Poor Mobilization of Peripheral Blood Stem Cells is a Risk Factor for Worse Outcome in Lymphoma Patients Undergoing Autologous Stem Cell Transplantation

Abstract

The effect of poor blood stem cells mobilization on the outcome of autologous stem cell transplantation (ASCT) has not been well studied. Our aim is to evaluate poor mobilization as a prognostic factor in lymphoma patients undergoing ASCT. We analyzed 90 consecutive patients with Hodgkin's (HD) and non-Hodgkin's lymphoma (NHL) who underwent ASCT. Poor mobilization was defined as the inability to obtain > or = 1 x 10(6) CD34+ cells/kg ideal body weight with two large volume aphereses. Patients were divided into 2 groups: group 1 = poor mobilizers, and group 2 = good mobilizers. The poor mobilizers received lower median transplant CD34+ cell dose (2 x 10(6) vs. 4.5 x 10(6)/kg for good mobilizers, P = 0.001), were more heavily pretreated (P = 0.01), and required higher number of aphereses for PBSC collection (P = 0.0006). The median progression-free survival (PFS) in groups 1 and 2 was 10 and 41 months (P = 0.04), while the median overall survival (OS) was 38 months and not reached (P = 0.02), respectively. Univariate analysis showed that > or = 3 pre-transplant treatments, CD34+ cell dose < or = 2 x 10(6), elevated LDH before transplant, and poor mobilization were significant prognostic factors for poor PFS, while only the first three were significant for worse OS. Multivariate analysis using these same four factors revealed that number of pre-transplant treatments (HR = 6.03, P = 0.001), CD34+ cell dose (HR = 0.1, P = 0.0007) were the only independent predictive factors for worse overall outcome. In conclusion, our data show that poor mobilization could indicate poor outcome in lymphoma patients undergoing ASCT, however, it is more likely to be a reflection of the heavy pre-transplant therapy and lower CD34+ cell dose re-infused in this group of patients.

Difficult stem cell mobilization despite adequate CD34+ cell dose predicts shortened progression free and overall survival after autologous HSCT for lymphoma

“…This is in accordance with two retrospective analyses strongly suggesting that lymphoma patients with poor mobilization have worse outcomes. 8,9 A third study showed no difference in event free and OS but a trend towards increased early death in the cohort of poor mobilizers. 10 Chemotherapy mobilization has been observed to yield larger numbers of CD34 þ progenitors than mobilization with G-CSF alone.…”

“…Three other studies have reported similar results, although none have been able to compare outcomes of different mobilization techniques. [8][9][10] A study from Stanford included 170 NHL patients mobilized with chemotherapy and G-CSF receiving purged autografts and reported no difference in the 3 year OS and event-free survival (EFS) between patients collecting greater or less than 2 Â 10 6 CD34 þ cells/kg. 10 Similar to our results, patients with poor mobilization had delayed engraftment and women were more likely to be poor mobilizers.…”

“…[8][9][10] To further address this, we prospectively studied patients with lymphoma planned for high dose therapy and autologous HSCT undergoing graft mobilization with G followed by chemotherapy plus G-CSF (CG). The primary end point of the study was to identify characteristics of patients who would successfully mobilize with G. Secondary end points were (1) to determine if G mobilization immediately prior impaired collections with CG mobilization and (2) to determine if transplant outcomes of OS, progression-free survival (PFS) and engraftment were different based on mobilization success.…”

Improving stem cell mobilization strategies: future directions

“…12,15 In some studies, higher stem cell doses have been associated with higher rates of survival for patients. 17,18 Other factors that affect collection efficiency and, therefore, the success of auto-HSCT include patient age, gender, exposure to previous irradiation and chemotherapy, previous mobilization attempts and disease characteristics such as the involvement of BM. [19][20][21] Unsuccessful initial stem cell mobilization leads to costly additional mobilization attempts and may prohibit auto-HSCT altogether.…”

Etoposide plus G-CSF priming compared with G-CSF alone in patients with lymphoma improves mobilization without an increased risk of secondary myelodysplasia and leukemia

“…Poor mobilization is a risk factor for worse outcome. 14 Patients mobilizing larger numbers of CD34 þ cells have improved survival following autologous transplantation for lymphoma. 15,16 VP-16 with G-CSF is an effective and useful method of mobilization in patients with lymphomas.…”