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.

Immunophenotypic aberrancies in acute lymphoblastic leukemia from 282 Iraqi patients

“…The overall frequency of LAIP in T‐ALL was 26.8%, with CD1a + /CD5 + /sCD3 + and CD34 + /sCD3 + patterns constituting around one half of LAIP cases. Such patterns have been reported by previous investigators, although at higher rates than among our patients . With regard to cross‐lineage antigens expression in T‐ALL, B‐cell antigen expression (cCD79a) constituted around a quarter of LAIP detected.…”

“…Such patterns are in contrast to that of hematogones, as they defy normal antigenic evolution of B‐cell precursors and asynchronously co‐express early and late antigens (eg, CD34 and CD20) or over or under‐express others . Such asynchronous expression of early and late B‐cell markers had been reported by many earlier studies on B‐ALL with variable rates . As individual markers, CD10 was the most frequent abnormally expressed marker, followed by nTdT, CD34, CD38, and CD20 (Table ).…”

Outcome prediction by immunophenotypic minimal residual disease detection in adult T‐cell acute lymphoblastic leukaemia

“…The role of immunophenotypic MRD detection in predicting clinical relapse has been documented in childhood ALL (Campana & Coustan‐Smith, 1999; Griesinger et al , 1999; San Miguel et al , 1999; Coustan‐Smith et al, 2000; Dworzak et al, 2002). The aim of our study was to assess the impact of this approach in adult T‐ALL.…”

2006 Bethesda International Consensus recommendations on the flow cytometric immunophenotypic analysis of hematolymphoid neoplasia: Medical indications

“…Assessment of response to therapy (including “minimal residual disease” testing) and persistence of FCI‐detectable MRD following therapy, which is often an adverse prognostic factor. However, the optimal frequency of such monitoring has not been established (112, 137–163). Documentation of progression or relapse. Diagnosis of additional intercurrent hematolymphoid neoplasm, either treatment‐ related (such as MDS/AML or PTLD) or coincidental (164–170).…”