trial to assess the efficacy of a tcr alfa beta depleted graft in pediatric affected by all or aml and receiving an hsct

Conditions: Acute Lymphoblastic Leukemia; Leukemia Acute Myeloid - AML; Non-Hodgkin Lymphoma; Myelodysplastic Syndromes

Summary: allocation: non-randomized endpoint classification: safety/feasibility intervention model: single group assignment masking: open label primary purpose: treatment study to assess the feasibility and safety of the infusion of a t cells receptor (tcr) alfa beta depleted graft in pediatric patients affected by malignant and non-malignant hematological disorders and receiving an hematopoietic stem cell transplantation (hsct) from a human leukocyte antigen (hla) partially matched family donor.

in this study the hypothesis is that the transplantation of peripheral blood stem cells (pbsc)selectively depleted of tcr alfa beta t lymphocytes would offers some advantages over the use of positively selected cd34+ stem cells because of the presence of other non-stem ancillary cells (in particular natural killer (nk) and alfa beta t cells) that might have potential positive effects on the outcome of the transplant. the clinical relevance of nk-cell alloreactivity has been demonstrated in adult patients affected by acute myeloid leukemia (aml) and given t-cell depleted hsct from an hla-disparate relative where a subgroup of patients had a particularly low risk of leukemia relapse. these patients belonged to the group transplanted from a donor having nk cells that were alloreactive towards recipient targets i.e. the patient cells express hla-class i alleles that do not share the inhibiting allelic determinants recognized by killer immunoglobulin-like receptors (kir) on donor nk cells. the emergence of this concept of nk-cell alloreactivity has represented a sort of revolution in the field of haplo-identical hematopoietic stem cell translantation (haplo-hsct), as the presence of alloreactive nk cells has been shown to positively affect the outcome of transplantation in adults and to display a graft versus leukemia (gvl) effect that can compensate for the lack of t-specific anti-tumor effect. the purpose of this study is to evaluate the feasibility and safety of the selective infusion of tcr alfa beta t cell depleted graft in pediatric patients affected by malignant or non malignant hematological disorders and receiving an hsct from a partially matched family donor. this study will provide new data on the feasibility and the safety of using a tcr alfa beta t cell depleted graft instead of fully t cell depleted graft to improve the outcome of patients receiving a haplo-hsct for the treatment of hematological disorders.

Eligibility criteria:
inclusion criteria: * patients aged ≥ 3 months and \< 21 years * patients diagnosed with malignant hemopathies (acute lymphoblastic leukemia (all), acute myeloid leukemia (aml), non-hodgkin lymphoma (nhl)) in complete morphological remission or myelodysplastic syndromes (mds), solid tumors or non malignant hematological disorders (scid, acquired and congenital aplastic anemia, other primary immunodeficiencies, life-threatening cytopenia) eligible for an allogeneic transplantation and lacking a related or unrelated hla-matched donor * patients displaying an hla-partially matched family donor * lansky/karnofsky score \> 40, who \> 4 * signed written informed consent exclusion criteria: * grade \>ii acute gvhd or chronic extensive gvhd at the time of inclusion * patient receiving an immunosuppressive treatment for gvhd treatment at the time of inclusion * dysfunction of liver (alt/ast \> 5 times normal value, or bilirubin \> 3 times normal value), or of renal function (creatinine clearance \< 30 ml / min) * severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or left ventricular ejection fraction \<40%) * current active infectious disease (including positive hiv serology or viral rna) * serious concurrent uncontrolled medical disorder * pregnant or breast feeding female patient * lack of parents' informed consent.

Keywords: hematologic malignant non-malignant allogeneic transplant non-hodgkin lymphoma pediatric acute lymphoblastic leukemia acute myeloid leukemia myelodysplastic syndromes t cells receptor alfa beta