Long-term follow-up of autologous stem cell transplantation after intensive chemotherapy in patients with myelodysplastic syndrome or secondary acute myeloid leukemia.

We report on the outcomes of 53 patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia secondary to MDS, autografted in first complete remission. Five (9.4%) died from the procedure whereas hematological reconstitution occurred in all the remaining patients. Forty patients (75%) relapsed, with 87.5% of the relapses occurring within 2 years of the autologous transplant. With a median follow-up of 6.2 years, the median actuarial disease-free survival and overall survival were 8 and 17 months after autograft, respectively. Karyotype was the only prognostic factor for disease-free and overall survival. The eight survivors (15%), including two patients with unfavorable or intermediate karyotype, remained in first complete remission 50+ to 119+ months after transplantation and are probably cured.

A phase II study of intensive chemotherapy with fludarabine, cytarabine, and mitoxantrone in P glycoprotein-negative high-risk myelodysplastic syndromes.

Since leukemic cells primed by exposure to fludarabine exhibit enhanced accumulation of cytarabine triphosphate (the cytotoxic nucleotide of cytarabine), especially with continuous cytarabine (AraC) infusion, a phase II trial was designed to explore the feasibility and efficacy of a combination chemotherapy associating fludarabine, mitoxantrone (MXN), and high-dose cytarabine (continuous infusion) for high-risk P glycoprotein (PGP)-negative myelodysplastic syndromes (MDS) (FAM protocol). The outcomes of FAM-treated patients were compared with those of 32 PGP-negative MDS patients fulfilling identical inclusion and response criteria treated with MXN+AraC (1 g/m(2)/12 h d(1-5), MA protocol). A total of 29 patients (median age 55 years) were included in the FAM group. Six (21%) died from the procedure, and 16 (55%) achieved complete remission (CR). Of these, nine received consolidation chemotherapy, five were autografted and two were allografted in first CR. Abnormal karyotype was the only factor associated with poor survival. The overall median follow-up was 10.9 months. There was no significant difference between FAM and MA protocols with respect to CR rate, treatment-related mortality, duration of leukopenia, neutropenia, autologous stem cell transplantation feasibility, relapse-free survival, or overall survival. The duration of thrombocytopenia was significantly longer in the FAM protocol. In conclusion, the present results suggest that the combination therapy of fludarabine, MXN, and high-dose AraC does not improve CR rate, survival, or disease-free survival in high-risk MDS.