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Summary: We explored the relevance of genomic microarrays (GM) in the refinement of prognosis in newly diagnosed low‐risk chronic lymphocytic leukaemia (CLL) patients as defined by isolated del(13q) or no lesions by a standard 4 probe fluorescence in situ hybridization (FISH) analysis. Compared to FISH, additional lesions were detected by GM in 27 of the 119 patients (22.7%). The concordance rate between FISH and GM was 87.4%. Discordant results between cytogenetic banding analysis (CBA) and GM were observed in 45/119 cases (37.8%) and were mainly due to the intrinsic characteristics of each technique. The presence of additional lesions by GM was associated with age > 65 years (p = 0.047), advanced Binet stage (p = 0.001), CLL‐IPI score (p < 0.001), a complex karyotype (p = 0.004) and a worse time‐to‐first treatment in multivariate analysis (p = 0.009). Additional lesions by GM were also significantly associated with a worse time‐to‐first treatment in the subset of patients with wild‐type TP53 and mutated IGHV (p = 0.025). In CLL patients with low‐risk features, the presence of additional lesions identified by GM helps to identify a subset of patients with a worse outcome that could be proposed for a risk‐adapted follow‐up and for early treatment including targeted agents within clinical trials. [ABSTRACT FROM AUTHOR]

Summary: Since 2000, we have investigated 67 consecutive patients with stage I/II follicular lymphoma (FL) for the presence of BCL2/IGH rearrangements by polymerase chain reaction (PCR), real time quantitative PCR (RQ‐PCR) and digital droplet PCR (ddPCR). All patients were treated with involved‐field radiotherapy (IF‐RT) (24–30 Gy). From 2005, patients with minimal residual disease (MRD) after IF‐RT received rituximab (R) (375 mg/m2, 4 weekly administrations). The median follow‐up is 82 months (17–196). At diagnosis, 72% of patients were BCL2/IGH+. Progression‐free survival (PFS) was significantly better in patients with undetectable/low levels (<10−5) of circulating BCL2/IGH+ cells at diagnosis and in those who were persistently MRD− during follow‐up (P = 0·0038). IF‐RT induced an MRD− status in 50% of cases; 16/19 (84%) MRD+ patients after IF‐RT became MRD− after R treatment. A significantly longer PFS was observed in MRD+ patients treated with R compared to untreated MRD+ patients (P = 0·049). In early stage FL, both circulating levels of BCL2/IGH+ cells at diagnosis and MRD status during follow‐up bear prognostic implications. Standard IF‐RT fails to induce an MRD‐negative status in half of patients. Most patients become MRD− following treatment with R and this is associated with a significantly better PFS. [ABSTRACT FROM AUTHOR]

The article discusses the study which aimed to screen BIRC3 disruption by copy number aberration (CNA) and mutation analysis and to explore the clinical significance of BIRC3 deletions and/or mutations among 11q-chronic lymphocytic leukaemia (CLL) patients. It states that biallelic BIRC3 inactivation in CLL patients with 11q deletion identifies a subgroup with very aggressive disease.

Summary: TP53‐disrupted chronic lymphocytic leukaemia (CLL) patients show a suboptimal long‐term response to ibrutinib. We hereby report that ibrutinib‐induced in vitro apoptosis and proliferation inhibition were significantly lower in TP53‐mutated (TP53‐M) CLL cells compared to TP53 wild‐type cells. Contrariwise, venetoclax effectively killed TP53‐M cells. Gene expression profile analysis of TP53‐M cells revealed a downmodulation of B‐cell receptor (BCR)‐related genes and an upmodulation of genes with anti‐apoptotic/pro‐survival activity, suggesting that the survival and proliferation of TP53‐M cells are less dependent on the BCR pathway. These observations further support the use of drug combinations for the optimal management of TP53‐M CLL patients. [ABSTRACT FROM AUTHOR]

BCL2/ IGH rearrangements were analysed by polymerase chain reaction ( PCR) at diagnosis in paired peripheral blood ( PB) and bone marrow ( BM) samples from 67 patients with stage I/ II follicular lymphoma ( FL). Real time quantitative PCR ( RQ- PCR) and digital droplet PCR (dd PCR) were performed in cases with a major breakpoint region (MBR+) at diagnosis and after localized radiotherapy and rituximab administration in order to investigate the applicability of dd PCR. The overall dd PCR/ RQ- PCR concordance was 81·9% (113/138 samples) and 97·5% in the 40/138 with quantifiable disease ( RQ- PCR≥10−5). At baseline, dd PCR allowed the recovery of a MBR+ marker in 8/18 (44·4%) samples that resulted MBR-negative/minor cluster region-negative/minor BCL2-negative by qualitative PCR. Moreover, the tumour burden at diagnosis significantly predicted progression-free survival ( PSF) only when quantified by dd PCR. Paired PB and BM samples analysis demonstrated a high concordance in the detection of BCL2/IGH+ cells by qualitative and quantitative methods; in particular, 40/62 samples were positive by dd PCR (25 PB+/BM+; 9 PB+/BM−; 6 PB−/BM+), with 34/40 (85%) identified by the study of PB only. In conclusion, in localized FL, dd PCR is a promising tool for monitoring minimal residual disease (MRD) that is at least comparable to RQ- PCR and potentially more accurate. PB is a suitable source for serial BCL2/ IGH MRD assessments, regardless of the methodology utilized. [ABSTRACT FROM AUTHOR]

The article presents a case of a 59-year-old man who developed a hairy cell leukaemia (HCL) during the course of chronic lymphocytic leukaemia (CLL). In the case, concomitant chronic lymphocytic leukaemia and hairy cell leukaemia evaluated for immunoglobulin heavy chain gene (IGHV-D-J) rearrangements and BRAF-V600E mutation.

Presents a letter to the editor about long-term follow-up of Philadelphia chromosome-positive chronic myeloid leukemia in children and adolescents managed at a single institution.

BCL2/IGH rearrangements were analysed by polymerase chain reaction (PCR) at diagnosis in paired peripheral blood (PB) and bone marrow (BM) samples from 67 patients with stage I/II follicular lymphoma (FL). Real time quantitative PCR (RQ-PCR) and digital droplet PCR (ddPCR) were performed in cases with a major breakpoint region (MBR+) at diagnosis and after localized radiotherapy and rituximab administration in order to investigate the applicability of ddPCR. The overall ddPCR/RQ-PCR concordance was 81·9% (113/138 samples) and 97·5% in the 40/138 with quantifiable disease (RQ-PCR≥10 -5 ). At baseline, ddPCR allowed the recovery of a MBR+ marker in 8/18 (44·4%) samples that resulted MBR-negative/minor cluster region-negative/minor BCL2-negative by qualitative PCR. Moreover, the tumour burden at diagnosis significantly predicted progression-free survival (PSF) only when quantified by ddPCR. Paired PB and BM samples analysis demonstrated a high concordance in the detection of BCL2/IGH+ cells by qualitative and quantitative methods; in particular, 40/62 samples were positive by ddPCR (25 PB+/BM+; 9 PB+/BM-; 6 PB-/BM+), with 34/40 (85%) identified by the study of PB only. In conclusion, in localized FL, ddPCR is a promising tool for monitoring minimal residual disease (MRD) that is at least comparable to RQ-PCR and potentially more accurate. PB is a suitable source for serial BCL2/IGH MRD assessments, regardless of the methodology utilized., (© 2017 John Wiley & Sons Ltd.)