Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Waldenstrom Macroglobulinemia

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

8 to 13 ml bone marrow sample for frozen storage within one of the 5 certified biobank of the canceropole area.

bone marrow sample

20 ml blood sample for frozen storage within one of the 5 certified biobank of the canceropole area.

blood sample

Waldenström Macroglobulinemia (WM) is defined by a bone marrow lymphoplasmacytic infiltration and the presence of a monoclonal immunoglobulin M (IgM) in blood. This chronic lymphoproliferative disorder requires treatment only in case of symptoms, according to accurate criteria described during the second Workshop on WM i.e. in case of cytopenia, bulky organomegaly, immunological or physicochemical consequences of the presence of IgM in circulating blood. A MYD88 mutation, typically a MYD88(L265P), is found in 90% of WM patients. Other gene abnormalities have been observed, the most frequent is a mutation in the CXCR4 gene. Overall, gene mutations in WM involve only a limited number of signalling pathways, yielding the activation of NFkB, namely : the TLR and MYD88 pathway (with an activation of NFkB and BTK in case of MYD88(L265P) mutation), the BCR pathway (involving btk and associated with activations of both NFkB, and erk akt pathway) and the CXCR4 pathway (CXCR4 is a receptor of CXCL12, it is also associated with activations of ERK/MAPK and PI3K). Abnormalities of some of genes, such as TP53, of the expression of the protein CXCL13 and genes involved in the interleukin 6 secretion have been associated with some clinical characteristics.

The purpose of this project is to define the prognostic role of the detection of circulating tumoral DNA (ctDNA) at the end of treatment for the progression/relapse risk within the first 3 years after the first 6 months of treatment.

Prognostic Value of Circulating Tumoral DNA After the First 6 Months of Treatment in Patients With Waldenström Macroglobulinemia

To define the prognostic role of the detection of circulating tumoral DNA (ctDNA) at the end of treatment for the progression/relapse risk within the first 3 years after the first 6 months of treatment.

Centre Henri Becquerel

University Hospital, Caen

University Hospital, Lille

Centre Hospitalier de Lens

Centre Hospitalier Universitaire, Amiens

Symptoms and General Pathology

Leukemia

Recurrence

Disease Attributes

Cohort study with a representative sample of patients

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

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

Maud D'AVENI, MD

Marie-Therese RUBIO, MD

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.

Immunoevasive Tactics Employed by Myeloid Malignancy After Allogeneic Stem Cell Transplantation

Study of the Immunoevasive Mecanisms and Especially Myeloid Suppressive Cells in the Medullar Microenvironment Employed by Myeloid Malignancy (AML and High Risk MDS) When Relapsing After Allogeneic Stem Cell Transplantation

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).

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.

Central Hospital, Nancy, France

Syndrome

Coagulants

All Drugs and Chemicals

Hemostatics

presence of unexplained elsewhere fundoscopic abnormalities AND either IgM concentration above 30 g/L (densitometry) or cryoglobulin activity

A central review of numerised fundoscopic picture will be performed.

fundoscopic picture

Two 10 ml blood vials will be sampled in addition to standard blood sampling for getting 6 to 7 200 μL aliquot.

One 5 ml EDTA vial for GP1bα expression study, only if this sample can be sent to hemostasis laboratory within the 4 hours after sampling

Five to 10 ml bone marrow sample will be collected in addition to standard bone marrow sampling for getting molecular characteristics of WM

Magalie JORIS, MD

Fabrice JARDIN, MD

Xavier TROUSSARD, MD

Gandhi DAMAJ, MD

Stéphanie POULAIN, MD

Daniela ROBU, MD

Walsdenström Macroglobulinemia (WM) is defined by a bone marrow lymphoplasmacytic infiltration and the presence of a monoclonal immunoglobulin M (IgM) in blood. Clinical manifestations of the hyperviscosity syndrome (HVS) are related to the large amount of IgM in circulating blood or to some physicochemical characteristics such as the presence of a cryoglobulin property. Although HVS is one of the most frequent criteria for initiating therapy in WM, few studies focused on its description and no diagnostic criteria are available.

The present study aims to identify a diagnostic system for HVS, taking into account objective symptoms such as bleedings, fundoscopic findings and also subjective symptoms such as fatigue and comorbidities that may influence the severity of symptoms.

Clinical Study of the Hyperviscosity Syndrome in Waldenström Macroglobulinemia

Correlation between items collected in questionnaires and HVS detection. Questionnaires are An oncogeriatric form for geriatric assessment, a comorbidity assessment form, a fatigue and quality of live assessment form, and an hemorrhagic assessment form.

Correlation between fundoscopic findings and HVS detection

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Prognostic Value of Circulating Tumoral DNA After the First 6 Months of Treatment in Patients With Waldenström Macroglobulinemia	NCT04893564	Waldenstrom's D... Waldenstrom Mac...	bone marrow sam... blood sample	18 Years -	Centre Hospitalier Universitaire, Amiens
Prognostic Value of Circulating Tumoral DNA After the First 6 Months of Treatment in Patients With Waldenström Macroglobulinemia	NCT04893564	Waldenstrom's D... Waldenstrom Mac...	bone marrow sam... blood sample	18 Years -	Centre Hospitalier Universitaire, Amiens
Immunoevasive Tactics Employed by Myeloid Malignancy After Allogeneic Stem Cell Transplantation	NCT03964922	Relapse Leukemi... Allogeneic Stem... Immune Evasion,...	blood sample bone marrow sam...	18 Years - 71 Years	Central Hospital, Nancy, France
Prognostic Value of Circulating Tumoral DNA After the First 6 Months of Treatment in Patients With Waldenström Macroglobulinemia	NCT04893564	Waldenstrom's D... Waldenstrom Mac...	bone marrow sam... blood sample	18 Years -	Centre Hospitalier Universitaire, Amiens
Clinical Study of the Hyperviscosity Syndrome in Waldenström Macroglobulinemia	NCT04898647	Hyperviscosity ... Waldenstrom Mac...	fundoscopic pic... blood sample bone marrow sam...	18 Years -	Centre Hospitalier Universitaire, Amiens
Immunoevasive Tactics Employed by Myeloid Malignancy After Allogeneic Stem Cell Transplantation	NCT03964922	Relapse Leukemi... Allogeneic Stem... Immune Evasion,...	blood sample bone marrow sam...	18 Years - 71 Years	Central Hospital, Nancy, France

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