Patient case: 1-year-old male with acute myeloid leukemia; genetic feature: IDH1

Clinical trial: Reduced-Intensity Conditioning (RIC) and Myeloablative Conditioning (MAC) for HSCT in AML/MDS

Summary: The purpose of this study is to compare safety and efficacy of reduced-intensity conditioning and myeloablative conditioning regimens prior to HSCT in high-risk AML/MDS pediatric and young adult patients. This study investigates the use of two novel conditioning therapies for hematopoietic stem cell transplant (HSCT). The primary focus of both the investigators' myeloablative and reduced-intensity conditioning regimens is to reduce overall toxicity so that pediatric and young adult patients with high-risk AML/MDS with significant pretransplant comorbidities who would have been ineligible to proceed to HSCT previously can now receive potentially life-saving treatment.


Eligibility: Inclusion Criteria:
  Eligibility Criteria for Myeloablative Conditioning Transplant
  1. Patient must be between 1 month to 22 years of age.
  2. Diagnosis of acute myeloid leukemia or myelodysplastic syndrome, either high-risk, relapsed or primary refractory, minimal residual disease (MRD)-positive without circulating myeloblasts or active extramedullary disease at the time of transplant. Active marrow disease is permitted. ("High-risk" AML features are defined by the following: greater than 15% blasts in the bone marrow after the first course of Induction chemotherapy; adverse cytogenetic abnormalities of monosomy 5, monosomy 7, or 5q deletion; presence of FLT3 positive internal tandem duplication (FLT3/ITD+), particularly high allelic ratio; or treatment-related AML.)
  3. Stem cell sources include bone marrow, peripheral blood stem cells, or umbilical cord blood.
  4. Related bone marrow, peripheral blood stem cell, or cord blood unit: Sibling should be human leukocyte antigen (HLA)-matched at A, B, and DR-B1 loci. Unrelated cord blood unit should be at a minimum of 4/6 matched at antigen level on HLA A and B, and allele level at HLA DR-B1 loci.
  Unrelated bone marrow or peripheral blood stem cell donor should be HLA allele level matched at A, B, C, and DR-B1.
  5. Minimum prefreezing cell dose for cord blood units: 3 x 10^7 total nucleated cells/kg and 1.5 x 10^5 CD34+ cells/kg (cluster of differentiation 34). If this is not attainable, then double cord blood transplant should be considered.
  6. Patient, parent, or legal guardian must have given written informed consent and/or assent.
  7. Patient must have adequate performance status (Lansky score ≥60% for patients <16 years; Karnofsky score ≥60% for patients ≥16 years).
  8. Patient must have adequate pre-transplant organ function as defined by:
  8a. Renal: Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥70 mL/min/1.73 m2.
  8b. Hepatic: Total bilirubin ≤2.0 mg/dL unless the increase in bilirubin is attributable to Gilbert's syndrome; and SGOT (AST) (serum glutamate oxaloacetate transaminase), SGPT (ALT) (serum glutamate pyruvate transaminase), and Alkaline Phosphatase <4 x upper limit of normal (ULN) for age.
  8c. Cardiac: Normal cardiac function by echocardiogram or radionuclide scan, as defined by left ventricular ejection fraction at rest >45%, or shortening fraction >26%.
  8d. Pulmonary: FEV1 (forced expiratory volume at one second), FVC (forced vital capacity), and DLCO (diffusing capacity of lung for carbon monoxide) (corrected for hemoglobin) ≥50% of predicted; if unable to perform pulmonary function tests, then oxygen saturation ≥92% on room air.
  Eligibility Criteria for Reduced-Intensity Conditioning Transplant
  1. Patient must be between 0 -22 years of age.
  2. Patient must meet criteria 5.1.2-5.1.7 of eligibility criteria.
  3. Patient is excluded from myeloablative conditioning transplant due to failure to meet any of the criteria outlined in 5.1.8.
  4. Patient must have adequate pre-transplant organ function as defined by:
  4a. Renal: Creatinine clearance or radioisotope GFR ≥70 mL/min/1.73 m2. 4b. Hepatic: Total bilirubin ≤2.5 mg/dL unless the increase in bilirubin is attributable to Gilbert's syndrome; and SGOT (AST), SGPT (ALT), and Alkaline Phosphatase <5 x upper limit of normal (ULN) for age.
  4c. Cardiac: Normal cardiac function by echocardiogram or radionuclide scan, as defined by left ventricular ejection fraction at rest >40%, or shortening fraction >26%.
  4d. Pulmonary: FEV1, FVC, and DLCO (corrected for hemoglobin) ≥40% of predicted; if unable to perform pulmonary function tests, then oxygen saturation ≥92% on room air.
  Exclusion Criteria:
  Exclusion Criteria for Myeloablative Conditioning Transplant
  1. Recipient of an autologous stem cell transplant.
  2. Allogeneic hematopoietic stem cell transplant within the previous 3 months.
  3. Uncontrolled bacterial, viral, fungal, or other infection at the time of cytoreduction. Uncontrolled infection defined by positive blood cultures and fevers >38.0 within 24-48 hours of start of conditioning therapy.
  4. Evidence of HIV/HTLV (human T-lymphotropic virus) infection or HIV/HTLV positive serology.
  5. Pregnancy or lactating. All females of 11 years of age or older and/or who have begun menstruating will be screened for HCG (human chorionic gonadotropin) by either urinalysis or a blood sample in order to screen for pregnancy status.
  6. Patients with any inherited bone marrow failure syndrome (including, but not limited to, Fanconi anemia, Shwachman-Diamond syndrome, and dyskeratosis congenital) or Down syndrome (defined as either constitutional trisomy 21 or constitutional mosaicism of trisomy 21).

Relevance to patient case: not relevant