Hematological characteristics, cytogenetic features, and post-induction measurable residual disease in thymic stromal lymphopoietin receptor (TSLPR) overexpressed B-cell acute lymphoblastic leukemia in an Indian cohort.

The overexpression of cytokine receptor-like factor-2 (CRLF2) identified by anti-thymic stromal lymphopoietin receptor/TSLPR flow cytometry (FCM) has been reported as a screening tool for the identification of BCR-ABL1-like B-cell acute lymphoblastic leukemia/B-ALL with CRLF2 re-arrangement. TSLPR expression was studied prospectively in consecutive 478 B-ALLs (≤ 12 years (n = 244); 13-25 years (n = 129); > 25 years (n = 105)) and correlated with various hematological parameters and end-of-induction measurable residual disease (day 29; MRD ≥ 0.01% by 10-color FCM). TSLPR positivity in ≥ 10% leukemic cells was detected in 14.6% (n = 70) of B-ALLs. CRLF2 re-arrangement was detected in eight cases (11.4%) including P2RY8-CRLF2 (n = 6), and IgH-CRLF2 (n = 2) with a median TSLPR positivity of 48.8% and 99% leukemic cells, respectively. Recurrent gene fusions/RGF (BCR-ABL1 (17.1%); ETV6-RUNX1 (4.2%), TCF3-PBX1 (1.4%)), other BCR-ABL1-like chimeric gene fusions/CGFs (PDGFRB-rearrangement (2.9%), IgH-EPOR (1.4%)), CRLF2 extra-copies/hyperdiploidy (17.1%), and IgH translocation without a known partner (10%) were also detected in TSLPR-positive patients. CD20 positivity (52.9% vs 38.5%; p = 0.02) as well as iAMP21 (4.3% vs 0.5%; p = 0.004) was significantly more frequent in TSLPR-positive cases. TSLPR-positive patients did not show a significantly higher MRD, compared to TSLPR-negative cases (37% vs 33%). Increasing the threshold cut-off (from ≥ 10 to > 50% or > 74%) increased the specificity to 88% and 100% respectively in identifying CRLF2 translocation. TSLPR expression is not exclusive for CRLF2 translocations and can be seen with various other RGFs, necessitating their testing before its application in diagnostic algorithms. In patients with high TSLPR positivity (> 50%), the testing may be restricted to CRLF2 aberrancies, while patients with 10-50% TSLPR positivity need to be tested for both CRLF2- and non-CRLF2 BCR-ABL1-like CGFs.

Clinicopathological and immunophenotypic features of early T cell precursor acute lymphoblastic leukaemia: A flow cytometry score for the initial diagnosis.

OBJECTIVE: To assess the prevalence of early T precursor-acute lymphoblastic leukaemia (ETP-ALL), study its clinicopathological features and devise a 'flow score' based on immunophenotypic profiles. MATERIAL METHODS: This was a retrospective study where clinical and laboratory data of all consecutive T-ALL cases were analysed to identify features differentiating ETP from non-ETP-ALL. The utility of a flow score based on the five commonly used markers in leukaemia panels for T-ALL (CD34, CD8, CD5, CD13 and CD33) was evaluated to differentiate ETP from non-ETP-ALL. RESULTS: Early T precursor-acute lymphoblastic leukaemia constituted 24.2% (n = 29) of all T-ALL cases. It was significantly more common in adults (30.2%) as compared to paediatric (17.5%) patients (P = .046). The median age of presentation was significantly higher than the non-ETP group. (24 vs 19 years; P = .01). Patients with ETP-ALL usually presented with organomegaly, lymphadenopathy, lower levels of haemoglobin, total leucocyte count, peripheral blood blast proportion and LDH levels as compared to non-ETP-ALL. The majority of ETP-ALL cases had L2 morphology with a moderate amount of cytoplasm showing frequent blebbing. A flow score cut-off value of ≥3 on ROC curve analysis had a sensitivity and specificity of 100% and 94.6% respectively. CONCLUSION: Early T precursor-acute lymphoblastic leukaemia had unique clinical and laboratory features. The prevalence of this entity is more common in the adult population. A flow score based on a minimum of five widely used markers can confidently identify ETP-ALL and should be included in the primary panel of markers used for flow cytometric analysis.