Care of Adult & Child With Malignant Proliferation of WBC’s

Cancer Treatment in Children

The lowest effective doses of drugs and radiation are used to treat cancer

Cardinal Symptoms of Cancer in Children

Unusual mass or swelling

Unexplained paleness or significant loss of energy

Sudden tendency to bruise; petechiae

Persistent, localized pain or limping

Un-resolving cold/ Fever, infection (neutropenia)

New onset of headaches, often with vomiting

Sudden eye or vision changes

Anorexia, excessive weight loss (proliferation/metabolic demands)

May initially be confused with rheumatoid arthritis or mononucleosis

General Diagnostic Tests

Routine History and Physical

Bone Marrow Aspiration & Biopsy

CBC / differential

Absolute Neutrophil Count (ANC)

Philadelphia Chromosome 22 (+) in 90% CML

Lumbar Puncture (brain mets)

X-rays and Imaging Studies IVP, CT, Ultrasounds, MRI

CBC/Differential

Absolute Neutrophil Count (ANC)

Philadelphia Chromosome 22 (+) in 90% CML

Leukemia

Broad term involving a Proliferation of immature WBC’s (leukocytes)

Malignant disease (cancer) of blood forming tissues

Disorder of bone marrow affecting the most vascular organs: blood, bone marrow, liver, spleen, lymph nodes

Effects: a massive production of immature (blast) abnormal WBC’s, effecting the bone marrow and all that the BM does. Hence: anemia, thrombocytopenia, neutropenia

Most Common Types of Leukemia

ACUTE:

**ALL – acute lymphocytic

AML- acute myelogenous

*CHRONIC:

*CML – chronic myelogenous

*CLL – chronic lymphocytic

*usually only seen in adults

** usually only seen in children <15 y/o

Acute Anemia Types

**ALL – acute lymphocytic

AML- acute myelogenous

This leukemia is usually only seen in children <15 y.o

Acute Lymphocytic Leukemia (ALL)

Acute Myelogenous Leukemia

Affects all ages

Acute Myelogenous Leukemia Risk Factors

Male and increasing age (>68 years of age)

Exposure to ionizing radiation or chemicals like benzene or pesticides

Bone marrow damage from pelvic radiation

Certain chemotherapy drugs (years after treatment of past malignancy) like alkylating agents or topoisomerase inhibitors

Blood disorders such as myeloproliferative diseases

Smoking

Down syndrome, trisomy 8, Fanconi anemia

Acute Myelogenous Leukemia Clinical Manifestations

Neutropenia- fever and infection

Anemia- pallor, fatigue, weakness, dizziness, dyspnea on exertion

Thrombocytopenia- ecchymoses (bruises), petechiae, epistaxis, gingival bleeding

Organ/Tissue Infiltration- pain from enlarged liver or spleen, hyperplasia of the gums, bone pain from marrow expansion, may also see infiltrates on skin (leukemic cutis)

Diagnostic Evaluation of Acute Myelogenous Leukemia

CBC- decreased rbc and platelets, total wbc may be low, normal, or increased

Bone Marrow Analysis- Hallmark diagnosis is an excess on blast cells

Acute Myelogenous Leukemia Treatment

Induction Therapy:

Consolidation Therapy:

Chronic Leukemia Types

Includes Chronic Myelogenous Leukemia (CML) and Chronic Lymphocytic Leukemia (CLL), typically affecting adults

Children Leukemia

Most common form of cancer in children

Most frequently ALL 80%; AML 20%

Annual incidence –3/4 cases /100,000 white children

M>F after age 1; peak incidence b/t 2-6 y/o;

2nd leading cause of death in children ages 1-14ys.

Demonstrated dramatic improvements in survival rates – 80-90% cure

Adults Leukemia

ALL uncommon in adults

AML seen in all age groups yet peak incidence @ age 60

CLL/CML seen primarily in adults

Chronic stages typically are untreated until symptoms become acute

May remain in chronic stage for 3-5 yrs (CML) or up to 14 yrs (CLL)

Acute Lymphoblastic Leukemia Diagnosis

CBC

Peripheral Blood Smear

Bone Marrow

• Morphology

• Flow Cytometry

• Cytogenetics

• Molecular Studies

Spinal Tap

LDH

Acute Lymphoblastic Leukemia Classification

Age: 1-10 y.o

WBC at diagnosis: <50k

Response to treatment: rapid

Higher risk: infants, CNS involvement, certain cytogenetic abnormalities

Acute Lymphoblastic Leukemia Treatments

Chemotherapy

• Remission Induction

• CNS Therapy

• Consolidation

• Intensification

• Maintenance

Acute Leukemia Clinical Manifestations

Abrupt, progressive, death occurs within weeks/months without treatment

Chronic Myelogenous Leukemia Risk Factors

Abnormal gene: BCR to ABL gene aka the Philadelphia chromosome

Older Age > 60

Male

Smoking

Radiation exposure

Chronic Myelogenous Leukemia Clinical Manifestations

Based on phases:

Chronic- leukocytosis in CBC

Accelerated- new chromosomal changes may be seen on analysis, symptoms consistent with leukemia may start to appear, such as fatigue, anemia, splenomegaly, or dyspnea

Blast Crisis- Symptoms like AML; leukocytosis, dyspneic , confused, leukostasis, enlarged, tender spleen/liver, malaise, anorexia, and weight loss. Lymphadenopathy is uncommon, but if present = late disease and a poor prognosis

Chronic Myelogenous Leukemia Treatment

Tyrosine Kinase Inhibitors- blocks signals from leukemic cells that work on the Philadelphia chromosome thus inducing remission

Imatinib is the standard of care.

Dasatinib and nilotinib also works.

Chronic Leukemia Clinical Manifestations

Progresses more slowly; adaptations can extent over years

Later Manifestations of Leukemia

Pancytopenia (marked decrease in RBC’s, WBC’s and platelets)

Hepatosplenomegaly more common than lymphadenopathy

CNS adaptations

Cranial nerve disturbances

HA, vomiting

Papilledema

Seizures

Organs infiltrated will show other manifestations

Hodgkin’s Lymphoma

Relatively rare; impressive cure rate

Painless, progressive proliferation of lymphocytes (WBC)

Etiology-

unknown; familial component;

compromised immune; viral component- Epstein-Barr virus

Two peaks of incidence:

15-34 (F>M) and

after 50 (M>F)

Hodgkin’s Lymphoma Risk Factors

The Epstein-Bar virus, known for causing mononucleosis

People infected with human immunodeficiency virus (HIV)

Families having a parent or a sibling with the disease. These cases are uncommon, but some experts are studying whether some people have a genetic predisposition to it.

Clinical Manifestations of Hodgkin’s Lymphoma

1st sign- painless/firm swelling of 1+ lymph nodes on one side of the neck

Can be neck (cervical, supraclavicular) and mediastinal; less common areas: iliac and inguinal.

Pruritus - cause unknown

ETOH sensitivity; pain involved after consumption, cause is unknown but this is brief and severe

All organs are vulnerable to the invasion of Hodgkin’s disease

“A” localized symptoms

“Cluster” or “B” Symptoms: Persistent fever, Night sweats, weight loss & malaise

Stage I Hodgkin Lymphoma

Localize disease, single lymph node region or single organ

Stage II Hodgkin Lymphoma

Two or more lymph node regions on the same side of the diaphragm

Stage III Hodgkin Lymphoma

Two or more lymph nodes, regions above and below the diaphragm

Stage IV Hodgkin Lymphoma

Widespread disease; multiorgan involvement, with or without lymph node involvement

Category A Hodgkin Lymphoma Symptoms

Indicates no symptoms are present

Category B Hodgkin’s Lymphoma Symptoms

Indicates the presence of "B symptoms:" Unexplained fevers; Drenching night sweats; Unexpected weight loss of more than 10 percent of body weight

Category E Hodgkin’s Lymphoma Symptoms

Indicates involvement of organs or tissues beyond the lymph system

Hodgkin’s Lymphoma Diagnostic Tests

Excisional Lymph Node Biopsy

• Presence of Reed-Sternberg cells (+) HL (-) NHL

• Staging

History and Physical

• “A” or“B” symptoms

• How many Lymph chains are affected

CBC – mild anemia

WBC may be altered

ESR and serum copper–

CT scan of chest, abdomen, and pelvis

Hodgkin’s Lymphoma Treatment

Children and young adults with HL are usually treated with one or more of the following approaches:

• Chemotherapy

• Radiation therapy

• Targeted therapy (monoclonal antibodies)

• Surgery (if a mass can be completely removed)

• High-dose chemotherapy with stem cell transplant

Chemotherapy Drug Combinations

Non-Hodgkin’s Lymphoma

Pediatric:

Treatment difference because of the type of cells present.

Treatment very similar to leukemia protocols.

• Usually diffuse rather than nodular so usually more difficult to dx early.

• Dissemination occurs earlier, more often and more rapidly

• Mediastinal involvement and invasion of meninges typical

• Still fairly good prognosis –

• Similar aggressive chemo treatment regimen as Leukemia

• BMT or PBSCT may be considered

Stage I Non-Hodgkin’s Lymphoma

Single tumor at single site

Stage II Non-Hodgkin’s Lymphoma

Single tumor with regional involvement on the same side of diaphram

Stage III Non-Hodgkin’s Lymphoma

Tumor on both sides of the abdomen, also primary thoracic, intra-abdominal, and paraspinal/epidural tumors

Stage IV Non-Hodgkin’s Lymphoma

Central nervous system and/or bone marrow involvement

Non-Hodgkin’s Lymphoma Planning & Interventions

Treatment – anti-neoplastics

Intrathecal chemo (CNS involvement)

Radiation- complication is hypothyroidism

Bone Marrow Transplant

Peripheral blood stem cell transplant (PBSCT)- similar to apheresis-cell separator

Other Modes of Therapy for Non-Hodgkin’s Lymphoma

Bone Marrow Transplant (25-50% remission)

Biologic response modifiers (BRMs)

Umbilical Cord Blood Stem Cell Transplantation

Peripheral blood stem cell transplant (PBSCT)

Not typical:

Surgery (more conservative)

Radiation therapy

Wilms Tumor AKA Nephroblastoma

Malignant renal and intraabdominal tumor of childhood

Three times more common in African-American children

Peak age of diagnosis is between 2-3 years

More frequent in males

Wilms Tumor Etiology

Unknown cause, but certain genetic syndromes or conditions increase the risk.

• Congenital abnormality- cryptorchidism or hypospadias

• Genetic syndromes-WAGR syndrome, Denys-Drash syndrome, and Beckwith-Wiedemann syndrome

• Genomic Alterations: Genes and chromosomal alterations involved: WT1, CTNNB1, WTX, and imprinting cluster regions on chromosome 11p15 (WT2)

• Race: More common in white and black children

WAGR Syndrome

Wilms tumor, aniridia, genitourinary anomalies, and cognitive impairment

Beckwith-Wiedemann Syndrome

Includes hemihypertrophy, macroglossia, omphalocele, and visceromegaly

Wilm’s Tumor Clinical Manifestation

Abdominal swelling or mass- typically firm, nontender, confined to one side, and deep within the flank. Hard to differentiate between the liver when on the right side, but unlike the liver, it does not move with respirations.

Pain in 40% of patients

Hematuria in > ¼ of children due to increased renin secretion

Hypertension in ¼ of children due to increased renin secretion

Internal hemorrhage manifestations: anemia, pallor, anorexia, lethargy, and hypertension

Internal Hemorrhage Manifestations of Wilms Tumor

Anemia, pallor, anorexia, lethargy, and hypertension

Wilms Tumor Diagnostic Tests

History and Physical Exam- Check for family history of cancers, clinical signs, and congenital abnormalities

Imaging Studies- abdominal x-ray, ultrasound, CT, or MRI and CT of chest to check for lung metastases. Studies to assess tumor rupture or intravascular extension are also performed

Lab Test- CBC, biochemical studies, and urinalysis (polycythemia is sometimes present). A von Willebrand disease workup is also included.

Stage I Wilms Tumor

Limited to one kidney and completely resected without rupture or previous biopsy. All lymph nodes negative for tumor.

Stage II Wilms Tumor

Extend beyond kidney but is resected; lymph nodes do not contain tumor cells

Stage III Wilms Tumor

No postoperative residual tumor. Confined to the abdomen. Lymph node in the abdomen or pelvis contains tumor cells.

Stage IV Wilms Tumor

Hematogenous metastases with disease in the lung, liver, bone, brain, and distant lymph nodes.

Stage V Wilms Tumor

Bilateral renal involvement is present at diagnosis.

Wilms Tumor Treatment

Keep the tumor intact (no palpation to inspect) to prevent dissemination

Surgery-

Radiation

Chemotherapy