As mentioned, the definition of “poor mobilizer” varies according to different parameters analyzed to evaluate PBSC mobilization: peak of CD34+
cells in PB, fold-increase of circulating CD34+
cells collected, number of candidate patients undergoing ASCT. As a consequence, different criteria have been proposed to define a successful PBSC mobilization and the adequate apheresis yield, but these data are difficult to analyze and compare to each other.3
The extensive review of predictive factors for poor mobilization is beyond the scope of this article (see 3
). However, it should be kept in mind that in addition to baseline parameters, during- and post-mobilization factors have been poorly exploited due to the lack, so far, of rescue strategies. For instance, febrile neutropenia is one major complication after administration of mobilizing chemotherapy.20
The release of pro-inflammatory cytokines may negatively affect stem cell proliferation and mobilization. Furthermore, genetic factors as well as polymorphisms in cytokine gene receptors are believed to be responsible for the great variability in mobilization responses in allogeneic donors.22
Need for supportive care such as antibiotics for febrile neutropenia and blood product support is associated with mobilization failure in patients with NHL.23
Moreover, in patients receiving chemomobilization, slow leukocyte and platelet recovery as well as anemia indicate poor marrow function. However, type and dose of chemotherapy may influence the risk of mobilization failure as severe thrombocytopenia induced by alkylating agents administered during mobilization can be a risk factor for mobilization failure while high-dose cytarabine mobilization regimen often induces severe thrombocytopenia and neutropenia without negatively affecting stem cell mobilization.24
Other factors predicting mobilization failure are: delayed or anticipated timing of apheresis (due to insufficient circulating stem cells monitoring) and/or small volume of processed blood which may affect PBSC collection even in patients showing a satisfactory peak of CD34+ cells in the PB.
For these reasons, a working group promoted by GITMO (Italian Group for Stem Cell Transplantation) proposed the definition of “poor mobilizer” identifying “proven poor mobilizer” and “predicted poor mobilizer”.25
In order to develop criteria for the definition of “poor mobilizer”, the working group used the analytic hierarchy process (AHP) which had been developed to establish priorities and to make the best decision when both the quantitative and qualitative aspects of a decision need to be considered and a poor information base is available. AHP is a multistep process that includes four major phases: 1) defining the goal; 2) decomposing the problem and identifying critical issues; 3) categorizing/framing the main criteria; 4) defining a hierarchy of the criteria.
GITMO panel selected two conceptual criteria to identify the “proven poor mobilizer”: the peak of circulating CD34+
cells during mobilization and the absolute number of harvested CD34+
cells. All participants agreed that pre-apheresis CD34+
count in PB is the best predictor of CD34+
cells in the aphaeresis products11
and, operationally, considered a peak of CD34+
cells >20 μl in PB, as a reliable indicator of a satisfactory mobilization ability. Moreover, the GITMO panel identified 2.0×106
cells/kg as the minimum safe dose for ensuring rapid neutrophil and platelet recovery both in lymphoma and in MM patients to be achieved with a maximum number of 3 aphereses.11
These parameters and indicators applied to both chemomobilization and G-CSF alone strategies although the timing of CD34+
cells peak and doses of G-CSF are different and should be considered.25
Furthermore, GITMO panel selected 3 major and 5 minor criteria to identify the “predicted poor mobilizer”.25
The most important criteria were felt to be: previous cytotoxic chemotherapy, irradiation on BM bearing bones and failure of previous mobilization attempt.
Among the other factors associated with unsuccessful mobilization, GITMO panel selected advanced phase disease (i.e. at least 2 prior cytotoxic lines), refractory disease, extensive BM involvement at mobilization, BM cellularity <30% at mobilization and age >65 years as minor criteria. The proposed definitions should be validated in prospective clinical studies.
In conclusion, poor mobilization of PBSCs is a major limitation for patients eligible for ASCT. The availability of new drugs, aimed at optimizing PBSC mobilization, requires a stringent definition of “poor mobilization”. In this view, GITMO panel recommended that patients previously failing at least one mobilization attempt should be candidate for new mobilizing strategies. In addition, the use of standard criteria for identifying both the “proven and the predicted poor mobilizer” before planning the use of new mobilizing agents was recommended. To this end, the GITMO working group tried to define simple, but stringent operational criteria for the identification/prediction of “poor mobilizer” in the setting of lymphoproliferative diseases.