Successful Hematopoietic Stem Cells (HSC) Mobilization in Patients Who Fail Plerixafor Mobilization for Autologous Stem Cells Transplant (ASCT)
Authors: Jain Tania , Veeraputhiran Muthu , Cronin Simon , Al-Kadhimi Zaid , Abidi Muneer H. , Ayash Lois , Ratanatharathorn Voravit , Lum Lawrence G , Uberti Joseph P. , Deol Abhinav 
Published: October 2019

Abstract
Abstract 1913
Plerixafor (P) is a novel hematopoietic stem cell (HSC) mobilizing agent approved in 2008 to enhance mobilization of HSC when used in conjunction with granulocyte colony stimulating factor (G-CSF). In spite of the enhanced ability of P to mobilize HSC, 25–35% of patients (pts) fail to mobilize sufficient HSC when P is used with G-CSF. There is dearth of data on mobilization strategies which could be used after P failure
We report our experience of re-mobilizing 24 pts who failed to collect ≥2 × 106 CD34+ cells/ Kg in the first mobilization attempt despite use of P. The clinical characteristics of these 24 pts are shown in Table 1. The median age of the pts was 61 years (range, 31 –70) and 14 (58%) were males. Underlying diagnosis for consideration of autologous stem cell transplant (ASCT) was non-Hodgkin lymphoma (NHL), multiple myeloma (MM) and Hodgkin disease (HD) in 14 (58%), 9 (38%) and 1 (4%) pts, respectively. The median CD34+ cells collected during the first mobilization in these pts using either G-CSF + P (22 pts) or cyclophosphamide (CY) + G-CSF+ P (2 pts) were 0.5 ×106CD34 + cells /Kg (range 0–1.5).
Mobilization outcomes of these 24 patients are shown in Table 2. Second mobilization was attempted a median of 22 days (range, 15–106) after the first failed mobilization. The agents used were, granulocyte macrophage colony stimulating factor (GM-CSF) + G-CSF, G-CSF + P, CY + G-CSF and bone marrow harvest in 19, three, one and one pts, respectively. The median CD34+ cell dose collected with the second attempt was 1.1 ×106 CD34 + cells/Kg (range 0–7.2). The median CD34+ cell dose/ Kg collected for the 19 pts who received GM-CSF+ G-CSF and 3 pts who received G-CSF + P were 0.8 ×106 CD34 + cells/Kg (range 0–7.2) and 1.8 ×106 CD34 + cells/Kg (range, 1.4–2.2), respectively; while the two pts who underwent a bone marrow harvest and CY + G-CSF collected 0.9 and 0 × 106CD34+ cells/ Kg, respectively. The cell dose collected when compared to the first attempt was higher in 13 (54%) pts, unchanged in six (25%) pts and lower in five (21%) pts.
Third mobilization was attempted in six pts at median of 51 days (range, 34–163) after the first failed mobilization. These pts mobilized a median of 1.1 × 106 CD34+ cells/ Kg (range, 0–6.5). Three of these pts underwent a bone marrow harvest and collected 0.6, 0.7 and 1.5 ×106 CD34+ cells/ Kg. One patient each received GM-CSF + G-CSF, G-CSF + P and CY+ G-CSF and collected 6.5, 4.2 and 0 × 106CD34+ cells/ Kg, respectively. The cell dose collected when compared to the first attempt was higher in four pts (17%), unchanged in one patient (4%) and lower in one patient (4%).
Total of 18 pts (75%) collected sufficient cells to undergo ASCT and 17 pts have undergone ASCT. All pts except one received all the collected cells. The median CD34+ cell dose for those who underwent ASCT was 2.8 × 106 CD34+ cells/ Kg (range, 1.4– 6). The median days to white blood cell and platelet engraftment were12 and 16 days post ASCT, respectively. One patient who received 1.4 × 106CD34+ cells/ Kg did not engraft platelets after ASCT.
After failing mobilization with P, nine pts (38%) were able to mobilize ≥2 × 106 CD34+ cells/ Kg in a single subsequent attempt which included 7/21 pts who received GM-CSF + G-CSF and 2/4 pts who received G-CSF + P. None of the pts were able to mobilize ≥2 × 106CD34+ cells/ Kg with bone marrow harvest or CY+ G-CSF. Our experience suggests that 75% of the pts who fail primary mobilization with P can be salvaged by a subsequent mobilization with combination of G-CSF with either P or GM-CSF.
Table 1. Patient Characteristics Pt Characteristics N Percent or (Range) Median Age 61 years (31–70) Gender Male 14 58% Female 10 42% Diagnosis NHL 14 58% MM 9 38% HD 1 4% Disease Status at First Mobilization CR/VGPR 11 46% PR 9 38% Stable 3 12% Refractory 1 4% Chemo regimens prior to mobilization 1–2 15 63% >2 9 37% Radiation (XRT)/Radio immunotherapy (RIT) Prior to Mobilization XRT 2 8% RIT 1 4% Mobilization Agent (s) used in First Attempt with Plerixafor G-CSF 22 92% CY + G-CSF 2 8% Median CD34+ Cell Dose collected at first mobilization 0.5 × 106 CD34 + cells/Kg (0–1.5)
Table 2. Mobilization Outcomes Mobilization agents N Apheresis No. of Patients who collected ≥2×106 cells/kg Collected Cell Dose (×106 cells/kg) Yes No Median Range Second Attempt (N=24) GM-CSF + G-CSF 19 11 8 6 0.8 0–7.2 G-CSF+P 3 2 0 1 1.8 1.4–2.2 CY + G-CSF 1 0 1 0 0 N/A Bone Marrow Harvest 1 N/A N/A 0 0.9 N/A Third Attempt (N=6) Bone marrow Harvest 3 N/A N/A 0 0.7 0.6–1.5 GM-CSF + G-CSF 1 1 0 1 6.5 N/A CY + G-CSF 1 0 1 0 0.0 N/A G-CSF + P 1 1 0 1 4.2 N/A

Disclosures:
No relevant conflicts of interest to declare.