G-CSF Primed Autologous Marrow Harvest and Transplantation in Cytapheresis “Mobilization Failure” Patients: A Descriptive Analysis

Abstract

Fifteen cancer patients, deemed blood HSC “mobilization failures” due to CD34+cell yields of < 0.5×10⁶/kg from two consecutive daily cytaphereses, underwent G-CSF primed autologous bone marrow harvest in an attempt to obtain adequate hematopoietic support for subsequent autotransplantation. CD34 + cell yields from the primed marrow harvest were variable; however, some patients had > 5-fold increases in CD34 + cell yields in the marrow compared to cytapheresis, and 4 patients had CD34 + cell yields of > 1.0 (i.e., 1.2, 1.44, 1.61 and 2.45)×10⁶/kg from the primed marrow harvest. None of the five patients previously exposed to stem cell toxins or fludarabine achieved > 0.85×10⁶/kg CD34 +cells with the primed marrow harvest. A significant difference was noted between G-CSF primed blood and marrow for CD34 + cells but not for GM-CFU (p = 0.011 and p = 0.135, respectively, paired t-test).

All evaluable patients engrafted; a median ANC > 0.5×10⁹/L recovery was achieved on D + 12 (range+9 to+17) in 12 of 13 evaluable patients—one died on D + 9 without recovery. The last day of platelet transfusion occurred at a median D + 13 (range + 8 to > + 66); only one patient remained platelet transfusion-dependent beyond D + 34. As anticipated, patients with higher numbers of CD34 + cells transplanted had somewhat more rapid recoveries.

Although stem cell damage is obviously a key factor in mobilization failure patients, these findings raise the possibility that poor mobilization, at least in some patients, results from a mechanism other than, or in addition to, simple stem cell damage. Moreover, they raise the issue of the minimum number of marrow CD34 +—or more arguably other—cells needed for adequate short- and long-term reconstitution. The role of G-CSF in this situation, especially regarding dose and/or schedule, is intriguing but remains to be clarified.

G-CSF primed marrow harvest is a potential option in certain poor mobilizers but, as fully expected, is frequently inadequate. Whether such is preferable to “steady-state” marrow harvest, continued or repeated G-CSF primed cytapheresis (with or without chemotherapy), or primed marrow with G-CSF in other schedules—or with other cytokines—is unclear and will be the subject of further study.

Keywords:

• G-CSF priming
• autologous
• transplantation
• blood
• marrow
• stem cells