Abstract
Objective: To describe
certain characteristics of acute leukemia regarding age, gender, cytomorphology
and immunophenotype at King
Hussein Medical
Center.
Methods: A retrospective
review of bone marrow aspirate and/or biopsy reports was conducted at Princess
Iman Research and Laboratory Sciences Center
at King Hussein Medical
Center during the period
between Jan 2004 and Dec 2008. A total of 226 patients were studied regarding: age,
gender, and cytomorphologic and immunophenotypic diagnosis. The age was
categorized into two groups (≤14 years as children group and >14 years as adult
group). Descriptive analysis using frequencies was used to describe the study
variables. This
study was conducted to study and analyze acute leukemia cases in children and
adults in King Hussein Medical
Center over the past five
years.
Results: One
hundred thirty-eight (61%) cases were males and 88 (39%) were females. Their
ages ranged between three months and 80 years. A total of 102 (45%) patients were
children ≤ 14 years old and 124 (55%) patients were > 14 years old. Acute lymphoblastic
leukemia constituted 75% of all childhood leukemias, the majority (83%) were of
B-cell phenotype mainly CD10+ve Precursor B-cell Acute lymphoblastic leukemia (74%);
only 17% of the childhood acute lymphoblastic leukemia was of T-cell phenotype.
Acute myeloid leukemia constituted 80% of all adult leukemias; most of the
cases were of the French-American-British M2 morphological subtype (34%).
Conclusion:
Distribution and patterns of acute leukemia differs between
children and adults. While CD10+ve Precursor B-cell acute lymphoblastic leukemia
was predominant in children, acute myeloid leukemia M2 was prevalent in adults.
Key
words: Acute lymphoblastic leukemia, Acute myeloid leukemia,
Bone marrow aspirate
JRMS
December 2010; 17(4): 11-14
Introduction
Acute leukemia is a malignant
proliferation and accumulation of immature lympho-hematopoietic cells.(1)
It represents a very aggressive, malignant transformation of an early
hematologic precursor. The malignant clone is arrested in an immature, blast form,
proliferates abnormally, and no longer has the ability to undergo maturation.
In contrast, chronic leukemias are characterized by resistance to apoptosis and
by accumulation of nonfunctional mature cells.(2) Leukemia is
the most common
childhood cancer.(3) Acute lymphoblastic (also termed
lymphocytic or lymphoid) leukemia (ALL) is the most common pediatric cancer,
accounting for 30%of all pediatric malignancies.(4,5)
According to the
National Cancer Institute, the age-adjusted overall incidence of ALL in the United States
was 1.6 per 100,000 (1.8 in males and 1.4 in females). The incidence is higher
in whites than in blacks. After an initial peak in children younger than five
years of age (8.3 per 100,000), the incidence decreases continuously. It increases
again above the age of 65 to a second peak in the age group above 85 years (2.0
per 100,000). The incidence of acute myeloid leukemia (AML) is relatively
constant during childhood, with slight peaks in the first two years of life and in late adolescence.(1)
Both ALL and AML are heterogeneous
diseases that comprise different biologic subtypes.(6-8) Classification
of the phenotype of the blast cells in acute leukemia requires morphologic and
cytochemical evaluations, immunophenotyping, cytogenetic, and molecular genetic
studies. However, morphology remains the
mean by which acute leukemia is initially detected and, together with
cytochemical reactions, is the major tool in distinguishing between ALL and AML.(1,9)
This study was conducted to
study and analyze acute leukemia cases in children and adults at King Hussein
Medical Center
over the past five years.
Methods
A retrospective review of bone
marrow aspirate and/or biopsy reports was conducted at Princess Iman Research
and Laboratory Sciences
Center at King Hussein
Medical Center
during the period between January 2004 and December 2008. A total of 226
patients were studied regarding age, gender, cytomorphologic and
immunophenotypic diagnosis. The patients were categorized into two groups according
to age (≤14 children and >14 adults). Bone marrow aspirate smears were
stained with May-Grunwald-Giemsa stain and immuno-phenotypic analysis using
flowcytometry was done. Both of these tests are prerequisites for
classification of acute leukemia by WHO criteria. Bone marrow biopsies of at
least 1cm length with immuno-histochemical studies were also included for
diagnosis in the majority of cases. The following markers were studied: CD34,
HLA-DR, TdT as Hematopoietic precursors; CD13, CD33, MPO, CD117 as Myeloid precursors;
CD14, CD11c, CD11b, CD64, CD68 as Monocytic lineage markers; Ab to HbA, Glycophorin A as
Erythroid lineage markers; CD41, CD61 as Megakaryoblastic Lineage markers; CD19,
CD20, CD22, CD79a, CD10 as B cell Lineage markers and CD2, CD3, CD7 as T cell
Lineage markers. Marrow blast count of 20% was sufficient for acute leukemia diagnosis.
The French-American-British (FAB)
classification was used to classify AML, while the World Health Organization
(WHO) classification was used to classify ALL.
Results
A total of 226 bone marrow aspirate
and biopsy reports were studied, 138 (%61) were males and 88 (39%) were
females. Their ages ranged between three months to 80 years. A total of 102 (45%)
cases were children (age ≤ 14 years) and 124 (55%) were above 14 years.
Table I shows, the age and gender
distribution of ALL and AML among the study group. ALL cases constituted 75% of
patients in the children’s group and 20% of the patients in the adults group.
ALL occurred in 47% of males, however 80% of those above 14 years had AML and
females constituted 58%.
Table II presents the age
distribution of ALL immunophenotypic diagnosis among the study group. CD10+ve precursor
B-cell ALL constituted 74%, however CD10-ve precursor B ALL were 9% of the
children’s group. Among the adults 64% had CD10+ve precursor B-cell ALL and 12%
had CD10-ve precursor B ALL. Precursor T ALL was more in among the adult group
(24% vs. 17%).
Table III illustrates the age
distribution of AML FAB classification among the study group. AML FAB M1 was
the commonest (28%), while M0 and M5 were 4% respectively among those ≤ 14
years. AML FAB M2 constituted 34% and M0 were 6% in those > 14 years. In
both age groups, AML FAB M6 was not reported.
Discussion
Leukemia accounts for 300,000 new cases each year (2.8%
of all new cancer cases) worldwide.(10) Unlike leukemia in
adults, childhood leukemia is acute in the vast majority of cases.(1)
Our study showed that ALL is the most common childhood leukemia, representing
about 75% of acute leukemia, whereas it comprises only 20% of adult acute
leukemia. AML accounts for 80% of all cases of adulthood acute leukemia as
shown in Table I.
Table I. Age and sex
distribution of ALL and AML
|
Variables
|
Number of bone marrow samples
|
Number of ALL cases (%)
|
Number of AML cases (%)
|
|
Age group
≤ 14 years
>14
years
|
102
124
|
77 ( 75 )
25 ( 20 )
|
25 (25)
99(80)
|
|
Gender
Males
Females
|
138
88
|
65 ( 47 )
37 ( 42 )
|
73 (53)
51 (58)
|
Table II. Age distribution of
ALL immunophenotypic diagnosis
|
Age group
|
Number of ALL cases
|
CD10+ve precursor B ALL n (%)
|
CD10-ve precursor B ALL n (%)
|
Precursor T
ALL n (%)
|
|
≤ 14 years
|
77
|
57 (74)
|
7 (9)
|
13 (17)
|
|
>14 years
|
25
|
16 (64)
|
3 (12)
|
6 (24)
|
Table III. Age distribution of AML FAB classification
|
Age group
|
No. of AML cases
|
M0 No.
(%)
|
M1 No.
(%)
|
M2 No.
(%)
|
M3 No.
(%)
|
M4 No.
(%)
|
M5 No.
(%)
|
M6 No.
(%)
|
M7 No.
(%)
|
|
≤
14 years
|
25
|
1
4
|
7
28
|
6
24
|
2
8
|
5
20
|
1
4
|
0
0
|
3
12
|
|
>14
years
|
99
|
6
6
|
15
15
|
34
34
|
17
17
|
18
18
|
8
8
|
0
0
|
1
1
|
This is supported by a study from El Salvador and Mexico city between 1996 and 2000, which
reported that the frequency rates leukemias for the Salvadoran group of
0-11 year olds were 34.2, 7.1,0.6, 0.2, and 43.2 per million children for ALL, AML,
CML, UL (unspecified leukemia), and total leukemia, respectively.(11)
Al-Barazanchi et al. from Iraq
found that out of sixty-four newly diagnosed ALL cases, 61% were children
(age<15 years), while 39% were adults (age 15-45 years). Al-Barazanchi et al. also addressed
the relation between ALL and gender, he found that males constituted 43 cases
and females 21 cases with male to female ratio 2 : 1.(7)
This is similar to a recent study done in the central region of Tunisia by
Jmili et al. in 2004 about the epidemiologic and cytological
characteristic of 193 patients with acute leukemia, who addressed the
predominance of males (ratio 1.27 : 1) and reported that 72% of acute
leukemia in children less than 10 years of age was of the lymphoblastic type.(12)
In our study we found that males are generally affected by acute leukemia more
often than females in all age groups with male to female ratio 1.76 : 1
in ALL and 1.43 : 1 in AML. Freedman et al. studied age-specific
rates of leukemia by gender in Jordanian population between 1996-1998 and found
that patients 10-29 years have no sex predilection, while those <10 years or
≥30 years have male predominance.(13)
The FAB Cooperative Group distinguishes three ALL groups (L1 to L3) based on
morphologic criteria.(6) The WHO proposed new
guidelines for the diagnosis. In
addition to lowering the blast count to 20% as sufficient for an ALL diagnosis,
the morphologic distinction of L1, L2, and L3 morphologies is abandoned as no
longer relevant. The WHO classification of ALL divides the disease into
precursor B-cell, precursor T-cell, and Burkitt-cell leuke mia. Although FAB
classification system relies heavily on morphological assessment, the recent
WHO International panel on ALL recommends that the FAB classification be
abandoned, since the morphological classification has no clinical or prognostic
relevance. It instead advocates the use of the immunophenotypic classification.(2) In our study,
CD10+ve precursor B- cell ALL is by far the most common immunophenotype
of ALL in all age groups, constituting 74% and 64% for childhood and adulthood
ALL respectively as shown in table II. This agrees with one study from Nordic
Countries in which Hjalgrim LL et al found that the incidence rate of B-cell
childhood ALL is about 10 times more than T-cell ALL.(14) Hann et al. who analyzed the
immunophenotype of children treated on the Medical Research Council United
Kingdom ALL Trial XI (MRC UKALLXI) found that T-cell ALL constitutes only 10.7%
of ALL cases.(15) An Italian study done by Consolini et al.
in 1998 found that CD10 was positive in 95.6% of patients with B-lineage ALL.(16)
There are two current systems to classify AML. In the WHO classification, the blast threshold for the
diagnosis of AML is reduced from 30 to 20% blasts in the blood or marrow. In
addition, patients with the clonal, recurring cytogenetic abnormalities
t(8;21)(q22;q22), inv(16) (p13.1;q22), or t(16;16) (p13.1;q22) and
t(15;17)(q22;q12) should be considered to have AML regardless of the blast
percentage.(9) The FAB
classification is also used and classifies AML into eight subtypes.(2,14)
FAB M5 and M7 are more common in early childhood, whereas older children are
more likely to have M0, M1, M2, M3.(6) Our study showed that
FAB M1, M2, and M4 were the predominant in childhood AML, comprising 28%, 24%,
20% respectively. On the other hand, adulthood AML were mainly FAB M2 (34%),
while M4 and M3 were less common constituting 18%, 17% respectively as shown in
Table III.
Conclusion
Childhood and adulthood acute leukemia differ
significantly in distribution. While, CD10+ve precursor B-cell ALL which has
good outcome is most common in children, AML M2 is predominant in adults, which accounts for the worse
prognosis of adulthood acute leukemia.
References
1.
Abeloff MD, Armitage JO, Niederhuber JE, et al. Childhood Leukemia, In: Campana D, et al, editors. Acute
Lumphocytic Leukemia in Adults, In: Hoelzer D, et al, editors. Abeloff's
Clinical Oncology. 4th edition. Philadelphia: Churchill Livingstone 2008.
2.
Abraham J, Gulley JL, Allegra CJ, et al. Acute Leukemia,
In: Craig M, et al, editors. Bethesda
Handbook of Clinical Oncology. 2nd Edition: Lippincott Williams & Wilkins 2005: 310-323.
3.
Wong DI, Dockerty JD. Birth
characteristics and the risk of childhood leukaemias and lymphomas in New Zealand:
a case-control study. BMC Blood Disorders 2006; 6: 5.
4.
Shi L, Zhang J, Wu P, et al. Discovery and identification of
potential biomarkers of pediatric Acute Lymphoblastic Leukemia. Proteome
Science 2009; 7: 7.
5. McNeil DE, Cote TR, Clegg L, et al. SEER update of incidence
and trends in pediatric malignancies:
acute lymphoblastic leukemia. Med Pediatr
Oncol 2002; 39(6): 554-557.
6. Lanzkowsky PH. Leukemias, in:
RednerA, editor. Manual of Pediatric Hematology and Oncology. 4th edition.
Elsevier Inc. 2005; 415-453.
7.
Al-Barazanchi ZA, Al-Sani AK, Naema
NF. Hematological
and cytomorphological study of Acute Lymphoblastic Leukemia (ALL). Bahrain
Med Bull 2005; 27(4).
8.
Xie Y, Davies SM, Xiang Y, et al. Trends in leukemia incidence and survival in the United States
(1973-1998). Cancer 2003; 97(9): 2224-2235.
9. Swerdlow SH, Campo E, Harris NL, et al. Introduction and overview of the classification of
the myeloid neoplasms. In: Vardiman JW, et al, editors. WHO classification
of tumours of hematopoietic and lymphoid tissues. 4th edition. Lyon : International Agency for Research on Cancer 2008:18-30
10. Parkin DM, Bray F, Ferlay J, et
al. Global cancer statistics, 2002. CA Cancer J
Clin 2005; 55: 74-108.
11. Mejia-Arangure JM, Bonilla M,
Lorenzana R, et al. Incidence
of leukemia in children from EL Salvador and Mexico city between 1996 and 2000:
Population-based data. BMC Cancer 2005; 5:33.
12. Jmili NB, Abdelaziz AB, Nagara
M, et al. Cytological features
of acute leukemia in the central region of Tunisia. Eastern
Mediterranean Health Journal 2004; 10(4/5).
13. Freedman LS, Barchana M,
Al-Kayed S, et al. A
comparison of population-based cancer incidence rates in Israel and Jordan. European Journal of
Cancer Prevention 2003; 12(5)
14. Hjalgrim LL, Rostgaard K,
Schmiegelow K, et al. Age- and sex-specific incidence of childhood
leukemia by immunophenotype in the Nordic Countries. JNCI Journal of the
National Cancer Institute 2003; 95(20):1539-1544
15. Hann IM, Richards SM, Eden OB, et al. Analysis of the immunophenotype of children treated on the Medical Research Council United Kingdom acute lymphoblastic leukaemia trial XI (MRC UKALLXI). Medical Research Council Childhood Leukaemia Working Party. Leukemia 1998 Aug; 12(8):1249-1255.
16. Consolini R, Legitimo A, Rondelli R, et al. Clinical relevance of CD10 childhood ALL. The Italian Association of Pediatric Hematology and Oncology expression in (AIEOP). Haematologica 1998; 83(11): 967-973.