36 Aplastic Anemia: Acquired and Inherited

Question 1

The diagnosis of Aplastic Anemia usually requires the presence of pancytopenia defined as:

Neutrophil count:
Platelet count:
Hemoglobon:
Absolute Reticulocyte count:

accompanied by a hypocellular marrow without abnormal or malignant cells or fibrosis

Answer 1

Neutrophil count: fewer than 1.5 × 109/L
Platelet count: fewer than 50 × 109/L
Hemoglobon: less than 100 g/L
Absolute Reticulocyte count: fewer than 40 × 109/L

Question 2

The highest frequency of aplastic anemia occurs in persons between the ages of_______years; a second peak occurs between the ages of ________ears.

Answer 2

15 and 25 years

65 and 69 years

Question 3

The male-to-female incidence ratio of aplastic anemia in most studies is approximately

Answer 3

One

Question 4

The final common pathway to the clinical disease is

Answer 4

A decrease in blood cell formation in the marrow

Question 5

Reduced hematopoiesis in most cases of aplastic anemia results from

Answer 5

Cytotoxic T-cell–mediated immune suppression of very early CD34+ hematopoietic multipotential progenitor or stem cells

Question 6

A relationship between acquired aplastic anemia and hereditary aplastic anemia (FA or dyskeratosis congenita) has been suggested because of the defects in _______________________

Answer 6

Telomerase and telomere repair

Question 7

The most notorious drug documented to cause aplastic anemia

Answer 7

Chloramphenicol

The occurrence of aplastic anemia appears to be idiosyncratic, perhaps related to an inherited sensitivity to the nitroso-containing toxic intermediates.

Question 8

Total-body exposure to radiation between _______Gy leads to gastrointestinal symptoms and depression of leukocyte counts, but most patients recover.

Answer 8

1 and 2.5 Gy

Question 9

Although unusual, severe marrow aplasia can follow use of the alkylating agent,________, and may persist indefinitely.

Answer 9

Busulfan

Marrow aplasia may develop in patients 2–5 years after discontinuation of alkylating agent therapy.

These cases often evolve into hypoplastic myelodysplastic syndromes.

Question 10

A rare exception to the negligible pathogenetic role of hematopoietic growth factors in the etiology of aplastic anemia is the homozygous or mixed heterozygous mutation of the TPO receptor gene, MPL, which can cause

Answer 10

Amegakaryocytic thrombocytopenia

Evolves later into aplastic anemia

Question 11

TRUE OR FALSE

Lymphadenopathy and splenomegaly are not features of aplastic anemia; such findings suggest an alternative diagnosis such as a clonal myeloid or lymphoid disease.

Answer 11

TRUE

Lymphadenopathy and splenomegaly are not features of aplastic anemia; such findings suggest an alternative diagnosis such as a clonal myeloid or lymphoid disease.

Question 12

TRUE OR FALSE

Significant qualitative changes of red cell, leukocyte, or platelet morphology on the blood film are features of classical acquired aplastic anemia.

Answer 12

FALSE

Significant qualitative changes of red cell, leukocyte, or platelet morphology on the blood film are not features of classical acquired aplastic anemia.

Question 13

TRUE OR FALSE

The plasma contains high levels of hematopoietic growth factors, including EPO, TPO, and myeloid colony-stimulating factors.

Answer 13

TRUE

The plasma contains high levels of hematopoietic growth factors, including EPO, TPO, and myeloid colony-stimulating factors.

Question 14

TRUE OR FALSE

Plasma iron values are usually high, and Fe clearance is prolonged, with decreased incorporation into red cells.

Answer 14

TRUE

Plasma iron values are usually high, and Fe clearance is prolonged, with decreased incorporation into red cells.

Question 15

Marrow Findings in Aplastic anemia

Answer 15

Numerous spicules with empty, fat-filled spaces, and relatively few hematopoietic cells

Question 16

Refers to spicules that are cellular or even hypercellular

Answer 16

“hot spots”

These focal areas of residual hematopoiesis do not appear to be of prognostic significance.

Question 17

Cytogenetic analysis in aplastic anemia is

Answer 17

Normal

Clonal cytogenetic abnormalities in otherwise apparent aplastic anemia is indicative of an underlying hypoplastic clonal myeloid disease.

Question 18

Imaging thaht can be used to distinguish between marrow fat and hematopoietic cells

Answer 18

Magnetic resonance imaging

Magnetic resonance imaging studies of bone may be useful in differentiating severe aplastic anemia from clonal myeloid syndromes. The former gives a fatty signal and the latter a diffuse cellular pattern.

Question 19

A reticulocyte percentage of less than ______% is strongly indicative of aplastic erythropoiesis and, when coupled with leukopenia and thrombocytopenia, points to aplastic anemia.

Answer 19

0.5%

Question 20

As many as_______ of patients with otherwise typical aplastic anemia have evidence of glycosylphosphatidylinositol molecule defects and diminished phosphatidylinositol-anchored protein on leukocytes and red cells as judged by flow cytometry, analogous to that seen in PNH.

Answer 20

50%

Question 21

As many as____% of patients with aplastic anemia have a five-year probability of myelodysplasia developing.

Answer 21

20%

Question 22

Mutations that are increased in prevelance with patient age

Answer 22

ASXL1 and DNMT3A

Question 23

Mutations that were of similar frequency in all age groups

Answer 23

BCOR, BCORL1, and PIGA

Question 24

Three principal options: for treatment in AA

Answer 24

(1) syngeneic or allogeneic hematopoietic cell transplantation
(2) combination immunosuppressive therapy with ATG and cyclosporine, and
(3) eltrombopag

Question 25

TRUE OR FALSE

In general, transplantation is the preferred treatment for children and most otherwise healthy younger adults.

Answer 25

TRUE

In general, transplantation is the preferred treatment for children and most otherwise healthy younger adults.

Question 26

The preferred stem cell source

Answer 26

A histocompatible sibling matched at the HLA-A, -B, -C, and -DR loci

**an allele-level HLA-matched unrelated donor can be used in younger patients.

Question 27

TRUE OR FALSE

Red cell and platelet transfusions be used sparingly in potential transplant recipients to minimize sensitization to histocompatibility antigen

Answer 27

TRUE

Red cell and platelet transfusions be used sparingly in potential transplant recipients to minimize sensitization to histocompatibility antigen

Question 28

Packed red cells to alleviate symptoms of anemia usually are indicated at hemoglobin values:

Answer 28

Below 80 g/L

Question 29

TRUE OR FALSE

It is important to transfuse patients with red cells (or platelets) from family members if transplantation within the family is possible

Answer 29

FALSE

It is important not to transfuse patients with red cells (or platelets) from family members if transplantation within the family is remotely possible

Because this approach may sensitize patients to minor histocompatibility antigens, increasing the risk of graft rejection after hematopoietic cell transplantation.

Question 30

Preferred platelet unit for previously pregnant or transfused patients who are already allosensitized or who become so after treatment with leukoreduced platelets

Answer 30

Single-donor HLA-matched apheresis-harvested platelets

Question 31

The major curative approach in AA

Answer 31

Hematopoietic Cell Transplantation

Question 32

TRUE OR FALSE

Marrow stem cells perform better than blood stem cells when used as a source for patients with aplastic anemia, although this is under continued study.

Answer 32

TRUE

Marrow stem cells perform better than blood stem cells when used as a source for patients with aplastic anemia, although this is under continued study.

Question 33

In patients older than age 40 years, survival in matched-sibling transplant is reduced to approximately________%.

Answer 33

50%.

Question 34

Regimen that appear to improve outcome by decreasing the frequency of chronic graft-versus-host disease, which could make it useful in treating older patients.

Answer 34

Alemtuzumab-containing regimens

Question 35

If there is an HLA mismatch at one or more loci, especially _____or ____, the outcome is compromised,and immunosuppression with combined therapy may be preferred initially

Answer 35

HLA-A or -DRB1

Question 36

Act principally by reducing cytotoxic T cells

Release hematopoietic growth factors from T cells

Answer 36

Antilymphocyte and Antithymocyte Globulin

Question 37

TRUE OR FALSE

Equine ATG is superior to rabbit and, if available, is recommended as the first line of therapy

Answer 37

FALSE

Equine ATG is superior to rabbit and, if available, is recommended as the first line of therapy

Question 38

TRUE OR FALSE

ATG treatment may accelerate platelet destruction, reduce the absolute neutrophil count, and cause a positive direct antiglobulin (Coombs’) test.

Answer 38

TRUE

ATG treatment may accelerate platelet destruction, reduce the absolute neutrophil count, and cause a positive direct antiglobulin (Coombs’) test.

Question 39

Characterized by spiking fevers, skin rashes, and arthralgia, commonly occurs 7–10 days from the first dose

Answer 39

Serum sickness

Question 40

Management of Serum sickness

Answer 40

Glucocorticoid (eg, prednisone 1 mg/kg) from day one of ATG treatment and for two weeks thereafter

Fever, rigors, rash, hypotention, and hypoxia can be minimized by administration of acetaminophen and diphenhydramine before each dose of ATG.

Supplementation with intravenous hydration for hypotension and oxygen administration for hypoxia.

In cases of severe reactions, the administration of ATG can be slowed or temporarily discontinued until improvement occurs, and then reinstituted at a slower rate of infusion if necessary.

Question 41

Approximately _______of patients no longer require transfusion support after treatment with ATG alone.

Answer 41

One-third

Question 42

A cyclic polypeptide that inhibits IL-2 production by T lymphocytes and prevents expansion of cytotoxic T cells in response to IL-2

Answer 42

Cyclosporine

Question 43

Initial dose of Cyclosporine

Answer 43

10–12 mg/kg per day for at least 6 months and with downward dose modification after six months for as long as 12 months.

Question 44

Trough blood levels of Cyclosporine

Answer 44

200–400 ng/mL

Question 45

A TPO receptor agonist used to stimulate platelet production in patients with immune thrombocytopenia

May expand stem cell numbers and promote DNA repair

Answer 45

Eltrombopag

Question 46

Combination Immunotherapy

Answer 46

ATG (40 mg/kg per day) for 4 day
Cyclosporine (6 mg/kg per day in divided doses every 12 hours) for 6 months
Methylprednisolone (1 mg/kg per day) for 2 weeks
Eltrombopag is given at 150 mg from day 1 for 6 months

Question 47

TRIUE OR FALSE

G-CSF added to the combined immunosuppressive therapy does not increase response rate or survival.

Answer 47

TRUE

G-CSF added to the combined immunosuppressive therapy does not increase response rate or survival.

Question 48

A monoclonal anti-CD52 antibody that targets that antigen on T lymphocytes, has been an effective immunosuppressive agent in both relapsed and refractory patients

Answer 48

Alemtuzumab

Question 49

An alternative thrombopoietin receptor agonist that is a larger molecule than eltrombopag and requires parenteral administration

It binds to the thrombopoietin receptor site, cMPL

Answer 49

Romiplostim

Question 50

Alemtuzumab produces profound and persistent___________.

Answer 50

Lymphopenia

Question 51

Stimulate the production of EPO, and their metabolites stimulate erythropoiesis when added to marrow cultures in vitro.

May be useful in the treatment of aplastic anemia syndromes resulting from shortened telomeres.

Answer 51

Androgens

Question 52

Therapy with myeloid growth factors is probably best reserved for

Answer 52

Episodes of severe infection

As a preventive measure before dental work or other procedures that would compromise mucosal barriers in patients who have not responded to hematopoietic cell transplant or immunotherapy

Question 53

TRUE OR FALSE

Prophylactic use of growth factors is warranted.

Answer 53

FALSE

Prophylactic use of growth factors is not warranted.

Question 54

The most important prognostic feature

Answer 54

Absolute neutrophil count

Question 55

Hematopoietic cell transplantation is curative for approximately:

Patients younger than 20 years of age:
Between the ages of 20 and 40 years:
Older than age 40 years:

Answer 55

Patients younger than 20 years of age: 80%–90%
Between the ages of 20 and 40 years: 70%
Older than age 40 years 50%

Question 56

The best outcomes occur in patients who have:

Answer 56

Allele-based HLA-matched sibling
Have not been exposed to immunosuppressive therapy before transplantation
Have not been exposed and sensitized to blood cell products
Have had a marrow rather than a blood stem cell donor product, and
Have not been subjected to high-dose radiation in the conditioning regimen for transplantation

Question 57

Predictive of a better response to therapy

Answer 57

Higher initial absolute reticulocyte and lymphocyte counts
High proportion of Treg B cells

Question 58

Hereditary cause of AA: pancreatic insufficiency, steatorrhea

Answer 58

Schwaman Diamond Syndrome

Question 59

Hereditary cause of AA: nail dystrophy, mucosal leukoplakia

Answer 59

Dyskeratosis congenita

Question 60

Hereditary cause of AA: cafe au lait spots, VACTERL phenotype

Answer 60

Fanconi anemia

Question 61

Hereditary cause of AA: bilateral sensorineural deafness, agranulocytosis, SCID

Answer 61

Reticular dysgenesis