Transplantation in Children and Adolescents with Acute Lymphoblastic Leukemia from a Matched Donor versus an HLA-Identical Sibling: Is the Outcome Comparable? Results from the International BFM ALL SCT 2007 Study.

• Outcomes are similar in pediatric acute lymphoblastic leukemia after peripheral blood stem cell transplantation (PBSCT) with HLA-identical sibling donors and matched unrelated donors. • There is a higher incidence of chronic graft-versus-host disease (GVHD) in HLA-identical sibling donor transplant recipients. • There is a higher incidence of acute and chronic GVHD after PBSCT. • Severe acute GVHD is associated with lower relapse but is detrimental for event-free survival and survival. • Severe acute and chronic GVHD are associated with higher nonrelapse mortality. • Adolescents have worse chronic GVHD, higher nonrelapse mortality, and poorer survival. 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. [ABSTRACT FROM AUTHOR]