Jugoslov. Med. Biohem. 2002.

; 21 (4) 351

UC 577,1; 61 ISSN 0354-3447

Jugoslov. Med. Biohem. 21: 351– 354, 2002 Originalni nau~ni rad
Original paper

BIOCHEMICAL ALTERATIONS IN PATIENTS WITH ACUTE LEUKAEMIA

Miroljub Petrovi}1, Miodrag Raji}2
1University School of Pharmacy, Belgrade
2Zvezdara Clinical and Hospital Centre, Belgrade

Summary: After statistical analysis of biochemical parameters in 60 patients with acute leukaemia, it was
concluded that most prominent alterations were elevated values of serum lactate-dehydrogenase, uric acid and
calcaemia. In patients with acute myeloid leukaemia, prothrombin time and partial thromboplastin time were sig-
nificantly prolonged, and in patients with acute lymphocytic leukaemia serum immunoglobuline levels were sig-
nificantly lower. Biochemical alterations may produce some implications for the general state of the patient, as
well as for the clinical course of the disease, its complications and outcome, with possible influence on the effect
of therapy.
Key words: biochemical alterations, acute leukaemia

Introduction and cytochemical stainings for peroxydase (8), Sudan

Acute leukaemias are clonal malignant neopla-
sias characterized by uncontrolled proliferation of pat-
hological leukaemic (£blast‹) cells and by impaired
genesis of normal blood cells (1).
The contemporary point of view of leukaemoge-
nesis defines it as a consequence of a mutation or am-
plification of the protooncogene (2), thus producing
the clonal character of neoplasia (3), confirmed by
cytochemical (4), cytogenetical (5) and immunophe-
notype analyses (6).
Black B (8), PAS (9) and non-specific esterases com-
bined with chlor-acetate staining (10). Analysis of
bichemical parameters was done according to the
classical laboratory techniques wided by immunoelec-
trophoretical analysis of proteins in agar gell with ve-
ronal-acetate buffer pH 8.2 (ionic strength 0.1 in the
chamber and 0.05 in gell) (11). Radial immunodiffu-
sion was done in agar gell with phosphate buffer pH
7.2 (12). Identification was done with monospecific
antisera to immunoglobuline classes manufactured by
Behringwerke.

In addition to the clinical, cytomorphological
and immunophenotype characteristics which can give
exact distinction between acute myeloid (AML) and
acute lymphoid leukaemia (ALL), it is of certain inte-
rest to find out possible corresponding biochemical
traits that could be of value in marking each of these
two groups of acute leukaemia.
All examined biochemical parameters were com-
pared with the corresponding ones in control group of
twenty healthy subjects.
Statistical analysis was done in programme SPSS
8.0 with data base formulated in Exel. Evaluation of
inter- and intragroup differences was done with Wilco-
xon range test.

Materials and Methods Results

In all subject classical May-Grünwald-Giemsa sta- The study included sixty patients with acute leu-
ining of peripheral blood smears (7) was performed, kaemia diagnosed at the Onco-Haematological Ward
of Zvezdara Clinical and Hospital Centre in Belgrade,
between 1991 and 2000, of whom 48 patients had
Address for correspondence acute myeloid leukaemia, and 12 acute lymphoid leu-
Miroljub Petrovi} kaemia. Control group consisted of twenty healty indi-
Gr~ica Milenka 1 viduals.
11000 Belgrade
352 Jugoslov. Med. Biohem. 2002.; 21 (4)

The following biochemical parameters were ana- are presented in Table I. The group of all patients
lysed: lactate-dehydrogenase (LDH), uric acid, sodium, (B+C) is marked as £A‹ in Table I.
potassium, calcium, phosphorus, IgA, IgG, IgM, elec-
Table I shows that most frequent biochemical
trophoresis and immunoelectrophoresis, prothrombin
alterations were elevated: uric acid and lactate-dehy-
time (PT) and partial thromboplastin time (PTT).
drogenase in serum, as well as electrolyte dysbalances
Results of biochemical parameters evaluation in ’ hyponatraemia and hypercalcaemia. Values of lac-
patients with AML (B), ALL (C) and control group (D) tate-dehydrogenase were more elevated in patients
with acute lymphoid leukaemia. Also, low levels of se-
rum immunoglobulins (especially IgG) were significan-
tly more frequent in patients with acute lymphoid leu-
Table I Detected biochemical alterations in acute myeloid kaemia than in those with acute myeloid leukaemia.
leukaemia (AML) and acute lymphoid leukaemia Table II shows that between the £all patients
group‹ (A) and control group (D) differences were sta-
all pts AML ALL cont. tistically significant with the following parameters: ele-
Alteration
(A) (B) (C) (D) vated values of lactate-dehydrogenase, uric acid, hyper-
elevated LDH 27 18 9 1 calcaemia, low serum IgG and prolonged prothrombin
elevated uric acid 30 24 6 2 time and partial thromboplastin time.
hyponatraemia 24 20 4 0 Comparison of AML group (B) and ALL group (C)
hypernatraemia 6 6 0 0 with control group (D) showed that the significant
difference of parameter values was similar to that obta-
hypokalaemia 15 12 3 0 ined by comparison of group A to group D; signifi-
hypercalcaemia 24 18 6 0 cantly non-fitting parameters were: hyponatraemia,
hypocalcaemia 12 12 0 0 hypokalaemia, hypocalcaemia, prothrombin time, par-
hypophosphataemia tial thromboplastin time and values of serum immu-
6 6 0 0
noglobulins. Abnormal values of these parameters
hyperphosphataemia 6 4 2 0 (except immunoglobulins) predominated in AML
prolonged PT 15 8 7 0 group, while lower values of immunoglobulins predo-
prolonged PTT 15 8 7 0 minated in ALL group.
low IgG 15 6 9 1 Comparison between AML and ALL groups re-
low IgA 6 0 6 0
vealed a statistically significant difference only regar-
ding the following parameters: hyponatraemia, hyper-
low IgM 9 3 6 0 phosphataemia and the levels of immunoglobulines.

Table II Results of statistical significance testing in investigated groups

Parameter A:D B:D C:D B:C

elevated LDH p < 0.05 p < 0.05 p < 0.01 n.s.
elevated uric acid p < 0.05 p < 0.05 p < 0.05 n.s.
hyponatraemia p = 0.015 p < 0.05 p = 0.01 p < 0.05
hypernatraemia n.s. n.s. n.s. n.s.
hypokalaemia n.s. p < 0.05 p = 0.01 n.s.
hypercalcaemia p < 0.05 p = 0.01 p < 0.01 n.s.
hypocalcaemia p = 0.012 p < 0.05 n.s. p = 0.015
hypophosphataemia n.s. n.s. n.s. p = 0.012
hyperphosphataemia n.s. n.s. p = 0.012 p < 0.05
prolonged PT p < 0.05 p < 0.05 p = 0.012 n.s.
prolonged PTT p < 0.05 p < 0.05 p = 0.01 n.s.
low IgG n.s. p = 0.015 p < 0.01 p < 0.01
low IgA p = 0.020 n.s. p < 0.05 p < 0.01
low IgM n.s. p = 0.015 p < 0.05

A ’ AML + ALL group; B ’ AML group; C ’ ALL group; D ’ control group; n.s. ’ not significant
Jugoslov. Med. Biohem. 2002.; 21 (4) 353

Discussion Low values of one or more classes of serum

There are data in literature describing high levels
of serum uric acid (13) and lactate-dehydrogenase
(14) in patients with acute myeloid leukaemia, especi-
ally those with higher proportion of monocytoid cells.
It was supposed that elevated value of uric acid might
be the consequence of chemotherapeutic cytolytic
effect. There are also some data on the frequently high
levels of sodium, potassium, calcium and hydrogen
ione in sera of patients with acute leukaemia; some
authors, however, have found lower values of parame-
ters mentioned (14, 15). On rare occasions a profo-
und hyponatraemia may be found due to disturbance
of antidiuretic hormone (ADH) secretion, or a signifi-
cant hypernatraemia due to diabetes insipidus. Also
hypokalaemia is described due to impaired function of
the proximal renal tubuli. Hypokalaemia may also be
enhanced by concomitant use of some medications
(e.g. diuretics and some antibiotics). In some instan-
ces serum potassium levels may be falsely elevated due
to in vitro release of potassium from leukaemic cells.
Hypercalcaemia is mostly an effect of pseudo-
hyperparathyreoidism (16), and hypophosphataemia
may be a consequence of phospate ions absorption by
leukaemic cells. Some authors (16) also stress the fre-
quent findings of abnormal values of prothrombin
time and partial thromboplastin time caused by multi-
factorial processes.
Lactate acidosis is frequent in acute myeloid
leukaemia (17), this study has not included the analy-
sis of the phenomenon.
immunoglobulins are a frequent finding in acute lym-
phoid leukaemia; this study confirms the findings of
hypoimmunoglobulinaemia in ALL (18). There are
also numerous reports on the high level of serum lac-
tate-dehydrogenase in acute leukaemia, as well as the
combined disturbances of serum electrolyte levels,
chiefly hyperphosphataemia, hyperphosphaturia, hy-
pocalcaemia, hyperkalaemia and hyperuricaemia (19).
Conclusion
While strictly haematological alterations have been
the object of thorough laboratory examination, other
biochemical alterations have been generally neglected
and hence inadequately studied. Yet, their frequency is
significant, which is confirmed by this study. Most fre-
quently are found elevated values of serum lactate-
dehydrogenase and uric acid, then pathological values
of serum electrolytes and (especially in ALL) serum
immunoglobulins. These biochemical alterations may
be the cause of important implication for the general
state of the patient, clinical course and outcome of the
disease, its complications and reaction to therapy.
Therefore, paying an appropriate attention to bioche-
mical alterations becomes unavoidable and has al-
most equal importance in diagnosis and treatment of
acute leukaemia as other haematological, cytochemi-
cal and cytogenetical analyses.

BIOHEMIJSKE PROMENE KOD BOLESNIKA SA AKUTNOM LEUKEMIJOM

Miroljub Petrovi}1, Miodrag Raji}2
1Farmaceutski fakultet, Beograd
2KBC £Zvezdara‹, Beograd

Kratak sadr`aj: Po obavljenom ispitivanju i statisti~koj obradi vrednosti biohemijskih parametara kod 60
pacijenata obolelih od akutne leukemije, utvr|ene su povi{ene vrednosti serumske laktat-dehidrogenaze, mo-
kra}ne kiseline i kalcijuma. Kod bolesnika sa akutnom mijeloidnom leukemijom otkriveno je zna~ajno produ`eno
protrombinsko i parcijalno tromboplastinsko vreme, dok su kod bolesnika sa akutnom limfoblastnom leukemi-
jom vrednosti serumskih imunoglobulina bile zna~ajno ni`e. Konstatovano je da biohemijske promene zna~ajno
uti~u na op{te stanje pacijenata, kao i na klini~ki tok, komplikacije i ishod bolesti. One tako|e mogu imati utica-
ja na efekte primenjene terapije.
Klju~ne re~i: biohemijske promene, akutna leukemija.
354
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Received: May 15, 2002
Accepted: October 21, 2002