Case Study #7
MICR 410 – Hematology
Spring 2010
Erik Bayona, Rosa E. Loyola, Lien Pham
John, a 4-year-old male is seen by his physician with a complaint
of easy fatigue and bruising. His mother states that until one
month ago he was a “typical kid”. Since then she has noticed
increased lassitude, a regression to more baby-like behavior, and
loss of appetite. For the past two days his temperature has been
100ºF. Upon physical examination the child presented as a pale,
quiet child of appropriate size for his age. Most systems were
unremarkable with the exception of several small shotty lymph
nodes felt in the cervical and auxiliary regions. His CBC revealed
a WBC count of 40.2 x 10⁹/L with 90% blasts.
CBC Results:
Hgb
Hct
RBC
WBC
Platlets
MCV
MCH
MCHC
9.7 g/dL
32%
3.45 x10¹²/L
40.2 x 10⁹ /L
63 x 10⁹ /L
92.7 fl
28.1 pg
30.3
Differential:
90% lymphoblasts
8% neutrophils
1% monocytes
1% eosinophils
Rare nucleated RBCs
Platelets appeared
decreased in number
Case Summary
Age – 4 year old male w/ immature cells
(90% blasts)
Sudden onset
Lack of promyelocytes and lack of Auer
rods
normocytic, normochromic anemia, low
platelets, and high WBC
fatigue, bruising, paleness
swollen lymph nodes
Key Information Pointing to Diagnosis
Precursor B cell Acute Lymphocytic
Leukemia (ALL) type L1
The Diagnosis for Case #7
Precursor B ALL-L1 is characterized by a malignant
transformation of B cells of the lymphoid cell line.
This leads to an unregulated proliferation of immature B
lymphocytes due to the arrest in maturation at the blast
stage.
The poorly differentiated malignant lymphocytes proliferate,
accumulate, and invade normal tissues and cause lesions.
The leukemic cells may replace normal cells, take over
normal parts of the bone marrow, and cause bone marrow
failure.
This disrupts normal hematopoiesis and may result in
pancytopenia with death from hemorrhaging and infections.
The exact cause is unknown but there are certain
predisposing factors :
◦ Inherited increased predisposition to develop leukemia
◦ Inherited tendency for chromosome fragility or abnormality
(chromosomal translocations)
◦ Those with hereditary immunodeficiencies
◦ Those with chronic marrow dysfunction
◦ Exposure to radiation, mutagenic chemicals or drugs
◦ Viral infections
Pathophysiology of Pre B ALL-L1
Bone Marrow Biopsy - usually needed to establish a definitive
diagnosis of leukemia because cell morphology must be examined
and bone marrow must be evaluated before calling it leukemia.
Cytochemistry- will be helpful once the diagnosis of leukemia
has been made, and can be used primarily to distinguish between
ALL and AML. Will help establish the lineage of the leukemic cell as
myeloid or lymphoid.
Acid Phosphatase – T lymphocytes have a high level of acid
phosphatase and this can be used to help make a diagnosis of acute
T-lymphocytic leukemia.
Cytogenetic studies – will be helpful for chromosome analysis
to identify the specific malignancy and then provide a prognosis.
Usually, a normal karyotype is usually associated with a better
prognosis.
Immunophenotyping - determining B cell or T cell lineage.
These tests rely on antibodies made against specific surface
markers.
Flow cytometry – clinical mainstay for diagnosis pre-cursor Bcell ALL.
Diagnostic Tests for Pre B ALL-L1
The prognosis is poor if the WBC count is > 20 x 10 /L
However, an affected B-cell lineage shows a better
therapeutic outcome
A younger age is also better for recovery
70% of children diagnosed with ALL may be cured and
have long term survival
Therapy:
 Give supportive care –
anemia, etc.
due to patient having bleeding issues, infection,
 Eradicate leukemic cell masses using:
1.
2.
Chemotherapy – combination of drugs (primary treatment)
Radiotherapy – targets rapidly dividing cells therefore decreasing
3.
Immunotherapy - stimulate patients’ own immune system to mount
4.
5.
proliferation
response against malignant cells
Monoclonal antibodies – antibodies that wipe out malignant cells
Bone marrow transplant – replacing bone marrow (used as last
resort if all the above don’t work)
Therapy and Prognosis for Pre B ALL-L1
Most information about the cause of ALL
comes from genetic studies – cytogenetics and
epigenetics.
Chromosomal translocations – the most
common for precursor B-cell ALL In children is
the t(12;21) occuring in 16-28% of unselected
cases. Results in fusion of TEL gene on
chromosoe 12 and the AML1 gene on
chromosome 21q.
Epigenetic studies show aberrant methylation
of DAPK gene and results suggest this may be
of clincal-pathologcal significance for childhood
ALL.
Prevention would focus on eliminating these
probable causes – further research will provide
answers and options.
Prevention of Pre B ALL-L1
The diagnosis is Precursor B cell Acute Lymphocytic
Leukemia type L1.
Typical symptoms are fatigue, pallor, fever, weight loss,
irritability, anorexia, infection, bleeding, and bone pain.
The cause of ALL L1 still largely speculative based on
genetic research data.
Diagnostic tests include acid phosphate ,terminal
deoxytidyl transferase, immunologic markers, and
cytogenetics to identify chromosomal abnormalities.
Treatment is to give supportive care and eradicate
malignant cells using chemotherapy which is the
primary and most useful treatment method.
Prognosis is good due to age of the patient (child).
Prevention will be further clarified with forthcoming
research in genetics.
Take Home Message
1. “FactSheet on ALL in children.” National Cancer Institute.
July 11, 2002. www.cancer.gov/cancertopics/factsheet. May
23, 2011.
2. McQueen, Nancy. “Introduction to Leukemia: Acute
Leukemias.” Micro 410 – Hematology Lecture Notes, Spring
2011.
3. Satake, Noriko. “Pediatric Acute Lymphoblastic Leukemia.”
4. MedEscape Reference: Drugs, Condition, and Procedures.
5. WebMd; May 2, 2011. Web. May 23, 2011.
6. Seisho T; Masahide M; Zimmermann, M; Takayuki, I;
Komatsu, N; Seriu, T; Schrappe, M; Bartram, C; Koeffler, H.
Clinical significance of aberrant DNA methylation in childhood
acute lymphoblastic leukemia, Leukemia Research, In Press,
Corrected Proof, Available online 17 May 2011, ISSN 01452126, DOI: 10.1016/j.leukres.2011.04.015.
References