Bortezomib in relapsed multiple myeloma complicated by extramedullary plasmacytomas.

A 58-year-old man suffered relapse of multiple myeloma complicated by large intra-abdominal extramedullary plasmacytomas and severe hepatic impairment secondary to biliary obstruction. Previous treatment had included two types of combination chemotherapy and high-dose therapy with autologous stem cell transplant. Combination therapy with bortezomib and dexamethasone resulted in partial response of the plasmacytomas and complete resolution of his hepatic impairment. Extramedullary plasmacytomas are rare. This report lends support to the efficacy of bortezomib in the treatment of plasmacytoma and describes the safe use of bortezomib despite hepatic upset.

Acquired copper deficiency following prolonged jejunostomy feeds.

A 19-year-old man who developed extensive oesophageal lye (Alkali) stricture and received long-term enteral nutrition (eight months) with a jejunostomy tube developed macrocytic anaemia (Hb: 41 g/L) with leucopenia (white blood cell [WBC]: 3.0 x 10(9)/L). The patient's serum vitamin B12, folate, iron and liver function tests were normal. Bone marrow examination revealed gross erythroid hyperplasia and cytoplasmic vacuolization of erythroid and myeloid elements. Further investigations revealed low serum copper (0.3 micromol/L) and ceruloplasmin concentrations (<30 mg/L) with marginally low normal serum concentration of red cell peroxidase (13 U/gHb), establishing the diagnosis of copper deficiency anaemia. The anaemia and leucopenia responded intermittently to intravenous copper therapy, but the serum copper concentration dropped when intravenous copper therapy was withdrawn. Enteral jejunostomy copper supplementation failed to maintain adequate serum copper concentrations. After stabilizing the general condition of the patient, a pharyngo-gastric anastamosis was performed and normal oral diet commenced, which restored normal serum copper concentration. This case report suggests that copper supplements in the form of copper sulphate are not adequately absorbed when administered through a jejunostomy tube.

Direct sequence analysis of TCR V delta 2-D delta 3 rearrangements in common acute lymphoblastic leukaemia and application to detection of minimal residual disease.

T cell receptor delta chain (TCR delta) gene rearrangements were studied by Southern blot analysis in 36 patients with common acute lymphoblastic leukaemia, including 14 adults and 22 children. The majority of patients (68%) had either a rearrangement or deletion of one or more TCR delta genes. The most frequent rearrangement involved a partial recombination of V delta 2 to D delta 3 (55%). D delta 2-D delta 3 rearrangements were present in five patients (14%). To investigate the TCR delta rearrangement as a tumour marker in minimal residual disease studies, presentation samples from 18 patients were amplified by PCR and directly sequenced. Although the size of the V delta 2-D delta 3 junction varied by only 40 bp, sequence analysis showed extensive diversity. This was derived from four factors: deletion of the 5' end of D delta 3 gene (15/18) and 3' end of V delta 2 gene (16/18); the presence of D delta 2 sequences (6/18); insertion of N nucleotides (15/18); association of P nucleotides with intact V delta 2 and D delta 3 genes (5/18). N nucleotides were the major feature, contributing to 75% of the junction. D delta 1 sequences were not involved. Twenty base oligonucleotide probes, constructed from the junctional sequences, were capable of detecting residual tumour cells at the 10(-4) sensitivity level. Cross hybridization studies confirmed the probes to be clone specific. Longitudinal studies on patients undergoing treatment were capable of detecting tumour in remission samples.

Determinants of symptom interval in childhood cancer.

The duration of symptoms before diagnosis (lag time) was defined for 184 of 236 children diagnosed as having a malignancy at the Royal Hospital for Sick Children, Edinburgh for the time period January 1982 until December 1990. The natural logarithm of the lag time was correlated with age, gender, diagnostic group, white cell count in acute leukaemia, clinical stage of disease in solid tumours, and event free survival. Age was significantly associated with lag time, older children presenting later. In the diagnostic groups, mean lag time ranged from 2.8 weeks in nephroblastoma to 13.3 weeks for brain tumours. Diagnostic group was predictive for lag time after adjustment for age, with for example, a significantly longer lag time for those with brain tumours. However lag time was not predictive of event free survival and it is likely that lag time has other major determinants. When compared with previous studies, there also appears to be a regional variation in lag time for diagnostic groups. It seems likely that this is a reflection of geographical difference in the structure of health systems and is therefore yet another important determinant.

Cytogenetic abnormalities in childhood acute lymphoblastic leukemia.

A review of the cytogenetic analyses of a cohort of unselected patients with acute lymphoblastic leukemia from a single institution (1981-1989) confirmed hyperdiploidy > 50 as a favorable prognostic feature and pseudodiploidy, especially with chromosomal rearrangements, as an adverse one. In the early years of the study, a high incidence of diploid karyotype was identified, but with time (better banding and more intensive search) the incidence has fallen to 7.7%. Many such patients have been shown to be pseudodiploid. Molecular genetic techniques are increasingly identifying clonal abnormalities.

Intracerebral recurrence of primary intrathoracic rhabdomyosarcoma.

We present two cases of intracerebral recurrence of primary intrathoracic rhabdomyosarcoma, occurring within 2 months of each other. Both had embryonal histological features. One (case 1) almost certainly arose within the lung adjacent to a developmental cyst; the intrathoracic site of origin of the other (case 2) was difficult to ascertain. Both were treated on SIOP MMT protocols. The intracerebral deposits became clinically apparent soon after completing chemotherapy. They were removed surgically and second-line chemotherapy was given both systemically and intrathecally. Neither received radiotherapy. The disease recurred in both children whilst on therapy and they died as a consequence of raised intracranial pressure.

Aortic aneurysms and consumptive coagulopathy.

We describe three cases of consumptive coagulopathy caused by extensive thrombus formation in otherwise 'uncomplicated' aortic aneurysms. These cases demonstrate the importance of performing a coagulation screen in any patient presenting with thrombocytopenia who may have an aortic aneurysm. Effective therapy with low-dose heparin was demonstrated with subsequent haemostasis being maintained with warfarin.