Philadelphia-negative selection and transplantation in the therapy of untreated patients with chronic myelogenous leukemia

Previous studies have demonstrated that Philadelphia (Ph') chromosome-negative progenitors persist in Ihe marrow of Ph'-positive CML patients and can now be mobilized in the blood of one third of patients who have previously received interferon (1FN) with no citogentic response. The following table reters to 114 patients with CML cvtogenetically refrac.tory_tp_ IFN and mobilized in our Unit. Elastic Accelerated Chronic Phase Crisis Crisis -1 year >I \ear R 11 X r if>S%( 1 I l5(l) Hieh-pradenon hématologie a I toxicii) 14 Ki3ei 1Ü l3S1u) : (19% (328'o) Procedure-related deaths 5 Hi1 117%) I (4i) PB PC: Peripheral Blood Progenitor Cells; MCyR: Major Cytogenetic Remission Between May 1993 and February 1997, 33 patients with a median age of 46 years not previously treated with IFN-a, were recently mobilized with ICE or mini-ICE protocols. (Carella et al., JCO. 15:1575. 1997). In the early phase of recovery a median of 4 leukophoreses were performed. Nineteen patients (58%) achieved a Complete Cytogenetic Remission (CCyR) while 7 patients (21%) achieved a Major Cytogenetic Remission (MCyR). Overall response was 26/33 patients (79%). There were no patient deaths from procedure-related or other causes. To date. 23 patients have undergone autoiirafting \vjth Ph'-negative (17 patients) or MCyR (0 patients). The high-dose therapy consisted of Busulphan (17 patients) or IVT protocol (Idarubicin, VP-16 and single dose TBI) (6 patients). Twenty-two patients are alive ai a median of 18 months after autografting; 6 patients maintain a CCyR (2-t-, 3-, 6+, 18+, 23+. 25+ months) and 8 patients MCyR (2+, 3+, 5. 8+, 18+. 21+. 30+, 30+ months). No procedure reiated deaths occurred. After engraftment. all patients were treated with IFN-a + low-doses 1L-In conclusion, the in vivo mobilization technique employed in our Unit has been demonstrated to be a safe procedure. It resulted in a high selection of Ph'-negative or MCyR cells in the blood if these cells are harvested after Idarubicin-containing regimens in patients in early CP not pretreated with IFN-a. After reinfusion, these cells were able lo engraft and sustain CCyR'MCyR in many patients.