Very High Efficacy of Stem Cell Mobilization Using Intermadiate-Dose Cytosine Arabinoside + G-CSF in Patients with Lymphoid Malignancies, Including Predicted and Proven Poor Mobilizers

High-dose therapy followed by autologous peripheral blood stem cell transplantation (autoPBSCT) is widely applied in the treatment of lymphoid malignancies. However, a significant proportion of patients fail to mobilize sufficient number of stem cells after commonly used protocols.

In this study we evaluated efficacy of first-line mobilization based on cytosine arabinoside (AraC) 1600 mg/m2 + G-CSF (filgrastim) 5–10 ug/kg. Results of 70 subsequent patients (diagnosis multiple myeloma, MM-39, Hodgkin's lymphoma, HD-9, non-Hodgkin lymphoma, NHL-22) were compared with 45 individuals mobilized with cyclophosphamide (CTX) (4 g/m2) + G-CSF in a preceding period (MM-25; HD-4; NHL-16). In respective groups, 39 (56%) and 30 (67%) patients were classified as “predicted” poor mobilizers, defined as the presence of at least one risk factor: age >60 years, thrombocytopenia, preceding treatment with melphalan, fludarabine, preceding radiotherapy on pelvis, >8 courses of chemotherapy for MM, >3 courses containing cisplatin or carboplatin for lymphomas, preceding high-dose treatment with autoHSCT. In addition, we analyzed efficacy of AraC+G-CSF in 14 patients who had failed previous chemo-mobilization, mostly with CTX+G-CSF.

All but three patients (96%) treated with AraC reached >15 CD34+ cells/uL in peripheral blood, compared to 67% in the CTX+G-CSF cohort (p<0.0001). Median peak level was 127 (3–780) CD34+ cells/uL vs. 33 (1–240), respectively (p<0.0001). After AraC, 68 (97%) patients collected >=2×10e6 CD34+ cells/kg and 58 (84%) collected >=5×10e6 CD34+ cells/kg with the median 14.9 (2.3–54.6), which was achieved with a single leukapheresis in 92% patients. Using CTX, 67% patients collected sufficient number of stem cells (p<0.0001) and 76% required 2 or more leukaphareses (p<0.0001). AraC+G-CSF was effective in 37 (97%) predicted poor mobilizers compared with 16 (64%) in the CTX+G-CSF group (p=0.0006). The toxicity related to both regimens was comparable. Among patients who proceeded to autoPBSCT the time to neutrophil recovery after transplantation was the same for AraC and CTX cohorts (median 12 days), while platelet engraftment was faster for patients mobilized with AraC (13 days vs. 14 days, p=0.06).

All 14 patients who had failed previous mobilization collected >=2×10e6 CD34+ cells/kg after AraC+G-CSF, with the median 9.3 (2.5–25.9). It was achieved with a single apheresis in 10 (71%) cases.

Mobilization based on intermediate doses of AraC+G-CSF is highly effective allowing adequate CD34+ harvest in almost all patients with lymphoproliferative diseases, including predicted and proven poor mobilizers. The level of mobilized CD34+ cells is four times higher compared to protocol based on CTX.

No relevant conflicts of interest to declare.