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Clinical Trial
. 2013 Sep;60(9):1520-7.
doi: 10.1002/pbc.24559. Epub 2013 Jun 3.

Transplant-related mortality following allogeneic hematopoeitic stem cell transplantation for pediatric acute lymphoblastic leukemia: 25-year retrospective review

Marion K Mateos  1 , Tracey A O'Brien, Cecilia Oswald, Melissa Gabriel, David S Ziegler, Richard J Cohn, Susan J Russell, Draga Barbaric, Glenn M Marshall, Toby N Trahair
Affiliations
Free PMC article
Clinical Trial

Transplant-related mortality following allogeneic hematopoeitic stem cell transplantation for pediatric acute lymphoblastic leukemia: 25-year retrospective review

Marion K Mateos et al. Pediatr Blood Cancer. 2013 Sep.
Free PMC article

Abstract

Background: Over the last 25 years, donor source, conditioning, graft-versus-host disease prevention and supportive care for children undergoing hematopoeitic stem cell transplantation (HSCT) have changed dramatically. HSCT indications for acute lymphoblastic leukemia (ALL) now include high-risk patients in first and subsequent remission. There is a large burden of infectious and pre-HSCT morbidities, due to myelosuppressive therapy required for remission induction. We hypothesized that, despite these trends, overall survival (OS) had increased.

Procedure: A retrospective audit of allogeneic pediatric HSCT for ALL was performed in our institution over 25 years. Outcomes for 136 HSCTs were analyzed in three consecutive 8-year periods (Period 1: 1/1/1984-31/8/1992, Period 2: 1/9/1992-30/4/2001, Period 3: 1/5/2001-31/12/2009).

Results: Despite a significant increase in unrelated donor HSCT, event-free and OS over 25 years improved significantly. (EFS 31.6-64.8%, P = 0.0027; OS 41.8-78.9%, P < 0.0001) Concurrently, TRM dropped from 33% to 5% (P = 0.0004) whilst relapse rate was static (P = 0.07). TRM reduced significantly for matched sibling and unrelated cord blood transplantation (UCT) in Period 3 compared with earlier periods (P = 0.036, P = 0.0098, respectively). Factors leading to improved survival in patients undergoing UCT include better matching, higher total nucleated cell doses, and significantly faster neutrophil engraftment. Length of initial HSCT admission was similar over time.

Conclusion: EFS and OS have increased significantly despite heightened HSCT complexity. This survival gain was due to TRM reduction. Contemporary patients have benefited from refined donor selection and improved supportive care. Overall rates of leukemic relapse post-HSCT are unchanged, and remain the focus for improvement.

Keywords: hematopoeitic stem cell transplant; lymphoblastic leukemia; outcomes; pediatric acute survival; transplant-related mortality.

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Figures

Figure 1
Figure 1
Significant recent improvement in survival and reduced TRM. Periods 1 and 2: 1/1/1984–30/4/2001 (n = 89), Period 3: 1/5/2001–31/12/2009 (n = 47). A and B: Overall survival post HSCT for Periods 1 and 2 compared to Period 3, for all patients (A) and for patients in ≥CR2 (B); C and D: TRM post HSCT for Period 1 and 2 compared to Period 3, for all patients (C) and for patients in ≥CR2 (D); E and F: Relapse post HSCT for Period 1 and 2 compared to Period 3, for all patients (E) and for patients in ≥CR2 (F).
Figure 2
Figure 2
Significant recent survival benefit for MSD and UCT. Periods 1 and 2: 1/1/1984–30/4/2001, Period 3: 1/5/2001–31/12/2009. MSD (matched sibling donor), UCT (umbilical cord blood transplant). A: Overall survival for MSD and UCT cohorts, for Periods 1 and 2 compared to Period 3; B: TRM post UCT for Period 2 compared to Period 3.
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