How I treat hematologic emergencies in adults with acute leukemia

Abstract

Acute myeloid leukemia and acute lymphoblastic leukemia remain devastating diseases. Only approximately 40% of younger and 10% of older adults are long-term survivors. Although curing the leukemia is always the most formidable challenge, complications from the disease itself and its treatment are associated with significant morbidity and mortality. Such complications, discussed herein, include tumor lysis, hyperleukocytosis, cytarabine-induced cellebellar toxicity, acute promyelocytic leukemia differentiation syndrome, thrombohemorrhagic syndrome in acute promyelocytic leukemia, L-asparaginase-associated thrombosis, leukemic meningitis, neutropenic fever, neutropenic enterocolitis, and transfussion-associated GVHD. IntroductionAlthough inadequate for the cure of most patients, the initial therapeutic approach to acute myeloid leukemia (AML) is standardized. However, the management of hematologic emergencies is challenging and may be controversial. We present clinical vignettes describing 10 emergencies encountered in practice and the questions such emergencies generate. We then provide our view of how to treat adults supported by studies if available and, if not, by clinical experience and consensus. The approach to these emergencies is as important as the antileukemia therapy, and in no clinical setting is it fairer to say that "the devil is in the details." Tumor lysis syndromeA 23-year-old man with a history of G6PD deficiency is diagnosed with pre-B acute lymphoblastic leukemia (B-ALL). At presentation, his white blood cell count (WBC) is 160 000/L with 90% lymphoblasts and 450/L neutrophils; the hemoglobin is 7.5 g/dL and platelet count is 10 000/L. His electrolytes and renal function are normal, the uric acid is 11.0 mg/dL, and lactate dehydrogenase (LDH) is 1500 IU/L (normal, 100-250 IU/L). Remission induction chemotherapy is planned. Questions What is the risk of tumor lysis syndrome (TLS)? What is the optimal treatment for preventing TLS? What is the role of rasburicase and urine alkalinization?TLS can appear before starting treatment (primary TLS) as a result of high turnover of the malignant cells or, more commonly, a short time after the beginning of treatment (secondary TLS). 1 The risk of developing TLS and its severity is influenced by many factors, including tumor burden, potential for rapid cell lysis, and preexisting nephropathy. 2 In acute leukemias, the risk is dependent on the WBC and the rate of response to therapy. In ALL with WBC Ͼ 100 000/L, the risk for TLS is high. With lower WBC, the risk is moderate and low. 3 A classification system has been developed, 4 which is based on separate definitions for laboratory and clinical TLS. Laboratory TLS loosely is defined as the presence of 2 or more abnormal laboratory values of uric acid, potassium, phosphorus, or calcium at presentation or a 25% change in values from the pretreatment measurements. Clinical TLS is defined as the presence of laboratory TLS plus renal dysfunction, seizures, cardiac arrhythmia, or sudden death. An expert TLS pane...

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