AMD3100 + G-CSF improves hematopoietic progenitor cell (HPC) collection in patients with hodgkin’s disease (HD)

Abstract

Autologous stem cell transplantation is indicated for patients with HD who have primary refractory disease or who relapse after a first remission. For these patients, as for other patients undergoing autologous transplantation, the number of CD34+ cells infused is a reliable predictor of neutrophil and platelet engraftment, and doses ≥ 5 x 10 6 CD34+ cells/kg are associated with faster count recovery. However, among the 98 patients with HD who have undergone G-CSF-alone mobilization at our institution in the past five years, 22% did not achieve a minimum HPC collection of 2 x 10 6 CD34+ cells/kg in ≤ 5 apheresis procedures, and only 15% achieved a collection ≥ 5 x 10 6 CD34+ cells/kg. AMD3100 mobilizes HPCs by reversibly inhibiting the interaction of CXCR4 and SDF-1α. It has been shown to improve HPC mobilization in patients with multiple myeloma and non-Hodgkin’s lymphoma. Here we present results for the first ten HD patients treated with a mobilization regimen of AMD3100 + G-CSF. To date, ten patients with relapsed (8) or refractory (2) HD have been mobilized with G-CSF (10 ug/kg/d) + AMD3100 (240 ug/kg/d) beginning on day 4. Apheresis was performed 11 hours after each AMD3100 dose. The first dose of AMD3100 produced a median (range) 3.0 (1.9–5.1) fold increase in the number of circulating CD34+ cells. Six patients (60%) achieved a collection of ≥ 5 x 10 6 CD34+ cells/kg, and all patients collected > 2 x 10 6 CD34+ cells/kg (range, 3.6–9.4 x 10 6 CD34+ cells/kg). The median (range) number of apheresis procedures performed per patient was 2 (1–4). No grade II-IV adverse events were ascribed to AMD3100. Eight patients have been transplanted with G-CSF + AMD3100 mobilized cells. All have had prompt and stable engraftment, with median neutrophil recovery at day +9 (9–11) and median platelet recovery at day +20 (15–23). Two patients had very early engraftment, with absolute neutrophil count greater than 100 on day +7. We conclude that AMD3100 + G-CSF is a well-tolerated and effective mobilization regimen in patients with HD. All patients (100%, 95% CI 69%-100%) mobilized with AMD3100 + G-CSF achieved the minimum collection of 2 x 10 6 CD34+ cells/kg, and a significantly higher proportion of patients (60%, 95% CI 26%–88%) achieved the goal collection of ≥ 5 x 10 6 CD34+ cells/kg than did the historical controls (15%). Importantly, the median collection in the first two days of pheresis was 5.4 x 10 6 CD34+ cells/kg, which is significantly better than historical controls, who collected a median 3.0 x 10 6 CD34+ cells/kg in the first two days of pheresis (p=0.014). Our results demonstrate that the mobilization regimen of AMD3100 + G-CSF can improve the number of HPCs collected and decrease the number of days of pheresis in HD patients. This regimen will be pursued further in this patient population.