Abnormalities of TP53 in chronic lymphocytic leukaemia (CLL) correlate with aggressive disease and transformation. We studied 115 patients with CLL including 90 untreated, 25 with heavily pretreated/refractory CLL using fluorescent in situ hybridisation (FISH) to detect allelic loss at chromosome 17p and flow cytometry (FC) to test p53 protein overexpression. A total of 17 cases were identified with TP53 deletion and/or protein expression. Both tests correlated in 10 of 17 patients; in six, one or the other abnormality was detected and in one case, with a deletion, flow cytometry failed. Material for direct DNA sequencing was available in 14 of 17 cases. Mutations were found in seven cases. Five of 14 patients with allelic loss and seven of 13 expressing p53 protein had a mutation. These were single-base substitutions and were located in exons 5, 7 or 8. Mutations were not found in 13 of 14 other cases without deletions by FISH or protein expression. The incidence of p53 abnormalities in this series was 15%, with a significant difference between untreated patients (7%) and the pretreated/refractory group (50%; P<0.01). Abnormal p53 was predicted for shorter survival, regardless of the method used. We confirm that p53 abnormalities are more common in refractory CLL and that mutations occur at the known hot spots. Testing for TP53 deletions by FISH and protein expression by FC is an effective and simple way of screening patients who are likely to have aggressive disease. DNA sequencing adds little to these methods in identifying the population at risk.

A dvances in therapeutics that improve outcomes of patients with myeloma are key drivers for imaging developments. If bone marrow disease is detected early, and patients are treated according to clinical risk, then survival advantages are conferred (1-8). Histologic confirmation of clonal bone marrow plasma cells of greater than 10% in bone marrow or biopsy-proven plasmacytoma is a core requirement of diagnosis that is related to disease burden. However, for a diagnosis of multiple myeloma requiring treatment, biopsy results must be supplemented with evidence of a myeloma-defining event (hypercalcemia, renal failure, anemia, or bone disease) or a biomarker of malignancy (clonal marrow plasma cell percentage  60%, involved:uninvolved serum free light chain ratio  100, or a positive finding at MRI) (9). Although the International Myeloma Working Group (IMWG) recommends a range of imaging investigations for bone disease (including low-dose CT, fluorine 18 [ 18 F] fluorodeoxyglucose [FDG] PET/CT, and MRI), the high sensitivity of whole-body (WB) MRI is recognized (10,11), and it is recommended for all patients suspected of having myeloma and who underwent low-dose WB CT or FDG PET/CT with negative findings (12). The IMWG definition of bone involvement as a myeloma-defining event remains the presence of more This copy is for personal use only. To order printed copies, contact

A number of phenotypic and functional alterations have been described in T cells of cancer patients. These changes are believed to reflect an impaired T-cell mediated immunity, which in turn, may result in a decreased capacity to generate an effective antitumor response. Several mechanisms have been proposed to explain depressed immunity in cancer patients including tumor-derived suppressor factors, abnormal cytokine production, deletion or inactivation of tumor-reactive T-cells. To investigate the mechanism underlying the immunodeficiency in Hodgkin's disease (HD) we studied the expression of T cell receptor zeta chain, which plays a vital role in the cascade of events leading to T and NK cell activation. The expression of the zeta chain of the T cell receptor/CD3 complex was analyzed by dual colour immunofluorescence on peripheral blood T lymphocytes: CD3+, CD4+, CD8+ and NK-cells (CD56+) in patients in different phases of the disease. Zeta chain was significantly reduced on CD3, CD4, CD8, and CD56 positive cells from patients in active phase of the disease compared with normal controls (p=0.05). In patients tested in complete clinical remission the values were normal except for the subpopulation of CD8+ cells in which the expression of zeta chain remained significantly reduced compared with controls. Downregulation of CD3/zeta-chain in PBLs and NK cells in active phase of HD- and to a lesser extent in clinical remission may contribute to immunodeficiency associated with the disease.

Summary. In a series of 24 patients with chronic T-lymphoid disorders [13 T-prolymphocytic leukaemia (T-PLL) and 11Sezary syndrome] we have studied (i) chromosome 17p abnormalities and p53 allele deletion by fluorescence in situ hybridization; (ii) mutation in the exons of the p53 gene by direct DNA sequencing; and (iii) p53 protein expression by immunocytochemistry and, in some cases, also by flow cytometry with DO-1, a monoclonal antibody to the p53 protein. The study revealed p53 deletion and accumulation of p53 protein in the absence of mutation in the exons that included the hot-spots and differs from that described in B-prolymphocytic leukaemia. Seven T-PLL and five Sezary syndrome patients had p53 overexpression, and five T-PLL and nine Sezary syndrome patients showed p53 deletion. Although the majority of cases with p53 accumulation had p53 deletion, the proportion of cells with the deletion did not correlate with the proportion of cells positive for p53 expression. Two cases of T-PLL showed strong p53 expression in the absence of p53 deletion, and one case of Sezary syndrome with p53 deletion in 97% of cells did not express p53. These findings suggest that a non-mutational mechanism exists for the accumulation of p53 protein in these T-cell disorders. The oncogenic effect of the accumulating wild-type protein has been reported in other malignancies. Whether haploidy resulting from p53 deletion contributes to this mechanism has yet to be determined. Alternatively, the frequent loss of the p53 gene could be associated with the deletion of an adjacent gene, which could be involved in the pathogenesis of these diseases.

8012 Background: Early and sensitive detection of bone marrow disease and stratified patient management according to clinical risk can confer survival advantages in multiple myeloma (MM). Whole body MRI (WB MRI) and Fluorodeoxyglucose (FDG) PET/CT are included in international guidelines for imaging in patients with a suspected diagnosis of MM. However prospective studies comparing detection of MM by contemporary WB MRI as per recent MY-RADS consensus against FDG PET/CT are lacking. We report here protocol-defined endpoints from the prospective iTIMM (NCT02403102) study, comparing WB MRI and PET/CT, their relationship with serum and bone marrow estimates of disease burden, as well as molecular tumor characteristics. Methods: Patients with newly diagnosed MM or at first relapse planned to receive chemotherapy and autologous stem cell transplantation were enrolled in iTIMM. Matched baseline WB MRI and FDG PET/CT were performed and baseline clinical data including tumor genetics collected. Scans were double reported for presence of focal and diffuse disease by expert MRI and PET/CT radiologists, blinded to each other’s assessment. Paired methods were used to compare burden and patterns of disease on WB MRI compared to FDG PET/CT at baseline. Primary and secondary trial endpoints include relationship between post-treatment WB MRI response and progression-free survival, for which follow-up is ongoing. Exploratory endpoints include comparison of baseline WB MRI and PET/CT and their correlation with laboratory parameters, for which data is complete and reported here. Results: From May 2015 to March 2018, sixty patients (35 male; mean age 60 years) underwent baseline WB MRI as per MY-RADS consensus and FDG PET/CT. At least one focal lesion was detected in 50/60 patients (83.3%) by WB MRI and in 36/60 patients (60%) by PET/CT. WB MRI was more sensitive ( P< 0.05) across anatomical regions except for ribs and cervical spine. Four patients in our study showed two or more focal lesions ≥5 mm only on WB MRI but not PET/CT. All lesions detected by WB MRI but not PET/CT resolved in follow-up scans after treatment, excluding false positives. In 49/60 (81.7%) patients, diffuse disease was detected by WB MRI, compared to 10/60 (16.7%) by PET-CT; WB MRI was more sensitive across all anatomical areas ( P< 0.05). Plasma cell infiltration and paraprotein levels were significantly higher for patients with diffuse disease on WB MRI, but not on PET/CT. All genetically high-risk tumours, defined by t(4;14), t(14;16), del(1p), gain(1q) or del(17p), showed diffuse infiltration on WB MRI. Conclusions: WB MRI increases detection of focal and diffuse disease compared with FDG PET/CT, including improved detection of focal lesions meeting criteria for active disease as per International Myeloma Working Group diagnostic criteria, proposing it as a gold standard for tumor imaging in MM. Clinical trial information: NCT02403102.