IN VIVO MOBILIZATION OF KARYOTyPICALLY NORMAL PERIPHERAL BLOOD PROGENITOR CELLS IN HIGH‐RISK MDS, SECONDARY OR THERAPY‐RELATED ACUTE MYELOGENOUS LEUKAEMIA

Abstract

We have previously reported that mobilization of Philadelphia (Ph) chromosome-negative progenitors is possible in a significant number of Ph1-positive acute lymphoblastic leukaemia (ALL) and chronic myelogenous leukaemia (CML) patients. In this pilot study we employed the same approach for patients with RAEB-t, secondary AML (sAML) and therapy-related AML (t-AML). All patients except one had double or complex cytogenetic abnormalities in marrow cells before mobilization therapy. All patients received an idarubicin-containing regimen (mini-ICE protocol) followed by rh-G-CSF and the first leukapheresis was performed as they were recovering from aplasia. In six out of nine patients the leukapheresis product was entirely karyotypically normal, combined with a significant number of CFU-GM. CD34+ cells and LTC-IC. Recovery time from mobilization therapy was short and no patient died as a result of the procedure. To date, three patients have undergone autografting using their karyotypically normal collections, of which two (sAML) are alive with karyotypically normal marrow a few months after autografting.

More efficient mobilisation of peripheral blood stem cells with HiDAC+AMSA+G-CSF than with mini-ICE+G-CSF in patients with AML

“…As for mini-ICE, consolidation with intermediate/ high-dose cytarabine7etoposide has been associated with adequate collection of PBSC in patients with AML. 13,14,20,26 Thus, it is tempting to speculate that the idarubicine component may have had a negative impact on mobilisation. Indeed, certain chemotherapeutic drugs, such as fludarabine, have been reported to impair mobilisation of PBSC.…”

“…11 On the other hand and arguing against a negative role of idarubicine, several previous investigators have reported a high percentage of successful PBSC collections in AML patients following consolidation with combination CT including idarubicine or other anthracyclines ( þ G-CSF). 8,14,27,28 The optimal scheduling of G-CSF, as combined with CT for mobilisation of PBSC, is not known and may depend on the CT regimen used. 12 In most protocols, G-CSF is started 1-2 days after CT and administered once daily until completion of leukapheresis.…”

“…14,15 However, due to the high proportion of poor mobilisers, we decided to add filgrastim already 2 days following HiDAC-AMSA (ie day 7) in the second cohort. We can only speculate whether postponing the addition of G-CSF after HiDAC-AMSA would result in comparable efficacy of mobilisation and, possibly, more predictable time of harvesting.…”

“…11 Promising results have been reported using ICE (idarubicin þ cytarabine þ etoposide) or modified ICE ('mini-ICE') in combination with G-CSF for mobilisation in patients with advanced myeloid leukaemias including AML. 14,15 In an attempt to find an efficient and practical mobilising regimen in AML CR1, we have studied the yield of PBSC following mobilisation with mini-ICE þ filgrastim (given as second consolidation) and HiDAC þ AMSA þ filgrastim (given as third consolidation), respectively, in two consecutive groups of patients receiving treatment according to a joint protocol. Successful mobilisation was defined as 'the collection of X2.0 Â 10 6 CD34 þ cells/kg b.w.…”

“…Starting 2 days after HiDAC-AMSA (day 7), filgrastim was administered for 18 (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24) days. Following 1-2 weeks of severe pancytopenia, leukocytes increased to 41.0 Â 10 9 /l on day 21 (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25), and 45.0 Â 10 9 /l on day 23 (14-29), respectively. Peak B-CD34 ((19 (2-262)m/l)) was observed on day 23 (17-31) ( Table 2).…”