Haematological malignancies in children

1. Hematological Malignancies
in Children
BY HARANOOP SINGH

2. Facts and figures
 Acute leukemia accounts for approximately 30 percent of all childhood malignancies
and is the most common cancer in children.
 Of which 80% is caused by ALL, 15% by AML and the remaining 5% - HL, NHL, Juvenile
myelomonocytic leukemia etc.
 Overall incidence stands at roughly 1 in 2000 ~ 400 children newly diagnosed cases
per year in the UK.
 Cure rates based on recent data and treatment developments stands at around 80% -
varies depending on which cancer. Eg: ALL has better prognosis with cure rate of 80%
while AML has a cure rate of 50-60%.

3. Epidemiology

6. Basic science

8. Scope of topic
 Myeloid
 Acute myeloid leukemia
 Lymphoid
 Acute lymphoblastic leukemia
 Non hodgkins lymphoma
 Hodgkins lymphoma

9. Acute lymphoblastic leukemia
 Overlap between leukemic and lymphoblastic – which means involving a
combination of blood and lymph nodes
 Collectively referred to as ALL/LBL
 Arises from Pre-B cells or T-cell precursors
 Most common form in childhood, especially in age group of 2-5 years old
 Blasts on PBF/BMA

10. Acute myeloid leukemia
 Second most common hematological maglinancy in children
 Stable incidence in childhood with increasing rates in adolescence, overall more
common in adults
 Arises from myeloid precursors
 Subdivided into 7 different morphologies based on the French American British (FAB)
classification system
 Has a known association with Down’s Syndrome – 10 to 20 times greater risk as
compared to a child without DS
 Features on peripheral blood film/bone marrow aspirate
 More than 20% blasts, which may be myeloblasts, promyelocytes, monoblasts,
promonocytes, promonocytes, megakaryoblasts

11. Non Hodgkin's lymphoma
 Divided into
 Lymphoblastic (T-cell) – presenting with anterior mediastinal mass
 Mature B cell (Burkitt) – has associated with EBV
 Large cell lymphoma
 Majority are high grade and aggressive requiring prompt diagnosis and
treatment
 Associated with hypercalcemia

12. Hodgkin’s lymphoma
 Increasing incidence with age
 High association with EBV infection
 Classical histology of Reed Sternberg cells in a lymph node biopsy

13. Approach

15. Clinical
assessment

16. Symptoms and signs
 Tend to present with non specific sign and symptoms depending on when the child presents to you
 Main challenge is to not falsely diagnose the child as having a typical self limiting viral illness
 However, there are recognized features of acute leukemias/lymphomas that should raise the suspicion
of an attending clinician. Studies show that a child with acute leukemia would at least have one of the
following
 Fever
 Pallor
 Bruising
 Hepato-splenomegaly or isolated organomegaly
 Lymphadenopathy
 Musculoskeletal pain – bone pain
 Parents complaints – ‘something just doesn’t seem right with my child’

18. Hepatomegaly & splenomegaly
 Hepatomegaly
 Cirrhosis
 Cancer
 CCF
 Inflammation
 Infiltration
 Splenomegaly
 Neoplasm
 Infection
 Haemolysis
 Infiltration
 Liver
 Inflammation
 Trauma
 Hepatosplenomegaly
 Cirrhosis
 Myeloproliferative
 Lymphoproliferative
 Infection
 Inflammation
 Infiltration

21. Diagnostic
evaluation

22. Investigations – important ones first
 Full blood count
 Peripheral blood smear
 Lymph node biopsy
 Bone marrow biopsy
 CXR

23. Peripheral blood smear
 Report should be obtained as urgent as possible
 White blood cells
 Mature neutrophils have segmented nucleus with 2 to 5 lobes joined by a thin filament. Less mature
forms include bands (stab, juvenile) forms, metamyelocyte, myelocyte, promyelocyte and myeloblast in
that order. The cytoplasm of a mature neutrophil is pink or nearly colorless and possesses moderate
azurophilic and specific granules.
 In a ALL, morphology may vary from small cells with scant cytoplasm, condensed nuclear chromatin, and
indistinct nucleoli to larger cells with moderate amounts of cytoplasm, dispersed chromatin, and
multiple nucleoli; coarse azurophilic cytoplasmic granules may be present.
 In AML, myeloblasts are immature cells with large nuclei, usually with prominent nucleoli, and a variable
amount of pale blue cytoplasm. Typically, myeloid blasts have more abundant cytoplasm compared with
lymphoid blasts and may have Auer rods or granules present.
 The appearance of lymphoblasts in biopsy specimens is relatively uniform, but the cells may include
round, oval, indented, or convoluted nuclei, finely dispersed chromatin, and nucleoli that can range
from inconspicuous to prominent.

24. Other investigations
 Bloods
 Renal profile
 Ca, Po4
 Liver function test
 Coagulation profile
 LDH
 Uric acid
 Sampling
 Biopsy –lymph nodes
 Bone marrow aspirate
 Lumbar puncture
 Special tests
 Cytogenetic studies
 Immunohistochemistry
 Cytochemistry
 Imaging
 CXR
 CT Scan
 MRI

25. Management

26. Management
 General principle of
 Induction +/- CNS treatment
 Consolidation or intensification
 Maintenance
 Drug regimes differ based on protocols
 Oncologic emergencies can occur prior, during or after treatment
 Once disease has remitted, monitor during maintenance phase with regular FBC,
if counts do not improve, consider repeat BMAT

27. Oncologic emergencies
 Tumor lysis syndrome
 Electrolyte abnormalities
 Hyperleukocytosis
 Coagulopathy
 SVC Obstruction
 Febrile neutropenia
 Cord compression
 Raised ICP
 Immunocompromised state

28. References
 UpToDate
 Chris, M., Hall, G., & Clarke, R. T. (2009). Acute leukaemia in children: Diagnosis
and management. BMJ, 338.
 MOH. (2018) Synopsis of childhood cancer incidence in Malaysia (2007-2011).
 Paediatric Protocol 4th Edition
 A. (2004). PERIPHERAL BLOOD FILM - A REVIEW. NCBI, 12(2).

29. Thank you
Questions?