title: Allogeneic hematopoietic stem cell transplantation for pediatric patients with treatment-related myelodysplastic syndrome or acute myelogenous leukemia.
abstract: 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.
authors.affiliation: Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. kobosr@mskcc.org
authors.forename: Rachel
authors.initials: R
authors.lastname: Kobos
authors.forename: Peter G
authors.initials: PG
authors.lastname: Steinherz
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Kernan
authors.forename: Susan E
authors.initials: SE
authors.lastname: Prockop
authors.forename: Andromachi
authors.initials: A
authors.lastname: Scaradavou
authors.forename: Trudy N
authors.initials: TN
authors.lastname: Small
authors.forename: Neerav
authors.initials: N
authors.lastname: Shukla
authors.forename: Ramzi
authors.initials: R
authors.lastname: Khalaf
authors.forename: Richard J
authors.initials: RJ
authors.lastname: O'Reilly
authors.forename: Farid
authors.initials: F
authors.lastname: Boulad
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000601:surgery*; D008297:Male; D009190:Myelodysplastic Syndromes / Q000209:etiology / Q000601:surgery*; D016609:Neoplasms, Second Primary / Q000601:surgery*; D014184:Transplantation, Homologous; D055815:Young Adult