In:
Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 3036-3036
Abstract:
Abstract 3036 Children with acute lymphoblastic leukemia (ALL) in first complete remission (CR1) and high risk (HR) characteristics can benefit from allogeneic hematopoietic stem cell transplantation (HSCT). We carried out a retrospective, multicenter study to analyze the outcome of 211 consecutive ALL pediatric patients who received either related or unrelated (UD) HSCT for ALL in CR1 and were reported to the Italian Association of Pediatric Hematology and Oncology (AIEOP)-HSCT Registry between 1990 and 2008. Sixty-nine patients (33%) were transplanted between 1990 and 1999, 58 (27%) between 2000 and 2005, and 84 (40%) between 2005 and 2008. A matched family donor (MFD) was employed in 138 patients (65%) and an UD in 73 (35%). The 10-year probability of overall survival and disease-free survival (DFS) was 63.4% (95% CI, 57–70) and 61% (95% CI, 54–68), respectively. In univariate analyses, the donor type had an impact on DFS only for patients transplanted between 1990 and 1999 (MFD: 65% [95% CI, 53–77], UD: 33% [95% CI, 3–64] , p=0.06). There were no differences between MFD and UD for patients who underwent HSCT after 2000. DFS was better in patients with grade 0-II aGvHD than in those with grade III-IV aGvHD (65% [95% CI, 58–62] and 40% [95% CI, 22–58] , p=0.002). In multivariate analyses, the occurrence of grade IV aGvHD (RR=3.8 [95% CI, 1.58–9.20], p=0.002) was an independent factor associated with worse DFS. On the contrary, the occurrence of grade I and II aGvHD (RR=0.54 [95% CI, 0.29–0.99] , p=0.05; RR=0.56 [95% CI 0.30–0.98], p=0.07) were independent favorable prognostic variables for DFS. The 10-year cumulative incidence of relapse incidence (RI) was 24% (95% CI, 19–30). In univariate analyses patients who experienced grade 0-I aGvHD (30% [95% CI, 23–40]) had higher RI than patients with grade II-IV aGvHD (15% [95% CI, 9–25) (p=0.013). In multivariate analysis, the occurrence of aGvHD remained an independent prognostic variable for RI. The 10-year cumulative incidence of transplant-related mortality (TRM) was 15% (95% CI, 11–21). In univariate analyses, TRM was lower for children aged 1–9 years at diagnosis as compared with those aged 10–14 years or older than 15 years (8% [95% CI, 4–15], 18% [95% CI, 11–31] , and 54% [95% IC, 34–84], respectively, p 〈 0.00001). The impact of donor type on TRM was only observed for patients transplanted between 1990 and 1999 (UD: 44%, [95% IC, 21–92], MFD: 8% [95% IC, 4–19] , p=0.0043). Patients with grade III and IV aGvHD had TRM of 32% (95% CI, 16–61) and 82% (95% CI, 62–100), respectively, versus 13% (95% CI, 7–25), 3% (95% CI, 1–14) and 12% (95% CI, 6–26) of patients with grade II, I and 0 aGvHD, respectively (p 〈 0.00001). In multivariate analysis the strongest predictors of TRM were grade IV aGvHD (RR 18.1 [95% IC, 4.37–75.3], p 〈 0.00001) and UD donor for HSCT performed between 1990 and 1999 (RR 4.83 [95% IC, 1.43–16.3], p=0.01).In this study, 27 and 73 out of the 100 patients investigated had minimal residual disease (MRD)-intermediate risk (IR) and MRD-high risk (HR) features, respectively. The 27 with MRD-IR were given the allograft for the presence of other characteristics rendering them classifiable as HR. The probability of DFS and RI of MRD-IR and MRD-HR was comparable. Thus, although the number of patients investigated was limited, our results seem to suggest that HSCT could reduce or, at best, abrogate the effects of MRD on patient outcome. Our results suggest that after 1999 transplant outcomes are remarkably similar in recipients of UD and MFD. No advantage of total body irradiation (TBI) over chemotherapy in the conditioning regimen in terms of DFS, RI and TRM was found. The benefit offered by the occurrence of GvHD in terms of reduction of disease recurrence was, however, offset by a higher incidence of TRM. Indeed, taking patients who did not have aGvHD as the reference group, a better probability of DFS was observed only in patients who developed grade I-II aGvHD, this suggesting that only GvHD of mild/moderate severity can favorably impact on disease outcome. In conclusion, our data support the choice of performing allogeneic HSCT in pediatric and adolescent patients with HR ALL in CR1 from either MFD or UD. Randomized prospective cooperative group studies are desirable to establish the role of TBI-based conditioning in these patients. Disclosures: No relevant conflicts of interest to declare.
Type of Medium:
Online Resource
ISSN:
0006-4971
,
1528-0020
DOI:
10.1182/blood.V120.21.3036.3036
Language:
English
Publisher:
American Society of Hematology
Publication Date:
2012
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
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