TY - JOUR
T1 - Influence of Age on Acute and Chronic GVHD in Children Undergoing HLA-Identical Sibling Bone Marrow Transplantation for Acute Leukemia
T2 - Implications for Prophylaxis
AU - Qayed, Muna
AU - Wang, Tao
AU - Hemmer, Michael T.
AU - Spellman, Stephen
AU - Arora, Mukta
AU - Couriel, Daniel
AU - Alousi, Amin
AU - Pidala, Joseph
AU - Abdel-Azim, Hisham
AU - Aljurf, Mahmoud
AU - Ayas, Mouhab
AU - Bitan, Menachem
AU - Cairo, Mitchell
AU - Choi, Sung Won
AU - Dandoy, Christopher
AU - Delgado, David
AU - Gale, Robert Peter
AU - Hale, Gregory
AU - Frangoul, Haydar
AU - Kamble, Rammurti T.
AU - Kharfan-Dabaja, Mohamed
AU - Lehman, Leslie
AU - Levine, John
AU - MacMillan, Margaret
AU - Marks, David I.
AU - Nishihori, Taiga
AU - Olsson, Richard F.
AU - Hematti, Peiman
AU - Ringden, Olov
AU - Saad, Ayman
AU - Satwani, Prakash
AU - Savani, Bipin N.
AU - Schultz, Kirk R.
AU - Seo, Sachiko
AU - Shenoy, Shalini
AU - Waller, Edmund K.
AU - Yu, Lolie
AU - Horowitz, Mary M.
AU - Horan, John
N1 - Publisher Copyright:
© 2017 The American Society for Blood and Marrow Transplantation
PY - 2018/3
Y1 - 2018/3
N2 - Relapse remains the major cause of mortality after hematopoietic cell transplantation (HCT) for pediatric acute leukemia. Previous research has suggested that reducing the intensity of calcineurin inhibitor-based graft-versus-host disease (GVHD) prophylaxis may be an effective strategy for abrogating the risk of relapse in pediatric patients undergoing matched sibling donor (MSD) HCT. We reasoned that the benefits of this strategy could be maximized by selectively applying it to those patients least likely to develop GVHD. We conducted a study of risk factors for GVHD, to risk-stratify patients based on age. Patients age <18 years with leukemia who received myeloablative, T cell-replete MSD bone marrow transplantation and calcineurin inhibitor-based GVHD prophylaxis between 2000 and 2013 and were entered into the Center for International Blood and Marrow Transplant Research registry were included. The cumulative incidence of grade II-IV acute GVHD (aGVHD) was 19%, that of grade II-IV aGVHD 7%, and that of chronic GVHD (cGVHD) was 16%. Compared with age 13 to 18 years, age 2 to 12 years was associated with a lower risk of grade II-IV aGVHD (hazard ratio [HR],.42; 95% confidence interval [CI],.26 to.70; P =.0008), grade II-IV aGVHD (HR,.24; 95% CI,.10 to.56; P =.001), and cGVHD (HR,.32; 95% CI,.19 to.54; P <.001). Compared with 2000-2004, the risk of grade II-IV aGVHD was lower in children undergoing transplantation in 2005-2008 (HR,.36; 95% CI,.20 to.65; P =.0007) and in 2009-2013 (HR,.24; 95% CI..11 to.53; P =.0004). Similarly, the risk of grade III-IV aGVHD was lower in children undergoing transplantation in 2005-2008 (HR,.23; 95% CI,.08 to.65; P =.0056) and 2009-2013 (HR,.16; 95% CI,.04 to.67; P =.0126) compared with those doing so in 2000-2004. We conclude that aGVHD rates have decreased significantly over time, and that children age 2 to 12 years are at very low risk for aGVHD and cGVHD. These results should be validated in an independent analysis, because these patients with high-risk malignancies may be good candidates for trials of reduced GVHD prophylaxis.
AB - Relapse remains the major cause of mortality after hematopoietic cell transplantation (HCT) for pediatric acute leukemia. Previous research has suggested that reducing the intensity of calcineurin inhibitor-based graft-versus-host disease (GVHD) prophylaxis may be an effective strategy for abrogating the risk of relapse in pediatric patients undergoing matched sibling donor (MSD) HCT. We reasoned that the benefits of this strategy could be maximized by selectively applying it to those patients least likely to develop GVHD. We conducted a study of risk factors for GVHD, to risk-stratify patients based on age. Patients age <18 years with leukemia who received myeloablative, T cell-replete MSD bone marrow transplantation and calcineurin inhibitor-based GVHD prophylaxis between 2000 and 2013 and were entered into the Center for International Blood and Marrow Transplant Research registry were included. The cumulative incidence of grade II-IV acute GVHD (aGVHD) was 19%, that of grade II-IV aGVHD 7%, and that of chronic GVHD (cGVHD) was 16%. Compared with age 13 to 18 years, age 2 to 12 years was associated with a lower risk of grade II-IV aGVHD (hazard ratio [HR],.42; 95% confidence interval [CI],.26 to.70; P =.0008), grade II-IV aGVHD (HR,.24; 95% CI,.10 to.56; P =.001), and cGVHD (HR,.32; 95% CI,.19 to.54; P <.001). Compared with 2000-2004, the risk of grade II-IV aGVHD was lower in children undergoing transplantation in 2005-2008 (HR,.36; 95% CI,.20 to.65; P =.0007) and in 2009-2013 (HR,.24; 95% CI..11 to.53; P =.0004). Similarly, the risk of grade III-IV aGVHD was lower in children undergoing transplantation in 2005-2008 (HR,.23; 95% CI,.08 to.65; P =.0056) and 2009-2013 (HR,.16; 95% CI,.04 to.67; P =.0126) compared with those doing so in 2000-2004. We conclude that aGVHD rates have decreased significantly over time, and that children age 2 to 12 years are at very low risk for aGVHD and cGVHD. These results should be validated in an independent analysis, because these patients with high-risk malignancies may be good candidates for trials of reduced GVHD prophylaxis.
KW - Children
KW - GVHD
KW - Leukemia
KW - Matched sibling donor transplantation
KW - Recipient age
UR - http://www.scopus.com/inward/record.url?scp=85039159224&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2017.11.004
DO - 10.1016/j.bbmt.2017.11.004
M3 - Article
C2 - 29155316
AN - SCOPUS:85039159224
SN - 1083-8791
VL - 24
SP - 521
EP - 528
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 3
ER -