Conventional intensive therapy can lead to overshoot of PH‐negative blood cells in chronic myeloid leukemia

Twenty‐six patients with Philadelphia chromosome (Ph)‐positive in advanced phase (AP) (24 patients) or in chronic phase (CP) (2 patients) chronic myeloid Leukemia (CML), who were inelegible for allogeneic BMT, were given a new intensive treatment consisting of Idarubicin, 6–8mg/m² per day for 5 days, ARA‐C, 600–800mg/m² per day for 5 days infused i.v. over 2h and Etoposide 150mg/m² per day for 3 days infused over 2h. During recovery of marrow aplasia, when the WBC count reached 0.3‐1×10⁹, blood The International Journal of Cell Cloning (BSC) were collected with 4–5 consecutive leukapheresis. In 8/24 (30%) AP‐CML and in 1/2 (50%) CP‐CML, these BSC were Ph‐negative. Moreover, in two cases (1 advanced and 1 chronic) the PCR analysis performed to detect the presence of minimal residual disease in the cells collected by leukapheresis were negative, further confirming that this approach may induce a very high degree of suppression of the Ph‐positive clone. After recovery, Ph negative patients were subsequently treated with high‐dose Cyclophosphamide ± Etoposide and Total body irradiation (10 Gy, single dose) followed by reinfusion of Ph‐negative cells. Subsequently, all these patients received Cyclosporine A post‐BSC reinfusion in an attempt to induce acute GVHD. Two of 8 patients in AP‐CML and the patient treated in CP remain in clinical and cytogenetic remission post‐transplant. We conclude that Ph‐negative BSC can be recovered from patients in CP‐CML but also in AP‐CML and used successfully to restore Ph‐negative hemopoiesis after very intensive chemoradiotherapy programs.