Tags

Type your tag names separated by a space and hit enter

Grade II Acute Graft-versus-Host Disease and Higher Nucleated Cell Graft Dose Improve Progression-Free Survival after HLA-Haploidentical Transplant with Post-Transplant Cyclophosphamide.
Biol Blood Marrow Transplant. 2018 02; 24(2):343-352.BB

Abstract

Compared with standard graft-versus-host disease (GVHD) prophylaxis platforms, post-transplantation cyclophosphamide (PTCy) after T cell-replete HLA-haploidentical (haplo) bone marrow transplantation (BMT) reduces the risk of grades III to IV acute (a) and chronic (c) GVHD, but maintains similar rates of grade II aGVHD. Given that mild GVHD has been associated with reduced treatment failure in HLA-matched BMT, we evaluated the risk factors for and effects of GVHD on survival in 340 adults with hematologic malignancies who engrafted after nonmyeloablative haplo-BMT with PTCy, mycophenolate mofetil, and tacrolimus. The cumulative incidence at 100 days of grade II and grades III to IV aGVHD were 30% (95% confidence interval [CI], 25% to 35%) and 2% (95% CI, 1% to 4%), respectively. The 1-year cumulative incidence of cGVHD was 10% (95% CI, 7% to 13%). In landmark analyses at 100 days, the 4-year probabilities of overall survival (OS) and progression-free survival (PFS) were, 48% (95% CI, 41% to 56%) and 39% (95% CI, 32% to 47%) for patients without grades II to IV aGVHD, compared with 63% (95% CI, 53% to 73%) and 59% (95% CI, 50% to 71%) for patients with grade II aGVHD (P = .05 and P = .009). In multivariable modeling, when compared with patients who never experienced GVHD, the hazard ratio (HR) for OS and PFS in patients with grade II aGVHD was .78 (95% CI, .54 to 1.13; P = .19) and .69 (95% CI, .48 to .98; P = .04). Higher nucleated cell graft dose was also associated with improved OS (HR, .88; 95% CI, .78 to 1.00; P = .05) and PFS (HR, .89; 95% CI, .79 to 1.0; P = .05) and decreased risk of grades III to IV aGVHD (subdistribution HR, .66; 95% CI, .46 to .96; P = .03). PTCy reduces grades III to IV aGVHD and cGVHD, but retains similar incidence of grade II aGVHD, the development of which improves PFS. Higher nucleated cell graft dose goals may also improve survival after nonmyeloablative haplo-BMT with PTCy.

Authors+Show Affiliations

Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: smccurd2@jhmi.edu.Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.Biostatistics & Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland.Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.Immunogenetics Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland.Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.Biostatistics & Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland.Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

29055682

Citation

McCurdy, Shannon R., et al. "Grade II Acute Graft-versus-Host Disease and Higher Nucleated Cell Graft Dose Improve Progression-Free Survival After HLA-Haploidentical Transplant With Post-Transplant Cyclophosphamide." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 24, no. 2, 2018, pp. 343-352.
McCurdy SR, Kanakry CG, Tsai HL, et al. Grade II Acute Graft-versus-Host Disease and Higher Nucleated Cell Graft Dose Improve Progression-Free Survival after HLA-Haploidentical Transplant with Post-Transplant Cyclophosphamide. Biol Blood Marrow Transplant. 2018;24(2):343-352.
McCurdy, S. R., Kanakry, C. G., Tsai, H. L., Kasamon, Y. L., Showel, M. M., Bolaños-Meade, J., Huff, C. A., Borrello, I., Matsui, W. H., Brodsky, R. A., Ambinder, R. F., Bettinotti, M. P., Fuchs, E. J., Rosner, G. L., Jones, R. J., & Luznik, L. (2018). Grade II Acute Graft-versus-Host Disease and Higher Nucleated Cell Graft Dose Improve Progression-Free Survival after HLA-Haploidentical Transplant with Post-Transplant Cyclophosphamide. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 24(2), 343-352. https://doi.org/10.1016/j.bbmt.2017.10.023
McCurdy SR, et al. Grade II Acute Graft-versus-Host Disease and Higher Nucleated Cell Graft Dose Improve Progression-Free Survival After HLA-Haploidentical Transplant With Post-Transplant Cyclophosphamide. Biol Blood Marrow Transplant. 2018;24(2):343-352. PubMed PMID: 29055682.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Grade II Acute Graft-versus-Host Disease and Higher Nucleated Cell Graft Dose Improve Progression-Free Survival after HLA-Haploidentical Transplant with Post-Transplant Cyclophosphamide. AU - McCurdy,Shannon R, AU - Kanakry,Christopher G, AU - Tsai,Hua-Ling, AU - Kasamon,Yvette L, AU - Showel,Margaret M, AU - Bolaños-Meade,Javier, AU - Huff,Carol Ann, AU - Borrello,Ivan, AU - Matsui,William H, AU - Brodsky,Robert A, AU - Ambinder,Richard F, AU - Bettinotti,Maria P, AU - Fuchs,Ephraim J, AU - Rosner,Gary L, AU - Jones,Richard J, AU - Luznik,Leo, Y1 - 2017/10/18/ PY - 2017/08/12/received PY - 2017/10/11/accepted PY - 2017/10/23/pubmed PY - 2019/3/26/medline PY - 2017/10/23/entrez KW - Bone marrow transplantation KW - Cyclophosphamide KW - Graft dose KW - Graft-versus-host disease KW - HLA-haploidentical SP - 343 EP - 352 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol. Blood Marrow Transplant. VL - 24 IS - 2 N2 - Compared with standard graft-versus-host disease (GVHD) prophylaxis platforms, post-transplantation cyclophosphamide (PTCy) after T cell-replete HLA-haploidentical (haplo) bone marrow transplantation (BMT) reduces the risk of grades III to IV acute (a) and chronic (c) GVHD, but maintains similar rates of grade II aGVHD. Given that mild GVHD has been associated with reduced treatment failure in HLA-matched BMT, we evaluated the risk factors for and effects of GVHD on survival in 340 adults with hematologic malignancies who engrafted after nonmyeloablative haplo-BMT with PTCy, mycophenolate mofetil, and tacrolimus. The cumulative incidence at 100 days of grade II and grades III to IV aGVHD were 30% (95% confidence interval [CI], 25% to 35%) and 2% (95% CI, 1% to 4%), respectively. The 1-year cumulative incidence of cGVHD was 10% (95% CI, 7% to 13%). In landmark analyses at 100 days, the 4-year probabilities of overall survival (OS) and progression-free survival (PFS) were, 48% (95% CI, 41% to 56%) and 39% (95% CI, 32% to 47%) for patients without grades II to IV aGVHD, compared with 63% (95% CI, 53% to 73%) and 59% (95% CI, 50% to 71%) for patients with grade II aGVHD (P = .05 and P = .009). In multivariable modeling, when compared with patients who never experienced GVHD, the hazard ratio (HR) for OS and PFS in patients with grade II aGVHD was .78 (95% CI, .54 to 1.13; P = .19) and .69 (95% CI, .48 to .98; P = .04). Higher nucleated cell graft dose was also associated with improved OS (HR, .88; 95% CI, .78 to 1.00; P = .05) and PFS (HR, .89; 95% CI, .79 to 1.0; P = .05) and decreased risk of grades III to IV aGVHD (subdistribution HR, .66; 95% CI, .46 to .96; P = .03). PTCy reduces grades III to IV aGVHD and cGVHD, but retains similar incidence of grade II aGVHD, the development of which improves PFS. Higher nucleated cell graft dose goals may also improve survival after nonmyeloablative haplo-BMT with PTCy. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/29055682/Grade_II_Acute_Graft_versus_Host_Disease_and_Higher_Nucleated_Cell_Graft_Dose_Improve_Progression_Free_Survival_after_HLA_Haploidentical_Transplant_with_Post_Transplant_Cyclophosphamide_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(17)30782-6 DB - PRIME DP - Unbound Medicine ER -