aquired bone marrow failure

1. Acquired Bone Marrow
Failure

2. • Overview
The bone marrow failure syndromes comprise a group of
disorders than can be either inherited or acquired.
These diseases are intrinsic disorders of the bone marrow
involving disruption in the homeostasis and function of
hematopoietic stem cells, resulting in inadequate production
of either a single or multiple cell lines (erythroid for red cells,
myeloid for white blood cells, megakaryocytic for platelets).

3. • The inherited bone marrow failure syndromes (IBMFS) include
1.Fanconi anemia
• The Acquired Bone Marrow Failure include:
1.Aplastic Anemia
2.Myelodysplastic syndrome (MDS)
• The most common cause of acquired bone marrow failure is aplastic
anemia.
• Diseases that can present in a manner similar to acquired bone marrow
failure include:
Myelodysplastic syndromes
Paroxysmal nocturnal hemoglobinuria
Large granular lymphocytic leukemia

4. Aplastic Anemia

5. Definition:(shut down of the bone marrow)
Destruction of hematopoietic cells of the bone marrow
leading to pancytopenia and hypocellular bone marrow
or selective aplasia of one or more elements.
Classification:
•Pleuri-potent defect : pancytopenia.
•Uni-potent defect.

6. Causes of pancytopenia:
Primary:
1. Idiopathic, acquired:
• An autoimmune mechanism may be responsible,
activated cytotoxic T cells are responsible for bone
marrow failure.
1. Congenital e.g., Fanconi anaemia.

7. Secondary:
1. Drugs:
• Antibiotics: chloramphenicol, sulfa drugs.
• Antithyroid drugs: Thiouracil and Carbimazol.
• Antidiabetics: Chlorpropamide.
• Chemotherapeutic agents: Chlorambucil.
• Antiemetics: Chlorpromazine.
• Antihistaminic.
• Antirheumatics: Indomethacin.
• Anticonvulsants: Phenytoin.
2. Chemicals and toxins:
• Heavy metals e.g., Gold.
• Solvents e.g., benzene.
• Insecticides.
Causes of pancytopenia:

8. Causes of pancytopenia:
3.Irradiations.
4.Infections: Parvovirus, EB virus, and viral hepatitis particularly non-
A, non-B.
5.Paroxysmal nocturnal hemoglobinuria.
6.Autoimmune e.g., SLE.
7. Pregnancy.
Secondary:

9. Causes of Uni-potent defect:
1. Pure red cell aplasia:
 Congenital: (Diamond - blackfan syndrome).
 Acquired: e.g.,
Thymoma,
Aplastic crisis of haemolytic anaemia.
2. Granulocytopenia.
3. Thrombocytopenia.

10. Presentations:
 Anaemia; Pallor with other manifestations.
 Bleeding within skin and mucous membranes,
hematuria and epistaxis are common. Intracranial
bleeding is always a risk.
 Necrotic mouth, throat ulcers and monilial infections
reflect the neutropenia.

11. Investigations:
1. Secondary Causes of aplastic anaemia must be excluded.
2. CBC " pancytopenia ":
Normocytic normochromic anaemia.
Leucopenia with relative lymphocytosis.
Thrombocytopenia.
Absence of reticulocytes.
3. Bone Marrow examination: Hypocellular fatty bone
marrow.

12. Differential diagnosis of pancytopenia:
Fulminant infections.
Megaloblastic anaemia.
Aplastic anaemia.
Myelodysplastic syndrome.
Fulminant infections.
Megaloblastic anaemia.
Aplastic anaemia.
Myelodysplastic syndrome.

13. Treatment (1):
1.Removal of the causative agent.
2.Management of anemia: red cell transfusions.
3.Management of infections:
Isolation in sterile environment.
Aggressive antibiotic therapy and antifungal drugs.
Granulocyte transfusion.
4.Management of bleeding: platelets transfusion.
5.Avoid exposure to myelosuppressive.

14. Treatment (2):
6.Bone marrow stimulation:
a.Conventional doses of glucocorticoids.
b. Androgens as testosterone: increase erythropoietin and stimulate
proliferation of erythroid and granulocyte population.
c.Folic acid.
7.Immunosuppressive agents:
a.Cyclosporine A.
b.Anti-thymocyte Globulin (ATG).
8.Bone marrow transplantation: the treatment of choice in:
Young patient.
There is a compatible donor.
Sever aplastic anemia.

15. Myelodysplastic syndrome

16. Definition:
Heterogeneous group of acquired bone marrow disorders due
to stem cells defect.
Characterized by macrocytosis, peripheral cytopenia,
hypogranular neutrophils with nuclear hypo or
hypersegmentation.
There is a hypercellular marrow with dysplastic changes in all
three cell lines. and have a variable risk of transformation to
acute leukemias.

17. Pathophysiology:
 Disordered maturation: ineffective hematopoiesis despite presence of
adequate numbers of progenitor cells in bone marrow (usually
hypercellular).
 Formed elements sometimes exhibit morphological and functional
defects.
 Intramedullary apoptosis: programmed cell death within bone
marrow.
 That lead to reduced mature cells in periphery.
 <30% develop AML.

18. Risk Factors
 Elderly.
 Post-chemotherapy.
 Exposures (benzene, tobacco, radiation).
 Inherited genetic abnormalities.

19. Clinical Features:
 May be asymptomatic.
 Commonly presents with symptoms of cytopenia:
Anemia (fatigue and dyspnea).
Thrombocytopenia (bruising, bleeding or petechiae).
Neutropenia (recurrent infections) over months-years.
 Splenomegaly in 25%.
 <30% develop AML.

20. Investigations:
•CBC:
Macrocytic with oval shaped red cells.
Thrombocytopenia.
Neutropenia.
•Bone marrow aspirate and biopsy:
Dysplastic and hypercellular.
Increased myeloblasts in BM.
•Chromosome analysis: Reveals abnormalities in
chromosomes 5 or 7.

21. Treatment
Supportive: Blood transfusion, platelets transfusion
and antimicrobials.
Specific:
Aggressive antileukemic therapy in patients with
excess blasts in the marrow.
Erythropoietin and G-CSF, GM-CSF.
Bone marrow transplantation.

22. Hematopoietic stem-cell transplantation
(HSCT)
(Bone marrow transplantation)

23. • Hematopoietic stem-cell transplantation is the
transplantation of multipotent hematopoietic stem cells,
usually derived from bone marrow, peripheral blood, or
umbilical cord blood are infused intravenously to restore
hematopoiesis and immune function after high dose
chemotherapy (conditioning) with or without radiation
therapy.

24. Definition:
•Hematopoietic stem-cell transplantation is the transplantation of multipotent
hematopoietic stem cells, usually derived from bone marrow, peripheral
blood, or umbilical cord blood are infused intravenously to restore
hematopoiesis and immune function after high dose chemotherapy
(conditioning) with or without radiation therapy.
Stem cells possess two defining properties:
 The capacity of self-renewal.
 The ability to differentiate into cell types with specialized cellular function.

25. Types of bone marrow transplants:
 Autologous bone marrow transplant: (the patient's own stem cells are used). Stem
cells are removed from the patient himself before receiving high-dose chemotherapy or
radiation treatment.
 Allogeneic bone marrow transplant: (the stem cells come from a donor). Stem cells
are removed from another person, called a donor.
 Syngeneic (from an identical twin).
 Umbilical cord blood transplant: This is a type of allogeneic transplant. Stem cells
are removed from a newborn baby's umbilical cord right after birth.

26. Indications for hematopoietic stem cell
transplantation:
•Malignant (cancerous):

Acute myeloid leukemia.

Acute lymphoblastic leukemia.

Hodgkin lymphoma (relapsed, refractory).

Non-Hodgkin lymphoma (relapsed, refractory).

Neuroblastoma.

Ewing sarcoma.

Multiple myeloma.

Myelodysplastic syndromes.

Gliomas, other solid tumors.
•Nonmalignant (noncancerous):
Thalassemia.
Sickle cell anemia.
Aplastic anemia.
Fanconi anemia.
Immune deficiency
syndromes.

27. Complications (1):
 Infections due to prolonged neutropenia (herpes, CMV,
fungal, pneumocystis carinii).
 Recurrence.
 Effects of cytotoxic drugs.
 Direct organ toxicities: mucositis, pulmonary, liver, renal, and
cardiac toxicities.
 Anemia.
 Bleeding in the lungs, intestines, brain, and other areas of the
body.
 Clotting disorders.

28. Complications (2):
 Delayed growth in children who receive a bone marrow transplant.
 Early menopause.
 Infertility and hypogonadism particularly with regimen containing
total body irradiation.
 Secondary malignancies: one complication of the chemotherapy or
radiation therapy (or both).
 Diarrhea, nausea, and vomiting.
 Graft failure.
 Graft rejection: Immunologically reactive cells of host (recipient)
origin destroyed the transplanted cells of donor origin.

29. Thank you