Higher Percentage of CD34+ CD38- Cells Detected by Multiparameter Flow Cytometry From Leukapheresis Products Predicts Unsustained Complete Remission in Acute Myeloid Leukemia
Condition: Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Study type: Observational

Summary: 
      Over recent decades, improvements have been made in the treatment of adult acute myeloid
      leukemia (AML). This has been mainly attributed to improvements in supportive therapy and to
      intensification of treatment strategies. The introduction of a post-induction myeloablative
      regimen followed by allogeneic stem cell transplant (SCT) has reduced the relapse rate in
      younger adults. However, this procedure is limited by the availability of human leukocyte
      antigen (HLA)-identical donors and conventional SCT preparative regimens according to patient
      age. In the absence of a compatible donor, myeloablative chemotherapy followed by autologous
      peripheral blood (PB) SCT remains one treatment strategy in adult patients with AML, allowing
      35 - 50% long-term survivors. Despite several advantages of the CD34+ cell mobilization
      procedure, recent data have shown that relapse was higher and leukemia-free survival (LFS)
      shorter compared with bone marrow (BM) autografts. Higher doses of CD34+ peripheral blood
      stem cells (PBSCs) are collected to ensure engraftment and possibly reduce the incidence of
      treatment-related mortality (TRM). Although there is a threshold CD34+ cell dose below which
      engraftment is delayed in AML, the positive linear correlation of the number of CD34+ cells
      and kinetics of engraftment reaches a limit above which an increase in the number of
      progenitor cells does not provide any additional benefit. Relapse has been shown to be higher
      and survival shorter for those who receive the highest CD34+ PB doses. Although highly active
      against the leukemia bulk, intensive chemotherapy often spares the hardiest leukemia stem
      cells (LSCs) responsible for relapse. Detection of minimal residual disease (MRD) in
      autologous PBSC products may reflect inadequate in vivo purging, at least in part responsible
      for relapse. Although representing a heterogeneous cell population including both normal and
      leukemia cells, and despite that recent data have challenged the CD34+ CD38- phenotype of
      LSCs in AML, the CD34+ CD38- cell population generally remains considered enriched for LSCs.

      In this setting, MRD remaining during morphological complete remission (CR) should be
      relatively enriched in CD34+ CD38- leukemia cells, and their persistence after CR achievement
      should correlate with disease recurrence. This was investigated in a cohort of 123 patients
      with AML following apheresis procedures after CR achievement. The investigators also studied
      the impact of the infused dose of subpopulations of CD34+ PB cells on the outcome of a subset
      of 71 patients who further underwent autologous PBSCT.
    


Intervention name(s): PBSC mobilization and leukapheresis
Intervention type(s): Other
Intervention description(s): Mobilization and harvest of autologous PBSCs was scheduled during the recovery phase after the consolidation course. Granulocyte colony stimulating factor (G-CSF) (150 µg/m2/day) was given by daily subcutaneous injection from day 20 of the chemotherapy course until completion of the blood stem cell collections. PBSC collections were performed on 1 - 5 consecutive days during the hematopoietic recovery phase, as soon as the leukocyte count exceeded 2x 109/L.
Collections were performed after induction or after consolidation. In cases in which the minimum number of CD34+ cells was not collected, an additional mobilization was performed in steady state.
Harvesting was performed using continuous flow blood cell separators. Cells were stored in liquid nitrogen until use, according to standard techniques.
Observational model: Cohort
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        Patients with a newly diagnosed de novo or secondary type AML (post myelodysplastic
        syndrome MDS or therapy-related AML) and achieving first CR after induction or salvage
        therapy. Three populations of CD34+ cells were distinguished based on differential
        expression of the CD34 and CD38 antigens
      
Keywords: Acute myeloid leukemia; prognosis; stem cell harvest; autologous transplant; leukemia stem cell