Chemotherapy for mobilisation of Ph-negative progenitor cells from patients with CML: impact of different mobilisation regimens

Abstract

Summary:Mobilised peripheral blood stem cells are widely used for autografting in patients with chronic myeloid leukaemia (CML) and it is generally thought that a high proportion of Ph-negative progenitor cells in the graft is desirable. We report here the results of 91 stem cell mobilisations performed with various chemotherapy regimens followed by G-CSF. We show that mobilisation of Ph-negative cells is possible after diagnosis as well as in advanced stages of the disease. The yield of Ph-negative cells is highly dependent on the chemotherapy regimen: while the combination of idarubicin and cytarabin for 3-5 days (IC3-5) mobilised Ph-negative cells in most patients, high-dose cyclophosphamide was ineffective. Mobilisation of Ph-negative progenitor cells after IC3 was at least as effective as after IC5; however, less apheresis sessions were required, and toxicity was much reduced after IC3. Compared to historical controls, IC was equally effective as the widely used ICE/minilCE (idarubicin, cytarabin, etoposide) protocol. No correlation was found between graft quality and the cytogenetic response to subsequent treatment with interferon-␣. We conclude that IC3 is an effective and well-tolerated regimen for mobilising Ph-negative cells that compares well with more aggressive approaches such as IC5 and ICE/minilCE. Bone Marrow Transplantation (2001) 27, 1125-1132.

Successful peripheral blood stem cell mobilisation with filgrastim in patients with chronic myeloid leukaemia achieving complete cytogenetic response with imatinib, without increasing disease burden as measured by quantitative real-time PCR

“…The yield may be improved with temporary interruption of imatinib, a manoeuvre that was also successful in individuals who failed mobilisation with prior continuing imatinib/filgrastim. The efficacy of G-CSF mobilisation in the context of continuing imatinib appears suboptimal when compared with most reported series of PBSC harvests from other CML patients using various chemotherapy-GCSF regimens 30,31 or an interferon-G-CSF combination. 32 Our decision to continue imatinib therapy during the cytokine mobilisation in a first cohort of patients was based on the absence of reported clinical data to support temporary interruption, and a postulated benefit that leukaemic stem cells stimulated into cell cycle may be rendered more susceptible to cellular inhibition induced by the continuous presence of imatinib.…”

Autologous stem cell transplantation for patients with chronic myeloid leukemia

“…The estimated probability of survival was 84% and 51% at 2 years and 4 years, respectively. The East German Study Group for Hematology‐Oncology published their experience with 91 stem cell mobilizations for autografting in patients with CML 26. Of the regimens used, they observed that, although the combination of idarubicin and Ara‐C for 3–5 days mobilized Ph negative cells in most patients, high‐dose Cy was remarkably less effective.…”

“…Patients received different treatments during the course of the disease, including α‐IFN, hydroxyurea, and/or other treatments, prior to mobilization chemotherapy. Fifty‐two of 53 patients received chemotherapy for mobilization: 33 patients received idarubicin, Ara‐C, and etoposide (ICE;12 idarubicin 6–8 mg/m 2 per day on days 1–5, Ara‐C 600–800mg/m 2 per day on days 1–5, and etoposide 150 mg/m 2 per day on days 1–3); 4 patients received mini‐ICE23 (ICE at similar doses but over 3 days); 10 patients received idarubicin and Ara‐C24 (idarubicin 10 mg/m 2 per day on days 1–2 and Ara‐C 600 mg/m 2 per day on days 1–5); 4 patients received high‐dose hydroxyurea25 (3.5 g/m 2 per day on days 1–7); and 1 patient received high‐dose cyclophosphamide (Cy) 26. In all patients, chemotherapy was followed by G‐CSF (5–10 μg/kg per day subcutaneously until the end of the harvest).…”