Haematology PAS Flashcards
What are the Principal subtypes of leukaemia
Acute: Acute lymphoblastic leukaemia (ALL),
Acute myeloid leukaemia (AML).
Chronic:
Chronic lymphocytic leukaemia (CLL), Chronic myeloid leukaemia (CML)
What is the approach to a patient with Leukocytosis?
Review smear (are abnormal cells present?) and obtain differential count.
What is the approach to patients with complaints of non-specific confusion/drowsiness?
do blood
cultures, FBC, U&E, LFT, Ca2+
, glucose, and clotting. Consider CNS bleeding—CT if in
doubt.
Explain neutropenic regimen ?
- Full barrier nursing in a side room and hand wash.
*Avoid IM injections. - Look for infection and Take swabs.
*blood ≈3—peripherally
± Hickman line
*Check vital signs 4-hrly
*Wash perineum after defecation
*Oral Candida and other infections prophylaxis are important.
What is the risk and management of of Hyperviscocity syndrome ?
leukostasis in heart, vessels and leukocytic thrombi in brain and other organs.
TX is hydroxycarbamide or leukapheresis.
Definition of DIC ?
DIC is defined as the release of procoagulants into the circulation causing widespread activation of coagulation, consuming clotting factors and platelets and increasing risk of
bleeding.
Signs of DIC ?
Bruising, bleeding, renal failure.
Laboratory markers of DIC ?
*Decreased Platelets
* Prolongation of PT; APTT due to consumption of coagulation factors.
* Decreased fibrinogen (correlates with severity)
*Increased fibrin degradation products (D-dimers).
Histology of DIC ?
*schistocytes
Treatment of DIC ?
- Replace platelets to overcome thrombocytopenia.
/L - cryoprecipitate to replace fibrinogen.
*FFP to replace coagulation factors
The commonest leukaemia with highest risk of DIC is acute pro myelocytic leukaemia: How is it treated?
all-transretinoic
acid (ATRA)
How to prevent sepsis in Leukaemia?
*Fluoroquinolone (eg ciprofl oxacin) before neutropenia gets
serious.
*Granulocyte colony stimulators (G-CSF) can increase the production of WBCs
(granulocytes) Careful during Chemotherapy.
*Herpes, pneumocystis, and CMV prophylaxis
Definition of Acute Lymphoblastic Leukaemia ?
A malignancy of lymphoid cells, affecting B- or T-lymphocyte cell lineages, arresting
maturation and promoting uncontrolled proliferation of immature blast cells, with
marrow failure and tissue infiltration
Risk factor for Acute Lymphoblastic Leukaemia ?
- Ionizing radiation during pregnancy.
*Down’s syndrome
The most common paediatric leukaemia ?
Acute Lymphoblastic Leukaemia ( CNS involvement is common)
Morphological classification of ALL?
L1, L2 and L3
L1 type ALL histology
Small
blasts with scanty cytoplasm
Histology of L2 subtype ALL?
Larger
blast cells with greater morphological variation and more abundant cytoplasm.
Histology of L3 subtype ALL?
Blasts with vacuolated basophilic cytoplasm.
What are the immunological classification of ALL?
Surface markers are used to classify ALL into:
*Precursor B-cell ALL
* T-cell ALL
* B-cell ALL.
What is the utility of cytogenic or chromosomal analysis based classification of ALL ?
To predict disease prognosis and recurrence.
Signs and symptoms of acute Lymphoblastic Leukaemia ?
- Marrow failure: anaemia (<Hb), Infection (< WBC), Bleeding (<platelets)
*Infiltration: Heapato and or splenomegaly, Lymphadenopathy, orchidomegaly. - CNS involvement: cranial nerve palsies and meningism.
Common infections in ALL?
*Bacterial septicaemia,
*zoster, CMV, measles,
*candidiasis, Pneumocystis pneumonia
Lab test in ALL are
- CBC look for blast cells and WBC count.
- CXR and CT chest to rule out mediastinal lymphadenopathy.
- LP to look for CNS involvement.
Management of ALL?
*SUpportive: blood and platelet transfusion. IV fluids, Alopurinol to prevent tumor lysis syndrome.
* Infections: immediate IV antibiotics + Neutropenic regimen + infection prophylaxis.
Chemotherapy for ALL remission induction?
vincristine, prednisolone, L-asparaginase + daunorubicin
Chemotherapy for remission consolidation in ALL?
HIgh to medium remission induction chemo in blocks.
What is the CNS prophylaxis of ALL ?
intrathecal (or high-dose IV) methotrexate ± CNS irradiation
Maintenance chemotherapy in ALL?
mercaptopurine (daily), methotrexate (weekly), and vincristine + prednisolone (monthly) for 2yrs.
what is meant by haematological remission of ALL ?
No evidence of leukaemia in blood + recoverning blood cells + <5% blasts in regenerating Marrow.
Prognosis of ALL?
- 70 to 90% cure in children
- 40% cure in adults, poor prognosis if t(9,22) philadalphia ALL .
- CNS presentation, low HB, significant leukocytosis or B cell ALL has poor prognosis.
- poor in philadelphia negative ALL relapse.
Acute myeloid leukaemia (AML) definition ?
Neoplastic proliferation of blast cells derived from marrow myeloid elements. It progresses rapidly (death in ~2 months if untreated; ~20% 3yr survival after Rx).
Incidence of Acute myeloid leukaemia (AML)?
Most common acute leukaemia in adults 1/ 10,000 per year.
Risk factors for AML ?
- Prior radiation and Chemotherapy
- Down syndrome and Bloom syndrome.
- Myelodysplastic syndromes and aplastic syndromes.
Morphological classification of AML ( based on WHO histological classification, cytogenetics, and
molecular genetics)?
1)AML with recurrent genetic abnormalities
2) AML multilineage dysplasia
3) AML, therapy related
4)AML, other (subclassified as M0–M7 by maturation)
Signs and symptoms of AML?
Marrow failure and infiltration of brain, spleen, liver etc causing organomegaly and leukocytic thrombi. CNS involvement at presentation is rare.
Diagnosis in AML?
Low or increased or normal WBC + blasts at least 20%
AML itself can cause ___
Fever
Septicemia organism prediction in AML ?
Common organisms rarely and rare orgnaisms such as candidia and aspergilus causes sepsis commonly.
Remission chemotherapy in AML ?
5 cycles of daunorubicin and
cytarabine in one week blocks to induce remission.
what mutation enhances sensitivity to Cytarabine ( 20% of patients )
RAS.
ALL histology
TdT , t(12, 21) in children, t(9,22) in adults) with Philadelphia +.
Specific markers of ALL of Lymphoid cells of T cell origin ?
CD3
Specific markers of ALL of Lymphoid cells of B cell origin ?
CD19, CD20, and CD22
Bone marrow transplant (BMT) in AML ?
*Pluripotent haematopoietic stem cells are collected from the marrow. Allogeneic transplants from HLA-matched donors are indicated in refractory or relapsing disease.
Steps of Bone marrow transplant in AML?
1) destroy leuk aemic cells and the immune system by, eg cyclophosphamide + total body irradiation.
2) repopulate the marrow with donor cells infused IV.
Note: Ciclosporin ± methotrexate to prevent GVHD.
Complications of BMT in AML
- GVHD, opportunistic infections, relapse of AML and infertility.
*~ 10% mortality.
AML causes gum ?
Hypertrophy
AML causes increased plasma urate from ?
Tumor lysis syndrome.
How is AML is differentiated from ALL based on bone marrow biopsy?
bone marrow biopsy shows Auer rods which are azurophilic cytoplasmic inclusions also seen in ApML, high grade myelodysplastic syndromes and not in ALL.
what is the definition of Myelodysplastic syndromes?
These are a heterogeneous group of disorders that manifest as marrow failure with risk of life-threatening infection and bleeding.
Median survival range of myelodysplastic syndromes ?
6 months to 6 years.
What percent of Myelodysplastic syndrome progress to acute leukaemia ?
30%
Laboratory findings in Myelodysplastic syndromes ?
- Pancytopenia with reduced reticulocyte count.
- Increased Marrow cellularity due to ineffective haematopoiesis.
- Ring sideroblasts in bone marrow.
What is the treatment of myelodysplastic syndromes ?
*Multiple transfusions of red cells or platelets as needed
* Erythropoietin ± G-CSF lower transfusion requirements.
* Allogeneic stem cell transplantation
*thalidomide analogues and hypomethylating agents to improve QL
Definition of Chronic myeloid Leukaemia ?
CML is characterized by an uncontrolled clonal proliferation of myeloid cells.
It accounts for 15% of leukaemias.
what is the age and gender predominance in CML ?
40–60yrs, Male Predominance.
Philadelphia chromosome (Ph) is present in what percentage of CML ?
> 80%
What is Philadelphia chromosome (Ph)?
A hybrid chromosome translocation of t(9,22) chromosomal long arms,giving raise to BCR/ABL fushion gene on chromosome 22.
Philadelphia chromosome (Ph)___ activity ?
tyrosine kinase
Those without Ph have ?
worse prognosis
Symptoms of CML
*Mostly chronic and insidious: <weight, tiredness, fever, sweats.
*features of gout
* Bleeding due to platelet dysfunction
*abdominal discomfort (splenic enlargement).
* ~30% are detected by chance.
SIgns of CML
- Splenomegaly >75%
- Hepatomegaly, anaemia, bruising
Laboratory findings in CML
- Leukocytosis with whole spectrum of myeloid cells, ie neutrophils, monocytes, basophils, eosinophils
- Low Hb
- variable platelets
- Bonemarrow hypercellularity
- increased urate and B12.
- Philadelphia chromosome in blood or bone marrow.
Survival in CML
Variable (5 to 6 years)
Phases of CML transformation?
- Chronic lasting months or years with little to no symptoms.
*Accelerated phase- increasing symptoms, spleen size, and difficulty in controlling counts - Blast transformation, with features of acute leukaemia ± death
Treating CML
- First line: BCR-ABL tyrosine kinase inhibitor.
*dasatinib has been used in imatinib-resistant blast crisis.
*Dasatinib and nilotinib allow more patients to achieve deeper,
more rapid responses.
*Those with lymphoblastic transformation may benefit from treatment as
for ALL.
*Stem cell transplantation. Allogeneic transplantation from an HLA-matched sibling or unrelated donor offers the only cure, but carries significant morbidity and
mortality
What is the Hallmark of CLL?
The hallmark of CLL is progressive accumulation of the malignant clones of functionally incompetent
B cells. Mutations, trisomies, and deletions increases risk.
What is the epidemiology of CLL
CLL is the commonest leukaemia (>25%; incidence: ~5/100 000/yr). M:F≈2:1
What is the staging of CLL?
Stage 0= Lymphocytosis alone Median survival >13yrs
Stage 01= Lymphocytosis + lymphadenopathy median surivial 8 years.
Stage 02= Lymphocytosis + spleno- or hepatomegaly, median survival 5 years.
Stage 03= Lymphocytosis + anaemia (Hb <110g/L) median survival 2 years.
Stage 04= Lymphocytosis + platelets <100 ≈ 109/L, median survival 1 year.
Symptoms of CLL?
Often none, presenting as a surprise finding on a routine FBC. Patients
may be anaemic or infection-prone, or have ,<weight, sweats, anorexia if severe.
Signs of CLL ?
Enlarged, rubbery, non-tender nodes+ Hepato or hepatosplenomegaly.
Complications of CLL?
*Autoimmune haemolysis
*increased Infection due to hypogammaglobulinaemia (= low IgG), bacterial, viral especially herpes zoster.
* Marrow failure
Treatment of CLL
- Drug therapy tailored to symptoms
*Fludarabine + rituximab ± cyclophosphamide is 1st line (there is synergism) - Radiotherapy
helps lymphadenopathy and splenomegaly.
*Supportive care: Transfusions, IV human immunoglobulin if recurrent infection.
*Stem-cell transplantation may have
a role in carefully selected patients
Natural Hx of CLL
*⅓ never progress (or even regress), ⅓ progress slowly, and ⅓ progress actively.
*CD23 and beta 2 microglobulin correlate with bulk of disease and rates of
progression.
*Death is from Richter’s syndrome.
What are Lymphomas ?
Lymphomas are malignant proliferation of Leukocytes that occur within the Lymph nodes as opposed to it in bone marrow as in in Leukemias.
What are the broad classification of lymphomas
Hodgkins lymphoma and non-hodgkins lymphoma.
What is the histological hallmark of Hodgkin’s Lymphoma ?
Reed-Sternberg cells in lymph node biopsy.
Epidemiology of Hodgkins Lymphoma ?
Two peaks: 15 to 24 years and elderly
Male to female ratio: 2:1
Risk factors for Hodgkin’s Lymphoma ?
An affected sibling; EBV, SLE; post-transplantation.
Symptoms of Hodgkin’s Lymphoma ?
- Enlarged, non-tender, Rubbery lymph nodes ( 60-70% cervical)
- 25% may have fever, weight loss,
night sweats, pruritus, and lethargy.
*alcohol-induced lymph node pain.
*Mediastinal lymph node involvement can cause mass effect,
*direct extension, eg causing pleural effusions.
Signs of H lymphoma ?
*Lymphadenopathy
*cachexia, anaemia, spleno- or hepatomegaly.
What is the tissue diagnosis in H lymphoma ?
Lymph node excision biopsy if possible. Image-guided needle biopsy, laparotomy, or mediastinoscopy may be needed.
What should be the blood test in Hodgkin’s’ Lymphoma ?
FBC, film, ESR, LFT,
LDH, urate, calcium.
Imaging in H lymphoma
CXR, CT/PET of thorax,abdo, and pelvis.
Ann Arbor staging of Hodgkin’s Lymphoma ?
Done by imaging ±marrow biopsy :
* 1 Confined to single lymph node region.
*2 Involvement of two or more nodal areas on the same side of the diaphragm.
*3 Involvement of nodes on both sides of the diaphragm.
*4 Spread beyond the lymph nodes, eg liver or bone marrow.
Ann Arbor staging of Hodgkin’s Lymphoma A or B classification.
- each stage is classified to A ( stage 01 A), if there is only Pruritus as associated symptom.
- Each stage is classified to B, if there are associated symptoms like weight lose, unexplained fever. B has worse prognosis.
Chemotherapy in Hodgkin’s disease ?
*Radiotherapy + short courses of chemotherapy for stages
I-A and II-A.
*Longer courses of chemotherapy for II-A with >3 areas involved through to IV-B.
Drugs used in Hodgkin’s disease?
Adriamycin (doxorubicin), Bleomycin, Vinblastine, Dacarbazine cures ~80% of patients.
what is the treatment of Hodgkin’s Lymphoma ?
High-dose chemotherapy followed by autologous stem cell transplantation.
Emergency presentation of Hodgkin’s Lymphoma ?
Infection; SVC obstruction— elevated JVP, sensation of fullness
in the head, dyspnoea, blackouts, facial oedema
What are the subtypes of Hodgkin’s Lymphoma ?
*Nodular sclerosing (70%) Good
Mixed cellularity (20–25%) Good
*Lymphocyte rich (5%) Good
Lymphocyte depleted (<1%) Poor
5 year survival in Hodgkin’s lymphoma ?
- depends of stage and grade.
*>95% in I-A lymphocyte predominant disease.
*<40% with IV-B lymphocyte-depleted.
what are non Hodgkin’s Lymphomas ?
All lymphomas without Reed-sternberg cells are grouped as non hodgkin’s lymphomas.
Most Non-Hodgkin’s Lymphoma’s are derived from?
B cells.
The most common Non-Hodgkin’s Lymphoma is ?
DLBCL
What are the causes of Non-Hodgkin’s Lymphomas ?
- high grade Lymphomas from EBV transformed cells.
- Immunodeficiency: HIV
*Drugs
*HTLV-1, H. Pylori - Toxins
- Congenital.
Signs and symptoms of Non-Hodgkin’s lymphoma?
- Superficial lymphadenopathy (75% at presentation).
** Extranodal disease (50%) Gut (commonest).
Gastric MALT is caused by
*H. pylori and usually regressess with eradication of the organism.
*MALT usually involves the antrum, is multifocal and metastasizes late
What are Non-malt Lymphomas ?
Non-MALT gastric lymphomas (60%) are usually diffuse
large-cell B lymphomas—high-grade and not responding well to H. pylori eradication.
What are the Non-hodgkin’s Lymphomas presents with diarrhoea, vomiting, abdominal pain, and weight loss + poor prognosis?
- immunoproliferative small intestine
disease (IPSID) - enteropathy/coeliac-associated intra-epithelial T-cell lymphoma (EATCL).
what is the pathology of cuataneous Lymphoma ?
clonal T cells in mycosis fungoides
Second most common type of Lymphoma is
cutaneous lymphoma (50% of the NH Lymphomas)
What is the oropharyngeal NH-Lymphoma ?
Waldeyer’s ring lymphoma causes
sore throat/obstructed breathing.
Systemic features of Non-hodgkin’s Lymphoma?
It is less common in Non- H lymphomas, when it does it indicates dissemination of the disease and the features are fever, night sweats, weight loss. Pancytopenia from marrow involvement—anaemia, infection,bleeding.
Blood test in NH lymphoma ?
FBC, U&E, LFT. >LDH ≈ worse prognosis,reflecting > cell turnover.
Marrow
and node biopsy in NH lympha
for staging based on Ann arbor classification.
Low grade NH Lymphomas are ?
indolent, often incurable and widely disseminated.
Examples of low grade NH Lymphomas are
follicular lymphoma, marginal zone lymphoma/MALT, lymphocytic lymphoma
Treatment of low grade NH lymphomas
They are closely related to CLL and are treated similarly.
Waldenström’s macroglobulinaemia is a ?
lymphoplasmacytoid lymphoma
and Produces IgM.
Examples of high grade Lymphomas are ?
They are more aggressive, but often curable. examples are DLBCL, Burkit’s Lymphoma.
Treatment of Low grade NH lymphomas ?
- None, if asymptomatic.
- Curative radiotherpay in localized disease.
- Remission maintenance therapy with interferon alfa or rituximab.
rituximab-refractory NH low grade Lymphomas ?
Bendamustine monotherapy or
Treatment of HIgh garde NH lymphoma ?
*R-CHOP’ regimen: Rituximab, Cyclophosphamide, Hydroxydaunorubicin, vincristine (Oncovin®) and Prednisolone.
*Granulocyte colony-stimulating factors (G-CSFs) help neutropenia.
Prognosis of NH Lymphomas ?
- poor prognosis if age >60 +/- Systemic symptoms, Bulky disease (abdominal mass >10cm), high LDH, Disseminated disease.
- 5 year survival is 30% for high grade and 50% for Low grade.
Histopathology of follicular lymphoma may show ?
‘buttock cells’ with
cleaved nuclei.
histology of Cutaneous T cell lymphomas may show
Sézary cells.
Rituximab in Follicular lymphoma ?
- Rituximab kills CD20 +ve cells by antibody-directed cytotoxicity ± apoptosis induction.
*It also sensitizes cells to CDVP( * cyclophosphamide, doxorubicin, vincristine, and prednisolone).
*It also has a role in maintaining remission, and in relapsed disease.
Immunophenotypes of AML ?
CD33 or CD13
Immunophenotypes of B lineage ALL?
CD10 and CD 19
Immunophenotypes of T lineage ALL?
CD3
