Title (Pediatric) The Role of Minimal Residual Disease Testing before and after Hematopoietic Cell Transplantation for Pediatric Acute Myeloid Leukemia


CC 14-139

Hospital Main Campus

Disease Blood & Marrow Transplant (BMT), Leukemia, Acute Myeloid (AML)



  1. Ascertain whether the accuracy in predicting 2-year EFS and relapse incidence is improved by combining both MRD assays or whether one assay is superior to the other.
  2. To explore if peripheral blood WT1 MRD assessment has similar sensitivity for prediction of 2-year EFS and relapse as bone marrow WT1 MRD assessment.
  3. To assess the feasibility of determining the chimerism status of MRD-positive flow cytometry sorted cells post-transplant.
  4. To describe outcomes of HCT based on the presence or absence of detectable MRD and by the type of myeloablative preparative regimen (busulfan-based vs. TBI-based vs. other) with respect to 2-year EFS, 2-year overall survival (OS), relapse incidence, day 100 non-relapse mortality, acute graft-versus-host disease (GVHD), chronic GVHD, and veno-occlusive disease.
Inclusion Criteria

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 ≥ 9mg/kg total dose (IV or PO). PK-based dosing is allowed, if intent is myeloablative dosing 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 ≥ 2.5x10^7/kg; if two units, combination of the two must have TNC≥ 2.5x10^7/kg
Exclusion Criteria

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 (negative serology, surface antigen, and core antibody may substitute for PCR).
  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.