TPO-Mimetic Use in Children for Hematopoietic Failure

Inclusion Criteria:

1. Age ≥ 0 to ≤ 21 years

2. Child should be receiving ongoing care with pediatric hematology/oncology providers

3. Those enrolled in Arm A of the study should have a confirmed diagnosis of any of thefollowing a. aplastic anemia i. Diagnosis of severe Aplastic anemia (newly diagnosed orrefractory based on history of prior treatments) is established if Bone marrowcellularity <25% or and at least two of the following criteria are met:- (i)absolute neutrophil count less than 0.5 × 10^9/L, (ii) platelet count less than 20 × 10^9/L, and (iii) reticulocyte count less than 20 × 10^9/L ii. Moderate aplasticanemia is defined as bone marrow cellularity <50 percent and depression of at leasttwo out of three blood counts below the normal values: criteria are met:- (i)absolute neutrophil count less than 1.2x10^9/m3, (ii) platelet count less than 70x10^9/L, and (iii) anemia with hemoglobin less than or equal to 8.5 g/dL andabsolute reticulocyte count less than or equal to 60x10^9/L in transfusion-dependentpatients but not fulfilling the criteria of severe aplastic anemia b. refractory cytopenia of childhood without monosomy 7 or 5q- and without anevidence of cytogenetic abnormality with predisposition to leukemia c. myelo-suppression contributing to severe pancytopenia (absolute neutrophil count <0.5 x 10^3/mm^3; platelet count less than 20 × 10^9/L, and reticulocyte count lessthan 20 × 10^9/L secondary to any other drug or infection d. diagnosis of inherited bone marrow failure without chromosomal fragility disorder

4. Those enrolled in Arm B of the study should have a confirmed diagnosis of any of thefollowing:

5. myelo-suppression specifically thrombocytopenia as defined by primaryoncologist in children with solid tumors secondary to chemotherapy or radiationtherapy contributing to delay in chemotherapy

6. patient undergoing stem cell transplantation and experiencing persistentthrombocytopenia. This will include children not requiring platelettransfusions with a platelet count of <10 x 109/L, as well as those requiringplatelet transfusions (transfusion dependent) for prevention of bleedingdiathesis regardless of their platelet count at the time of recruitment (note:due to delayed engraftment these patients may have a higher platelet countbecause of platelet transfusion needs at the time of recruitment).

7. Adequate organ function within 7 days of enrollment defined as:

8. Creatinine: ≤ 2.0 mg/dL

9. Hepatic function:

• For arm A, elevation of liver enzymes is acceptable for patients withhepatitis induced SAA as long as patient does not have history of chronicliver problem. If necessary, liver biopsy will be performed.
• For Arm B, elevation of liver enzymes will be accepted as long as nochronic liver problem. Liver biopsy will be performed if necessary.

6. Females of childbearing potential agree to use effective contraception during thestudy period and for 4 months after completion of therapy

7. Must be able to provide written and voluntary informed consent.

Exclusion Criteria:

1. Gestational age < 32 weeks or Age > 21 years at the time of study enrolment

2. Preexisting condition with predisposition for thrombosis

3. Diagnosis of bone marrow failure syndrome with cancer predisposition includingchromosomal fragility disorders (Fanconi anemia, Bloom syndrome, AtaxiaTelangiectasia) and other conditions with known association towards cancerpredisposition

4. Presence of complex karyotype or monosomy 7 or 5q- or other cytogenetic abnormalitywith known predisposition to cancer.

5. Diagnosis of MDS with excess blasts in transformation

6. Female subjects who are nursing or pregnant (positive serum or urine β-humanchorionic gonadotropin [β-hCG] pregnancy test) at screening or pre-dose on Day 1.

7. Current alcohol or drug abuse.

8. Treatment with an investigational drug within 30 days or 5 half-lives (whichever islonger) preceding the first dose of study medication.

9. Active and uncontrolled infections (e.g. sepsis, hepatitis B, hepatitis C).

10. Chronic liver disease ie. Fibrosis or cirrhosis

11. Subjects infected with Human Immunodeficiency Virus (HIV).

12. Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugschemically related to Romiplostim that contraindicates the subjects' participation

13. Known history of sensitivity or allergy to the active substance, to any of theexcipients, or to any E. coli-derived product.

14. Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary,infectious, or metabolic disease of such severity that it would preclude thepatient's ability to tolerate protocol therapy, or that death within 7-10 days islikely.

15. Subjects who have participated in any study using an investigational drug during theprevious 30 days.

16. Non-English-speaking families who cannot speak or read English