Early Myeloablative Allogeneic Stem Cell Transplantation during High-Dose Cytarabin Induced Cytopenia in Patients with Refractory or Relapsed Myeloid Leukemias.

Allogeneic stem cell transplantation is the most effective therapy for myeloid leukemias. Still, especially patients with refractory disease, unfavourable cytogenetics or blast transformation of a myeloproliferative disorder (mpd) have a poor prognosis as a result of a high rate of treatment related mortality and relapse with conventional conditioning regimens. Recently, Kolb et al. have introduced a sequential protocol utilizing early TBI-based non-myeloablative transplantation following conventional induction therapy in high-risk patients.

In this study, in dependence to Kolb, we have treated 21 patients (median age 51 years, range 17–63, 4 female, 17 male) with advanced leukemias according to an intensified sequential high-dose protocol. Diagnoses were AML (primary refractory 2, relapsed 5), MDS (refractory 7, untreated 1) and blast transformation of a MPD (refractory 6, untreated 0). The median blast count at induction was 22% (range 1–90) and 9 patients (43 %) had unfavourable cytogenetics. Induction therapy consisted of fludarabine, high-dose cytarabine with or without idarubicine, amsacrine or topotecan. ATG, high-dose melphalan with or without high-dose thiotepa was used for conditioning while patients were still cytopenic from the preceeding induction therapy. Following transplantation of a median of 6.1x10E6 CD34+ cells/kg (range 0.85–12.0) from related (6) or unrelated (15) donors, the median time to a wbc>1000/μl and plt>20000/μl was 15 days (range 10–24) and 17 days (range 8–30), respectively. No toxic death was observed during the first 30 days and 95% of patients achieved CR by day 28, 100% by day 50. Twelve patients (57%) developed aGvHD (12I-II°, 0III-IV°) and 7 patients (33%) at risk have developed chronic GvHD (5 limited, 2 extensive) so far. After a median time of 181 days (range 3 – 596 days) fifteen patients (72%) are alive and all are in complete remission. Six patients died, one of infection (5%), two of a combination of a chronic GvHD and infections (9%), two of disease progression (9%) and one patient from a second malignancy (SCLC).

We conclude that early sequential transplantation during induction therapy induced cytopenia using high-dose melphalan and thiotepa based conditioning is feasible and highly effective in patients with advanced myeloid leukemias and poor prognosis. Although these early results are promising, a longer follow up and comparison with standard regimens are required.