MDS and HSCT Flashcards
What is MDS?
Diverse hematological malignancy characterized by cytopenias, ineffective hematopoiesis, and recurrent cytogenetic abnormalities
What is the median age of onset for MDS?
70 years
Which gender is predominantly affected by MDS?
Males
What percentage of blasts in bone marrow is diagnostic for MDS?
<20%
What are the main presenting symptoms of MDS?
Fatigue, Infections, Bruising, Some patients are asymptomatic
What are the diagnostic cytopenias criteria for MDS?
Hemoglobin <100g/L, Absolute neutrophil count <1800/microL, Platelets <100,000/microL
What findings may be seen on peripheral blood smear in MDS?
Tear drop cells, Elliptocytes, Howell Jolly bodies, Reduced segmentation of WBC
What is the standard treatment for high-risk MDS cases?
Hypomethylating agent azacitidine
What is a potentially curative therapy in young, high-risk MDS cases?
HLA matched allogeneic stem cell transplantation
What genetic mutation is associated with MDS classification?
SF3B1
In which classification systems is the SF3B1 mutation considered?
Both ICC and WHO
What is azacitidine?
Hypomethylating agent used in MDS treatment
For which risk category is azacitidine the standard of care?
High-risk MDS
What is lenalidomide?
Treatment agent for specific MDS subtype
In which genetic subtype of MDS is lenalidomide particularly effective?
Del5q
What benefit does lenalidomide provide?
Reduces need for blood transfusions
What is Del5q?
Genetic abnormality in MDS
What specific treatment is effective for Del5q variant?
Lenalidomide
What is AutoSCT?
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.
What are the indications for an AutoSCT?
Leukaemia, lymphomas, MM, solid tumours, amyloidosis, SCID, aplastic anaemia
What are the stem cell sources for AutoSCT?
BM aspiration from the posterior superior iliac spine, peripheral blood stem cell transplant, cord blood
What is the preferred HSC source for AutoSCT?
Bone marrow
What are the advantages of AutoSCT?
Low risk of GVHD and late onset post-transplant infections, low risk of graft rejection
What are the disadvantages of AutoSCT?
Higher risk of early onset post-transplant infections due to significant neutropenia, no graft vs tumour effect
What is AlloSCT?
Where the HSC are transplanted from a healthy donor to the patient
What is the main indication for AlloSCT?
Leukaemia
What is the aim of SCT?
To permit haemopoietic reconstitution after potentially curative but myeloablative doses of chemotherapy or chemoradiotherapy
What is the Graft-versus-Disease Effect?
Immune response by donor cells against recipient tissue, which can have both therapeutic and harmful effects
What therapeutic effect can Graft-versus-Disease have?
Graft-versus-leukaemia (GvL) effect
In which type of transplant does GvL occur?
Only in allogeneic transplants
What major toxicity is linked to GvL?
Graft-versus-host disease (GvHD)
What happens to GvL effect when GvHD is intensively prevented?
It is abrogated (eliminated)
What is BMT?
Stem cell transplantation using cells harvested directly from bone marrow through multiple aspirations
How are stem cells collected in BMT?
Multiple bone marrow aspirations under general anesthesia
What is the main disadvantage of BMT compared to PBSCT?
Requires general anesthesia for the donor
What is PBSCT?
Stem cell transplantation using cells collected from peripheral blood after mobilization
How are stem cells collected in PBSCT?
Through apheresis after mobilization
What is the engraftment time for PBSCT?
7 days
What advantage does PBSCT have over BMT?
Avoids general anesthesia and provides more rapid engraftment
What is the main disadvantage of PBSCT?
Higher incidence of chronic GvHD
What is conditioning?
Medical procedure using high-dose chemotherapy or chemo-radiotherapy to prepare a patient for bone marrow transplantation
What agents may be added to standard conditioning therapy?
Antibodies like alemtuzumab
What is Reduced Intensity Conditioning?
Modified conditioning approach that relies more on graft-versus-disease effect
How does Reduced Intensity Conditioning differ from standard conditioning?
Less intensive therapy, greater reliance on graft-versus-disease effect
What is engraftment?
Process where transplanted bone marrow or stem cells begin producing new blood cells
What is the typical timeframe for engraftment to occur?
7-25 days
What three cell types indicate successful engraftment?
WBCs, platelets, and RBCs
What period precedes engraftment?
Profound myelosuppression where fulminant infections are seen more often
Why is immunosuppression required after allogeneic transplantation?
To prevent graft failure, GvHD, and graft rejection
How are bone marrow or PBSC administered?
Intravenously (IV)
What is HSCT?
A procedure where healthy blood-forming stem cells are transplanted to replace diseased or damaged bone marrow
What is the general age limit for HSCT recipients?
≤70 years old
What is the chance of a full HLA match between siblings?
1:4
What should be considered regarding CMV status between donor and recipient?
Positive donors preferred for positive patients, negative donors for negative patients
What is RIC?
Conditioning regimen with reduced toxicity allowing transplantation in older patients
What main benefit does RIC provide for patient selection?
Allows increased age limit for transplantation
What outcomes are acceptable with RIC?
Toxicity, treatment-related mortality, and morbidity
What factor most influences the risk of GvHD?
Degree of HLA mismatching
What type of transplant has the lowest risk of GvHD?
Fully matched sibling transplant
What is HLA Matching?
The process of matching tissue types between donor and recipient
What is the primary reason for HLA matching?
To reduce risk of GvHD and graft rejection
When might a haplo-identical or mismatched donor be considered?
When no matched sibling or volunteer donor is available and risks are acceptable
How are donor cells administered in Allogeneic SCT?
Intravenously through a central line
How long after infusion until engraftment typically occurs?
7-21 days
What is the traditional myeloablative regimen?
Cyclophosphamide 120mg/kg + 14Gy fractionated TBI
What is the alternative to chemoradiotherapy in myeloablative conditioning?
Cyclophosphamide 120mg/kg + busulfan 16mg/kg
What is a key difference of RIC from traditional conditioning regarding radiation?
No TBI used
What advantage does RIC offer regarding patient selection?
Allows treatment of older patients and those with comorbidities
What post-transplant therapy does RIC enable?
Donor lymphocyte infusion for residual disease
For which patients is RIC discouraged?
Those with progressive or refractory disease
What is alemtuzumab?
Humanized anti-CD52 monoclonal antibody used for T-cell depletion
In which transplant types is alemtuzumab commonly used?
Unrelated donor or haploidentical SCT
Why is alemtuzumab given before conditioning?
To reduce risk of graft rejection
What is aplastic anemia?
A condition requiring modified stem cell transplantation
What modified conditioning regimen is used for aplastic anemia?
Cyclophosphamide with antithymocyte globulin
What is Fanconi anemia?
An inherited condition affecting DNA repair
Why is conditioning modified for Fanconi anemia patients?
Due to sensitivity to alkylating agents
What is SCID?
Severe Combined Immunodeficiency
What unique aspect of conditioning is possible in SCID?
Can engraft selected cell lineages without conditioning therapy
What are the two main causes of infective death in Allogeneic SCT?
CMV pneumonitis and invasive fungal infections
What common endocrine complications occur after Allogeneic SCT?
Infertility, early menopause, hypothyroidism
When do cataracts typically develop post-transplant?
> 12 months post-transplant
What viral infections commonly occur after Allogeneic SCT?
HSV and HZV with fulminant extensive lesions
What type of secondary malignancy is especially common after Allogeneic SCT?
Skin cancer
How common are psychological disturbances after Allogeneic SCT?
Common, but serious psychoses are rare
What is Graft versus Host Disease?
A complication where donor immune cells attack recipient tissues
When does the acute form of GvHD occur?
Within 100 days of transplant
When does the chronic form of GvHD occur?
After 100 days of transplant
What is PTLD?
Post-transplant lymphoproliferative disorder
What virus is associated with PTLD?
EBV
What is CMV Pneumonitis?
Cytomegalovirus infection of the lungs
What is its significance in transplant patients?
Major cause of post-transplant death
