Monoclonal antibodies in the management of acute leukemia

Abstract

This report reviews the diagnostic significance of immune markers, their relationship to patient outcome, and the therapeutic uses of monoclonal antibodies (MoAbs) in acute leukemia. Immunophenotyping allows for rapid and reproducible diagnosis in the majority of cases of acute leukemia. It is of particular importance in recognizing the major immunologic subclasses of acute lymphoblastic leukemia (ALL), and in identifying subtypes of acute myeloblastic leukemia (AML) which cannot be differentiated by morphology and cytochemistry alone, such as FAB M0 or M7. Immune marker analysis has been used to detect minimal residual disease in patients' bone marrow and CSF after treatment. However, the presence of leukemia-associated phenotypes on small numbers of normal cells may reduce the sensitivity of detection in some cases. The prognostic value of immune markers in AML is limited. In ALL, the prognostic significance of the different immunophenotypic subtypes has been lessened by modern treatment protocols. The relationship of mixed-lineage or biphenotypic antigen expression to patient outcome in both AML and ALL is unclear. Therapeutic applications of MoAbs in acute leukemia include immunologic techniques for purging malignant cells from autografts prior to transplantation, T-lymphocyte depletion from allografts as a strategy to reduce graft-versus-host disease, and the use of flow cytometry to monitor the timing and extent of leukapheresis in peripheral stem cell transplantation. MoAbs have also enabled the recent development of transplantation protocols using positively-selected CD34+ stem cells.

Flow cytometry with or without cytochemistry for the diagnosis of acute leukemias?

“…Improved ability to detect non-lineage antigens may have significance for future monoclonal antibody therapy and for the assessment of minimal residual disease. It is unclear whether better therapies will make minor immunophenotype distinctions irrelevant (22). However, at least for M3 leukemias, recent evidence has suggested that directed therapy can be beneficial (23).…”

Clinical significance of phenotypic features of blasts in patients with myelodysplastic syndrome

“…32 The present data, that is, 97% of the cases expressed CD34 and 58% of the cases were MPO Ϫ , indicate that the phenotype of MDS blasts is more immature compared with de novo AML blasts, in which 35% to 60% of cases are CD34 ϩ and 5% to 10% of cases are MPO Ϫ . 20,[33][34][35][36] As shown in Table 5, 47% of our de novo AML cases were CD34 ϩ . Although blasts of minimally differentiated de novo AML (AML-M0) show, by definition, a negative cytochemical reaction for MPO in all cases and are CD34 ϩ in nearly 90% to 100% of cases, [35][36][37] MDS EBCs are CD34 ϩ in most cases, irrespective of the MPO status.…”

Therapeutic Options in the Management of Acute Myelogenous Leukemia in Adults

“…6 Monoclonal antibodies are useful diagnostic tools in AML and are somewhat helpful as prognostic factors. 7,8 The findings of CD34, a marker associated with the hematopoietic stem cell, and MDR1, a marker associated with the multidrug resistance phenotype, confer a poor prognosis. In elderly patients (ie, those older than age 55) with AML, the presence of MDR1 is associated with lower complete remission (CR) rates independently of cytogenetics.…”