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Haematology Infectology and Immunology > MDS and HSCT > Flashcards

MDS and HSCT Flashcards

1
Q

What is MDS?

A

Diverse hematological malignancy characterized by cytopenias, ineffective hematopoiesis, and recurrent cytogenetic abnormalities

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2
Q

What is the median age of onset for MDS?

A

70 years

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3
Q

Which gender is predominantly affected by MDS?

A

Males

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4
Q

What percentage of blasts in bone marrow is diagnostic for MDS?

A

<20%

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5
Q

What are the main presenting symptoms of MDS?

A

Fatigue, Infections, Bruising, Some patients are asymptomatic

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6
Q

What are the diagnostic cytopenias criteria for MDS?

A

Hemoglobin <100g/L, Absolute neutrophil count <1800/microL, Platelets <100,000/microL

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7
Q

What findings may be seen on peripheral blood smear in MDS?

A

Tear drop cells, Elliptocytes, Howell Jolly bodies, Reduced segmentation of WBC

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8
Q

What is the standard treatment for high-risk MDS cases?

A

Hypomethylating agent azacitidine

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9
Q

What is a potentially curative therapy in young, high-risk MDS cases?

A

HLA matched allogeneic stem cell transplantation

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10
Q

What genetic mutation is associated with MDS classification?

A

SF3B1

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11
Q

In which classification systems is the SF3B1 mutation considered?

A

Both ICC and WHO

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12
Q

What is azacitidine?

A

Hypomethylating agent used in MDS treatment

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13
Q

For which risk category is azacitidine the standard of care?

A

High-risk MDS

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14
Q

What is lenalidomide?

A

Treatment agent for specific MDS subtype

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15
Q

In which genetic subtype of MDS is lenalidomide particularly effective?

A

Del5q

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16
Q

What benefit does lenalidomide provide?

A

Reduces need for blood transfusions

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17
Q

What is Del5q?

A

Genetic abnormality in MDS

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18
Q

What specific treatment is effective for Del5q variant?

A

Lenalidomide

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19
Q

What is AutoSCT?

A

To permit haemopoietic reconstitution after potentially curative but myeloablative doses of chemotherapy
or chemoradiotherapy (high-dose therapy (HDT)) in the treatment of malignant disease;

or

To replace congenital or acquired life-threatening abnormal BM or immune function with a normal haematopoietic and immune system.

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20
Q

What are the indications for an AutoSCT?

A

Leukaemia, lymphomas, MM, solid tumours, amyloidosis, SCID, aplastic anaemia

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21
Q

What are the stem cell sources for AutoSCT?

A

BM aspiration from the posterior superior iliac spine, peripheral blood stem cell transplant, cord blood

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22
Q

What is the preferred HSC source for AutoSCT?

A

Bone marrow

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23
Q

What are the advantages of AutoSCT?

A

Low risk of GVHD and late onset post-transplant infections, low risk of graft rejection

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24
Q

What are the disadvantages of AutoSCT?

A

Higher risk of early onset post-transplant infections due to significant neutropenia, no graft vs tumour effect

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25
Q

What is AlloSCT?

A

Where the HSC are transplanted from a healthy donor to the patient

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26
Q

What is the main indication for AlloSCT?

A

Leukaemia

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27
Q

What is the aim of SCT?

A

To permit haemopoietic reconstitution after potentially curative but myeloablative doses of chemotherapy or chemoradiotherapy

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28
Q

What is the Graft-versus-Disease Effect?

A

Immune response by donor cells against recipient tissue, which can have both therapeutic and harmful effects

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29
Q

What therapeutic effect can Graft-versus-Disease have?

A

Graft-versus-leukaemia (GvL) effect

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30
Q

In which type of transplant does GvL occur?

A

Only in allogeneic transplants

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31
Q

What major toxicity is linked to GvL?

A

Graft-versus-host disease (GvHD)

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32
Q

What happens to GvL effect when GvHD is intensively prevented?

A

It is abrogated (eliminated)

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33
Q

What is BMT?

A

Stem cell transplantation using cells harvested directly from bone marrow through multiple aspirations

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34
Q

How are stem cells collected in BMT?

A

Multiple bone marrow aspirations under general anesthesia

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35
Q

What is the main disadvantage of BMT compared to PBSCT?

A

Requires general anesthesia for the donor

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36
Q

What is PBSCT?

A

Stem cell transplantation using cells collected from peripheral blood after mobilization

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37
Q

How are stem cells collected in PBSCT?

A

Through apheresis after mobilization

38
Q

What is the engraftment time for PBSCT?

A

7 days

39
Q

What advantage does PBSCT have over BMT?

A

Avoids general anesthesia and provides more rapid engraftment

40
Q

What is the main disadvantage of PBSCT?

A

Higher incidence of chronic GvHD

41
Q

What is conditioning?

A

Medical procedure using high-dose chemotherapy or chemo-radiotherapy to prepare a patient for bone marrow transplantation

42
Q

What agents may be added to standard conditioning therapy?

A

Antibodies like alemtuzumab

43
Q

What is Reduced Intensity Conditioning?

A

Modified conditioning approach that relies more on graft-versus-disease effect

44
Q

How does Reduced Intensity Conditioning differ from standard conditioning?

A

Less intensive therapy, greater reliance on graft-versus-disease effect

45
Q

What is engraftment?

A

Process where transplanted bone marrow or stem cells begin producing new blood cells

46
Q

What is the typical timeframe for engraftment to occur?

A

7-25 days

47
Q

What three cell types indicate successful engraftment?

A

WBCs, platelets, and RBCs

48
Q

What period precedes engraftment?

A

Profound myelosuppression where fulminant infections are seen more often

49
Q

Why is immunosuppression required after allogeneic transplantation?

A

To prevent graft failure, GvHD, and graft rejection

50
Q

How are bone marrow or PBSC administered?

A

Intravenously (IV)

51
Q

What is HSCT?

A

A procedure where healthy blood-forming stem cells are transplanted to replace diseased or damaged bone marrow

52
Q

What is the general age limit for HSCT recipients?

A

≤70 years old

53
Q

What is the chance of a full HLA match between siblings?

A

1:4

54
Q

What should be considered regarding CMV status between donor and recipient?

A

Positive donors preferred for positive patients, negative donors for negative patients

55
Q

What is RIC?

A

Conditioning regimen with reduced toxicity allowing transplantation in older patients

56
Q

What main benefit does RIC provide for patient selection?

A

Allows increased age limit for transplantation

57
Q

What outcomes are acceptable with RIC?

A

Toxicity, treatment-related mortality, and morbidity

58
Q

What factor most influences the risk of GvHD?

A

Degree of HLA mismatching

59
Q

What type of transplant has the lowest risk of GvHD?

A

Fully matched sibling transplant

60
Q

What is HLA Matching?

A

The process of matching tissue types between donor and recipient

61
Q

What is the primary reason for HLA matching?

A

To reduce risk of GvHD and graft rejection

62
Q

When might a haplo-identical or mismatched donor be considered?

A

When no matched sibling or volunteer donor is available and risks are acceptable

63
Q

How are donor cells administered in Allogeneic SCT?

A

Intravenously through a central line

64
Q

How long after infusion until engraftment typically occurs?

A

7-21 days

65
Q

What is the traditional myeloablative regimen?

A

Cyclophosphamide 120mg/kg + 14Gy fractionated TBI

66
Q

What is the alternative to chemoradiotherapy in myeloablative conditioning?

A

Cyclophosphamide 120mg/kg + busulfan 16mg/kg

67
Q

What is a key difference of RIC from traditional conditioning regarding radiation?

A

No TBI used

68
Q

What advantage does RIC offer regarding patient selection?

A

Allows treatment of older patients and those with comorbidities

69
Q

What post-transplant therapy does RIC enable?

A

Donor lymphocyte infusion for residual disease

70
Q

For which patients is RIC discouraged?

A

Those with progressive or refractory disease

71
Q

What is alemtuzumab?

A

Humanized anti-CD52 monoclonal antibody used for T-cell depletion

72
Q

In which transplant types is alemtuzumab commonly used?

A

Unrelated donor or haploidentical SCT

73
Q

Why is alemtuzumab given before conditioning?

A

To reduce risk of graft rejection

74
Q

What is aplastic anemia?

A

A condition requiring modified stem cell transplantation

75
Q

What modified conditioning regimen is used for aplastic anemia?

A

Cyclophosphamide with antithymocyte globulin

76
Q

What is Fanconi anemia?

A

An inherited condition affecting DNA repair

77
Q

Why is conditioning modified for Fanconi anemia patients?

A

Due to sensitivity to alkylating agents

78
Q

What is SCID?

A

Severe Combined Immunodeficiency

79
Q

What unique aspect of conditioning is possible in SCID?

A

Can engraft selected cell lineages without conditioning therapy

80
Q

What are the two main causes of infective death in Allogeneic SCT?

A

CMV pneumonitis and invasive fungal infections

81
Q

What common endocrine complications occur after Allogeneic SCT?

A

Infertility, early menopause, hypothyroidism

82
Q

When do cataracts typically develop post-transplant?

A

> 12 months post-transplant

83
Q

What viral infections commonly occur after Allogeneic SCT?

A

HSV and HZV with fulminant extensive lesions

84
Q

What type of secondary malignancy is especially common after Allogeneic SCT?

A

Skin cancer

85
Q

How common are psychological disturbances after Allogeneic SCT?

A

Common, but serious psychoses are rare

86
Q

What is Graft versus Host Disease?

A

A complication where donor immune cells attack recipient tissues

87
Q

When does the acute form of GvHD occur?

A

Within 100 days of transplant

88
Q

When does the chronic form of GvHD occur?

A

After 100 days of transplant

89
Q

What is PTLD?

A

Post-transplant lymphoproliferative disorder

90
Q

What virus is associated with PTLD?

A

EBV

91
Q

What is CMV Pneumonitis?

A

Cytomegalovirus infection of the lungs

92
Q

What is its significance in transplant patients?

A

Major cause of post-transplant death

Haematology Infectology and Immunology (1 decks)

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