequency (up to two donations per month), rather than on a small number of donors donating at a high frequency.","PeriodicalId":501203,"journal":{"name":"medRxiv - Hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140047013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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