Plerixafor added to G-CSF-supported paclitaxel-ifosfamide-cisplatin salvage chemotherapy enhances mobilization of adequate numbers of hematopoietic stem cells for subsequent autografting in hard-to-mobilize patients with relapsed/refractory germ-cell tumors

Abstract

An appreciable percentage of patients with relapsed/refractory germ-cell tumors (GCTs), candidates for high-dose chemotherapy (HDC) and autologous hematopoietic cell transplantation (HCT), fail to mobilize adequate hematopoietic stem cells (HSCs) numbers with granulocyte colony-stimulating factor (G-CSF)±salvage chemotherapy. Plerixafor has shown a potential to mobilize adequate CD34+HSCs numbers in this context. Here, we applied plerixafor in combination with G-CSF after salvage chemotherapy in ‘poor’ mobilizers with relapsed/refractory GCTs for HDC+HCT. Patients with relapsed/refractory GCTs (n=10) received salvage paclitaxel-ifosfamide-cisplatin (TIP) chemotherapy+G-CSF to mobilize adequate HSCs to support HDC, mainly with two courses of high-dose thiotepa-etoposide-carboplatin (TEC). Patients failing to achieve the minimum collection threshold of 2.0×10⁶/kg CD34+ cells, to support at least one cycle of HDC, were administered plerixafor before the anticipated HSC collection during subsequent cycle(s). Overall, seven patients mobilized adequate CD34+ cells (>5.0×10⁶/kg) aiming to support two cycles of HDC. Three patients did not mobilize adequate numbers of CD34+ cells after previous G-CSF plus salvage TIP, and plerixafor was added in subsequent cycle(s). This led to a collection of adequate CD34+ cells, able to support HDC with TEC (1–2 cycles). Hematopoietic engraftment for neutrophils (absolute neutrophil count>500/μl) and platelets (platelet count>20 000/μl) with plerixafor-mobilized HSCs occurred after a median of 9 and 14 days, respectively. Salvage TIP+G-CSF leads to successful HSC mobilization in patients with less heavily pretreated GCTs, whereas the addition of plerixafor to G-CSF+TIP led to mobilization of adequate HSCs that supported autografting after one to two TEC cycles.