Mirta Mikulić

Biological features and outcome of biphenotypic acute leukemia: a case series

BACKGROUND Biphenotypic acute leukemia (BAL) is a distinct entity that is immunophenotypically defined by the European Group for the Immunological Classification of Leukemia (EGIL) scoring system and accounts for less than 5% of all acute leukemia cases. Since it is a rare and heterogeneous form of acute leukemia with an allegedly poor outcome, there is no consensus on the best treatment approach in these patients. Our objective was to analyze the biological features and outcome of patients diagnosed with BAL in our institution. PATIENTS AND METHODS Using the EGIL system, we identified 21 cases (3.9%) of BAL from 535 newly diagnosed acute leukemia patients in an 11-year period. RESULTS There were ten cases of myeloid+B-lymphoid leukemia, eight cases of myeloid+T-lymphoid, one case of B+T-lymphoid and two cases of trilineage (myeloid+B+T-lymphoid leukemia). The complete remission (CR) rate with high-dose chemotherapy was 72% and overall survival at 5 years was 21%. Patients that received acute lymphoblastic leukemia-oriented chemotherapy had a higher CR rate compared with those who received acute myeloid leukemia-oriented chemotherapy (100% vs. 60%, P = .007). The white blood cell count at diagnosis was found to have statistically significant impact on survival. CONCLUSION Despite the progress in the treatment of acute leukemia, the prognosis of BAL remains poor and treatment protocols devised explicitly for this entity should be investigated in prospective collaborative studies.

HLA-DPB1 matching in unrelated hematopoietic stem cell transplantation program contributes to a higher incidence of disease relapse

The impact of patient/donor matching for HLA-A, -B, -C, -DRB1 and -DQB1 genes in hematopoietic stem cell transplantation (HSCT) is well-recognized, but typing for additional genes, such as HLA-DPB1, is still controversial. Based on defined T-cell epitope (TCE) groups, all HLA-DPB1 mismatches can be classified as permissive or non-permissive. In this retrospective study we analysed 82 patient-matched unrelated donor (MUD) pairs who underwent HSCT, and explored the impact of HLA-DPB1 matches, permissive and non-permissive mismatches on transplantation outcomes. Patient-MUD pairs matched for HLA-DPB1 alleles in univariate analysis were associated with a significantly higher incidence of disease relapse compared to pairs who were permissive/non-permissive HLA-DPB1 mismatched according to the TCE3 and TCE4 algorithms (P=0.025 and P=0.026, respectively), although the significance was lost in multivariate analysis. The analysis did not reveal any significant influence of HLA-DPB1 alleles on overall survival (OS), non-relapse mortality (NRM) or graft-versus-host disease (GvHD) incidence. In conclusion, our study presents evidence that HLA-DPB1 matching influenced the relapse rate in patients after HSCT so the HLA-DPB1 alleles should be implemented in the MUD search algorithm as a transplantation determinant.

P003 CD11a, myeloperoxidase and alkaline phosphatase expression in bone marrow mature granulopoietic cells in patients with AML and ALL

Observed differences in mature granulopoietic cells (MGC)expression of CD11a, MPO of bone marrow in patients with acute leukemia and remssion of disease in comparison to control group of patients implicated that MGCs retain some differences. However, this differences can be linked to infections due to impaired immunodefense in AL patients after cytostatic therapy.

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.