1. Treatment of Aplastic Anemia
MGR Review
Treatment of Aplastic Anemia
Department of Hemato-Oncology
R4 손주웅/Prof. 윤휘중

2. Definition A disorder of hematopoiesis characterized by pancytopenia
A marked reduction or depletion of erythroid, granulocytic, and megakaryocytic cells in bone marrow

3. Epidemiology Europe and Israel Thailand and China
Two cases per million persons annually
Thailand and China
Five to seven cases per million persons annually
Age distribution is biphasic
first peak in the teens and twenties and
second rise in the elderly

4. Etiology

5. Pathophysiology Immune-mediated injury
Respond to immunosuppressive therapy
50~60% of syngeneic grafts fail to engraft
Achieve hematologic reconstitution if adquate immunosuppression is given before a second transplant

6. Pathophysiology

7. Clinical features
Progressive weakness, fatigue, headaches, dyspnea on exertion, petechia, ecchymoses, epistaxis, metrorrhagia, gum bleeding
Caused by anemia and thrombocytopenia
Infection is an unusual first symptom
Prior drug use, chemical exposure, preceding viral illness

8. Laboratory studies Blood Bone marrow Large erythrocytes
Paucity of platelets and granulocytes
MCV is commonly increased
Reticulocyte are absent or few
Bone marrow
Hypocellular with a decrease in all elements
Fatty biopsy specimen
Infiltration of the bone marrow with malignant cells or fibrosis is not present
Hematopoietic cells occupying < 25% of the marrow space

10. Determination of severity
Moderate aplastic anemia
Bone marrow cellularity < 30%
Absence of severe pancytopenia
Depression of at least two of three blood elements
Severe aplastic anemia : at least two of the following
Granulocyte < 500/uL
Platelet < 20,000/uL
Corrected reticulocyte count < 1%
Very severe aplastic anemia
Severe aplastic anemia with granulocyte < 200/uL

11. Treatment
three different treatment strategies, based on the level of cytopenia
moderate cytopenia, not requiring transfusions
Supportive care or outpatient treatment with anabolic steroids and/or low-dose steroids or cyclosporine
Severe aplastic anemia
either IST or BMT
severity of the disease and patient age

13. Immunosuppressive treatment
Antithymocyte globulin (ATG)
Superior survival compared with supportive care
The probability of becoming transfusion independent
vary from 40% to 80% according to the IST regimen and the patient population
Median time to achieve a response is 120 days
Combinations with Cyclosporin A
Improve the overall response rates

15. Cyclosporin dependence and relapse
Current IST regimens including CsA for 6 months
CsA is tapered, and it is unclear exactly
when and how fast this should be done
the Italian pediatric group
it is safe to start taper CsA at 12 months of treatment (rather than 6 months)
taper should be very slow (less than 10% of the dose/month) for at least 1 year, to minimize the risk of relapse

16. Growth factors The potential advantages of using G-CSF Disadvantages
faster neutrophil recovery
early identification of non-responders
early referral for BMT
Disadvantages
expensive
apparently does not improve survival at 3 years
increased risk of clonal disorders

17. Relapse The risk of relapse after ATG is around 35% In some cases
associated with cyclosporin withdrawal
sometimes respond to re-introduction of cyclosporin
If not, a second course of ATG would be appropriate

18. Algorithms for treatment of acquired aplastic anemia

19. Allogeneic hematopoietic stem cell transplantation
Most effective therapy
Usefulness declines with age because of fatal complications
the International Bone Marrow Transplant Registry showed 77% 5-year survival
children and patients who were minimally transfused, survival of 80–90% may be routinely achieved
Acute grade II–IV GVHD occurs in about 20–30%
chronic GVHD in 30–40%

20. The Treatment of Severe Acquired Aplastic Anemia
Blood, Vol 85, No 12 (June 15). 1995: pp

21. Matched unrelated donor transplant
the outcome for an unrelated donor HSCT remains less favorable compared with a matched-related transplant
due to more GVHD
mortality rate that is about twice that observed in matched sibling transplants
long term survival of about 50%
A multicenter prospective study compared the outcomes of a second course of IST to a MUD HSCT
MUD HSCT had a higher failure free survival
no difference in overall survival

22. Current concepts in the pathophysiology and treatment of aplastic anemia
BLOOD, 15 OCTOBER VOLUME 108, NUMBER 8

23. Allogeneic Stem Cell Transplantation for Aplastic Anemia
Biology of Blood and Marrow Transplantation 13: (2007)