Plerixafor Overcomes the Adverse Effect of Diabetes On Hematopoietic Progenitor Cell Mobilization

Plerixafor overcomes the adverse effect of diabetes on hematopoietic progenitor cell mobilization

Chunzhi Xia, XiaoBo Zhong, Binod Dhokal, Jonathan Thompson, Timothy Fenske, Jean Esselmann, Carolyn Keever-Taylor, Anand Padmanabhan, Parameswaran Hari

Background:

Use CXCR4 inhibitor Plerixafor for autologous hematopoietic progenitor cell (HPC) mobilization in myeloma (MM) and lymphoma has been associated with reduction of mobilization failure. However, poor mobilization (mobilopathy) still results in multiple days of collection, increased resource utilization, morbidity and overall lower numbers of HPCs. Mobilopathy is associated with exposure to some chemotherapeutic agents, older age and female sex. Ferraro et al recently postulated a diabetes-associated mobilopathy. We analyzed mobilization patterns in a retrospective cohort of 221 patients undergoing mobilization prior to autologous transplantation for MM (136) or lymphoma (84).

Methods: 

Our algorithm for mobilization: A rescue (“just in time”) plerixafor strategy was used after daily GCSF 10ug/kg x5days in those failing to develop adequate (<10 /uLCD34+HPC in peripheral blood (n=8) or failing to mobilize 1e6 CD34+HPC/kg on day 1of collection (n=34). For those predicted to be poor mobilizers based on prior myelotoxic therapy or low platelet counts, 2 strategies were used - planned  Plerixafor  after 5 days of GCSF or chemotherapy followed by GCSF for those with no insurance coverage for plerixafor.

Only 2 pts (<1%) failed to collect > 2e6 CD34+HPC/kg. Major outcomes of interest for the remaining 219 pts were: Collection of >2e6 CD34+HPC/kg on day1 and total CD 34+HPC collected over entire collection episode. Multivariate regression models were used to evaluate potential predictors of poor mobilization. Diabetes requiring drug therapy (n=32) was considered in all models.

Results:

Majority (75%) pts collected >2e6 CD34+HPC/kg on day1. Among the 32 pts with diabetes, inadequate day 1 mobilization occurred in 40% (13/32) compared to 21% (40/187) without diabetes. The use of HyperCVAD chemotherapy was associated in 50% cases with inadequate CD34+HPC on day1. In multivariate models, successful mobilization on day1 was associated with absence of diabetes (odds ratio 2.49, P=0.04) and lack of HyperCVAD exposure (odds ratio 4.14, P=0.02).  

Interestingly, although a significant number received “just in time” plerixafor, its use improved the total CD34+HPC collection significantly (odds ratio 2.98, 95% CI P=0.0038) in all pts including 12 diabetic recipients.

In multivariate analysis, lower total yield of CD34+HPC/kg was associated with increasing age (P=0.0002) and the use of conventional chemotherapy.

Conclusions:

In our analysis of an unselected cohort of pts undergoing mobilization, diabetes was an independent predictor of slower mobilization with its effects mitigated by plerixafor.