Pub Date : 2024-12-01DOI: 10.1016/j.jtct.2024.09.020
Zaid Abdel Rahman , Tamer Othman , Rima M. Saliba , Yenny Alejandra Moreno Vanegas , Razan Mohty , Celina Ledesma , Gabriela Rondon , Nitin Jain , Elias Jabbour , Vinod Pullarkat , Hassan B Alkhateeb , Hagop M. Kantarjian , Patricia T. Greipp , Ryotaro Nakamura , Mohamed A. Kharfan-Dabaja , Richard E. Champlin , Stephen J. Forman , Elizabeth J. Shpall , Mark R. Litzow , James M. Foran , Partow Kebriaei
Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subset of B-cell ALL with a poor prognosis with conventional therapies. Diagnostic challenges and lack of standardized treatment protocols contribute to suboptimal outcomes. Additionally, while allogeneic hematopoietic cell transplantation (HCT) is frequently recommended in adults with Ph-like ALL given its high-risk nature, data supporting its role remains limited. We conducted a multicenter retrospective study evaluating outcomes of adult patients undergoing HCT in first complete remission (CR1) for Ph-like ALL compared to Philadelphia chromosome positive ALL (Ph-pos) and other B-cell Philadelphia negative (Ph-neg) ALL. Data was collected from five academic centers across the US, focusing on HCT outcomes for patients with ALL. Patients undergoing HCT in CR1 between 2006 and 2021 were included. Among 673 patients, 83 (12.3%) had Ph-like ALL, while 271 (40.3%) had Ph-pos and 319 (47.4%) had Ph-neg ALL. Outcomes following HCT in CR1 for Ph-like ALL were comparable to Ph-neg ALL, with no significant differences in 3-year overall survival (66% vs. 59%, P = .1), progression-free survival (59% and 54%, P = .1), or relapse rates (22% vs. 20%, P = .7). In contrast, Ph-pos ALL had superior outcomes; 3-year OS (75%, P < .001), PFS (70%, P = .001) and relapse (12%, P = .003), this is likely attributed to tyrosine kinase inhibitor therapy. Our study suggests that HCT, coupled with effective 2nd line therapies can possibly mitigate the poor prognosis associated with Ph-like ALL and offers promising outcomes for patients with Ph-like ALL.
背景：费城样急性淋巴细胞白血病（Ph-like ALL）是B细胞ALL的高危亚型，传统疗法预后较差。诊断难题和标准化治疗方案的缺乏导致疗效不理想。此外，虽然异基因造血细胞移植（HCT）经常被推荐用于高危的成人类Ph-like ALL患者，但支持其作用的数据仍然有限：我们开展了一项多中心回顾性研究，评估了首次完全缓解（CR1）的Ph样ALL成人患者接受HCT治疗的疗效，并与费城染色体阳性ALL（Ph-pos）和其他B细胞费城阴性ALL（Ph-neg）进行了比较：研究设计：从全美五个学术中心收集数据，重点关注ALL患者的HCT疗效。研究结果：在673名患者中，83人（12人）接受了HCT治疗：在673名患者中，83人（12.3%）为Ph-like ALL，271人（40.3%）为Ph-pos ALL，319人（47.4%）为Ph-neg ALL。Ph-样ALL在CR1期接受造血干细胞移植后的结果与Ph-neg ALL相当，3年总生存率（66% vs 59%，P=0.1）、无进展生存率（59%和54%，P=0.1）或复发率（22% vs 20%，P=0.7）均无显著差异。相比之下，Ph-pos ALL 的疗效更佳；3 年 OS（75%，p=0.1），或复发率（22% vs 20%，p=0.7）：我们的研究表明，造血干细胞移植与有效的二线疗法相结合，有可能减轻与Ph-like ALL相关的不良预后，并为Ph-like ALL患者提供有希望的治疗结果。
{"title":"A Multicenter Analysis of Allogeneic Transplant Outcomes in Adults with Philadelphia-Like B-Cell Acute Lymphoblastic Leukemia in First Complete Remission","authors":"Zaid Abdel Rahman , Tamer Othman , Rima M. Saliba , Yenny Alejandra Moreno Vanegas , Razan Mohty , Celina Ledesma , Gabriela Rondon , Nitin Jain , Elias Jabbour , Vinod Pullarkat , Hassan B Alkhateeb , Hagop M. Kantarjian , Patricia T. Greipp , Ryotaro Nakamura , Mohamed A. Kharfan-Dabaja , Richard E. Champlin , Stephen J. Forman , Elizabeth J. Shpall , Mark R. Litzow , James M. Foran , Partow Kebriaei","doi":"10.1016/j.jtct.2024.09.020","DOIUrl":"10.1016/j.jtct.2024.09.020","url":null,"abstract":"<div><div>Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subset of B-cell ALL with a poor prognosis with conventional therapies. Diagnostic challenges and lack of standardized treatment protocols contribute to suboptimal outcomes. Additionally, while allogeneic hematopoietic cell transplantation (HCT) is frequently recommended in adults with Ph-like ALL given its high-risk nature, data supporting its role remains limited. We conducted a multicenter retrospective study evaluating outcomes of adult patients undergoing HCT in first complete remission (CR1) for Ph-like ALL compared to Philadelphia chromosome positive ALL (Ph-pos) and other B-cell Philadelphia negative (Ph-neg) ALL. Data was collected from five academic centers across the US, focusing on HCT outcomes for patients with ALL. Patients undergoing HCT in CR1 between 2006 and 2021 were included. Among 673 patients, 83 (12.3%) had Ph-like ALL, while 271 (40.3%) had Ph-pos and 319 (47.4%) had Ph-neg ALL. Outcomes following HCT in CR1 for Ph-like ALL were comparable to Ph-neg ALL, with no significant differences in 3-year overall survival (66% vs. 59%, <em>P</em> = .1), progression-free survival (59% and 54%, <em>P</em> = .1), or relapse rates (22% vs. 20%, <em>P</em> = .7). In contrast, Ph-pos ALL had superior outcomes; 3-year OS (75%, <em>P</em> < .001), PFS (70%, <em>P</em> = .001) and relapse (12%, <em>P</em> = .003), this is likely attributed to tyrosine kinase inhibitor therapy. Our study suggests that HCT, coupled with effective 2nd line therapies can possibly mitigate the poor prognosis associated with Ph-like ALL and offers promising outcomes for patients with Ph-like ALL.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"30 12","pages":"Pages 1197-1205"},"PeriodicalIF":3.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354541","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 : 2024-12-01DOI: 10.1016/j.jtct.2024.09.016
Andrew C. Harris , Alina Markova , Sean Devlin , Amandeep Singh , Pamela Susman , Soni Brown , Christine Grasso , Christian Custodio , Cherry Estilo , Katarzyna Ibanez , Michelle Myers , Grigory Syrkin , SaeHee Yom , Miguel-Angel Perales , Doris M. Ponce
Graft-versus-host disease (GVHD) is a complication following allogeneic hematopoietic cell transplant that frequently causes multiorgan affection and decrease in quality of life. Global assessment and care of these patients require a multidisciplinary approach, but access to focused clinics is limited given their scarcity and location in major cities, as well as mobility and transportation challenges that frequently affect these patients. Thus, we established a multispecialty GVHD telehealth (TH) clinic and hypothesized that a virtual platform will expand access to clinical care in children and adults. The clinic team members included BMT specialist, nursing, dermatologist, dentist, nutritionist, physiatrist, research personnel, and others as needed. We evaluated all GVHD-related visits (in-person and TH) conducted in a single center from 01/2022 to 12/2022. Ninety-three patients received a total of 308 visits, and one-third were via TH. Approximately half of the in-person group had at least 1 TH visit, and 10 patients were seen exclusively via TH. Most patients had advanced chronic GVHD. More male patients were seen in GVHD clinic, but female patients had increased in clinic visits via TH (41% TH versus 32% in-person). One-third of clinic visits were from patients of racial and ethnic minorities. While only 6% (n = 12/217) of in-person visits were for patients living >100 miles from the center, 34% (n = 31/91) of TH visits were from far distances including out-of-state. At baseline, the most common patient-reported symptoms in a subset of patients included fatigue, disturbed sleep, and distress. Fifteen patients completed a follow-up symptom survey and reported significantly reduced distress regarding their GVHD (P = .02), although other symptoms remained stable. A multidisciplinary TH clinic provided care for adult and pediatric patients with GVHD. We demonstrated preliminary feasibility of building a robust TH platform with a collaborative multispecialty approach that allowed access and continuity of medical care. Gender inequalities were reduced, and distance to our center represented a lesser barrier to attending specialized care via TH. Additionally, patients reported a significant reduction in distress. Our findings support the ongoing development of a virtual platform to improve access to specialized GVHD care.
{"title":"Establishing a Graft-Versus-Host Disease (GVHD)-Focused Multidisciplinary Telehealth Clinic","authors":"Andrew C. Harris , Alina Markova , Sean Devlin , Amandeep Singh , Pamela Susman , Soni Brown , Christine Grasso , Christian Custodio , Cherry Estilo , Katarzyna Ibanez , Michelle Myers , Grigory Syrkin , SaeHee Yom , Miguel-Angel Perales , Doris M. Ponce","doi":"10.1016/j.jtct.2024.09.016","DOIUrl":"10.1016/j.jtct.2024.09.016","url":null,"abstract":"<div><div>Graft-versus-host disease (GVHD) is a complication following allogeneic hematopoietic cell transplant that frequently causes multiorgan affection and decrease in quality of life. Global assessment and care of these patients require a multidisciplinary approach, but access to focused clinics is limited given their scarcity and location in major cities, as well as mobility and transportation challenges that frequently affect these patients. Thus, we established a multispecialty GVHD telehealth (TH) clinic and hypothesized that a virtual platform will expand access to clinical care in children and adults. The clinic team members included BMT specialist, nursing, dermatologist, dentist, nutritionist, physiatrist, research personnel, and others as needed. We evaluated all GVHD-related visits (in-person and TH) conducted in a single center from 01/2022 to 12/2022. Ninety-three patients received a total of 308 visits, and one-third were via TH. Approximately half of the in-person group had at least 1 TH visit, and 10 patients were seen exclusively via TH. Most patients had advanced chronic GVHD. More male patients were seen in GVHD clinic, but female patients had increased in clinic visits via TH (41% TH versus 32% in-person). One-third of clinic visits were from patients of racial and ethnic minorities. While only 6% (<em>n</em> = 12/217) of in-person visits were for patients living >100 miles from the center, 34% (<em>n</em> = 31/91) of TH visits were from far distances including out-of-state. At baseline, the most common patient-reported symptoms in a subset of patients included fatigue, disturbed sleep, and distress. Fifteen patients completed a follow-up symptom survey and reported significantly reduced distress regarding their GVHD (<em>P</em> = .02), although other symptoms remained stable. A multidisciplinary TH clinic provided care for adult and pediatric patients with GVHD. We demonstrated preliminary feasibility of building a robust TH platform with a collaborative multispecialty approach that allowed access and continuity of medical care. Gender inequalities were reduced, and distance to our center represented a lesser barrier to attending specialized care via TH. Additionally, patients reported a significant reduction in distress. Our findings support the ongoing development of a virtual platform to improve access to specialized GVHD care.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"30 12","pages":"Pages 1215.e1-1215.e11"},"PeriodicalIF":3.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296374","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 : 2024-12-01DOI: 10.1016/j.jtct.2024.09.009
Ibrahim N. Muhsen , Kristen E. Shaver , Tao Wang , Mengfen Wu , Premal Lulla , Carlos A. Ramos , Rammurti T. Kamble , Helen E. Heslop , George Carrum , LaQuisa C. Hill
In vivo T-cell depletion (TCD) using alemtuzumab decreases the risk of Graft vs Host Disease (GvHD) in recipients of allogeneic hematopoietic stem cell transplant (allo-HSCT). However, this approach increases the risk of infections post-allo-HSCT, including Cytomegalovirus (CMV). Letermovir is approved for the use in CMV prophylaxis post-allo-HSCT. Few studies have investigated the efficacy of letermovir in patients receiving alemtuzumab. This is a single-center retrospective study describing our institutional experience using letermovir in recipients of alemtuzumab TCD allo-HSCT from unrelated donors (URD). The primary outcome was the cumulative incidence of significant CMV infection (defined as viremia leading to preemptive antiviral therapy or CMV disease) within 100 days post-transplant. Secondary outcomes included the cumulative incidence of acute GvHD (grade ≥ 2), the cumulative incidence of extensive chronic GvHD, and overall survival. A total of 84 alemtuzumab TCD URD allo-HSCT recipients were included in the analysis, 30 of whom received letermovir (letermovir group) and 54 who did not receive letermovir (control group). The median age was 59 years (range: 26-75 years) and 55.5 years (range: 20-73 years) in the letermovir and control group, respectively. Most recipients (66.7%) in both groups received unrelated matched allografts, and myeloid neoplasms were the most common indication for allo-HSCT. A significantly lower cumulative incidence of significant CMV infection within 100 days was seen in the letermovir group compared to the control group (10.0% [95% CI: 2.5-23.9%] versus 55.6% [95% CI: 41.2-67.8%], P < .0001). There was no statistically significant difference in the incidence of acute GvHD (grade ≥ 2) or overall survival between the 2 groups. However, lower rates of extensive chronic GvHD were noted in the letermovir group (10.5% [95% CI: 2.6-24.9%] versus. 36.5% [95% CI: 23.6-49.5%], P = .0126). These results demonstrate the efficacy of letermovir in decreasing the rates of clinically significant CMV infection in patients undergoing alemtuzumab T-cell depleted allo-HSCT.
{"title":"Efficacy of Letermovir for Cytomegalovirus Prophylaxis Following Alemtuzumab T-Cell Depleted Allogeneic Hematopoietic Stem Cell Transplant","authors":"Ibrahim N. Muhsen , Kristen E. Shaver , Tao Wang , Mengfen Wu , Premal Lulla , Carlos A. Ramos , Rammurti T. Kamble , Helen E. Heslop , George Carrum , LaQuisa C. Hill","doi":"10.1016/j.jtct.2024.09.009","DOIUrl":"10.1016/j.jtct.2024.09.009","url":null,"abstract":"<div><div><em>In vivo</em> T-cell depletion (TCD) using alemtuzumab decreases the risk of Graft vs Host Disease (GvHD) in recipients of allogeneic hematopoietic stem cell transplant (allo-HSCT). However, this approach increases the risk of infections post-allo-HSCT, including Cytomegalovirus (CMV). Letermovir is approved for the use in CMV prophylaxis post-allo-HSCT. Few studies have investigated the efficacy of letermovir in patients receiving alemtuzumab. This is a single-center retrospective study describing our institutional experience using letermovir in recipients of alemtuzumab TCD allo-HSCT from unrelated donors (URD). The primary outcome was the cumulative incidence of significant CMV infection (defined as viremia leading to preemptive antiviral therapy or CMV disease) within 100 days post-transplant. Secondary outcomes included the cumulative incidence of acute GvHD (grade ≥ 2), the cumulative incidence of extensive chronic GvHD, and overall survival. A total of 84 alemtuzumab TCD URD allo-HSCT recipients were included in the analysis, 30 of whom received letermovir (letermovir group) and 54 who did not receive letermovir (control group). The median age was 59 years (range: 26-75 years) and 55.5 years (range: 20-73 years) in the letermovir and control group, respectively. Most recipients (66.7%) in both groups received unrelated matched allografts, and myeloid neoplasms were the most common indication for allo-HSCT. A significantly lower cumulative incidence of significant CMV infection within 100 days was seen in the letermovir group compared to the control group (10.0% [95% CI: 2.5-23.9%] versus 55.6% [95% CI: 41.2-67.8%], <em>P</em> < .0001). There was no statistically significant difference in the incidence of acute GvHD (grade ≥ 2) or overall survival between the 2 groups. However, lower rates of extensive chronic GvHD were noted in the letermovir group (10.5% [95% CI: 2.6-24.9%] versus. 36.5% [95% CI: 23.6-49.5%], <em>P</em> = .0126). These results demonstrate the efficacy of letermovir in decreasing the rates of clinically significant CMV infection in patients undergoing alemtuzumab T-cell depleted allo-HSCT.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"30 12","pages":"Pages 1193.e1-1193.e8"},"PeriodicalIF":3.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296373","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 : 2024-12-01DOI: 10.1016/j.jtct.2024.09.023
Aimee Merino , Claudio C. Brunstein , Ryan Shanley , Faridullah Rashid , Rose Wangen , Veronika Bachanova , Mark Juckett , Joseph Maakaron , Martin Felices , Daniel Weisdorf , Jeffrey S. Miller
Maintenance therapy may improve natural killer (NK) cell surveillance after allogeneic donor hematopoietic cell transplant (HCT) for myeloid malignancies and represents a potential approach to improve cure rates. Interleukin-15 (IL-15) enhances lymphocyte proliferation and antitumor activity. In a prior Phase 1 study of an IL-15 superagonist (N-803) in patients with AML who relapsed after HCT, we observed in vivo expansion of NK cells and antitumor responses. The primary objective of this Phase 2 trial was to determine if post-transplant N-803 could reduce relapse. We administered N-803 (n = 20) (dosed 6 mcg/kg subcutaneously [SQ] at day 60 after HCT to patients with myelodysplastic syndrome [MDS] or acute myeloid leukemia [AML] who were in complete remission [CR]). N-803 treatment was planned weekly, biweekly or every 4 weeks in 2 sequential cohorts. The most common adverse events after administration were self-limited injection sites skin rashes (n = 20). One week after an N-803 dose, we observed enhanced NK cell proliferation and improved antitumor cytotoxicity without inducing immune exhaustion. Five patients who developed acute graft versus host disease (aGVHD) after N-803 responded promptly to steroids and 4 patients developed chronic GVHD. Patients receiving >4 doses of N-803 had a 3-fold decrease in relapse at two years (P = .06). These findings support the safety, immune activation, and potential efficacy of N-803 to prevent relapse of AML/MDS after HSCT.
{"title":"N-803, an IL-15 Superagonist Complex as Maintenance Therapy After Allogeneic Donor Stem Cell Transplant for Acute Myeloid Leukemia or Myelodysplastic Syndrome; A Phase 2 Trial","authors":"Aimee Merino , Claudio C. Brunstein , Ryan Shanley , Faridullah Rashid , Rose Wangen , Veronika Bachanova , Mark Juckett , Joseph Maakaron , Martin Felices , Daniel Weisdorf , Jeffrey S. Miller","doi":"10.1016/j.jtct.2024.09.023","DOIUrl":"10.1016/j.jtct.2024.09.023","url":null,"abstract":"<div><div>Maintenance therapy may improve natural killer (NK) cell surveillance after allogeneic donor hematopoietic cell transplant (HCT) for myeloid malignancies and represents a potential approach to improve cure rates. Interleukin-15 (IL-15) enhances lymphocyte proliferation and antitumor activity. In a prior Phase 1 study of an IL-15 superagonist (N-803) in patients with AML who relapsed after HCT, we observed in vivo expansion of NK cells and antitumor responses. The primary objective of this Phase 2 trial was to determine if post-transplant N-803 could reduce relapse. We administered N-803 (<em>n</em> = 20) (dosed 6 mcg/kg subcutaneously [SQ] at day 60 after HCT to patients with myelodysplastic syndrome [MDS] or acute myeloid leukemia [AML] who were in complete remission [CR]). N-803 treatment was planned weekly, biweekly or every 4 weeks in 2 sequential cohorts. The most common adverse events after administration were self-limited injection sites skin rashes (<em>n</em> = 20). One week after an N-803 dose, we observed enhanced NK cell proliferation and improved antitumor cytotoxicity without inducing immune exhaustion. Five patients who developed acute graft versus host disease (aGVHD) after N-803 responded promptly to steroids and 4 patients developed chronic GVHD. Patients receiving >4 doses of N-803 had a 3-fold decrease in relapse at two years (<em>P</em> = .06). These findings support the safety, immune activation, and potential efficacy of N-803 to prevent relapse of AML/MDS after HSCT.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"30 12","pages":"Pages 1206.e1-1206.e12"},"PeriodicalIF":3.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372957","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 : 2024-12-01DOI: 10.1016/j.jtct.2024.09.010
James Fan Wu , Noel Estrada-Merly , Binod Dhakal , Meera Mohan , Ravi Kishore Narra , Marcelo C. Pasquini , Anita D'Souza
Despite the use of autologous hematopoietic cell transplantation (AHCT) in treatment of multiple myeloma (MM) for almost 40 years and its persistence as standard of care in transplantation-eligible patients with MM even after the advent of novel agents, AHCT remains underutilized, especially in racial and ethnic minority populations. As part of a multipronged effort to quantify disparities in AHCT utilization in MM by race and ethnicity and over time in our own cancer center, we conducted an institutional review of all new patients seen at an academic transplant center for consultation for MM between 2012 and 2022, to calculate AHCT utilization and investigate the factors associated with AHCT utilization. Race and ethnicity were self-reported. Baseline characteristics were analyzed in 3 groups: non-Hispanic White (NHW), non-Hispanic Black (NHB), and Others. Reasons for not undergoing AHCT in the EHR were recorded. Multivariate analyses evaluated the effect of group on AHCT utilization, controlling for covariates related to patients not undergoing AHCT by overall cohort and consult period. Of the 1266 patients, 13.4% were NHB. The median age at consult was 66 (IQR, 23-97) years overall, 66 (IQR, 23-97) years for NHWs, 63 (IQR, 25-85) years for NHBs, and 59.5 (IQR, 31-79) years for Others (P < .01). AHCT utilization was 76% overall, 64.7% in NHBs, 76.8% in Others, and 77.8% in NHWs (P < .01). Age, cytogenetics, stage, comorbidities, and time from diagnosis to consult were associated with receipt of AHCT. From 2012-2017 to 2018-2022, NHB AHCT utilization increased from 57.5% to 69.8% (P = .10). For those who did not receive AHCT, patient preference, older age, comorbidity, early mortality, and lack of caregiver support were the most frequently documented reasons. The NHW group had greater AHCT utilization compared to the NHB group (odds ratio [OR], 3.32; 95% confidence interval [CI], 2.17-5.08; P < .0001). Absent cardiac (OR, 1.88; 95% CI, 1.35-2.62; P = .0002) or renal comorbidity (OR, 3.23; 95% CI, 2.03-5.15; P < .0001) was associated with receipt of AHCT. Older age at consult (OR, .89; 95% CI, .87-.90; P < .0001) and longer time from diagnosis to consult (OR, .97; 95% CI, .95-.98; P < .0001) were associated with lower AHCT utilization. While AHCT utilization increased from 2012-2017 to 2018-2022 in NHBs compared to NHWs, it remained significantly lower. Racial and ethnic AHCT underutilization has improved over time, but disparities persist. Younger age at consult, shorter time from diagnosis to consult, and lack of cardiac and renal comorbidities also are associated with AHCT utilization.
{"title":"Racial and Ethnic Disparities in Autologous Hematopoietic Cell Transplantation Utilization in Multiple Myeloma Have Persisted Over Time Even After Referral to a Transplant Center","authors":"James Fan Wu , Noel Estrada-Merly , Binod Dhakal , Meera Mohan , Ravi Kishore Narra , Marcelo C. Pasquini , Anita D'Souza","doi":"10.1016/j.jtct.2024.09.010","DOIUrl":"10.1016/j.jtct.2024.09.010","url":null,"abstract":"<div><div>Despite the use of autologous hematopoietic cell transplantation (AHCT) in treatment of multiple myeloma (MM) for almost 40 years and its persistence as standard of care in transplantation-eligible patients with MM even after the advent of novel agents, AHCT remains underutilized, especially in racial and ethnic minority populations. As part of a multipronged effort to quantify disparities in AHCT utilization in MM by race and ethnicity and over time in our own cancer center, we conducted an institutional review of all new patients seen at an academic transplant center for consultation for MM between 2012 and 2022, to calculate AHCT utilization and investigate the factors associated with AHCT utilization. Race and ethnicity were self-reported. Baseline characteristics were analyzed in 3 groups: non-Hispanic White (NHW), non-Hispanic Black (NHB), and Others. Reasons for not undergoing AHCT in the EHR were recorded. Multivariate analyses evaluated the effect of group on AHCT utilization, controlling for covariates related to patients not undergoing AHCT by overall cohort and consult period. Of the 1266 patients, 13.4% were NHB. The median age at consult was 66 (IQR, 23-97) years overall, 66 (IQR, 23-97) years for NHWs, 63 (IQR, 25-85) years for NHBs, and 59.5 (IQR, 31-79) years for Others (<em>P</em> < .01). AHCT utilization was 76% overall, 64.7% in NHBs, 76.8% in Others, and 77.8% in NHWs (<em>P</em> < .01). Age, cytogenetics, stage, comorbidities, and time from diagnosis to consult were associated with receipt of AHCT. From 2012-2017 to 2018-2022, NHB AHCT utilization increased from 57.5% to 69.8% (<em>P</em> = .10). For those who did not receive AHCT, patient preference, older age, comorbidity, early mortality, and lack of caregiver support were the most frequently documented reasons. The NHW group had greater AHCT utilization compared to the NHB group (odds ratio [OR], 3.32; 95% confidence interval [CI], 2.17-5.08; <em>P</em> < .0001). Absent cardiac (OR, 1.88; 95% CI, 1.35-2.62; <em>P</em> = .0002) or renal comorbidity (OR, 3.23; 95% CI, 2.03-5.15; <em>P</em> < .0001) was associated with receipt of AHCT. Older age at consult (OR, .89; 95% CI, .87-.90; <em>P</em> < .0001) and longer time from diagnosis to consult (OR, .97; 95% CI, .95-.98; <em>P</em> < .0001) were associated with lower AHCT utilization. While AHCT utilization increased from 2012-2017 to 2018-2022 in NHBs compared to NHWs, it remained significantly lower. Racial and ethnic AHCT underutilization has improved over time, but disparities persist. Younger age at consult, shorter time from diagnosis to consult, and lack of cardiac and renal comorbidities also are associated with AHCT utilization.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"30 12","pages":"Pages 1189.e1-1189.e10"},"PeriodicalIF":3.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296357","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 : 2024-12-01DOI: 10.1016/j.jtct.2024.11.005
Anthony D. Sung
{"title":"Courage To Try Something New","authors":"Anthony D. Sung","doi":"10.1016/j.jtct.2024.11.005","DOIUrl":"10.1016/j.jtct.2024.11.005","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"30 12","pages":"Pages 1115-1117"},"PeriodicalIF":3.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781143","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 : 2024-12-01DOI: 10.1016/S2666-6367(24)00753-X
{"title":"Masthead (Purpose and Scope)","authors":"","doi":"10.1016/S2666-6367(24)00753-X","DOIUrl":"10.1016/S2666-6367(24)00753-X","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"30 12","pages":"Page A4"},"PeriodicalIF":3.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143095551","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 : 2024-12-01DOI: 10.1016/j.jtct.2024.09.014
Mallory R. Taylor , Steve W. Cole , Miranda C. Bradford , Chuan Zhou , Kaitlyn M. Fladeboe , Jennifer M. Knight , K. Scott Baker , Joyce P. Yi-Frazier , Abby R. Rosenberg
Overactivation of the stress response can influence cancer outcomes through immune-related pathways. Adolescents and young adults (AYAs) undergoing hematopoietic cell transplantation (HCT) are at risk for poor outcomes, yet there are limited behavioral interventions and no psychosocial biomarker data for this population. The Conserved Transcriptional Response to Adversity (CTRA) is an inflammation-related pattern observed in conditions of heightened stress and is associated with HCT outcomes. The objective of the current study was to explore the CTRA gene regulatory impact of Promoting Resilience in Stress Management (PRISM) intervention among AYAs receiving HCT. We hypothesized that patients who received the intervention would have favorable gene expression signatures compared to those in the control arm. This was an ancillary study within a randomized trial testing the PRISM intervention on psychosocial outcomes among AYAs aged 12 to 24 years receiving HCT (NCT03640325). CTRA was quantified through genome-wide transcriptional profiles obtained from whole blood collected at baseline, 1-, and 3-month post-HCT. Group differences in CTRA gene expression were estimated using mixed-effect linear models. There were no baseline group differences in CTRA expression, but PRISM participants showed a greater decline in CTRA at 1 month compared to controls (β –0.301 ± SE 0.114, P = .016), even when controlling for demographic (Group × Time interaction: F(2, 18) = 7.41, P = .004; β –0.386 ± 0.127, P = .007) and clinical covariates (Group × Time interaction: F(2, 20) = 7.03, P = .005; β –0.480 ± 0.144, P = .003). These differences were not detectable at 3 months (β –0.147 ± SE 0.120, P = .235). There was a change in stress-related gene expression among AYAs randomized to a psychosocial intervention. The stress-inflammation axis may be a targetable pathway in the AYA HCT population.
背景：应激反应的过度激活可通过免疫相关途径影响癌症预后。接受造血细胞移植（HCT）的青少年和年轻成人（AYAs）面临不良预后的风险，但针对这一人群的行为干预措施有限，也没有心理社会生物标志物数据。对逆境的保守转录反应（CTRA）是在压力增加的情况下观察到的一种炎症相关模式，与 HCT 结果有关：本研究旨在探讨 PRISM 干预对接受 HCT 的亚健康人群中 CTRA 基因调控的影响。我们假设，与对照组相比，接受干预的患者将具有有利的基因表达特征：这是一项随机试验的辅助研究，该试验测试了 "促进压力管理中的复原力（PRISM）"干预对接受 HCT（NCT03640325）的 12-24 岁亚健康人群的社会心理结果的影响。通过从基线、HCT 后 1 个月和 3 个月采集的全血中获得的全基因组转录谱，对 CTRA 进行了量化。采用混合效应线性模型估计了CTRA基因表达的组间差异：结果：CTRA 基因表达没有基线组间差异，但 PRISM 参与者在 1 个月后的 CTRA 下降幅度大于对照组（β -0.301 ± SE 0.114，p = 0.016），即使控制了人口统计学因素（组 x 时间交互作用，F（2，18） = 7）：F(2, 18) = 7.41, p = 0.004; β -0.386 ± 0.127, p = 0.007）和临床协变量（组 x 时间交互作用：F(2, 20) = 7.41, p = 0.004; β -0.386 ± 0.127, p = 0.007）：F(2, 20) = 7.03, p = 0.005; β -0.480 ± 0.144, p = 0.003）。这些差异在 3 个月时检测不到（β -0.147 ± SE 0.120，p=0.235）：结论：在随机接受心理干预的亚健康人群中，压力相关基因的表达发生了变化。结论：在随机接受心理干预的亚健康人群中，应激相关基因表达发生了变化，应激-炎症轴可能是亚健康 HCT 群体的一个目标途径。
{"title":"Resilience Intervention Improves Stress-Related Gene Expression in Adolescent and Young Adult HCT Recipients","authors":"Mallory R. Taylor , Steve W. Cole , Miranda C. Bradford , Chuan Zhou , Kaitlyn M. Fladeboe , Jennifer M. Knight , K. Scott Baker , Joyce P. Yi-Frazier , Abby R. Rosenberg","doi":"10.1016/j.jtct.2024.09.014","DOIUrl":"10.1016/j.jtct.2024.09.014","url":null,"abstract":"<div><div>Overactivation of the stress response can influence cancer outcomes through immune-related pathways. Adolescents and young adults (AYAs) undergoing hematopoietic cell transplantation (HCT) are at risk for poor outcomes, yet there are limited behavioral interventions and no psychosocial biomarker data for this population. The Conserved Transcriptional Response to Adversity (CTRA) is an inflammation-related pattern observed in conditions of heightened stress and is associated with HCT outcomes. The objective of the current study was to explore the CTRA gene regulatory impact of Promoting Resilience in Stress Management (PRISM) intervention among AYAs receiving HCT. We hypothesized that patients who received the intervention would have favorable gene expression signatures compared to those in the control arm. This was an ancillary study within a randomized trial testing the PRISM intervention on psychosocial outcomes among AYAs aged 12 to 24 years receiving HCT (NCT03640325). CTRA was quantified through genome-wide transcriptional profiles obtained from whole blood collected at baseline, 1-, and 3-month post-HCT. Group differences in CTRA gene expression were estimated using mixed-effect linear models. There were no baseline group differences in CTRA expression, but PRISM participants showed a greater decline in CTRA at 1 month compared to controls (<em>β</em> –0.301 ± SE 0.114, <em>P</em> = .016), even when controlling for demographic (Group × Time interaction: <em>F</em>(2, 18) = 7.41, <em>P</em> = .004; <em>β</em> –0.386 ± 0.127, <em>P</em> = .007) and clinical covariates (Group × Time interaction: <em>F</em>(2, 20) = 7.03, <em>P</em> = .005; <em>β</em> –0.480 ± 0.144, <em>P</em> = .003). These differences were not detectable at 3 months (<em>β</em> –0.147 ± SE 0.120, <em>P</em> = .235). There was a change in stress-related gene expression among AYAs randomized to a psychosocial intervention. The stress-inflammation axis may be a targetable pathway in the AYA HCT population.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"30 12","pages":"Pages 1209.e1-1209.e7"},"PeriodicalIF":3.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296358","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 : 2024-12-01DOI: 10.1016/j.jtct.2024.09.012
Mihkai M. Wickline , Paul A. Carpenter , Jeffrey R. Harris , Sarah J. Iribarren , Kerryn W. Reding , Kenneth C. Pike , Stephanie J. Lee , Catherine J. Lee , Masumi Ueda Oshima , Phuong T. Vo , Donna L. Berry
Comprehensive survivorship care after hematopoietic cell transplantation (HCT) includes revaccination to restore immunity to vaccine-preventable diseases (VPDs). There is complexity to revaccination in this setting, and revaccination rates are sub-optimal. HCT survivors are at high-risk for morbidity and mortality from infections including VPDs, underscoring the importance of interventions to improve revaccination rates among survivors. Determining associations between survivor characteristics and revaccination uptake may guide interventions. The overall study objective was to advance our understanding of factors influencing revaccination uptake among adult HCT survivors living in the United States The specific study aims were to: (1) determine the prevalence of adult survivors who are completely, partially, or not revaccinated at 2 to 8 years after HCT and (2) examine associations between demographic variables, social determinants of health, clinical variables, past vaccination behaviors, vaccine hesitancy (Vaccination Confidence Scale), and revaccination status in adult HCT survivors. This study employed a one-time cross-sectional revaccination survey of adults who were surviving 2 to 8 years after HCT and living in the United States. The survey was sent to eligible survivors in the Fred Hutchinson Cancer Center Long-term Follow-up research cohort. The point prevalence of revaccination outcomes was determined from all the respondents (n = 338), differences in intent to revaccinate for people not yet fully revaccinated were explored using Fisher's exact test (n = 126), and associations were examined between revaccination outcomes and predictors using multivariable logistic regression (n = 292). Survey response rate was 30%. Among respondents, 62% were completely revaccinated, 33% were partially revaccinated, and 4% were not revaccinated. Most respondents (77%) who were not yet fully revaccinated planned to complete the revaccination protocol. However, fewer not-revaccinated respondents than partially revaccinated respondents planned to complete revaccination (50% versus 80%, P = .032). Factors associated with incomplete revaccination were shorter time from HCT, inadequate immune reconstitution, and not having received all childhood vaccines as a child. Our analysis has identified multiple variables associated with revaccination outcomes, indicating the potential for interventions to enhance post-HCT revaccination rates. Since many survivors cannot be revaccinated promptly due to delayed immune recovery, clinicians should iteratively re-evaluate for revaccination readiness as long as it takes to ensure eventual revaccination. Broader efforts by the healthcare community to increase childhood vaccine uptake might eventually support revaccination uptake. Future research that builds on these findings should focus on intervention testing.
背景：造血细胞移植（HCT）后的综合生存护理包括重新接种疫苗，以恢复对疫苗可预防疾病（VPDs）的免疫力。在这种情况下重新接种疫苗非常复杂，接种率也不理想。HCT 幸存者因感染（包括 VPDs）而发病和死亡的风险很高，这凸显了采取干预措施提高幸存者重新接种率的重要性。确定幸存者特征与再接种率之间的关联可为干预措施提供指导：研究的总体目标是进一步了解影响美国成年 HCT 幸存者重新接种疫苗的因素：1）确定成年 HCT 幸存者在 HCT 后 2-8 年完全、部分或未重新接种疫苗的流行率；2）研究成年 HCT 幸存者的人口统计学变量、健康的社会决定因素、临床变量、过去的疫苗接种行为、疫苗犹豫不决（疫苗接种信心量表）和重新接种疫苗状况之间的关联：本研究采用一次性横断面再接种调查的方法，调查对象为美国弗雷德-哈钦森癌症中心（Fred Hutchinson Cancer Center）长期随访研究队列中符合条件的HCT存活2-8年的成人。从所有受访者（人数=338）中确定了重新接种结果的点流行率，使用费雪精确检验（人数=126）探讨了尚未完全重新接种者重新接种意向的差异，并使用多变量逻辑回归（人数=292）研究了重新接种结果与预测因素之间的关联：调查回复率为 30%。受访者中，62%完全重新接种疫苗，33%部分重新接种疫苗，4%未重新接种疫苗。大多数尚未完全接种疫苗的受访者（77%）计划完成疫苗接种。但是，计划完成疫苗接种的未接种者少于部分接种者（50% vs 80%，P=0.032）。与未完成再接种相关的因素包括：距离造血干细胞移植的时间较短、免疫重建不足以及小时候未接种过所有儿童疫苗：我们的分析确定了与再接种结果相关的多个变量，表明有可能采取干预措施来提高造血干细胞移植后的再接种率。由于许多幸存者因免疫力恢复延迟而无法及时接种疫苗，临床医生应反复重新评估接种疫苗的准备情况，以确保最终接种疫苗。医疗保健界为提高儿童疫苗接种率所做的更广泛努力可能最终会支持重新接种。在这些研究结果的基础上，未来的研究应侧重于干预测试。
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