Use of Plerixafor in Predicted and Proven Poor Mobilizer (according to GITMO criteria). Experience of Policlinico Universitario Tor Vergata

Autologous stem cell transplantation (ASCT) of PBSCs has become a widely applied treatment for Multiple Mieloma (MM), non- Hodgking's lymphoma (NHL) and Hodgking's lymphoma (HL). Successful engraftment correlates with the number of CD34 hemopoietic progenitors cells infused. However, a part of MM or lymphoma patients (5% to 40%) fail to mobilize adequate numbers of PBSCs and thus cannot undergo to ASCT. The success of PBSCs mobilization is usually assessed by the total number of CD34+ stem cells collected, with a cutoff of 2.0–2.5 ×10⁶ CD34+ cells/kg recipient body weight being considered as a minimum requirement for transplant. Poor mobilization of PBSCs is a major limitation to ASCT. Recently GITMO Working Group worked to define operational criteria for the identification/prediction of the poor mobilizer (PM) patients (Olivieri et al. 2011). Plerixafor, a CXCR4 chemochine antagonist, has been showed to improve significantly PBSC mobilization in PM patients. We present our experience using Plerixafor in PM patients classified according to GITMO criteria.

Between September 2009 and June 2012, a total of 17 patients (9F-8M) were enrolled. The diagnosis were: 10 MM (5F-5M), 1HL (1M), 6 NHL (4F-2M). The median age was 57 (range 15–66). 7 patients (3MM, 4NHL) were defined “Proven PM” and 10 patients (7MM, 2NHL, 1HL) “Predicted PM” according to GITMO criteria. The mobilization protocol included G-CSF, administered at a dose of 10μg/kg daily on 4 consecutive days. In the evening of the fourth day, patients received subcutaneous plerixafor at a dose of 0,24 mg/kg. Apheresis was initiated on the fifth day, 10–12 h after plerixafor and 1 h after G-CSF administration. Apheresis and daily administration of G-CSF and plerixafor continued until the patient collected enough CD34+ cells for auto- HSCT (> 2 ×10⁶/kg; max 7 plerixafor injections if required). PBSC collection was initiated if peripheral CD34+ cells count was >10μl. A successful mobilization was defined as a total yeld of > 2×10⁶/kg.

13 patients (76,5%) collected the minimum number of CD34 cells > 2×10⁶/kg. The diagnosis were: 8MM, 1HL,1 NHL. 7 patients (2NHL; 4 MM; 1 LH; 7 predicted) were able to collect > 5×10⁶/Kg. Only 4 patients (3 MM; 1 LNH; 4 proven) failed the mobilization because the numbers of cells CD34 were < 10μL and these patients did not undergo to apheresis procedures. The collection target of 2×10⁶/Kg was reached in a median of 2 apheresis session (range 1–3). The technical characteristics of the procedures were (median value): blood volume processed 12 L (range 9–14), total CD34+/Kg collected 3,06 × 10⁶(range 2,21-8,62), procedure efficiency 47,5% (range 35,3–79), duration of the procedure 261 minutes (range 210–309). Plerixafor was well tolerated and mild side effects were: reactions in the injection site, gastrointestinal disturbs, muscle pain. During administration of plerixafor we did not observe any significant laboratory abnormalities of liver or renal function.

Unsuccessful mobilization represents an important limitation to ASCT in lymphoma and MM. In our experience plerixafor allowed to collect an appropriate amount of CD34 also in patients defined “proven PM” significantly reducing the percentage of patients that could not undergo ASCT (target value obtained in 43% of “proven PM”). Confirming the recent literature plerixafor is well tolerated with minimal side effects. We retrospectively applied GITMO criteria for PM patients and our experience, although limited, confirm that the use of a correct definition of PM allows the appropriate use of new mobilizing agents like plerixafor increasing significantly the therapeutic options also in patients who had no possibilities to receive an ASCT with the traditional mobilizing therapy.

No relevant conflicts of interest to declare.