Yazarlar : Kobos R, Steinherz PG, Kernan NA, Prockop SE, Scaradavou A, Small TN, Shukla N, Khalaf R, O'Reilly RJ, Boulad F.

Yayın : Biol Blood Marrow Transplant.

Pubmed Linki : http://www.ncbi.nlm.nih.gov/pubmed/22079789

Konu : Kemik İliği Nakli

Literatür İçeriği :  

Abstract

The development of treatment-related myelodysplastic syndrome (tMDS) or acute myelogenous leukemia (tAML) is a complication that can occur following chemotherapy or radiation therapy. Eighteen patients with a previous malignancy treated at our institution and three patients with a non-malignant primary received an allogeneic HSCT on the pediatric bone marrow transplant 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 following 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 (0.8mg/kg/dose every 6 hours X 10 doses), melphalan (70mg/m2/dose X 2 doses), and fludarabine (25mg/m2/dose X 5 doses) for cytoreduction; three patients received a total body irradiation 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 grafts; four patients received unmodified grafts; one patient received a double unit cord blood transplant (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 time of HSCT was: morphologic and cytogenetic CR (n=12); refractory anemia (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 five-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 to 0% for patients with >5% residual marrow blasts (p=0.015). Nine patients died; cause of death was relapse of MDS/AML (n=4) or of primary disease (n=2), graft versus host disease (GVHD) (n=2), and infection (n=1). Four patients developed grade II-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 T-cell depleted transplant with busulfan-melphalan-fludarabine as cytoreduction may decrease the toxicity of transplantation in heavily pre-treated patients without an increase in relapse rate.

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