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Sharma, Akshay

https://orcid.org/0000-0003-3281-2081

Mayo Clinic

St. Jude Children's Research Hospital

Citations 15

Impact of Publicly Reported Outcomes on Patient Selection for Hematopoietic Cell Transplantation
Strouse, Christopher , Logan, Brent R. , Estrada‐Merly, Noel, Peterson, Andrew C. , Preussler, Jaime M. , Truong, Tony H. , Khera, Nandita , Wood, William A. , Rangarajan, Hemalatha G. , Akard, Luke P., Sharma, Akshay , Rizzo, J. Douglas , Saber, Wael , Logan, Brent , Estrada-Merly, Noel , Preussler, Jaime M , Truong, Tony H , Khera, Nandita , Wood, William A , Bhatt, Neel S , Sharma, Akshay , Rizzo, J Douglas , Saber, Wael , Strouse, Christopher S , Juckett, Mark , Peterson, Andrew, Troy, Jesse D , Bhatt, Neel S.

JCO Oncology Practice | October 2, 2025 | Volume: 22 | Issue: 5 | Pages: 844-851

10.1200/op-25-00115 Get It

PURPOSE Public reporting of health care outcomes can have unintended effects such as inappropriate risk aversion in patient selection. METHODS The center-specific survival analysis annually assigns all hematopoietic cell transplantation (HCT) centers in the United States a +1, −1, or 0 score for observed outcomes that are above, below, or within a center-specific predicted range of outcome. For each index year (2012-2016), centers receiving a −1 score after 0 scores in the preceding 2 years were compared with contemporaneous centers with as-predicted outcomes (0 score). Changes in the patient population characteristics in the 3 years before versus the 3 years after the index years were compared between the newly below-expected centers (NBCs) and the controls. A multivariate model adjusted for baseline patient population characteristics and center volume. RESULTS No differences in patient selection behavior were identified when comparing the NBCs with the controls across eight key patient population characteristics. For the statistically modeled (predicted) 1-year overall survival (OS), reflecting a holistic measure of centers' patient population risk, we observed no statistically significant difference in change (−0.23% [95% CI, −1.4 to 0.9]; P = .70). The observed OS increased in both NBCs and controls by 0.9% and 4.5%, respectively, without statistically significant difference in change. CONCLUSION Centers receiving a −1 score were not observed to deviate significantly from patient selection trends in the HCT field. These findings suggest that public reporting of HCT outcomes in the United States does not result in unintended bias against HCT for high-risk patients.
Infection after CD19 chimeric antigen receptor T-cell therapy for large B-cell lymphoma: real-world analysis from CIBMTR
Wudhikarn, Kitsada , Chen, Min , Baird, John H. , Gowda, Lohith , Rangarajan, Hemalatha G. , Abid, Muhammad Bilal , Kharfan‐Dabaja, Mohamed A. , Ganguly, Siddhartha , Young, Jo‐Anne H. , Sharma, Akshay , Modi, Dipenkumar , Salem, Baheyeldin , Vergidis, Paschalis , Smith, Melody , Boghdadly, Zeinab El , Dandoy, Christopher E. , Huppler, Anna R. , Chemaly, Roy F. , Hill, Joshua A. , Riches, Marcie , Herr, Megan M. , Martens, Michael J , Baird, John , Rangarajan, Hemalatha G , Abid, Muhammad Bilal , Kharfan-Dabaja, Mohamed A , Young, Jo-Anne H , Sharma, Akshay , Fatobene, Giancarlo , Jain, Tania , Modi, Dipenkumar , Grover, Natalie S , Salem, Baheyeldin , Batista, Marjorie Vieira , Vergidis, Paschalis , Yin, Dwight E , Kelkar, Amar H , Nishihori, Taiga , Holter Chakrabarty, Jennifer , Gergis, Usama , Smith, Melody , Dandoy, Christopher E , Murthy, Hemant S , Huppler, Anna R , Perales, Miguel-Angel , Chemaly, Roy F , Hill, Joshua A , Auletta, Jeffery J , Martens, Michael J. , Williams, Kirsten M. , Jain, Tania , Kanakry, Christopher G. , Grover, Natalie S. , Beitinjaneh, Amer , Nishihori, Taiga , Holter‐Chakrabarty, Jennifer , Murthy, Hemant S. , Perales, Miguel‐Angel , Auletta, Jeffery J.

Blood Advances | May 28, 2025 | Volume: 9 | Issue: 21 | Pages: 5460-5472

10.1182/bloodadvances.2025016141 Get It

Abstract Infection is increasingly recognized as a significant cause of morbidity and mortality in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) receiving CD19 chimeric antigen receptor (CAR) T-cell therapy. The current study analyzed the natural history, risk factors, and outcomes of infection in 3350 patients with R/R LBCL receiving commercial CD19 CAR T-cell therapy (n = 2804 axicabtagene ciloleucel [axi-cel], n = 546 tisagenlecleucel) from December 2017 to June 2022. Infection developed in 834 patients (24.9%) within 100 days after infusion, resulting in an infection density of 0.43 per 100 patient days and a 100-day cumulative incidence of 22%. Bacterial, viral, and fungal infections were recorded in 527 (15.7%), 374 (11.2%), and 108 patients (3.2%), respectively, with corresponding infection densities of 0.23, 0.15, and 0.04 per 100 patient days. After a 24-month median follow-up, 1482 patients (44%) had died, with infection as the primary cause in 173 cases (12%). The 100-day infection-related mortality (IRM) was 1.6% (95% confidence interval, 1.2-2.0). Patients with a Karnofsky performance score of ≤80, infection history before CAR T-cell therapy, axi-cel therapy, severe cytokine release syndrome (grade ≥3), and severe immune effector cell–associated neurotoxicity syndrome (grade ≥3) had increased infection risk. Infections within 100 days were an independent risk factor for inferior overall survival beyond day 100 after CD19 CAR T-cell therapy. In conclusion, study results show a significant incidence of infection and IRM in patients with R/R LBCL treated with CD19 CAR T-cell therapy. Furthermore, results identify patients at a heightened risk of infection, offering insights to guide potential interventions aimed at mitigating infection and improving patient outcomes after CAR T-cell therapy.
Efficacy of Total‐Body Irradiation‐based Intensified Myeloablative Regimens for Acute Leukemia—An International Collaborative Study
Arai, Yasuyuki , Brazauskas, Ruta , He, Naya, Al‐Homsi, A. Samer, Yanada, Masamitsu , Steinberg, Amir , Hong, Sanghee , Bashey, Asad, Frangoul, Haydar , Verdonck, Leo F. , Aljurf, Mahmoud , Dias, Ajoy , Wirk, Baldeep , Freytes, César O. , Zeidan, Amer M., Lehmann, Leslie , Rangarajan, Hemalatha G. , Hashmi, Shahrukh K. , Yano, Shingo , Ozawa, Yukiyasu , Doki, Noriko, Kanda, Yoshinobu , Fukuda, Takahiro , Katayama, Yuta, Tanaka, Junji, Okamoto, Shinichiro , Saber, Wael , Yanada, Masamitsu , Kanda, Junya , Badawy, Sherif M , Sharma, Akshay , Abid, Muhammad Bilal , Wirk, Baldeep , Hashmi, Shahrukh, Kanda, Yoshinobu , Ichinohe, Tatsuo , Teshima, Takanori , Okamoto, Shinichiro , Atsuta, Yoshiko , Arai, Yasuyuki , Brazauskas, Ruta , Chhabra, Saurabh , Battiwalla, Minoo , Díaz, Miguel Ángel , Badawy, Sherif M. , Lazarus, Hillard M. , Yared, Jean A. , Hashem, Hasan , Sharma, Akshay , Abid, Muhammad Bilal , Zeidan, Amer M. , Gergis, Usama , Beitinjaneh, Amer , Askar, Medhat , Pu, Jeffrey J , Wood, William A. , Kako, Shinichi , Doki, Noriko , Katayama, Yuta

eJHaem | May 28, 2025 | Volume: 6 | Issue: 3 | Pages: No page available

10.1002/jha2.70061 Get It

ABSTRACTBackgroundIn this study, we compared outcomes of intensified myeloablative conditioning regimens using large registry data from Japan (Japanese Society for Transplantation and Cellular Therapy) and the United States (Center for International Blood and Marrow Transplant Research).MethodsAdult patients who underwent their first myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) for acute leukemia in remission between 2010 and 2018 using conditioning regimens of cyclophosphamide plus total‐body irradiation (CY/TBI), CY/TBI+cytarabine (AraC), or CY/TBI+etoposide (VP16) were included.ResultsThe acute myeloid leukemia (AML) cohort (N = 480, 38.8%) indicated that overall survival (OS) was poorer in CY/TBI+AraC (hazard ratio [HR] 1.46, p < 0.001) and CY/TBI+VP16 (HR 1.39, p = 0.059) compared to CY/TBI. Relapse was not suppressed, while treatment‐related mortality (TRM) was significantly higher (HR 1.78 and 1.74, p < 0.001 and 0.018, respectively). In the acute lymphoblastic leukemia (ALL) cohort (N = 3901, 61.2%), OS was comparable among these regimens. With intensified regimens, relapse was significantly suppressed in CY/TBI+VP16 (HR 0.74, p = 0.005), while TRM was higher (HR 1.21, p = 0.077). No interactions were observed regarding the country.ConclusionIn AML adding AraC and VP16 to CY/TBI had an adverse effect on OS. Conversely, in ALL, adding VP16 or AraC to CY/TBI did not affect survival, but the addition of VP16 reduced the risk of relapse.Clinical Trial RegistrationThe authors have confirmed clinical trial registration is not needed for this submission.
Trial in Progress: Cureaa - a Clinical Trial of Upfront Haploidentical or Unrelated Donor BMT to Restore Normal Hematopoiesis in Aplastic Anemia, Blood and Marrow Transplant Clinical Trials Network (BMT CTN) #2207
Mangaonkar, Abhishek A. , Fritz, Amber R. , Bellach, Anna , Malmberg, Craig, Henderson, Lori, DiFronzo, Nancy, Geller, Nancy L. , Ritzau, Nicole M., Sanikommu, Srinivasa Reddy , Tsai, Steven , Horowitz, Mary M. , Arai, Sally , Sharma, Akshay , Kassim, Adetola A , Saldaña, Blachy J. Dávila , Ball, Brian J. , Babushok, Daria V. , Pandey, Manu Raj , Martens, Michael J. , Patel, Sagar S. , Devine, Steven M. , Broglie, Larisa , Dezern, Amy Elizabeth

Blood | December 5, 2024 | Volume: 144 | Issue: Supplement 1 | Pages: 2134.1-2134.1

10.1182/blood-2024-207952 Get It

Background: Immunosuppressive therapy (IST) is considered the standard front-line treatment for acquired severe aplastic anemia (SAA) for pts &gt;40 years. For pts aged &lt;40 years who have a suitable human leukocyte antigen (HLA)-matched sibling donor (MSD), hematopoietic stem cell transplantation (HSCT) is recommended. This recommendation is based on the toxicity associated with alternative donors; haploidentical (HAPLO) and unrelated donor (URD) HSCT for patients who lack a MSD. However, the hematopoietic response after IST is ~ 70-80%, even after augmentation with eltrombopag in the front-line setting, and failure-free survival (FFS, defined as patients alive and in remission without clonal disease more than 10 years after IST) remains &lt; 40%. HSCT is often employed as a second line salvage therapy for those who do not respond to IST or have disease recurrence. However, outcomes after HSCT are often compromised because of IST-related complications such as clonal evolution, development of donor specific antibodies, infectious adverse events and organ dysfunction. In contrast, a successful allogeneic HSCT leads to relatively prompt hematopoietic and immune reconstitution and mitigates the risk of secondary clonal disease. Innovations in recent decades, such as improved graft versus host disease (GVHD) prophylaxis and supportive care, have steadily reduced the morbidity and mortality of adults undergoing HSCT from unrelated or mismatched donors and expanded the donor pool such that almost all pts with SAA have a potential donor available. The use of post-transplant cyclophosphamide (PTCy) is now a well-established approach to facilitate engraftment and mitigate the risk of GVHD. It was successfully used in relapsed/refractory SAA pts using HAPLO donors in the multi-center BMT CTN #1502 trial (NCT02918292). Similar PTCy based approaches have been effective in the upfront setting with HAPLO and URD in small single center studies. Opened in July 2024, the CureAA trial (NCT06517641), seeks to increase donor options for SAA pts who have not yet received IST by using PTCy based GVHD prophylaxis for HSCT using HAPLO or URD. Study Design and Methods: This BMT CTN study (#2207) is a prospective multi-center phase II trial to assess efficacy of HSCT using HAPLO or URD bone marrow with a reduced intensity, thymoglobulin (ATG)-containing preparative regimen and PTCy GVHD prophylaxis in previously untreated SAA pts. This trial has two parallel cohorts for each donor type, HAPLO and URD, with an accrual goal of 30 participants in each cohort. All will receive ATG (0.5mg/kg on day -9 and 2mg/kg on days -8 and -7), cyclophosphamide (14.5mg/kg on days -6 and -5), fludarabine (30mg/m2 on days -6 to -2), 400 cGy total body irradiation (day -1 in a single fraction), a marrow graft (goal &gt;2.5 x 108 nucleated cells per kg of recipient) on day 0 and PTCy (50mg/kg on days +3 and +4). Additionally, participants receive tacrolimus (until day +180) and mycophenolate mofetil days +5-35. The primary objective of the trial is to estimate the GVHD-free failure-free survival (GFFS) rate at 1 year after initiation of conditioning. GFFS is a composite endpoint of survival without grade III-IV acute GVHD, chronic GVHD requiring immunosuppression, or primary or secondary graft failure requiring second definitive therapy within 1 year after initiation of conditioning. Secondary objectives will evaluate patient survival, engraftment, transfusion dependence, cumulative incidence of GVHD and hematologic response. Health related quality of life, healthcare utilization and financial toxicity data will also be collected. These endpoints will allow clinical comparison with current results achieved with upfront IST in other studies. We hypothesize that this HSCT approach will improve survival without significant transplant-associated morbidity by using a low toxicity regimen that reduces rates of GVHD and provides rapid hematologic recovery without graft failure, thereby making HAPLO and URD HSCT a viable option for initial upfront treatment of SAA. The ability to use mismatched donors will also ensure that a HSCT option is more widely available to all racial/ethnic groups. This collaborative study was funded by grants U10HL069294, U24HL138660 to the BMT CTN from the NHLBI/ NCI, along with funding from Sanofi. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Trends in volumes and survival after hematopoietic cell transplantation in racial/ethnic minorities
Khera, Nandita , Brazauskas, Ruta , Patel, Jinalben , Üstün, Celalettin , Ballen, Karen K. , Abid, Muhammad Bilal , Díaz, Miguel Ángel , Al‐Homsi, A. Samer, Hong, Sanghee , Munker, Reinhold , Schears, Raquel M. , Ciurea, Stefan O. , Wirk, Baldeep , LeMaistre, Charles F. , Aljurf, Mahmoud , Sharma, Akshay , Černý, Jan , Kindwall‐Keller, Tamila L. , Winestone, Lena E. , Steinberg, Amir , Arnold, Staci D. , Seo, Sachiko , Preussler, Jaime M. , Hossain, Nasheed , Hashmi, Shahrukh K. , Lehmann, Leslie , Wood, William A. , Rangarajan, Hemalatha G. , Saber, Wael , Hahn, Theresa , Patel, Jinalben , Ustun, Celalettin , Abid, Muhammad Bilal , Diaz Perez, Miguel Angel , Hashem, Hasan , Ciurea, Stefan O , Badawy, Sherif M , Savani, Bipin N , LeMaistre, C Fred , Bhatt, Neel S , Sharma, Akshay , Cerny, Jan , Knight, Jennifer M , Kelkar, Amar H , Winestone, Lena E , Arnold, Staci D , Seo, Sachiko , Preussler, Jaime M , Hossain, Nasheed M , Fingrut, Warren B , Hashmi, Shahrukh K , Rangarajan, Hemalatha G , Wood, William A , Ailawadhi, Sikander , Jacobs, Benjamin, Hashem, Hasan , Lazarus, Hillard M. , Badawy, Sherif M. , Savani, Bipin N. , Bhatt, Neel S. , Beitinjaneh, Amer , Knight, Jennifer M. , Yared, Jean A. , Fingrut, Warren , Agrawal, Vaibhav

Blood Advances | April 25, 2024 | Volume: 8 | Issue: 13 | Pages: 3497-3506

10.1182/bloodadvances.2023012469 Get It

Abstract There has been an increase in volume as well as an improvement in overall survival (OS) after hematopoietic cell transplantation (HCT) for hematologic disorders. It is unknown if these changes have affected racial/ethnic minorities equally. In this observational study from the Center for International Blood and Marrow Transplant Research of 79 904 autologous (auto) and 65 662 allogeneic (allo) HCTs, we examined the volume and rates of change of autoHCT and alloHCT over time and trends in OS in 4 racial/ethnic groups: non-Hispanic Whites (NHWs), non-Hispanic African Americans (NHAAs), and Hispanics across 5 2-year cohorts from 2009 to 2018. Rates of change were compared using Poisson model. Adjusted and unadjusted Cox proportional hazards models examined trends in mortality in the 4 racial/ethnic groups over 5 study time periods. The rates of increase in volume were significantly higher for Hispanics and NHAAs vs NHW for both autoHCT and alloHCT. Adjusted overall mortality after autoHCT was comparable across all racial/ethnic groups. NHAA adults (hazard ratio [HR] 1.13; 95% confidence interval [CI] 1.04-1.22; P = .004) and pediatric patients (HR 1.62; 95% CI 1.3-2.03; P &lt; .001) had a higher risk of mortality after alloHCT than NHWs. Improvement in OS over time was seen in all 4 groups after both autoHCT and alloHCT. Our study shows the rate of change for the use of autoHCT and alloHCT is higher in NHAAs and Hispanics than in NHWs. Survival after autoHCT and alloHCT improved over time; however, NHAAs have worse OS after alloHCT, which has persisted. Continued efforts are needed to mitigate disparities for patients requiring alloHCT.
Impact of Publicly Reported Center Specific Analysis on Patient Selection Practices for Hematopoietic Stem Cell Transplantation
Strouse, Christopher , Logan, Brent R. , Estrada‐Merly, Noel, Preussler, Jaime M. , Truong, Tony H. , Khera, Nandita , Rangarajan, Hemalatha G. , Akard, Luke P., Saber, Wael , Strouse, Christopher S , Juckett, Mark , Troy, Jesse D , Wood, William A. , Bhatt, Neel S. , Sharma, Akshay

Blood | December 1, 2023 | Volume: 142 | Issue: Supplement 1 | Pages: 373-373

10.1182/blood-2023-182013 Get It

Introduction Public reporting of outcomes drives healthcare improvement in many fields, including hematopoietic cell transplantation (HCT), although with possible unintended consequences. The Center for International Blood & Marrow Transplant Research (CIBMTR) publishes an annual Center-Specific Survival Analysis (CSA), which compares HCT centers' observed 1-year overall survival (OS) with their statistically modeled expected 1-year OS, with 95% confidence intervals (CI). Centers with OS within their 95% CI receive a 0 score, indicating as expected outcomes. Those with OS below / above their 95% CI receive a -1 / +1 score, indicating below / above expected OS, respectively. After a -1 report, centers may change their patient selection criteria, causing unintentional systematic exclusion of patient populations who could benefit from HCT. We analyzed how the CSA report influences patient selection practices among centers receiving a -1 score. Methods Centers receiving a -1 report between 2012 and 2016 that had ‘as expected’ survival in the preceding 2 years were classified as newly below expected OS centers (NBCs). The year of their -1 report was used as the index year. Centers with ‘as expected’ OS in the 3 years before and after each index year were identified as control centers, reflecting expected evolution of patient selection in the HCT field. The patient population variables analyzed are shown in Table 1. The difference in patient population characteristics in the 3 years before vs the 3 years after the index years defined the change in patient selection behavior at the NBCs and the controls. A multivariate model adjusting for baseline patient population characteristics and center size was used to compare the change in patient population from before and after the index year in the NBCs and that of the controls. The difference in differences (ΔinΔ) were calculated as ΔNBC - ΔControl. A significance threshold of p&lt;0.01 was used to account for multiple testing. Results After adjusting for overall trends, center size, and baseline patient population characteristics, no differences in patient selection behavior meeting the pre-specified threshold for statistical significance were identified when comparing the NBCs (n=24 centers) with the controls (n=195 centers). In the 3 years following the index years, 4,150 and 25,013 patients were transplanted at NBCs and controls, respectively. The proportion of patients receiving reduced intensity or non-myeloablative conditioning regimens decreased 4.1% in NBCs and increased 5.0% in controls, for a net difference of -9.1% (95% CI: -16.7% to -1.6%, p=0.02). All other patient characteristic proportions changed in the same direction at NBCs and controls, albeit to varying degrees (Table 1). In some high-risk characteristics, (e.g. HCT-CI &gt; 3), a greater increase was seen at NBCs vs controls (ΔinΔ 2.1% 95% CI: -2.8% to 6.9%, p=0.40). In others, (e.g. age 60+ years), a greater increase was seen at controls vs NBCs (ΔinΔ -2.6% 95% CI: -5.9% to 0.7%, p=0.12). To capture a holistic measure of centers' patient population risk, the predicted 1-year survival was compared in the NBCs vs controls using the logistic regression model generated for each year's CSA. The predicted OS increased by 3.08% and 3.30% in the NBCs and controls respectively, with no statistically significant difference (-0.23%, 95% CI: -1.4% to 0.9%, p=0.70, Figure 1). The observed overall survival (adjusted for predicted 1 year OS) also increased in both BECs and controls by 0.9% and 4.5% respectively, without statistically significant difference (-3.6%, 95% CI: -6.7% to -0.7%, p=0.02). Discussion For centers receiving a -1 report, no statistically significant changes were seen in patient population characteristics in the following 3 years when compared to centers with OS was as expected. There was variability in the changes in high-risk patient characteristics at the NBCs relative to the controls, and in some cases more patients with high-risk characteristics were selected at these centers compared to those at controls. The change in predicted overall survival at 1 year, a summary indicator of survival risk, was similar between BECs and control centers. Although the number of patients in centers with below expected OS was small, these findings suggest the public reporting of outcomes in HCT in the US does not unintentionally affect access to HCT for high-risk patients at NBCs.
Allogeneic hematopoietic cell transplantation for blastic plasmacytoid dendritic cell neoplasm: a CIBMTR analysis
Murthy, Hemant S. , Zhang, Mei‐Jie , Chen, Karen , Ahmed, Sairah , Ganguly, Siddhartha , Kansagra, Ankit , Michelis, Fotios V. , Nishihori, Taiga , Patnaik, Mrinal M. , Aljurf, Mahmoud , Arai, Yasuyuki , Badar, Talha , Ballen, Karen K. , Bejanyan, Nelli , Brown, Valerie I. , Martino, Rodrigo , Cahn, Jean‐Yves , Castillo, Paul , Černý, Jan , Copelan, Edward A. , Daly, Andrew , Freytes, César O. , Hashmi, Shahrukh K. , Hildebrandt, Gerhard , Jamy, Omer , Joseph, Jacinth , Kanakry, Christopher G. , Khera, Nandita , Krem, Maxwell M. , Kuwatsuka, Yachiyo , Lekakis, Lazaros J. , Liu, Hongtao , Modi, Dipenkumar , Munshi, Pashna N. , Palmisiano, Neil , Rizzieri, David A. , Seo, Sachiko , Sharma, Akshay , Sohl, Melhm, Solomon, Scott R. , Ulrickson, Matthew L. , Üstün, Celalettin , Poel, Marjolein van der , Verdonck, Leo F. , Wagner, John L. , Wang, Trent , Wirk, Baldeep , Zeidan, Amer M. , Litzow, Mark R. , Weisdorf, Daniel J. , Saber, Wael , Kharfan‐Dabaja, Mohamed A. , Kansagra, Ankit , Michelis, Fotios V , Nishihori, Taiga , Patnaik, Mrinal , Arai, Yasuyuki , Badar, Talha , Bejanyan, Nelli , Bhatt, Vijaya Raj , Chhabra, Saurabh , Dholaria, Bhagirathbhai R , Diaz Perez, Miguel Angel , Freytes, Cesar O , Hashmi, Shahrukh K , Jamy, Omer , Krem, Maxwell M , Lazarus, Hillard M , Liu, Hongtao , Modi, Dipenkumar , Mussetti, Alberto , Patel, Sagar , Shah, Mithun V , Sharma, Akshay , Ustun, Celalettin , Wagner, John , Litzow, Mark R. , Hourigan, Christopher S , Weisdorf, Dan , Kharfan-Dabaja, Mohamed A , Murthy, Hemant S , Martino, Rodrigo , Ahmed, Sairah , Zeidan, Amer M , Deotare, Uday , Abid, Muhammad Bilal , Bacher, Ulrike , Badawy, Sherif M. , Battiwalla, Minoo , Beitinjaneh, Amer , Bhatt, Vijaya Raj , Chhabra, Saurabh , Dholaria, Bhagirathbhai , Díaz, Miguel Ángel , Grunwald, Michael R. , Lazarus, Hillard M. , Mussetti, Alberto , Patel, Sagar S. , Shah, Meera , Kebriaei, Partow , Hourigan, Christopher S.

Blood Advances | October 4, 2023 | Volume: 7 | Issue: 22 | Pages: 7007-7016

10.1182/bloodadvances.2023011308 Get It

Abstract Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with a poor prognosis and considered incurable with conventional chemotherapy. Small observational studies reported allogeneic hematopoietic cell transplantation (allo-HCT) offers durable remissions in patients with BPDCN. We report an analysis of patients with BPDCN who received an allo-HCT, using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). We identified 164 patients with BPDCN from 78 centers who underwent allo-HCT between 2007 and 2018. The 5-year overall survival (OS), disease-free survival (DFS), relapse, and nonrelapse mortality (NRM) rates were 51.2% (95% confidence interval [CI], 42.5-59.8), 44.4% (95% CI, 36.2-52.8), 32.2% (95% CI, 24.7-40.3), and 23.3% (95% CI, 16.9-30.4), respectively. Disease relapse was the most common cause of death. On multivariate analyses, age of ≥60 years was predictive for inferior OS (hazard ratio [HR], 2.16; 95% CI, 1.35-3.46; P = .001), and higher NRM (HR, 2.19; 95% CI, 1.13-4.22; P = .02). Remission status at time of allo-HCT (CR2/primary induction failure/relapse vs CR1) was predictive of inferior OS (HR, 1.87; 95% CI, 1.14-3.06; P = .01) and DFS (HR, 1.75; 95% CI, 1.11-2.76; P = .02). Use of myeloablative conditioning with total body irradiation (MAC-TBI) was predictive of improved DFS and reduced relapse risk. Allo-HCT is effective in providing durable remissions and long-term survival in BPDCN. Younger age and allo-HCT in CR1 predicted for improved survival, whereas MAC-TBI predicted for less relapse and improved DFS. Novel strategies incorporating allo-HCT are needed to further improve outcomes.
Association of ABO mismatch with the outcomes of allogeneic hematopoietic cell transplantation for acute leukemia
Murthy, Guru Subramanian Guru , Logan, Brent R. , Bo‐Subait, Stephanie, Beitinjaneh, Amer , Devine, Steven M. , Farhadfar, Nosha , Gowda, Lohith , Hashmi, Shahrukh K. , Nathan, Sunita , Sharma, Akshay , Stefanski, Heather E. , Hsu, Jack W., Panch, Sandhya R. , Shaw, Bronwen E. , Murthy, Guru , Devine, Steven , Hashmi, Shahrukh, Sharma, Akshay , Lazarus, Hillard M. , Yared, Jean A. , Pulsipher, Michael A. , Switzer, Galen E.

American Journal of Hematology | January 6, 2023 | Volume: 98 | Issue: 4 | Pages: 608-619

10.1002/ajh.26834 Get It

Abstract Allogeneic hematopoietic cell transplantation (allo‐HCT) is a potentially curative treatment for acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). While many factors influence the outcomes of allo‐HCT, the independent impact of donor–recipient ABO mismatching remains unclear. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we identified patients aged ≥18 years with AML or ALL who underwent allo‐HCT between 2008 and 2018. Our objectives were to analyze the outcomes of allo‐HCT based on the donor–recipient ABO status (match, minor mismatch, major mismatch, bidirectional mismatch). Among 4946 eligible patients, 2741 patients (55.4%) were ABO matched, 1030 patients (20.8%) had a minor ABO mismatch, 899 patients (18.1%) had a major ABO mismatch, and 276 patients (5.6%) had a bidirectional ABO mismatch. In multivariable analyses, compared to ABO matched allo‐HCT, the presence of a major ABO mismatch was associated with worse overall survival (HR 1.16, 95% CI 1.05–1.29; p = 0.005), inferior platelet engraftment (HR 0.83, 95% CI 0.77–0.90; p < 0.001), and higher primary graft failure (HR 1.60, 95% CI 1.12–2.30, p = 0.01). Relapse, acute graft versus host disease (GVHD) grades III‐IV and chronic GVHD were not significantly associated with ABO status. While donor age was not significantly associated with outcomes, older recipient age was associated with worse survival and non‐relapse mortality. Our study demonstrates that donor–recipient ABO status is independently associated with survival and other post‐transplantation outcomes in acute leukemia. This underscores the importance of considering the ABO status in donor selection algorithms and its impact in acute leukemia.
Impact of Allogeneic Hematopoietic Cell Transplantation (HCT) As Consolidation Following CD19 Chimeric Antigen Receptor (CAR) T Cell Therapy for Treatment of Relapsed Acute Lymphoblastic Leukemia (ALL)
Park, Jae H. , Nikiforow, Sarah , Hu, Zhen‐Huan , Bredeson, Christopher , Brown, Valerie I. , Cairo, Mitchell S. , Dholaria, Bhagirathbhai , Ganguly, Siddhartha , Hanna, Rabi , Kohorst, Mira A. , Lekakis, Lazaros J. , Rizzieri, David A. , Savani, Bipin B., Thakar, Monica S. , Wagner, John L. , Qiu, Xianmiao, Pasquini, Marcelo C. , Dholaria, Bhagirathbhai R , Kim, Soyoung , Moskop, Amy , Ahmed, Sairah , Abid, Muhammad Bilal , Badar, Talha , Díaz, Miguel Ángel , Grover, Natalie S. , Hematti, Peiman , Lazarus, Hillard M. , Locke, Frederick L. , Murthy, Hemant S. , Mussetti, Alberto , Pulsipher, Michael A. , Qayed, Muna , Reshef, Ran , Salas, María Queralt , Sharma, Akshay , Schultz, Kirk R. , Turtle, Cameron J. , Yared, Jean A. , Perales, Miguel‐Angel

Blood | November 23, 2021 | Volume: 138 | Issue: Supplement 1 | Pages: 3880-3880

10.1182/blood-2021-148652 Get It

Abstract Background: CD19 CAR T cell therapies have demonstrated high initial complete remission (CR) rates of 70-80% in relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) with durable remissions observed in a subset of patients. Despite the remarkable initial CR rate, relapses occur in 20-45% of patients and with increasing use of CD19 CAR T cell therapies in ALL, a key remaining clinical question is the role of post-CAR HCT. Methods: Patients up to 26 years treated with the commercial (i.e., tisagenlecleucel) or investigational CD19 CAR T cell products from 2014 to 2019 in the United States were included. The objectives were to examine the impact of post-CAR HCT on mortality, disease-free survival (DFS), leukemia relapse, GVHD and transplant related mortality among HCT recipients. The intent of HCT was analyzed as consolidation when there was no evidence of post-CAR T cell relapse prior to HCT. Cox regression multivariable analysis used HCT as time-dependent variable along with age, performance status and time from diagnosis to CAR-T cell infusion to evaluate its impact on outcomes. Results: We identified 347 patients who received CD19 CAR T cells from 86 centers. Median age was 13 (range, 0.4-26 years) with 39% of patients from Hispanic or Latino ethnic origin. Patients were high risk and heavily pretreated; 56% had poor cytogenetics, 51% had ≥3 line of prior therapies and 34% had prior HCT. Most of the patients (74%) received tisagenlecleucel. Disease burden at the time of CAR T cell infusion included morphologic disease (≥5% bone marrow blasts) (65%), measurable residual disease (MRD) positive (16%) and negative CR (18%). CRS of all grades was observed in 57.6% and grade 3-4 CRS in 13%; neurotoxicity of all grades was observed in 25% and grade 3-4 in 8%. With a median follow-up of 12.7 months (range, 2.2-60.3), DFS at 3, 6 and 12 months following CAR T cell infusion was 80.9% % (95% CI: 76.6%-84.9%), 71.2% (95% CI: 66.1%-76.0%) and 57.6% (95% CI: 51.8%-63.3%), respectively. OS at 3, 6 and 12 months was 93.6% (95% CI: 90.8%-96.0%), 89.8% (95% CI: 86.4%-92.8%) and 79.4% (95% CI: 74.7%-83.6%), respectively. Incidences of relapse without censoring at subsequent HCT at month 3, 6 and 12 were 18.5% (95% CI: 14.5%-22.8%), 28.2% (95% CI: 23.5%-33.3%), and 40.6% (95% CI: 35.0%-46.3%), respectively. Of the 347 patients who received CD19 CAR therapy, 62 patients (18%) had subsequent HCT in CR as a consolidation post-CAR with a median time from CAR T to HCT of 4.7 months (range, 1.1-18.6). 36% had a prior HCT (i.e., pre-CAR), 87% received myeloablative regimen and among the 57 patients with MRD evaluation 56 were negative (98%). Frequencies of post-CAR HCT did not change during the 5-year study period. Overall, transplant related mortality (TRM) at month 6 was 8.9% (95% CI: 3.6-16.1), and grade 2-4 acute GvHD was observed in 38.0% (95% CI: 28.4-48.2) of patients at month 6. Post-CAR HCT used as a consolidation was associated with lower relapse (hazard ratio (HR) 0.37; p=0.037) but no significant impact on mortality (HR 0.75, p=0.51) or DFS (HR=0.46, p=0.057). When accounting for any HCT performed after CAR T cell, HCT was associated with higher mortality (Figure). Conclusions: This is the largest clinical series to date examining the impact of post-CAR HCT on clinical outcome of R/R B-ALL patients. We found that 18% of the patients had post-CAR HCT as a consolidation therapy with a favorable safety profile of 8.9% TRM rate despite a prior transplant rate of 36%. Consolidation HCT after CAR T cell resulted in significant reduction in leukemia relapse with a trend towards better DFS. Consolidation HCT seem safe and incurred a benefit by reducing disease relapse. Further studies in understanding the role of consolidation HCT as planned, or post-CAR T cell response-based strategy or treatment for early B-cell recovery are needed to further define the best candidates for HCT after tisagenlecleucel . Figure 1 Figure 1. Disclosures Park: BMS: Consultancy; Affyimmune: Consultancy; Kite Pharma: Consultancy; Curocel: Consultancy; Novartis: Consultancy; Minerva: Consultancy; Innate Pharma: Consultancy; PrecisionBio: Consultancy; Intellia: Consultancy; Amgen: Consultancy; Autolus: Consultancy; Servier: Consultancy; Artiva: Consultancy; Kura Oncology: Consultancy. Nikiforow: Kite/Gilead: Other: ad HOC Advisory Boards; Novartis: Other: ad Hoc Advisory Boards; Iovance: Other: ad Hoc Advisory Boards; Glaxo Smith Kline (GSK): Other: ad Hoc Advisory Boards. Hu: Kite/Gilead: Research Funding; Novartis: Research Funding; Celgene: Research Funding. Ahmed: Merck: Research Funding; Tessa Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Seagen: Research Funding; Xencor: Research Funding. Badar: Pfizer Hematology-Oncology: Membership on an entity's Board of Directors or advisory committees. Cairo: Servier: Speakers Bureau; Sanofi: Speakers Bureau; Amgen: Speakers Bureau; Jazz Pharmaceutical: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sobi: Speakers Bureau; Omeros: Membership on an entity's Board of Directors or advisory committees; Nektar: Membership on an entity's Board of Directors or advisory committees. Dholaria: Janssen: Research Funding; Takeda: Research Funding; Jazz: Speakers Bureau; MEI: Research Funding; Pfizer: Research Funding; Angiocrine: Research Funding; Poseida: Research Funding; Celgene: Speakers Bureau. Grover: Kite: Other: Advisory Board; Genentech: Research Funding; ADC: Other: Advisory Board; Tessa: Consultancy; Novartis: Consultancy. Locke: Gerson Lehrman Group: Consultancy; Emerging Therapy Solutions: Consultancy; Moffitt Cancer Center: Patents & Royalties: field of cellular immunotherapy; Calibr: Consultancy, Other: Scientific Advisory Role; BMS/Celgene: Consultancy, Other: Scientific Advisory Role; Wugen: Consultancy, Other; Legend Biotech: Consultancy, Other; Janssen: Consultancy, Other: Scientific Advisory Role; Iovance Biotherapeutics: Consultancy, Other: Scientific Advisory Role; Novartis: Consultancy, Other, Research Funding; GammaDelta Therapeutics: Consultancy, Other: Scientific Advisory Role; Takeda: Consultancy, Other; EcoR1: Consultancy; Cowen: Consultancy; Umoja: Consultancy, Other; Kite, a Gilead Company: Consultancy, Other: Scientific Advisory Role, Research Funding; Cellular Biomedicine Group: Consultancy, Other: Scientific Advisory Role; Bluebird Bio: Consultancy, Other: Scientific Advisory Role; Amgen: Consultancy, Other: Scientific Advisory Role; Allogene Therapeutics: Consultancy, Other: Scientific Advisory Role, Research Funding. Murthy: CRISPR Therapeutics: Research Funding. Mussetti: GILEAD: Other: Clinical trials participation, Research Funding; TAKEDA: Honoraria; NOVARTIS: Honoraria, Other: Clinical trials participation. Pulsipher: Jasper Therapeutics: Honoraria; Adaptive: Research Funding; Equillium: Membership on an entity's Board of Directors or advisory committees. Qayed: Novartis: Membership on an entity's Board of Directors or advisory committees; Medexus: Membership on an entity's Board of Directors or advisory committees; Mesoblast: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; BMS: Other. Reshef: Gilead, BMS, Precision, Immatics, Atara, Takeda, Shire, Pharmacyclics, Incyte: Research Funding; Gilead and Novartis: Honoraria; Bayer, BMS, Regeneron, TScan, Synthekine, Atara, Jasper: Consultancy. Rizzieri: Kite: Honoraria, Speakers Bureau; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Stemline: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Acrotech: Membership on an entity's Board of Directors or advisory committees; Teva: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; AROG: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees; Celltrion: Membership on an entity's Board of Directors or advisory committees; Mustang: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Honoraria; Pharmacyclics: Honoraria. Sharma: Vertex Pharmaceuticals/CRISPR Therapeutics: Other: Salary support paid to institution; Medexus Inc: Consultancy; CRISPR Therapeutics: Other, Research Funding; Vindico Medical Education: Honoraria; Spotlight Therapeutics: Consultancy; Novartis: Other: Salary support paid to institution. Schultz: BMS DSMB: Other: payment; Sobi: Membership on an entity's Board of Directors or advisory committees. Turtle: Century Therapeutics Ad hoc advisory boards (last 12 months): Nektar Therapeutics, Allogene, PACT Pharma, Astra Zeneca, Amgen: Membership on an entity's Board of Directors or advisory committees; Precision Biosciences: Membership on an entity's Board of Directors or advisory committees; Eureka Therapeutics: Membership on an entity's Board of Directors or advisory committees; Caribou Biosciences: Membership on an entity's Board of Directors or advisory committees; T-CURX: Membership on an entity's Board of Directors or advisory committees; Myeloid Therapeutics: Membership on an entity's Board of Directors or advisory committees; ArsenalBio: Membership on an entity's Board of Directors or advisory committees; Minerva: Other; Nektar Therapeutics: Other; Juno Therapeutics/BMS: Other: Payments, Patents & Royalties: Patent licensed to Juno Therapeutics.; Precision Biosciences, Eureka Therapeutics, Caribou Biosciences, Myeloid Therapeutics, ArsenalBio: Current holder of stock options in a privately-held company. Pasquini: Kite Pharma: Research Funding; Novartis: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; GlaxoSmithKline: Research Funding. Perales: MorphoSys: Honoraria; Cidara: Honoraria; Bristol-Myers Squibb: Honoraria; Miltenyi Biotec: Honoraria, Other; Sellas Life Sciences: Honoraria; Takeda: Honoraria; Karyopharm: Honoraria; Celgene: Honoraria; Omeros: Honoraria; Nektar Therapeutics: Honoraria, Other; Equilium: Honoraria; Novartis: Honoraria, Other; NexImmune: Honoraria; Incyte: Honoraria, Other; Kite/Gilead: Honoraria, Other; Merck: Honoraria; Servier: Honoraria; Medigene: Honoraria.