Effect of Mobilization Method on Immune Reconstitution Post High Dose Chemotherapy and Autologous Stem Cell Transplantation

Introduction: Plerixafor is a reversible CXCR4 antagonist that has been approved by the food and drug administration for autologous hematopoietic stem cell mobilization in patients with multiple myeloma and non-hodgkin’s lymphoma. Patients mobilized with Plerixafor were shown to have a higher proportion of primitive stem cells (CD34+/CD133+/CD38-), CD4+ T cells and Natural killer cells (CD3-/CD16+/CD56+) in the graft composition when compared to patients mobilized with chemotherapy plus G-CSF alone .We investigated the effect of Plerixafor on immune reconstitution at thirty and sixty days post autologous stem cell transplantation.

Methods: Patients eligible for autologous stem cell transplantation were enrolled on a single arm prospective immune reconstitution trial. A complete blood count, differential and lymphocyte flow cytometry panel (T cell, NK cell and B cell markers) was checked on Days 30 and 60 post autologous transplantation. Stem cell mobilization was carried per our institutional standards. All patients received subcutaneous G-CSF at a dose of 10 µg per kilogram body weight for four consecutive days. On Day4, patient with a peripheral CD34 count of ≤20/µl received plerixafor 0.24mg/kg. Collection was started on day 5 and continued till collection goal was reached or patient failed to get the minimal cell dose after 4 consecutive days of pheresis.

 Results: 49 patients were enrolled during the period from September 2010 till May 2012. Median age at time of transplantation was 54 years (range 21;72 years).  35 patients had multiple myeloma and 14 had non-Hodgkin’s lymphoma. 16 patients received GCSF alone (group A) and 33 had plerixafor plus GCSF (group B) for mobilization. All patients achieved the minimum target of CD34 collection. The mean number of collection days was 1.9 and 1.4 days (p=0.05) with a total collection dose of 7.76 and 7.61 CD34 x10⁶/Kg for groups A and B respectively. The percentage proportion of CD34 in the aphaeresis product was 0.73% and 0.75% (p=0.9) for group A and B. Total infused CD34 dose was similar in both groups (4.88 and 4.56 CD34x10⁶/kg) with  time to engraftment of 11.68 vs 11.69 days for neutrophils and  20.62 vs 21.39 for platelets in groups A and B respectively. There was no difference between day 30 absolute lymphocyte count (1.09 vs 1.44 x10³/mm³ p=0.18); Absolute NK cell (0.31 vs 0.35 x10³/µl; p=0.51); absolute T cell count (0.71 vs 0.96 x10³/µl  p=0.33) and absolute neutrophil  count (2.98 vs 2.63 x10³/mm³ p=0.37).  The cell count recovery was also not significantly different when analyzed per disease (myeloma or non-Hodgkin’s lymphoma) and at day 60.

Conclusion: Our study shows that patient mobilized with plerixafor and G-CSF have similar immune reconstitution at 30 and 60 days post autologous transplantation compared to patients  mobilized with G-CSF alone.