EVADE: Immunoevasive Tactics Employed by Myeloid Malignancy After Allogeneic Stem Cell Transplantation
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: immune escape mecanims Cohort study with a representative sample of patients |
Biological: blood sample
20 ml at inclusion, and 20ml at 1, 3, 6 and 12 months after allo HSCT
Biological: bone marrow sample
3 ml at inclusion, and 3 ml at 1, 3, 6 and 12 months after allo HSCT
|
Outcome Measures
Primary Outcome Measures
- Myeloid suppressive cells and relapse incidence [2 years]
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).
Secondary Outcome Measures
- Myeloid suppressive cells and the medullar microenvironment (regulatory T cells and mesenchymal stem cells) [2 years]
To correlate levels of bone marrow MDSC and regulatory T cells (Tregs) and exhausted T cells and the quality of mesenchymal cells in bone marrow.
- percentage of myeloid suppressive cells [2 years]
- incidence of acute GVHD [2 years]
- incidence of chronic GVHD [2 years]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patients with acute myeloid leukemia in complete cytological remission with intermediate or high risk prognosis according to ELN 2017
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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.
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Patients with indication of first allo-HSCT with a matched related or unrelated donor
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Patients receiving non-myeloablative or reduced toxicity conditioning
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Patients affiliated to a social security scheme
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Patients who have received a complete information on the organization of the research and signed his informed consent
Exclusion Criteria:
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Patients with an alternative donor (HLA 5/10 or unit cord blood)
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Patients with another active cancer or a history of cancer diagnosed in the previous 5 years
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Patients with uncontrolled infection at the time of inclusion, or with positive HIV (1
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- or HTLV (1 + 2), Hepatitis C or active hepatitis B
- Patients referred to in Articles L. 1121-5, L. 1121-7 and L1121-8 of the Public Health Code.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Central Hospital, Nancy, France
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- D'Aveni M, Rossignol J, Coman T, Sivakumaran S, Henderson S, Manzo T, Santos e Sousa P, Bruneau J, Fouquet G, Zavala F, Alegria-Prévot O, Garfa-Traoré M, Suarez F, Trebeden-Nègre 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.
- 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:e330. doi: 10.1038/bcj.2015.58.
- 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.
- 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. Epub 2007 Jan 11.
- 2019-A00842-55