Immunoevasive Tactics Employed by Myeloid Malignancy After Allogeneic Stem Cell Transplantation

NCT03964922 | Unknown DMC

• 1 other identifier: 2019-A00842-55
• Study Type: interventional
• Target: 104
• Locations: 0 countries
• Sites: N/A

Brief Summary

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is still the only treatment available to cure acute myeloid leukemia and high risk myelodysplasia. Allo-HSCT has an anti-tumor effect (called the graft versus leukemia effect= GVL) mediated by donor lymphocytes. This GVL effect is often associated with graft-versus-host disease (GVHD). Several studies have shown that the relapse incidence is lower in patients developing chronic GVHD. These studies confirm the impact of donor immune system on leukemic residual cells. In fact, the relapse incidence increased in patients with no sign of GVHD. The investigators assume that leukemic cells probably use mechanisms to inhibit the allogeneic response. These escape mechanisms to immunosurveillance have been described in other malignancies. Out of context of the allo-HSCT, in acute myeloid leukemias and myelodysplasia, correlations between the severity of the disease and the presence of regulatory T cells (Tregs) or exhausted T cells (PD1 positive) in the bone marrow and in the blood of patients were described at the time of diagnosis or relapse. Myeloid Derived Suppressive Cells (MDSCs) have been described as capable of inducing Tregs and exhausted T cells in the tumor microenvironment.The investigators want to evaluate the role of myeloid suppressive cells in bone marrow after allo HSCT. They hypothesize that their presence in bone marrow and / or blood recipient is correlated to the relapse incidence.

Conditions

Relapse Leukemia; Allogeneic Stem Cell Transplantation; Immune Evasion, Tumor

Outcome Measures

Primary Outcomes (1)

• Myeloid suppressive cells and relapse incidence

  To investigate the relationship between the percentage of myeloid derived suppressive cells (MDSCs) in total leukocytes in peripheral blood and the relapse incidence after allogeneic stem cell transplantation. The patients will be grouped according to median MDSC frequency values. Relapse incidence will be compared across the two groups (low and high frequency of MDSC).

  2 years

Secondary Outcomes (4)

• Myeloid suppressive cells and the medullar microenvironment (regulatory T cells and mesenchymal stem cells)

  2 years

• percentage of myeloid suppressive cells

  2 years

• incidence of acute GVHD

  2 years

• incidence of chronic GVHD

  2 years

Study Arms (1)

immune escape mecanims

EXPERIMENTAL

Cohort study with a representative sample of patients

Biological: blood sample; Biological: bone marrow sample

Interventions

blood sample BIOLOGICAL

20 ml at inclusion, and 20ml at 1, 3, 6 and 12 months after allo HSCT

immune escape mecanims

bone marrow sample BIOLOGICAL

3 ml at inclusion, and 3 ml at 1, 3, 6 and 12 months after allo HSCT

immune escape mecanims

Eligibility Criteria

• Age: 18 Years - 71 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with acute myeloid leukemia in complete cytological remission with intermediate or high risk prognosis according to ELN 2017
• Patients with myelodysplasia according to the WHO 2016 definition, with IPSS ≥1.5 and disease status is : stable or in partial response or complete response according to IWG 2006.
• Patients with indication of first allo-HSCT with a matched related or unrelated donor
• Patients receiving non-myeloablative or reduced toxicity conditioning
• Patients affiliated to a social security scheme
• Patients who have received a complete information on the organization of the research and signed his informed consent

You may not qualify if:

• Patients with an alternative donor (HLA 5/10 or unit cord blood)
• Patients with another active cancer or a history of cancer diagnosed in the previous 5 years
• Patients referred to in Articles L. 1121-5, L. 1121-7 and L1121-8 of the Public Health Code.

Sponsors & Collaborators

• Central Hospital, Nancy, France: lead

Related Publications (4)

• D'Aveni M, Rossignol J, Coman T, Sivakumaran S, Henderson S, Manzo T, Santos e Sousa P, Bruneau J, Fouquet G, Zavala F, Alegria-Prevot O, Garfa-Traore M, Suarez F, Trebeden-Negre H, Mohty M, Bennett CL, Chakraverty R, Hermine O, Rubio MT. G-CSF mobilizes CD34+ regulatory monocytes that inhibit graft-versus-host disease. Sci Transl Med. 2015 Apr 1;7(281):281ra42. doi: 10.1126/scitranslmed.3010435.

  PMID: 25834108 BACKGROUND

• Kumar B, Garcia M, Weng L, Jung X, Murakami JL, Hu X, McDonald T, Lin A, Kumar AR, DiGiusto DL, Stein AS, Pullarkat VA, Hui SK, Carlesso N, Kuo YH, Bhatia R, Marcucci G, Chen CC. Acute myeloid leukemia transforms the bone marrow niche into a leukemia-permissive microenvironment through exosome secretion. Leukemia. 2018 Mar;32(3):575-587. doi: 10.1038/leu.2017.259. Epub 2017 Aug 17.

  PMID: 28816238 BACKGROUND

• Nadal E, Garin M, Kaeda J, Apperley J, Lechler R, Dazzi F. Increased frequencies of CD4(+)CD25(high) T(regs) correlate with disease relapse after allogeneic stem cell transplantation for chronic myeloid leukemia. Leukemia. 2007 Mar;21(3):472-9. doi: 10.1038/sj.leu.2404522. Epub 2007 Jan 11.

  PMID: 17215853 BACKGROUND

• Kong Y, Zhang J, Claxton DF, Ehmann WC, Rybka WB, Zhu L, Zeng H, Schell TD, Zheng H. PD-1(hi)TIM-3(+) T cells associate with and predict leukemia relapse in AML patients post allogeneic stem cell transplantation. Blood Cancer J. 2015 Jul 31;5(7):e330. doi: 10.1038/bcj.2015.58.

  PMID: 26230954 BACKGROUND

MeSH Terms

Conditions

Neoplasms

Interventions

Blood Specimen Collection

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Central Study Contacts

Maud D'AVENI, MD

CONTACT

+33383153289; m.daveni-piney@chru-nancy.fr

Marie-Therese RUBIO, MD

CONTACT

+33383153282; m.rubio@chru-nancy.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2019
• First Posted: May 28, 2019
• Study Start: September 1, 2019
• Primary Completion: June 30, 2022
• Study Completion: November 1, 2022
• Last Updated: May 28, 2019

Record last verified: 2019-05