Successful mobilization of Ph-negative blood stem cells with intensive chemotherapy + G-CSF in patients with chronic myelogenous leukemia in first chronic phase

Abstract

The aim of the study was to investigate the feasibility of mobilizing Philadelphia chromosome negative (Ph−) blood stem cells (BSC) with intensive chemotherapy and lenograstim (G-CSF) in patients with CML in first chronic phase (CP1).

During 1994 – 1999 12 centers included 37 patients <56 years. All patients received 6 months' IFN, stopping at median 36 (1 – 290) days prior to the mobilization chemotherapy. All received one cycle of daunorubicin 50 mg/m² and 1 hour infusion on days 1 – 3, and cytarabine (ara-C) 200 mg/m² 24 hours' i.v. infusion on days 1 – 7 (DA) followed by G-CSF 526 μg s.c. once daily from day 8 after the start of chemotherapy. Leukaphereses were initiated when the number of CD 34⁺ cells was >5/μl blood. Patients mobilizing poorly could receive a 4-day cycle of chemotherapy with mitoxantrone 12 mg/m²/day and 1 hour i.v infusion, etoposide 100 mg/m²/day and 1 hour i.v. infusion and ara-C 1 g/m²/twice a day with 2 hours' i.v infusion (MEA) or a second DA, followed by G-CSF 526 μg s.c once daily from day 8 after the start of chemotherapy. Twenty-seven patients received one cycle of chemotherapy and G-CSF, whereas 10 were mobilized twice.

Twenty-three patients (62%) were successfully (MNC >3.5 × 10⁸/kg, CFU-GM >1.0 × 10⁴/kg, CD34⁺ cells >2.0 × 10⁶/kg and no Ph+ cells in the apheresis product) [n = 16] or partially successfully (as defined above but 1 – 34% Ph+ cells in the apheresis product) [n = 7] mobilized. There was no mortality during the mobilization procedure.

Twenty-one/23 patients subsequently underwent auto-SCT. The time with PMN <0.5 × 10⁹/l was 10 (range 7 – 49) and with platelets <20 × 10⁹/l was also 10 (2 – 173) days. There was no transplant related mortality. The estimated 5-year overall survival after auto-SCT was 68% (95% CI 47 – 90%), with a median follow-up time of 5.2 years.

We conclude that in a significant proportion of patients with CML in CP 1, intensive chemotherapy combined with G-CSF mobilizes Ph− BSC sufficient for use in auto-SCT.

Keywords:

• CML
• stem cell mobilization
• autologous transplantation
• G-CSF