MRD Testing Before and After Hematopoietic Cell Transplantation Transplantation for Pediatric Acute Myeloid Leukemia

Participating institutions (transplant centers)

Inclusion Criteria:

1. Subject or legal guardian to understand and voluntarily sign an informed consent.
2. Age 0-21 at time of transplant.
3. Karnofsky score ≥ 70% (age ≥ 16 years old), or Lansky score ≥ 70% (age<16 years old).

4. Patients with adequate physical function as measured by:

   • Cardiac: Left ventricular ejection fraction at rest must be > 40%, or shortening fraction > 26%
   • Hepatic: Bilirubin ≤ 2.5 mg/dL; and ALT, AST and Alkaline Phosphatase≤ 5 x ULN
   • Renal: Serum creatinine within normal range for age, or if serum creatinine outside normal range for age, then renal function (creatinine clearance or GFR) > 70 mL/min/1.73 m2.
   • Pulmonary: DLCO, FEV1, FVC (diffusion capacity) > 50% of predicted (corrected for hemoglobin); if unable to perform pulmonary function tests, then O2 saturation > 92% in room air.

5. Acute myelogenous leukemia (AML) at the following stages:

   • High risk first complete remission (CR1), defined as:

     • Having preceding myelodysplasia (MDS) -or-
     • Diagnostic high risk karyotypes: del (5q) -5, -7, abn (3q), t (6;9), abnormalities of 12, t (9:22), complex karyotype (≥3 abnormalities), the presence of a high FLT3 ITD-AR (> 0.4) -or-
     • Having >15% bone marrow blasts after 1st cycle and/or >5% after 2nd cycle before achieving CR -and-
     • <5% blasts in the bone marrow, with peripheral ANC>500

   • Intermediate risk first complete remission (CR1), defined as:

     • Diagnostic karyotypes that are neither high-risk (as defined above) nor low risk (inv(16)/t(16:16); t(8;21); t(15;17)). Included are cases where cytogenetics could not be performed. -and-
     • <5% blasts in the bone marrow, with peripheral ANC>500

   • High risk based upon COG AAML 1031 criteria:

     • High allelic ratio FLT3/ITD+, monosomy 7, del(5q) with any MRD status or standard risk cytogenetics with positive MRD at end of Induction I.
     • <5% blasts in the bone marrow, with peripheral ANC>500

   • Second or greater CR

     • <5% blasts in the bone marrow, with peripheral ANC>500

   • Therapy-related AML at any stage

     • Prior malignancy in remission for >12 months.
     • <5% blasts in the bone marrow, with peripheral ANC>500

6. Myeloablative preparative regimen, defined as a regimen including one of the following as a backbone agent*:

   • Busulfan ≥ 12.8mg/kg total dose (IV or PO). PK-based dosing allowed, if intent is total overall dose ≥ 12.8mg/kg OR
   • Total Body Irradiation≥1200cGy fractionated OR
   • Treosulfan ≥ 42g/m2 total dose IV *Regimens may include secondary agents such as, but not limited to Ara-C, Fludarabine, VP-16. Regimens that combine Busulfan and TBI or treosulfan and TBI are allowed as long as the Busulfan or treosulfan meets or exceeds the dose listed and the TBI is below the dose listed.

7. Graft source:

   • HLA-identical sibling PBSC, BM, or cord blood
   • Adult related or unrelated donor PBSC or BM matched at the allelic level for HLA-A, HLA-B, HLA-C, and HLA-DRB1 with no greater than a single antigen mismatch.

   • One or two unrelated cord blood units:

     • HLA≥4:6 at the low resolution level for HLA-A, HLA-B, at high resolution level at HLA-DRB1 for one or both units.
     • If one unit, must have TNC≥2.5x107/kg; if two units, combination of the two must have TNC≥2.5x107/kg

Exclusion Criteria:

1. Women who are pregnant (positive HCG) or breastfeeding.
2. Evidence of HIV infection or HIV positive serology.
3. Positive viral load (PCR) for Hepatitis B or C.
4. Current uncontrolled bacterial, viral or fungal infection (currently taking medication and progression of clinical symptoms).
5. Autologous transplant < 12 months prior to enrollment.
6. Prior allogeneic hematopoietic stem cell transplant.