Biphenotypic Acute Leukemia: A Report of Two Cases

Biphenotypic Acute Leukemia
Vol. 1 No. 1 : 2006 (53-60)

Azma RZ Azma RZ
Hamidah NH Hamidah NH
C-F Leong C-F Leong
O Ainoon O Ainoon
Fadilah SAW Fadilah SAW
S-K Cheong S-K Cheong
Salwati S Salwati S
Sharifah NA Sharifah NA

Abstract
We report two cases of biphenotypic acute leukaemia diagnosed in Hospital Universiti Kebangsaan Malaysia (HUKM), their clinical, haematological characteristics and response to chemotherapy. Both patients are middle-aged ladies who presented with hepatosplenomegaly and high white cell count, mainly composed of blast cells. Their bone marrow aspirations were hypercellular comprising of more than 90% heterogenous blast cells. Cytochemical analyses show  more than 3% positivity towards peroxidase, with smaller blasts showing block positivity towards PAS. Immunophenotypically, the blasts showed dual expression of CD 33 and CD 19, CD 19 and CD34, intra CD22, intra TdT and intraMPO. One of the patients showed presence of the Philadelphia chromosome on cytogenetic analysis which was confirmed by Fluorecsence In Situ Hybridisation (FISH). Molecular analysis also showed presence of the BCR-ABL fusion protein. Both patients were given combination chemotherapy consisting of daunorubicin and cytosine arabinoside.However, the patient with positive Philadelphia chromosome BCR-ABL did not achieve morphological remission after induction chemotherapy. In view of the poor prognosis of this disease, both the patients were planned for upfront peripheral blood stem cell transplantation.
Keywords : biphenotypic acute leukaemia, cytogenetic, immunophenotyping, prognostic factors, treatment,
Abstrak
Kami melaporkan dua kes leukemia akut bifenotipik yang didiagnos di Hospital Universiti Kebangsaan Malaysia (HUKM), ciri-ciri klinikal, hematologi dan tindakbalas penyakit ini terhadap kemoterapi. Kedua-dua pesakit adalah wanita pertengahan umur yang menunjukkan pembengkakan hati dan limpa serta bilangan sel darah putih yang tinggi.  Sum-sum tulang menunjukkan kepadatan sel dimana 90% terdiri dari sel-sel leukemia pelbagai saiz. Analisa sitokimia menunjukkan lebih daripada 3% adalah positif terhadap ujian peroksidase dan sel-sel leukaemia yang lebih kecil menunjukkan positiviti secara blok terhadap ujian periodic acid-schiff (PAS).  Ujian imunofenotip menunjukkan ko-ekspresi dwi penanda sel CD 33 dan CD 19, CD 19 dan CD34, intra CD22, intra TdT dan intraMPO.  Analisa sitogenetik daripada salah seorang pesakit tersebut menunjukkan kehadiran kromosom Philadelphia  yang disahkan dengan ujian Fluorescence In Situ Hybridisation (FISH). Analisa molekular juga menunjukkan kehadiran protein fusi BCR-ABL.  Kedua-dua pesakit menerima rawatan kemoterapi yang terdiri daripada daunorubicin dan cytosine arabinoside. Namun begitu, pesakit yang mempunyai kromosom Philadelphia BCR-ABL tidak berjaya mencapai remisi morfologi selepas kemoterapi induksi. Memandangkan prognosis buruk pesakit leukemia ini,  pemindahan sel-sel stem periferi dirancangkan untuk kedua-dua pesakit ini.
Kata Kunci : faktor-faktor prognosis, immunofenotip, leukemia akut bifenotipik, rawatan kemoterapi, sitogenetik,

Correspondance Address
Dr. Raja Zahratul Azma bt. Raja Sabudin, Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia (UKM), Jalan Yaacob Latif, Bandar Tun Razak, 56000 Kuala Lumpur, Malaysia. E-mail: zahratul@mail.hukm.ukm.my