Poor Mobilization of Hematopoietic Stem Cells—Definitions, Incidence, Risk Factors, and Impact on Outcome of Autologous Transplantation

Abstract

As more efficient agents for stem cell mobilization are being developed, there is an urgent need to define which patient population might benefit from these novel drugs. For a precise and prospective definition of "poor mobilization" (PM), we have analyzed the efficiency of mobilization in patients intended to receive autologous transplantation at our center in the past 6 years. Between January 2003, and December 2008, 840 patients with the following diagnoses were scheduled to undergo leukapheresis: multiple myeloma (MM, n = 602) and non-Hodgkin lymphoma (NHL, n= 238). Most patients mobilized readily: close to 85% of the patients had a level of 20/microL to >500/microL of CD34(+) cells at the peak of stimulation. Of the 840 patients, 129 (15.3%) were considered to be PMs, defined as patients who had a peak concentration of <20/microL of CD34(+) cells upon stimulation with granulocyte-colony stimulating factor (G-CSF) subsequent to induction chemotherapy appropriate for the respective disease. Among them, 38 (4.5%) patients had CD34(+) levels between 11 and 19/microL at maximum stimulation, defined as "borderline" PM, 49 (5.8%) patients had CD34(+) levels between 6 and 10/microL, defined as "relative" PM, and 42 patients (5%) with levels of <5/microL, defined as "absolute" PM. There was no difference in the incidence of PM between patients with MM versus those with NHL. Sex, age, body weight (b.w.) and previous irradiation therapy did not make any significant difference. Only the total number of cycles of previous chemotherapy (P = .0034), and previous treatment with melphalan (Mel; P = .0078) had a significant impact on the ability to mobilize. For the good mobilizers, the median time to recovery of the white blood cells (WBCs) to 1.0/nL or more was 13 days with a range of 7 to 22 days, whereas for the PM group it was 14 days with a range of 8 to 37 days. This difference was statistically not significant. The median time to recovery of the platelets counts to an unmaintained level of >20/nL was 11 days with a range of 6 to 17 days for the good mobilizers, whereas for the PM it was 11 days with a range of 7 to 32 days. Again, this difference was not significant. The majority of the patients today intended for autologous transplantations were able to mobilize readily. As long as > or =2.0 x 10(6) of CD34(+) cells/kg b.w. have been collected, PM was not associated with inferior engraftment.

Plerixafor in patients with lymphoma and multiple myeloma: effectiveness in cases with very low circulating CD34+ cell levels and preemptive intervention vs remobilization

“…[7][8][9][10][11][12][13][14][15][16] However, the value of patient characteristics and prior treatment clinical factors to successfully score and accurately predict the risk of poor mobilization is controversial, and recent studies do suggest that they are inaccurate predictors and should not be used to identify candidates for optimized strategies to prevent mobilization failure. 17,18 At present, the measurement of preapheresis levels of CD34+ cells in PB 7,[19][20][21][22] is the most robust and recommended indicator to identify potential poor mobilizers and efficiently rescue them with novel mobilization strategies, including the use of plerixafor.…”

“…[7][8][9][10][11][12][13][14][15][16] However, the value of patient characteristics and prior treatment clinical factors to successfully score and accurately predict the risk of poor mobilization is controversial, and recent studies do suggest that they are inaccurate predictors and should not be used to identify candidates for optimized strategies to prevent mobilization failure. 17,18 At present, the measurement of preapheresis levels of CD34+ cells in PB 7,[19][20][21][22] is the most robust and recommended indicator to identify potential poor mobilizers and efficiently rescue them with novel mobilization strategies, including the use of plerixafor. 23,24 Plerixafor in combination with steady-state G-CSF mobilization in patients with lymphoma and multiple myeloma has been shown very reproducibly to increase PBSC yields and the number of patients yielding target cell doses, both in first-line mobilization [25][26][27][28] and as remobilization strategy in patients who failed prior mobilization attempts, including those with a variety of high-risk clinical factors.…”

“…4,5 Hence, inadequate PBSC mobilization may lead to treatment delays and failures, potentially rendering some patients ineligible for the planned HCT. 6,7 Therefore, the need for management strategies that identify patients at risk in a timely manner and optimize their treatment algorithms to prevent mobilization failure is imperative.…”

Plerixafor with and without chemotherapy in poor mobilizers: results from the German compassionate use program

“…Although poor mobilizers are difficult to identify in advance, the following risk factors for poor mobilization are accepted in general: age 460 years, progressive disease, severe BM involvement, previous chemo-and/or radiotherapy, type of chemotherapy, previously failed mobilization attempts, platelet counts o100 Â 10 9 /L before apheresis and the occurrence of neutropenic fever during mobilization. 3,[9][10][11][12][13] The bicyclam plerixafor (formerly known as AMD3100) was found to interrupt the interaction between the chemokine stroma-derived factor-1 alpha, which is constitutively expressed on BM stromal cells, 14,15 and its cognate receptor CXCR4 on CD34 þ HSC, 16 resulting in a rapid increase of PBSC. 12 Initially designed as a CXCR4 entry-inhibitor for the treatment of HIV-1 infections, 17 the transient leukocytosis monitored in healthy individuals, as well as in HIV positive patients, led to a change in its use.…”

Plerixafor and granulocyte colony-stimulating factor for first-line steady-state autologous peripheral blood stem cell mobilization in lymphoma and multiple myeloma: results of the prospective PREDICT trial

“…5 The target number of CD34 + cells utilized for a single autologous hematopoietic stem cell transplant may vary between sites, but it has been suggested to be ≥5×10 6 CD34 + cells/kg recipient body weight with 2×10 6 CD34 + cells/kg being the minimum number required to guarantee successful engraftment. 6,7 The number of circulating hematopoietic stem cells increases during the recovery phase of chemotherapy-induced myelosuppression, as well as after the administration of various cytokines and hematopoietic growth factors including granulocyte colony-stimulating factor (G-CSF). 2,8,9 Over the last two decades, clinical practices have taken advantage of these observations.…”