Second Stem Cell Transplantation for Relapse of Childhood Hematologic Malignancies Following Initial Transplantation.

Abstract 3448

Treatment options for patients with hematologic malignancies who relapsed after stem cell transplantation (SCT) are limited. Second SCT could be an effective salvage therapy in some patients who relapsed after initial transplantation. However, most studies of second SCT have focused on adult patients, and the significance of this treatment option in pediatric cohorts is largely unknown. To identify prognostic factors, we retrospectively evaluated the outcome of second SCT in 44 children (25 boys and 19 girls) with hematologic malignancies who received second SCT for disease recurrence after initial transplantation between September 1986 and January 2008 at three transplant units in Nagoya, Japan. The influence of potential risk factors on overall survival (OS), disease-free survival (DFS), relapse rate (RR), and non-relapse mortality (NRM) was assessed using Cox proportional-hazards regression model, taking the background of the first and second SCT into account. Median age at second SCT was 9 years (range, 1–18 years). Underlying diseases were AML/MDS in 22 patients and ALL/ML in 22 patients. Disease status at second SCT was complete remission (CR) in 18 patients and non-CR in 26 patients. Median time from first SCT to relapse and second SCT was 6 months (range, 1–84 months) and 11 months (range, 4–92 months), respectively. For the first SCT, donor type was autologous (n=14), related (n=21), or unrelated (n=9), the stem cell source was peripheral blood (PB) in 6 patients, bone marrow (BM) in 37, or cord blood (CB) in 1, and conditioning regimen was myeloablative (n=35) or non-myeloablative (n=9). For second SCT, donor type was related (n=20) or unrelated (n=24), the stem cell source was PB (n=2), BM (n=39), or CB (n=3), and conditioning regimen was myeloablative (n=37) or non-myeloablative (n=7). Overall, 10 patients were alive with a median follow-up of 67 months from second SCT, and the probability of OS at 5 years was 22%. The 5-year DFS, RR, and NRM was 19%, 53%, and 55%, respectively. Of the 44 patients, 34 patients died following second SCT; 14 patients died owing to relapse and 20 from complications. The survival of patients with non-CR status at second SCT was significantly inferior to survival of patients in remission (8% vs. 40%; P = .01). Notably, all 14 patients who died after relapse were not in remission at second SCT. In multivariate analysis, non-CR at second SCT was the only risk factor for survival (P = .01). In addition, non-CR at second SCT (P = .005) was the most significant risk factor for relapse, and followed by use of unrelated bone marrow as source of stem cells at first SCT (P = .01) and age at second SCT of ≥10 years (P = .01). No significant risk factors were identified for NRM. In summary, second SCT offers only limited chance of cure for patients with a history of unrelated bone marrow transplantation at first SCT or non-CR status at second SCT. On the other hand, the results of this study indicate that second SCT represents a sufficiently effective therapeutic option for the subset of children who are in remission at second SCT, with 40% of long-term survival.