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Higher Total Body Irradiation Dose Intensity in Fludarabine/TBI-Based Reduced-Intensity Conditioning Regimen Is Associated with Inferior Survival in Non-Hodgkin Lymphoma Patients Undergoing Allogeneic Transplantation.
Biol Blood Marrow Transplant. 2020 Jun; 26(6):1099-1105.BB

Abstract

Disease relapse is the most common cause of therapy failure in patients with non-Hodgkin lymphoma (NHL) undergoing reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (allo-HCT). It is not known whether or not increasing total body irradiation (TBI) dose from 2 to 4 Gy in a RIC platform can provide improved disease control without increasing nonrelapse mortality (NRM). Using the Center for International Blood & Marrow Transplant Research (CIBMTR) database, we evaluated the outcomes of patients with NHL receiving RIC allo-HCT with either fludarabine (Flu)/2-Gy TBI versus Flu/4-Gy TBI. In the CIBMTR registry, 413 adult patients with NHL underwent a first allo-HCT using either a matched related or unrelated donor between 2008 and 2017, using a RIC regimen with either Flu/2-Gy TBI (n = 349) or Flu/4-Gy TBI (n = 64). The primary endpoint was overall survival (OS). Secondary endpoints included acute (a) and chronic (c) graft-versus-host disease (GVHD), NRM, relapse/progression, and progression-free survival (PFS). At baseline, the Flu/2-Gy TBI cohort had significantly fewer patients with Karnofsky performance status ≥90 and significantly more patients had a higher HCT-comorbidity index. On multivariate analysis, the 2 conditioning cohorts were not significantly different in terms of risk of grade 3 to 4 aGVHD or cGVHD. Compared to Flu/2-Gy TBI, the Flu/4-Gy TBI conditioning was associated with a significantly higher risk of NRM (hazard ratio [HR], 1.79; 95% confidence interval [CI], 1.11 to 2.89; P = .02) and inferior OS (HR, 1.51; 95% CI, 1.03 to 2.23, P = .03). No significant differences were seen in the risk of relapse/progression (HR, 0.78; 95% CI, 0.47 to 1.29, P = .33) or PFS (HR, 1.09; 95% CI, 0.78 to 1.54, P = .61) between the 2 regimens. Comparing Flu/2-Gy TBI versus Flu/4-Gy TBI cohorts, the 5-year adjusted outcomes were NRM (28% versus 47%; P = .005), relapse/progression (35% versus 29%; P = .28), PFS (37% versus 24%; P = .03), and OS (51% versus 31%; P = .001), respectively. Relapse was the most common cause of death in both cohorts. In patients with NHL undergoing Flu/TB I-based conditioning, augmenting TBI dose from 2 to 4 Gy is associated with higher NRM and inferior OS, without any significant benefit in terms of disease control. The optimal dose is 2-Gy in the RIC Flu/TBI platform for lymphomas.

Authors+Show Affiliations

BMT and Cellular Therapy Program, Medical College of Wisconsin, Milwaukee, Wisconsin; Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin. Electronic address: mhamadani@mcw.edu.Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, Wisconsin.Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, Wisconsin.Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.Division of Medical Oncology, Fred Hutchinson Cancer Research Center, Seattle, Washington.Colorado Blood Cancer Institute, Denver, Colorado.Division of Hematology and Oncology, Northwestern University, Chicago, Illinois.Blood & Marrow Transplant Program, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio.BMT and Cellular Therapy Program, Medical College of Wisconsin, Milwaukee, Wisconsin.Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, New York.Division of Hematology-Oncology, Blood and Marrow Transplantation Program, Mayo Clinic Florida, Jacksonville, Florida.Division of Hematology and Oncology, UT Southwestern Medical Center, Dallas, Texas.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32165327

Citation

Hamadani, Mehdi, et al. "Higher Total Body Irradiation Dose Intensity in Fludarabine/TBI-Based Reduced-Intensity Conditioning Regimen Is Associated With Inferior Survival in Non-Hodgkin Lymphoma Patients Undergoing Allogeneic Transplantation." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 26, no. 6, 2020, pp. 1099-1105.
Hamadani M, Khanal M, Ahn KW, et al. Higher Total Body Irradiation Dose Intensity in Fludarabine/TBI-Based Reduced-Intensity Conditioning Regimen Is Associated with Inferior Survival in Non-Hodgkin Lymphoma Patients Undergoing Allogeneic Transplantation. Biol Blood Marrow Transplant. 2020;26(6):1099-1105.
Hamadani, M., Khanal, M., Ahn, K. W., Litovich, C., Chow, V. A., Eghtedar, A., Karmali, R., Winter, A., Fenske, T. S., Sauter, C., Kharfan-Dabaja, M. A., & Awan, F. T. (2020). Higher Total Body Irradiation Dose Intensity in Fludarabine/TBI-Based Reduced-Intensity Conditioning Regimen Is Associated with Inferior Survival in Non-Hodgkin Lymphoma Patients Undergoing Allogeneic Transplantation. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 26(6), 1099-1105. https://doi.org/10.1016/j.bbmt.2020.02.025
Hamadani M, et al. Higher Total Body Irradiation Dose Intensity in Fludarabine/TBI-Based Reduced-Intensity Conditioning Regimen Is Associated With Inferior Survival in Non-Hodgkin Lymphoma Patients Undergoing Allogeneic Transplantation. Biol Blood Marrow Transplant. 2020;26(6):1099-1105. PubMed PMID: 32165327.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Higher Total Body Irradiation Dose Intensity in Fludarabine/TBI-Based Reduced-Intensity Conditioning Regimen Is Associated with Inferior Survival in Non-Hodgkin Lymphoma Patients Undergoing Allogeneic Transplantation. AU - Hamadani,Mehdi, AU - Khanal,Manoj, AU - Ahn,Kwang W, AU - Litovich,Carlos, AU - Chow,Victor A, AU - Eghtedar,Alireza, AU - Karmali,Reem, AU - Winter,Allison, AU - Fenske,Timothy S, AU - Sauter,Craig, AU - Kharfan-Dabaja,Mohamed A, AU - Awan,Farrukh T, Y1 - 2020/03/09/ PY - 2020/01/16/received PY - 2020/02/17/revised PY - 2020/02/29/accepted PY - 2021/06/01/pmc-release PY - 2020/3/14/pubmed PY - 2020/3/14/medline PY - 2020/3/14/entrez KW - Allogeneic hematopoietic cell transplant KW - Fludarabine KW - Reduced-intensity conditioning KW - TBI SP - 1099 EP - 1105 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol. Blood Marrow Transplant. VL - 26 IS - 6 N2 - Disease relapse is the most common cause of therapy failure in patients with non-Hodgkin lymphoma (NHL) undergoing reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (allo-HCT). It is not known whether or not increasing total body irradiation (TBI) dose from 2 to 4 Gy in a RIC platform can provide improved disease control without increasing nonrelapse mortality (NRM). Using the Center for International Blood & Marrow Transplant Research (CIBMTR) database, we evaluated the outcomes of patients with NHL receiving RIC allo-HCT with either fludarabine (Flu)/2-Gy TBI versus Flu/4-Gy TBI. In the CIBMTR registry, 413 adult patients with NHL underwent a first allo-HCT using either a matched related or unrelated donor between 2008 and 2017, using a RIC regimen with either Flu/2-Gy TBI (n = 349) or Flu/4-Gy TBI (n = 64). The primary endpoint was overall survival (OS). Secondary endpoints included acute (a) and chronic (c) graft-versus-host disease (GVHD), NRM, relapse/progression, and progression-free survival (PFS). At baseline, the Flu/2-Gy TBI cohort had significantly fewer patients with Karnofsky performance status ≥90 and significantly more patients had a higher HCT-comorbidity index. On multivariate analysis, the 2 conditioning cohorts were not significantly different in terms of risk of grade 3 to 4 aGVHD or cGVHD. Compared to Flu/2-Gy TBI, the Flu/4-Gy TBI conditioning was associated with a significantly higher risk of NRM (hazard ratio [HR], 1.79; 95% confidence interval [CI], 1.11 to 2.89; P = .02) and inferior OS (HR, 1.51; 95% CI, 1.03 to 2.23, P = .03). No significant differences were seen in the risk of relapse/progression (HR, 0.78; 95% CI, 0.47 to 1.29, P = .33) or PFS (HR, 1.09; 95% CI, 0.78 to 1.54, P = .61) between the 2 regimens. Comparing Flu/2-Gy TBI versus Flu/4-Gy TBI cohorts, the 5-year adjusted outcomes were NRM (28% versus 47%; P = .005), relapse/progression (35% versus 29%; P = .28), PFS (37% versus 24%; P = .03), and OS (51% versus 31%; P = .001), respectively. Relapse was the most common cause of death in both cohorts. In patients with NHL undergoing Flu/TB I-based conditioning, augmenting TBI dose from 2 to 4 Gy is associated with higher NRM and inferior OS, without any significant benefit in terms of disease control. The optimal dose is 2-Gy in the RIC Flu/TBI platform for lymphomas. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/32165327/Higher_Total_Body_Irradiation_Dose_Intensity_in_Fludarabine/TBI_Based_Reduced_Intensity_Conditioning_Regimen_Is_Associated_with_Inferior_Survival_in_Non_Hodgkin_Lymphoma_Patients_Undergoing_Allogeneic_Transplantation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(20)30112-9 DB - PRIME DP - Unbound Medicine ER -
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