Early T Acute Lymphoblastic Leukemia in Childhood: Prevalence and Clinical Characteristics

Background: Early T precursor ALL has been defined as a poor prognosis subtype, characterized phenotypically by absence of CD1a and CD8, CD5 weak expression and presence of at least one myeloid and progenitor cell marker.

Objectives: Our aims were to identify Early T-ALL among our T ALL cases, based on the characteristic phenotype and thus evaluate the prevalence, biological characteristics and outcome of this particular subset of T-ALL

Methods: From April ’94 to December ’13, 197 T-ALL cases were diagnosed and 20 of them showed the typical Early T marker profile by flow cytometry (FC). Conventional cytogenetics, FISH and RT-PCR studies were performed according to standard techniques. Clonality assessment for TRG, TRB, TRD, IGH and IGK was performed by PCR (Biomed-2), heteroduplex and sequencing.

Results: Sex distribution was: 16 males and 4 females; median of age: 7.9 (range: 0.3-16.6) years; median WBC: 14.9 (range: 0.6-254.0) x10⁹/L. All but one case expressed CD34, 70% HLA-DR, 61% CD117 and 50% TdT. The most frequently expressed myeloid markers were: CD33 (85%) and CD13 (55%). Three cases expressed g/d TCR. Chromosomal abnormalities were detected in 14 of 16 evaluated cases, in 5 of them compromising 12p13 region. TCR/IgH rearrangements were detected in 63% (10/16). FLT3-ITD mutations were found in 14 % (2/14).

Patients were treated with BFM-based ALL schedules and were stratified as Intermediate Risk ALL (n: 7) and High Risk ALL (n: 13) according to protocol criteria. Early response to treatment was poor in 16 cases: 6 presented poor response to prednisone (day 8), 3 MRD >10%, 5 presented bone marrow M2-M3 and 2 non response. Seventeen cases (85%) achieved CR on day 33 and 2 achieved CR later. Five patients underwent HSCT in first CR. Three patients relapsed at 5, 6 and 65 months from diagnosis and one showed lineage switch to M5-AML at 12 months from CR. Three pts died in CR (2 after HSCT and 1 patient with primary immunodeficiency due to pneumonia) and one is in palliative care. Twelve patients remain in CR with a median follow-up of 54 (r: 8-144) months.

Conclusions: The prevalence of Early T precursor phenotype within T ALL was 10.5% in our setting. The most frequent progenitor marker was CD34 and CD33 among myeloid markers. Of note, translocations involving 12p13 region were found in 5 patients. Sixty percent of patients remain disease free, although longer follow-up is needed in order to define prognosis of this group in our cohort of patients. The lineage switch case supports the notion of the myeloid differentiation potential of these blasts.