, for the GMALL Study GroupImmunophenotyping disclosed CD10 negativity in 70 of 2408 cases of B-lineage acute lymphoblastic leukemia (ALL), although other criteria followed classification of pre-B ALL (eg, cytoplasmic immunoglobulin positivity). These blasts showed high myeloid antigen expression (60% CD65 positivity) and reacted with antibody 7.1 in 95% of the cases. MLL-AF4 fusion transcripts or an 11q23/MLL rearrangement or both were evident in 46 of 56 samples (82%). Although 83% of the patients achieved complete remission, the remission duration remained remarkably low: 141 days for MLL rearrangement-positive and 245 days for MLL rearrangement-negative CD10 ؊ pre-B ALL. Thus, the overall survival probability 3 years after diagnosis was 0. 34
IntroductionImmunologic subtyping and molecular genetic analysis allow riskadapted treatment of acute lymphoblastic leukemia (ALL). One poorprognosis subgroup of adult B-lineage precursor ALL is characterized by translocations involving the mixed lineage leukemia (MLL) gene on chromosome 11q23. These translocations occur in approximately 3% to 6% of all adult ALL and correlate with a younger age, a higher leukocyte count, and a CD19 ϩ /CD10 Ϫ /cytoplasmic(cy)IgM Ϫ immunophenotype (pro-B ALL) coexpressing myeloid marker. [1][2][3] Recent reports have shown that 11q23 translocations occur in up to 8% of T-ALLs, which were characterized by a poor clinical outcome. 4,5 Here, we present evidence of another high-risk group with frequent MLL gene translocations involving 82% (46 or 56) of the distinct CD19 ϩ /CD10 Ϫ /cyIgM ϩ pre-B ALL subset.
Study designDual-staining immunophenotyping of 3168 newly diagnosed ALL specimens was performed with commercially available fluorochrome monoclonal antibody conjugates (Dako, Hamburg, Germany; BD Biosciences, San Jose, CA; BeckmanCoulter, Fullerton, CA) identifying pro-B ALL, TdT ϩ /CD19 ϩ /CD10 Ϫ /cyIgM Ϫ / surface(S)Ig Ϫ ; c-ALL, TdT ϩ /CD19 ϩ /CD10 ϩ /cyIgM Ϫ /SIg Ϫ ; and pre-B ALL, TdT ϩ /CD19 ϩ /CD10 ϩ /cyIgM ϩ /SIg Ϫ . 1,6,7 Ambiguous cases of CD10 ϩ B-lineage marker-positive blasts (5%-15% CD10 positivity) were rechecked by a second antibody (BD Biosciences, Dako). Only consistently negative samples (Ͻ 20% positive cells) were considered for CD10 negativity. Molecular detection of MLL-AF4 and BCR-ABL fusion as well as cytogenetic analysis were carried out as described elsewhere. [6][7][8][9][10][11] Fluorescence in situ hybridization (FISH) used directly labeled dual-color break-apart MLL rearrangement probes (Vysis, Downers Grove, IL). 7 At least 200 nuclei were scored, setting the cut-off value for false-positive nuclei at 10%. Patients were treated according the German Multicenter Adult ALL (GMALL) trials, 1,6,12 allocating MLL-AF4 ϩ patients to the high-risk arm. 13 The median follow-up was 25.6 months (range, 1.8-70.4 months) for survivors. The protocols were reviewed and approved by institutional review boards at each of the participating sites, and all patients provided informed consent prior to enrollment.
Results and di...