Malignant Hematology

Question 1

What are the two types of bone marrow?

Answer 1

RED and YELLOW. All bone marrow is red at birth then converts to yellow as one ages. Red consists of hematopoietic stem cells and originates in the flat and long bones; whereas yellow consists of fat cells and resides in the hollow interior of the middle portion of long bones

Question 2

Where is the majority of stem cells found in adults?

Answer 2

Pooled in the bone marrow of the pelvis, vertebra, and sternum. Also major centres for blood production.

Question 3

All blood cells arise from where in the body?

Answer 3

From hematopoietic stem cells which are found in bone marrow. Erythrocytes (RBCs), platelets, white blood cells (WBCs), and
lymphocytes (B and T‐cell) originate from one single cell type – an undifferentiated parent cell
called the stem cell or “pluripotent” stem cell.

Question 4

What is hematopoiesis?

Answer 4

Hematopoiesis describes the process of blood cell development from a
pluripotent stem cell to a mature blood cell. It is the process of growth, division and
differentiation of blood cells. The end products of hematopoiesis are mature red blood cells
(RBCs), white blood cells (WBCs), platelets, and lymphocytes.

Question 5

What happens upon maturation of either myeloid or lymphoid cells?

Answer 5

It is released from the bone marrow into the blood stream.

Question 6

What do MYELOID stem cells develop into?

Answer 6

 Red blood cells - carry oxygen to all tissues of the body.
 Platelets - form clots in damaged blood vessels to prevent bleeding. Platelet life span is between 7-10 days.
 White blood cells – destroy bacteria and help fight infection. WBC life span varies depending on the types of WBCs (e.g. neutrophils 7-12 hours).

Question 7

What are Granulocytes and what are the three types?

Answer 7

Destroy bacteria to fight infection. 3 different types of granulocytes:
o Neutrophils – the main cells that fight infection. They ingest or engulf foreign cells
o Eosinophils – help control inflammation and allergic reaction. They attack and destroy certain parasitic organisms
o Basophils – play a role in a certain allergic reaction.

Question 8

What do Monocytes do?

Answer 8

o Help fight infection by ingesting substances like bacteria and
fungi.

Question 9

What do LYMPHOID stem cells develop into?

Answer 9

e LYMPHOID stem cells develop into lymphocytes – cells that make antibodies to fight
infection (Devine, 2013). Lymphocytes are found in the lymph nodes, thymus, spleen, tonsils,
adenoids, bone marrow and in lymphatic tissue in other parts of the body, such as the stomach
and intestinal lining. There are 3 different types of lymphocytes:
o B-Lymphocyte cells produce antibodies to fight bacteria, viruses and fungi
o T-Lymphocytes cells activate the B cells to produce antibodies
o Natural Killer (NK) cells attack any foreign cells.

Question 10

What do “Colony Stimulating Factors” (CSF) do?

Answer 10

If a higher number of WBCs is required by the body to combat infection, the “Colony‐Stimulating Factors” (CSFs) will stimulate
the stem cell to divide. One daughter cell from the division becomes committed to the blood cell line for WBCs and becomes what is known as a “precursor cell” for WBCs. The other daughter stem cell remains in the original pool so that the life time supply of stem cells is not depleted.

Question 11

What are blast cells and what are they responsible for?

Answer 11

The term “blast cells” refers to myeloblasts or myeloid blasts. These are the very earliest and most immature cells of the myeloid cell line. They are undifferentiated and unable to carry normal functions of normal mature cells. When the normal process of hematopoiesis becomes unregulated, many of the myeloblast cells fail to mature and begin to overcrowd the bone marrow. This overcrowding condition suppresses the production of other important cells, such as platelets, RBCs and healthy WBCs. The presence of blast cells on a complete blood count (CBC) is highly indicative of leukemia.

Question 12

What is Anemia?

Answer 12

Anemia is characterized by a reduction in the oxygen carrying capacity of the blood. This reduction is caused by inadequate levels of hemoglobin (Hb), inadequate numbers of erythrocytes (low hematocrit), or both. Severe anemia associated with hemoglobin level drop below 8 g/dl.

Question 13

What are common causes of anemia?

Answer 13

Some common causes of anemia include, but are not limited to:
* Dietary deficiencies of iron, vitamin B12 or folic acid.
* Hemorrhage
* Hemolysis
* Bone marrow failure
* Kidney disease
* Chemotherapy, biotherapy
* Radiation therapy (if radiated sites are areas of active marrow development)
* Surgery (blood loss)
* Stem cell transplant

Question 14

What are common symptoms of anemia?

Answer 14

Some common symptoms of anemia include, but are not limited to:
* Fatigue
* Increased heart rate
* Shortness of breath
* Low blood pressure
* Pale color
* Headaches
 Difficulty concentrating
* Feeling cold
* Irritable

Question 15

What are interventions for anemia?

Answer 15

Interventions for anemia may include medications (oral iron, erythropoietin/Eprex™, darbepoetin/Aranesp™), blood transfusions, oxygen, conservation of energy, nutrition

Question 16

What is thrombocytopenia?

Answer 16

Refers to a condition where the platelet count drops below 100,000 per microlitre. Normal human platelet count ranges from 150,000 to 450,000 platelets per microlitre of blood.

Question 17

What are thrombocytes?

Answer 17

Thrombocytes (or platelets) are developed in the bone marrow and are necessary for clotting. Bleeding due to thrombocytopenia is more common in hematological cancers than solid tumor
cancers.

Question 18

What are common causes of thrombocytopenia?

Answer 18

Some common causes of thrombocytopenia include:
* Splenomegaly (secondary to diseases, infections, etc)
* Diseases (leukemia, anemia, medications, alcohol, HIV, autoimmune diseases, infection)
* Pregnancy
 Idiopathic thrombocytopenic purpura (ITP). In ITP, your body’s immune system mistakenly identifies platelets as a threat and forms antibodies that attack them; autoimmune diseases; bacteria in blood
* Thrombotic thrombocytopenic purpura (TTP). A rare condition that occurs when small blood clots suddenly form throughout your body, using up large numbers of platelets
* Hemolytic uremic syndrome. This rare disorder causes a sharp drop in platelets, destruction of red blood cells and impairment of kidney function. Sometimes it can occur in association with a bacterial Escherichia coli infection, such as may be acquired from eating raw or undercooked meat
* Medications (chemotherapy, biotherapy, radiation, aspirin, estrogens, furosemide, tricyclic antidepressants, benzene, heparin, NSAIDS, quinine)

Question 19

What are symptoms of thrombocytopenia?

Answer 19

Some common symptoms of thrombocytopenia include:
* Easy or excessive bruising
* Superficial bleeding into the skin that appear as a rash of pinpoint-sized
reddish-purple spots (petechiae), usually on the lower legs
* Prolonged and/or perfuse bleeding
* Spontaneous bleeding from gums or nose
* Blood in urine or stools
* Unusually heavy menstrual flows

Question 20

What are interventions for thrombocytopenia?

Answer 20

Interventions may include platelet transfusions, patient/family teaching about preventative
measures to decrease risks of bleeding (e.g. avoid suppository, avoid using razor blade, avoid
contact sports, avoid flossing if it causes gums to bleed, take pills with food if indicated to
prevent GI bleed, prevent constipation).

Question 21

What is Neutropenia?

Answer 21

Refers to a condition where there is a decrease in circulating neutrophils (below 1.5 x 109/L).
Severe neutropenia refers to when the neutrophils count drop below 0.5 x 109/L, which put
patient at highest risk for developing an infection or sepsis.

Question 22

What are common risk factors of anemia?

Answer 22

Some common risk factors of neutropenia include:
 Pre-existing neutropenia condition
 Previous radiation to the bone marrow
 Highly myelosuppressive chemotherapy protocol
 Disease of the bone marrow (e.g. leukemia)
 Aging
 Renal and/or hepatic dysfunction
 Malnutrition
 Medications (e.g. steroids, phenothiazides, diuretics)

Question 23

What are common symptoms of neutropenia?

Answer 23

 Fever – often can be the only symptom when patient is severely neutropenic, with/without chills or rigor
 Redness, swelling, tracking along the central venous catheter lines
 Urinary: burning sensation, frequency, strong odour, pelvic pain, flank pain
 Cough, wheezing, sore throat
 Alter mental status (e.g. decrease alertness, confusion, lethargy)
 Lightheadedness, weakness
 Hypotension, tachycardia
 Rash (petechiae)

Question 24

What are interventions for neutropenia?

Answer 24

Interventions may include the use of hematopoietic growth factors (filgrastim or Neupogen™ –
short acting, and pegfilgrastim or Neulasta™ – long acting) and antibiotics (broadspectrum
initially). Patient and family teaching about preventative measures to decrease risks of infection,
such as frequent hand washing, avoid crowds if it is not essential, safe food handling, good
hygiene and oral care, avoid changing pet litter or handling pet stool, practice safe sex, avoid
the use of suppository if it is not essential.

Question 25

What is leukemia?

Answer 25

Leukemia is a cancer of the bone marrow that is characterized by two defects in the hematopoietic process: 1) Incomplete maturation of the white blood cells (WBCs) 2) Uncontrolled proliferation of these abnormal cells. Unlike normal blood cells, leukemia cells don’t die when they become old or damaged. As a result, leukemia cells can build up and crowd out normal blood cells. The low level of normal blood cells can make it harder for the body to get oxygen to the tissues, control bleeding, or fight infections.

Question 26

Which type of leukemia involves malignant proliferation of immature lymphoid cells in the bone marrow that also spread to the blood, CNS, and other organs.

Answer 26

Acute Lymphocytic Leukemia (ALL). It occurs in either the B- or T- precursor cells at different phases in their development.

Question 27

What is the significance of Philadelphia (Ph+) Chromosome and ALL?

Answer 27

25-30% of patients diagnosed with ALL have Philadelphia chromosome mutation. These patients have poorer prognosis, with long term survival less than 10%. Philadelphia chromosome is the result of a reciprocal translocation between chromosome 9 and 22. In simple words, a piece of chromosome 9 and a piece of chromosome 22 breaks off and switch places with each other. Presence of Philadelphia chromosome can be detected through cytogenetic testing.

Question 28

How do they confirm ALL?

Answer 28

Various tests and procedures are required to confirm a diagnosis of ALL:  Physical examination to determine patient’s functional status.  Complete Blood tests with differential.  Chemistry panel: electrolytes, liver profile, group & screen, clotting factors (PT, aPTT, INR), microbiology (serology for Hepatitis A, B, C, & cytomegalovirus), Reticulocyte count, Human Leukocyte Antigen (HLA) typing for patients 70 years old and younger.  Bone marrow aspiration and biopsy: Samples sent to pathology for morphology, flow cytometry, cytogenetics and molecular genetics (i.e. RT-PCR and FISH for evidence of the bcr-abl fusion gene).  Lumbar puncture: A spinal tap will be conducted if CNS involvement is in question.  Others: This may include ultrasound (if the patient has enlarged liver/spleen), MRI (as needed), CT scans (baseline lung view), and ECG.

Question 29

How do you classify acute leukemias?

Answer 29

There is no staging system for acute leukemias. Treatment is based on classification of the disease. Age and cytogenetic features are the most important predictors of prognosis in ALL. Older adults (greater than 60 years old) usually have a poorer prognosis than children.

Question 30

What are the presenting symptoms of ALL?

Answer 30

Patients with ALL rarely present any symptoms more than six weeks prior to diagnosis. The presented symptoms are the results of the reduction of normal hematopoietic cells, such as:  Anemia-related symptoms include: dyspnea, fatigue, malaise, pallor, decreased exercise tolerance  Thrombocytopenia-related symptoms include: bruises, petechiaea, purpura, ecchymosis, bleeding (gingival, cutaneous, epistaxis), hematuria, or GI bleed  Granulocytopenia-related symptoms include: infection, fever, chills, frequent infections  Bone and joint pain are the most common complaint resulting from increased blast in the bone marrow  Hepatomegaly, splenomegaly, and enlargement of testicles may be present  CNS involvement is rarely seen on presentation

Question 31

What are treatments of ALL?

Answer 31

The goal of treatment is to achieve cure through chemotherapy. In adults less than 60 years of age, approximately 80% to 90% of patients will achieve complete remission; however, the 5 year disease‐free survival rate is only 35% to 40%. Another important part of the treatment includes control of infections with antibiotics, and maintenance of stable hemodynamic state with transfusions of blood product and electrolyte replacement therapy. The nursing process is vital to management and support of the patient and their families during treatment.

Question 32

What are the 4 phases in the treatment of ALL?

Answer 32

1. Induction 2. CNS therapy 3. Consolidation 4. Maintenance / Continuation

Question 33

What occurs in the induction phase of ALL treatment?

Answer 33

The goal of the induction phase is to induce complete remission if possible (e.g. normal CBC with less than 5% blasts in the marrow and absence of ALL-related symptoms in the brain and anywhere in the body). For this part of the treatment, the patient is usually admitted in the leukemia inpatient unit for at least 4 weeks, sometimes even longer if complications arise.

Question 34

What occurs in the CNS phase of ALL treatment?

Answer 34

In 5-10% of individuals with ALL, the cancer has spread to the central nervous system (CNS) at diagnosis. In this phase, the goal of treatment is to kill any of the remaining leukemic cells that may have taken sanctuary in the brain. It is known that leukemic cells tend to spread to the brain in about 30-50% of patients will develop CNS involvement without prophylactic CNS treatment. The CNS phase starts after the induction has been completed, and takes 21 days to complete. Treatment protocol is the same regardless of patient’s age; however, treatment is different based on patient’s Philadelphia chromosome status.  For Ph+ ALL patients, treatment includes vinblastine, doxorubicin, imatinib, mercaptopurine or 6-MP), intrathecal methotrexate and cranial radiation  For Ph- ALL patients, treatment includes vincristine, mercaptopurine, doxorubicin, IT methotrexate and cranial radiation

Question 35

What occurs in the Maintenance/continuation phase of ALL treatment?

Answer 35

The maintenance/continuation phase is lower‐dose treatment given continuously over 2 to 3 years. It consists of 24 cycles; each cycle is 3 weeks for a total of 72 weeks. The goal of this treatment phase is to prolong the period of remission. Chemotherapeutic agents used may include vinblastine, dexamethasone, mercaptopurine, and methotrexate. Imatinib (Gleevec™) will only be given for patients who have the philadelphia chromosome. Intrathecal chemotherapy of methotrexate/cytarabine/ hydrocortisone is administered every 18 weeks.

Question 36

Which type of leukemia occurs in the precursor cells of the myeloid cell line?

Answer 36

Acute Myelogenous Leukemia (AML)

Question 37

What are risk factors of AML?

Answer 37

Risk factors may include: o Blood disorders o Genetic disorders (trisomy 21) o Age (older age is more at risk to develop AML) o Gender (Men > Women) o Viruses – the true role of viruses in leukemia development is unclear o Chemicals (e.g. benzene, pesticides, radiation rays, cigarette, solvent) o Drugs (e.g. alkylating agent, antibiotic chloramphenicol, phenylbutazone)

Question 38

How do they diagnose AML?

Answer 38

Diagnostic Test (Ososki & O’Riley, 2007): The following procedures are done to aid with the AML diagnosis:  Complete physical examination  Complete blood work (e.g. CBC, chemistry, coagulation)  Peripheral blood smear – shows increased number of blast cells. Presence of Auer rods is the only 100% marker of AML, platelet below 20,000/mm3 , and total WBC may be normal, elevated or low  Bone marrow biopsy – results are send for cytogenetic and flow cytometry testing

Question 39

What are the presenting signs of AML?

Answer 39

Anemia-Pallor, headache, palpitation, dyspnea, fatigue, foot swelling Thrombocytopenia -Mucosal and gum bleeding, petechiae, GI bleed Neutropenia-Local or systemic infection, recurrent infection, mouth and pharyngeal ulcerations, skin abscesses, chills, fever Infiltration by the leukemia cells-Swollen, reddened gums, hepatomegaly, splenomegaly, bone and join pain, granulocytic sarcoma

Question 40

Which type of stem cell transplant is preferred?

Answer 40

Allogeneic stem cell transplant (SCT) is preferred over an autologous SCT. In allogeneic SCT, the stem cells donor comes from someone other than the patient; therefore, it eliminates the risk of giving back some of the leukemia cells. Another benefit of allogeneic SCT is the “graft vs. host disease (GVHD)” – where the donor immune cells recognize the leukemia cells as “foreign” and attack them (ACS, 2014).

Question 41

What is Acute Promyelocytic Leukemia (APL)?

Answer 41

APL is an aggressive form of AML (M3), but highly treatable. It is characterized by a chromosomal translocation involving the retinoid acid receptor alpha (RARα or RARA) gene [Leukemia & Lymphoma Research (LLR), 2011; Walker & Held-Warmkessel, 2010]. This leads to excessive accumulation of promyelocytic cells (immature granulocytes) in the bone marrow (figure 9).

Question 42

What is DIC?

Answer 42

Patients with APL are prone to sudden onset of severe bleeding that can rapidly progress to severe or even fatal hemorrhage. This condition is known as Disseminated Intravascular Coagulopathy (DIC). It is a complex, lifethreatening condition that causes a hypercoagulative state. The coagulation cascade is triggered by the release of tissue factor (TF) – leading to abnormal bleeding event, clot formation and organ failures

Question 43

What do you monitor for in DIC?

Answer 43

Thus, it is important to monitor patient closely for S&S of bleeding, such as: o Skin/oral mucosa: petechiae, bruishing, gum bleed o GI: frank blood or coffee ground emesis, melena, abd. pain/distention o CNS: rapid onset of severe headache, vomiting, confusion, decrease level of consciousness, restlessness, and interval lucidness o Others: nose bleed, hematuria, fatigue, anemia, vaginal bleeding, coughing blood, hypotensive, tachycardia

Question 44

How do you manage DIC?

Answer 44

DIC management:  Monitor platelet count and coagulation.  Recognize early S&S of DIC and treat promptly – DIC is an Oncologic ER!!  Administer platelet (keep above 50), Fresh Frozen Plasma and cryoprecipitate.  Start ATRA promptly (see APL treatment). The use of ATRA prior to and during chemotherapy treatment has greatly reduced severe coagulopathies in APL patients. 38 | P a g e  Institute safety precaution to prevent injury and bleeding (e.g. minimize invasive procedure, fall prevention).