Hyperleukocytosis and leukostasis in hematologic malignancies
- Charles A Schiffer, MD
Charles A Schiffer, MD
- Professor of Medicine and Oncology
- Barbara Ann Karmanos Cancer Institute
- Wayne State University School of Medicine
Hyperleukocytosis refers to a laboratory abnormality that has been variably defined as a total leukemia blood cell count greater than 50 x 109/L (50,000/microL) or 100 x 109/L (100,000/microL). In contrast, leukostasis (also called symptomatic hyperleukocytosis) is a medical emergency most commonly seen in patients with acute myeloid leukemia (AML) or chronic myeloid leukemia (CML) in blast crisis. It is characterized by an extremely elevated blast cell count and symptoms of decreased tissue perfusion.
Leukostasis is a pathologic diagnosis in which white cell plugs are seen in the microvasculature. Clinically, leukostasis is typically diagnosed empirically when a patient with leukemia and hyperleukocytosis presents with respiratory or neurological distress. Prompt treatment is indicated since, if left untreated, the one-week mortality rate is approximately 20 to 40 percent.
The epidemiology, clinical presentation, diagnosis, and management of hyperleukocytosis and leukostasis in hematologic malignancies will be reviewed here. Other complications of leukemia are presented separately. (See "Overview of the complications of acute myeloid leukemia" and "Overview of the complications of chronic lymphocytic leukemia".)
The incidence of hyperleukocytosis and leukostasis vary by leukemia type and patient population. In general, symptoms of leukostasis are more common in leukemias with large, poorly deformable blasts, such as acute myeloid leukemia.
●Acute myeloid leukemia – Hyperleukocytosis is present in 10 to 20 percent of patients with newly diagnosed acute myeloid leukemia (AML). It is more common in patients with myelomonocytic (FAB-M4) leukemia, monocytic (FAB-M5) leukemia, or the microgranular variant of acute promyelocytic leukemia (FAB-M3) [1,2]. Symptoms of leukostasis occur less frequently and typically affect patients with white blood cell (WBC) counts over 100 x 109/L (100,000/microL).
- Cuttner J, Conjalka MS, Reilly M, et al. Association of monocytic leukemia in patients with extreme leukocytosis. Am J Med 1980; 69:555.
- Daver N, Kantarjian H, Marcucci G, et al. Clinical characteristics and outcomes in patients with acute promyelocytic leukaemia and hyperleucocytosis. Br J Haematol 2015; 168:646.
- Porcu P, Cripe LD, Ng EW, et al. Hyperleukocytic leukemias and leukostasis: a review of pathophysiology, clinical presentation and management. Leuk Lymphoma 2000; 39:1.
- Eguiguren JM, Schell MJ, Crist WM, et al. Complications and outcome in childhood acute lymphoblastic leukemia with hyperleukocytosis. Blood 1992; 79:871.
- Lichtman MA, Weed RI. Peripheral cytoplasmic characteristics of leukocytes in monocytic leukemia: relationship to clinical manifestations. Blood 1972; 40:52.
- Lichtman MA, Rowe JM. Hyperleukocytic leukemias: rheological, clinical, and therapeutic considerations. Blood 1982; 60:279.
- Lester TJ, Johnson JW, Cuttner J. Pulmonary leukostasis as the single worst prognostic factor in patients with acute myelocytic leukemia and hyperleukocytosis. Am J Med 1985; 79:43.
- Stucki A, Rivier AS, Gikic M, et al. Endothelial cell activation by myeloblasts: molecular mechanisms of leukostasis and leukemic cell dissemination. Blood 2001; 97:2121.
- Azoulay E, Fieux F, Moreau D, et al. Acute monocytic leukemia presenting as acute respiratory failure. Am J Respir Crit Care Med 2003; 167:1329.
- Schiffer CA, Wiernik PH. Functional evaluation of circulating leukemic cells in acute non-lymphocytic leukemia. Leuk Res 1977; 1:271.
- Lichtman MA. Rheology of leukocytes, leukocyte suspensions, and blood in leukemia. Possible relationship to clinical manifestations. J Clin Invest 1973; 52:350.
- Myers TJ, Cole SR, Klatsky AU, Hild DH. Respiratory failure due to pulmonary leukostasis following chemotherapy of acute nonlymphocytic leukemia. Cancer 1983; 51:1808.
- Dombret H, Hunault M, Faucher C, et al. Acute lysis pneumopathy after chemotherapy for acute myelomonocytic leukemia with abnormal marrow eosinophils. Cancer 1992; 69:1356.
- Tryka AF, Godleski JJ, Fanta CH. Leukemic cell lysis pneumonopathy. A complication of treated myeloblastic leukemia. Cancer 1982; 50:2763.
- Würthner JU, Köhler G, Behringer D, et al. Leukostasis followed by hemorrhage complicating the initiation of chemotherapy in patients with acute myeloid leukemia and hyperleukocytosis: a clinicopathologic report of four cases. Cancer 1999; 85:368.
- Dutcher JP, Schiffer CA, Wiernik PH. Hyperleukocytosis in adult acute nonlymphocytic leukemia: impact on remission rate and duration, and survival. J Clin Oncol 1987; 5:1364.
- van Buchem MA, te Velde J, Willemze R, Spaander PJ. Leucostasis, an underestimated cause of death in leukaemia. Blut 1988; 56:39.
- Vaughan WP, Kimball AW, Karp JE, et al. Factors affecting survival of patients with acute myelocytic leukemia presenting with high wbc counts. Cancer Treat Rep 1981; 65:1007.
- Bug G, Anargyrou K, Tonn T, et al. Impact of leukapheresis on early death rate in adult acute myeloid leukemia presenting with hyperleukocytosis. Transfusion 2007; 47:1843.
- Kasner MT, Laury A, Kasner SE, et al. Increased cerebral blood flow after leukapheresis for acute myelogenous leukemia. Am J Hematol 2007; 82:1110.
- Porcu P, Farag S, Marcucci G, et al. Leukocytoreduction for acute leukemia. Ther Apher 2002; 6:15.
- Porcu P, Danielson CF, Orazi A, et al. Therapeutic leukapheresis in hyperleucocytic leukaemias: lack of correlation between degree of cytoreduction and early mortality rate. Br J Haematol 1997; 98:433.
- Oberoi S, Lehrnbecher T, Phillips B, et al. Leukapheresis and low-dose chemotherapy do not reduce early mortality in acute myeloid leukemia hyperleukocytosis: a systematic review and meta-analysis. Leuk Res 2014; 38:460.
- Grund FM, Armitage JO, Burns P. Hydroxyurea in the prevention of the effects of leukostasis in acute leukemia. Arch Intern Med 1977; 137:1246.
- Eisenstaedt RS, Berkman EM. Rapid cytoreduction in acute leukemia. Management of cerebral leukostasis by cell pheresis. Transfusion 1978; 18:113.
- Bloom R, Taveira Da Silva AM, Bracey A. Reversible respiratory failure due to intravascular leukostasis in chronic myelogenous leukemia. Relationship of oxygen transfer to leukocyte count. Am J Med 1979; 67:679.
- Karp DD, Beck JR, Cornell CJ Jr. Chronic granulocyte leukemia with respiratory distress. Efficacy of emergency leukapheresis. Arch Intern Med 1981; 141:1353.
- Lane TA. Continuous-flow leukapheresis for rapid cytoreduction in leukemia. Transfusion 1980; 20:455.
- Mehta AB, Goldman JM, Kohner E. Hyperleucocytic retinopathy in chronic granulocytic leukaemia: the role of intensive leucapheresis. Br J Haematol 1984; 56:661.
- Giles FJ, Shen Y, Kantarjian HM, et al. Leukapheresis reduces early mortality in patients with acute myeloid leukemia with high white cell counts but does not improve long- term survival. Leuk Lymphoma 2001; 42:67.
- Thiébaut A, Thomas X, Belhabri A, et al. Impact of pre-induction therapy leukapheresis on treatment outcome in adult acute myelogenous leukemia presenting with hyperleukocytosis. Ann Hematol 2000; 79:501.
- PATHOPHYSIOLOGY OF LEUKOSTASIS
- SIGNS AND SYMPTOMS
- LABORATORY ABNORMALITIES
- - Induction chemotherapy
- - Hydroxyurea
- - Leukapheresis
- Supportive care
- Is there a role for cranial irradiation?
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS