Stem Cell Disorders

Question 1

What is aplastic anemia?

Answer 1

A condition in which there are a reduced number of RBCs, WBCs, and platelets due to bone marrow aplasia/hypoplasia.

Question 2

Differentiate between aplastic anemia and aplastic crisis.

Answer 2

Aplastic anemia is a misnomer and actually refers to the presence of pancytopenia. Aplastic crisis involves a decrease in the red cell line only.

Question 3

What are some known causes of aplastic anemia?

Answer 3

The cause is unknown in >50% of cases, with the remainder due to certain drugs, toxins, infections, or radiation exposure.

Question 4

What are some dose-related causes of aplastic anemia?

Answer 4

Benzene and radiation.

Question 5

What are some drugs/toxins which can be implicated in the development of aplastic anemia?

Answer 5

Sulfa drugs, gold, chloramphenicol, and insectisides.

Question 6

What are some infections for which testing should be included in the initial evaluation of aplastic anemia?

Answer 6

Hepatitis, CMV, EBV, HIV, and parvovirus.

Question 7

What genetic workup should be performed in patients with aplastic anemia?

Answer 7

These patients should be evaluated for inherited bone marrow failure syndromes in addition to the rest of the recommended workup.

Question 8

What hemotologic disorder can develop in patients with paroxysmal nocturnal hemoglobinuria?

Answer 8

About 20% of patients with PNH eventually develop aplastic anemia as well.

Question 9

List 6 potential etiologies for pancytopenia.

Answer 9

Aplastic anemia, HLH, primary hematologic malignancies, folic acid deficiency, B12 deficiency, and fibrosis or infiltration with neoplastic cells, such as in neuroblastoma.

Question 10

What physical exam findings would be concerning for a hematologic disorder affecting >1 cell line?

Answer 10

The combination of bruising and pallor.

Question 11

What procedure is required as part of the evaluation of pancytopenia?

Answer 11

Bone marrow biopsy/aspiration

Question 12

What would be the typical bone marrow finding in a patient with aplastic anemia?

Answer 12

Hypocellular or acellular bone marrow.

Question 13

What are the treatment options for children with aplastic anemia?

Answer 13

Immunosuppressive therapy with antithymocyte globulin (ATG), cyclosporine, and prednisone offers a complete response rate of 65%, although relapses are common. Matched bone marrow transplant, if available, has a 10-year survival rate of >80%.

Question 14

Which medically treated patients with aplastic anemia are at higher risk for a secondary malignancy?

Answer 14

Patients with inherited bone marrow failure syndromes are at higher risk for secondary malignancy if treated medically.

Question 15

Why should blood products be leukoreduced and irradiated in patients with aplastic anemia?

Answer 15

To prevent pretransplant alloimmunization, minimize the number of transfusions if possible. If transfusions are required: do not use family members as donors, use single-donor platelets, and use leukocyte-filtered and irradiated blood components.

Question 16

What is the inheritance pattern associated with Fanconi anemia?

Answer 16

Autosomal recessive

Question 17

What is the underlying defect that leads to the clinical manifestations of Fanconi anemia?

Answer 17

It is due to the presence of poor DNA repair mechanisms.

Question 18

Describe some congenital anomalies which can be seen in children with Fanconi anemia.

Answer 18

Short stature, absent or abnormal thumbs, abnormal radii, microcephaly, café-au-lait spots, dark pigmentation, and renal anomalies.

Question 19

What is the typical presentation of Fanconi anemia?

Answer 19

It can present with congenital anomalies, but they are not required for diagnosis. Most children are diagnosed around 8-9 years of age when they are found to have pancytopenia or an isolated macrocytic anemia.

Question 20

What is the average lifespan of patients with Fanconi anemia?

Answer 20

On average, patients live into their mid-30s. Most deaths are due to infection (neutropenia), or bleeding (thrombocytopenia), but aerodigestive cancers are also common.

Question 21

Children with Fanconi anemia are at risk for which malignancies?

Answer 21

They have a 15% risk for developing AML. Hepatic malignancy, aerodigestive cancers, and squamous cell carcinomas are also more common in patients with Fanconi anemia than in the general population.

Question 22

How is red cell aplasia defined?

Answer 22

Red cell aplasia is defined by the presence of anemia in the setting of reticulocytopenia.

Question 23

What are (6) known causes of red cell aplasia in the pediatric population?

Answer 23

Most common: parvovirus B19-associated RBC aplasia, transient erythroblastopenia of childhood (TEC), and congenital hypoplastic anemia (Diamond-Blackfan anemia). Can also be: idiopathic, secondary to drugs (phenytoin and chloramphenicol), or secondary to immune disorders (thymoma, SLE, chronic lymphocytic leukemia).

Question 24

Which virus infects RBCs and results in aplastic crisis in children with congenital hemolytic anemias?

Answer 24

Parvovirus B19

Question 25

How does parvovirus B19 cause red cell aplasia?

Answer 25

It infects the erythroid progenitors, causing an acute or chronic red cell aplasia.

Question 26

What clinical features, in conjunction with red cell aplasia, should point one toward the diagnosis of Parvovirus B19?

Answer 26

Fever, rash, and/or arthropathy. Rash can have the "slapped cheek" appearance classically associated with parvovirus B19.

Question 27

What is the typical treatment for red cell aplasia caused by infection with parvovirus B19?

Answer 27

Treatment is usually supportive, but IVIG can be given for complicated cases in immunocompromised patients.

Question 28

Describe the typical presentation of transient erythroblastopenia of childhood (TEC).

Answer 28

Affected children are usually 1-3 years of age and present with pallor and decreased activity without petechiae or organomegaly. Labs will reveal a normocytic anemia with isolated reticulocytopenia.

Question 29

What is the typical treatment for transienct erythroblastopenia of childhood (TEC)?

Answer 29

Treatment includes supportive care, with transfusion for symptomatic anemia. In most cases, the anemia resolves within 1-2 months without need for transfusion.

Question 30

What is the relationship between the diagnosis of transient erythroblastopenia of childhood and future risk of additional hematologic problems?

Answer 30

Patients diagnosed with TEC have no increased risk for the development of future hematologic problems.

Question 31

How does Diamond-Blackfan anemia usually present?

Answer 31

DBA usually presents in infancy with macrocytic anemia and reticulocytopenia without other cytopenias. About 1/3 of patients also have congenital anomalies: thumb anomalies, short stature, glaucoma, renal anomalies, hypogonadism, short webbed necks, congenital heart disease, and intellectual disability.

Question 32

How is red cell aplasia typically managed in patients with Diamond-Blackfan anemia?

Answer 32

Manage these children with transfusions until 6-12 months of age, then try corticosteroids. The anemia responds to steroids in up to 80% of patients. Spontaneous remission occurs in about 25% of cases. Chronic transfusions are required for those who are steroid refractory or dependent. Consider bone marrow transplant for patients requiring chronic RBC transfusion therapy.

Question 33

How do you differentiate among the 3 most common causes of red cell aplasia?

Answer 33

Parvovirus B19 usually occurs in school-aged children and has associated fever, rash, and arthropathy. TEC typically occurs in children 1-4 years of age and has normocytic RBCs without associated rash, fever, or arthropathy. DBA is most commonly diagnosed in children <1 year of age and has macrocytic RBCs. Patients also commonly have associated congenital anomalies.