Leonardo Javier Arcuri , Marcelo Schirmer , Marta Colares , Simone Maradei , Rita Tavares , Maria Claudia Rodrigues Moreira , Renato de Castro Araujo , Decio Lerner , Antonio Guilherme Fonseca Pacheco
{"title":"Impact of Anti-CMV IgG Titers and CD34 Count Prior to Hematopoietic Stem Cell Transplantation from Alternative Donors on CMV reactivation","authors":"Leonardo Javier Arcuri , Marcelo Schirmer , Marta Colares , Simone Maradei , Rita Tavares , Maria Claudia Rodrigues Moreira , Renato de Castro Araujo , Decio Lerner , Antonio Guilherme Fonseca Pacheco","doi":"10.1016/j.bbmt.2020.07.034","DOIUrl":"10.1016/j.bbmt.2020.07.034","url":null,"abstract":"<div><p>Cytomegalovirus (CMV) reactivation remains one of the main infectious complications following hematopoietic stem cell transplantation (HSCT). In this study, we explored the role of anti-CMV antibody titers in HSCT from alternative donors and to compare the risk of CMV reactivation between posttransplant cyclophosphamide-based haploidentical HSCT and antithymocyte globulin-based unrelated donor (URD) HSCT. We included 98 CMV-positive patients, 30 undergoing haploidentical HSCT and 68 undergoing URD HSCT. The majority of patients had a malignant disease (84%), received a myeloablative conditioning regimen (78%), and received a bone marrow graft (90%). The median pretransplantation anti-CMV IgG level was 109 U/mL. With median follow-up of 2.2 years, a total of 72 CMV reactivations occurred in 50 patients. There was no difference in CMV reactivation pattern between haploidentical HSCT recipients and URD HSCT recipients. In multivariable analysis until the first event, the incidence of CMV reactivation was higher in patients with anti-CMV IgG levels >100 U/mL (hazard ratio [HR], 2.38; <em>P</em> = .005) and in patients diagnosed with grade II-IV acute graft-versus-host disease (GVHD) (HR, 10.8; <em>P</em> = .003) after day +50 and lower in patients who received higher doses of CD34 cells (HR, .44; <em>P</em> = .006). In multivariable analysis for recurring events, the incidence of CMV reactivation was higher in patients receiving reduced-intensity conditioning (HR, 1.69: <em>P</em> = .04) and in patients with acute GVHD (HR, 1.88; <em>P</em> = .02), and lower in those who received higher doses of CD34 cells (HR, .55; <em>P</em> = .01). In summary, we have shown that pretransplantation anti-CMV IgG titers are correlated with CMV reactivation risk. More studies are needed to assess how this information can be incorporated in HSCT. The use of high-dose cellular grafts, a modifiable risk factor, also protects against CMV reactivation.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.07.034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38225932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Officers and Directors of ASTCT","authors":"","doi":"10.1016/S1083-8791(20)30635-2","DOIUrl":"https://doi.org/10.1016/S1083-8791(20)30635-2","url":null,"abstract":"","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1083-8791(20)30635-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"137415556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"HLA-Matched Unrelated Donors for Patients with Sickle Cell Disease: Results of International Donor Searches","authors":"Karina Tozatto-Maio , Margareth Afonso Torres , Neifi Hassan Saloum Degaide , Juliana Fernandes Cardoso , Fernanda Volt , Ana Cristina Silva Pinto , Danielli Oliveira , Hanadi Elayoubi , Simone Kashima , Pascale Loiseau , Hendrik Veelken , Alina Ferster , Barbara Cappelli , Evandra Strazza Rodrigues , Graziana Maria Scigliuolo , Chantal Kenzey , Annalisa Ruggeri , Vanderson Rocha , Belinda Pinto Simões , Ryad Tamouza , Eliane Gluckman","doi":"10.1016/j.bbmt.2020.07.015","DOIUrl":"10.1016/j.bbmt.2020.07.015","url":null,"abstract":"<div><p>Sickle cell disease (SCD) is the most common inherited hemoglobinopathy. Hematopoietic stem cell transplantation (HCT) is the sole curative therapy for SCD, but few patients will have a matched sibling donor. Patients with SCD are mostly of African origin and thus are less likely to find a matched unrelated donor in international registries. Using HaploStats, we estimated HLA haplotypes for 185 patients with SCD (116 from a Brazilian center and 69 from European Society for Blood and Marrow Transplantation [EBMT] centers) and classified the ethnic origin of haplotypes. Then we assessed the probability of finding an HLA-matched unrelated adult donor (MUD), considering loci A, B, and DRB1 (6/6), in international registries. Most haplotypes were African, but Brazilians showed a greater ethnic admixture than EBMT patients. Nevertheless, the chance of finding at least one 6/6 potential allelic donor was 47% for both groups. Most potential allelic donors were from the US National Marrow Donor Program registry and from the Brazilian REDOME donor registry. Although the probability of finding a donor is higher than previously reported, strategies are needed to improve ethnic diversity in registries. Moreover, predicting the likelihood of having an MUD might influence SCD management.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.07.015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38195359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Polona Novak , Tatjana Zabelina , Christine Wolschke , Francis Ayuk , Maximilian Christopeit , Nicolaus Kröger
{"title":"Allogeneic Stem Cell Transplantation for Patients with Lower-Risk Myelodysplastic Syndrome","authors":"Polona Novak , Tatjana Zabelina , Christine Wolschke , Francis Ayuk , Maximilian Christopeit , Nicolaus Kröger","doi":"10.1016/j.bbmt.2020.07.018","DOIUrl":"10.1016/j.bbmt.2020.07.018","url":null,"abstract":"<div><p>The indication for allogeneic stem cell transplantation (SCT) in patients with lower-risk myelodysplastic syndrome (MDS) is controversial. Here we report 60 patients with a low risk (n = 32) or intermediate risk (n = 28) classification according to the revised International Prognostic Scoring System (IPSS-R) who underwent allogeneic SCT with a reduced-intensity conditioning (n = 45) or myeloablative conditioning (n = 15) regimen from an HLA-identical sibling (n = 9), a matched unrelated donor (n = 36), or a mismatched unrelated donor (n = 15). The rates of grade II-IV and grade III-IV acute graft-versus-host disease were 32% and 7%, respectively, resulting in a transplantation-related mortality (TRM) of 17% at 3 years. The cumulative incidence of relapse at 5 years was only 7%, resulting in a 5-year disease-free survival of 72% and overall survival (OS) of 79%. Transplantation from a fully matched donor resulted in significantly improved OS at 5 years (91% versus 70%). Allogeneic SCT in lower-risk MDS (IPSS-R low or intermediate risk) from an HLA-matched donor resulted in excellent OS with a low risk of relapse.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.07.018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38205687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jeremy D. Rubinstein , Christa Krupski , Adam S. Nelson , Maureen M. O'Brien , Stella M. Davies , Christine L. Phillips
{"title":"Chimeric Antigen Receptor T Cell Therapy in Patients with Multiply Relapsed or Refractory Extramedullary Leukemia","authors":"Jeremy D. Rubinstein , Christa Krupski , Adam S. Nelson , Maureen M. O'Brien , Stella M. Davies , Christine L. Phillips","doi":"10.1016/j.bbmt.2020.07.036","DOIUrl":"10.1016/j.bbmt.2020.07.036","url":null,"abstract":"<div><p>Autologous CD19-directed chimeric antigen receptor T lymphocyte (CAR-T) therapy is an approved and effective treatment for the management of patients with refractory and multiply relapsed B cell precursor acute lymphoblastic leukemia (B-ALL). Experience using this therapy in pediatric patients with extramedullary (EM) disease is limited, in part because these patients have frequently been excluded from clinical trials owing to concerns for an increased risk of immune effector cell-associated neurotoxicity syndrome (ICANS). We infused 7 patients with refractory or multiply relapsed B-ALL who presented with isolated EM relapse with tisagenlecleucel. Six patients had isolated central nervous system (CNS) leukemia, and 1 patient had an isolated testicular relapse. An initial complete response was seen in all patients, with 5 patients remaining in CAR-T-induced remission at a median of 18 months from first infusion. Reversible ICANS was seen in 1 patient with CNS leukemia. Durable B cell aplasia occurred in 3 patients, with a median time to B cell recovery of 6.5 months in the other patients. These data suggest that CAR-T therapy has promising safety and efficacy in treating EM leukemia, although definitive conclusions are limited by the small size of the cohort and limited follow-up period.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.07.036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38231957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Updated Comparison of 7/8 HLA Allele-Matched Unrelated Bone Marrow Transplantation and Single-Unit Umbilical Cord Blood Transplantation as Alternative Donors in Adults with Acute Leukemia","authors":"Kotaro Miyao , Seitaro Terakura , Fumihiko Kimura , Takaaki Konuma , Koichi Miyamura , Masamitsu Yanada , Shinichi Kako , Satoko Morhishima , Naoyuki Uchida , Takashi Toya , Yukiyasu Ozawa , Takahiro Fukuda , Masatsugu Tanaka , Masashi Sawa , Satoru Takada , Shuro Yoshida , Takafumi Kimura , Tatsuo Ichinohe , Yoshiko Atsuta , Junya Kanda","doi":"10.1016/j.bbmt.2020.08.001","DOIUrl":"10.1016/j.bbmt.2020.08.001","url":null,"abstract":"<div><p>The outcomes of 7/8 allele-matched unrelated bone marrow transplantation (7/8 UBMT) and umbilical cord blood transplantation (UCBT) have been improving. We retrospectively analyzed adults with acute leukemia who underwent their first 7/8 UBMT or UCBT in Japan. Between January 2008 and December 2017, a total of 4150 patients were recorded, including 488 who underwent 7/8 UBMT and 3662 who underwent UCBT. Only 32 patients with 7/8 UBMT had graft-versus-host-disease (GVHD) high-risk HLA mismatched pairs. Overall survival at 3 years was 54% for 7/8 the UBMT group and 46% for the UCBT group, a nonsignificant difference in multivariate analysis (hazard ratio [HR], 1.01; 95% confidence interval [CI], .88 to 1.17; <em>P</em> = .89). The 7/8 UBMT and UCBT groups showed a similar nonrelapse mortality rate (HR, 1.16; 95% CI, .96 to 1.45; <em>P</em> = .16) and relapse rate (HR, .85; 95% CI, .71 to 1.02; <em>P</em> = .08). However, the UCBT group had a lower risk of grade II-IV acute GVHD (HR, .76; 95% CI, .65 to .88; <em>P</em> < .001) and chronic GVHD (HR, .77; 95% CI, .66- .91; <em>P</em> = .002) compared with the 7/8 UBMT group. In stratified analyses combining disease risk with conditioning intensity, 7/8 UBMT showed superior overall survival to UCBT in standard risk and myeloablative conditioning (HR, .72; 95% CI, .56 to .93; <em>P</em> = .014). Both 7/8 UBMT and UCBT are appropriate alternative donor procedures. The stem cell source can be selected on the basis of disease risk, patient tolerability, or concerns regarding GVHD.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.08.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38253488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"ASTCT Notes","authors":"","doi":"10.1016/j.bbmt.2020.09.002","DOIUrl":"10.1016/j.bbmt.2020.09.002","url":null,"abstract":"","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.09.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25510023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joyce J. Johnsrud , Isabelle T. Nguyen , Walter Domingo , Balasubramanian Narasimhan , Bradley Efron , Janice (Wes) Brown
{"title":"Letermovir Prophylaxis Decreases Burden of Cytomegalovirus (CMV) in Patients at High Risk for CMV Disease Following Hematopoietic Cell Transplant","authors":"Joyce J. Johnsrud , Isabelle T. Nguyen , Walter Domingo , Balasubramanian Narasimhan , Bradley Efron , Janice (Wes) Brown","doi":"10.1016/j.bbmt.2020.07.002","DOIUrl":"10.1016/j.bbmt.2020.07.002","url":null,"abstract":"<div><p>Despite effective therapies, cytomegalovirus (CMV) continues to have a significant impact on morbidity and mortality in hematopoietic cell transplant recipients. At particular risk are recipients of alternative grafts such as umbilical cord blood (UCB), haploidentical transplants (haplo), or patients conditioned with T-cell depleting regimens such as anti-thymocyte globulin (ATG). With the approval of letermovir, its impact on high-risk patients is of particular interest. To evaluate the impact of letermovir prophylaxis at our center, we performed a retrospective analysis of 114 high-risk patients who received letermovir as prophylaxis (LET PPX) between January 2018 through December 2019, including 30 UCB and 22 haplo recipients, compared with 637 historical controls with comparable risk between January 2013 and December 2019. By post-transplant day 100 (D+100), letermovir prophylaxis significantly decreased the incidence of both CMV DNAemia compared with controls (45.37% versus 74.1%; <em>P</em> < .001) and clinically significant CMV infection (12.04% versus 48.82%; <em>P</em> < .001). The impact of LET PPX was even more profound on the incidence of clinically significant CMV infection (CSI), defined as the administration of antiviral therapy as preemptive therapy for CMV DNAemia or treatment for CMV disease. CSI was significantly lower in haplo recipients on LET PPX compared with controls (13.64% versus 73.33%; <em>P</em>= .02) and UCB recipients on LET PPX compared with controls (3.45% versus 37.5%; <em>P</em> < .001). No patients on LET primary PPX developed CMV disease in any treatment group by D+100 compared with controls (0% versus 5.34%, respectively; <em>P</em> = .006). Patients on LET PPX had fewer hospitalizations involving initiation of anti-CMV therapy compared with controls (0.93% versus 15.23%, respectively). Our analysis of the largest cohort of patients at high risk for CMV reactivation published to date demonstrates that letermovir prophylaxis significantly reduces the number of patients who receive CMV-active antiviral therapy for either DNAemia or disease due to CMV.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.07.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38143803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sarah A. Holstein , Alan Howard , David Avigan , Manisha Bhutani , Adam D. Cohen , Luciano J. Costa , Madhav V. Dhodapkar , Francesca Gay , Nicole Gormley , Damian J. Green , Jens Hillengass , Neha Korde , Zihai Li , Sham Mailankody , Paola Neri , Samir Parekh , Marcelo C. Pasquini , Noemi Puig , G. David Roodman , Mehmet Kemal Samur , Philip L. McCarthy
{"title":"Summary of the 2019 Blood and Marrow Transplant Clinical Trials Network Myeloma Intergroup Workshop on Minimal Residual Disease and Immune Profiling","authors":"Sarah A. Holstein , Alan Howard , David Avigan , Manisha Bhutani , Adam D. Cohen , Luciano J. Costa , Madhav V. Dhodapkar , Francesca Gay , Nicole Gormley , Damian J. Green , Jens Hillengass , Neha Korde , Zihai Li , Sham Mailankody , Paola Neri , Samir Parekh , Marcelo C. Pasquini , Noemi Puig , G. David Roodman , Mehmet Kemal Samur , Philip L. McCarthy","doi":"10.1016/j.bbmt.2020.06.011","DOIUrl":"10.1016/j.bbmt.2020.06.011","url":null,"abstract":"<div><p>The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Myeloma Intergroup has organized an annual workshop focused on minimal residual disease (MRD) testing and immune profiling (IP) in multiple myeloma since 2016. In 2019, the workshop took place as an American Society of Hematology (ASH) Friday Scientific Workshop titled “Immune Profiling and Minimal Residual Disease Testing in Multiple Myeloma.” This workshop focused on 4 main topics: the molecular and immunologic evolution of plasma cell disorders, development of new laboratory- and imaging-based MRD assessment approaches, chimeric antigen receptor T cell therapy research, and statistical and regulatory issues associated with novel clinical endpoints. In this report, we provide a summary of the workshop and discuss future directions.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.06.011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38094484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}