Study On The Role Of Fusion Gene And Non-Cytotoxic Drugs In Treatment Of Acute Promyelocytic Leukemia

Acute promyelocytic leukemia (APL) is a rare type of leukemia, characterized byt(15;17) translocation leading to PML-RARa fusion gene and it is sensitivity to the differentiating agent all-trans retinoic acid (ATRA). This subtype has favorable survival when treated with chemotherapy; however coagulopathy associated with induction, with additional risk of cytopenia leading to limitation of this treatmentThe introduction of ATRA and ATO into clinical practice offered the potential to alleviate some of these obstacles, but the optimal timing remains to be determined. Many studies used ATRA and/or ATO in the regimen have been introduced. ATRA and/or ATO were used to induce remission and then chemotherapy for consolidation, this approach significantly improved disease outcome without significant complications.The aim of these cases report is to support the regimen of ATRA treatment alone in induction therapy followed by chemotherapy as consolidation, and the importance of detection of fusion gene in response to treatment.We reported5cases of newly diagnosed APL in children (3male and2female). All the patients suspected to have malignancy from peripheral blood as they diagnosed by hematological and bone marrow sample and smear, and confirmed by cytogenetic and molecular study by the presence of t(15;17) and PML/RARa fusion gene by chromosomal analysis and reverse transcriptase-polymerase chain reaction (RT-PCR), and by the presence of translocation by Fluorescent in situ hybridization test (FISH), except one patient with negative fusion gene. All of them treated with ATRA as a first line drug until complete remission (CR), with two doses of prophylactic intrathecal (IT) injection of methotrexate (MTX) and Cytarabine (Ara-c) and dexamethasone, followed by two courses of chemotherapy:Daunomycin (DNR) and Ara-c with2-4weeks interval. After waiting time (few days to week) allowing bone marrow to recover from suppression effect of chemotherapy, maintenance treatment (for2years) will follow, which consist of3months cycles as follows:15days ATRA followed by6mercaptopurin (6MP) daily orally and (MTX) once weekly orally for the rest of the3months. Three cases responded well to ATRA and one case with intolerance to drug with severe side effects treated with arsenic trioxide (ATO), and one patient with negative fusion gene showed resistance to all kinds of drugs, and ultimately died because of CNS hemorrhage. All other patients are still in remission with regular follow up every3months.In conclusion, presence of PML/RARa fusion gene is the most important point to ensure full effect of ATRA or ATO, and also using ATRA as front line treatment in these patients have good outcome if we compare the outeome to other regimens; have fewer side effects; that are mild and tolerable, And also using ATRA in maintenance treatment may reduce the risk of relapse.