High-dose chemo-radiotherapy followed by autologous Philadelphia chromosome-negative blood progenitor cell transplantation in patients with chronic myelogenous leukemia

Twenty-three patients with chronic myelogenous leukemia in early chronic phase (ECP) and not previously treated with alpha-interferon (IFN-α) (10 patients), in ECP but pretreated with IFN-α (12 months) (six patients) underwent autografting with Philadelphia (Ph) chromosome-negative blood progenitor cells (BPCs) (20 patients), or partially/totally Ph-positive BPCs (three patients), previously mobilized during the early phase of recovery after aplasia induced by intensive chemotherapy. The conditioning regimen consisted of high-dose chemotherapy alone or followed by total body irradiation (TBI). Recombinant G-CSF was given after BPCs infusion on day +8. All patients in ECP not pretreated with IFN-α are alive and five of them are Ph-negative in the marrow after autografting. Six of seven patients autografted with Ph-negative BPCs in the group of ECP pretreated with IFN-α (12 months are alive but Ph-positive after autografting. The other three patients of the same group died of procedure-related toxicity (two patients) and blastic transformation (one patient). Seventeen patients (10/10 ECP not pretreated with IFN-α; 5/7 ECP pretreated with IFN-α and 2/6 LCP pretreated with IFN-α) of 23 autografted patients were treated with IFN-α a IL-2. Toxicities after autografting were mostly related to myelosuppression, particularly thrombocytopenia. All patients of the two groups pretreated with IFN-α developed febrile episodes during the aplastic phase following BPCs reinfusion. No patient autografted in ECP and those not pretreated with IFN-α developed febrile episodes. This is also probably due to the use of i.v. antibiotic and antimicotic prophylaxis when neutrophils were ≤1x10⁹/l after autografting. Greater toxicity was observed in patients pretreated with IFN-α, being lethal in two cases in LCF. In conclusion, the 'in vivo' manipulation approach employed in our institution is a safe procedure and it results in a high collection of Ph-negative cells in the blood if the cells are harvested: (1) in early chronic phase; (2) in early phase of recovery after chemotherapy-inducing aplasia; (3) in patients not extensively pretreated with IFN-α. The data presented here have shown encouraging trends in chronic phase of CML and offer new perspectives for patients without an HLA-identical donor or for patients who do not respond to IFN-α.