In myeloma, the prognostic impact of different strategies used to detect chromosome 13 deletion (D13) remains controversial. To address this, we compared conventional cytogenetics and interphase fluorescence in situ hybridization (iFISH) in a large multicenter study (n ¼ 794). The ability to obtain abnormal metaphases was associated with a poor prognosis, which was worse if D13, p53 deletion or t(4;14) was present, but only D13 remained significant on multivariate analysis. Patients with D13, by either cytogenetics or iFISH, had a poor prognosis. However, when cases with D13 detectable by both cytogenetics and iFISH were separated from those detected by iFISH only, the poor prognosis of iFISH-detectable D13 disappeared; their outcome matched that of patients with no detectable D13 (P ¼ 0.115). Addition of ploidy status to iFISH-D13 did not affect the prognostic value of the test. Indeed both cytogenetics and iFISH D13 divided both hyperdiploidy and nonhyperdiploidy into two groups with similar prognoses, indicating that the poor prognosis of ploidy is entirely due to its association with D13. We conclude that D13 detected by metaphase analysis is a critical prognostic factor in myeloma. Absence of D13, even in those patients yielding only normal or no metaphases, is associated with a relatively good prognosis.

BackgroundMultiple myeloma, monoclonal gammopathy of undetermined significance and smoldering multiple myeloma harbor common chromosomal abnormalities but the prevalence and relative association of aberrations in these diagnostic groups remains controversial. We investigated these aspects in a large series of patients. Design and MethodsChromosome 13 deletion (∆13), deletion of TP53, ploidy status and immunoglobulin heavy chain (IgH) translocations were evaluated by fluorescence in situ hybridization in patients with monoclonal gammopathy of undetermined significance (n=189), smoldering multiple myeloma (n=127) and multiple myeloma (n=400). ResultsOverall, ∆13 (25%, 34% and 47%), 16q23 deletions (6%, 8% and 21%) and 17p13 deletions (3%, 1% and 10%) were less frequent in patients with monoclonal gammopathy of undetermined significance and smoldering multiple myeloma than in those with multiple myeloma. When distinct genetic groups were considered, no differences in the prevalence of ∆13 were found with t(4;14)(p16;q32) and t(14;16)(q32;q23) among the three diagnostic groups; in contrast ∆13 was rarer in t(11;14)(q13;q32) in patients with monoclonal gammopathy (1/28) and smoldering myeloma (2/13) than in those with multiple myeloma (40%). Similar results were seen for the few t(6;14)(p21;q32) cases: 0/3 patients with monoclonal gammopathy or smoldering myeloma had the ∆13, whereas 4/6 (67%) patients with multiple myeloma and this translocation also had the deletion. In multiple myeloma patients with both an IgH translocation and ∆13, the proportions of cells affected by the two abnormalities were similar, as was the case for t(4;14) and t(14;16) monoclonal gammopathy patients positive for ∆13. In contrast, in monoclonal gammopathy patients with t(14;20)(q32;q11), the translocation was present in almost all cells, while the ∆13 was present in only a sub-population. ConclusionsThese results indicate that the presence and time of occurrence of ∆13 depends on the presence of specific concurrent abnormalities. The observation that ∆13 was extremely rare in monoclonal gammopathy of undetermined significance and smoldering multiple myeloma with translocations directly involving cyclin D genes (CCND1 and CCND3) suggest a possible role of ∆13 in the progression of the disease specifically in these genetic sub-groups. (clinicaltrials.gov identifier: ISRCTN 68454111; UKCRN ID 1176).

Objective: This study aimed to assess the prevalence of anxiety and depression among Jordanian lower limb amputees with different clinical characteristics and sociodemographic data (gender, marital status, social support, income, type and level of amputation, and occupation). Methods: Participants were 56 patients with unilateral lower limb amputation with mean duration (8.4 ± 5.75 years). They were recruited from inpatient and outpatient clinics of Jordan University hospital, Royal Farah Rehabilitation Center, and Al-basheer hospital in Amman, Jordan. Participants responded to a questionnaire that included a battery of questions requesting brief information about sociodemographic variables and characteristics of amputation. The level of depression and anxiety in each participating patient was assessed by the Hospital Anxiety and Depression Scale (HADS). Results:The prevalence of anxiety and depressive symptoms were 37% and 20%, respectively. Factors associated with high prevalence of psychological symptoms included female gender, lack of social support, unemployment, traumatic amputation, shorter time since amputation, and amputation below the knee. These fi ndings were confi rmed by a signifi cant reduction of anxiety and depression scores in patients who received social support, patients with amputation due to disease, and patients with amputation above the knee. Presence of pain and use of prosthesis had no effect on the prevalence. Conclusions:The fi ndings of the present study highlight the high incidence of psychiatric disability and depression in amputees; it also showed the importance of sociodemographic factors in psychological adjustment to amputation. It is suggested that psychiatric evaluation and adequate rehabilitation should form a part of their overall management.

A simple high throughput micro-fluorescence in situ hybridisation technique (FISH) was used to detect chromosome 13 deletions (D13), immunoglobulin heavy chain (IgH) rearrangements, t(11;14)(q13;q32), t(4;14)(p16;q32), t(14;16)(q23;q32), p53 loss, and numerical changes of chromosomes 3, 6, 7, 9, 10, 11 and 17 in 228 cases of multiple myeloma (MM), including 33 asymptomatic/smouldering MM (SMM). The patients were not part of a clinical trial and were from 30 different hospitals. In all, 98.4% of cases were abnormal, with 43% having IgH rearrangements and 42% D13. The low incidence of IgH rearrangements was due to a decrease in this finding with age (P ¼ 0.001) and the relatively high proportion of elderly patients in our study population (41% 470 years old). The incidence of specific IgH translocations was t(4;14) 11%, t(11;14) 16% and t(14;16) 3%. Univariate statistical testing showed D13 (P ¼ 0.002), and t(14;16) (P ¼ 0.005) to be associated with shorter survival. This effect was exaggerated for patient's aged 70 years or under but no effect on survival was seen for those over 70 years. In younger patients t(4;14) (P ¼ 0.044) and p53 deletion (Po0.001) were also significant poor prognostic indicators. Multivariate analysis showed D13 and t(14;16) to be independent prognostic variables when considered with age and clinical parameters.