Predicting poor peripheral blood stem cell collection in patients with multiple myeloma receiving pre-transplant induction therapy with novel agents and mobilized with cyclophosphamide plus…

Predicting poor peripheral blood stem cell collection in patients with multiple myeloma receiving pre-transplant induction therapy with novel agents and mobilized with cyclophosphamide plus granulocyte-colony stimulating factor: results from a Gruppo Italiano Malattie EMatologiche dell’Adulto Multiple Myeloma Working Party study

Stem Cell Research & Therapy, April 2015

25889496

Pellegrino Musto, Vittorio Simeon, Alberto Grossi, Francesca Gay, Sara Bringhen, Alessandra Larocca, Roberto Guariglia, Giuseppe Pietrantuono, Oreste Villani, Giovanni D’Arena, Carmela Cuomo, Clelia Musto, Fortunato Morabito, Maria Teresa Petrucci, Massimo Offidani, Elena Zamagni, Paola Tacchetti, Concetta Conticello, Giuseppe Milone, Antonio Palumbo, Michele Cavo, Mario Boccadoro

A still not well defined proportion of patients with multiple myeloma (MM) and eligible for autologous stem cell transplantation (AuSCT) fails to mobilize CD34+ peripheral blood stem cells (PBSC) at all or to collect an adequate number for a safe procedure or sufficient for multiple transplants. These so-called "poor-mobilizers" are difficult to be predicted, due to marked difference across previous heterogeneous studies. We aimed to develop a method based on simple clinical parameters for predicting unsuccessful (<2 × 10(6)/kg) or sub-optimal (<5 × 10(6)/kg) collections of CD34+ PBSC in newly diagnosed MM patients eligible for AuSCT, treated with novel agents and receiving an homogeneous mobilizing therapy with cyclophosphamide and granulocyte-colony stimulating factor (G-CSF). To this purpose, 1.348 patients enrolled in five consecutive Italian clinical trials were retrospectively analysed. Age, baseline low peripheral blood cell counts, use of lenalidomide, and haematological toxicity developed during induction were taken into account as possible factors associated with poor mobilization. Overall, 280 patients (20.8%) showed either sub-optimal (167 patients, 12.4%) or unsuccessful (113 patients, 8.4%) collections. All analysed parameters negatively influenced the procedure, but only age and haematological toxicity during induction maintained their significance at multivariate analysis. Based on ordinal logistic regression model, we constructed a risk heat-map where the four parameters were pooled and weighted according to their relevance as single or combined variables. This model was predictive for different probabilities of failure, suboptimal or optimal outcomes. We found that about one fifth of newly diagnosed MM fails to collect an adequate number of PBSC. Our model, based on a large group of patients treated frontline with novel agents and receiving the most popular mobilizing approach currently employed in Europe, is applicable in individual subjects and may contribute to the early identification of "poor mobilizer" phenotypes.