Tags

Type your tag names separated by a space and hit enter

Association of Reduced-Intensity Conditioning Regimens With Overall Survival Among Patients With Non-Hodgkin Lymphoma Undergoing Allogeneic Transplant.
JAMA Oncol. 2020 Jun 04 [Online ahead of print]JO

Abstract

Importance

Reduced-intensity conditioning and nonmyeloablative conditioning (RIC-NMAC) regimens are frequently used in allogeneic hematopoietic cell transplant (HCT) for non-Hodgkin lymphoma. However, the optimal RIC-NMAC regimen in allogeneic HCT for non-Hodgkin lymphoma is not known.

Objective

To investigate whether RIC-NMAC regimens at a higher end of the intensity spectrum are associated with increased nonrelapse mortality and lower overall survival compared with RIC-NMAC regimens at the lower end of the intensity spectrum in patients with non-Hodgkin lymphoma undergoing allogeneic HCT.

Design, Setting, and Participants

This cohort study used data from 1823 adult patients with non-Hodgkin lymphoma in the Center for International Blood and Marrow Transplant Research registry. Included patients underwent allogeneic HCT using matched related or unrelated donors between January 2008 and December 2016. Statistical analysis was performed from June 1, 2019, to February 10, 2020.

Interventions

Patients received 1 of 4 RIC-NMAC regimens: fludarabine-intravenous busulfan (Flu-Bu), approximately 6.4 mg/kg (n = 458); fludarabine-melphalan (Flu-Mel140), 140 mg/m2 (n = 885); fludarabine-cyclophosphamide (Flu-Cy) (n = 391); or Flu-Cy with 2 Gy total body irradiation (Flu-Cy-2GyTBI) (n = 89).

Main Outcomes and Measures

The primary outcome was overall survival. Secondary outcomes were nonrelapse mortality, incidence of relapse, progression-free survival, and the incidence of acute and chronic graft-vs-host disease (GVHD).

Results

Of 1823 patients, 1186 (65%) were male, with a mean (SD) age of 54.8 (9.9) years. The 4-year adjusted OS was 58% in the Flu-Bu cohort, 67% in the Flu-Cy-2GyTBI cohort, 49% in the Flu-Mel140 cohort, and 63% in the Flu-Cy cohort (P < .001). After adjustment for age, Karnofsky performance score, HCT comorbidity index, NHL subtype, remission status at HCT, and the use of antithymocyte globulin or alemtuzumab, the regression analysis showed a significantly higher mortality risk associated with Flu-Mel140 compared with Flu-Bu (hazard ratio [HR], 1.34; 95% CI, 1.13-1.59; P < .001). Compared with the Flu-Cy cohort, the Flu-Mel140 cohort had a higher risk of chronic GVHD (HR, 1.38; 95% CI, 1.15-1.65; P < .001). The Flu-Mel140 regimen was associated with a higher nonrelapse mortality risk (HR, 1.78; 95% CI, 1.37-2.31; P < .001) compared with the Flu-Bu regimen.

Conclusions and Relevance

The findings suggest that use of the more intense RIC-NMAC regimen, Flu-Mel140, may have a negative association with overall survival and may be associated with higher nonrelapse mortality. The Flu-Bu and Flu-Cy regimens with or without 2GyTBI regimens appeared to provide comparable overall survival.

Authors+Show Affiliations

Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Atrium Health, Charlotte, North Carolina.Department of Myeloma and Lymphoma, University of Texas, MD Anderson Cancer Center, Houston.Department of Medicine, Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee. Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee.Department of Medicine, Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee. Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee.Department of Medicine, Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee.Department of Oncology, King Faisal Specialist Hospital Center and Research, Riyadh, Saudi Arabia.Department of Hematology, Inselspital, Bern University Hospital, University of Bern, Switzerland.The Ottawa Hospital Blood and Marrow Transplant Program, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.Division of Hematology, Department of Medicine, The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus.Division of Hematology and Oncology, University of Florida College of Medicine, Gainesville.Texas Transplant Institute, San Antonio, Texas.Division of Hematological Malignancy and Cellular Therapeutics, University of Kansas Health System, Kansas City.Department of Medicine, University of Colorado Hospital, Aurora, Colorado.Division of Hematology, Mayo Clinic, Rochester, Minnesota.Division of Hematology and Oncology, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas.Department of Hematology and Oncology, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, Ohio.Department of Medicine, University of Miami, Miami, Florida.Division of Hematology-Oncology, Blood and Marrow Transplantation Program, Mayo Clinic Florida, Jacksonville.Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida.Lymphoma, Bone Marrow Transplant and Cellular Therapy Program, UT Southwestern Medical Center, Dallas, Texas.Division of Hematologic Malignancies and Cellular Therapy, Duke University, Durham, North Carolina.Division of Hematology and Oncology, Department of Medicine, Greenebaum Comprehensive Cancer Center, Blood and Marrow Transplantation Program, University of Maryland, Baltimore.Division of Hematology-Oncology, Blood and Marrow Transplantation Program, Mayo Clinic Florida, Jacksonville.Institut Català d'Oncologia-Hospitalet, Hematology Department, University of Barcelona, Barcelona, Spain.Department of Medicine, Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32496525

Citation

Ghosh, Nilanjan, et al. "Association of Reduced-Intensity Conditioning Regimens With Overall Survival Among Patients With Non-Hodgkin Lymphoma Undergoing Allogeneic Transplant." JAMA Oncology, 2020.
Ghosh N, Ahmed S, Ahn KW, et al. Association of Reduced-Intensity Conditioning Regimens With Overall Survival Among Patients With Non-Hodgkin Lymphoma Undergoing Allogeneic Transplant. JAMA Oncol. 2020.
Ghosh, N., Ahmed, S., Ahn, K. W., Khanal, M., Litovich, C., Aljurf, M., Bacher, V. U., Bredeson, C., Epperla, N., Farhadfar, N., Freytes, C. O., Ganguly, S., Haverkos, B., Inwards, D., Kamble, R. T., Lazarus, H. M., Lekakis, L., Murthy, H. S., Nishihori, T., ... Hamadani, M. (2020). Association of Reduced-Intensity Conditioning Regimens With Overall Survival Among Patients With Non-Hodgkin Lymphoma Undergoing Allogeneic Transplant. JAMA Oncology. https://doi.org/10.1001/jamaoncol.2020.1278
Ghosh N, et al. Association of Reduced-Intensity Conditioning Regimens With Overall Survival Among Patients With Non-Hodgkin Lymphoma Undergoing Allogeneic Transplant. JAMA Oncol. 2020 Jun 4; PubMed PMID: 32496525.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of Reduced-Intensity Conditioning Regimens With Overall Survival Among Patients With Non-Hodgkin Lymphoma Undergoing Allogeneic Transplant. AU - Ghosh,Nilanjan, AU - Ahmed,Sairah, AU - Ahn,Kwang Woo, AU - Khanal,Manoj, AU - Litovich,Carlos, AU - Aljurf,Mahmoud, AU - Bacher,Vera Ulrike, AU - Bredeson,Christopher, AU - Epperla,Narendranath, AU - Farhadfar,Nosha, AU - Freytes,César O, AU - Ganguly,Siddhartha, AU - Haverkos,Bradley, AU - Inwards,David, AU - Kamble,Rammurti T, AU - Lazarus,Hillard M, AU - Lekakis,Lazaros, AU - Murthy,Hemant S, AU - Nishihori,Taiga, AU - Ramakrishnan,Praveen, AU - Rizzieri,David A, AU - Yared,Jean A, AU - Kharfan-Dabaja,Mohamed A, AU - Sureda,Anna, AU - Hamadani,Mehdi, Y1 - 2020/06/04/ PY - 2021/06/04/pmc-release PY - 2020/6/5/entrez PY - 2020/6/5/pubmed PY - 2020/6/5/medline JF - JAMA oncology JO - JAMA Oncol N2 - Importance: Reduced-intensity conditioning and nonmyeloablative conditioning (RIC-NMAC) regimens are frequently used in allogeneic hematopoietic cell transplant (HCT) for non-Hodgkin lymphoma. However, the optimal RIC-NMAC regimen in allogeneic HCT for non-Hodgkin lymphoma is not known. Objective: To investigate whether RIC-NMAC regimens at a higher end of the intensity spectrum are associated with increased nonrelapse mortality and lower overall survival compared with RIC-NMAC regimens at the lower end of the intensity spectrum in patients with non-Hodgkin lymphoma undergoing allogeneic HCT. Design, Setting, and Participants: This cohort study used data from 1823 adult patients with non-Hodgkin lymphoma in the Center for International Blood and Marrow Transplant Research registry. Included patients underwent allogeneic HCT using matched related or unrelated donors between January 2008 and December 2016. Statistical analysis was performed from June 1, 2019, to February 10, 2020. Interventions: Patients received 1 of 4 RIC-NMAC regimens: fludarabine-intravenous busulfan (Flu-Bu), approximately 6.4 mg/kg (n = 458); fludarabine-melphalan (Flu-Mel140), 140 mg/m2 (n = 885); fludarabine-cyclophosphamide (Flu-Cy) (n = 391); or Flu-Cy with 2 Gy total body irradiation (Flu-Cy-2GyTBI) (n = 89). Main Outcomes and Measures: The primary outcome was overall survival. Secondary outcomes were nonrelapse mortality, incidence of relapse, progression-free survival, and the incidence of acute and chronic graft-vs-host disease (GVHD). Results: Of 1823 patients, 1186 (65%) were male, with a mean (SD) age of 54.8 (9.9) years. The 4-year adjusted OS was 58% in the Flu-Bu cohort, 67% in the Flu-Cy-2GyTBI cohort, 49% in the Flu-Mel140 cohort, and 63% in the Flu-Cy cohort (P < .001). After adjustment for age, Karnofsky performance score, HCT comorbidity index, NHL subtype, remission status at HCT, and the use of antithymocyte globulin or alemtuzumab, the regression analysis showed a significantly higher mortality risk associated with Flu-Mel140 compared with Flu-Bu (hazard ratio [HR], 1.34; 95% CI, 1.13-1.59; P < .001). Compared with the Flu-Cy cohort, the Flu-Mel140 cohort had a higher risk of chronic GVHD (HR, 1.38; 95% CI, 1.15-1.65; P < .001). The Flu-Mel140 regimen was associated with a higher nonrelapse mortality risk (HR, 1.78; 95% CI, 1.37-2.31; P < .001) compared with the Flu-Bu regimen. Conclusions and Relevance: The findings suggest that use of the more intense RIC-NMAC regimen, Flu-Mel140, may have a negative association with overall survival and may be associated with higher nonrelapse mortality. The Flu-Bu and Flu-Cy regimens with or without 2GyTBI regimens appeared to provide comparable overall survival. SN - 2374-2445 UR - https://www.unboundmedicine.com/medline/citation/32496525/Association_of_Reduced-Intensity_Conditioning_Regimens_With_Overall_Survival_Among_Patients_With_Non-Hodgkin_Lymphoma_Undergoing_Allogeneic_Transplant L2 - https://jamanetwork.com/journals/jamaoncology/fullarticle/10.1001/jamaoncol.2020.1278 DB - PRIME DP - Unbound Medicine ER -
Try the Free App:
Prime PubMed app for iOS iPhone iPad
Prime PubMed app for Android
Prime PubMed is provided
free to individuals by:
Unbound Medicine.