Allogeneic HCT Using Conditioning Regimen of BuFluATG for AML CR1

1. Study Objectives * To evaluate the effect of various clinical variables including HLA-disparity and NK cell-related variables, upon outcomes of allogeneic hematopoietic cell transplantation (HCT) using uniform conditioning regimen including busulfan, fludarabine, and antithymocyte globulin (ATG) in patients with acute myeloid leukemia (AML) in the first complete remission (CR). The donors for allogeneic HCT include HLA-matched siblings, matched unrelated donors, and haploidentical family donors. * The endpoints of the study are engraftment, secondary graft failure, acute and chronic graft- versus-host disease (GVHD), immune recovery, infections, leukemia recurrence, non-relapse mortality, and relapse-free (RFS) and overall survival (OS) of patients. 2. Patient Eligibility * Patients with non-promyelocytic AML (intermediate-risk or high-risk diseases by NCCN guideline 2016) in the first CR * Patients should be 16 years of age or more and 75 years of age or less * The performance status of the patients should be 70 or over by Karnofsky performance scale * Patients should have adequate hepatic function (bilirubin less than 2.0 mg/dl, AST less than three times the upper normal limit) * Patients should have adequate renal function (creatinine less than 2.0 mg/dl) * Patients should have adequate cardiac function (ejection fraction \> 40% on MUGA scan) * Patients and stem cell donors must sign informed consent * For hematopoietic cell donor, if a patient has an HLA-matched sibling (65 years or younger), that sibling will be a cell donor. If a patient does not have an HLA-matched sibling but an HLA-A, B, C, DRB1 7-8/8 matched unrelated donor, the unrelated donor will be a cell donor. If a patient has neither HLA-matched sibling nor unrelated donor, an HLA-haploidentical familial donor will be a cell donor. 3. Treatment Plan Patients in the study will receive conditioning therapy with busulfan, fludarabine, and antithymocyte globulin. If patients are 54 years old or younger, the patients will receive three days' busulfan administration. If patients are older than 54 years or have co-morbidity, the patients will receive two days' busulfan administration. Graft is non-T cell depleted mobilized peripheral blood hematopoietic cells. GVHD prophylaxis will be given with cyclosporine 1.5 mg/kg iv infusion q12 hrs beginning day -1; methotrexate 15 mg/m2 iv push one day after HCT, then 10 mg/m2 3 days and 6 days after HCT 4. Treatment Evaluation Regimen related toxicities will be graded by NCI, Common Toxicity Criteria, v 4.0. The status of mixed chimerism will be evaluated by PCR analysis of short tandem repeats (STRs) of one of nine polymorphic introns or amelogenin. The chimerism status will be analyzed from mononuclear cells on 1, 3, and 6 months after HCT. Immune recovery of the patients after stem cell transplantation will be monitored by lymphocyte subset count and measurement of Ig G, Ig M, Ig A levels and Ig G subset (G1, G2, G3) on 1, 3, 6, and 12 months. In the study, at least 200 evaluable cases of HCT will be performed.

Sex

All

Minimum age

16 Years

Maximum age

75 Years

Inclusion Criteria:

3.1. Patients with non-promyelocytic AML, intermediate- or poor-risk categories by NCCN ver 2 (2016) guidelines (Appendix I), who achieve CR after induction chemotherapy.

3.2. Patients should be 16 years of age or more, and 75 years of age or less. 3.4. The performance status of the patients should be 70 or over by Karnofsky performance scale (Appendix II).

3.5. Patients should have adequate hepatic function (bilirubin less than 2.0 mg/dl, AST less than three times the upper normal limit).

3.6. Patients must have adequate renal function (creatinine less than 2.0 mg/dl).

3.7. Patients must have adequate cardiac function (ejection fraction \> 40% on MUGA scan).

3.8. Patients must sign informed consent.

Donor selection process (See appendix III)

3.9. Donor selection process may begin before or when the patients achieve CR. 3.9.1. If a patient has a willing HLA-matched sibling of 65 years or younger, that sibling will be a cell donor.

3.9.2. If a patient has no HLA-matched sibling of 65 years or younger, but a willing HLA- matched unrelated donor is available (younger than 55 years as regulated by KMDP), this will be a cell donor. The donor must be matched with the patient for 7-8 of 8 HLA-A, -B, -C, and -DRB1 allele match.

3.9.3. If a patient does not have an HLA-matched sibling nor unrelated donor, but an HLA- haplotype mismatched family member (offspring, parents, haploidentical sibling) available, this will be a cell donor.

3.9.4. Hematopoietic cell donor must sign informed consent.

Exclusion Criteria:

Patients who do not meet the inclusion criteria

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