Outcomes of Second Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in Children.

Introduction: Relapse of the malignancy, secondary malignancy and rejection of the graft (GF) remain important risk factors for mortality after HSCT. The optimal treatment strategy for GF is second HSCT, but for recurrent malignancy it has yet to be determined; however, second HSCT provides a chance for long term survival. This study reports outcomes and clinical experience of HSCT retransplantation in pediatric patients with GF, relapse or secondary malignancy after primary HSCT.

Methods: Outcomes of all pediatric recipients of second HSCT for recurrent malignancy or GF between June 1, 1996 and June 30, 2006 at SickKids Hospital were reviewed. Demographic data, the conditioning regimen chosen, morbidity and mortality after second HSCT were described. EFS was defined as evidence of relapse of malignancy or failure to engraft. Univariate analysis was utilized to assess factors that may influence survival.

Results: Forty-one children (25 male; median age 7.8yrs (range 0.6–17.5yrs)) received a second HSCT during the study period. Initial diagnosis was malignancy in 25 (AML/MDS-11, ALL-6, lymphoma-4, CML-3, JMML-1) and nonmalignant disease in 16 (SAA-4, SCID-4, inherited marrow failure symdrome-5, HLH- 1, MPS-1, thalasemia-1). Indications for second HSCT were: malignancy (recurrent/ secondary) in 21 and GF in 20. Mean time to second HSCT in children with GF was 10.5 months (range: 0.8–57.2 months) compared to 22.7 months (range: 10.1–58.1months) for malignancy (p=0.004). All patients transplanted for malignancy received the second HSCT ≥ 6 months from the first HSCT and only 5 (24%) were transplanted within a year from first HSCT. 8 patients (40%) receiving a second HSCT for GF were retransplanted within the first 6 months. Conditioning regimens at second HSCT included myeloablative treatment (23); reduced intensity (RIC) (16) and none (2). The following factors were not statistically associated with survival: underlying disease, type of conditioning regimen (myeloablative vs reduced intensity) and indication for second HSCT (GF vs. malignancy). Overall survival (OS) and EFS rates are summarized below. Non-relapse related mortality was 45%; 9 patients died from infections.

Discussion and conclusion: Children who underwent second HSCT had an OS of 43%. We conclude that a second HSCT can result in prolonged EFS in children relapsing more than 6months after first HSCT and provides an acceptable therapeutic option for patients with GF.