Hematologic Cancers: Leukemia and Lymphoma Notes

Hematologic Cancers

Learning Objectives

• Compare and contrast the clinical and laboratory findings of the four major types of leukemia (AML, CML, ALL, CLL).

• Explain the nursing and interprofessional management of acute and chronic leukemias, including potential treatment options and the care of patients with pancytopenia and Leukostasis.

• Understand the benefits of combination chemotherapy.

• Explain the 3 different types of chemotherapy regimens in leukemia (induction, consolidation, and maintenance).

• Identify different remission states by clinical features (complete, minimal residual disease, partial, molecular).

• Compare Hodgkin lymphoma and non-Hodgkin lymphomas in terms of clinical manifestations, staging, and interprofessional and nursing management.

• Identify differences in clinical manifestations for leukemias and lymphomas

• Understand the unique characteristics of cancer cells

Key Terms

• Anemia

• Hodgkin lymphoma

• Leukemia

• Lymphoblastic leukemia

• Lymphoma

• Myeloblastic leukemia

• Neutropenia

• Non-Hodgkin lymphomas (NHLs)

• Pancytopenia

• Thrombocytopenia

• Angiogenesis

Normal Cells

1. Respond to normal growth signals from their environment, such as hormones or chemical messengers from distant glands or nearby cells. Every attachment is between proteins that provide the cell with constant signals about its environment and its "belongingness."

2. Respond to non-(anti) growth signals.

3. Die when triggered (Apoptosis: An orderly, programmed type of cell death).

4. Don’t stray from boundaries.

5. Live on the nutrients from an established, normal nutrient supply.

Cancer Cells

1. Become self-sufficient in growth signals.

   1. Maybe respond to growth signals that body produces

   2. Produces own growth signals

2. Ignore anti-growth or non-growth signals.

3. Don’t die per normal timing triggers (apoptosis).

   1. Continue living past the normal length of cell and how long they’re supposed to live for

4. Invade tissues nearby and at a distance (metastasis).

   1. Stray from boundaries

5. Develop their own blood supply (angiogenesis).

   1. AKA hemorrhagic tumor

   2. Removal of the tumor can lead to lot of bleeding because it has created its own blood supply

Leukemia

• A group of cancers affecting the blood and blood-forming tissues:

  • Bone marrow

    • Creates all formed blood cells (RBCs, WBCs)

  • Lymph system

    • Serves as weight station for migrating cancer cells

    • Once cells move into lymph system, they can move everywhere

  • Spleen

    • Removes abnormal blood cells and component through phagocytosis.

• Caused by the rapid production of abnormal white blood cells, due to loss of regulation in cell division.

• Fatal if untreated.

• Occurs in all age-groups; accounts for 28% of all childhood cancers.

Leukemia: Etiology and Pathophysiology

• No single cause; combination of genetic and environmental influences:

  • Oncogenes (abnormal genes) can cause many types of cancers.

  • Chemical agents, chemotherapy drugs, viruses, radiation, and immunologic deficiencies increase the risk of leukemia.

    • How these react to HLAs in the body (they live on cells

  • Exposure to pesticides and smoking.

  • Occurs more frequently in certain congenital disorders (e.g., Down Syndrome).

    • Due to translocation of chromosomes that create new proteins and causes genes to proliferate.

Leukemia: Pathophysiology

• Proliferation of immature cells (malignant, blast cells).

• Bone marrow failure (blast cells replace…)

  • Erythrocytes (RBCs) → anemia (not delivering enough oxygen to the tissues).

    • Effects: Weakness and pallor.

  • WBCs → decreases immunity (more prone to infections).

    • Effects: Immunosuppression (infection, fever).

  • Platelets → increased bleeding (less platelets).

    • Effects: Thrombocytopenia (bleeding, decreased clotting, petechiae, bruising, purpura).

• Cells infiltrate sites outside of the bone marrow.

  • Most common sites:

    • Central nervous system

    • Testicles

  • Other sites of involvement:

    • Joints

    • Spleen

    • Liver

    • Lymph nodes

Leukemia Classification

• Acute versus chronic:

  • Acute: Clonal proliferation of immature hematopoietic cells and onset is rapid.

    • All the immature cells overcrowd the healthy.

  • Chronic: More mature forms of WBCs and onset is gradual.

    • These cells have some properties of a correct cell but they aren’t a full mature cell, so they aren’t fully functional.

• Based on type of WBC:

  • Myelogenous (myeloblasts)

    • Acute myelogenous leukemia (AML)

    • Chronic myelogenous leukemia (CML)

    • These cancers are more likely to get anemia and thrombocytopenia due to myeloid production of RBCs and platelets

  • Lymphocytic

    • Acute lymphocytic leukemia (ALL)

    • Chronic lymphocytic leukemia (CLL)

    • These cancers are more likely to get immune problems due to lymphoid production of WBCs apart of the immune response

• Myeloid cells → RBCs, platelets, myeloid blasts

  • Myeloid blasts → Eosinophil, basophil, neutrophil (very immature cells & non-functional)

• Lymphoid cell → lymphoblast = B lymphocytes, T lymphocytes, and natural killer cells.

  • B lymphocytes (not enough = not producing antibodies)

  • T lymphocytes (not enough = not producing an immune response)

    • Organ: Thymus

  • NK cells (not enough = not as big of an immune response)

Acute Myelogenous Leukemia (AML)

• Abrupt, dramatic onset.

• Serious infection or abnormal bleeding.

  • Pts may come in with epistaxsis (bloody nose) and can’t get it to stop.

  • Abnormal bleeding due to myeloid production of RBCs and platelets

• 1/3 of all leukemias.

• 80% of the acute leukemias in adults.

• Increased incidence >60y age, or children 0-7y old

• Characterized by uncontrolled proliferation of myeloblasts.

• Hyperplasia of bone marrow.

  • Overgrowth of bone marrow

  • Too much bone marrow (overcrowding) and proliferation = bone pain from pressure

Acute Lymphocytic Leukemia (ALL)

• Most common type of leukemia in children; 20% of acute leukemia in adults.

• Immature, small lymphocytes proliferate in the bone marrow

  • Most are of B-cell origin.

    • Not producing antibodies

  • If T-cell origin, the thymus organ will be affected.

• Signs and symptoms may appear:

  • Abruptly: Fever or bleeding.

  • Insidiously: Progressive weakness, fatigue, bone and/or joint pain, bleeding tendencies (ex. Bruising easily, gums bleeding, finger nail short wont stop bleeding).

• CNS manifestations are common.

  • Confusion, irritability, ALOC

Chronic Myelogenous Leukemia (CML)

• Excessive development of neoplastic granulocytes in bone marrow

  • In all stages of development.

  • Move into peripheral blood in massive numbers.

  • Infiltrate liver and spleen.

    • May cause hepatomegaly and splenomegaly and complain of sense of fullness. Feels larger upon palpating.

• Philadelphia chromosome

  • Genetic marker (translocation/change of chromosomes that create a new protein). Hard to fight off due to rapid gene proliferation.

  • Present in 98% or more CML patients.

• Chronic, stable phase → no symptoms and understand they have cancer.

  • Followed by acute, aggressive (blastic) phase where symptoms are intense.

Chronic Lymphocytic Leukemia (CLL)

• Most common leukemia in adults.

• Production and accumulation of functionally inactive but long-lived, mature-appearing lymphocytes

  • B cells usually involved.

  • Lymphocytes infiltrate bone marrow, spleen, liver.

    • Infiltration of bone marrow s/s: bone pain

    • Spleen s/s: Splenomegaly

    • Liver: Hepatomegaly, glucose problems, altered bile production

  • Lymphadenopathy throughout body.

    • Increase of lymph nodes throughout body

• Complications are rare in early stage.

  • Common: Pain, paralysis from pressure caused by enlarged lymph nodes.

  • Mediastinal node enlargement leads to pulmonary symptoms.

    • Presses onto the lungs and decreases oxygenation

• Many patients in early stages may require no treatment.

Other Leukemias

• Subtype may be difficult to identify

  • May have lymphoid, myeloid, or mixed characteristics

  • Poor prognosis

• Overlap with non-Hodgkin lymphoma

  • Both involve proliferation of lymphocytes or their precursors

  • Lymphoma = more cancerous cells in lymphatic organs rather than in the blood and bone marrow

    • If a pt has cancer in their lymphatic organs, then the pt may present with enlarged lymph nodes and splenomegaly (pain in LUQ)

Leukemia: Clinical Manifestations

• Bone marrow failure

  • Overcrowding by abnormal cells

  • Inadequate production of normal marrow elements

    • Anemia

      • Weakness, pale, tired, confusion (a little bit)

      • Lack of oxygenation to tissues

    • Thrombocytopenia

      • S/s bruising, excessive bleeding (ex. Epistaxis), pietichial rash

    • Decreased number and function of WBCs; leukopenia and neutropenia

      • Leukopenia: CBC shows decrease in WBCs.

      • Neutropenia: CBC w/ Differential shows decrease in neutrophils.

      • Most hospitals will look at the absolute neutrophil count (ANC)to determine if someone is going to be on reverse isolation.

        • Reverse isolation = we protect them from us (neutropenic precautions).

  • As leukemia progresses, fewer normal blood cells are made

• Other manifestations, related to leukemic infiltrates:

  • Splenomegaly

  • Hepatomegaly

  • Lymphadenopathy

    • Swollen lymph nodes

  • Bone pain

    • From hyperplasia → overgrowth of bone marrow within bone.

    • To treat pain → radiation.

  • CNS manifestations - Meningeal irritation/meningitis

    • Nuchal rigidity

    • Increased ICP

    • ALOC / confusion

    • Short term memory loss

  • Oral lesions

    • MM compromised

  • Solid masses (chloromas)

    • Increase in blood cells → move out and create solid masses called chloromas & may be treated with chemotherapy.

Leukemia Complications: Leukostasis

• Life-threatening complication

• Caused by stasis of the blood cells with a high leukemic WBC count in peripheral blood

  • WBC > 100,000 cells/µL

    • Immature WBCs

• Blood thickens and blocks circulatory pathways

  • Pts may have tissue hypoxia, decreased mental ion, decreased oxygen delivery

• Treatment Options:

  • Leukapheresis

    • Similar to dialysis; takes a lot of WBCs out and replace with normal healthy plasma

  • Hydroxyurea

    • Medication that helps decrease cells

Leukemia: Diagnostic Studies

• Peripheral blood evaluation

  • Take blood sample and look under microscope to see if immature or mature and how many.

• Bone marrow examination - most definitive

  • Tells what type of cell and how far along disease is

  • Painful & given local anesthetic (lidocaine)

• Lumbar puncture

  • Especially with CNS involvement

• PET/CT scan

  • Shows metastasis, splenomegaly, hepatomagaly, etc.

Leukemia Treatment: Combination Chemotherapy

• Mainstay of treatment

• Three purposes

  • Decrease drug resistance

  • Minimize drug toxicity by using multiple drugs

  • Interrupt cell growth at multiple points in cell cycle

    • Cancer cells can become dormant

Leukemia: Chemotherapy Stages

1. Induction therapy

2. Consolidation (Postinduction or postremission)

3. Maintenance

Leukemia Chemotherapy: Induction Therapy

• Attempt to induce remission

  • Pts get large amount of this treatment to hopefully restore normal hematopoiesis.

• Seeks to destroy leukemic cells in tissues, peripheral blood, and bone marrow

• Patient may become critically ill

  • Neutropenia, thrombocytopenia, anemia

  • Decreased appetite (anorexia), sores in the mouth, etc.

• 70% of patients younger than 50 achieve complete remission

Leukemia Chemotherapy: Consolidation

• Intensification therapy

  • High-dose therapy; start after induction therapy

  • Uses drugs that target cell in a different way than those administered during induction

• Consolidation therapy

  • Started after remission is achieved

  • Eliminate remaining leukemic cells that may not be clinically or pathologically evident

Leukemia Chemotherapy: Maintenance Therapy

• Goal is to keep body free of leukemic cells

• Duration varies from 6 weeks to 2 years

Leukemia: Types of Remission

• Chemotherapy goal is to attain remission.

• 4 types:

  • Partial – evidence of disease in bone marrow

    • Not a lot of symptoms and pt may decide to stop treatment

  • Minimal Residual Disease – cancer cells not seen in bone marrow but PCR still positive for cancer cells

    • There might be an HLA or something that shows there’s still disease

  • Molecular – PCR neg for cancer cells (“cured”)

    • May develop cancer again

  • Complete – no signs of disease

    • CBC might be clear & no symptoms

• Prognosis is directly related to ability to maintain remission. With each relapse, prognosis gets worse.

Leukemia: Other Treatments

• Corticosteroids (First-line treatment for increased ICP)

  • Used to help decrease inflammation especially in pts who have had changes in CNS.

• Radiation therapy

  • Total body radiation in preparation for bone marrow transplantation

    • Want to kill all normal cells and transplant with a Hematopoietic cell

  • Organ- or field-specific such as liver or spleen

    • Field = abdominal

  • Cranial radiation when CNS involved

    • Except for children under age 5

• Immunotherapy and targeted therapy

  • Monoclonal Antibodies

    • Ex. Rituximab, Alemtuzumab

Leukemia: Hematopoietic Stem Cell Transplant (HSCT)

• Goal of HSCT = Eliminate all leukemic cells using combinations of chemotherapy w/ or w/out total body irradiation

• Eradicates patient’s hematopoietic stem cells

  • Replaced with those of an HLA-matched:

    • Sibling (full sibling)

    • HLA-half-matched relative

    • Volunteer donor (allogenic)

    • Identical twin (syngeneic)

• This changes the persons DNA (you may develop the same allergic reactions as you donor as well as actual DNA and blood type)

• Potential complications: Graft v. Host rejection/disease, a severe infection

Leukemia: Nursing Management

• Considerations for pancytopenia:

  • (All blood cells diminished)

    • Anemia

      • Educate on s/s of anemia (exertional dyspnea, fatigue, pallor, increased cap refill)

      • Not related to an iron deficiency

      • Blood transfusion usually if <7

    • Thrombocytopenia

      • Monitor for s/s of bleeding

        • Use soft bristle toothbrush, electric razor, don’t blow nose too hard.

      • Avoid high-risk activities (climbing ladder, motorcycle, sports, etc.)

      • Fall risk

    • Neutropenia

      • Routine Vaccinations

      • Avoiding high-risk situations (large events) or people (small children, obvious respiratory illnesses or sickness)

    • Acute Care → watch CBC closely and transfuse PRN

Life Span of Blood Components (DONT MEMORIZE)

• RBC: 90-120 days

• Platelet: 7-8 days

• Neutrophil: 7-12 hours

  • Live longer in leukemia patients & cause problems

• Monocyte: 3 days

• Macrophage: 3 days

• Eosinophil: 3-8 hours

• Basophil: 7-12 hours

Leukemia: Nursing Management (Psychosocial)

• Many physical and psychologic needs:

  • Diagnosis evokes great fear

  • Family needs help adjusting to stress of sick role

  • May be viewed as hopeless, horrible disease

• Important nursing interventions:

  • Teaching patients that acute side effects of treatment are usually temporary

  • Encouraging patients to discuss quality-of-life issues

Leukemia Complications: Tumor Lysis Syndrome (TLS)

• Metabolic complication characterized by rapid release of intracellular components in response to chemotherapy (big cause) or radiation therapy (less often).

• Massive cell destruction releases intracellular components that are metabolized to uric acid by liver.

• Multiple blood abnormalities: hyperuricemia, AKI to kidney failure (elevated BUN and creatinine), hyperphosphatemia, hyperkalemia (worry about cardiac), hypocalcemia (worry about muscles)

Lymphomas

• Cancers originating in bone marrow and lymphatic structures

  • Result in proliferation of lymphocytes (these help with viruses)

• Comprise 4% to 5% of all cancers in United States

• Two major types

  • Hodgkin lymphoma

  • Non-Hodgkin lymphoma (NHL)

Hodgkin Lymphoma

• Makes up about 10% of all lymphomas

• Proliferation of abnormal giant, multinucleated cells in the lymph nodes

  • Reed-Sternberg cells

• Bimodal age-specific incidence

  • 15 to 30 years of age

  • Above 55 years of age

• Long-term survival exceeds 85% for all stages

Hodgkin Lymphoma: Etiology and Pathophysiology

• Cause remains unknown

• Key factors

  • Infection with Epstein-Barr virus (EBV)

  • Genetic predisposition

    • Related to someone with an HLA that ends up getting it

  • Exposure to occupational toxins

    • Radon, asbestos, etc.

• Incidence increased in those with HIV infection

  • HIV infects and attacks T cells

Hodgkin Lymphoma: Clinical Manifestations

• Usually gradual onset

• Enlargement of cervical, axillary, or inguinal lymph nodes (lot of lymph nodes in those areas)

  • Typically starts in the lymph nodes, as opposed to Non-Hodgkin Lymphoma (commonly extranodal → meaning starts outside)

  • Nodes are movable and nontender

  • Not painful unless nodes exert pressure on adjacent nerves

• Second most common location is a mediastinal node mass

Hodgkin Lymphoma: Clinical Manifestations (Common Symptoms)

• Weight loss

• Fatigue and weakness

• Fever and chills

  • Increased risk of infections

• Tachycardia

• Night sweats

• Advanced cases (moved form lymphatic system into other organs of immunity)

  • Hepatomegaly

  • Splenomegaly

  • Anemia

• Other physical signs vary, depending on disease location

Hodgkin Lymphoma: Clinical Manifestations (Other)

• EtOH consumption → may have a rapid onset of pain at the site of disease; cause for this is unknown. Usually in liver or spleen (abdominal organs)

• With mediastinal node involvement:

  • cough, dyspnea, stridor, dysphagia (especially if its pressing on to any of those organs living within the mediastinum)

• Initial findings that correlate with a worse prognosis

  • Called B symptoms

    • Fever greater than 100.4 ° F (38° C)

    • Drenching night sweats

    • Weight loss exceeding 10% in 6 months

Hodgkin Lymphoma: Diagnostic Studies

• Peripheral blood analysis

  • Increased ESR and LDH, hypercalcemia

• Excisional lymph node biopsy

  • Pulls out cells and looks for Reed-Sternberg cells

• Bone marrow examination

• Radiologic evaluation – CT/PET scan

Hodgkin Lymphoma: Interprofessional Management

• Combination chemotherapy

  • 2-8 cycles of chemo, no maintenance therapy

• Once in remission, a curative option may be intensive chemotherapy with the use of autologous (self) or allogeneic (volunteer) HSCT

• Involved site radiation as a supplement to chemotherapy

  • Helps if pt has a lot of lymph node involvement

• Response to therapy determined by PET/CT scans, other diagnostic tests

Hodgkin Lymphoma: Treatment Complications

• Potentially life-threatening problems are encountered in an attempt to achieve remission

  • Aggressive chemotherapy → bone marrow suppression, organ toxicity

• Increased risk for secondary cancers

  • May occur 10 years after treatment for Hodgkin lymphoma

  • Most common secondary cancers = lung cancer, breast cancer

• Increased risk of long-term treatment toxicity

  • Endocrine, heart, or lung dysfunction (may develop fibrotic or scar tissue, which decreases breathing or cardiac output)

Non-Hodgkin Lymphomas

• Broad group of cancers of immune system affecting all ages

  • Primarily B, T, or Natural Killer cells

  • Over 75 types

• All NHLs involve lymphocytes arrested in various stages of development

  • Aren’t mature cells

• NHL does not have a hallmark feature that parallels the Reed-Sternberg cell of Hodgkin lymphoma.

Non-Hodgkin Lymphomas: Etiology

• Unknown cause

• More common in people who have:

  • Inherited immunodeficiency syndromes

  • Have used immunosuppressive agents

  • Received chemotherapy or radiation

• Other risk factors: chromosomal translocations, infections, environmental factors (carcinogens)

Non-Hodgkin Lymphoma: Clinical Manifestations

• Widespread disease usually present at time of diagnosis

• Painless lymph node enlargement

  • Primary clinical manifestation

  • Lymphadenopathy can wax and wane

    • Started outside and moved inside to the lymph nodes (not always going to be there)

    • If this is the primary manifestation, then it’s a later stage disease.

• Other symptoms depending on where disease is present

  • Hepatomegaly

  • Splenomegaly

  • CNS tumors

Non-Hodgkin Lymphoma: Diagnostic and Staging Studies

• Resemble those used for Hodgkin lymphoma

• Since NHL is more often extranodal:

  • MRI, lumbar puncture, bone marrow biopsy, barium enema or upper endoscopy

• Precise histologic subtype through biopsy is extremely important

• In early NHL, CBC may be normal

  • Generally found at a later stage

Non-Hodgkin’s Lymphoma: Treatment

• Chemotherapy

• Biotherapy – monoclonal antibodies (“-mabs”)

• Radiation

• Sometimes phototherapy and topical therapy

• Hematopoietic stem cell transplant (HSCT)

  • Important for a curative

• Complete remission is uncommon. However, improvement in symptoms is expected in the majority of patients.