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Díaz, Miguel Ángel

https://orcid.org/0000-0001-5286-1329

Mayo Clinic

Hospital Infantil Universitario Niño Jesús

Citations 18

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.
Delayed T-cell recovery after hematopoietic cell transplantation is associated with decreased overall survival in adults
Perales, Miguel‐Angel , Riches, Marcie , He, Naya, Chemaly, Roy F. , Dandoy, Christopher E. , Hill, Joshua A. , Díaz, Miguel Ángel , Hashmi, Shahrukh K. , Prockop, Susan E. , Hildebrandt, Gerhard , Szabolcs, Paul , Hill, Joshua A. , Martens, Michael J , Chemaly, Roy F , Dandoy, Christopher E , Hill, Joshua A , Diaz Perez, Miguel Angel , Hashmi, Shahrukh K , Prockop, Susan E , Lazarus, Hillard M , Auletta, Jeffery J , Szabolcs, Paul , Perales, Miguel-Angel , Hill, Joshua A , Martens, Michael J. , Lazarus, Hillard M. , Beitinjaneh, Amer , Auletta, Jeffery J.

Blood Advances | April 18, 2025 | Volume: 9 | Issue: 14 | Pages: 3502-3517

10.1182/bloodadvances.2024015288 Get It

Abstract Allogeneic hematopoietic cell transplantation (allo-HCT) can provide curative treatment for hematologic malignancies but is associated with prolonged lymphopenia that may contribute to an increased risk of infection and relapse, resulting in decreased survival. We hypothesized that patients with rapid and robust CD4 T- and B-cell recovery have improved survival and decreased treatment-related mortality (TRM). A total of 2089 patients were included who underwent first allo-HCT for acute myeloid leukemia/acute lymphoblastic leukemia/myelodysplastic syndrome from 2008 to 2019 reported to the Center for International Blood and Marrow Transplant Research with available CD4 counts at days 100 and 180. Patients (median age, 51 years [range, 2-75]) were categorized into 4 groups based on graft-versus-host disease (GVHD) prophylaxis: ex vivo T-cell depletion (TCD/CD34), posttransplant cyclophosphamide, calcineurin inhibitor alone (CNI), or CNI with antithymocyte globulin. Based upon survival, we could identify optimal cutoff points for CD4+ T cells in pediatric (age of &lt;20 years) patients: 248 × 106/L and 420 × 106/L at days 100 and 180, respectively; and in adult (age of &gt;20 years) patients: 104 × 106/L and 115 × 106/L at days 100 and 180, respectively. In adults, day-100 CD4 count was associated with overall survival (OS), progression-free survival (PFS), and TRM but not relapse, incidence of infections, or chronic GVHD. Similarly, CD4 counts above the cutoff point at day 180 in adults were associated with improved OS, PFS, and TRM but no other outcomes. No clinical associations for CD4 counts were identifiable in pediatric patients. These findings underscore the importance of tailoring transplant strategies for adults to optimize immune recovery and improve patient outcomes.
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.
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.
A simple prognostic system in patients with myelofibrosis undergoing allogeneic stem cell transplantation: a CIBMTR/EBMT analysis
Tamari, Roni , McLornan, Donal P. , Ahn, Kwang Woo , Estrada‐Merly, Noel, Hernández‐Boluda, Juan Carlos , Giralt, Sergio , Palmer, Jeanne , DeFilipp, Zachariah , Marks, David I. , Poel, Marjolein van der , Verdonck, Leo F. , Gupta, Vikas , Ali, Haris , Litzow, Mark R. , Bashey, Asad, Hashmi, Shahrukh K. , Bredeson, Christopher , Rizzieri, David A. , Abid, Muhammad Bilal , Ganguly, Siddhartha , Wirk, Baldeep , Aljurf, Mahmoud , Kindwall‐Keller, Tamila L. , Kharfan‐Dabaja, Mohamed A. , Hildebrandt, Gerhard , Pawarode, Attaphol , Solh, Melhem , Nathan, Sunita , Seo, Sachiko , Scott, Bart L. , Nakamura, Ryotaro , Yakoub‐Agha, Ibrahim , Saber, Wael , DeFilipp, Zachariah , Gupta, Vikas , Ali, Haris , Litzow, Mark R. , Hashmi, Shahrukh K , Pu, Jeffrey J , Bacher, Ulrike , Jain, Tania , Cutler, Corey S. , Kharfan-Dabaja, Mohamed A , Yared, Jean A , Nishihori, Taiga , Seo, Sachiko , Scott, Bart , Nakamura, Ryotaro , Czerw, Tomasz , Yakoub-Agha, Ibrahim , Hernández-Boluda, Juan Carlos , McLornan, Donal , Abid, Muhammad Bilal , Giralt, Sergio , Gale, Robert Peter , Battiwalla, Minoo , Díaz, Miguel Ángel , Lazarus, Hillard M. , Gergis, Usama , Liesveld, Jane L. , Beitinjaneh, Amer , Savani, Bipin N. , Agrawal, Vaibhav , Jain, Tania , Yared, Jean A. , Grunwald, Michael R. , Nishihori, Taiga , Oran, Betül

Blood Advances | May 3, 2023 | Volume: 7 | Issue: 15 | Pages: 3993-4002

10.1182/bloodadvances.2023009886 Get It

AbstractTo develop a prognostic model for patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) for myelofibrosis (MF), we examined the data of 623 patients undergoing allo-HCT between 2000 and 2016 in the United States (the Center for International Blood and Marrow Transplant Research [CIBMTR] cohort). A Cox multivariable model was used to identify factors prognostic of mortality. A weighted score using these factors was assigned to patients who received transplantation in Europe (the European Bone Marrow Transplant [EBMT] cohort; n = 623). Patient age &gt;50 years (hazard ratio [HR], 1.39; 95% confidence interval [CI], 0.98-1.96), and HLA-matched unrelated donor (HR, 1.29; 95% CI, 0.98-1.7) were associated with an increased hazard of death and were assigned 1 point. Hemoglobin levels &lt;100 g/L at time of transplantation (HR, 1.63; 95% CI, 1.2-2.19) and a mismatched unrelated donor (HR, 1.78; 95% CI, 1.25-2.52) were assigned 2 points. The 3-year overall survival (OS) in patients with a low (1-2 points), intermediate (3-4 points), and high score (5 points) were 69% (95% CI, 61-76), 51% (95% CI, 46-56.4), and 34% (95% CI, 21-49), respectively (P &lt; .001). Increasing score was predictive of increased transplant-related mortality (TRM; P = .0017) but not of relapse (P = .12). The derived score was predictive of OS (P &lt; .001) and TRM (P = .002) but not of relapse (P = .17) in the EBMT cohort as well. The proposed system was prognostic of survival in 2 large cohorts, CIBMTR and EBMT, and can easily be applied by clinicians consulting patients with MF about the transplantation outcomes.
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.
Haploidentical vs sibling, unrelated, or cord blood hematopoietic cell transplantation for acute lymphoblastic leukemia
Wieduwilt, Matthew J. , Metheny, Leland , Zhang, Mei‐Jie , Wang, Hailin , Estrada‐Merly, Noel, Marks, David I. , Al‐Homsi, A. Samer, Muffly, Lori , Chao, Nelson J. , Rizzieri, David A. , Gadalla, Shahinaz M. , Cairo, Mitchell S. , Gore, Steven D. , Patel, Sagar S. , Michelis, Fotios V. , Inamoto, Yoshihiro , Copelan, Edward A. , Palmisiano, Neil , Kharfan‐Dabaja, Mohamed A. , Ganguly, Siddhartha , Bredeson, Christopher , Ballen, Karen K. , Martino, Rodrigo , Wirk, Baldeep , Aljurf, Mahmoud , Bashey, Asad, Murthy, Hemant S. , Farhadfar, Nosha , Liu, Hongtao , Abdel‐Azim, Hisham , Solh, Melhem , Seftel, Matthew D. , Poel, Marjolein van der , Kamble, Rammurti T., Munker, Reinhold , Cahn, Jean‐Yves , Freytes, César O. , Krem, Maxwell M. , Winestone, Lena E. , Nathan, Sunita , Verdonck, Leo F. , Sharma, Akshay , Ringdén, Olle , Černý, Jan , Choe, Hannah , Seo, Sachiko , Baxter‐Lowe, Lee Ann , Hildebrandt, Gerhard , Litzow, Mark R. , Abid, Muhammad Bilal , Weisdorf, Daniel J. , Saber, Wael , Chao, Nelson , Rizzieri, David A , Gadalla, Shahinaz M , Bhatt, Vijaya Raj , Patel, Sagar , Michelis, Fotios V , Kharfan-Dabaja, Mohamed A , Savani, Bipin N , Martino, Rodrigo , Bacher, Ulrike , Liu, Hongtao , Waller, Edmund K , McGuirk, Joseph , Krem, Maxwell M , Winestone, Lena E , Olsson, Richard F , Sharma, Akshay , Ringden, Olov , Friend, Brian D , Cerny, Jan , Chhabra, Saurabh , Nishihori, Taiga , Seo, Sachiko , George, Biju , Baxter-Lowe, Lee Ann , Hildebrandt, Gerhard C , de Lima, Marcos , Litzow, Mark R. , Hourigan, Christopher S , Weisdorf, Dan , Murthy, Hemant S , Muffly, Lori , Abid, Muhammad Bilal , Gale, Robert Peter , Mussetti, Alberto , Bhatt, Vijaya Raj , Badawy, Sherif M. , Lazarus, Hillard M. , Díaz, Miguel Ángel , Cassaday, Ryan D. , Savani, Bipin N. , Yared, Jean A. , Aldoss, Ibrahim , Waller, Edmund K. , Grunwald, Michael R. , Liesveld, Jane L. , McGuirk, Joseph P. , Lee, Jong Wook , Gergis, Usama , Olsson, Richard F. , Chhabra, Saurabh , Nishihori, Taiga , Lima, Marcos de , Kebriaei, Partow , Hourigan, Christopher S.

Blood Advances | September 21, 2021 | Volume: 6 | Issue: 1 | Pages: 339-357

10.1182/bloodadvances.2021004916 Get It

Abstract The role of haploidentical hematopoietic cell transplantation (HCT) using posttransplant cyclophosphamide (PTCy) for acute lymphoblastic leukemia (ALL) is being defined. We performed a retrospective, multivariable analysis comparing outcomes of HCT approaches by donor for adults with ALL in remission. The primary objective was to compare overall survival (OS) among haploidentical HCTs using PTCy and HLA-matched sibling donor (MSD), 8/8 HLA-matched unrelated donor (MUD), 7 /8 HLA-MUD, or umbilical cord blood (UCB) HCT. Comparing haploidentical HCT to MSD HCT, we found that OS, leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and acute graft-versus-host disease (aGVHD) were not different but chronic GVHD (cGVHD) was higher in MSD HCT. Compared with MUD HCT, OS, LFS, and relapse were not different, but MUD HCT had increased NRM (hazard ratio [HR], 1.42; P = .02), grade 3 to 4 aGVHD (HR, 1.59; P = .005), and cGVHD. Compared with 7/8 UD HCT, LFS and relapse were not different, but 7/8 UD HCT had worse OS (HR, 1.38; P = .01) and increased NRM (HR, 2.13; P ≤ .001), grade 3 to 4 aGVHD (HR, 1.86; P = .003), and cGVHD (HR, 1.72; P ≤ .001). Compared with UCB HCT, late OS, late LFS, relapse, and cGVHD were not different but UCB HCT had worse early OS (≤18 months; HR, 1.93; P &lt; .001), worse early LFS (HR, 1.40; P = .007) and increased incidences of NRM (HR, 2.08; P &lt; .001) and grade 3 to 4 aGVHD (HR, 1.97; P &lt; .001). Haploidentical HCT using PTCy showed no difference in survival but less GVHD compared with traditional MSD and MUD HCT and is the preferred alternative donor HCT option for adults with ALL in complete remission.
Reduced intensity conditioning for acute myeloid leukemia using melphalan- vs busulfan-based regimens: a CIBMTR report
Zhou, Zheng , Nath, Rajneesh , Černý, Jan , Wang, Hai-Lin, Zhang, Mei-Jie , Abdel‐Azim, Hisham , Agrawal, Vaibhav , Ahmed, Gulrayz , Al‐Homsi, A. Samer, Aljurf, Mahmoud , Battiwalla, Minocher, Byrne, Michael , Cahn, Jean‐Yves, Cairo, Mitchell S. , Choe, Hannah , Copelan, Edward A. , Damlaj, Moussab , DeFilipp, Zachariah , Farhadfar, Nosha , Foran, James M. , Freytes, César O. , Gul, Zartash , Hashmi, Shahrukh K. , Hildebrandt, Gerhard , Hossain, Nasheed , Inamoto, Yoshihiro , Isola, Luis , Jain, Tania , Kamble, Rammurti T., Khan, Muhammad , Kharfan‐Dabaja, Mohamed A. , Kekre, Natasha , Khera, Nandita , Litzow, Mark R. , Liu, Hongtao , Marks, David I. , Martino, Rodrigo , Mathews, Vikram , Mishra, Asmita , Murthy, Hemant S. , Nagler, Arnon , Nakamura, Ryotaro , Nathan, Sunita , Olin, Rebecca L. , Palmisiano, Neil , Patnaik, Mrinal M. , Pawarode, Attaphol , Politikos, Ioannis , Rizzieri, David A. , Seo, Sachiko , Shah, Nirav N. , Uy, Geoffrey L. , Verdonck, Leo F. , Wang, Youjin , Weisdorf, Daniel J. , Wirk, Baldeep , Saber, Wael , Hashmi, Shahrukh, Jain, Tania , Murthy, Hemant S , Weisdorf, Dan , Martino, Rodrigo , Liu, Hongtao , Mathews, Vikram , Uy, Geoffrey , Ahmed, Gulrayz , Zhang, Mei‐Jie , Alkhateeb, Hassan B. , Assal, Amer , Bacher, Ulrike , Bajel, Ashish R. , Bashir, Qaiser , Battiwalla, Minocher, Bhatt, Vijaya Raj , Cahn, Jean‐Yves , Cutler, Corey S. , Lima, Marcos de , Díaz, Miguel Ángel , Gerds, Aaron T. , Gergis, Usama , Grunwald, Michael R. , Hamadani, Mehdi , Hertzberg, Mark , Kebriaei, Partow , Lazarus, Hillard M. , Liesveld, Jane L. , Nishihori, Taiga , Olsson, Richard F. , Patel, Sagar S. , Perales, Miguel‐Angel , Politikos, Ioannis , Popat, Uday R , Sandmaier, Brenda M , Savani, Bipin N. , Valcárcel, David , Waller, Edmund K. , Wong, Eric Y.L. , Yared, Jean A.

Blood Advances | July 1, 2021 | Volume: 4 | Issue: 13 | Pages: 3180-3190

10.1182/bloodadvances.2019001266 Get It

Abstract There is a lack of large comparative study on the outcomes of reduced intensity conditioning (RIC) in acute myeloid leukemia (AML) transplantation using fludarabine/busulfan (FB) and fludarabine/melphalan (FM) regimens. Adult AML patients from Center for International Blood and Marrow Transplant Research who received first RIC allo-transplant between 2001 and 2015 were studied. Patients were excluded if they received cord blood or identical twin transplant, total body irradiation in conditioning, or graft-versus-host disease (GVHD) prophylaxis with in vitro T-cell depletion. Primary outcome was overall survival (OS), secondary end points were leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and GVHD. Multivariate survival model was used with adjustment for patient, leukemia, and transplant-related factors. A total of 622 patients received FM and 791 received FB RIC. Compared with FB, the FM group had fewer transplant in complete remission (CR), fewer matched sibling donors, and less usage of anti-thymocyte globulin or alemtuzumab. More patients in the FM group received marrow grafts and had transplantation before 2005. OS was significantly lower within the first 3 months posttransplant in the FM group (hazard ratio [HR] = 1.82, P &lt; .001), but was marginally superior beyond 3 months (HR = 0.87, P = .05). LFS was better with FM compared with FB (HR = 0.89, P = .05). NRM was significantly increased in the FM group during the first 3 months of posttransplant (HR = 3.85, P &lt; .001). Long-term relapse was lower with FM (HR = 0.65, P &lt; .001). Analysis restricted to patients with CR showed comparable results. In conclusion, compared with FB, the FM RIC showed a marginally superior long-term OS and LFS and a lower relapse rate. A lower OS early posttransplant within 3 months was largely the result of a higher early NRM.
Neighborhood poverty and pediatric allogeneic hematopoietic cell transplantation outcomes: a CIBMTR analysis
Bona, Kira , Brazauskas, Ruta , He, Naya, Lehmann, Leslie , Abdel‐Azim, Hisham , Ahmed, Ibrahim , Al‐Homsi, A. Samer, Aljurf, Mahmoud , Arnold, Staci D. , Badawy, Sherif M. , Beattie, Sara , Dalal, Jignesh , Dandoy, Christopher E. , Frangoul, Haydar , Freytes, César O. , Ganguly, Siddhartha , Hahn, Theresa , Kamble, Rammurti T., LeMaistre, Charles F. , Law, Jason , Majhail, Navneet S. , Preussler, Jaime M. , Schears, Raquel M. , Seo, Sachiko , Sharma, Akshay , Steinberg, Amir , Szwajcer, David , Wirk, Baldeep , Khera, Nandita , Wood, William A. , Hashmi, Shahrukh K. , Duncan, Christine , Saber, Wael , Hashmi, Shahrukh, Majhail, Navneet S , Sharma, Akshay , Badawy, Sherif M , Arnold, Staci D , Dandoy, Christopher E , Wood, William A , Battiwalla, Minoo , Bhatt, Neel S. , Díaz, Miguel Ángel , George, Biju , Gómez‐Almaguer, David , Knight, Jennifer M. , Lazarus, Hillard M. , Olsson, Richard F. , Savani, Bipin N. , Srivastava, Alok , Yoshimi, Ayami

Blood | October 26, 2020 | Volume: 137 | Issue: 4 | Pages: 556-568

10.1182/blood.2020006252 Get It

Abstract Social determinants of health, including poverty, contribute significantly to health outcomes in the United States; however, their impact on pediatric hematopoietic cell transplantation (HCT) outcomes is poorly understood. We aimed to identify the association between neighborhood poverty and HCT outcomes for pediatric allogeneic HCT recipients in the Center for International Blood and Marrow Transplant Research database. We assembled 2 pediatric cohorts undergoing first allogeneic HCT from 2006 to 2015 at age ≤18 years, including 2053 children with malignant disease and 1696 children with nonmalignant disease. Neighborhood poverty exposure was defined a priori per the US Census definition as living in a high-poverty ZIP code (≥20% of persons below 100% federal poverty level) and used as the primary predictor in all analyses. Our primary outcome was overall survival (OS), defined as the time from HCT until death resulting from any cause. Secondary outcomes included relapse and transplantation-related mortality (TRM) in malignant disease, acute and chronic graft-versus-host disease, and infection in the first 100 days post-HCT. Among children undergoing transplantation for nonmalignant disease, neighborhood poverty was not associated with any HCT outcome. Among children undergoing transplantation for malignant disease, neighborhood poverty conferred an increased risk of TRM but was not associated with inferior OS or any other transplantation outcome. Among children with malignant disease, a key secondary finding was that children with Medicaid insurance experienced inferior OS and increased TRM compared with those with private insurance. These data suggest opportunities for future investigation of the effects of household-level poverty exposure on HCT outcomes in pediatric malignant disease to inform care delivery interventions.