Aplastic Anemias & Bone Marrow Transplant I

1. APLASTIC ANEMIAS
&
BONE MARROW TRANSPLANT I
Dr. Sookun Rajeev K
(MD)
Dept of General Medicine
Anna Medical College

2. Definition:
A gross reduction or absence of
Haemopoietic precursors in all 3
cell lineages in bone marrow
resulting in pancytopenia in
peripheral blood.

3. Etiology
Congenital/inherited (20%):
Patients usually have dysmorphic features or
physical stigmata. Occasionally, marrow failure
may be the initial presenting feature.
Fanconi anemia
Dyskeratosis congenita
Shwachman-Diamond syndrome
Familial aplastic anemia

4. Etiology
Acquired:
Drugs
Cytotoxic drugs - Antibiotics
 Chloramphenicol - Anti-inflammatory
Anti-convulsant - Sulphonamides

5. Etiology
Viruses:
Hepatitis A, Non-A and Non-B
Herpes simplex
E-B virus
Parvovirus: Transient
Important clinically in patients with
hemolytic anemias

6. Etiology
Radiations
Chemicals e.g., Benzene and pesticides,
chloramphenicol, phenylbutazone, and
gold.
Immune: SLE, RA (rheumatoid arthritis)
Pregnancy
Idiopathic: 75%

7. Classification According to Severity
Moderate aplastic anemia
Marrow cellularity <30%
Absence of severe pancytopenia
Depression of at least two of three
blood elements below normal.

8. Classification According to Severity
Severe
Bone marrow cellularity <25% or marrow showing
<50% normal with two of three peripheral blood
count criteria:
Absolute Neutrophil Count (ANC) <500
Plt <20000
Reticulocyte count <40000
Very Severe
All of above plus ANC less than 200.

9. Clinical Features
Mouth infection,Sore throat ( Mucositis)
Ulcers of : Mouth & throat , Skin, Anus
Features of Sepsis (Gm +ve &–ve):
Fever +/-
Hypotension,
Multiple Organ Dysfunction Syndrome
In prolonged neutropenia Fungal infections are
likely to develop: Candida (Oral), Aspergillus(Pulm)

10. Clinical Features
Adenopathy or organomegaly should suggest an
alternative diagnosis.
In any case of aplastic anemia, look for physical
stigmata of inherited marrow failure syndromes such
as
skin pigmentation,
short stature,
microcephaly,
hypogonadism,
mental retardation,
skeletal anomalies.

11. Differential Diagnosis
Pancytopenia with hypocellular bone marrow
Acquired aplastic anemia Inherited aplastic anemia
Hypoplastic MDS Hypoplastic AML
Hypocellular Bone Marrow with or without cytopenia
Q Fever Legionaires Disease
Mycobacteria Tuberculosis
Hypothyroidism Anorexia Nervosa

12. Differential Diagnosis
Pancytopenia with Cellular Bone Marrow
Primary Bone Marrow
Diseases
Hypersplenism
Myelofibrosis Vit B12 and Folate Deficiency
Myelophthisis Overwhelming Infection
Bone Marrow Lymphoma Alcoholism
Hairy Cell leukemia Brucellosis
SLE, Sjogren’s disease Sarcoidosis
Tuberculosis

13. Investigations
FBC
Reticulocyte count
Blood film.
B12/folate.
Liver function tests
Virology
Bone marrow aspirate & trephine
PNH screen.

14. Aplastic Anemia – FBC
•Anemia is common, and red cells appear morphologically
normal. The reticulocyte count usually is less than 1%.
•Thrombocytopenia, with a paucity of platelets in the
blood smear.
•Agranulocytosis (ie, decrease in all granular white blood
cells, including neutrophils, eosinophils, and basophils) and
a decrease in monocytes are observed. A relative
lymphocytosis occurs.
•The degree of cytopenia is useful in assessing the severity of
aplastic anemia.

15. Bone marrow exam
•A bone marrow biopsy is performed in addition to the
aspiration. In aplastic anemia, these specimens are
hypocellular.
•Aspirations alone may appear hypocellular because of
technical reasons (eg, dilution with peripheral blood), or
they may appear hypercellular because of areas of focal
residual hematopoiesis.
•A core biopsy provides a better idea of cellularity; the
specimen is considered hypocellular if it is less than 30%
cellular in individuals younger than 60 years or less than
20% in those older than 60 years.

16. BM Aspiration BM Biopsy

17. Normal Marrow

18. BM biopsy hypocellular ,increased fat spaces

19. Other Investigations
• Hemoglobin electrophoresis - may show elevated fetal hemoglobin.
• Biochemical profile, including evaluation of transaminases,
bilirubin, lactic dehydrogenase, Coombs test, and kidney function, is
useful in evaluating etiology and differential diagnosis.
• Serologic testing for hepatitis EBV, CMV, and HIV
• Autoimmune disease evaluation for evidence of collagen-vascular
disease
• The Ham test or sucrose hemolysis test frequently is performed for
excluding PNH.
• Histocompatibility testing should be conducted early to establish
potential related donors, especially in younger patients.

20. PREVENTION
a)Insecticide
b)Herbicides
c)Organic solvents
d)Toxic chemical
Figure 8: Exposure to herbicides

21. TREATMENT
1.Stem cell transplant
2.Immunosuppressant
3.Blood transfusion
4.Bone marrow stimulant
5.Antibiotics & antiviral

22. Treatment
Withdrawal of etiological agents.
Supportive.
Restoration of marrow activity:
Bone marrow transplant
Immunosuppressive treatment
- Prednisolone - Antilymphocyte glob.
- Cyclosporin - Anti T cells abs.
- Splenectomy
Androgens
Growth factors

23. Treatment
Supportive care
Transfusion
Treatment of anemia
Treatment of bleeding
Prevention and treatment of
infection

24. Hematopoietic stem cell transplatation in
severe aplastic anemia
1. Advantages
 correction of hematopoietic defect
 long-term survival: 80% - 90%
 majority of the patients appear to be
cured

25. Hematopoietic stem cell transplatation in severe
aplastic anemia
Restrictions
- age below 40
- suitable donor available in less than 30%
(sibling)
-5-15% risk of graft failure in multitransfused
patients
- high mortality
- solid tumors (12%)

26. Immunosuppressive therapy
•Indicated for patients > 40 years
•Patients with no HLA matched sibling donors.
•Anti-Thymocyte Globulin(ATG) or anti-
lymphocyte globulin (ALG), cyclosporin,
methylprednisolone.
•Best results are for combination therapy.
•Response is slow, 4-12 weeks to see early
improvement.

27. Immunosuppressive therapy
•Immunosuppressive therapy
• Antithymocyte globulin, equine (Atgam) - 10-20 mg/kg/day for
8-14 days.
• Antithymocyte globulin, rabbit (Thymoglobulin) - 0,75
mg/kg/day for 8 days.
• Cyclosporine (Sandimmune, Neoral) - 1.5-2 mg/kg IV q12h,
• Methylprednisolone (Medrol, Solu-Medrol) - :5 mg/kg IV on
days 1-8; then tapered using PO 1 mg/kg on days 9-14; further
tapering over days 15-29. Stop after 1 mo except in evidence of
serum sickness.
• Cyclophosphamide (Cytoxan) : 45 mg/kg/d IV for 4 d.

28. Treatment
•Other treatments :
• Androgens :
these agents push the resting hematopoietic stem
cells into cycle, making them more responsive to
differentiation by hematopoietic growth factors and
stimulate endogenous secretion of erythropoietin.
most are masculinizing and poorly tolerated by
females and children.
The response rate is limited to approximately 45%,
and results may require 6-10 months of therapy.

29. Treatment
•Other treatments :
•Hematopoietic growth factors - G-CSF and GM-CSF,
may be useful in patients with neutropenia who have
infections, without requiring a WBC transfusion.