acute promyelocytic leukemia ( apl ) is a specific type of acute myeloid leukemia ( aml ) characterized by the presence of abnormal promyelocytes in bone marrow and peripheral blood , young age at presentation , specific chromosomal abnormalities , coagulopathy , and a unique response to treatment with retinoic acid . until recently , combination of all - trans retinoic acid ( atra ) and chemotherapy with cytarabine and anthracyclines although treatment with atra has improved the outcome of apl , early bleeding due to coagulopathy and relapse are the main causes of death in patients with apl . however , cns involvement at relapse is rare and is generally associated with a poor prognosis . we present a case of long - term survival in an apl patient who had achieved hematologic and molecular complete remission ( cr ) after treatment of meningeal relapse using atra , idarubicin and cytarabine . her complete blood count ( cbc ) showed a white blood cell ( wbc ) count of 8,600/l consisting of 75% blasts , hemoglobin level of 9.4 g / dl , and platelet count of 13,000/l . coagulation test showed prothrombin time of 13.5 sec , partial thromboplastin time of 26.1 sec , and fibrinogen level of 80 mg / dl . apl was diagnosed on the basis of findings from bone marrow ( bm ) examination , and was confirmed by chromosomal analysis , which indicated the presence of t(15;17 ) ( q22;q11.2 ) and molecular analysis , which indicated the presence of promyelocytic leukemia ( pml)/retinoic acid receptor - a ( rara ) rearrangement . induction chemotherapy with idarubicin ( intravenous administration of idarubicin 12 mg / m / day on days 2 , 4 , 6 , and 8) and atra ( 45 mg / m ) was administered to achieve cr . the patient received consolidation therapy with 2 consecutive courses of idarubicin and 1 course of mitoxantrone , followed by maintenance therapy with atra ( 45 mg / m on days 1 - 15 , every other month for 2 years ) . after 17 months , the patient complained of non - specific headache for 1 month . her physical examination was unremarkable and her cbc was normal . enhanced t1-weighted magnetic resonance image showed focal meningeal enhancement in the right parietal lobe ( fig . cerebrospinal fluid ( csf ) microscopic finding showed numerous leukemic promyelocytes - containing prominent nuclear irregularities and variably granulated cytoplasm ( fig . the patient was diagnosed with meningeal relapse of apl and treated with intrathecal administration of methotrexate and cytarabine ( methotrexate 12 mg and cytarabine 50 mg administered 3 times a week until the wbc count in the csf reached zero ) , followed by whole - brain radiotherapy and systemic chemotherapy ( cytarabine 2.0 g / m i.v . b.i.d . on days 1 - 3 , etoposide 70 mg / m i.v . on days 1 - 4 ) . skin , cns , middle ear , lung , lymph node , mediastinum , thymus , spine , breast , pelvis , and gingival are the common extramedullary sites . the symptoms of cns involvement in apl are headache , vertigo , nausea , vomiting , visual disturbance , motor weakness , and seizure . in our case , although meningeal infiltration of leukemia is rare , csf should be examined when symptoms of suspected cns involvement are present . interestingly , in our patient , cns relapse did not coincide with hematologic and molecular relapse . among the reported cases of apl , 6 continued to show hematologic and molecular remission despite cns relapse [ 3 - 7 ] . atra induces differentiation of abnormal promyelocytes into mature granulocytes and induces cr in 80 - 90% of newly diagnosed and first - relapsed cases of apl [ 1 , 8 , 9 ] . after the advent of atra treatment , an increasing number of apl cases with the involvement of extramedullary sites at relapse have been reported . several biologic effects such as atra - mediated increase in the expression of certain adhesion molecules ( e.g. , cd11c , cd13 , and cd56 ) have been suggested to play a role in extramedullary involvement of leukemic cells [ 10 , 11 ] . a gimema study compared the relapse pattern in apl patients receiving different treatments ( atra+chemotherapy group vs. chemotherapy alone ) . unlike patients receiving chemotherapy alone , patients receiving atra and chemotherapy these findings suggest that with the advent of atra and subsequent combination chemotherapy , a substantially higher fraction of patients who achieve long - term remission are at the risk of developing cns relapse than patients who were treated with chemotherapy alone in the past . in particular , patients with multifocal cns involvement had short survival time [ 3 , 8 ] . our findings indicate that after multimodal treatment , patients with focal involvement of the cns have longer survival times than patients with multifocal involvement of the cns . treatment of cns relapse consists of intrathecal chemotherapy , radiation therapy , systemic chemotherapy with high - dose cytarabine , and treatment with agents such as atra . although atra does not cross the blood - brain - barrier ( bbb ) , it induces the differentiation of apl blasts present in the csf of patients with cns relapse . high - dose cytarabine and arsenic trioxide ( as2o3 ) pass through the bbb and could be effective for apl patients with cns relapse [ 14 , 15 ] . in summary , we presente a case of long - term survival in an apl patient with isolated meningeal relapse . therefore , precise evaluation and diagnosis by using approaches such as lumbar puncture and csf examination should be performed , if cns symptoms occur in patients with apl .
the meningeal involvement is rare in acute promyelocytic leukemia . 
 we experienced a 39-year - old woman who achieved complete remission with all - trans retinoic acid , idarubicin and cytarabine therapy . 
 several months later , she complained of non - specific headache . 
 her complete blood cell count was normal , but magnetic resonance image of brain revealed focal meningeal enhancement and cerebrospinal fluid showed leukemic promyelocytes and pml / rara rearrangement . 
 bone marrow study showed hematologic , cytogenetic and molecular remission . 
 she was treated with intrathecal and systemic chemotherapy and whole brain radiotherapy . 
 the patient has survived for 68 months since the last systemic chemotherapy .