Abstract
Background: Intracranial hemorrhage (ICH) is a common complication in acute leukemia that is associated with significant morbidity and mortality. While evidence supports prophylactic platelet transfusions at a threshold < 10 x 109/L to reduce the risk of bleeding in acute leukemia, there is little data to guide platelet transfusion practice in patients following ICH. The objectives of this study were to characterize the clinical features and outcomes of acute leukemia patients with ICH and to understand current platelet transfusion practice following ICH.
Methods: This was a retrospective study conducted at a large, quaternary, academic cancer centre. We included all adult patients with a diagnosis of acute leukemia who had a documented ICH at our centre between January 1, 2009 and December 31, 2016. We assessed demographics, medications, infection and bleeding history in the week preceding ICH, characteristics of ICH including site of bleed, acute management, transfusion practice in the first 90 days, and clinical outcomes. Radiologic scans were re-assessed by neuroradiology to determine if the ICH was stable or if new or progressive bleeding had developed. Transfusion practice following the ICH was compared between the two groups with longitudinal data analysis using platelet counts as outcome. Kaplan-Meier product limit method was used to estimate overall survival (OS) rates as well as to obtain median survival; log-rank test was used to compare OS among those without new or progressive ICH vs. those with progression.
Results: During the study period, of 2576 patients diagnosed with acute leukemia, 101 suffered from ICH and were included in the study. Most patients (94) had AML, of which 9 had APL, 6 had ALL, and 1 had MPAL. At the time of ICH, 61 patients were newly diagnosed or receiving induction chemotherapy, 33 had relapsed disease and 7 were in complete remission. Spontaneous ICH occurred in 76 patients. Within the week preceding ICH, 7 patients were on medications known to increase bleeding risk and 39 were on tranexamic acid. Sixty-four patients had clinical evidence of bleeding elsewhere and 22 had evidence of infection.
On the day of ICH, the median platelet count was 16 x 109/L (range 0- 433 x109/L). Thirty-one patients had a platelet count < 10 x 109/L and 10 of these patients received a platelet transfusion prior to the bleed. Seventy patients had a platelet count ≥10 x109/L and 17 of these received a platelet transfusion prior to the bleed. Six patients (6%) exhibited evidence of platelet transfusion refractoriness.
In the 90 days following ICH, 21% of platelet transfusions were given for a platelet count < 10 x 109/L, 55% were given with a platelet count between 10-29 x109/L, and 24% were given with a platelet count ≥ 30 x 109/L. New or progressive ICH occurred in 28 patients. The median platelet transfusion threshold was 19 x 109/L (range 0-114 x 109/L) for those without new or progressive ICH and 21 x 109/L (range 0-93 x 109/L) for those with progression (p=0.04; Figure 1). Of the 101 study patients, 79 have died. Median OS was 5.6 months for those without new or progressive ICH and 2.9 months for those with progression (p=0.002) (Figure 2). Cause of death was attributed to non-ICH causes in the majority of patients 65/79 (82%).
Conclusions: In this retrospective study, we evaluated the outcomes of 101 patients with acute leukemia and ICH. At the time of the bleed, the majority of patients had active disease and more than two thirds had platelet counts of 10 x 109/L or higher. During 90 days of follow-up, nearly one third of patients developed new or progressive ICH. Platelet transfusion practice was variable and the median threshold was, in fact, higher in those who subsequently developed new or progressive bleeding. The reasons for this were unclear from our chart review, but we hypothesize that these patients may have had additional risk factors, e.g. fever, infection. The outcomes of patients with acute leukemia and ICH are poor. Factors other than platelet transfusion threshold likely contribute to secondary ICH events and the overall poor prognosis.
Maze:Novartis: Consultancy, Honoraria.
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