Pub Date : 2024-08-01DOI: 10.1016/j.jtct.2024.07.012
{"title":"Into the (Second) Valley of Death, Rode the Six Hundred","authors":"","doi":"10.1016/j.jtct.2024.07.012","DOIUrl":"10.1016/j.jtct.2024.07.012","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.1016/j.jtct.2023.06.009
{"title":"Corrigendum to ‘Multicenter Long-Term Follow-Up of Allogeneic Hematopoietic Cell Transplantation with Omidubicel: A Pooled Analysis of Five Prospective Clinical Trials’","authors":"","doi":"10.1016/j.jtct.2023.06.009","DOIUrl":"10.1016/j.jtct.2023.06.009","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666636723013568/pdfft?md5=fc35795e00fd95117c81c66c7c0828fa&pid=1-s2.0-S2666636723013568-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10137672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.1016/j.jtct.2024.05.018
Haploidentical (Haplo) allogeneic HCTs (alloHCT) have been used more frequently over the last decade as survival is similar to HLA-matched related donor (MRD) alloHCTs. We aimed to identify donor and recipient immune signatures before alloHCT that are associated with clinically meaningful outcomes in MRD vs Haplo alloHCT recipients. This retrospective cohort study of 165 MRD (n = 132) and Haplo (n = 33) alloHCT recipients and their related donors between 2007-2019 with paired peripheral blood samples immunophenotyped for T-cell, B-cell, NK cell and dendritic cell (DC) subsets. Immune cells were quantified before alloHCT in donors and recipients; calculations of immune cell ratios were classified as high, intermediate, and low and analyzed with alloHCT outcomes. Haplo donors were younger than MRD donors (median: 35 vs 51 years), whereas Haplo recipients were older than MRD recipients (median: 68 vs 54 years), were more likely to have a Karnofsky Performance Score ≤ 70 (76% vs 57%), 3+ comorbidities (54% vs 47%), and were in complete remission prior to alloHCT (58% vs 42%).
In MRD alloHCT, a lower ratio of CD4+ to CD8+ effector memory cells in the donor was associated with lower 4-yr overall survival (OS; 25% vs 61%; P = .009), lower 4-yr progression free survival (PFS; 25% vs 58%; P = .014) and higher incidence of 1-yr transplant-related mortality (TRM; 39% vs 7%; P = .009) in recipients. A higher ratio of CD8+ effector memory to total NK cells measured in MRD recipients was associated with a higher incidence of grade II-IV aGvHD (63% vs 37%; P = .004) but was not statistically significant for III-IV aGvHD (23% vs 12%).
In Haplo alloHCT, a lower ratio of total T-regulatory to CD4+ central memory cells in the donor was associated with lower 4-yr PFS (22% vs 60%; P = .0091). A higher ratio of CD4+ effector memory to CD8+ effector memory cells measured in Haplo recipients pre-alloHCT was associated with lower 4-yr OS (25% vs 88%; P = .0039). In both MRD and Haplo recipients, a higher ratio of CD4+ naïve to CD4+ central memory cells was associated with a higher incidence of grade II-IV aGvHD (64% vs 38%; P = .04). Evaluation of pre-alloHCT immune signatures of the donor and recipient may influence clinically meaningful patient outcomes in both MRD and Haplo transplants.
{"title":"Outcomes of Human Leukocyte Antigen-Matched Related Donor and Haploidentical Allogeneic Hematopoietic Cell Transplantation Recipients by Immune Profiles of Recipients and Donors","authors":"","doi":"10.1016/j.jtct.2024.05.018","DOIUrl":"10.1016/j.jtct.2024.05.018","url":null,"abstract":"<div><p>Haploidentical (Haplo) allogeneic HCTs (alloHCT) have been used more frequently over the last decade as survival is similar to HLA-matched related donor (MRD) alloHCTs. We aimed to identify donor and recipient immune signatures before alloHCT that are associated with clinically meaningful outcomes in MRD vs Haplo alloHCT recipients. This retrospective cohort study of 165 MRD (n = 132) and Haplo (n = 33) alloHCT recipients and their related donors between 2007-2019 with paired peripheral blood samples immunophenotyped for T-cell, B-cell, NK cell and dendritic cell (DC) subsets. Immune cells were quantified before alloHCT in donors and recipients; calculations of immune cell ratios were classified as high, intermediate, and low and analyzed with alloHCT outcomes. Haplo donors were younger than MRD donors (median: 35 vs 51 years), whereas Haplo recipients were older than MRD recipients (median: 68 vs 54 years), were more likely to have a Karnofsky Performance Score ≤ 70 (76% vs 57%), 3+ comorbidities (54% vs 47%), and were in complete remission prior to alloHCT (58% vs 42%).</p><p>In MRD alloHCT, a lower ratio of CD4+ to CD8+ effector memory cells in the donor was associated with lower 4-yr overall survival (OS; 25% vs 61%; <em>P</em> = .009), lower 4-yr progression free survival (PFS; 25% vs 58%; <em>P</em> = .014) and higher incidence of 1-yr transplant-related mortality (TRM; 39% vs 7%; <em>P</em> = .009) in recipients. A higher ratio of CD8+ effector memory to total NK cells measured in MRD recipients was associated with a higher incidence of grade II-IV aGvHD (63% vs 37%; <em>P</em> = .004) but was not statistically significant for III-IV aGvHD (23% vs 12%).</p><p>In Haplo alloHCT, a lower ratio of total T-regulatory to CD4+ central memory cells in the donor was associated with lower 4-yr PFS (22% vs 60%; <em>P</em> = .0091). A higher ratio of CD4+ effector memory to CD8+ effector memory cells measured in Haplo recipients pre-alloHCT was associated with lower 4-yr OS (25% vs 88%; <em>P</em> = .0039). In both MRD and Haplo recipients, a higher ratio of CD4+ naïve to CD4+ central memory cells was associated with a higher incidence of grade II-IV aGvHD (64% vs 38%; <em>P</em> = .04). Evaluation of pre-alloHCT immune signatures of the donor and recipient may influence clinically meaningful patient outcomes in both MRD and Haplo transplants.</p></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.1016/j.jtct.2024.04.007
Chimeric antigen receptor T cell therapy (CAR-T) has revolutionized the management of relapsed and/or refractory multiple myeloma (RRMM). However, CAR-T treatment failure is not uncommon and remains a major therapeutic challenge. There is substantial variability across transplantation and cellular therapy programs in assessing and managing post-CAR-T failures in patients with RRMM. The American Society for Transplantation and Cellular Therapy (ASTCT) Committee on Practice Guidelines conducted an online cross-sectional survey between September 2023 and December 2023 to determine myeloma, transplantation, and cellular therapy physicians’ practice patterns for the surveillance, diagnosis, and management of CAR-T failure. The intent of this survey was to understand clinical practice patterns and identify areas for further investigation. Email surveys were sent to 1311 ASTCT physician members, of whom 80 (6.1%) completed the survey. The respondents were 58% white and 66% male, and 51% had >10 years of clinical experience. Most (89%) respondents were affiliated with a university/teaching center, and 56% had a myeloma-focused transplantation and/or cellular therapy practice. Post-CAR-T surveillance laboratory studies were commonly done every 4 weeks, and surveillance bone marrow biopsies and/or imaging surveillance were most commonly done at 3 months. Sixty-four percent of the respondents would often or always consider biopsy or imaging to confirm relapse. The most popular post-CAR-T failure rescue regimen was GPRC5D-directed immunotherapy (30%) for relapses occurring ≤3 months and BCMA-directed bispecific therapies (32.5%) for relapse at >3 months. Forty-one percent of the respondents endorsed post-CAR-T prolonged cytopenia as being “often” or “always” a barrier to next-line therapy; 53% had offered stem cell boost as a mitigation approach. Substantial across-center variation in practice patterns raises the need for collaborative studies and expert clinical recommendations to describe best practices for post-CAR-T disease surveillance, optimal workup for treatment failure, and choice of rescue therapies.
{"title":"ASTCT Committee on Practice Guidelines Survey on Evaluation and Management of Relapsed/Refractory Multiple Myeloma after Failure of Chimeric Antigen Receptor T Cell Therapy","authors":"","doi":"10.1016/j.jtct.2024.04.007","DOIUrl":"10.1016/j.jtct.2024.04.007","url":null,"abstract":"<div><p>Chimeric antigen receptor T cell therapy (CAR-T) has revolutionized the management of relapsed and/or refractory multiple myeloma (RRMM). However, CAR-T treatment failure is not uncommon and remains a major therapeutic challenge. There is substantial variability across transplantation and cellular therapy programs in assessing and managing post-CAR-T failures in patients with RRMM. The American Society for Transplantation and Cellular Therapy (ASTCT) Committee on Practice Guidelines conducted an online cross-sectional survey between September 2023 and December 2023 to determine myeloma, transplantation, and cellular therapy physicians’ practice patterns for the surveillance, diagnosis, and management of CAR-T failure. The intent of this survey was to understand clinical practice patterns and identify areas for further investigation. Email surveys were sent to 1311 ASTCT physician members, of whom 80 (6.1%) completed the survey. The respondents were 58% white and 66% male, and 51% had >10 years of clinical experience. Most (89%) respondents were affiliated with a university/teaching center, and 56% had a myeloma-focused transplantation and/or cellular therapy practice. Post-CAR-T surveillance laboratory studies were commonly done every 4 weeks, and surveillance bone marrow biopsies and/or imaging surveillance were most commonly done at 3 months. Sixty-four percent of the respondents would often or always consider biopsy or imaging to confirm relapse. The most popular post-CAR-T failure rescue regimen was GPRC5D-directed immunotherapy (30%) for relapses occurring ≤3 months and BCMA-directed bispecific therapies (32.5%) for relapse at >3 months. Forty-one percent of the respondents endorsed post-CAR-T prolonged cytopenia as being “often” or “always” a barrier to next-line therapy; 53% had offered stem cell boost as a mitigation approach. Substantial across-center variation in practice patterns raises the need for collaborative studies and expert clinical recommendations to describe best practices for post-CAR-T disease surveillance, optimal workup for treatment failure, and choice of rescue therapies.</p></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666636724003476/pdfft?md5=e5d8aff6fdfa73f6fcf93f166288bcc0&pid=1-s2.0-S2666636724003476-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140615391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.1016/j.jtct.2024.04.021
Patients undergoing allogenic hematopoietic stem cell transplantation (HSCT) are at an increased risk of mortality due to transplantation-related complications in the first year post-transplantation, owing in part to the profound immune dysregulation with T cell and B cell lymphopenia and functional impairment. Although several large studies have reported higher mortality rates from Coronavirus disease 2019 (COVID-19) in HSCT recipients, to date no study has focused on the impact of early COVID-19 infection on immune reconstitution post-transplantation and the correlation with transplantation outcomes. We retrospectively analyzed 61 consecutive adult patients who underwent their first allogeneic HSCT at our institution. Thirteen patients (21.3%) experienced early COVID-19 infection, with a median time to diagnosis of 100 days post-transplantation. In multivariable analysis, patients with early COVID-19 infection had significantly worse overall survival (adjusted hazard ratio [aHR], 4.06; 95% confidence interval [CI], 1.26 to 13.05; P = .019) and progression-free survival (aHR, 6.68; 95% CI, 2.11 to 21.11; P = .001). This was attributed mainly to higher nonrelapse mortality (NRM) among early COVID-19 patients (P = .042). Allogeneic HSCT recipients with early COVID-19 infection had significant delays in absolute lymphocyte count (95% CI, -703.69 to -56.79; P = .021), CD3+CD4+ cell (95% CI, -105.35 to -11.59; P = .042), CD3+CD8+ cell (95% CI, -324.55 to -57.13; P = .038), and CD3−CD56+ cell (95% CI, -193.51 to -47.31; P = .014) recovery compared to those without early COVID-19 infection. Our findings suggest that patients with early COVID-19 infection after allogeneic HSCT have higher NRM and worse survival, at least in part due to impaired immune reconstitution post-transplantation.
{"title":"Persistent Impairment in Immune Reconstitution and Worse Survival Outcomes in Allogeneic Stem Cell Transplantation Patients with Early Coronavirus Disease 2019 Infection","authors":"","doi":"10.1016/j.jtct.2024.04.021","DOIUrl":"10.1016/j.jtct.2024.04.021","url":null,"abstract":"<div><p>Patients undergoing allogenic hematopoietic stem cell transplantation (HSCT) are at an increased risk of mortality due to transplantation-related complications in the first year post-transplantation, owing in part to the profound immune dysregulation with T cell and B cell lymphopenia and functional impairment. Although several large studies have reported higher mortality rates from Coronavirus disease 2019 (COVID-19) in HSCT recipients, to date no study has focused on the impact of early COVID-19 infection on immune reconstitution post-transplantation and the correlation with transplantation outcomes. We retrospectively analyzed 61 consecutive adult patients who underwent their first allogeneic HSCT at our institution. Thirteen patients (21.3%) experienced early COVID-19 infection, with a median time to diagnosis of 100 days post-transplantation. In multivariable analysis, patients with early COVID-19 infection had significantly worse overall survival (adjusted hazard ratio [aHR], 4.06; 95% confidence interval [CI], 1.26 to 13.05; <em>P</em> = .019) and progression-free survival (aHR, 6.68; 95% CI, 2.11 to 21.11; <em>P</em> = .001). This was attributed mainly to higher nonrelapse mortality (NRM) among early COVID-19 patients (<em>P</em> = .042). Allogeneic HSCT recipients with early COVID-19 infection had significant delays in absolute lymphocyte count (95% CI, -703.69 to -56.79; <em>P</em> = .021), CD3<sup>+</sup>CD4<sup>+</sup> cell (95% CI, -105.35 to -11.59; <em>P</em> = .042), CD3<sup>+</sup><span>CD8</span><sup>+</sup> cell (95% CI, -324.55 to -57.13; <em>P</em> = .038), and CD3<sup>−</sup>CD56<sup>+</sup> cell (95% CI, -193.51 to -47.31; <em>P</em> = .014) recovery compared to those without early COVID-19 infection. Our findings suggest that patients with early COVID-19 infection after allogeneic HSCT have higher NRM and worse survival, at least in part due to impaired immune reconstitution post-transplantation.</p></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140860442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.1016/j.jtct.2024.05.009
Allogeneic stem cell transplantation (alloSCT) offers curative potential for older patients with myeloid malignancies. We evaluated the efficacy and safety of alloSCT using post-transplantation cyclophosphamide (PTCy) in combination with a very short duration of immune suppression (IS) in this population. We retrospectively analyzed 92 consecutive patients aged 65 years and older who underwent an alloSCT for myeloid malignancies between February 2018 and December 2022 at our institution. Data on patient characteristics, treatment modalities, and outcomes were collected. Ninety-two patients received an alloSCT with PTCy-based graft versus host disease (GVHD) prophylaxis. The majority had minimal comorbidities and were diagnosed with acute myeloid leukemia. Patients mostly received conditioning regimens with low to intermediate transplant conditioning intensity scores. In 43% of patients, IS could be permanently stopped at day +90, resulting in a median time of IS of 2.93 months in high-risk patients. At a median follow-up of 21.3 months, the 1- and 2-year overall survival rates were 89% and 87%, respectively. Relapse-free survival rates were 88% and 84% at 1 and 2 years, respectively. The 1- and 2-year cumulative incidences of relapse were 8% and 13%, while treatment-related mortality (TRM) estimates were 9% at both time points. Acute GVHD grade 3 to 4 occurred in 7% within the first 180 days and severe chronic GVHD in 6% of patients. This all resulted in a 1- and 2-year graft versus host and relapse-free survival of 74% and 70%, respectively. AlloSCT using PTCy in combination with a short duration of IS in older patients with myeloid malignancies demonstrates favorable survival outcomes due to low relapse rates and a low TRM. The low incidence of relapse and acceptable rates of graft-versus-host disease suggest the efficacy and safety of this approach. Further studies are warranted to validate these findings and optimize transplant strategies for older patients with myeloid malignancies.
{"title":"Improved Outcome of Allogeneic Transplantation in Older Patients Treated for Myeloid Malignancies Using Post-Transplantation Cyclophosphamide and Reduced Duration of Immune Suppression","authors":"","doi":"10.1016/j.jtct.2024.05.009","DOIUrl":"10.1016/j.jtct.2024.05.009","url":null,"abstract":"<div><p>Allogeneic stem cell transplantation (alloSCT) offers curative potential for older patients with myeloid malignancies. We evaluated the efficacy and safety of alloSCT using post-transplantation cyclophosphamide (PTCy) in combination with a very short duration of immune suppression (IS) in this population. We retrospectively analyzed 92 consecutive patients aged 65 years and older who underwent an alloSCT for myeloid malignancies between February 2018 and December 2022 at our institution. Data on patient characteristics, treatment modalities, and outcomes were collected. Ninety-two patients received an alloSCT with PTCy-based graft versus host disease (GVHD) prophylaxis. The majority had minimal comorbidities and were diagnosed with acute myeloid leukemia. Patients mostly received conditioning regimens with low to intermediate transplant conditioning intensity scores. In 43% of patients, IS could be permanently stopped at day +90, resulting in a median time of IS of 2.93 months in high-risk patients. At a median follow-up of 21.3 months, the 1- and 2-year overall survival rates were 89% and 87%, respectively. Relapse-free survival rates were 88% and 84% at 1 and 2 years, respectively. The 1- and 2-year cumulative incidences of relapse were 8% and 13%, while treatment-related mortality (TRM) estimates were 9% at both time points. Acute GVHD grade 3 to 4 occurred in 7% within the first 180 days and severe chronic GVHD in 6% of patients. This all resulted in a 1- and 2-year graft versus host and relapse-free survival of 74% and 70%, respectively. AlloSCT using PTCy in combination with a short duration of IS in older patients with myeloid malignancies demonstrates favorable survival outcomes due to low relapse rates and a low TRM. The low incidence of relapse and acceptable rates of graft-versus-host disease suggest the efficacy and safety of this approach. Further studies are warranted to validate these findings and optimize transplant strategies for older patients with myeloid malignancies.</p></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666636724004068/pdfft?md5=dde0796a0711bc74de05b53c4cda0dcc&pid=1-s2.0-S2666636724004068-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140917292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.1016/j.jtct.2024.06.006
The use of immunotherapies for the treatment of cancer in children, adolescents, and young adults has become common. As the use of immunotherapy has expanded, including in earlier lines of therapy, it has become evident that several aspects of how these immunotherapies impact longer-term outcomes among survivors are understudied. Traditional cancer therapies like alkylating and platin agents carry the greatest risk of infertility, but little is known about the impact of novel immunotherapies on fertility. This topic is of great interest to patients, patient advocates, and clinicians. In this article, we review immunotherapeutic agents used to treat childhood and young adult cancers and discuss potential mechanisms by which they may impact fertility based on the known interplay between the immune system and reproductive organs. We highlight the relative paucity of high-quality literature examining these late effects. We discuss interventions to optimize fertility preservation (FP) for our patients. Conducting longitudinal, collaborative, and prospective research on the fertility outcomes of pediatric and young adult patients with cancer who receive immunotherapy is critical to learn how to effectively counsel our patients on long-term fertility outcomes and indications for FP procedures. Collection of patient-level data will be necessary to draft evidence-based guidelines on which providers can make therapy recommendations.
{"title":"Pediatric Cancer Immunotherapy and Potential for Impact on Fertility: A Need for Evidence-Based Guidance","authors":"","doi":"10.1016/j.jtct.2024.06.006","DOIUrl":"10.1016/j.jtct.2024.06.006","url":null,"abstract":"<div><p>The use of immunotherapies for the treatment of cancer in children, adolescents, and young adults has become common. As the use of immunotherapy has expanded, including in earlier lines of therapy, it has become evident that several aspects of how these immunotherapies impact longer-term outcomes among survivors are understudied. Traditional cancer therapies like alkylating and platin agents carry the greatest risk of infertility, but little is known about the impact of novel immunotherapies on fertility. This topic is of great interest to patients, patient advocates, and clinicians. In this article, we review immunotherapeutic agents used to treat childhood and young adult cancers and discuss potential mechanisms by which they may impact fertility based on the known interplay between the immune system and reproductive organs. We highlight the relative paucity of high-quality literature examining these late effects. We discuss interventions to optimize fertility preservation (FP) for our patients. Conducting longitudinal, collaborative, and prospective research on the fertility outcomes of pediatric and young adult patients with cancer who receive immunotherapy is critical to learn how to effectively counsel our patients on long-term fertility outcomes and indications for FP procedures. Collection of patient-level data will be necessary to draft evidence-based guidelines on which providers can make therapy recommendations.</p></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141311826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.1016/j.jtct.2023.08.024
{"title":"Corrigendum to’ UM171 expansion of cord blood improves donor availability and HLA matching for all patients, including minorities’ [Transplantation and Cellular Therapy 28/7 (2022) 410-410","authors":"","doi":"10.1016/j.jtct.2023.08.024","DOIUrl":"10.1016/j.jtct.2023.08.024","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666636723015063/pdfft?md5=2680771597bc0cf27ec9d03eab1c178b&pid=1-s2.0-S2666636723015063-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41135137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.1016/j.jtct.2024.05.021
Preemptive therapy (PET) historically has been the primary strategy to reduce early-onset cytomegalovirus (CMV) reactivation after allogeneic hematopoietic cell transplantation (HCT) but is associated with antiviral-associated toxicities and increases in healthcare resource utilization and cost. Despite its high cost, letermovir (LTV) prophylaxis has largely supplanted PET due to its effectiveness and tolerability. Direct comparisons between LTV and PET approaches on economic and clinical outcomes after allogeneic HCT remain limited. Objective: To compare total cost of care (inpatient and outpatient) between LTV prophylaxis and PET through day+180 after allogeneic HCT. Adult allogeneic CMV seropositive (R+) HCT recipients who initiated LTV <30 days after HCT between 01/01/18 and 12/31/18 were matched 1:1 to allogeneic CMV R+ HCT recipients between 01/01/15 and 12/31/17 (PET cohort). Patients were grouped into high-risk (HR) or standard-risk (SR) for CMV to compare the LTV and PET cohorts. Direct costs for each patient's index HCT admission and all subsequent inpatient and outpatient care through day+180 after HCT were determined and converted into 2021 US dollars and then to Medicare proportional dollars (MPD). A secondary analysis using 2019 average wholesale price was conducted to specifically evaluate anti-CMV medication costs. There were a total of 176 patients with 54 HR CMV pairs and 34 SR CMV pairs. No differences in survival between LTV and PET for both HR and SR CMV groups were observed. The rate of clinically significant CMV infection decreased for both HR CMV (11/54, 20.4% versus 38/54, 70.4%, P < .001) and SR CMV (1/34, 2.9% versus 12/34, 35.3%, P < .001) patients who were given LTV prophylaxis with corresponding reductions in val(ganciclovir) and foscarnet (HR CMV only) use. Among HR CMV patients, LTV prophylaxis was associated with reductions in CMV-related readmissions (3/54, 5.6% versus 18/54, 33.3%, P < .001) and outpatient visits within the first 100 days after HCT (20 versus 25, P = .002), and a decreased median total cost of care ($36,018 versus $75,525, P < .001) in MPD was observed. For SR CMV patients on LTV, a significant reduction in the median inpatient cost ($15,668 versus $27,818, P < .001) was found, but this finding was offset by a higher median outpatient cost ($26,145 versus $20,307, P = .030) that was not CMV-driven. LTV prophylaxis is highly effective in reducing clinically significant CMV reactivations for both HR and SR HCT recipients. In this study, LTV prophylaxis was associated with a decreased total cost of care for HR CMV patients through day+180. Specifically, reductions in CMV-related readmissions, exposure to CMV-directed antiviral agents, and outpatient visits in the first 100 days after HCT were observed. SR CMV patients receiving LTV prophylaxis benefited by having a reduced inpatient cost of care du
背景:预防性治疗(PET)历来是减少异基因造血细胞移植(HCT)后早发巨细胞病毒(CMV)再激活的主要策略,但与抗病毒相关的毒性反应以及医疗资源利用率和成本的增加有关。尽管成本高昂,但由于其有效性和耐受性,来特莫韦(LTV)预防在很大程度上取代了 PET。异基因造血干细胞移植后,LTV 和 PET 方法对经济和临床结果的直接比较仍然有限:比较同种异体 HCT 后 LTV 预防和 PET 至 180 天的总护理成本(住院和门诊):研究设计:开始LTV治疗的成人异基因CMV血清阳性(R+)HCT受者:共有 176 名患者,其中有 54 对 HR CMV 和 34 对 SR CMV。在 HR 和 SR CMV 组中,LTV 和 PET 的存活率均无差异。接受LTV预防治疗的HR CMV(11/54,20.4% vs 38/54,70.4%,P< .001)和SR CMV(1/34,2.9% vs 12/34,35.3%,P< .001)患者中,有临床意义的CMV感染率均有所下降,相应减少了缬更昔洛韦(ganciclovir)和福斯卡尼(foscarnet)(仅HR CMV)的使用。在 HR CMV 患者中,LTV 预防与 CMV 相关再住院率的降低有关(3/54,5.6% vs 18/54,33.3%,PC 结论:对于HR和SR HCT受者来说,LTV预防治疗在减少临床上显著的CMV再激活方面非常有效。在这项研究中,LTV 预防与 HR CMV 患者在 180 天后总护理成本的降低有关。具体来说,在 HCT 后的前 100 天内,观察到与 CMV 相关的再入院、接触 CMV 引导的抗病毒药物和门诊就诊次数均有所减少。接受LTV预防治疗的SR CMV患者因病房和药房费用的降低而减少了住院治疗费用。
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Pub Date : 2024-08-01DOI: 10.1016/j.jtct.2024.05.010
Genetically modified cell therapies (GMCT), particularly immune effector cells (IEC) such as chimeric receptor antigen (CAR) T cells, have shown promise in curing cancer and rare diseases after a single treatment course. Following close behind CAR T approvals are GMCT based on hematopoietic stem cells, such as products developed for hemoglobinopathies and other disorders. Academically sponsored GMCT products, often developed in academic centers without industry involvement, face challenges in sustaining access after completion of early phase studies when there is no commercial partner invested in completing registration trials for marketing applications. The American Society for Transplantation and Cellular Therapy (ASTCT) formed a task force named ACT To Sustain (Adoptive Cell Therapy to Sustain) to address the “valley of death” of academic GMCT products. This paper presents the task force's findings and considerations regarding financial sustainability of academically sponsored GMCT products in the absence of commercial development. We outline case scenarios illustrating barriers to maintaining access to promising GMCT developed by academic centers. The paper also delves into the current state of GMCT development, commercialization, and reimbursement, citing examples of abandoned products, cost estimates associated with GMCT manufacturing and real-world use of cost recovery. We propose potential solutions to address the financial, regulatory, and logistical challenges associated with sustaining access to academically sponsored GMCT products and to ensure that products with promising results do not languish in a “valley of death” due to financial or implementational barriers. The suggestions include aligning US Food and Drug Administration (FDA) designations with benefit coverage, allowing for cost recovery of certain products as a covered benefit, and engaging with regulators and policy makers to discuss alternative pathways for academic centers to provide access. We stress the importance of sustainable access to GMCT and call for collaborative efforts to develop regulatory pathways that support access to academically sponsored GMCT products.
转基因细胞疗法(GMCT),尤其是免疫效应细胞(IEC),如嵌合受体抗原(CAR)T细胞,已显示出在单疗程治疗后治愈癌症和罕见疾病的前景。紧随 CAR T 获批之后的是基于造血干细胞的 GMCT,如针对血红蛋白病和其他疾病开发的产品。学术赞助的 GMCT 产品通常由学术中心开发,没有业界参与,在完成早期阶段研究后,如果没有商业合作伙伴投资完成上市申请的注册试验,则在持续获取方面面临挑战。美国移植与细胞治疗学会(ASTCT)成立了一个名为 "ACT To Sustain"(支持性细胞治疗)的特别工作组,以解决学术性 GMCT 产品的 "死亡之谷 "问题。本文介绍了特别工作组的研究结果,以及在没有商业开发的情况下,学术界赞助的基因改造CT产品在财务上的可持续性的考虑因素。我们概述了一些案例,说明了学术中心开发的有前景的基因改造CT在维持使用方面存在的障碍。本文还深入探讨了 GMCT 开发、商业化和报销的现状,列举了被遗弃产品的实例、与 GMCT 生产相关的成本估算以及成本回收在现实世界中的应用。我们提出了潜在的解决方案,以解决与持续获得学术赞助的基因改造CT产品相关的财务、监管和后勤挑战,并确保具有良好效果的产品不会因财务或实施障碍而在 "死亡之谷 "徘徊。这些建议包括使美国食品和药物管理局(FDA)的指定与福利覆盖范围相一致,允许将某些产品的成本回收作为福利覆盖范围,以及与监管机构和政策制定者合作,讨论学术中心提供获取途径的其他途径。我们强调可持续获取基因改造治疗技术的重要性,并呼吁各方通力合作,开发支持获取学术赞助的基因改造治疗技术产品的监管途径。
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