Intracranial hemorrhage in patients with a hematological disorder requiring intensive chemotherapy and/or a stem cell transplant: a systematic review (0563)

Background. To advance the quality of care for hematology patients receiving intensive chemotherapy it is important to gain a greater understanding of the risk factors for life-threatening haemorrhage. This systematic review concentrates on intra-cranial hemorrhage (ICH) because it is the most serious type of bleed caused by significant thrombocytopenia. If an ICH does not cause death it may lead to significant long-term morbidity. However, this complication is rare, its exact incidence is uncertain, and predisposing risk factors are currently unknown. Aims. A systematic review of cases published in the literature during the last decade to determine its incidence and possible risk factors. Methods. We searched MEDLINE, EMBASE, CENTRAL, NLH CINAHL, and the SRI RCT Handsearch(www.transfusionevidencelibrary.com) electronic bibliographic databases for studies published between January 2001 and December 2010. There were no language restrictions. We included studies of patients, of any age, with hematological disorders, who required intensive chemotherapy or a stem cell transplant, and were expected to develop a significant thrombocytopenia. If trials consisted of mixed populations of patients, with diagnoses of solid tumours, only data from the haematological sub-groups were used. We excluded studies if fewer than 80% of participants had a hematological disorder and sub-group data was not provided. We also excluded studies if the participants were receiving palliative treatment; fewer than 33% of participants were expected to become significantly thrombocytopenic, or participants had immune thrombocytopenia. Data were collected on baseline characteristics of the cases (age, diagnosis, treatment and presumed risk-factors for ICH(e.g sepsis, anticoagulants, coagulopathy)) as well as any data on the same characteristics that were reported for the entire study population. Results. 6852 studies were initially identified, 6002 studies were excluded on the basis of the abstract. 850 full text articles were reviewed and of these, 254 studies were included in the review (183 cohort studies, 22 case series, and 49 case studies). 1099 cases of ICH were described within the included studies. Over half(55%) died due to ICH. The majority of cases were poorly described, for example, only 26.7%(294/1099) reported whether the patient was thrombocytopenic, 18.1% whether patient had a coagulopathy and only 4.9% described the presence or absence of anticoagulants. The majority of patients (93.4%;511/547) whose disease status was known had active disease at the time of the ICH. Data on incidence ratios will be presented at the meeting. Studies which included patients with acute promyelocytic leukemia (APL), which is well known to have a high incidence of hemorrhage, were more likely to report the presence or absence of ICH. Overall, approximately a third of acute leukemia patients within the included studies had APL, whereas the actual incidence of APL is approximately 10%. Summary and Conclusions. Cases of ICH are poorly reported in the literature, and the literature is biased in favor of APL. To provide a more unbiased picture of the incidence and risk-factors for ICH in hematology patients we have set up a UK-wide prospective reporting system (Haematology Active Surveillance System (HASS)) with a case-control study (InCiTe study) embedded within it.