Successful Hematopoietic STEM CELL Mobilization with GRANULOCYTE Colony Stimulating FACTOR PLUS Plerixafor (MOZOBIL, AMD3100) IN POOR Mobilizers: A Single CENTER STUDY
Authors: Mallouri Despina , Sakellari Ioanna , Apostolou Chrisa , Baliakas Panayotis , Papalexandri Apostolia , Tsobanakou Aliki , Batsis Ioannis , Yannaki Evangelia , Smias Christos , Sotiropoulos Damianos , Fassas Athanasios , Anagnostopoulos Achilles 
Published: October 2019

Abstract 4444

Background:

According to published data mobilization of sufficient number of CD 34+ cells with cytokines alone or with chemo-mobilization fails in 5–30% of patients. Plerixafor is a novel chemokine receptor 4 antagonist (CXCR4) that reversibly inhibits the interaction with its ligand SDF-1 (Stromal Derived Factor 1). Phase III studies have demonstrated that plerixafor combined with granulocyte-colony stimulating factor (GCSF) improves CD 34+ cell collection in patients with Multiple Myeloma (MM) or Non Hodgkin Lymphoma (NHL). It has been shown to be efficacious in combination with GCSF to mobilize adequate number of CD 34+ cells in patients proven to be poor mobilizers yielding a success rate of 60–100% in several reports. Plerixafor is currently approved for administration in combination with GCSF to enhance mobilization of hematopoietic stem cells in patients with lymphoma and MM whose cells mobilize poorly.

Patients/methods:

We administered plerixafor in combination with GCSF in 14 patients (in 4/14 as part of compassionate use protocol) and 2 sibling donors after an informed consent was obtained. Individuals were defined as poor mobilizers either due to unsuccessful collection of CD34+ >2×106/kg or due to peripheral blood CD34+ peak <20/μ l in spite of adequate mobilization treatment. Data of the individuals were collected retrospectively. Eight patients suffered from MM, 3 of NHL, 3 of H°dgkin Lymphoma (HL). Marrow involvement was present in 1 patient suffering from MM. The median number of previous chemotherapy regimens was 4(1-8). Two patients had a history of previous autologous hematopoietic cell transplantation (autoHCT) and 4 patients had received multiple radiotherapy courses. Patients had a median of 2 (1-3) previous unsuccessful attempts of mobilization before plerixafor plus GCSF administration. Nine patients had received GCSF alone and 5 patients chemotherapy plus GCSF. Patients received GCSF for 4 consecutive days and plerixafor was administered at the evening of the forth day, 10–11 hours before the scheduled aphaeresis procedure. In case of not sufficient or suboptimal number of CD34+ cells collection the procedure was repeated for maximum of 3 days plerixafor administration (7 days of GCSF).

Results:

Mobilization with plerixafor plus GCSF and collection of adequate number of CD 34+ cells was successful in 12/14 patients. The median number of CD 34+ cells collected was 2.5×106/kg in a median of 2 (1-4) apheresis days. Two of 14 patients proceeded to a second mobilization with plerixafor plus GCSF, eventually succeeding a sufficient cell dose graft collection. In 2 sibling female donors, aged 47 and 54 years, after administration of GCSF 10μ g/kg/day for 5 consecutive days mobilization was poor and collection of a graft with an acceptable CD 34+ cell dose was not possible. Administration of plerixafor improved mobilization and eventually grafts consisting of 2.55 ×106 and 5.34×106 CD34+/kg were collected by apheresis. Patients reported a grade ≤ II according to WHO scale toxicity following plerixafor administration. Most common side effects were hyperhidrosis, facial numbness and abdominal pain. None of the two healthy donors reported any adverse side effect. Engraftment was uneventfully in predictive time according to our historical data.

Discussion:

In our experience mobilization with either cytokines alone or cytokines following chemotherapy fails in a number of otherwise eligible for transplantation patients, mostly heavily pretreated or with advanced disease. In addition a small minority of healthy donors with no identifiable risk factors for poor mobilization, also fail mobilization with GCSF. The combination of plerixafor and GCSF seems to augment peripheral blood stem cells mobilization in poor mobilizers and offers a new treatment to collect sufficient CD 34+ cells and benefit from the transplantation procedure

Disclosures:

Off Label Use: Plerixafor was used for the mobilization of two healthy sibling donors after a signed concept was optained, due to poor mobilization with GCSF and failure of addequate graft collection.