Acute Leukemias - Republican Scientific Medical Library

Emergencies in Acute Lymphoblastic Leukemia
Olga Frankfurt, Martin S. Tallman
Contents
23.1 Introduction .................. 281
23.2 Metabolic Complications ......... 281
23.3 Lactic Acidosis ................ 282
23.4 Hypercalcemia ................ 283
23.5 Hyperleukocytosis ............. 283
23.6 SVC/Mediastinal Mass ........... 284
23.7 DIC ......................... 284
23.8 L-Asparaginase and Coagulopathy . 285
23.9 Neurological Complications ...... 285
23.10 Other Organ Involvement ........ 286
References ......................... 286
23.1 Introduction
The clinical presentation of acute lymphoblastic leukemia
(ALL) may range from nonspecific symptoms such
as progressive malaise, fever, and fatigue to severe lifethreatening
manifestations, requiring immediate medical
intervention.
23.2 Metabolic Complications
Severe metabolic disturbances may accompany the initial
diagnosis of ALL as well as the first phase of the induction
chemotherapy [1].
Patients with high leukemic burden are at risk of developing
acute tumor lysis syndrome (ATLS), manifesting
by hyperuricemia, hyperkalemia, hyperphosphatemia,
and secondary hypocalcemia. Such electrolyte abnormalities
may lead to the development of oliguric renal
failure due to the tubular precipitation of urate and
calcium phosphate crystals, fatal cardiac arrhythmias,
hypocalcemic tetany, and seizures.
Administration of vigorous intravenous hydration of
2–4 times daily fluid maintenance (approximately 3 l/
m 2 /d), sodium bicarbonate to alkalinize the urine (must
be given with caution since it may potentiate hypocalcemia),
oral or intravenous allopurinol to control hyperuricemia,
and phosphate binders to treat hyperphosphatemia
remain the standard therapy for management
of ATLS in the USA.
Although urine alkalinization (urine pH > 7) historically
has been recommended for the prophylaxis and
treatment of ATLS [2], it remains controversial. Since
maximum uric acid solubility occurs at the pH of 7.5,
alkalinization of urine promotes the urinary excretion
of the urate. However, solubility of urate precursors –
xanthine and hypoxanthine – is dramatically reduced
at such pH, leading to the development of urinary
xanthine crystals and xanthine obstructive uropathy
[2, 3].
A xanthine analog allopurinol, which competitively
inhibits xanthine oxidase and the conversion of xanthine
and hypoxanthine to uric acid, has been demonstrated
to effectively decrease the formation of uric acid
and reduce the incidence of uric acid obstructive uropathy
[4, 5]. However, allopurinol has several significant
limitations. First, allopurinol only prevents further uric
acid formation and has no effect of already existing uric