HIGH-DOSE CHEMORADIOTHERAPY 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 chron ic phase (ECP) and not previously treated with alpha-interferon (IFN-a lpha) (10 patients), in ECP but pretreated with IFN-alpha (<12 months) (seven patients) and in late chronic phase (LCP) pretreated with IFN- alpha (>12 months) (six patients) underwent autografting with Philadel phia (Ph) chromosome-negative blood progenitor cells (BPCs) (20 patien ts), or partially/totally Ph-positive BPCs (three patients), previousl y mobilized during the early phase of recovery after aplasia induced b y intensive chemotherapy. The conditioning regimen consisted of high-d ose chemotherapy alone or followed by total body irradiation (TBI). Re combinant G-CSF was given after BPCs infusion on day +8. All patients in ECP not pretreated with IFN-alpha are alive and five of them are Ph -negative in the marrow after autografting. Six of seven patients auto grafted with Ph-negative BPCs in the group of ECP pretreated with IFN- alpha (<12 months) are alive and two of them are still Ph-negative in the marrow. In the same group, the only patient transplanted with part ially Ph-positive BPCs, died of blastic transformation 2 months after reinfusion. Three patients (two patients autografted with Ph-negative BPCs and one patient with Ph-positive BPC) in the group of LCP pretrea ted with IFN alpha >12 months are alive but Ph-positive after autograf ting, The other three patients of the same group died of procedure-rel ated toxicity (two patients) and blastic transformation (one patient). Seventeen patients (10/10 ECP not pretreated with IFN-alpha; 5/7 ECP pretreated with IFN-alpha and 2/6 LCP pretreated with IFN-alpha) of 23 autografted patients were treated with IFN-alpha + IL-2. Toxicities a fter autografting were mostly related to myelosuppression, particularl y thrombocytopenia. All patients of the two groups pretreated with IFN -alpha developed febrile episodes during the aplastic phase following BPCs reinfusion. No patient autografted in ECP and those not pretreate d with IFN-alpha developed febrile episodes, This is also probably due to the use of i,v. antibiotic and antimicotic prophylaxis when neutro phils were less than or equal to 1x10(9)/I after autografting. Greater toxicity was observed in patients pretreated with IFN-alpha, being le thal in two cases in LCF. In conclusion, the 'in vivo' manipulation ap proach 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 ar e harvested: (1) in early chronic phase; (2) in early phase of recover y after chemotherapy-inducing aplasia; (3) in patients not extensively pretreated with IFN-alpha. The data presented here have shown encoura ging trends in chronic phase of CML and offer new perspectives for pat ients without an HLA-identical donor or for patients who do not respon d to IFN-alpha.