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Haematology > Bone Marrow Failure and Haematopoietic Stem Cell Transplantation > Flashcards

Bone Marrow Failure and Haematopoietic Stem Cell Transplantation Flashcards

1
Q

What is pancytopenia?

A

Marked reduction in the count of red blood cells, white blood cells, and platelets in peripheral blood.

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2
Q

What are possible causes of Pancytopenia?

A
  1. Increased destruction
  2. Sequestration
  3. Decreased Production
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3
Q

What is Bone Marrow failure?

A

Pancytopenia due to the failure of bone marrow to produce blood cells.

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4
Q

What are some of the symptoms of pancytopenia from bone marrow failure?

A

1Symptoms of anemia including difficulty breathing, chest pain, and fatigue

  1. Symptoms of leukopenia/neutropenia including fever, infection and mouth sores.
  2. Symptoms of thrombocytopenia including bleeding.
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5
Q

Causes of Bone marrow failure?

Hypercellular Marrow

A
  1. Hypercellular marrow
    - bone marrow infiltration
    - leukemias, myeloma, lymphoma
    - carcinoma
    - storage disorders
    - myelodysplastic syndromes
    - B12 or Folate deficiency
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6
Q

Causes of bone marrow failure?

Hypocellular marrow

A

1.Aplastic anemia
-Fanconi’s anemia
Acquired
-Idiopathic
- Myelodysplastic syndromes
-Drugs/Chemicals
-Radiation
-Viruses

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7
Q

What is Aplastic Anemia?

A

A severe, life threatening syndrome in which production of all blood cells and platelets has failed.

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8
Q

What characterizes Aplastic Anemia?

A
  1. Peripheral Pancytopenia

2. Hypocellular Bone Marrow

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9
Q

What ages and sex are most prone to Aplastic anemia?

A

Occurs in all age groups and both genders.

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10
Q

What is the Pathophysiology of Aplastic anemia?

A

The primary defect is a reduction of haematopoietic precursor stem cells with decreased production of all cell lines.

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11
Q

What are possible causes of the loss or depletion of haematopoietic stem cells in Aplastic anemia?

A
  1. May be due to quantitative and qualitative damage to the pluripotent stem cells.
  2. May be the result of a dfective bone marrow microenvironment.
  3. Cellular or humoral immunosuppression of hematopoiesis
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12
Q

What is Fanconi’s Anemia?

A

Autosomal recessive aplastic anemia manifesting in childhood or early adult characterized by mental retardation, absence of thumb and radius, small stature, hypogonadism, and patchy brown discoloration of the skin.

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13
Q

At what age does Fanconi’s generally become symptomatic?

A

~5

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14
Q

How does Fanconi’s affect the bone marrow?

A

The bone marrow usually suffers with progressive hypoplasia.

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15
Q

What is Familial aplastic anemia?

A

A subset of Fanconi’s in which the congenital defects are absent.

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16
Q

What is the cause of most cases of Aplastic anemia?

A

Idopathic, no history or exposure to known causative substances.

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17
Q

What are other causes of Aplastic anemia?

A
  • Ionizing radiation 300-500 rads
  • Chemical agents i.e Benzene
  • Idiosyncratic reactions to some drugs such ad Chloramphenicol or quinacrine
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18
Q

What are some other causes of Aplastic Anemia?

A

Viral and Bacterial infections; Mononucleosis, infectious hepatitis, parvovirus, and cytomegalovirus as well as miliary tuberculosis

  1. Pregnancy
  2. PNH
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19
Q

What are the lab findings in Aplastic Anemia?

A
  1. Severe pancytopenia with relative lymphocytosis (due to live of lyphocytes)
  2. Normochromic and normocytic RBCs
  3. Mild to moderate anisocytosis and poikilocytosis
  4. Decreased reticulocyte count
  5. Hypocellular bone with >70% yellow marrow
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20
Q

What is the treatment of AA?

A
  1. Withdrawal of potentially offending agents
  2. Supportive care (e.g transfusion antibiotics)
  3. Immunosuppressive regimens i.e anti-thymocyte, globulin, cyclosporine, steroids can improve cell count in cases where AA is auto-immune mediated
  4. Hematopoietic cell transplantation
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21
Q

What is Pure Red Cell Aplasia?

A

Characterized by a selective decrease in erythroid precursor cells in the bone marrow and WBCs and platelets are unaffected.

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22
Q

What are possible causes of Pure Red Cell Aplasia?

A
  1. Transitory with viral and bacterial infections
  2. Patients with hemolytic anemias may suddenly halt erythropoiesis
  3. Patients with Thymoma can develop a T-cell mediated response against bone marrow erythroblasts and erythropoietin
23
Q

What is the treatment of Pure Red cell Aplasia?

A
  1. Supportive care

2. Immunosuppression

24
Q

What are myelodysplastic syndromes?

A

Primary neoplastic stem cell disorders that tend to terminate in acute leukemia.

25
Q

What are the findings in myelodysplastic syndromes?

A
  1. Bone marrow is usually normocellular or hypercellular with evidence of QUALITATIVE abnormalities in one or more cell lines resulting in ineffective erythropoiesis and or granulopoiesis and or megakaryopoiesis
  2. Peripheral smear would display dysplastic cells including nucleated RBCs, oval macrocytes psseudo-Pelger-Huet PMNs (hyposegmented neutrophils) with hyperchromatin clumping, hypogranulated neutrophils, and giant bizarre platelets
  3. Bone marrow would display ringed sideroblasts
26
Q

What is thought to be the cause of Myelodysplastic syndromes?

A

Thought to arise from mutations in the multipotent bone marrow stem cell.

  • Differentiation of blood precursor cell is impaired.
  • Significant increase in apoptotic cell death in bone marrow cells
27
Q

How can MDS be differentiated from AA?

A

The presence of a neoplastic clone differentiates MDS from AA.
-In MDS there is clonal expansion of abnormal cells which results in the loss of the ability to differentiate

28
Q

How does one tell when MDS has progressed to AML?

A

When the percentage of bone marrow blasts rises over 20% (WHO) of 30% (FAB)

29
Q

What are treatments for MDS?

A
  1. In 2005 Lenalidomide was approved for treatment of the 5q- syndrome subset of MDS
  2. Haematopoietic Stem cell transplantation particularly in younger patients i.e less than 60
30
Q

What is HSCT?

A

The transplantation of haematopoietic progenitor cells that have the ability to proliferate and repopulate marrow spaces.

31
Q

How are stem cells collected?

A
  1. Traditionally from marrow

2. More modern techniques include mobilizing stem cells into the peripheral blood and harvesting via apheresis

32
Q

What characteristics make HSCs transplant possible?

A
  1. Their ability to regenerate in the marrow
  2. Their ability to find their way back to the marrow following IV transfusion
  3. Their ability to be cryopreserved with little or no damage
33
Q

What is an Autologus HSC transplant?

A

Use of stem cell collected from a patient stored in a freezer to be reinfused or transplanted at a later date following high dose chemotherapy.

34
Q

What is the risk of immune reaction in autologous HSCT?

A

Because the stem cells belong to the recipientthere is minimal to no risk of a reaction between the and the recipient.

35
Q

What is the purpose of the Chemotherapy in Autologous HSCT?

A

To wipe out the recipient’s current syfunctional HSC and allow it to be rescued by the infused cells.

36
Q

When is HSCT mostly used?

A

In treatment of

  1. Lymphomas
  2. Multiple Myeloma
37
Q

What is meant by Allogenic HSCT?

A

Uses related or non-related HLA matched donors as the source of stem cell

38
Q

How is matching performed?

A

On the basis of variability at 3 or more loci of the HLA gene, and a perfect match at these loci is preferred to prevent GVHD

39
Q

WHat is required in Allogenic HSCT?

A

Immunosuppresive medications to mitigate GVHD. Even if there is a good HLA match.

40
Q

What is an alternative source of HSC especially in patients without an HLA match?

A

Umbilical cord blood.

41
Q

What are the advantages of allogenic vs autologous?

A

1Can be used when recepient’s bone marrow fails such as in AA and MDS
2.When recipient has leukemia and lymphoma, the donor cells can attack these tumor cells via graft versus host disease effect to prevent relapse of the tumor.

42
Q

What are disadvantages of allogeneic stem cell transplant?

A
  1. Higher risk of chemotherapy related complications with myeloablative transplant..such as mucositis, hepatic veno-occlusive disease
  2. Higher risk infection compared to AUTO SCT….increased risk of infections such as EBV CMV Fungal and parasitic infection
  3. Risk of rejection is minimal in current era is minimal but GVHD can be devastating and life threatening
43
Q

What are the types of Allogeneic HSCT?

A

Non-myeloablative and Myeloablative

44
Q

What is Non-myeloablative HSCT?

A
  1. Use low dose chemotherapy not enough to eradicate the recipeint’s bone marrow cells but enough to prevent the donor cells from being rejected.
  2. These transplants are less associated with lower risk of transplant-related mortality allowing high risk patients to undergo potential allogeneic HSCT.
45
Q

What is Myeloablative Allogeneic HSCT?

A
  1. A “conditioning or preparative” chemotherapy regimen given before the transplant is designed to eradicate the recepient’s bone marrow cells.
  2. A combination of cyclophosphamide and busulfan or total body irradiation is commonly used
  3. The chemotherapy also doubles as immunosupressive effect which works to prevent rejection of the HSC by the recipient’s immune system
  4. There are high rates of complications with myeloablative HSCTs especially in older patients
46
Q

What are some of the complications of HSCT

A
  1. Infection (due to pre-transplant marrow ablation, immunosuppressive drugs, loss of acquired immunity, need for re-vaccination)
  2. Veno-occlusive disease (severe liver injury) Elevated bilirubin, hepatomegaly and fluid retention are signs of VOD.
  3. Mucositis, injury to mucosal lining of the mouth and throat common to ablative therapy, not life threatening but painful prevents eating and drinking.
  4. GVHD-inflammatory disease unique to allogenic transplantation-is an attack of new bone marrow cells against the recipients tissues, CAN OCCUR EVEN IF THE DONOR AND RECIPIENT ARE HLA IDENTICAL immune system can recognize other differences.
47
Q

When does acute GVHD typically occur?

A

Within the first 3 months after the transplant may involve skin, intestine, or liver and is often fatal.

48
Q

WHat drugs can be used for prevention of GVHD?

A

Cyclosporine and Methotrexate to suppress immune response of donor red cells.

49
Q

What is used for the treatment of acute GVHD?

A

High dose steroids which can lead to infection if given long term

50
Q

When does Chronic Graft vs Host disease typically occur?

A

Usually occurs >3 after transplant

51
Q

What are other complications besides inflammation of chronic GVHD?

A

Fibrosis of organs such as skin liver intestine conjunctiva mucosa and lungs, similar to scleroderma

52
Q

What is GVHD mediated by?

A

Typically mediated by T-cells when they react to foreign peptides presented on the MHC of host

53
Q

What is the benefit of GVHD?

A

Termed Graft Versus Tumor or Graft vs Leukemia due to therapeutic immune reaction of grafted donor T-cells against diseased marrow of the recipient

54
Q

When is GVT/GVL most beneficial?

A

In diseases with slow progress e.g CLL, low grade lymphoma and some cases multiple myeloma has less effect against faster growing acute leukemias.

Haematology (16 decks)

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