title: CD34+-selected versus unmanipulated autologous stem cell transplantation in multiple myeloma: impact on dendritic and immune recovery and on complications due to infection.
abstract: BACKGROUND
  Large-scale CD34+ enrichment has been demonstrated a safe method in autologous transplantation for multiple myeloma. However, the high CD34+ enrichment and the consequent plasma cell purging result in concomitant T-cell and dendritic-cell (DC) depletion, theoretically increasing the risk of life-threatening infections.
  
  
  METHODS
  We evaluated immunological and dendritic reconstitution in 72 myeloma patients who had undergone CD34+-selected (n = 45) and unmanipulated (n = 27) stem cell transplant, and its correlation with infections.
  
  
  RESULTS
  Haematological recovery occurred promptly in all patients. Only a slight delay in platelet recovery to >50 x 10(9)/l was observed in patients receiving CD34+-enriched graft. Natural killer (NK) cell count recovered in all patients within 2 months and B-cell count had recovered by 6 months post-transplant in both groups. CD3 cells remained lower than normal in both groups. CD8 cells increased above the normal level, reaching a peak at day 90, and lowered to normal level within 1 year post-transplant. CD4 lymphocytes remained <50% of normal, especially in selected patients. In both groups, both DC1 and DC2 counts were already significantly lower than in normal individuals before conditioning therapy. Pre-conditioning levels of DC1 were reached in unmanipulated patients at day 30 and became normal at 6 months. In selected patients, DC1 pre-transplant level was observed at day 60 and was maintained thereafter. DC2 recovery showed a similar trend. In unselected patients, DC2 count increased to pre-conditioning level at haematological recovery and was normal after 1 year. In selected transplants, DC2 increased more slowly than DC1 in the same patients: pre-transplant level was detected at day 90 but was still significantly lower than normal 1 year after transplant. The incidence of infection was similar in both groups. Sepsis had Gram+ aetiology in the majority of cases. After engraftment only viral infections were recorded, mostly due to herpes reactivation, with no difference between groups.
  
  
  CONCLUSIONS
  In spite of a delay in immune recovery, CD34 enrichment is not associated with a significant increase of complications due to infection. Relatively fast NK cell recovery to pre-transplant levels and the presence of functionally efficient DCs can justify the low incidence of infections.
authors.affiliation: Division of Haematology, Bone Marrow Transplant Unit, Department of Medical and Morphological Research, University Hospital, Udine, Italy. daniela.damiani@drmm.uniud.it
authors.forename: D
authors.initials: D
authors.lastname: Damiani
authors.forename: R
authors.initials: R
authors.lastname: Stocchi
authors.forename: P
authors.initials: P
authors.lastname: Masolini
authors.forename: A
authors.initials: A
authors.lastname: Michelutti
authors.forename: A
authors.initials: A
authors.lastname: Geromin
authors.forename: A
authors.initials: A
authors.lastname: Sperotto
authors.forename: C
authors.initials: C
authors.lastname: Skert
authors.forename: M
authors.initials: M
authors.lastname: Michieli
authors.forename: M
authors.initials: M
authors.lastname: Baccarani
authors.forename: R
authors.initials: R
authors.lastname: Fanin
mesh_terms: D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000276:immunology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D018189:Immunomagnetic Separation; D007239:Infections / Q000209:etiology* / Q000276:immunology; D007694:Killer Cells, Natural / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology* / Q000628:therapy*; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects; D012307:Risk Factors; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D018952:Antigens, CD34; D016179:Granulocyte Colony-Stimulating Factor