RATIONALE: Giving chemotherapy before a donor stem cell transplant using stem cells that closely match the patient's stem cells, helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving antithymocyte globulin before transplant and cyclosporine, tacrolimus, and methotrexate before and after transplant may stop this from happening. PURPOSE: Natural Killer (NK) cells from the donor's bone marrow may be important in fighting leukemia. Bone marrow donors can be selected based on the type of NK cells they have, specifically the killer immunoglobulin receptor (KIR) type. This study provides information on KIR type from potential donors, which can be used in selecting the bone marrow donor. This phase II trial of unrelated donor stem cell transplant in patients with high risk AML (monosomy 7, -5/5q-, high FLT3-ITD AR, or refractory or relapsed AML) in which KIR typing of the patients and potential donors will be available to the treating transplant physician at the time of donor selection.
OBJECTIVES: * To define the relationship between the status of donor NK-cell receptor and patient outcomes after killer immunoglobulin-like receptor-incompatible unrelated donor (URD) and umbilical cord blood (UCB) hematopoietic cell transplantation (HCT) in young patients with acute myeloid leukemia with monosomy 7, -5/5q-, high FLT3 internal tandem duplication allelic ratio (High-FLT3-ITD AR), or refractory or relapsed acute myelogenous leukemia. * To correlate the relationships between factors affecting NK receptor status and clinical events. * To assess NK-cell development after URD and UCB HCT in patients with poor prognosis AML. * To evaluate NK-cell reconstitution and receptor-acquisition pattern in these patients. OUTLINE: This is a multicenter study. * Preparative regimen: Patients receive 1 of the following regimens: * Hematopoietic stem cell transplantation (SCT): Patients receive busulfan IV every 6 hours on days -9 to -6, high-dose cyclophosphamide IV over 1 hour on days -5 to -2, anti-thymocyte globulin IV once or twice daily over 4 hours on days -3 to -1, and methylprednisolone IV on days -3 to -1. * Umbilical cord blood (UCB) transplantation: Conditioning regimen, infusion procedures, and post-transplant immunoprophylaxis for patients with an UCB donor are according to institutional guidelines and standards. * Allogeneic hematopoietic stem cell transplantation (SCT) or umbilical cord blood (UCB) transplant: Patients undergo allogeneic SCT or UCB transplant on day 0. * Graft-vs-host disease (GVHD) prophylaxis: Patients receive cyclosporine or tacrolimus IV or orally beginning on day -2 and continuing until day 50, followed by a taper until week 24. Patients also receive methotrexate IV on days 1, 3, 6, and 11. Blood samples will be collected periodically from both patients and donors for studies of natural killer cells in support of the study objectives. After completion of study treatment, patients are followed every 6 months for 2 years and then annually for 3 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
158
Given IV
Given IV
Given IV
Given IV or orally
Given IV
Given IV
Given IV
Correlative studies
Correlative studies
allogeneic bone marrow transplantation
Undergo allogeneic hematopoietic SCT
UAB Comprehensive Cancer Center
Birmingham, Alabama, United States
Phoenix Children's Hospital
Phoenix, Arizona, United States
Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
Long Beach, California, United States
Children's Hospital Central California
Madera, California, United States
Rady Children's Hospital - San Diego
San Diego, California, United States
Overall Survival (OS)
OS - Time from HSCT until death
Time frame: At 5 years from HSCT date
Cumulative Incidence of NK Cell Reconstitution
Cumulative incidence of successful reconstitution to donor level is calculated.
Time frame: At 5 years from HSCT date
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