Pre-/Post-HSCT Imatinib Improves Survival of Childhood with BCR/ABL⁺ Acute and Chronic Leukemia

Objective:To evaluate the effect of hematopoietic stem cell transplantation (HSCT) for children with leukemia in our center in recent years.

Methods: We retrospectively analyzed data of 87 patients with leukemia underwent HSCT at a median age of 8 years from February 2006 to December 2013 in our center. The median follow-up time was 28 months (range, 2-96), the ratio of male to female patients was 59:28. Conditioning regimen included cyclophosphamide, fludarabine, busulfan with or without (w/o) thiotepa. Anti-thymocyte globulin and cytarabine were individually used for the patients with lymphoid leukemia and myeloid leukemia. GVHD prophylaxis included tacrolimus, mycophenolate mofetil w/o post-transplant cyclophosphamide. Median nucleated cells: 3.75 (1.16`7.56) × 10⁷/Kg. Patients with BCR/ABL⁺ acute lymphoblastic leukemia (ALL) received imatinib before and after transplant over 6 months per each one. Twenty-six patients received transplant from sibling donors, 31 from haploidentical donor, 30 from unrelated donors; Status before transplant were grouped as CR1 (n= 57), CR 2 (n=13), CR 3 (n=1) and NR (n=16). Source of stem cells included PBSC in 40 cases, UCB in 3 cases, BM in 24 cases, BM+PBSC in 9 cases, and mixed stem cells (BM /PBSC+ UCB) in 11 cases.

Results: The estimated 5-year overall survival (OS) was 56.8 ± 5.8% in total.Among them, OS was 54.3 ± 8.0% in 45 patients with ALL; 85.7 ± 13.2% in 8 patients with BCR/ABL⁺ALL; 48.6 ± 8.7% in 37 patients with BCR/ABL^-ALL. 32.8 ± 15% in 29 patients with acute myeloid leukemia and 82.5 ± 11.3% in 13 patients with chronic myelogenous leukemia, respectively. Single factor analysis showed there was no significant difference for OS in comparison of BCR/ABL⁺ALL, BCR/ABL^-ALL, AML and CML (P=0.057), but patients with BCR/ABL⁺ALL had higher OS compared to those with BCR/ABL-ALL (P=0.048) and to AML (P=0.040). In comparison of difference status before transplant, OS were 55.2 ± 11.6%, 54.9 ± 15.6%, 0,and 27.5 ± 11.6% in CR1, CR2, CR3 and NR, respectively (P=0.025). OS was higher in CR1 than NR (P=0.005). When comparing stem cell source, OS was 65.5 ± 8.5%, 0%, 41.7 ± 11.4%, 33.3 ± 15.7%, and 72 ± 17.8% in PBSC, unrelated CB (UCB), BM, BM+PBSC, and BM/PBSC+UCB transplants, respectively (P=0.003); PBSC transplant associated with higher OS than BM (P=0.049) and BM+PBSC (P=0.009); and BM/PBSC⁺UCB mixed transplant had highest OS (P=0.026).

Multivariate analysis showed Risk factors for OS only remained stem cell source (P=0.046) and status before transplantation (P=0.048). the transplant types (P=0.023), and follow up time(P=0.017).

Conclusion: Comparing with data reported in literature we have similar outcomesin total for childhood with leukemia. Use of imatinib pre-/post-transplant for patients with BCR/ABL⁺ALL conduces to the highest OS in current study. Stem cell sources and the status before transplant have a significant effect on OS.