Selection of Allogeneic Hematopoietic Cell Donors Based on KIR and HLA Genotypes

Study Overview
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Brief Summary
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This study tests whether adding certain genetic factors to the process of picking a stem cell donor can decrease the chances that the patient's leukemia will come back after bone marrow transplantation. Stem cell donors are matched based on genes called human leukocyte antigens (HLA). Currently, donors are selected largely on the basis of HLA gene typing alone. There is published data to show that donors with specific other genes called killer immunoglobulin-like receptors (KIR) may protect AML patients from having their leukemia return after a transplant. In this study, the best HLA matched donors will be tested for the KIR genes. If there is more than 1 donor available, a recommendation will be provided to study doctors as to which donors have potentially favorable KIR genes. The study doctors may or may not choose to use this donor for transplant or not based on his/her own judgment. Transplant care will not change otherwise as a result of this study. This study is being done to demonstrate that AML patients who have donors with specific KIR and HLA genes will have a better outcome following transplant.

Official Title
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Selection of Allogeneic Hematopoietic Cell Donors Based on KIR and HLA Genotypes

Conditions
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Leukemia

Intervention / Treatment
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* Genetic: KIR genotyping
* Genetic: HLA genotyping


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: RECIPIENT Persons of all ages are eligible for this study. Patient must have diagnosis of acute myelogenous leukemia (AML) at MSK or a collaborating treating institution. Patients with de novo AML or AML with preceding myelodysplastic syndrome (MDS) are eligible. Patient must be a potential candidate for an unrelated transplantation procedure at the time of enrollment even though patient may not be eligible for transplantation in the future due to relapse or presence of co-morbidity(ies). An unrelated donor does not need to be identified at the time of enrollment. If an HLA-compatible unrelated donor is not identified for the patient, the patient will be removed from the study. Exclusion Criteria: Recipients with an available sibling donor matched at HLA-A, HLA-C, and HLA-DRB1 (excluding identical twin siblings). Patients for whom post-transplant treatment is planned are not excluded from enrollment. Patients with prior allogeneic hematopoietic cell transplantation for AML. Note: Patients who have undergone prior hematopoietic cell transplantation for a diagnosis other than AML are still eligible for this study.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| For patients with 1 HLA-compatible donor for URD HCT<br>For patients with 1 URD: donor KIR genotyping will be performed on the donor. Because donor selection will not depend on KIR/HLA genotyping, completion of donor KIR genotyping is not required prior to transplant. | Genetic: HLA genotyping<br> <br> |
| For patients with >1 HLA-compatible donor for URD HCT<br>For patients with 1 or more donor candidates, KIR genotyping may be performed for up to 5 donors. For patients with HLA-B alleles harboring the Bw4 epitope, KIR3DL1 allele typing will be performed at MSKCC. | Genetic: KIR genotyping<br> <br> Genetic: HLA genotyping<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| relapse | Demonstration of evidence of leukemia (>5% blasts in the bone marrow, peripheral blood blasts, or development of extramedullary disease) after initial achievement of either a CR or CRi. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | Overall survival (OS). The time from study enrollment until death from any cause. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Allogeneic Hematopoietic Cell Donors, KIR and HLA Genotypes, 15-059