title: 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.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Scientific Direction, IRCCS, Referral Cancer Centre of Basilicata, Rionero in Vulture, PZ, Italy. p.musto@tin.it.
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Musto
authors.affiliation: Laboratory of Pre-clinical and Translational Research, IRCCS, Referral Cancer Centre of Basilicata, Rionero in Vulture, PZ, Italy. vittorio.simeon@crob.it.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Simeon
authors.affiliation: Haematology, Centro Oncologico Fiorentino, Florence, Italy. alberto_grossi@libero.it.
authors.forename: Alberto
authors.initials: A
authors.lastname: Grossi
authors.affiliation: Myeloma Unit, AOU Città della Salute e della Scienza, Turin, Italy. fgay@cittadellasalute.to.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Gay
authors.affiliation: Myeloma Unit, AOU Città della Salute e della Scienza, Turin, Italy. sarabringhen@yahoo.com.
authors.forename: Sara
authors.initials: S
authors.lastname: Bringhen
authors.affiliation: Myeloma Unit, AOU Città della Salute e della Scienza, Turin, Italy. alelarocca@hotmail.com.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Larocca
authors.affiliation: Haematology and Stem Cell Transplantation Unit, IRCCS, Referral Cancer Centre of Basilicata, Rionero in Vulture, PZ, Italy. robertoguariglia@libero.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Guariglia
authors.affiliation: Haematology and Stem Cell Transplantation Unit, IRCCS, Referral Cancer Centre of Basilicata, Rionero in Vulture, PZ, Italy. ematologia45@tele2.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pietrantuono
authors.affiliation: Haematology and Stem Cell Transplantation Unit, IRCCS, Referral Cancer Centre of Basilicata, Rionero in Vulture, PZ, Italy. oreste.villani@crob.it.
authors.forename: Oreste
authors.initials: O
authors.lastname: Villani
authors.affiliation: Haematology and Stem Cell Transplantation Unit, IRCCS, Referral Cancer Centre of Basilicata, Rionero in Vulture, PZ, Italy. giovannidarena@libero.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: D'Arena
authors.affiliation: Transfusional Medicine, IRCCS, Referral Cancer Centre of Basilicata, Rionero in Vulture, PZ, Italy. carmela.cuomo@crob.it.
authors.forename: Carmela
authors.initials: C
authors.lastname: Cuomo
authors.affiliation: Transfusional Service, S. Carlo Hospital, Potenza, Italy. clelia.musto@ospedalesancarlo.it.
authors.forename: Clelia
authors.initials: C
authors.lastname: Musto
authors.affiliation: Haematology Unit, AO Cosenza, Cosenza, Italy. fortunato_morabito@tin.it.
authors.forename: Fortunato
authors.initials: F
authors.lastname: Morabito
authors.affiliation: Haematology Unit, La Sapienza University, Rome, Italy. petrucci@bce.uniroma1.it.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Petrucci
authors.affiliation: Clinica di Ematologia, AOU Ospedali Riuniti, Ancona, Italy. m.offidani@ospedaliriuniti.marche.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Offidani
authors.affiliation: Seràgnoli Institute of Haematology, University School of Medicine, Bologna, Italy. e.zamagni@unibo.it.
authors.forename: Elena
authors.initials: E
authors.lastname: Zamagni
authors.affiliation: Seràgnoli Institute of Haematology, University School of Medicine, Bologna, Italy. paola.tacchetti2@unibo.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Tacchetti
authors.affiliation: Department of Clinical and Molecular Biomedicine, Section of Haematology, University of Catania, Catania, CT, Italy. ettaconticello@libero.it.
authors.forename: Concetta
authors.initials: C
authors.lastname: Conticello
authors.affiliation: Hemopoietic Transplant Program, AOU Policlinico Vittorio Emanuele, Catania, Italy. giuseppe.milone@gmail.com.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Milone
authors.affiliation: Myeloma Unit, AOU Città della Salute e della Scienza, Turin, Italy. appalumbo@yahoo.com.
authors.forename: Antonio
authors.initials: A
authors.lastname: Palumbo
authors.affiliation: Seràgnoli Institute of Haematology, University School of Medicine, Bologna, Italy. michele.cavo@unibo.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Cavo
authors.affiliation: Myeloma Unit, AOU Città della Salute e della Scienza, Turin, Italy. mario.boccadoro@unito.it.
authors.forename: Mario
authors.initials: M
authors.lastname: Boccadoro
mesh_terms: D000368:Aged; D000375:Aging; D018952:Antigens, CD34 / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D002452:Cell Count; D002469:Cell Separation; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D060828:Induction Chemotherapy; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy*; D012189:Retrospective Studies; D013792:Thalidomide / Q000031:analogs & derivatives / Q000627:therapeutic use; D014182:Transplantation, Autologous / Q000379:methods*; D017211:Treatment Failure
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers; D013792:Thalidomide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide; D000077269:Lenalidomide