TY - JOUR
T1 - Transplantation in Children and Adolescents with Acute Lymphoblastic Leukemia from a Matched Donor versus an HLA-Identical Sibling
T2 - Is the Outcome Comparable? Results from the International BFM ALL SCT 2007 Study
AU - Balduzzi, Adriana
AU - Dalle, Jean Hugues
AU - Wachowiak, Jacek
AU - Yaniv, Isaac
AU - Yesilipek, Akif
AU - Sedlacek, Petr
AU - Bierings, Marc
AU - Ifversen, Marianne
AU - Sufliarska, Sabina
AU - Kalwak, Krzysztof
AU - Lankester, Arjan
AU - Toporski, Jacek
AU - Di Maio, Lucia
AU - Glogova, Evgenia
AU - Poetschger, Ulrike
AU - Peters, Christina
N1 - Funding Information:
The authors thank the clinical and laboratory team of all transplant centers that participated in the study and the Parents’ Associations for their continuous support of clinical and research activities. This research was supported by DKMS, Fresenius, Medac, Riemser, Jazz, AOP Orphan Pharmaceuticals, Sanofi, and grants to the St Anna Children's Cancer Research Institute.
Publisher Copyright:
© 2019 American Society for Transplantation and Cellular Therapy
PY - 2019/11/1
Y1 - 2019/11/1
N2 - Eligibility criteria for hematopoietic stem cell transplantation (HSCT) in acute lymphoblastic leukemia (ALL) vary according to disease characteristics, response to treatment, and type of available donor. As the risk profile of the patient worsens, a wider degree of HLA mismatching is considered acceptable. A total of 138 children and adolescents who underwent HSCT from HLA-identical sibling donors (MSDs) and 210 who underwent HSCT from matched donors (MDs) (median age, 9 years; 68% male) in 10 countries were enrolled in the International-BFM ALL SCT 2007 prospective study to assess the impact of donor type in HSCT for pediatric ALL. The 4-year event-free survival (65 ± 5% vs 61 ± 4%; P =.287), overall survival (72 ± 4% versus 68 ± 4%; P =.235), cumulative incidence of relapse (24 ± 4% versus 25 ± 3%; P =.658) and nonrelapse mortality (10 ± 3% versus 14 ± 3%; P =.212) were not significantly different between MSD and MD graft recipients. The risk of extensive chronic (cGVHD) was lower in MD graft recipients than in MSD graft recipients (hazard ratio [HR],.38; P =.002), and the risks of severe acute GVHD (aGVHD) and cGVHD were higher in peripheral blood stem cell graft recipients than in bone marrow graft recipients (HR, 2.06; P =.026). Compared with the absence of aGVHD, grade I-II aGVHD was associated with a lower risk of graft failure (HR,.63; P =.042) and grade III-IV aGVHD was associated with a higher risk of graft failure (HR, 1.85; P =.020) and nonleukemic death (HR, 8.76; P <.0001), despite a lower risk of relapse (HR,.32; P =.021). Compared with the absence of cGVHD, extensive cGVHD was associated with a higher risk of nonleukemic death (HR, 8.12; P <.0001). Because the outcomes of transplantation from a matched donor were not inferior to those of transplantation from an HLA-identical sibling, eligibility criteria for transplantation might be reviewed in pediatric ALL and possibly in other malignancies as well. Bone marrow should be the preferred stem cell source, and the addition of MTX should be considered in MSD graft recipients.
AB - Eligibility criteria for hematopoietic stem cell transplantation (HSCT) in acute lymphoblastic leukemia (ALL) vary according to disease characteristics, response to treatment, and type of available donor. As the risk profile of the patient worsens, a wider degree of HLA mismatching is considered acceptable. A total of 138 children and adolescents who underwent HSCT from HLA-identical sibling donors (MSDs) and 210 who underwent HSCT from matched donors (MDs) (median age, 9 years; 68% male) in 10 countries were enrolled in the International-BFM ALL SCT 2007 prospective study to assess the impact of donor type in HSCT for pediatric ALL. The 4-year event-free survival (65 ± 5% vs 61 ± 4%; P =.287), overall survival (72 ± 4% versus 68 ± 4%; P =.235), cumulative incidence of relapse (24 ± 4% versus 25 ± 3%; P =.658) and nonrelapse mortality (10 ± 3% versus 14 ± 3%; P =.212) were not significantly different between MSD and MD graft recipients. The risk of extensive chronic (cGVHD) was lower in MD graft recipients than in MSD graft recipients (hazard ratio [HR],.38; P =.002), and the risks of severe acute GVHD (aGVHD) and cGVHD were higher in peripheral blood stem cell graft recipients than in bone marrow graft recipients (HR, 2.06; P =.026). Compared with the absence of aGVHD, grade I-II aGVHD was associated with a lower risk of graft failure (HR,.63; P =.042) and grade III-IV aGVHD was associated with a higher risk of graft failure (HR, 1.85; P =.020) and nonleukemic death (HR, 8.76; P <.0001), despite a lower risk of relapse (HR,.32; P =.021). Compared with the absence of cGVHD, extensive cGVHD was associated with a higher risk of nonleukemic death (HR, 8.12; P <.0001). Because the outcomes of transplantation from a matched donor were not inferior to those of transplantation from an HLA-identical sibling, eligibility criteria for transplantation might be reviewed in pediatric ALL and possibly in other malignancies as well. Bone marrow should be the preferred stem cell source, and the addition of MTX should be considered in MSD graft recipients.
KW - Acute lymphoblastic leukemia
KW - Chronic graft-versus-host disease
KW - Hematopoietic stem cell transplantation
KW - Pediatric
KW - Transplantation-related mortality
UR - http://www.scopus.com/inward/record.url?scp=85071473419&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2019.07.011
DO - 10.1016/j.bbmt.2019.07.011
M3 - Article
C2 - 31319153
AN - SCOPUS:85071473419
SN - 1083-8791
VL - 25
SP - 2197
EP - 2210
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 11
ER -