Identification of New Immune Factors Specific of Relapse in Childhood B Lineage Acute Lymphoblastic Leukemia (LABMI)

Identification of New Immune Factors Specific of Relapse in Childhood B Lineage Acute Lymphoblastic Leukemia

Identification of New Immune Factors Specific of Relapse in Childhood B Lineage Acute Lymphoblastic Leukemia

B-acute lymphoblastic leukaemia (ALL) is the most common childhood malignancy. Despite enhancement of childhood B-ALL outcome, relapses remain difficult to treat. Several studies in adult acute myeloid leukaemia have shown that proliferation of immunosuppressive cells -particularly T regulatory (Treg) cells and deficient natural killer (NK) cells- was associated with poor response to chemotherapy. However, few studies have been done on childhood ALL and none on relapse of B-ALL. Moreover, a newly described immunosuppressive B cells subset (Breg cells) seems to have a role in oncogenesis in mice model, but its significance has never been evaluated in human cancers. The purpose of this study is to prospectively evaluate the immune status of children newly diagnosed with first relapse of B-cell ALL, and to compare results with those of children treated for B-ALL in complete remission. Classic lymphocytic phenotype, proportions of immunosuppressive cells (Treg cells, deficient NK cells, Cytotoxic T-lymphocyte-associated protein 4 and/or Programmed T cell death 1) and thymopoiesis will be evaluated. The investigators assume that increase of immunosuppressive cells proportions could be associated with B-ALL relapse.

Collection of blood samples will be done in newly diagnosed relapse of B-ALL children at the time of relapse diagnosis. Children aged from 1 to 18 years at the time of first B-ALL relapse diagnosis.

Collection of blood samples will be done at the same stage of treatment as the relapse group has been collected. Children aged from 1 to 18 years enrolled into FRALLE (protocol of treatment) or EORTC (European Organisation for Research and Treatment of Cancer) treatment protocols, treated for B-ALL and who are in complete molecular remission. These control patients will be recruited at the same time from the beginning of B-ALL treatment as paired-relapsed control patients.

Measure of Treg (CD4+,CD25+, Foxp3+) and deficient natural killer (NK) cells (CD3-,CD56+,NKp30-) proportions by FACS in children newly diagnosed with their first relapse of B-ALL.

Comparison of the immune status of patients at the diagnosis of their first relapse diagnosis with those of children treated for B-ALL who are in complete remission and at the same stage of treatment.

Measure of the number of T CD4+ lymphocytes (Cluster of Differentiation 4), T CD8+ lymphocytes (Cluster of Differentiation 8), NK cells and Natural killer T (NKT) cells by FACS.

Measure of TRECs (T cell receptor excision circle) by QPCR and naïve CD4+CD45RA+CD31+ T cells by FACS.

Inclusion Criteria for relapse Group : Children aged from 1 to 18 years at the time of first B-ALL relapse diagnosis Obtention of oral and written consent of the parents Parents affiliated with the social security system Inclusion Criteria for control Group : Children aged from 1 to 18 years enrolled into FRALLE or EORTC treatment protocols, treated for B-ALL and who are in complete molecular remission Obtention of oral and written consent of the parents Parents affiliated with the social security system Exclusion criteria for control Group are the same as for relapsed Group : Children with hematologic syndrome predisposing to hematologic neoplasia (such as Fanconi's anaemia, Diamond Blackfan anaemia …) or acute leukemia secondary to previous treatment, or who have had allogenic hematopoietic stem cell transplantation before relapse