LETTER TO THE EDITOR
Epidural leukemic involvement and intracranial hemorrhage
as initial manifestations in a newly diagnosed chronic
myeloid leukemia patient
Shih-Feng Cho
&Ta-Chih Liu
&Chi-Yu Lu
&Chao-Sung Chang
Received: 5 July 2010 / Accepted: 18 August 2010 / Published online: 9 September 2010 # Springer-Verlag 2010
Dear Editor,
Intracranial leukemic involvement is an extremely rare
initial manifestation in the chronic phase of chronic
myeloid leukemia (CML) patients. We present the case of
a 33-year-old Taiwanese man who was admitted to the
hematology ward in December 2007 because of abnormal
findings in the white blood cell count in the hemogram
(total, 186,260 cells/μl; blast cells, 2%; promyelocytes,
5.5%; myelocytes, 16%; metamyelocytes, 12%; band cells,
14%; segmented cells, 43.5%; monocytes, 2%; and
lym-phocytes, 5%) since October 2007. The findings of the
cytogenetic study and molecular examination revealed that
the patient was positive for Philadelphia (Ph’) chromosome
and Bcr-Abl, respectively. The patient was diagnosed with
CML in the chronic phase.
This patient had severe headache, vomiting, and
drows-iness 3 days after admission. Computed tomography (CT)
revealed a right parietal epidural hemorrhage (Fig.
1
, panel
a). An emergent craniotomy was performed, and an
epidural hematoma with intact dura mater and some brain
tissue-like substance were observed. The excised tissue was
mixed with hematoma and some friable yellowish
speci-men. Microscopic examination of this mixed tissue (Fig.
1
,
panels d–f) revealed a tumor composed of hemorrhage
mixed with focally increased large blast-like cells.
Immu-nohistochemical analysis showed positive myeloperoxidase
and positive lysozyme staining. On the day after the
operation, we observed dilation of the right pupil and
weakness in the left-side muscles of the patient. Repeated
CT showed right parietal epidural, subdural, and putaminal
hemorrhage. A second craniotomy was performed to
remove the hematoma and for drainage. After the operation,
the patient was initially administered hydroxyurea (1 g/day)
and then switched to imatinib mesylate (IM; 400 mg/day)
from January 2008 with the approval of the National Health
Insurance program. The postoperative brain CT scan
showed resolved hematoma (Fig.
1
, panel b). This patient
had mild weakness in the left side at discharge. Complete
hematologic remission was achieved by March 2008. The
brain CT and cerebrospinal fluid (CSF) analysis yielded a
completely normal result (Fig.
1
, panel c). Since the patient
showed a suboptimal response, wherein the 3-log reduction
S.-F. Cho
:
T.-C. Liu:
C.-S. Chang Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, TaiwanT.-C. Liu
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University,
Kaohsiung, Taiwan C.-Y. Lu
Department of Biochemistry, College of Medicine, Kaohsiung Medical University,
Kaohsiung, Taiwan C.-S. Chang
Graduate Institute of Healthcare Administration,
College of Health Science, Kaohsiung Medical University, Kaohsiung, Taiwan
C.-S. Chang (*) No.100, Tzyou 1st Road,
Kaohsiung 807, Taiwan, Republic of China e-mail: [email protected]
Ann Hematol (2011) 90:607–609 DOI 10.1007/s00277-010-1061-7
in the Bcr-Abl transcript levels was not achieved after
2 years of IM therapy, imatinib was substituted with
dasatinib in December 2009. Currently, the patient is in
hematologic remission and has follow-ups in our
hematol-ogy outpatient clinic regularly.
Pharmacokinetic analyses have shown that IM penetrates
poorly into the central nervous system (CNS); the ratio of
the IM concentration in the serum to that in CSF was 40
–
155 [
1
–
5
]. The poor IM penetration rate in the CNS may be
a potential cause for the CNS relapse in approximately 20%
of the CML patients, especially in patients in the advanced
CML stages [
6
–
8
]. Our patient has been in hematologic
remission without CNS relapse for approximately 2 years
after craniotomy and IM therapy. We analyzed the IM
concentrations in the CSF and the serum during stable
remission by using liquid chromatography and
spectropho-tometric assay. The results of these analyses showed that
the ratio of the IM concentration in the serum to that in the
CSF was 25, which was lower than that reported in
previous studies.
In conclusion, initial leukemic involvement of the CNS
is quite unusual in the chronic phase of CML. Interestingly,
in this case, we observed that even partial penetration of IM
through the blood–brain barrier due to operative damage
could lead to disease recovery and durable remission of
leukemia in the CNS.
Authors’ disclosures of potential conflicts of interest The author(s) have no potential conflicts of interest.
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