Very high efficacy of intermediate-dose cytarabine in combination with G-CSF as a second-line mobilization of hematopoietic stem cells

Autologous hematopoietic stem cell transplantation (autoHSCT) is used widely in the treatment of patients with lymphoid malignancies. Currently, 99 % of such procedures are performed using peripheral blood as a source of stem cells [1]. The generally accepted minimal level of CD34 cells required for rapid neutrophil and platelet recovery after autoHSCT is 2 9 10/kg. However, some data indicate that higher numbers are associated with less need for blood product transfusions and administration of antibiotics [2–4]. Mobilization regimens are based either on the use of granulocyte-colony stimulating factor (G-CSF) alone or G-CSF in combination with chemotherapy, most frequently cyclophosphamide 1.5–7 g/m or lymphoma-specific salvage regimens [5]. Unfortunately, a significant proportion of patients fail to mobilize sufficient number of CD34 cells, thus requiring additional attempts [6]. New mobilization strategies are being explored, including the use of plerixafor, CXCR4 inhibitor, in combination with G-CSF, with or without chemotherapy. This agent enabled sufficient CD34 cell harvest in 64.8–81.6 % of proven or predicted poor mobilizers [7, 8]. Unfortunately, such treatment is very expensive, which limits its worldwide application. Hence, the development of new strategies is still warranted. Although current studies focus on small molecules interfering with stem cell–stroma interactions, traditional chemotherapy-based salvage mobilization regimens have not been sufficiently explored. In our center, between November 2010 and September 2011, 14 patients who had failed chemotherapy-based mobilization were treated with salvage regimen including intermediate-dose cytarabine (ID-AraC) in combination with G-CSF. Most of the patients were referred for transplantation due to multiple myeloma (n = 8) or lymphoma (n = 5), while the remaining one had ovarian cancer. Patients had previously been treated with a median of 2 (range 1–5) lines of chemotherapy and most of them had received irradiation. Previous mobilization was usually based on cyclophosphamide plus G-CSF (Table 1). Six patients received AraC 400 mg/m (2 h infusions) every 12 h for three consecutive days (total dose, 2400 mg/m), while the following eight patients were treated with AraC for 2 days (total dose, 1600 mg/m). G-CSF 5–10 lg/kg was started on day 5 and continued daily until last leukapheresis. Leukaphereses were started once the peripheral blood CD34 cell count exceeded 15/lL and were performed using the Spectra-Optia Apheresis System (CaridianBCT Inc, Lakewood, CO, USA). The target number of CD34 cells collected was 5 9 10/kg for multiple myeloma (all planned for tandem autoHSCT) and 2 9 10/kg for the remaining patients. The maximum number of peripheral blood CD34 cells/lL after AraC ? G-CSF was 86 (17–312) and was significantly higher compared to the first-line mobilization: 8 (0–35) (Mann–Whitney U test, P = 0.002). No difference could be found according to the AraC dose: 80 (17–174) for 1.6 g/m versus 88 (24–312) for 2.4 g/m, P = 0.85. All patients collected required number of CD34 cells, which was achieved with a single apheresis in 10/14 (71.5 %) patients (Table 1). Although all patients experienced profound cytopenia and most required T. Kruzel M. Sadus-Wojciechowska J. Najda T. Czerw M. Glowala-Kosinska J. Holowiecki S. Giebel (&) Department of Bone Marrow Transplantation, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeze Armii Krajowej 15 Street, 44-101 Gliwice, Poland e-mail: sgiebel@io.gliwice.pl