Hematological and Oncology

Question 1

SICKLE CELL ANEMIA
Sickle cell anemia is an inherited disorder that affects the shape of red blood cells.

Sickle cell anemia affects approximately 100,000 individuals in the U.S (CDC, 2019). The disease primarily affects African Americans, but can also affect other individuals from Mediterranean countries.

In the African American population, 1 in 365 African American infants will have sickle cell disease and 1 in 13 will have the trait (CDC, 2019).

Question 2

Sickle Cell

Individuals with sickle cell inherit the HbS gene from both parents. HbS causes the RBC to have a sickle shape, which alters the transport of oxygen and movement of RBC.

RBC are often clustered together causing vaso-occlusion. Individuals present with following symptoms: pain (primarily in the joints), generalized fatigue, fever, swelling to hands, and feet, tachypnea, priapism (in males) GI symptoms (nausea, vomiting, and abdominal pain). Physical assessment may reveal hepatomegaly and splenomegaly.

Question 3

Sickle cell anemia

affects several lab values.

Hemoglobin decreased

Hematocrit levels 20-30%

Reticulocyte count elevation

WBC elevation

Peripheral blood smear will show sickle shaped cells

Liver enzymes have the potential to be elevate

** Hemoglobin electrophoresis confirms the diagnosis.

Additional diagnostics: Joint x-rays, CT, MRI, blood cultures, and CBC.

Oxygen therapy required for patients with hypoxia.

In some instances, individuals may require blood transfusions. The following represent some factors that may warrant transfusion: symptomatic/recurrent anemia, sepsis, pre-operative treatment, and chronic hypoxia (Barkley, 2021).

Care for sickle cell patients also includes education on crisis prevention. Individuals should have yearly vaccinations for flu and pneumonia. It is common for individuals to take folic acid on a daily basis. Regular physical exams and family planning counseling is also necessary.

Question 4

MANAGEMENT of Sickle Cell

The mainstay of treatment in sickle cell crisis include pain medications, IV fluids, and supplemental oxygen. Opioid medications (IV/PO) are used in the outpatient and inpatient setting to control pain during crisis. Medications that are used include: Morphine and Dilaudid. If the pain is not severe, NSAIDS maybe used to control pain. Ensure the patient is properly hydrated, NS bolus. Patients who exhibit symptoms of dehydration without hypovolemic shock NS or Lactated Ringers up to 1 liter ( Barkley, 2021). 1/2 NS is used with ongoing therapy

Question 5

LEUKEMIA
Leukemia is a form of cancer that develops in the bone marrow.

The hematopoietic cells are altered which results in a decrease in normal blood cells. There are various types of leukemia, this sections will focus on ALL, AML, CML, and CLL.

The following are some symptoms associated with leukemia include: fatigue, bleeding gums, shortness of breath, pain (especially in joints and bones), fever, skin changes (petechia, ecchymosis), pale color, and lymphadenopathy (Barkley, 2021).

The individual maybe completely asymptomatic and some symptoms may or may not be present in the different types of leukemia.

Question 6

Leukemia-diagnosis

Patient assessment findings and peripheral smears are used to diagnose leukemia.

Bone marrow aspiration/biopsy is needed to definitively diagnose leukemia.

The following are labs that appear abnormal:

WBC elevation
HGB, HCT, and platelets decreased
ESR elevation
Labs maybe variable depending on the type of leukemia.

Question 7

Leukemia -Management

Individuals diagnosed with leukemia should be referred to an oncologist.

The management of leukemia is typically chemotherapy. Individuals may also undergo bone marrow transplantation.

Additional therapies include: IVF, blood transfusions, antibiotics for infections and allopurinol for patients who develop hyperuricemia.

Question 8

ALL (Acute lymphocytic leukemia)

Typically occurs in children, but can occur in adults.

5-year survival rate in adults up to 40%

Greater than 30% lymphoblasts in bone marrow or blood.

Reciprocal translocation results in abnormal chromosome.

Occurs between chromosomes 9 and 22.

Hallmark: Pancytopenia with circulating blasts

Fatigue, fever, large/bleeding gums, lymphadenopathy, joint pain
Peripheral smear/Bone marrow aspiration/biopsy
Chemotherapy

Possible bone marrow transplant

Question 9

AML (Acute myelogenous leukemia
Most common in adults

Remission rates up to 85%

Survival rates up to 40%

Abnormal proliferation of myeloid precursor cells

Decreased rate of apoptosis

Arrest in cellular differentiation

Mutation in the receptor tyrosine kinase FLT3
Ecchymosis, fever, fatigue
Peripheral smear/Bone marrow aspiration/ biopsy
Chemotherapy

Question 10

CML (Chronic myelogenous leukemia)
A myeloproliferative disorder that also includes polycythemia vera, primary thrombocytosis, and idiopathic myelofibrosis.

Cause: Unknown

Hallmark: Philadelphia chromosome

Affects the neutrophilic or eosinophilic or clonal; arise from a hematopoietic stem cell

Elevated WBC, 5% blasts
BCR-ABL1 causes initiation of CML will be seen in peripheral smear

Weight loss, fatigue, enlarged spleen abdominal fullness, bone tenderness/pain
Peripheral smear/Bone marrow aspiration/ biopsy
Chemotherapy(Tyrosine kinase inhibitor)- Imatinib
typically, not started immediately unless WBC< 200 or the patient has symptoms such as: dyspnea, confusion, priapism, blurred vison or DVT.

Question 11

TWO Types of LEUKEMIA

MYELOID AND LYMPHOCYTIC

MYELOID AFFECTS THE MYELOID CELLS -WHICH BECOME WBC, RBC AND PLTS

LYMPHOCYTIC AFFECTS THE LYMPHOCYTES (SPECIFICALLY B OR T CELLS )

Question 12

AML
EPIDEMIOLOGY- OLDER ADULTS

ACUTE ONSET OF SYMPTOMS -
-Signs of anemia
-Spontaneous bleeding
-petechiae
-ecchymosis

LABS
-normocytic anema
-neutropenia
-thrombocytopenia
PBS->30% myeloblasts and has Auer rods (occur in myeloid blast cells )

Question 13

CML
Epidemiology
occurs in age 25-50 years

Insidious onset of symptoms -
Mild signs of anemia
Splenomegaly
May be asymptomatic depending on level of WBC

LABS
-leukocytosis
-increased eosinophils and increased basophils

Question 14

ALL
Epidemiology
-Most common form in children

S/S
acute onset of symptoms
-CNS deficiencies

labs
- Normocytic anemia
-Thrombocytopenia
-WBC variable count
-PBS-less than 30% lymphoblasts

Question 15

CLL
Epidemiology -
Most common form in adults prognosis of 10 years without tx

S/S
insidious onset of symptoms
-Nonspecific fatigue and malaise
-Hepatosplenomegaly
-usually asymptomatic until end stage of disease

labs
-isolated lymphocytosis
-thrombocytopenia
-PBS-smudge cells

Question 16

TOM TIP: The key differentiating features to remember for exams are:

ALL is the most common leukaemia in children and is associated with Down syndrome

CLL is associated with warm haemolytic anaemia, Richter’s transformation and smudge cells

CML has three phases, including a long chronic phase, and is associated with the Philadelphia chromosome

AML may result in a transformation from a myeloproliferative disorder and is associated with Auer rods

Question 17

Chronic Myeloid Leukaemia
Chronic myeloid leukaemia has three phases:

Chronic phase
Accelerated phase
Blast phase

The chronic phase is often asymptomatic, and patients are diagnosed after an incidental finding of a raised white cell count. This phase can last several years before progressing.

The accelerated phase occurs when the abnormal blast cells take up a high proportion (10-20%) of the bone marrow and blood cells. In the accelerated phase, patients are more symptomatic and develop anaemia, thrombocytopenia and immunodeficiency.

The blast phase follows the accelerated phase and involves an even higher proportion (over 20%) of blast cells in the blood. The blast phase has severe symptoms and pancytopenia and is often fatal.

Chronic myeloid leukaemia is particularly associated with the Philadelphia chromosome. This refers to an abnormal chromosome 22 caused by a reciprocal translocation (swap) of genetic material between a section of chromosome 9 and chromosome 22. This translocation creates an abnormal gene sequence called BCR-ABL1, which codes for an abnormal tyrosine kinase enzyme that drives the proliferation of the abnormal cells.

Question 18

Acute Lymphoblastic Leukaemia
Acute lymphoblastic leukaemia (ALL) affects one of the lymphocyte precursor cells, causing acute proliferation of a single type of lymphocyte, usually B-lymphocytes. Excessive accumulation of these cells replaces the other cell types in the bone marrow, leading to pancytopenia.

Question 19

Chronic lymphocytic leukaemia is where there is slow proliferation of a single type of well-differentiated lymphocyte, usually B-lymphocytes. It usually affects adults over 60 years of age. It is often asymptomatic but can present with infections, anaemia, bleeding and weight loss. It may cause warm autoimmune haemolytic anaemia.

Richter’s transformation refers to the rare transformation of CLL into high-grade B-cell lymphoma.

Smear or smudge cells are ruptured white blood cells that occur while preparing the blood film when the cells are aged or fragile. They are particularly associated with chronic lymphocytic leukaemia.

Question 20

Acute Myeloid Leukaemia

There are many subtypes of acute myeloid leukaemia, with slightly different cytogenetics and presentations.

It can present at any age but normally presents from middle age onwards. It can be the result of a transformation from a myeloproliferative disorder, such as polycythaemia ruby vera or myelofibrosis.

A blood film and bone marrow biopsy will show a high proportion of blast cells. Auer rods in the cytoplasm of blast cells are a characteristic finding in AML.

General Management
An oncology and haematology multi-disciplinary team will coordinate treatment. Leukaemia is mainly treated with chemotherapy and targeted therapies, depending on the type and individual features.

Examples of targeted therapies include (mainly used in CLL):

Tyrosine kinase inhibitors (e.g., ibrutinib)
Monoclonal antibodies (e.g., rituximab, which targets B-cells)

Other treatments options include:

Radiotherapy
Bone marrow transplant
Surgery

Complications of Chemotherapy
Chemotherapy comes with a long list of complications and adverse effects:

Failure to treat cancer
Stunted growth and development in children
Infections due to immunosuppression
Neurotoxicity
Infertility
Secondary malignancy
Cardiotoxicity (heart damage)
Tumour lysis syndrome

Tumour Lysis Syndrome
Tumour lysis syndrome results from chemicals released when cells are destroyed by chemotherapy, resulting in:

High uric acid
High potassium (hyperkalaemia)
High phosphate
Low calcium (as a result of high phosphate)

Uric acid can form crystals in the interstitial space and tubules of the kidneys, causing acute kidney injury. Hyperkalaemia can cause cardiac arrhythmias. The release of cytokines can cause systemic inflammation.

Very good hydration and urine output before chemotherapy is required in patients at risk of tumour lysis syndrome. Allopurinol or rasburicase may be used to suppress the uric acid levels.

Question 21

LYMPHOMA
Lymphomas are conditions that affect the lymphatic system. Lymphoma can be classified as Hodgkin and Non-Hodgkin.

Question 22

HODGKIN LYMPHOMA
Hodgkin Lymphoma typically affects one specific groups of lymph nodes, has a predictable spread, and is identified earlier resulting in improved patient outcomes.
The condition typically develops in young adulthood, especially males, but can be diagnosed at any age.
Reed Sternberg cells are diagnostic for Hodgkin’s.
The American Cancer Society estimates in 2017 there will be over 8000 new cases and over 1000 deaths attributed to Hodgkin’s (About Hodgkin’s Disease,2017).

Symptoms associated with this condition include: painless lymphadenopathy (usually in the neck), night sweats, weight loss, itching, and weakness (Barkely , 2021)

Question 23

HODGKINS
DIAGNOSTICS
Physical exam and history
Biopsy of lymph nodes (Reed Sternberg cells present)
Other exams: CT, Chest x-ray, CBC, Bone scan, Gallium scan

STAGING
I - 1 lymph node
II - > 1 lymph node on 1 side of the diaphragm
III - Lymph nodes affected on both side of the diaphragm
IV - Disease spread to bone marrow and liver
Stage A : No symptoms
Stage B : Symptoms present (fever, night sweats, and weight loss)- Barkley, 2021

MANAGEMENT
Again, referral to oncologist is necessary. Therapies use to manage lymphoma include both chemotherapy and radiation. The type of therapy used depends on the staging of the condition.