Impact of Disease and Mobilizing Agents on Initial and Remobilization Failure.
Authors: DiPersio John F. , Smith Angela , Sempek Dianne , Baker Albert , Jiang Steven , Vij Ravi , Cashen Amanda , Westervelt Peter 
Published: October 2019

Background: High-dose chemotherapy with autologous stem cell transplantation (ASCT) is a widely used treatment strategy in lymphoma and myeloma; however, no standard approach for the mobilization of peripheral hematologic stem and progenitor cells (HSPCs) has been established. Levels of circulating CD34+ cells, a surrogate marker for mobilization efficiency, vary widely between pts, and may be influenced by disease state, prior therapy, and/or mobilization regimen.

Methods: The Washington University (St. Louis, MO) transplantation database includes clinical parameters from 407 multiple myeloma (MM), 562 non-Hodgkin’s Lymphoma (NHL), and 164 Hodgkin’s disease (HD) pts who received an ASCT between 1995 and 2006. A retrospective analysis of this large (1133 pts) population was conducted to determine factors associated with mobilization efficiency. Mobilization failure was defined as collection of < 2 × 10^6 CD34+ cells/kg within 5 apheresis days. Statistical analysis included analysis of variance (ANOVA) with Scheffe Test to determine differences in mobilization between the various mobilization regimens (G-CSF, G-CSF/chemotherapy, G-/GM-CSF, G-CSF/AMD3100).

Results: All pts were included in the analysis; 87% received G-CSF alone as the initial mobilization regimen. Mobilization failure rates are summarized in Table 1. NHL and HD pts had an approx. 4-fold higher failure rate than MM pts. The combination of G-CSF with chemotherapy increased the median CD34+ yield compared to G-CSF alone, although no obvious impact on the failure rate was noted in this relatively small group of pts. Remobilization was associated with high failure rates in NHL (79.2%), HD (77.1%), and MM (73.3%). Pooled collections were <2 × 10^6 CD34+/kg in 33.6%, 37.1%, and 36.7% of failed mobilizers, respectively. ANOVA analysis indicated a significant difference in outcome based on remobilization regimen. A post hoc comparison using the Scheffe Test determined that G-CSF mobilization failures remobilized with G-CSF plus AMD3100 collected significantly more CD34+ cells than G-CSF-failures remobilized with either G-CSF, G/GM-CSF or G-CSF/chemo (1-way ANOVA: F(3, 233) = 27.878, F0.5(3, 233).05 = 2.643, p < .0001). The compared groups did not significantly differ in initial mobilization efficiency with G-CSF (as determined by ANOVA and Scheffe Test).

Conclusions: The mobilization failure rate is substantially higher in NHL and HD pts than MM pts. Pts who fail initial mobilization are highly likely to fail a 2nd mobilization, regardless of disease state. As the combination of chemotherapy to G-CSF may not be sufficient to reduce failure rates, alternative mobilization strategies are needed to improve HSPC collection, particularly in NHL/HD pts and failed mobilizers.

First mobilization failure rates (< 2×10^6 CD34+/kg) Mobilization regimen N Failures Median yield (×10^6) 95% C.I (×10^6) * Incl. pts mobilized w. alternative regimens NHL G-CSF 471 26.5% 2.89 2.76–3.04 G-CSF/Chemo 35 22.9% 4.68 2.8–8.53 All* 564 28.7% HD G-CSF 130 26.2% 3.01 2.75–3.37 G-CSF/Chemo 12 16.7% 5.38 2.35–9.52 All* 165 24.8% MM G-CSF 386 6.5% 4.62 4.16–4.98 G-CSF/Chemo 17 5.9% 8.52 4.46–16.3 All* 409 6.6%