acute promyelocytic leukemia ( apl ) is characterized by the presence of atypical promyelocytes in bone marrow and peripheral blood . apl is distinguished from other subtypes of acute myeloid leukemia ( aml ) by its distinctive morphology , younger patient age at presentation , specific chromosomal abnormality , associated coagulopathy , and unique response to treatment with retionic acid . all - trans retinoic acid ( atra ) and intensive chemotherapy with ara - c and anthracycline is recommended as the standard treatment for apl ( 1 ) . although atra has improved the outcome of apl , early bleeding diathesis and recurrence are main causes of death in patients with apl . the involvement of central nervous system ( cns ) in aml is an uncommon finding . patients at the highest risk for developing the leukemia in cns include those with a high circulating blast count , elevated lactate dehydrogenase activity , and one of the monocytic leukemic subtypes ( 2 , 3 ) . moreover , leptomeningeal leukemic infiltration is rarely observed in patients with apl . we report a case of leptomeningeal relapse in a patient with a variant apl who had achieved complete remission after atra , idarubicin and cytarabine therapy . furthermore , we discuss the clinical manifestation and treatment of apl in cns in comparison of the results from our patients with those of the previously reported cases . the full blood count showed a hemoglobin level of 7.7 g / dl , a wbc count of 38.310/l consisting of 84% blasts , and a platelet count of 2510/l . a coagulation test demonstrated severe disseminated intravascular coagulation ( dic ) , with a prothrombin time of 15 sec , a partial thromboplastin time of 81 sec , and a fibrinogen of 100 mg / dl . a bone marrow examination showed apl , which was confirmed by the presence of t(15;17)(q22;q21 ) on karyotypic analysis and pml / rara on molecular analysis . flow cytometry revealed leukemic cells positive for cd13 and cd33 expression , and negative for the expression of hla - dr . induction chemotherapy with idarubicin , ara - c ( idarubicin 12 mg / m / day intravenous i.v . on days 1 - 3 , ara - c100 mg / m / day continuous iv for 24 hr on days 1 - 7 ) and atra at 45 mg / m , which was scheduled to be given until 30 days after complete remission , led to complete remission on day 25 of the treatment . analysis of bone marrow revealed a normal karyotype as well as absence of the pml / rara rearrangement . the patient received a consolidation with three consecutive courses of idarubicin , and then a maintenance with atra ( at 45 mg / m on days 1 - 15 , every other month for 2 yr ) . ten months later , he complained of a mild non - specific headache for two weeks of duration . magnetic resonance imaging study showed multifocal leptomeningeal enhancement in both the frontal and parietal areas in enhanced t1-weighted image . examination of cerebrospinal fluid ( csf ) showed the presence of atypical promyelocytes ( fig . 1 ) . the bone marrow smear showed a complete hematologic and cytogenetic remission , but molecular studies showed the presence of pml / rara rearrangement in the bone marrow and in the csf . the diagnosis of meningeal relapse of apl was made , and he was treated with intrathecal methotrexate and ara - c ( methotrexate 12 mg and ara - c 100 mg administered twice a week for four weeks ) , followed by high - dose systemic chemotherapy ( ara - c 3.0 g / m i.v . on days 1 - 4 , mitoxantrone 12 mg / m / day i.v . on days 3 - 5 ) . at the end of the intrathecal chemotherapy his csf analysis became normal , but blood and bone marrow evaluations at this time showed hematologic relapse . the extramedullary sites reported are skin , cns , middle ear , lung , lymph node , mediastinum , thymus , spine , breast , pelvis , and gingiva . only 31 cases of apl in cns have been reported ( 4 - 25 ) . the age range of these patients was from 13 to 73 yr with a median age of 39 . only one case who had been treated for a non - hodgkin 's lymphoma with chemotherapy and radiotherapy ten months ago had an intracerebral leukemic mass at the onset of leukemia ( 18 ) . of the 20 relapsed patients , the duration of remission ranged from 1 to 144 months , with a median of five months . magnetic resonance imaging study or ct scan was performed on ten patients ; seven cases showed evidence of mass and three cases did not show any pathologic alteration . magnetic resonance imaging study from our case showed leptomeningeal enhancement only without mass formation . lumbar puncture was performed in all patients , and the result showed that all patients had leukemic cells in the csf . the symptoms of apl in cns are headache , vertigo , nausea , vomiting , visual disturbance , motor weakness , and seizure . in our case although cns involvement of apl is rare , csf studies should be performed when symptoms of cns occur . hematologic remission was maintained in nine cases when a cns relapse was found ( 5 , 7 , 9 - 12 , 14 , 15 , 19 ) . a molecular study to find the rara rearrangement in the bone marrow was performed in five cases at the time of cns relapse . because an increasing number of reports have been published on extramedullary localization in apl , at the time of relapse , following the advent atra treatment , the question arises as to whether treatment of apl with atra predisposes patients to the development of extramedullary relapse . there are two reports of cns relapse after arsenic trioxide ( as2o3 ) treatment ( 7 , 9 ) . several biologic effects , modulated by atra , have been suggested to play a role in extramedullary leukemic infiltration , such as increased expression of certain adhesion molecule ( 26 , 27 ) . it is possible that a similar differentiation and regulation of adhesion molecules , as seen with atra therapy , occurs with the use of as2o3 . the risk factors associated with extramedullary relapse are high wbc count on presentation and the atra syndrome ( 8 , 13 ) . a gimema study compared the relapse pattern in apl patients enrolled into two consecutive large studies . patients receiving atra , in addition to chemotherapy , have no increased risk of developing extramedullary disease at the time of relapse as compared with apl patients treated with chemotherapy alone . however , higher prevalence of cns involvement was detected in patients receiving atra ( 28 ) . in the literature review , despite the impressive complete remission and survival results of apl , the prognosis for relapsed apl is generally poor . treatment of cns relapse consists of intrathecal chemotherapy , radiotherapy , systemic chemotherapy ( with high - dose cytarabine which passes through the blood brain barrier ) , and agents for cytodifferentiation such as atra . six cases with cns relapse were treated with combination therapy including atra , and they achieved the complete remission as next ( 5 , 6 , 12 , 16 , 17 , 25 ) . four of the six cases who were treated with atra for relapsed apl had received atra previously ( 5 , 6 , 12 , 25 ) . the durations of their first complete remission are 2 , 6 , 11 and 144 months . in our case , because he received atra for maintenance therapy when the cns relapse was found , we treated him with intrathecal therapy and with high - dose systemic chemotherapy . recently , as2o3 has represented a useful salvage treatment for apl patients who relapsed after or refractory to atra and chemotherapy ( 29 ) . as2o3 may also be an option for patients with relapsed apl in the cns . in summary cns involvement of apl is rare , but cns is a possible site of relapse in a patient with complete remission after treatment of apl . we think that it is necessary to do a complete evaluation and diagnostic approach , including csf studies , if cns symptoms occur in patients with apl , even though hematologic parameters sustain remission .
the involvement of central nervous system is rare in acute promyelocytic leukemia ( apl ) . 
 we report a apl patient of a 41 yr - old korean male who presented with fever and petechia . 
 complete molecular remission was achieved with all - trans retinoic acid ( atra ) , idarubicin , and cytarabine . 
 ten months later , he complained of a mild headache . 
 the results of the physical examination and the complete blood counts were normal . 
 the examination of cerebrospinal fluid showed the presence of promyelocyte . 
 bone marrow studies showed cytogenetic remission but with molecular relapse . 
 he was treated with intrathecal and systemic chemotherapy .