High Level of Pretransplant Leukemic Blasts and the Absence of Chronic Graft-Versus-Host Disease Provide Negative Effects on Clinical Outcome of Transplantation with Fludarabine-Busulfex Based Reduced Intensity Conditioning for Patients with the De Novo Myelodysplastic Syndrome According to WHO Criteria.

Background: Allogeneic hematopoietic cell transplantation (HSCT) is the only curative potential for patients with MDS. HSCT following reduced-intensity conditioning (RIST) have enabled the extension of transplantation to include older or medically infirm patients with myeloid malignancies. However, it is very difficult to determine the value of outcomes of RIST for myelodysplastic syndrome (MDS) because of the heterogeneity of diseases included in most trials and the small number of MDS.

Method: Twenty-two patients with de novo MDS classified by WHO criteria received an allograft using a Fludarabine (30 mg/m²/day for 5 days)/Busulfex (3.2 mg/kg/day for 2 days) (14 patients) or Fludarabine (30 mg/m²/day for 5 days)/Busulfex (3.2 mg/kg/day for 2 days)/ATG (2.5 mg/kg/day for 2 days) (8 patients). The median age of patients was 43 years (range, 16–55). Donors were HLA-compatible sibling (n = 19) or matched unrelated (n = 3).

Result: Nineteen patients (86.4%) achieved engraftment. At a median follow-up of 18.9 months (range, 13.1–24.8 months), the estimated 2-year overall survival (OS), event-free survival (EFS), transplantation-related mortality and relapse incidence were 78.7%, 67.7%, 12.6%, and 22.5%, respectively. Acute GVHD greater than grade II was developed in 3 patients (15.8%). Chronic GVHD were developed in 10 patients (55.6%) and all of them did not receive ATG as conditioning. Variables influencing EFS were chronic GVHD (None/Limited [20.8%] versus Extensive [100%], P = 0.001), marrow blasts before transplantation (<10% [85.1%] versus >10% [20.8%], P = 0.006), and WHO criteria (RA [100%] versus RCMD [75%] versus RAEB-1 [80%] versus RAEB-2 [20.8%], P = 0.043).

Conclusion: These observations indicate that high level of pretransplant leukemic blasts and the absence of chronic graft-versus-host disease provide negative effects on clinical outcome of transplantation with Fludarabine-Busulfex based reduced intensity conditioning for patients with the de novo myelodysplastic syndrome according to WHO criteria.