Week 3 - Lecture 3b - Clinical Models Pt. 2 Flashcards
difference between Luekaemia and lymphoma
leukaemia is a term used for neoplasms with widespread involvement of the bone marrow and peripheral blood
lymphoma is used for proliferations that arise as discrete tissue Masses
check slides
leukaemia pathophysiology
malignant neoplasms of blood and blood forming organs
most common cancer in children
- can occur in adults
classification is based on predominant cell type and condition
ALL
AML
CLL
CML
what are B cells
B-lymphocyte
mature into plasma cells that produce antibodies to fight off an infection
also other B cells mature into memory B-cells
T and B cells are part of the acquired immune system
what are T cells
t-lymphocyte
type of white blood cell that circulates that body, scanning for cellular abnormalities and infections
killer T-cells and Helper T-cells
kill T cells have “x-ray vision” scan cells
helper T cells orchestrate an immune response to deal with germs and infection
T cells are responsible for rejection of a transplanted organ
- virtually all autoimmune diseases ( diabetes, MS, RA)
- allergic reactions for gluten intolerance
What are natural killer cells
they are a type of lymphocyte and a component of the innate immune system
-play a main role in the host- rejection of both tumours and virally infected cells
Acute leukaemia clinical manifestations
leukaemic cells are immature and poorly differentiated
- proliferate and long life span
- circulate in bloodstream, cross blood-brain barrier, infiltrate many body organs
80% of ALL has a B cell as precursor
-all is associated with
- alterations in the number of chromosomes
chromosomal translocation
-identifying alterations has prognostic significance
among non lymphocytic leukaemia :
myoblastic cell line involvement is prevalent - AML
- immature myeloid cells proliferate in bone marrow
-lack of ability to differentiate into specific functional blood cells
- anaemia (replaced by RBCs) leukopenia (reduced leukocytes) thrombocytopenia (reduced platelets)
chromosomal alterations have prognostic significance
Acute leukaemia clinical manifestations cont’
similar in ALL & in AML
sudden onset (acute) is related to
-immaturity of WBC’s and other cells originating in the bone marrow
- increased infection
- crowding of leukaemic cells in bone marrow
- suppressing RBC’s and platelet production
- anaemia, bruising, bleeding problems: frequent nose bleeds (epistaxis)
- anaemia leads to fatigue
- crowding leads to increase pressure and pain
- infiltration of leukaemic cells in the CNS, lymph nodes, liver, spleen
- in lymph nodes, spleen, liver: enlargement and tenderness of organs
unexplained weight loss, fever
acute leukaemia diagnostic criteria
history P/E
complete blood cell count
- >20% immature WBCs
cytologic examination of blood cells for leukaemia subtype
Acute Leukaemia treatment
ALL
ALL
systemic combination chemotherapy
prophylactic CNS intrathecal (into spinal canal) chemotherapy with and without radiation cranial radiation
- treatment protocol consists of induction, intensification, maintenance
-monitoring : myelosuppression and immunosuppression due to intense chemotherapy
goal : achieve remission
- 95% of children with ALL achieve remission
- 85% 5 survival rate
AML Treatment
systemic combination chemotherapy in 2 phases:
1. introduction to achieve remission
2. post remission
70% adults with AML can expect complete remission
Better prognosis - younger age, lack of CNS involvement, lack of systemic infection
chronic leukaemia pathophysiology
gradual onset
most common in middle and older adults
CLL
- over proliferation of B-lymphocytes
- relatively mature but not fully functional
- do not readily form antibodies in presence of antigens
- infection
CML
insidious onset
immature myeloid cells are involved
relatively mature but not fully functional
Chronic leukaemia patho 2
chronic leukaemia are differentiated by presenting
- certain B-cell antigens
- genetic aberrations
- chromosomal aberrations
philadelphia chromosome in CML : 95%
- chromosome 9 and 22 translocation
- activates the ABL oncogene.
Chronic leukaemia clinical manifestations
subtle or not present until the disease is well advanced
once present, clinical manifestations are similar to acute leukaemia’s
*same as the acute *
Chronic leukaemia diagnostic criteria
due to subtle onset, accidental diagnosis before symptom manifestations
complete blood count : elevated WBC count
Diagnosed through a bone marrow biopsy
cytologic examination of blood cells
- cytogenetic analysis of Philadelphia chromosome translocation (for CML diagnosis)
Chronic leukemia treatmetn
optimal treatment regimen is still under investigation
>50% patients may be cured by bone marrow or stem cell transplantation
- transplantation option Is limited
- age
- overall health
- inability to locate suitable donor
-extremely high WBCs (>100,000/mm3) ( normal value 5-10,000/mm3
- immediate chemotherapeutic treatment to avoid death from obstructed blood perfusion
- splenectomy may be required due to physical discomfort and haematologic disorders caused by enlargement
mediant survival
- CLL 8-12 years
- CML 4-6 yrs
Lymphoma pathophysiology
lymphomas (like some leukemias) have lymphoid stem cell origin
orm solid organ tumours in the lymph tissue and later in the bone marrow
diverse group of solid tumours
lymphoma can be present in the spleen
classified as
Hodgkin
non - hodgkin
Hodgkin lymphoma pathophysiology
painless, progressive enlargement of cervical (neck) lymph nodes
exact cause unknown
risk factors
- exposure to viruses such as Epstein-Barr virus
-genetic factors
-Immunosuppression
Childhood form of HL is similar to the adult onset
- 82% of children do not relapse within 5 years
- 5 year survival rate is 95%
adult mortality has declined most among malignancies
- improved radiation
- improved chemotherapy
Hodgkin lymphoma patho cont’
HL characterised by the presence of
- binucleated/multinucleated giant cells (macrophages) : Reed-Sternberg cells
- Mononuclear giant cells : Hodgkin cells
- other inflammatory cells
pathogenesis is still unclear
- Reed - Sternberg or Hodgkin cell is neoplastic origin with clonal section capability
- RS cell originates in the cell components of lymph nodes following B lymphocyte linage
HL arises In B-cells that cannot synthesise immunoglobulin and are resistant to apoptosis
After the primary tumour established
- spread to contagious lymph nodes and can infiltrate vascular system
-HL is organ tropic to lung, liver, bones and bone marrow
Hodgkin lymphoma patho pt 3
HL is classified according to histologic characteristics of affected cells
- two main categories differ based on B-cell immunophemotypew
- classic HL with subcategories
-nodular lymphocyte dominant HL
Staging ranges from - I (involvement of single lymph node) to
IV (disseminated involvement of one or more organs outside the lymphatic system)
These stages are further divided
- A: absence of specific system manifestations
B: presence of specific system manifestations
Specific systemic manifestations are related to rapid growth of abnormal lymphoid cells and tissues
- unexplained weight loss / unexplained fever/ drenching night sweats
Hodgkin lymphoma clinical manifestations
80% of patients with HL : nontender enlargement of cervical (neck) lymph nodes
- lymph nodes are form and rubbery in texture
- Reed-Sternberg or Hodgkin cells release inflammatory mediators lymphokines and cytokines
- low grade fever, night sweats, pruritus, weight loss fatigue
20% of patients have mass at the mediastinum
- greater than 1/3 of chest diameter
Splenomegaly, hepatomegaly may also be present
Lymphoma diagnostic criteria : Hodgkin
diagnosis and staging is based on history taking and P/E laboratory studies thoracic and abdominal CT scans most signifant: presence of reed Sternberg cells
Lymphoma treatment : hodgkin
treatment is based on clinical staging
- 77% relapse free survival in all patients newly diagnosed with HL
- Patient with stage IA or IIA are clinical early- stage
- chemo
- chemo radiation therapy
- radiation therapy alone
Patients with stage III and IV
- combination therapy with / without adjunct radiation therapy
reduced doses are used for children
high risk patients (poor prognosis) : 42-51% 5 year survival rate
Non hodgkin lymphoma
generic classifications of B-cell and T-cell malignancies with immune system
- NHL occurs more frequently than HL
-Does not exhibit Reed-Sternberg or Hodgkin cells
more likely to affect noncontagious lymph nodes
-aetiology Is unknown
- virus
- immunodeficiency
- genetic factors
Pathophysiology of non-hodgkin lymphoma
genetic susceptibility is highly variable
depends on specific cell affected by neoplasia
follicular lymphoma : alterations of BCL-2 gene is present in 90% of patients
- overexpression of BCL - 2 protein
- BCL 2 prevents apoptosis, leading to overproliferation of lymph tissue
NHL can spread via lymphatic and vascular system
NHL organ tropic to liver, spleen, bone marrow
non-hodgkin clinical manifestations
depends on tumour type and extent of disease
most common occurrence (as with HL)
Painless enlargement of lymph nodes
- other lymph nodes can also be affected
Specific systemic manifestations are related to rapid growth of abnormal lymphoid cells and tissues
- unexplained weight loss/unexplained fever/ drenching night sweats
increased risk of infection
paraneoplastic syndromes
Diagnosis of NHL
history PE
lymph node biopsy to confirm NHL
histopathologic analysis. immunophenotyping to determine linage
chest and abdominal CT/MRI/PET scan to visualise tumour size and
Treatment of NHL
treatment is based on categorising NHL’s into two prognostic groups
1. indolent (passive, painless) lymphomas
