Intracranial Hemorrhage (ICH) In Patients (Pts) Presenting with Myeloid Leukemia to a Tertiary Care Center

ICH is a significant source of morbidity and mortality in pts with acute leukemias. Only relatively small retrospective series of pts with ICH have been reported previously. We evaluated the clinical characteristics of a large cohort of contemporary pts who developed ICH at MD Anderson Cancer Center (MDACC) to help better define the characteristics of pts at risk.

We retrospectively searched the leukemia database at MDACC and identified 2421 pts who presented from 2005–2009 to MDACC with de novo acute myeloid leukemia (AML; n=1265), acute lymphoblastic leukemia (ALL; n=304), myelodysplastic syndrome (MDS; n=728), or blast-crisis CML (BC-CML; n=124). Clinical characteristics were obtained by chart review.

Among 2421 pts, a total of 119 pts developed ICH, as diagnosed by either CT or MRI brain (AML, n=72, 5.7%; ALL, n=19, 6.3%; MDS, n=13, 1.6%; CML-BC, n=15, 12.1%). Median age was 58years (range: 14–81), 58 (48.7%) were male, median WBC at the time of ICH was 2200/ul (0-186,000), platelet count 19,000/ul (0-318,000),hemoglobin 9.0 g/dl (4.5-14.7), peripheral blast count 0% (0-92%), INR 1.4 (0.4-12), PTT 29sec (17-66), creatinine 0.9mg/dl, and albumin 3.0g/dl (1.4-4.9). The localization of the bleed was intraparenchymal (IPH) in 58%, subdural (SDH) in 30%, subarachnoid (SAH) in 12%, and epidural (EDH) in 2.5%. Three pts had 2 different types of bleed. Median time from diagnosis to ICH was 210 days (0-1953). Only 18.5% of the patients bled within 30 days of diagnosis. Three patients had acute promyelocytic leukemia (APL), 2/3 bled within 2 days of diagnosis. Among 72 AML patients, the most common cytogenetic abnormality was del(5-, 7-) (26/72; 36.1%), and only 1/15 pts with diploid cytogenetics had a Flt3 point mutation. Surgical intervention for ICH was performed in 12 patients (10.1%). Median OS for all 119 patients was 40wks (0-257), and for those 12 undergoing surgery 42 wks (3-257). OS by type of bleed was as follows: IPH 33 wks (0-257), SDH 40 wks (1-174), SAH 41wks (1-86), EDH 8 wks(0-13).

To our knowledge, we report here the largest cohort of contemporary pts with leukemia who develop ICH. While most previous studies highlight APL as the premier cause of ICH, in our cohort of over 2400 pts only 3 pts with APL developed ICH, likely due to heightened awareness for bleeding complications in these pts and aggressive transfusion. Pts in BC-CML have the highest relative proportion of ICH, suggesting a low threshold for head imaging in these pts. Most pts with ICH are profoundly thrombocytopenic at the time of the bleed, whereas the majority of them are not significantly coagulopathic. Less than 5% of all pts present with ICH at diagnosis or shortly thereafter, indicating that the major cause for developing ICH is chemotherapy-related thrombocytopenia or relapsed disease. Analyses to identify independent predictors of ICH in patients with leukemia are currently underway. The goal is to establish a novel predictive and/or prognostic model for ICH in patients with acute leukemias and MDS.

Wierda: Abbott: Research Funding; Genentech: Honoraria, Speakers Bureau. Thomas: Novartis: Honoraria; Bristol-Meyer-Squibb: Honoraria; Pfizer:; Amgen: Research Funding. Kantarjian: AstraZeneca: Research Funding.