Sanja Mrsić

Acute promyelocytic leukemia M3: cytomorphologic, immunophenotypic, cytogenetic, and molecular variants.

Acute promyelocytic leukemia (APL) M3 is an acute myeloid leukemia (AML) subtype characterized by proliferation of malignant promyelocytes with mature myeloid immunophenotype and the translocation t(15;17)(q22;q11), which results in the fusion of retinoic acid receptor-alpha (RARalpha) gene on chromosome 17 and the gene PML on chromosome 15. There are three M3 morphologic variants: the typical hypergranular form and the microgranular and basophilic variants. Although most leukemic cells in M3 patients express t(15;17), other cytogenetic abnormalities have also been reported. Also, there are three molecular variants of the PML/RARalpha transcript (bcr1, bcr2, bcr3). Blasts had typical hypergranular appearance (13 patients) with a mature myeloid immunophenotype (HLA-DR(-),CD13(+), and/or CD33(+)) (10 patients) in the majority of patients with M3 followed in this study. The typical translocation [t(15;17)(q22;q11)] was detected by cytogenetic analysis in 5 M3 patients, but PML/RARalpha was positive in 13 out of 15 patients, as assessed by RT-PCR (8 patients with bcr1 and 5 with bcr3 subtype). Cytogenetic diversity was found in three patients (1 with t(17;17), 1 with +8, and 1 with add (7)(q22); -7; +8). According to many studies, leukemic cell heterogeneity in APL influences the clinical outcome of disease. The analysis of certain leukemic cell characteristics on the clinical outcome in our study revealed that patients with bcr3 had shorter medians of first remission and survival in comparison to patients with the bcr1 isoform of PML/RARalpha. Also, the clinical relapse of disease in 4 APL patients with reverted PML/RAR alpha positivity is consistent with the view that detection of PML/RARalpha by RT-RCR in patients in remission implies a poor prognosis. On the contrary, lack of detection of PML/RARalpha by RT-PCR at least three times is a sign of long remission and survival.

P015 Outcome in a small series of biphenotypic acute leukemia (BAL) patients

Background: Less than 5% of all cases of acute leukemia are classified as biphenotypic acute leukemia (BAL). Being a distinct entity recognized by the WHO classification, BAL is immunophenotypically defined by the European Group for the Immunological Classification of Leukemia (EGIL) scoring system, whereas according to FAB classification BAL may present as one of the ALL or AML subtypes. Since BAL is both a rare form of acute leukemia and shows diverse biological features, there is no consensus on the best treatment approach in these patients. Aim: Our aim was to analyze the laboratory characteristics and the outcome of patients diagnosed with BAL. Patients and methods: Using the EGIL system, we identified 21 cases (4%) of BAL from 535 newly diagnosed acute leukemia patients in the Zagreb Clinical Hospital Center in the period from end 1994-2006. Results: There were 16 male and 5 female patients with median age of 44 years (16- 74). Among them, there were 12 cases of B+myeloid leukemia (55%), 8 cases of T+myeloid (36%), 1 case of B+T lymphoid (5%) and 1 case of trilineage B+T+myeloid leukemia (5%). Morphologic assessment showed myeloid features in 9, lymphoid features in 6 and undifferentiated in 6 patients. Cytogenetic findings revealed normal as well as a wide range of aberrant karyotypes. The patients were treated according to the protocols for AML or ALL or with low-dose chemotherapy - 8, 10 and 3 patients, respectively. In the majority of patients overall survival was poor with a median of 7 months (1- 100) and with a probability of survival at two years of 35%. Conclusion: Despite the progress in the treatment of acute leukemia, the definition and the prognosis of BAL remains poor. Current treatment approach is heterogeneous and still based on cytomorphology. Treatment protocols designed specifically for this type of leukemia should be devised and studied in larger groups of patients.