Natural History and Biology of Long-Term Late Effects Following Hematopoietic Cell Transplant for Childhood Hematologic Malignancies

This is a prospective non-therapeutic study, assessing the long-term toxicity of pediatric
HCT for hematologic malignancies. This study is a collaboration between the Pediatric Blood
and Marrow Transplant Consortium (PBMTC), the Center for International Blood and Marrow
Transplant Research (CIBMTR), the National Marrow Transplant Program (NMDP) and the Resource
for Clinical Investigation in Blood and Marrow Transplantation (RCI-BMT) of the CIBMTR. The
study will enroll pediatric patients who undergo myeloablative HCT for hematologic
malignancies at PBMTC sites.

The study examines the hypothesis that survivors of pediatric HCT are at risk for late organ
toxicity and they will have identifiable biomarkers present within the first two years
following HCT which will be predictive for late adverse outcomes allowing for early
identification of patients at risk.

Inclusion Criteria:

1. Age less than 22 years at admission for HCT

2. Planned allogeneic HCT from any donor and stem cell source. There are no
study-specific criteria for HLA-matching

3. Disease and disease status criteria

1. Acute lymphoblastic leukemia/lymphoma in complete morphologic remission defined
as a M1 marrow (<5% blasts) with no evidence of active extramedullary disease
within 30 days of the start of the conditioning regimen; OR

2. Myelodysplasia (regardless of subtype) with less than 10% marrow blasts within 30
days of the start of the conditioning regimen; OR

3. Acute myelogenous leukemia in complete morphologic remission defined as an M1
marrow (<5% blasts) with no evidence of extramedullary disease within 30 days of
the start of the conditioning regimen; OR

4. Juvenile myelomonocytic leukemia; OR

5. Chronic myelogenous leukemia excluding refractory blast crisis.

4. Planned myeloablative conditioning regimen, defined as a regimen including one of the
following as a backbone agent:

1. Busulfan ≥ 12.8 mg/kg total dose (IV or PO). PK-based dosing allowed, if the
intent is total overall dose ≥ 12.8 mg/kg; OR

2. Total Body Irradiation ≥ 1200 cGy fractionated; OR

3. Treosulfan ≥ 30 g/m2 total dose IV

5. Enrollment in the following NMDP research protocols:

1. Protocol for a Research Database for Hematopoietic Cell Transplantation, Other
Cellular Therapies and Marrow Toxicity Injuries

2. Protocol for a Research Sample Repository for Allogeneic Hematopoietic Stem Cell
Transplantation and Marrow Toxic Injuries

6. Written informed consent document signed by patient if the age is greater than or
equal to 18 years and the patient is developmentally able to provide consent. The
informed consent document is to be signed by the parent or legal guardian if the
patient's age is less than 18 years or if the patient is older than 18 years, but
developmentally unable to provide consent. Assent will be obtained according to the
guidelines of the patient's transplant institution.

Exclusion Criteria:

1. Prior allogeneic or autologous HCT

2. Patients with renal disease prior to the start of HCT conditioning requiring the use
of dialysis at the time of enrollment and/or GFR < 60 mL/min/1.73 m2

3. Patients with osteopenia or osteoporosis treated with a bisphosphonate medication at
any time prior to enrollment

4. Patients with preexisting diabetes or hyperglycemia treated with insulin or oral
hypoglycemic medication at the time of enrollment

5. Patients with uncontrolled viral, bacterial, fungal or protozoal infection at the time
of study enrollment

6. Karnofsky performance score or Lansky Play-Performance Scale Score <60 at the time of
study enrollment

7. Known inherited or constitutional predisposition to cancer including, but not limited
to Down Syndrome, Li-Fraumeni syndrome, Fanconi Anemia, and patients with BRCA1 and
BRCA2 mutations