Leukaemia‐associated immunophenotypes (LAIP) are observed in 90% of adult and childhood acute lymphoblastic leukaemia: detection in remission marrow predicts outcome

Abstract

Summary. Analysis of differentiation antigens on leukaemic blasts is routinely done for diagnostic purposes, i.e. determination of stage of differentiation and lineage assignment. Acute lymphoblastic leukaemias are also frequently characterized by a leukaemia-associated immunophenotype (LAIP), either the coexpression of differentiation antigens physiologically restricted to other stages of differentiation (asynchronous LAIP) or cell lineages (aberrant LAIP). We defined LAIP in 241 consecutive unselected B-lineage (n ¼ 193) and T-lineage (n ¼ 48) ALL by three-colour flow cytometry using directly conjugated monoclonal antibodies. The incidence of LAIP was found to be 91·7%. In 63% of patients two to six leukaemia-associated expression patterns were detected. In order to study the specificity of LAIP in a therapy-relevant setting, remission bone marrow samples from patients with B-lineage ALL were analysed for the expression of T-lineage-associated phenotypes on the normal bone marrow cells and vice versa. The frequency of all Tlineage LAIP þ cells and all aberrant B-lineage LAIP þ cells was <1% in regenerating bone marrow samples at different timepoints. The incidence and clinical significance of LAIP þ cells was studied in 196 remission marrows of 70 ALL patients (55 remaining in CCR, 14 with bone marrow relapse, one with isolated CNS relapse). The presence of >1% LAIP þ at two consecutive timepoints predicted 5/8 bone marrow relapses in B-lineage ALL. The occurrence of LAIP þ cells >1% in T-lineage ALL after induction therapy predicted relapse in 7/7 cases. In conclusion, flow cytometric detection of LAIP þ cells appears to be a powerful tool for the prediction of outcome in ALL.

Minimal residual disease diagnostics in myeloid malignancies in the post transplant period

“…In CML monitoring of the BCR-ABL transcript levels is included in routine strategies in the post transplantation period to identify the need for adoptive immunotherapy or TKI treatment, 34,128 but in all other myeloid malignancies, AML, MDS and the BCR-ABL-negative CMPD, comparable approaches still have to be developed with regard to quantitative PCR, 18,20,147 multiparameter flow cytometry, [53][54][55] and interphase FISH. 45 Studies that analyze these methods for their predictive value within the post transplantation period are still limited.…”

“…80 The decrease of cells with a specific LAIP when compared at diagnosis and shortly after initial therapy correlates significantly with the achievement of CR and with survival, [53][54][55][56] and the reduction of aberrant cells to a threshold of 0.1% after chemotherapy was assessed as predictor for long-time survival in another study. 105 However, in the post transplantation setting the use of multiparameter flow cytometry still has to be validated as changes of the immunophenotype might be more frequent in relapse following SCT than after standard therapy where complete loss of the previous LAIP is seen in B25%.…”

“…Thus, immunophenotyping by multiparameter flow cytometry with sensitivities up to 1:10 2 -1:10 4 provides an additional suitable method for the post transplant period. The definition of leukemia-associated immunophenotypes (LAIPs) of the blasts is possible in 495% of patients [53][54][55][56] and should be performed in AML and advanced MDS at diagnosis and before SCT as basis for MRD diagnostics within the post transplant period.…”

Assessing minimal residual disease (MRD) in leukemia: a changing definition and concept?

“…Luckily, the detection of aberrant markers on leukemic cells is successful in the majority of patients with ALL or AML. 4,7,[26][27][28][29][30][31] Granted, chemotherapy may affect antigen expression patterns. 6 However, the high incidence of leukemia-associated immunophenotypes (80-85% of cases) stands in sharp contrast to the percentage of patients with AML, who can be followed with cytogenetic markers or their molecular equivalents (eg AML1/ETO, PML/RAR␣, possibly FLT3 gene mutations).…”

Interactive diagnostics in the indication to allogeneic SCT in AML

“…[41][42][43] These are based on aberrant coexpression of lymphatic Ags (for example, of CD7), asynchronous coexpression of Ags of different maturation stages, aberrant low or bright Ag expression, or Ag loss, for example, loss of HLA-DR in myeloid blasts. Sensitivities of 10 À2 to 10 À4 are achieved.…”