Summary Immunophenotypic studies, fluorescence in situ hybridization (FISH) and conventional karyotyping were used to define the clinicobiological significance of 14q32 translocations involving the immunoglobulin gene locus (14q32/IGH) in 252 chronic lymphocytic leukaemia (CLL) patients. The following regions were studied: 13q14, centromere 12, 6q21; 11q22/ATM; 17p13/TP53, 14q32/IGH. Patients were classified as group 1 (favourable, i.e. 13q‐single or normal), group 2 (intermediate risk, i.e. +12, 6q‐, 1–2 anomalies), group 3 (unfavourable, i.e. 17p‐, 11q‐, complex karyotype), or group 4 (14q32/IGH translocation). Endpoints were treatment‐free survival (TFS) and overall survival (OS). One hundred and ten patients were included in group 1, 99 in group 2, 25 in group 3 and 18 in group 4. 14q32/IGH translocation partners were identified in eight cases (BCL2 in five cases, BCL11A, CCND3 and CDK6 in one case each). group 4 showed shorter TFS versus groups 2 and 1 (25% patients treated at 2 months vs. 12 (P = 0·02) and 20 months (P = 0·002), respectively) and shorter OS (25% patients dead at 18 months versus 50 (P = 0·0003) and >60 months (P < 0·0001) respectively. The 14q32/IGH translocation maintained prognostic significance at multivariate analysis on TFS (P = 0·025) and OS (P < 0·001), along with advanced stage and CD38+. These findings show that the 14q32/IGH translocation predicts for an unfavourable outcome in CLL and that this cytogenetic subset might be included as a separate entity in a hierarchical cytogenetic classification of CLL.

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The patient was treated with a target immune approach receiving a therapeutic vaccine that consisted of an immunogenic 25-mer b2a2 breakpoint-derived peptide (CMLb2a2-25) with binding properties for several HLA-DR molecules. After nine boosts of vaccine the patient developed an adequate b2a2-25 peptide-specific CD4(+) T-cell response and BCR-ABL1 transcript started to decline in peripheral blood. No hematological or extrahematological effects were documented during therapy. At the last evaluation, 39 months since vaccinations commenced, the patient is in complete molecular response with an undetectable level of BCR-ABL1 transcript both in peripheral blood and in bone marrow and she continues to receive boosts of vaccine every 3 months as the only treatment.

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