Achievement of Low or Intermediate-1 Risk Score after Combination Chemotherapy before Stem Cell Transplantation (SCT) May Be Associated with Prolonged Disease-Free Survival (DFS) in Patients with Advanced Myelodysplastic Syndrome (MDS).

No definitive consensus whether to treat or not to treat patients with advanced MDS with combination chemotherapy before SCT has been obtained yet. Between 1998 and 2003, fifty patients with primary MDS underwent allogeneic SCT from HLA-matched related (31 cases) or unrelated donors (19 cases). Twenty-five patients with less advanced disease (RA and RAEB with <10% of blasts according to the FAB classification) were transplanted either after myeloablative preparative regimen ( cyclophosphamide + total body iradiation [Cy+TBI] or busulphan + cyclophosphamide [Bu+Cy] intensified by idarubicin in patients with ≥ 8% of blasts) or after reduced intensity conditioning (fludarabine + busulphan [Flu+Bu]) in 5 patients. Fifteen patients with advanced disease (RAEB with >10% of blasts or RAEB-T) were pretreated with combination chemotherapy (anthracycline + standard dose cytosine arabinoside [ARA-C] +/− etoposide for induction, intermediate or high dose ARA-C +/− anthracycline for 1 or 2 consolidation courses) followed by myeloablative conditioning in all but one patient; ten patients were transplanted immediately after myeloablative preparative regimen (Bu+Cy, Cy+TBI or Flu+TBI) intensified by idarubicin(21mg/m²x2) as initial therapy. Complete remission (CR) rate after combination chemotherapy was 72% (11 patients); 3 patients (19%) achieved partial remission (PR), 1 patient had resistant disease. Median age, median survival, 3 year DFS, transplant related mortality (TRM) and relapse rate in different subgroups of patients according to the FAB criteria are shown in the Table.

No significant difference in relapse rate was observed between patients pretreated with chemotherapy and those transplanted directly after intensified conditioning; nevertheless, median survival and 3 year DFS were 31,5 months and 54% in pretreated patients compared to 6,8 months and 40% in non-pretreated patients. Five of the six patients who relapsed after SCT were transplanted either in PR or with resistant disease after chemotherapy (3 patients) or with the initial number of bone marrow blasts ranging from 21 to 24% before immediate SCT (2 patients); 1 patient relapsed after SCT with reduced conditioning performed in the first CR. On the other hand, seven out of eight patients with advanced disease surviving more than 3 years without signs of the disease had low or intermediate-1 score according to IPSS at the time of SCT. We conclude, that the reduction of bone marrow blasts using combination chemotherapy prior to SCT may benefit patients with advanced MDS and may contribute to prolonged DFS after transplantation.

Results of SCT in different groups classified according to the FAB criteria