Complications of treatment
Posted by admin on August 27th, 2010Infections are the major cause of morbidity and mortality in the acute leukemias. They result from the severe leukopenia and destruction of normal cutaneous and mucosal barriers. Polymorphonuclear leukocytes, about 500 to 1000^L, are needed to protect against infection. In many palients, endogenous bowel flora is the source of infection, but the pharynx, lungs, perirectal area, and skin are also common sources. The GU tract and meninges are rare sites. Because the source of infection is internal, isolation has limited value. Viruses, protozoa, and anaerobic bacteria are uncommon pathogens early in therapy.
Fungal infections usually occur after 7 to 14 days of antibiotic therapy in neutropenic patients. The initial choice of antibiotics depends on the predominant organisms causing infection in a given hospital. An aminoglycoside plus a semisynthetic penicillin or a cephalosporin is usually the combination of choice because the most common organisms in most hospitals are Pseudomonas and Escherichia coli. Trimethoprim-sulfamethoxazole has been suggested as prophylaxis, particularly in patients who have had frequent admissions with fever and neutropenia.
Metabolic problems are common during induction therapy. Hyperuricemia should be treated prophylactically with allopurinol 300 mg/day. Often natriuresis and hyponatremia develop from increased os-molar clearance due to electrolytes, water, and urea released from dead blasts. Hypokalemia can occur from natriuresis, SIADH, physiologic hypervasopressinemia, or proximal renal tubular dysfunction. A renal tubular acidosis-like syndrome, with hypokalemia, aminoaciduria, and hyperphosphaturia, occurs but is probably not related to lysozyme. Metabolic alkalosis, metabolic acidosis, hypocalcemia, and hyperphosphatemia are also common complications. Oliguric renal failure will develop from uric acid nephropathy unless the patient is vigorously hydraled, treated with allopurinol, and has the urine alkalin-ized.
Aggregates of blasts and thrombi may occlude small blood vessels throughout the body, particularly in the brain and lungs. Therapy consists of hydration and rapid reduction of the blast count by promptly initiating chemotherapy. Leukapheresis and cranial irradiation may be temporizing measures.
The CNS is the most common site of extramedullar relapse in acute leukemia. The need for prophylactic meningeal therapy with cranial irradiation and intrathecal methotrexate or cytarabine has not been formally addressed in the elderly. Therefore, these methods currently must be used with extreme caution, if at all. Spinal cord compression, when it occurs, usually responds to local radiation. The acute T-cell lymphocytic leukemias are mosl likely to cause either CNS or gonadal invasion. However, the role of prophylactic testicular irradiation in the elderly is currently unclear.
Disseminated intravascular coagulation (DIC) is an uncommon complication seen mainly in promyelocytic (M3) leukemia. This bleeding disorder results from an underlying illness in which the clotting factors and platelets are consumed because of intravascular coagulation. The patient presents either with massive sudden bleeding (acute DIC) or, more usually, with slow bleeding (chronic DIC). Generally, DIC is self-limited and is most problematic during the rapid cell lysis of induction chemotherapy. The use of prophylactic heparin continues to be controversial.
