1. Mary E. MacBlane MS, PNP-BC
Childhood Leukemia
Mary E. MacBlane MS, PNP-BC

2. Goals Incidence Etiology Diagnosis Types/Classification Treatment
Primary Care Pearls

3. Incidence 30% of all cancers in childhood
Peak incidence 2-5 years of age
males > females
Caucasian > African American
Incidence of ALL (acute lymphoblastic leukemia) is 5 times higher than incidence than AML (acute myeloid leukemia)

4. Etiology Exact cause is NOT known Genetics Environmental
Identical twin with leukemia
Chromosome abnormalities
Down Syndrome
Other
Severe Combined Immunodeficiency
Neurofibromatosis
Fanconi’s Anemia
Bloom Syndrome
Environmental
Ionizing Radiation
Chemotherapy
Viruses
Pesticides

5. 5 – Year Survival 1960 – Less than 10% Today Why? ALL: 80-85%
AML: about 65%
Why?
Research
Standardized treatment protocols

6. COG Childrens Oncology Group
International Organization
Ongoing Studies
Chemo combinations & timing, radiation, etc…
Quality of Life
Epidemiology
Standards of Care
Treatment Protocols
Nursing Discipline
Shared Data
Meetings

7. Diagnosis: Symptoms Fatigue Pallor Anorexia Bruising/Bleeding Fever
Bone/joint pain
Belly pain
H/A

8. Diagnosis: Exam Findings
Pallor
Bruises
Petechiae
Lymphadenopathy
Hepatosplenomegaly
Cranial Nerve Palsies
Testicular enlargement
Chloromas
Leukemia Cutis
Mediastinal Mass
Superior Vena Cava Syndrome

9. Leukemia Cutis
Petechiae

10. Differential Diagnosis
Viral Illness
ITP
Aplastic Anemia
Arthritis
Lupus
Transient Erythroblastic Anemia of Childhood
Other Malignancies

11. Diagnostic Studies CBC Other Chemistries Uric Acid LFT’s LDH
Viral Titers
Chest x-ray

12. CBC w/ Differential WBC’s Hgb ↓ Platelet Ct ↓ Diff ↑ or ↓ Neutropenia
Peripheral Blasts

13. Types of Childhood Leukemia
ALL – Acute Lymphoblastic Leukemia
AML – Acute Myeloid Leukemia
CML – Chronic Myeloid Leukemia

14. Classification by Cell Lineage

16. Acute Lymphocytic Leukemia (ALL)
Most common cause of childhood leukemia
Peak age: 2-5 years
Males > females

17. ALL – Best Prognosis Ages 1-9 Females Initial WBC < 10,000
Favorable cytogenetics
Early response to treatment

18. ALL –Poor Prognosis Ages < 1 year or > 10 years
Initial WBC > 50,000
Extramedullary sites
CNS
Testes
Steroid Pre-Treatment
Unfavorable cytogenetics
Lack of remission after induction treatment

19. ALL - Cytogenetics Examples
Favorable
Unfavorable
Hyperdiploid (extra chromosomes)
Hypodiploid (fewer than 54 chromosomes)
Trisomies 4, 10, 17
t(9;22) BCR/ABL translocation (Philadelphia chromosome)
t (12;21) TEL-AML1
t(4;11) MLL rearrangement

20. ALL - Risk Stratification
Low Risk
Average (Standard) Risk
High Risk
Very High Risk

21. ALL Induction Therapy Lasts 35 Days Medications
Intrathecal Medications weekly (Cytarabine or Methotrexate)
Vincristine IV weekly
Peg-Asparaginase on Day 4
28 days of steroids
Examine peripheral blood for remission at Day 8 and Day 29
Bone marrow recheck at Day 29
Expect remission by the end of induction

22. ALL - Phases of Treatment
Induction (first month)
Consolidation (1 month)
Interim Maintenance I (2 months)
Delayed Intensification (2 months)
Interim Maintenance II (2 months)
Maintenance
2 years for females
3 years for males

24. Acute Myeloid Leukemia (AML)
No Peak Age
20-25% of acute leukemia in children
Overall prognosis about 65%

25. AML – Favorable Prognosis
Down syndrome
Cytogenetics: t(8;21) t(15;17), inv 16

26. AML – Unfavorable Prognosis
WBC > 100,000 at diagnosis
Cytogenetics: t(9;11), 11q23
Therapy-related AML
Lack of remission after induction

27. AML – General Treatment
Very Intensive Therapy
Induction I and II
Intensification I and II
About 6 months
Inpatient for most of therapy

28. Bone Marrow Transplant
High Risk ALL
AML

29. Complications of Leukemia Treatment
Tumor Lysis Syndrome
Infection/Sepsis
Thrombosis
Hemorrhage / DIC
Leukostasis

30. Infection Risk Central Lines Prolonged Neutropenia
Immunocompromise after BMT

31. Infection Risk Tidbits
Alpha Strep
Fungal
PCP
Bactrim
Dapsone
Pentamidine

33. Primary Care Diagnosis During Treatment Late Effects
Monitoring for relapse

34. Primary Care Pearls Diagnosis History Exam CBC No Steroids
Avoid Transfusion
CXR
Make the phone call

35. Primary Care Pearls After Diagnosis General Care Immunizations
Flu Shots
No Live-Virus Vaccines
Maintaining Normalcy and Hope
Sibling Considerations
Virus
Varicella

36. Primary Care Pearls Late Effects Alert for Relapse Avascular necrosis
Cardiotoxicity
Neuro-cognitive
Secondary malignancies
Endocrine abnormalities
Alert for Relapse

38. Case Study 1 2 year old female brought to primary care provider
Parents report a 1 week hx of fatique that has gotten worse; pain that began in her feet and progressed to legs; and a petechial rash over her arms and legs with some bruising. She had a brief episode of epistaxis on day prior to appointment. They also felt that her belly has seemed more prominent for the past 2 weeks.
Primary provider obtained a CBC which revealed peripheral blasts

39. Case Study 1 Initial labs at admission: CBC Chemistries: WBC: 27,000
Blasts: 34%
Neutrophils 1%
Hgb: 4.9 ( )
Platelets: 6,000 (150, ,000)
Chemistries:
Uric Acid: 3.4 ( )
Potassium: 3.9 ( )
Creat: 0.2 (.2-.7)
Bili: 0.2 (.1-1.0)
LDH: 341 ( )

40. Case Study 1 Treated following standard risk ALL protocol
2 unplanned admissions
Both for fever and neutropenia
On one admission found to have pneumonia
Otherwise did well and completed therapy in 25 months

41. Case Study 2
12 year old male with bulky lymphadenopathy, change in voice, difficulty breathing.
Seen in local ED and prescribed 4 day course of prednisone
Symptoms initially resolved but recurred and seemed much worse 3 days later (very hoarse voice, could not lay down flat to sleep)
Again seen in ED and 5 day course of prednisone and then 4 day taper prescribed
On last day of steroids there was a biopsy of a lymph node. 2 days later the primary care provider was notified that the results were consistent with T-cell leukemia.

42. Case Study 2 Admitted to our facility with initial studies: CBC:
WBC: 58.6
Creatinine: 1.1 ( )
Uric Acid: 8.3 ( )
Chest x-ray reveals large mediastinal mass and tracheal deviation

43. Case Study 2 High Risk T-Cell ALL Already in tumor lysis
Age – 12 years
Initial WBC – 58,000
Pretreated with Steroids
Already in tumor lysis
Creatinine 1.1
Uric acid 8.3

44. Case Study 3
15 year male who moved to the US about 6 months earlier. He was seen in primary care office for routine well-child check. Only complaint was headache on and off for 2 weeks.
Exam: nl except mild submandibular adenopathy
CBC
WBC 6.8
32% Blasts
9% Neutrophils
Hgb 12.6 (13-17)
Plt 308

45. Case Study 3
Admitted to the hospital and lumbar puncture and bone marrow completed
Lumbar puncture: No evidence of malignancy
Bone Marrow consistent with Acute Myeloid Leukemia with favorable cytogenetics: t(8,21)

46. Case Study 3 Received 4 courses of chemotherapy over 4 admissions
Admission #1 and #2 each lasted about 1 month. Received prophylactic antibiotics and antifungals. Occasional transfusions of packed cells and platelets

47. Case Study 3 Admission 3: Lots of issues (1 month stay)
Persistent fever despite prophylaxis. Had to change to treatment dose of meds. All cultures were negative throughout stay
Ambisome for fungal coverage and then needed Amiloride to prevent potassium wasting
Anorexia – Started periactin. Needed N-D tube for feeds
Multiple transfusions of packed red blood cells and platelets

48. Case Study 3 Admission 4: Over 6 weeks stay
Persistent fever despite prophylaxis. Positive blood cultures for Staph hominis. Required Vanco and Zosyn for 10 days and then returned to prophylaxis.
Ambisome again for fungal coverage. Required electrolyte supplementation (Magnesium, Potassium) in addition to Amiloride
Anorexia – Periactin at first. Changed to Marinol. Tube feedings not tolerated. TPN required.
C-diff infection. Treated with Flagyl
Lip lesion positive for HSV-1
Multiple transfusions of packed red blood cells and platelets

49. Case Study 3 Now doing GREAT! Returned to school
Visits the clinic about every 6 weeks currently

50. Thank You