Complications of Hyperleukocytosis and Leukapheresis in Pediatric Acute Leukemias.
Authors: Abla Oussama , Khanani M. F. , Hitzler J. K. , Sung L. , Geary D. , Abdelhaleem M. , Weitzman S. , Naqvi A. 
Published: October 2019

Abstract
Leukapheresis is commonly used in children with acute leukemia and hyperleukocytosis (WBC >100 x 109/L). We analyzed the frequency of early complications of hyperleukocytosis in children with acute lymphoblastic leukemia(ALL) and acute myeloid leukemia(AML) and the frequency of complications attributed to leukapheresis. We included all children with acute leukemia and hyperleukocytosis, presenting to HSC between January 1992 and May 2002. ICH/stroke, pulmonary leukostasis, acute renal failure (ARF) and death were considered severe complications of hyperleukocytosis. 61 ALL and 8 AML were reviewed. All children received intravenous hyperhydration, urinary alkalinization and allopurinol. Of 61 ALL children, 16 (26.2%) underwent leukapheresis; median WBC count was 559 x 109/L (range 200–969). Median WBC of non-leukapheresed ALL children was 181 x 109 /L (range 101–392). Five (62.5%) of 8 AML children underwent leukapheresis; median WBC was 376 x 109/L (range 167–470). The remaining 3 had a median WBC of 146 x 109/L (range 114–230). 10/61(16.3%) ALL patients presented with severe complications within 6 to 8 hours of arrival; 9 were leukapheresed. ICH occurred in 2, one of whom failed to receive platelet transfusion at presentation because of a falsely high automated platelet count corrected after 12 hours by more senior staff. Six had respiratory distress thought to be related to pulmonary leukostasis; all but 1 improved after leukapheresis. Three developed ARF due to hyperuricemia pre-leukapheresis. While 2 received leukapheresis, all required dialysis. One early death occurred on day 22 due to enterococcal sepsis. 3/8 (37.5%) AML children developed complications related to hyperleukocytosis: 2 had pulmonary leukostasis, only 1 improved after leukapheresis; 1 died at 72 hours due to stroke. Three non-leukapheresed AML patients remained clinically well with hyperhydration and early chemotherapy. Leukapheresis reduced the WBC by an average of 40–45% in both ALL/AML. Procedural complications secondary to leukapheresis occurred in 18/21(85.7%) children. Femoral vein thrombosis occurred in 5 patients. Five became hypocalcemic; while only one was symptomatic, all were given calcium infusions. Other complications were: coagulopathy(n=6), sinus bradycardia(n=4), hypotension(n=4), hypertension(n=3), hypokalemia(n=4), and hypomagnesemia(n=1). The leukapheresis circuits of 5 children (3 ALL, 2 AML) were primed with undiluted packed RBC; 3 had new or progressive pulmonary leukostasis following leukapheresis, 1 of whom also developed a stroke. In summary, severe complications in children with hyperleukocytosis are common. Leukapheresis reduced WBC in most patients and appeared to improve pulmonary leukostasis in some. However, it did not prevent progression of ARF. Also, procedural-related complications are considerable. We have identified the following sources of potentially preventable morbidity: 1. Calcium infusions during the procedure should be used with extreme caution; 2. Circuits should not be primed with undiluted red blood cells as this may exacerbate hyperviscosity; and 3. Manual platelet counts must be performed in hyperleukocytosis. Furthermore, it is insufficient for these issues to be appreciated by senior staff only. Continuous education of inexperienced staff and leukapheresis team regarding the most appropriate use of this procedure should be emphasized. A randomized evaluation of the benefits versus risks of leukapheresis is needed.