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 7 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-year 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). 3-year 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.

Response to treatment with azacitidine in children with advanced myelodysplastic syndrome prior to hematopoietic stem cell transplantation

“…This was seen despite a trend towards a higher median percentage of blast cells in the bone marrow at presentation in the AZA treatment group and the longer time interval from diagnosis to HSCT, the latter having been previously associated with poorer survival. 13 OS showed similar trends towards better survival after AZA treatment, although not reaching statistical significance. In adults, survival was improved with AZA treatment compared to conventional care, 23 low-dose cytarabine prior to HSCT, 23 and was similar or possibly better than induction chemotherapy.…”

“…8 The administration of AML-type induction chemotherapy to children with RCEB prior to HSCT did not improve outcome. 13 However, the occurrence of progression to MDR-AML leads to reduction in survival by about 50%, and intensive pre-transplant chemotherapy is typically given, resulting in significant toxicity. 8 There is currently no pre-HSCT treatment that has been established in children with RCEB to prevent progression to MDR-AML, and patients are closely monitored and typically managed without any cytoreductive treatment prior to HSCT.…”

“…12 Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the only curative treatment for RCEB. 8 Earlier HSCT correlates with better outcome, 13 but preparations for HSCT are often lengthy and appropriate stem cell donors may not be readily available. The main causes of poor outcome include progression to leukemia, high treatment-related toxicity and high relapse incidence of MDS or occurrence of MDR-AML after HSCT.…”

Hematopoietic Stem Cell Transplantation in Children with Refractory Cytopenia of Childhood: Single-Center Experience Using High-Dose Cytarabine Containing Myeloablative and Aplastic Anemia Oriented Reduced-Intensity Conditioning Regimens

“…Reported disease-free survival rates after HSCT in patients with MDS range between 30% and 75% in previous reports, most of which included patients with various subtypes of MDS, ranging from RCC to advanced MDS, juvenile myelomonocytic leukemia, and therapy-related MDS [5][6][7][8][9][10]. However, limited data are available on the outcome of HSCT focusing on patients with RCC [3,11].…”

“…Naïve and terminally differentiated T cells expressed CD45RA, whereas other memory T cells do not. Naïve T cells after activation in lymphoid organs have been implicated in the genesis of GVHD in experimental models [7,8]. Conversely, alloreactive effector memory T cells are immediate effectors [9][10][11].…”