Predicting Autologous Stem Cell Mobilization Failure In Hematologic Malignancies

Autologous stem cell transplantation (ASCT) after high-dose chemotherapy improves remission rates and prolongs survival in a number of hematologic malignances including multiple myeloma (MM), non-Hodgkin’s lymphoma (NHL), and Hodgkin’s lymphoma (HL).The prerequisite to ASCT is the collection of an adequate number of CD34+ cells; the minimum dose needed to ensure hematopoietic recovery is 2.0x10⁶cells/kg, but recent studies have suggested that 5.0x10⁶cells/kg is the optimal dose as it results in more rapid and sustained engraftment. An estimated 15-30% of patients fail to mobilize the required number of cells for ASCT, although the number of mobilization failures is declining due to advances in mobilization regimens. Previously identified variables for predicting mobilization failure include: advanced age, the type of chemotherapy and number of cycles administered, and prior radiotherapy.

We performed retrospective chart review of 803 consecutive patients who underwent apheresis for autologous stem cell collection at the Siteman Cancer Center from January 2008 through December 2011. Patients were considered eligible for analysis if they had a diagnosis of MM, NHL or HL and had not undergone previous stem cell collection. Univariate analysis was performed to identify predictors associated with successful collection of > 2.0x10⁶ cells/kg and > 5.0x10⁶ cells/kg. Variables analyzed were: mobilization regimen; age; gender; BMI; weight/ideal body weight; diagnosis; prior radiation; number of chemo cycles administered; alkylating agent exposure; lenalidomide exposure; blood glucose level; blood triglycerides level; glucocorticoid use at apheresis; statin use at apheresis; and history of diabetes mellitus, coronary artery disease, hypertension, or hyperlipidemia.

706 patients met the eligibility criteria for analysis. The median age was 57.9 years (range 18.5-74.6) and 58% (411) were male. 53% (373) had MM, 38% (266) had NHL, and 9% (67) had HL. 63% (444) of patients were mobilized with plerixafor and G-CSF, 17% (117) with chemotherapy and G-CSF, and 21% (145) with G-CSF alone.

After one apheresis procedure, 75% (531) of patients collected > 2.0x10⁶ cells/kg and 50% (356) collected > 5.0x10⁶ cells/kg. 42% (295) of patients underwent more than one apheresis procedure. During their mobilization, 94% (664) of patients were able to collect > 2.0x10⁶ cells/kg and 68% (480) collected > 5.0x10⁶ cells/kg.

Data was available on >99% of the population for all variables with the exceptions of number of chemo cycles administered (n= 667), blood triglyceride level (n= 358), and glucocorticoid use at apheresis (n= 660). Significant results from univariate analysis are summarized in table 1.

The most significant predictors of mobilization failure identified were mobilization regimen, diagnosis, alkylating agent exposure, and number of chemo cycles. Lenalidomide exposure was associated with a reduced risk of mobilization failure, but this is likely attributed to the reduced risk of mobilization failure for MM, as 99% (255) of patients with lenalidomide exposure had MM. Interestingly, diagnosis of hypertension was associated with a reduced risk of mobilization failure. The mobilization failure rate in the study population is 6%, which is below the expected rate found in historical studies. This is likely a result of advances in mobilization regimens as only 21% of the study population was mobilized with G-CSF alone.

Abboud: Novartis: Membership on an entity’s Board of Directors or advisory committees; Ariad: Membership on an entity’s Board of Directors or advisory committees; Alexion: Membership on an entity’s Board of Directors or advisory committees; Teva: Speakers Bureau. Schroeder:Celgene: Research Funding; Sanofi: Research Funding. Uy:Celgene: Research Funding; Sanofi: Research Funding. Vij:Celgene: Research Funding, Speakers Bureau; Onyx: Research Funding, Speakers Bureau; Millennium: Speakers Bureau; BMS: Honoraria; Lilly: Honoraria. Westervelt:Celgene: Honoraria, Research Funding. Stockerl-Goldstein:Celgene: Speakers Bureau; Millennium: Speakers Bureau.