The development of treatment-related
myelodysplastic syndrome (tMDS) or treatment-related
acute myelogenous leukemia (tAML) is a complication that can occur after
chemotherapy or
radiation therapy. Eighteen patients with a previous
malignancy treated at our institution and three patients with a nonmalignant primary
tumor received an allogeneic hematopoietic stem cell transplant (HSCT) on the pediatric bone marrow (BM)
transplantation service for the treatment of tMDS/tAML over a 15-year period. Five patients proceeded to HSCT without
induction chemotherapy. Fourteen patients received high-dose
cytarabine according to the Capizzi II regimen as first-line induction
therapy with 13 of them achieving complete remission (CR) or
refractory anemia (RA) with persistent
cytogenetic abnormalities after this treatment. Two patients received an
anthracycline-based induction
therapy. Conditioning regimens were selected according to previous
therapies: 11 patients received
busulfan-
melphalan-
fludarabine (BU-MEL-FLU), which consisted of
busulfan (0.8 mg/kg/dose every 6 hours ×10 doses),
melphalan (70 mg/m(2)/dose × two doses), and
fludarabine (25 mg/m(2)/dose × five doses) for cytoreduction; three patients received a total body irradiation (TBI)-containing regimen; seven patients received myeloablative regimens containing
busulfan and/or
melphalan and/or
thiotepa with doses modified for organ toxicity. Sixteen patients received T cell-depleted (TCD) grafts; four patients received unmodified grafts; one patient received a double-unit cord blood
transplantation (DUCBT). Donors included HLA-matched (n = 9), or mismatched (n = 3) related donors, or HLA-matched (n = 4), or mismatched (n = 4) unrelated donors, or DUCBT (n = 1). Disease status at the time of HSCT was: morphologic and cytogenetic CR (n = 12); RA with positive cytogenetics (n = 6); and refractory disease (n = 3). With a median follow-up of 5.9 years (2.2-15.7 years), the 5-year overall survival (OS) and disease-free survival (DFS) rates for the entire group were 61.1% with 12 patients alive without evidence of either primary disease or tMDS/tAML. The OS and DFS rate for the 11 patients who received the BU-MEL-FLU cytoreduction with TCD grafts was 54.5%. DFS was 65.7% for patients in RA or CR at HSCT compared with 0% for patients with >5% residual marrow blasts (P = .015). Nine patients died; the cause of death was relapse of MDS/AML (n = 4) or primary disease (n = 2),
graft-versus-host disease (GVHD; n = 2), and
infection (n = 1). Four patients developed grade II to IV acute GVHD. One patient developed localized chronic GVHD. Our results suggest that the strategy of induction with high-dose
cytarabine therapy followed by allogeneic
stem cell transplantation improves the overall outcome for patients with tMDS/tAML. In addition, the use of a TCD
transplantation with BU-MEL-FLU as cytoreduction may decrease the toxicity of
transplantation in heavily pretreated patients without an increase in relapse rate.