Clinical trial NCT02842112: Higher Percentage of CD34+ CD38- Cells Detected by Multiparameter Flow Cytometry From Leukapheresis Products Predicts Unsustained Complete Remission in Acute Myeloid Leukemia
Official title: Higher Percentage of CD34+ CD38- Cells Detected by Multiparameter Flow Cytometry From Leukapheresis Products Predicts Unsustained Complete Remission in Acute Myeloid Leukemia
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acute Myeloid Leukemia
Keywords: Acute myeloid leukemia
prognosis
stem cell harvest
autologous transplant
leukemia stem cell
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2016-07-22
Enrollment: 123
Sex: ALL
Minimum age (years): 25
Maximum age (years): 72
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
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

Brief 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.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* With a newly diagnosed de novo or secondary type AML (post myelodysplastic syndrome (MDS) or therapy-related AML)
* Patients achieving first CR after induction or salvage therapy

Exclusion Criteria:

* Patients with acute promyelocytic leukemia (APL)
* Concomitant uncontrolled infection, organ dysfunction or medical disease
* left ventricular ejection fraction (LVEF) \< 45% as assessed by echocardiography

Primary outcomes:
measure: Event-free survival (EFS)
timeFrame: During the study (1 year)
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: During the study (1 year)
Other outcomes:
Locations:
city: Pierre-Bénite
country: France
facility: Hospices Civils de Lyon - Centre Hospitalier Lyon Sud, 165 Chemin du Grand Revoyet
Study officials:
affiliation: Hospices Civils de Lyon - Centre Hospitalier Lyon Sud
name: Xavier THOMAS, MD-PhD
role: PRINCIPAL_INVESTIGATOR
References: