Pub Date : 2020-11-01DOI: 10.1016/j.bbmt.2020.07.010
Sandra S. Rohr , Raul C. Maranhão , Thauany M. Tavoni , Aleksandra T. Morikawa , Kelsy Areco , Debora F. Deus , José S.R. Oliveira
Allogeneic hematopoietic cell transplantation (HCT) is the treatment of choice for acute myelogenous leukemia (AML) not responding to induction therapy. It is a therapeutic choice for the blast phase of chronic myelogenous leukemia (CML-BP) in patients failing to respond to tyrosine kinase inhibitors (TKIs). Lipid core nanoparticles (LDEs) concentrate severalfold more in blast cells than in corresponding normal cells. Incorporation of anticancer drugs to LDE formulations increases the pharmacologic action and decreases the toxicity. We tested a drug-targeting system, LDE-etoposide plus total body irradiation (TBI; 1200 cGy dose), in 13 patients with AML not responding to the induction therapy and in 2 patients with CML-BP refractory to second-generation TKIs. The mean patient age was 46.7 years (range, 22 to 66 years). The LDE-etoposide dose was escalated at 20, 30, 40, 50, and 60 mg/kg. No patients developed grade 4 or 5 toxicity; however, mucositis grade 3 occurred in 6 patients, 3 patients experienced diarrhea, and 1 patient had an elevated total bilirubin level. No deaths were related to conditioning. All patients were successfully engrafted. The median times to neutrophil and platelet engraftment were 20 ± 5 days and 16 ± 4 days, respectively. Five patients (33.4%) had acute graft-versus-host-disease (GVHD), including 4 grade I, and 1 with grade II, and 8 patients (57.1%) had moderate-to-severe chronic GVHD. This pilot study shows the potential of LDE-etoposide plus TBI as an HCT conditioning regimen in AML patients not responding to the induction and refractory therapies for CML-BP patient. These findings pave the way for subsequent larger clinical trials.
{"title":"Novel Approach for Bone Marrow Transplantation Conditioning in Acute Myelogenous Leukemia not Responding to the Induction Therapy Using Etoposide Carried in Lipid Core Nanoparticles: A Pilot Clinical Study","authors":"Sandra S. Rohr , Raul C. Maranhão , Thauany M. Tavoni , Aleksandra T. Morikawa , Kelsy Areco , Debora F. Deus , José S.R. Oliveira","doi":"10.1016/j.bbmt.2020.07.010","DOIUrl":"10.1016/j.bbmt.2020.07.010","url":null,"abstract":"<div><p>Allogeneic hematopoietic cell transplantation (HCT) is the treatment of choice for acute myelogenous leukemia (AML) not responding to induction therapy. It is a therapeutic choice for the blast phase of chronic myelogenous leukemia (CML-BP) in patients failing to respond to tyrosine kinase inhibitors (TKIs). Lipid core nanoparticles (LDEs) concentrate severalfold more in blast cells than in corresponding normal cells. Incorporation of anticancer drugs to LDE formulations increases the pharmacologic action and decreases the toxicity. We tested a drug-targeting system, LDE-etoposide plus total body irradiation (TBI; 1200 cGy dose), in 13 patients with AML not responding to the induction therapy and in 2 patients with CML-BP refractory to second-generation TKIs. The mean patient age was 46.7 years (range, 22 to 66 years). The LDE-etoposide dose was escalated at 20, 30, 40, 50, and 60 mg/kg. No patients developed grade 4 or 5 toxicity; however, mucositis grade 3 occurred in 6 patients, 3 patients experienced diarrhea, and 1 patient had an elevated total bilirubin level. No deaths were related to conditioning. All patients were successfully engrafted. The median times to neutrophil and platelet engraftment were 20 ± 5 days and 16 ± 4 days, respectively. Five patients (33.4%) had acute graft-versus-host-disease (GVHD), including 4 grade I, and 1 with grade II, and 8 patients (57.1%) had moderate-to-severe chronic GVHD<strong>.</strong> This pilot study shows the potential of LDE-etoposide plus TBI as an HCT conditioning regimen in AML patients not responding to the induction and refractory therapies for CML-BP patient. These findings pave the way for subsequent larger clinical trials.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":"26 11","pages":"Pages 2027-2033"},"PeriodicalIF":4.3,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.07.010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38167339","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}
Pub Date : 2020-11-01DOI: 10.1016/j.bbmt.2020.07.006
Silvia Park , Gi June Min , Sung Soo Park , Seung-Ah Yahng , Young-Woo Jeon , Seung-Hwan Shin , Jae-Ho Yoon , Sung-Eun Lee , Byung Sik Cho , Ki-Seong Eom , Yoo-Jin Kim , Seok Lee , Chang-Ki Min , Seok-Goo Cho , Dong-Wook Kim , Jong Wook Lee , Hee-Je Kim
Relapse is a major concern with reduced-intensity conditioning. We analyzed 257 patients with acute myeloid leukemia (AML) who received allogeneic stem cell transplantation (SCT) and fulfilled the following criteria: intermediate- or poor-risk disease by National Comprehensive Cancer Network guidelines (2017, version 3), in first complete remission (CR1) at SCT, received either myeloablative conditioning (MAC; busulfan plus cyclophosphamide or cyclophosphamide plus total body irradiation) or reduced-intensity conditioning (RIC; FluBu2TBI400) peripheral blood SCT from 8/8 matched sibling or unrelated donor, and having bone marrow Wilms tumor gene 1 (WT1) expression results before transplant. We and other groups serially published a predictive value for pretransplant WT1 expression in patients with AML to identify patients at higher risk of relapse. Among the total 257 patients, 191 (74.3%) and 66 (25.7%) patients received MAC and RIC transplants, respectively. WT1 ≥250 copies/104ABL was defined as WT1high. WT1high before SCT was found to be an independent prognostic factor for inferior overall survival (OS), disease-free survival (DFS), and higher cumulative incidence of relapse (CIR). There were 201 patients with WT1 low expression based upon pretransplant analysis. There was no significant difference in OS, DFS, CIR, and nonrelapse mortality between MAC and RIC patients. To conclude, post-transplant survival or relapse was not different by conditioning intensity in AML CR1 patients whose WT1 level was below 250 copies per 104ABL at transplantation.
{"title":"Comparison of Myeloablative (CyTBI, BuCy) versus Reduced-Intensity (FluBu2TBI400) Peripheral Blood Stem Cell Transplantation in Acute Myeloid Leukemia Patients with Pretransplant Low WT1 Expression","authors":"Silvia Park , Gi June Min , Sung Soo Park , Seung-Ah Yahng , Young-Woo Jeon , Seung-Hwan Shin , Jae-Ho Yoon , Sung-Eun Lee , Byung Sik Cho , Ki-Seong Eom , Yoo-Jin Kim , Seok Lee , Chang-Ki Min , Seok-Goo Cho , Dong-Wook Kim , Jong Wook Lee , Hee-Je Kim","doi":"10.1016/j.bbmt.2020.07.006","DOIUrl":"10.1016/j.bbmt.2020.07.006","url":null,"abstract":"<div><p>Relapse is a major concern with reduced-intensity conditioning. We analyzed 257 patients with acute myeloid leukemia (AML) who received allogeneic stem cell transplantation (SCT) and fulfilled the following criteria: intermediate- or poor-risk disease by National Comprehensive Cancer Network guidelines (2017, version 3), in first complete remission (CR1) at SCT, received either myeloablative conditioning (MAC; busulfan plus cyclophosphamide or cyclophosphamide plus total body irradiation) or reduced-intensity conditioning (RIC; FluBu2TBI400) peripheral blood SCT from 8/8 matched sibling or unrelated donor, and having bone marrow Wilms tumor gene 1 (<em>WT1</em>) expression results before transplant. We and other groups serially published a predictive value for pretransplant <em>WT1</em> expression in patients with AML to identify patients at higher risk of relapse. Among the total 257 patients, 191 (74.3%) and 66 (25.7%) patients received MAC and RIC transplants, respectively. <em>WT1</em> ≥250 copies/10<sup>4</sup> <em>ABL</em> was defined as <em>WT1<sup>high</sup>. WT1<sup>high</sup></em> before SCT was found to be an independent prognostic factor for inferior overall survival (OS), disease-free survival (DFS), and higher cumulative incidence of relapse (CIR). There were 201 patients with <em>WT1</em> low expression based upon pretransplant analysis. There was no significant difference in OS, DFS, CIR, and nonrelapse mortality between MAC and RIC patients. To conclude, post-transplant survival or relapse was not different by conditioning intensity in AML CR1 patients whose <em>WT1</em> level was below 250 copies per 10<sup>4</sup> <em>ABL</em> at transplantation.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":"26 11","pages":"Pages 2018-2026"},"PeriodicalIF":4.3,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.07.006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38154686","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}
Pub Date : 2020-11-01DOI: 10.1016/j.bbmt.2020.08.004
Andrea Z. Pereira , Sandra Elisa Adami Gonçalves , Morgani Rodrigues , Nelson Hamerschlak , Mary E. Flowers
There is a paucity of information about nutrition in chronic graft-versus-host disease (GVHD). The role of nutrition is important because malnutrition is strongly associated with severe chronic GVHD manifestations. There is a high prevalence of metabolic syndrome and osteoporosis in this setting. Here we review the literature, describe main aspects of nutrition and discuss macronutrients (ie, vitamins), micronutrients (ie, Mg, Zn, Ca, and K) and supplements (probiotics and omega 3 fatty acids). A search was carried out in March 2020 using PubMed. Databases were screened for searching terms in titles and abstracts referring to chronic GVHD, nutrition intervention, protein, and body composition. Data were extracted for the following outcomes: nutrition, nutrition intervention, chronic GVHD, nutrition deficiencies, diet, vitamin, dry eye, probiotic, protein, and body composition. In this report, we summarize interventional nutrition studies reported in oncology and metabolic syndrome settings and describe our nutritional clinical practice in hematopoietic cell transplantation and chronic GVHD. The impact of nutrition evaluation and intervention on muscle mass loss, dry eye, dysgeusia, metabolic syndrome, osteoporosis, and comorbidities associated with chronic GVHD need to be studied prospectively.
{"title":"Challenging and Practical Aspects of Nutrition in Chronic Graft-versus-Host Disease","authors":"Andrea Z. Pereira , Sandra Elisa Adami Gonçalves , Morgani Rodrigues , Nelson Hamerschlak , Mary E. Flowers","doi":"10.1016/j.bbmt.2020.08.004","DOIUrl":"10.1016/j.bbmt.2020.08.004","url":null,"abstract":"<div><p>There is a paucity of information about nutrition in chronic graft-versus-host disease (GVHD). The role of nutrition is important because malnutrition is strongly associated with severe chronic GVHD manifestations. There is a high prevalence of metabolic syndrome and osteoporosis in this setting. Here we review the literature, describe main aspects of nutrition and discuss macronutrients (ie, vitamins), micronutrients (ie, Mg, Zn, Ca, and K) and supplements (probiotics and omega 3 fatty acids). A search was carried out in March 2020 using PubMed. Databases were screened for searching terms in titles and abstracts referring to chronic GVHD, nutrition intervention, protein, and body composition. Data were extracted for the following outcomes: nutrition, nutrition intervention, chronic GVHD, nutrition deficiencies, diet, vitamin, dry eye, probiotic, protein, and body composition. In this report, we summarize interventional nutrition studies reported in oncology and metabolic syndrome settings and describe our nutritional clinical practice in hematopoietic cell transplantation and chronic GVHD. The impact of nutrition evaluation and intervention on muscle mass loss, dry eye, dysgeusia, metabolic syndrome, osteoporosis, and comorbidities associated with chronic GVHD need to be studied prospectively.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":"26 11","pages":"Pages e265-e270"},"PeriodicalIF":4.3,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.08.004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38255033","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}
Pub Date : 2020-11-01DOI: 10.1016/j.bbmt.2020.08.011
Alexander H. Schmidt , Deborah Buk , Alexander Platz , Marcel R.M. van den Brink
{"title":"Cryopreservation for All Is No Option in Unrelated Stem Cell Transplantation. Comment on Dholaria B, et al. Securing the Graft During Pandemic: Are We Ready for Cryopreservation for All? Biol Blood Marrow Transplant. 2020;26:e145-e146.","authors":"Alexander H. Schmidt , Deborah Buk , Alexander Platz , Marcel R.M. van den Brink","doi":"10.1016/j.bbmt.2020.08.011","DOIUrl":"10.1016/j.bbmt.2020.08.011","url":null,"abstract":"","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":"26 11","pages":"Pages e298-e299"},"PeriodicalIF":4.3,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.08.011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38296339","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}
Pub Date : 2020-11-01DOI: 10.1016/j.bbmt.2020.07.016
Alexandra Gomez-Arteaga , Gunjan L. Shah , Raymond E. Baser , Michael Scordo , Josel D. Ruiz , Adam Bryant , Parastoo B. Dahi , Arnab Ghosh , Oscar B. Lahoud , Heather J. Landau , Ola Landgren , Brian C. Shaffer , Eric L. Smith , Guenther Koehne , Miguel-Angel Perales , Sergio A. Giralt , David J. Chung
Allogeneic hematopoietic cell transplantation (alloHCT) for multiple myeloma (MM), with its underlying graft-versus-tumor capacity, is a potentially curative approach for high-risk patients. Relapse is the main cause of treatment failure, but predictors for postrelapse survival are not well characterized. We conducted a retrospective analysis to evaluate predictors for postrelapse overall survival (OS) in 60 MM patients who progressed after myeloablative T cell-depleted alloHCT. The median patient age was 56 years, and 82% had high-risk cytogenetics. Patients received a median of 4 lines of therapy pre-HCT, and 88% achieved at least a partial response (PR) before alloHCT. Of the 38% who received preemptive post-HCT therapy, 13 received donor lymphocyte infusions (DLIs) and 10 received other interventions. Relapse was defined as very early (<6 months; 28%), early (6 to 24 months; 50%), or late (>24 months; 22%). At relapse, 27% presented with extramedullary disease (EMD). The median postrelapse overall survival (OS) by time to relapse was 4 months for the very early relapse group, 17 months for the early relapse group, and 72 months for the late relapse group (P = .002). Older age, relapse with EMD, <PR before alloHCT, <PR by day +100, and no maintenance were prognostic for inferior postrelapse OS on univariate analysis. On multivariate analysis adjusted for age and sex, very early relapse (hazard ratio [HR], 4.37; 95% confidence interval [CI], 1.42 to 13.5), relapse with EMD (HR, 5.20; 95% CI, 2.10 to 12.9), and DLI for relapse prevention (HR, .11; 95% CI, 2.10 to 12.9) were significant predictors for postrelapse survival. Despite their shared inherent high-risk status, patients with MM have significantly disparate post-HCT relapse courses, with some demonstrating long-term survival despite relapse.
{"title":"Prognostic Factors for Postrelapse Survival after ex Vivo CD34+-Selected (T Cell-Depleted) Allogeneic Hematopoietic Cell Transplantation in Multiple Myeloma","authors":"Alexandra Gomez-Arteaga , Gunjan L. Shah , Raymond E. Baser , Michael Scordo , Josel D. Ruiz , Adam Bryant , Parastoo B. Dahi , Arnab Ghosh , Oscar B. Lahoud , Heather J. Landau , Ola Landgren , Brian C. Shaffer , Eric L. Smith , Guenther Koehne , Miguel-Angel Perales , Sergio A. Giralt , David J. Chung","doi":"10.1016/j.bbmt.2020.07.016","DOIUrl":"10.1016/j.bbmt.2020.07.016","url":null,"abstract":"<div><p>Allogeneic hematopoietic cell transplantation (alloHCT) for multiple myeloma (MM), with its underlying graft-versus-tumor capacity, is a potentially curative approach for high-risk patients. Relapse is the main cause of treatment failure, but predictors for postrelapse survival are not well characterized. We conducted a retrospective analysis to evaluate predictors for postrelapse overall survival (OS) in 60 MM patients who progressed after myeloablative T cell-depleted alloHCT. The median patient age was 56 years, and 82% had high-risk cytogenetics. Patients received a median of 4 lines of therapy pre-HCT, and 88% achieved at least a partial response (PR) before alloHCT. Of the 38% who received preemptive post-HCT therapy, 13 received donor lymphocyte infusions (DLIs) and 10 received other interventions. Relapse was defined as very early (<6 months; 28%), early (6 to 24 months; 50%), or late (>24 months; 22%). At relapse, 27% presented with extramedullary disease (EMD). The median postrelapse overall survival (OS) by time to relapse was 4 months for the very early relapse group, 17 months for the early relapse group, and 72 months for the late relapse group (<em>P</em> = .002). Older age, relapse with EMD, <PR before alloHCT, <PR by day +100, and no maintenance were prognostic for inferior postrelapse OS on univariate analysis. On multivariate analysis adjusted for age and sex, very early relapse (hazard ratio [HR], 4.37; 95% confidence interval [CI], 1.42 to 13.5), relapse with EMD (HR, 5.20; 95% CI, 2.10 to 12.9), and DLI for relapse prevention (HR, .11; 95% CI, 2.10 to 12.9) were significant predictors for postrelapse survival. Despite their shared inherent high-risk status, patients with MM have significantly disparate post-HCT relapse courses, with some demonstrating long-term survival despite relapse.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":"26 11","pages":"Pages 2040-2046"},"PeriodicalIF":4.3,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.07.016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38195358","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}
Pub Date : 2020-11-01DOI: 10.1016/j.bbmt.2020.07.020
Eduardo Rodríguez-Arbolí , Myriam Labopin , Johanna Tischer , Arne Brecht , Arnold Ganser , Jürgen Finke , Igor Wolfgang Blau , Nicolaus Kröger , Peter Kalhs , Edouard Forcade , Donald Bunjes , Alexandros Spyridonidis , Bipin Savani , Arnon Nagler , Mohamad Mohty
The use of myeloablative conditioning (MAC) in the setting of active relapsed/refractory (R/R) acute myeloid leukemia (AML) has been hindered by high historical rates of nonrelapse mortality (NRM). FLAMSA (fludarabine, Ara-C, and amsacrine) chemotherapy (CT) followed by reduced-intensity conditioning (RIC) has been proposed as an effective and potentially safer alternative in this scenario. As improvements in supportive care have contributed to decreasing NRM rates after MAC, a comparative reassessment of these two strategies was performed. This was a registry-based analysis by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Eligibility criteria included age 18 to 50 years, primary refractory, first or second relapsed active AML, first allogeneic stem cell transplantation from a matched sibling donor (MSD) or an unrelated donor (UD) performed between 2005 and 2018, MAC or FLAMSA-RIC. A total of 1018 patients were included. The median patient age was 39 years (range, 18 to 50). Two hundred and fifty-eight patients received busulfan (Bu)/cyclophosphamide (Cy), 314 received Cy/total body irradiation (TBI), 318 received FLAMSA-TBI, and 128 received FLAMSA-CT. The median duration of follow-up was 50 months. In univariate analysis, the 2-year relapse incidence (RI) (54%; 95% confidence interval (CI), 50%-57%), leukemia-free survival (LFS) (30%; 95% CI, 27%-33%), and refined graft-versus-host disease-free, relapse-free survival (GRFS) (21%; 95% CI, 18%-24%) were not significantly different between cohorts. Lower 2-year NRM was observed in the FLAMSA-CT group (7% versus 16% in Bu/Cy, 19% in Cy/TBI, and 18% in FLAMSA-TBI; P = .04), as well as increased 2-year overall survival (OS) (50% versus 33% in Bu/Cy, 34% in Cy/TBI, and 36% in FLAMSA-TBI; P = .03). These results were maintained in the multivariate analysis (hazard ratio [HR] for NRM: .40, P = .01; HR for OS: .65, P = .01; Bu/Cy as reference). These data suggest that FLAMSA-CT may be a preferred conditioning regimen in patients with active R/R AML due to lower NRM. Yet, the high relapse rates observed in our analyses emphasize the need for novel therapeutic strategies in this clinical setting.
{"title":"FLAMSA-Based Reduced-Intensity Conditioning versus Myeloablative Conditioning in Younger Patients with Relapsed/Refractory Acute Myeloid Leukemia with Active Disease at the Time of Allogeneic Stem Cell Transplantation: An Analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation","authors":"Eduardo Rodríguez-Arbolí , Myriam Labopin , Johanna Tischer , Arne Brecht , Arnold Ganser , Jürgen Finke , Igor Wolfgang Blau , Nicolaus Kröger , Peter Kalhs , Edouard Forcade , Donald Bunjes , Alexandros Spyridonidis , Bipin Savani , Arnon Nagler , Mohamad Mohty","doi":"10.1016/j.bbmt.2020.07.020","DOIUrl":"10.1016/j.bbmt.2020.07.020","url":null,"abstract":"<div><p>The use of myeloablative conditioning (MAC) in the setting of active relapsed/refractory (R/R) acute myeloid leukemia (AML) has been hindered by high historical rates of nonrelapse mortality (NRM). FLAMSA (fludarabine, Ara-C, and amsacrine) chemotherapy (CT) followed by reduced-intensity conditioning (RIC) has been proposed as an effective and potentially safer alternative in this scenario. As improvements in supportive care have contributed to decreasing NRM rates after MAC, a comparative reassessment of these two strategies was performed. This was a registry-based analysis by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Eligibility criteria included age 18 to 50 years, primary refractory, first or second relapsed active AML, first allogeneic stem cell transplantation from a matched sibling donor (MSD) or an unrelated donor (UD) performed between 2005 and 2018, MAC or FLAMSA-RIC. A total of 1018 patients were included. The median patient age was 39 years (range, 18 to 50). Two hundred and fifty-eight patients received busulfan (Bu)/cyclophosphamide (Cy), 314 received Cy/total body irradiation (TBI), 318 received FLAMSA-TBI, and 128 received FLAMSA-CT. The median duration of follow-up was 50 months. In univariate analysis, the 2-year relapse incidence (RI) (54%; 95% confidence interval (CI), 50%-57%), leukemia-free survival (LFS) (30%; 95% CI, 27%-33%), and refined graft-versus-host disease-free, relapse-free survival (GRFS) (21%; 95% CI, 18%-24%) were not significantly different between cohorts. Lower 2-year NRM was observed in the FLAMSA-CT group (7% versus 16% in Bu/Cy, 19% in Cy/TBI, and 18% in FLAMSA-TBI; <em>P</em> = .04), as well as increased 2-year overall survival (OS) (50% versus 33% in Bu/Cy, 34% in Cy/TBI, and 36% in FLAMSA-TBI; <em>P</em> = .03). These results were maintained in the multivariate analysis (hazard ratio [HR] for NRM: .40, <em>P</em> = .01; HR for OS: .65, <em>P</em> = .01; Bu/Cy as reference). These data suggest that FLAMSA-CT may be a preferred conditioning regimen in patients with active R/R AML due to lower NRM. Yet, the high relapse rates observed in our analyses emphasize the need for novel therapeutic strategies in this clinical setting.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":"26 11","pages":"Pages 2165-2173"},"PeriodicalIF":4.3,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.07.020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38205688","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}
Pub Date : 2020-11-01DOI: 10.1016/j.bbmt.2020.07.031
Megan M. Herr, George L. Chen, Maureen Ross, Hillary Jacobson, Renee McKenzie, Laura Markel, Sophia R. Balderman, Christine M. Ho, Theresa Hahn, Philip L. McCarthy
A consensus grading schema for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) resulting from chimeric antigen receptor (CAR) T cell therapy was published in 2019. Although this consensus grading schema has been imperative in identifying and monitoring CRS and ICANS in our CAR T cell population, we observed patients exhibiting subtle neurotoxicity symptoms prior to a decrease in their immune effector cell-associated encephalopathy (ICE) score, which is one component of ICANS. Because we treat grade 1 ICANS at our institution, identification of early neurotoxicity symptoms is important. Additionally, we found changes in personality, occupational confusion, or inability to answer dichotomous questions were early signs of neurotoxicity. Therefore, we developed a 3-step command tool to supplement the ICE evaluation. We present 2 examples of patients who exhibited early neurotoxicity symptoms and led us to develop this tool and 1 in whom it was effective. We propose that CAR T cell patients are consistently followed by a clinical care provider who is familiar with the patient to recognize early changes in personality, behavior, and cognition. Additionally, we propose that the multistep command tool be used in conjunction with the ICE score to detect early symptoms of ICANS. Early intervention has the potential to prevent irreversible neurotoxicity.
{"title":"Identification of Neurotoxicity after Chimeric Antigen Receptor (CAR) T Cell Infusion without Deterioration in the Immune Effector Cell-Associated Encephalopathy (ICE) Score","authors":"Megan M. Herr, George L. Chen, Maureen Ross, Hillary Jacobson, Renee McKenzie, Laura Markel, Sophia R. Balderman, Christine M. Ho, Theresa Hahn, Philip L. McCarthy","doi":"10.1016/j.bbmt.2020.07.031","DOIUrl":"10.1016/j.bbmt.2020.07.031","url":null,"abstract":"<div><p>A consensus grading schema for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) resulting from chimeric antigen receptor (CAR) T cell therapy was published in 2019. Although this consensus grading schema has been imperative in identifying and monitoring CRS and ICANS in our CAR T cell population, we observed patients exhibiting subtle neurotoxicity symptoms prior to a decrease in their immune effector cell-associated encephalopathy (ICE) score, which is one component of ICANS. Because we treat grade 1 ICANS at our institution, identification of early neurotoxicity symptoms is important. Additionally, we found changes in personality, occupational confusion, or inability to answer dichotomous questions were early signs of neurotoxicity. Therefore, we developed a 3-step command tool to supplement the ICE evaluation. We present 2 examples of patients who exhibited early neurotoxicity symptoms and led us to develop this tool and 1 in whom it was effective. We propose that CAR T cell patients are consistently followed by a clinical care provider who is familiar with the patient to recognize early changes in personality, behavior, and cognition. Additionally, we propose that the multistep command tool be used in conjunction with the ICE score to detect early symptoms of ICANS. Early intervention has the potential to prevent irreversible neurotoxicity.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":"26 11","pages":"Pages e271-e274"},"PeriodicalIF":4.3,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.07.031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38212624","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}
Pub Date : 2020-11-01DOI: 10.1016/j.bbmt.2020.10.012
{"title":"ASTCT Notes","authors":"","doi":"10.1016/j.bbmt.2020.10.012","DOIUrl":"https://doi.org/10.1016/j.bbmt.2020.10.012","url":null,"abstract":"","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":"26 11","pages":"Pages 2174-2175"},"PeriodicalIF":4.3,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.10.012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"137415573","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}
Pub Date : 2020-11-01DOI: 10.1016/j.bbmt.2020.07.017
Gina Jiang , Jose-Mario Capo-Chichi , Aijun Liu , Eshetu G. Atenafu , Rajat Kumar , Mark D. Minden , Hong Chang
NPM1 mutation status and the allelic ratio (AR) of FLT3-internal tandem duplication (FLT3-ITD) are routinely tested for disease risk stratification in patients with normal karyotype (NK) acute myelogenous leukemia (AML); however, the predictive impact of immunophenotypic markers on different NPM1/FLT3 genotypes remains unclear. We performed a retrospective analysis of 423 patients with NK-AML subclassified into groups based on NPM1/FLT3 genotype. Allogeneic hematopoietic stem cell transplantation (HSCT) was performed in 124 of 423 patients (29%) and was significantly associated with longer event-free survival (EFS) and overall survival (OS), except for patients with the favorable genotype, defined as mutated NPM1 (NPM1mut) combined with normal FLT3 status (FLT3-ITDneg) or FLT3-ITD AR <.5 (FLT3-ITDlow). A subset of AML patients bearing the favorable NPM1mut/FLT3-ITDneg/low genotype share similar outcomes with AML patients who have the intermediate FLT3/NPM1 genotype defined by normal NPM1 (NPM1wt) and FLT3-ITDneg/low. In these individuals, the lack of CD13 expression (CD13neg) was associated with shorter EFS (P = .041) and OS (P = .017). CD13neg was an independent predictor for shorter OS (hazard ratio, 1.985; P = .028).
{"title":"Combination of FLT3-ITD Allelic Ratio, NPM1 Mutation, and Immunophenotypic Markers to Modulate Outcome Prediction in Patients with Normal Karyotype Acute Myelogenous Leukemia Undergoing Hematopoietic Stem Cell Transplantation","authors":"Gina Jiang , Jose-Mario Capo-Chichi , Aijun Liu , Eshetu G. Atenafu , Rajat Kumar , Mark D. Minden , Hong Chang","doi":"10.1016/j.bbmt.2020.07.017","DOIUrl":"10.1016/j.bbmt.2020.07.017","url":null,"abstract":"<div><p><em>NPM1</em> mutation status and the allelic ratio (AR) of <em>FLT3-</em>internal tandem duplication (FLT3-ITD) are routinely tested for disease risk stratification in patients with normal karyotype (NK) acute myelogenous leukemia (AML); however, the predictive impact of immunophenotypic markers on different <em>NPM1/FLT3</em> genotypes remains unclear. We performed a retrospective analysis of 423 patients with NK-AML subclassified into groups based on <em>NPM1/FLT3</em> genotype. Allogeneic hematopoietic stem cell transplantation (HSCT) was performed in 124 of 423 patients (29%) and was significantly associated with longer event-free survival (EFS) and overall survival (OS), except for patients with the favorable genotype, defined as mutated <em>NPM1</em> (<em>NPM1</em><sup>mut</sup>) combined with normal <em>FLT3</em> status (<em>FLT3</em>-ITD<sup>neg</sup>) or <em>FLT3</em>-ITD AR <.5 (<em>FLT3</em>-ITD<sup>low</sup>). A subset of AML patients bearing the favorable <em>NPM1</em><sup>mut</sup>/<em>FLT3</em>-ITD<sup>neg/low</sup> genotype share similar outcomes with AML patients who have the intermediate <em>FLT3/NPM1</em> genotype defined by normal <em>NPM1</em> (<em>NPM1</em><sup>wt</sup>) and <em>FLT3</em>-ITD<sup>neg/low</sup>. In these individuals, the lack of CD13 expression (CD13<sup>neg</sup>) was associated with shorter EFS (<em>P</em> = .041) and OS (<em>P</em> = .017). CD13<sup>neg</sup> was an independent predictor for shorter OS (hazard ratio, 1.985; <em>P</em> = .028).</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":"26 11","pages":"Pages 1995-2000"},"PeriodicalIF":4.3,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.07.017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38195357","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}
Pub Date : 2020-11-01DOI: 10.1016/j.bbmt.2020.07.008
Edward W. Li , Anna Lee , Maryam Vaseghi-Shanjani , Alexander Anagnostopoulos , Gabriele Jagelaviciute , Elena Kum , Tanya Petraszko , Heidi Elmoazzen , David Allan , Warren Fingrut
Whiteboard videos are a popular video format, allowing viewers to see drawings of concepts alongside explanatory text and speech. We hypothesized that whiteboard videos could support the education and recruitment of unrelated stem cell donors in Canada. A series of 5 sharable whiteboard videos about stem cell donation was produced and posted online in September 2018, including 1 full-length video (https://youtu.be/V4fVBtxnWfM) and 4 shorter videos titled “What Is Stem Cell Transplantation?” “How Does the Matching Process Work?” “How Are Stem Cells Donated?” and “How Can I Register as a Stem Cell Donor?” In the videos, metaphorical interpretations of stem cells as factories and genetic markers as barcode labels are employed to communicate complex concepts. The particular need for young, male, and ethnically diverse donors is reflected in the characters portrayed. Surveys demonstrated the videos (1) were used and valued by stakeholders in donor recruitment and (2) significantly improved objective and self-reported knowledge about stem cell donation and reduced donation-related ambivalence among viewers from the most-needed donor demographics. Use of the whiteboard videos was also associated with improved donor recruitment outcomes in Canada. Our work is relevant to donor registries and recruitment organizations worldwide that seek to improve their recruitment efforts.
{"title":"Development and Evaluation of a Whiteboard Video Series to Support the Education and Recruitment of Committed Unrelated Donors for Hematopoietic Stem Cell Transplantation","authors":"Edward W. Li , Anna Lee , Maryam Vaseghi-Shanjani , Alexander Anagnostopoulos , Gabriele Jagelaviciute , Elena Kum , Tanya Petraszko , Heidi Elmoazzen , David Allan , Warren Fingrut","doi":"10.1016/j.bbmt.2020.07.008","DOIUrl":"10.1016/j.bbmt.2020.07.008","url":null,"abstract":"<div><p>Whiteboard videos are a popular video format, allowing viewers to see drawings of concepts alongside explanatory text and speech. We hypothesized that whiteboard videos could support the education and recruitment of unrelated stem cell donors in Canada. A series of 5 sharable whiteboard videos about stem cell donation was produced and posted online in September 2018, including 1 full-length video (<span>https://youtu.be/V4fVBtxnWfM</span><svg><path></path></svg>) and 4 shorter videos titled “What Is Stem Cell Transplantation?” “How Does the Matching Process Work?” “How Are Stem Cells Donated?” and “How Can I Register as a Stem Cell Donor?” In the videos, metaphorical interpretations of stem cells as factories and genetic markers as barcode labels are employed to communicate complex concepts. The particular need for young, male, and ethnically diverse donors is reflected in the characters portrayed. Surveys demonstrated the videos (1) were used and valued by stakeholders in donor recruitment and (2) significantly improved objective and self-reported knowledge about stem cell donation and reduced donation-related ambivalence among viewers from the most-needed donor demographics. Use of the whiteboard videos was also associated with improved donor recruitment outcomes in Canada. Our work is relevant to donor registries and recruitment organizations worldwide that seek to improve their recruitment efforts.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":"26 11","pages":"Pages 2155-2164"},"PeriodicalIF":4.3,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.07.008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38159944","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}