Intracranial hemorrhage in adult patients with hematological malignancies

BMC Medicine

Hwei-Fang Tien⁵  Jih-Luh Tang¹  Ming Yao⁵  Shang-Yi Huang⁵  Pey-Ying Chen³  Jia-Hau Liu¹  Woei Tsay⁵  Hung-Chang Wu⁴  Aristine Cheng⁵  Chan-Hwei Tai²  Chien-Yuan Chen⁵ 

[1] Tai-Cheng Stem Cell Therapy Center, National Taiwan University Hospital, Taipei, Taiwan;Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan;Department of Nursing, National Taiwan University Hospital, Taipei, Taiwan;Department of Internal Medicine, Division of Hematology and Oncology, Chi-Mei Hospital, Tainan, Taiwan;Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

关键词: neuroimage;    prognosis;    hematological malignancy;    cerebral hemorrhage;    central nervous system (CNS) involvement;   

Others  :  857361
DOI  :  10.1186/1741-7015-10-97

 received in 2012-02-03, accepted in 2012-08-29,  发布年份 2012

【 摘 要 】

Background

Clinical characteristics and outcomes of intracranial hemorrhage (ICH) among adult patients with various hematological malignancies are limited.

Methods

A total of 2,574 adult patients diagnosed with hematological malignancies admitted to a single university hospital were enrolled into this study between 2001 and 2010. The clinical characteristics, image reports and outcomes were retrospectively analyzed.

Results

A total of 72 patients (48 men and 24 women) with a median age of 56 (range 18 to 86) had an ICH. The overall ICH incidence was 2.8% among adult patients with hematological malignancies. The incidence of ICH was higher in acute myeloid leukemia (AML) patients than in patients with other hematological malignancies (6.3% vs 1.1%, P = 0.001). ICH was more common among patients with central nervous system (CNS) involvement of lymphoma than among patients with CNS involved acute leukemia (P <0.001). Sites of ICH occurrence included the cerebral cortex (60 patients, 83%), basal ganglia (13 patients, 18%), cerebellum (10 patients, 14%), and brainstem (5 patients, 7%). A total of 33 patients (46%) had multifocal hemorrhages. In all, 56 patients (77%) had intraparenchymal hemorrhage, 22 patients (31%) had subdural hemorrhage, 15 patients (21%) had subarachnoid hemorrhage (SAH), and 3 patients (4%) had epidural hemorrhage. A total of 22 patients had 2 or more types of ICH. In all, 46 (64%) patients died of ICH within 30 days of diagnosis, irrespective of the type of hematological malignancy. Multivariate analysis revealed three independent prognostic factors: prolonged prothrombin time (P = 0.008), SAH (P = 0.021), and multifocal cerebral hemorrhage (P = 0.026).

Conclusions

The incidence of ICH in patients with AML is higher than patients with other hematological malignancies. But in those with intracranial malignant disease, patients with CNS involved lymphoma were more prone to ICH than patients with CNS involved acute leukemia. Mortality was similar regardless of the type of hematological malignancy. Neuroimaging studies of the location and type of ICH could assist with prognosis prediction for patients with hematological malignancies.

【 授权许可】

   
2012 Chen et al; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Rogers LR: Cerebrovascular complications in patients with cancer. Semin Neurol 2010, 30:311-319.
• [2]Chen CY, Tai CH, Tsay W, Chen PY, Tien HF: Prediction of fatal intracranial hemorrhage in patients with acute myeloid leukemia. Ann Oncol 2009, 20:1100-1104.
• [3]Dayyani F, Mougalian SS, Naqvi K, Shan J, Ravandi F, Cortes J, Weinberg J, Jabbour E, Faderl S, Wierda W, Thomas D, O'Brien S, Pierce S, Kantarjian H, Garcia-Manero G: Prediction model for mortality after intracranial hemorrhage in patients with leukemia. Am J Hematol 2011, 86:546-549.
• [4]Kim H, Lee JH, Choi SJ, Lee JH, Seol M, Lee YS, Kim WK, Lee JS, Lee KH: Risk score model for fatal intracranial hemorrhage in acute leukemia. Leukemia 2006, 20:770-776.
• [5]Yamauchi K, Umeda Y: Symptomatic intracranial haemorrhage in acute nonlymphoblastic leukaemia: analysis of CT and autopsy findings. J Neurol 1997, 244:94-100.
• [6]Rickles FR, Falanga A, Montesinos P, Sanz MA, Brenner B, Barbui T: Bleeding and thrombosis in acute leukemia: what does the future of therapy look like? Thromb Res 2007, 120(Suppl 2):S99-106.
• [7]Rogers LR: Management of stroke in cancer. Curr Oncol Rep 2008, 10:72-77.
• [8]Rogers LR: Cerebrovascular complications in cancer patients. Neurol Clin 2003, 21:167-192.
• [9]Glass J: Neurologic complications of lymphoma and leukemia. Semin Oncol 2006, 33:342-347.
• [10]Grisold W, Oberndorfer S, Struhal W: Stroke and cancer: a review. Acta Neurol Scand 2009, 119:1-16.
• [11]Rebulla P, Finazzi G, Marangoni F, Avvisati G, Gugliotta L, Tognoni G, Barbui T, Mandelli F, Sirchia G: The threshold for prophylactic platelet transfusions in adults with acute myeloid leukemia. Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto. N Engl J Med 1997, 337:1870-1875.
• [12]Blajchman MA, Slichter SJ, Heddle NM, Murphy MF: New strategies for the optimal use of platelet transfusions. Hematology Am Soc Hematol Educ Program 2008, 198-204.
• [13]Thomas X, Le QH: Central nervous system involvement in adult acute lymphoblastic leukemia. Hematology 2008, 13:293-302.
• [14]McMillan A: Central nervous system-directed preventative therapy in adults with lymphoma. Br J Haematol 2005, 131:13-21.
• [15]Shiber JR, Fines RE: Cerebral hemorrhage due to hyperleukocytosis. J Emerg Med 2011, 40:674-677.
• [16]Naunheim MR, Nahed BV, Walcott BP, Kahle KT, Soupir CP, Cahill DP, Borges LF: Diagnosis of acute lymphoblastic leukemia from intracerebral hemorrhage and blast crisis. A case report and review of the literature. Clin Neurol Neurosurg 2010, 112:575-577.
• [17]Wetzler M, Dodge RK, Mrózek K, Carroll AJ, Tantravahi R, Block AW, Pettenati MJ, Le Beau MM, Frankel SR, Stewart CC, Szatrowski TP, Schiffer CA, Larson RA, Bloomfield CD: Prospective karyotype analysis in adult acute lymphoblastic leukemia: the cancer and leukemia Group B experience. Blood 1999, 93:3983-3993.
• [18]de Labarthe A, Rousselot P, Huguet-Rigal F, Delabesse E, Witz F, Maury S, Réa D, Cayuela JM, Vekemans MC, Reman O, Buzyn A, Pigneux A, Escoffre M, Chalandon Y, MacIntyre E, Lhéritier V, Vernant JP, Thomas X, Ifrah N, Dombret H, Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL): Imatinib combined with induction or consolidation chemotherapy in patients with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia: results of the GRAAPH-2003 study. Blood 2007, 109:1408-13.
• [19]Cheng AL, Yeh KH, Uen WC, Hung RL, Liu MY, Wang CH: Systemic chemotherapy alone for patients with non-acquired immunodeficiency syndrome-related central nervous system lymphoma: a pilot study of the BOMES protocol. Cancer 1998, 82:1946-1951.
• [20]Anderson H, Scarffe JH, Lambert M, Smith DB, Chan CC, Chadwick G, McMahon A, Chang J, Crowther D, Swindell R: VAD chemotherapy--toxicity and efficacy--in patients with multiple myeloma and other lymphoid malignancies. Hematol Oncol 1987, 5:213-222.
• [21]Lazzarino M, Corso A, Barbarano L, Alessandrino EP, Cairoli R, Pinotti G, Ucci G, Uziel L, Rodeghiero F, Fava S, Ferrari D, Fiumanò M, Frigerio G, Isa L, Luraschi A, Montanara S, Morandi S, Perego D, Santagostino A, Savarè M, Vismara A, Morra E: DCEP (dexamethasone, cyclophosphamide, etoposide, and cisplatin) is an effective regimen for peripheral blood stem cell collection in multiple myeloma. Bone Marrow Transplant 2001 28:835-839.
• [22]Mehta J, Singhal S: Hyperviscosity syndrome in plasma cell dyscrasias. Semin Thromb Hemost 2003, 29:467-471.
• [23]Rubenstein J, Fischbein N, Aldape K, Burton E, Shuman M: Hemorrhage and VEGF expression in a case of primary CNS lymphoma. J Neurooncol 2002, 58:53-56.
• [24]Kim IY, Jung S, Jung TY, Kang SS, Choi C: Primary central nervous system lymphoma presenting as an acute massive intracerebral hemorrhage: case report with immunohistochemical study. Surg Neurol 2008, 70:308-311.
• [25]Kimura N, Ishibashi M, Masuda T, Morishige M, Abe T, Fujiki M, Kashima K, Kumamoto T: Primary central nervous system lymphoma with cortical laminar hemorrhage. J Neurol Sci 2009, 287:281-284.
• [26]Anda T, Haraguchi W, Miyazato H, Tanaka S, Ishihara T, Aozasa K, Nakamichi I: Ruptured distal middle cerebral artery aneurysm filled with tumor cells in a patient with intravascular large B-cell lymphoma. J Neurosurg 2008, 109:492-496.
• [27]Ganguly S: Acute intracerebral hemorrhage in intravascular lymphoma: a serious infusion related adverse event of rituximab. Am J Clin Oncol 2007, 30:211-212.
• [28]Hunault-Berger M, Chevallier P, Delain M, Bulabois CE, Bologna S, Bernard M, Lafon I, Cornillon J, Maakaroun A, Tizon A, Padrazzi B, Ifrah N, Gruel Y, GOELAMS (Groupe Ouest-Est des Leucémies Aiguës et Maladies du Sang): Changes in antithrombin and fibrinogen levels during induction chemotherapy with L-asparaginase in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma. Use of supportive coagulation therapy and clinical outcome: the CAPELAL study. Haematologica 2008, 93:1488-1494.
• [29]Alatoom A, Elsabrouty R, Willis J, Boils C, Sarode R, Hashim I, Wang HY: Fatal cerebral hemorrhage in a patient with CD19-positive IgM-producing aggressive plasma cell myeloma, hyperviscosity syndrome and cryoglobulinemia. Int J Clin Exp Pathol 2009, 2:498-507.
• [30]Reddy N, Karampelas I, Chanan-Khan A, Fenstermaker R, Padmanabhan S: Aggressive relapse of multiple myeloma with intracerebral extension and associated hemorrhage. Leuk Lymphoma 2007, 48:1228-1230.
• [31]Bleggi-Torres LF, Werner B, Gasparetto EL, de Medeiros BC, Pasquini R, de Medeiros CR: Intracranial hemorrhage following bone marrow transplantation: an autopsy study of 58 patients. Bone Marrow Transplant 2002, 29:29-32.
• [32]Elliott J, Smith M: The acute management of intracerebral hemorrhage: a clinical review. Anesth Analg 2010, 110:1419-1427.
• [33]Goldstein LB, Simel DL: Is this patient having a stroke? JAMA 2005, 293:2391-2402.
• [34]Bleggi-Torres LF, de Medeiros BC, Werner B, Neto JZ, Loddo G, Pasquini R, de Medeiros CR: Neuropathological findings after bone marrow transplantation: an autopsy study of 180 cases. Bone Marrow Transplant 2000, 25:301-307.
• [35]Qureshi AI, Tuhrim S, Broderick JP, Batjer HH, Hondo H, Hanley DF: Spontaneous intracerebral hemorrhage. N Engl J Med 2001, 344:1450-1460.
• [36]Ferro JM, Canhao P, Peralta R: Update on subarachnoid haemorrhage. J Neurol 2008, 255:465-479.
• [37]Mayer SA, Rincon F: Treatment of intracerebral haemorrhage. Lancet Neurol 2005, 4:662-672.
• [38]Falanga A, Rickles FR: Management of thrombohemorrhagic syndromes (THS) in hematologic malignancies. Hematology Am Soc Hematol Educ Program 2007, 165-171.
• [39]Franchini M, Dario Di Minno MN, Coppola A: Disseminated intravascular coagulation in hematologic malignancies. Semin Thromb Hemost 2010, 36:388-403.
• [40]Siao D, Seetapah A, Ryman A, Guerin V, Mesli A, Maurette P: Optimal management of an aneurysmal subarachnoid hemorrhage in a patient with known factor XI deficiency: a case report. Clin Appl Thromb Hemost 2008, 14:108-111.
• [41]Adeoye O, Broderick JP: Advances in the management of intracerebral hemorrhage. Nat Rev Neurol 2010, 6:593-601.
• [42]Aguilar MI, Demaerschalk BM: Intracerebral hemorrhage. Semin Neurol 2007, 27:376-384.
• [43]Mayer SA, Brun NC, Begtrup K, Broderick J, Davis S, Diringer MN, Skolnick BE, Steiner T, FAST Trial Investigators: Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med 2008, 358:2127-2137.