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CD34+-selected versus unmanipulated autologous stem cell transplantation in multiple myeloma: impact on dendritic and immune recovery and on complications due to infection.

AbstractBACKGROUND:
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.
PATIENTS AND 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.
DISCUSSION:
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.
AuthorsD Damiani, R Stocchi, P Masolini, A Michelutti, A Geromin, A Sperotto, C Skert, M Michieli, M Baccarani, R Fanin
JournalAnnals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 14 Issue 3 Pg. 475-80 (Mar 2003) ISSN: 0923-7534 [Print] England
PMID12598356 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antigens, CD34
  • Granulocyte Colony-Stimulating Factor
Topics
  • Adult
  • Aged
  • Antigens, CD34 (immunology)
  • Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
  • Dendritic Cells (immunology)
  • Female
  • Granulocyte Colony-Stimulating Factor (administration & dosage)
  • Humans
  • Immunomagnetic Separation
  • Infections (etiology, immunology)
  • Killer Cells, Natural (physiology)
  • Male
  • Middle Aged
  • Multiple Myeloma (immunology, therapy)
  • Peripheral Blood Stem Cell Transplantation (adverse effects)
  • Risk Factors
  • T-Lymphocytes (immunology)

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