Early hematopoietic stem cell transplant is associated with favorable outcomes in children with MDS

Abstract

Background: Although hematopoietic stem cell transplantation (HSCT) is the treatment of choice for childhood myelodysplastic syndrome (MDS), there is no consensus regarding patient or disease characteristics that predict outcomes.

Procedure: We reviewed 37 consecutive pediatric MDS patients who received myeloablative HSCT between 1990 and 2010 at a single center.

Results: Twenty had primary MDS and 17 had secondary MDS. Diagnostic cytogenetics included monosomy 7 (n = 21), trisomy 8 (n = 7) or normal/other (n = 8). According to the modified WHO MDS classification, thirty had refractory cytopenia and seven had refractory anemia with excess blasts. IPSS scores were: low risk (n = 1), intermediate-1 (n = 15), and intermediate-2 (n = 21). OS and DFS at 10 years in the entire cohort was 53% and 45%. Relapse at 10 years was 26% and 1 year TRM was 25%. In multivariate analysis, factors associated with improved 3 years DFS were not receiving pre-HSCT chemotherapy (RR = 0.30, 95% CI 0.10-0.88; P = 0.03) and a shorter interval (<140 days) from time of diagnosis to transplant (RR = 0.27, 95% CI 0.09-0.80; P = 0.02). Three years DFS in patients who did not receive pre-HSCT chemotherapy and those who had a shorter interval to transplant (n = 16) was 80%.

Conclusion: These results suggest that children with MDS should be referred for allogeneic HSCT soon after diagnosis and that pre-HSCT chemotherapy does not appear to improve outcomes.

Figure 1. Kaplan-Meier Analysis of Overall Survival and Disease Free Survival

A. Overall Survival. OS was 70% (95% CI 53–82%) at 1 year and 53% (95% CI 36–68%) at 3 years and beyond. B. Disease Free Survival and Relapse. DFS was 62% (95% CI 44–75%) at 1 year and 48% (95% CI 31–63%) at 3 years and 45% (95% CI 28–60%) at 10 years. The incidence of relapse was 20% (95% CI 7–33%) at 2 years and 26% (95% CI 11–41%) at 10 years.

Figure 1. Kaplan-Meier Analysis of Overall Survival and Disease Free Survival

A. Overall Survival. OS was 70% (95% CI 53–82%) at 1 year and 53% (95% CI 36–68%) at 3 years and beyond. B. Disease Free Survival and Relapse. DFS was 62% (95% CI 44–75%) at 1 year and 48% (95% CI 31–63%) at 3 years and 45% (95% CI 28–60%) at 10 years. The incidence of relapse was 20% (95% CI 7–33%) at 2 years and 26% (95% CI 11–41%) at 10 years.

Figure 2

A. Kaplan-Meier Analysis of 3-year DFS by Pre HSCT Chemotherapy Status. 3-year DFS was 60% (95% CI 40–75%) for patients who did not receive pre HSCT chemotherapy and 0% for patients who received pre HSCT chemotherapy (p<0.01). B. Kaplan-Meier Analysis of 3-year DFS by Time from Diagnosis to HSCT. 3-year DFS was 71% (95% CI 44–87%) in patients who had a diagnosis to HSCT time of <140 days and 26% (95% CI 10–47%) in those with diagnosis to HSCT time of ≥140 days (p<0.01). C. Kaplan-Meier Analysis of 3-year DFS in Patients who did not receive pre HSCT Chemotherapy and who were transplanted <140 days from Diagnosis. 3-year DFS was 80% (95% CI 51–93%) in the 16 patients who did not receive pre HSCT chemotherapy and were transplanted <140 days from diagnosis.

Figure 2

A. Kaplan-Meier Analysis of 3-year DFS by Pre HSCT Chemotherapy Status. 3-year DFS was 60% (95% CI 40–75%) for patients who did not receive pre HSCT chemotherapy and 0% for patients who received pre HSCT chemotherapy (p<0.01). B. Kaplan-Meier Analysis of 3-year DFS by Time from Diagnosis to HSCT. 3-year DFS was 71% (95% CI 44–87%) in patients who had a diagnosis to HSCT time of <140 days and 26% (95% CI 10–47%) in those with diagnosis to HSCT time of ≥140 days (p<0.01). C. Kaplan-Meier Analysis of 3-year DFS in Patients who did not receive pre HSCT Chemotherapy and who were transplanted <140 days from Diagnosis. 3-year DFS was 80% (95% CI 51–93%) in the 16 patients who did not receive pre HSCT chemotherapy and were transplanted <140 days from diagnosis.

Figure 2

A. Kaplan-Meier Analysis of 3-year DFS by Pre HSCT Chemotherapy Status. 3-year DFS was 60% (95% CI 40–75%) for patients who did not receive pre HSCT chemotherapy and 0% for patients who received pre HSCT chemotherapy (p<0.01). B. Kaplan-Meier Analysis of 3-year DFS by Time from Diagnosis to HSCT. 3-year DFS was 71% (95% CI 44–87%) in patients who had a diagnosis to HSCT time of <140 days and 26% (95% CI 10–47%) in those with diagnosis to HSCT time of ≥140 days (p<0.01). C. Kaplan-Meier Analysis of 3-year DFS in Patients who did not receive pre HSCT Chemotherapy and who were transplanted <140 days from Diagnosis. 3-year DFS was 80% (95% CI 51–93%) in the 16 patients who did not receive pre HSCT chemotherapy and were transplanted <140 days from diagnosis.