Mobilizing Chemotherapy Followed by G-CSF, Additioned by Plerixafor on Demand, Is Safe and Allows Both Adequate PBSC (Peripheral Blood Stem Cell) Collection and Safe ASCT (Autologous Stem Cell Transplantation) In Multiple Myeloma and Lymphoma Patients

Autologous Stem Cell Transplantation (ASCT) is an effective anti-tumor strategy in multiple myeloma (MM) and lymphoma patients. However, a significant proportion of patients cannot mobilize a sufficient number of CD34+cells to proceed to transplantation. Plerixafor addition to G-CSF significantly increases the proportion of lymphoma and MM patients, mobilizing ≥2×1010⁶ /kg CD 34+ cells, considered the minimum dose safe for ASCT; however there are very few data about the use of Plerixafor after mobilizing chemotherapy (CHT).

We report here 39 MM or lymphoma patients, candidate for ASCT, who received Plerixafor to collect peripheral blood stem cells (PBSC) after CHT, followed by granulocyte colony-stimulating factor (G-CSF); 17 were affected by non-Hodgkin Lymphoma, 16 by MM and 6 by Hodgkin's Lymphoma; 21 were male and 18 female and the median age was 58 years (20-72). In this population the PBSC collection was planned after disease-specific chemotherapy, followed by G-CSF. These patients were considered poor mobilizers (PM), and therefore eligible for Plerixafor addition, according to the following criteria: ì-previous failure of at least one mobilization attempt (proved PM); ìì- presence of factors predicting unsuccessful harvest (predicted PM), such as: advanced disease, extensive Bone Marrow involvement, previous treatment with extensive radiotherapy or previous prolonged treatment with stem cell poisons (Fludarabine, Alkylating agents, Lenalidomide); ììì- CD34⁺ cells count <10 cells/μL in Peripheral Blood (PB), during the recovery phase after CHT plus G-CSF for at least 7 consecutive days (probable PM). All patients had advanced disease and the median number of previous CHT regimens was 2 (range:1-4); 24 failed at least one mobilization attempt (proven PM); 5 had been considered predicted PM, according to disease status and/or previous treatment; 10 patients have been considered “probable PM”, due to the persistently low CD34+ cell count after G-CSF for at least 7 consecutive days. Retrospectively only 10 out of the 39 mobilized patients reached a CD34+ cell count ≥10/mcl in PB, before receiving Plerixafor. Plerixafor (0.24 mg/Kg), was administered subcutaneously for up to 3 consecutive days (median 2 days; range: 1–3), while continuing G-CSF, 9–11 hours before the planned leukapheresis. G-CSF was administered starting 48–96 hrs after the end of the mobilizing CHT. In all cases the mobilizing CHT was part of a disease-specific protocol: 13 patients received high-intermediate-dose Cytoxan (3-7 g/m2), 13 DHAP, 5 high-dose VP16 (2 g/m2), 4 HyperC-VAD and 4 other CHT (Dexa-BEAM, DCEP, IVAC, High-dose ARA-C).

Plerixafor administration was safe and no significant adverse events were recorded. Following Plerixafor we observed a 3,3 median fold-increase (range 0–20) of the circulating CD34⁺ cells, (median CD34+ peak: 31; range: 0–202/mcl) as compared to the day before Plerixafor (median CD 34+ peak: 5; range 0–32/mcl). In 30/39 patients we collected ≥2×10⁶ CD34⁺ cells/Kg (median 3.7×10⁶ /kg; range 0–15) after 1–3 leukaphereses (median 2). Twenty-five patients have been transplanted with Plerixafor-mobilized PBSCs, 24 of them showing a rapid and durable hematological recovery. The median time to reach PMN recovery (PMN≥500/mcl) was 13 days (9-23); median days to reach unsupported Platelet count ≥20.000/mcl and ≥50.000/mcl were 15 (89-88) and 22 (15-180) respectively. At present 22 patients are alive and maintain stable engraftment after ASCT; 1 died before engraftment while 2 died of disease progression. Our results suggest that “on-demand” addition of Plerixafor to G-CSF after disease-oriented-CHT is safe and may allow a satisfactory harvest in lymphoma and MM patients, considered to be proven or predicted PM, but still eligible for ASCT.

No relevant conflicts of interest to declare.