High dose ifosfamide in combination with etoposide and epirubicin followed by autologous stem cell transplantation in the treatment of relapsed/refractory Hodgkin's disease: a report on toxicity and efficacy.

Patients with Hodgkin's disease (HD) refractory to first line chemotherapy and those who have rapid or multiple relapses have a very poor prognosis. With the increasing use of hybrid chemotherapy these patients will have been exposed to many of the drugs active in HD so it is important to develop salvage regimens that are novel and demonstrate activity in this group of patients. We report the use of a continuous high dose infusion of ïfosfamide at a dose of 9g/m(2) over 3 days in combination with etoposide and epirubicin followed by autologous stem cell transplant with either BEAM or Melphalan/VP16 conditioning in this difficult group. Forty six patients (28M:18F) with a median age of 28 years (range 13-45) were treated. Overall 39 out of 46 (85%) patients responded to treatment, with 17 achieving complete remission and 11 a good partial remission; 28 proceeded to autologous bone marrow/stem cell transplantation. In total, 23 patients are alive and in continuous remission with a follow up of between 12 and 61 months. Median overall survival for the whole group is 36 months. Haematological toxicity, particularly neutropenia (WHO grade IV), was observed in all cases but improved over the 3 courses of treatment in all patients. Non-haematological toxicity was not a major problem; no significant cardiac, hepatic, renal, pulmonary or neuro toxicity was observed and there were no deaths on treatment. This regime shows promise in patients with difficult Hodgkin's disease and warrants further study.

Constrictive pericarditis post allogeneic bone marrow transplant for Philadelphia-positive acute lymphoblastic leukaemia.

We describe two cases of severe constrictive pericarditis arising after allogeneic BMT conditioning involving total body irradiation and melphalan to treat Philadelphia-chromosome positive ALL. Both patients required pericardectomy, resulting in marked improvement in ventricular filling. However, a degree of right-sided cardiac failure persisted in both patients secondary to restrictive cardiomyopathy. Constrictive pericarditis has not been previously described after BMT, but has been observed following thoracic radiotherapy for malignancy, usually involving a substantially higher radiation dose. Pericardial constriction and restrictive cardiomyopathy should be considered as causes of breathlessness and/or oedema occurring late after BMT. Bone Marrow Transplantation (2000) 25, 571-573.

A truncated human chromosome 16 associated with alpha thalassaemia is stabilized by addition of telomeric repeat (TTAGGG)n.

The instability of chromosomes with breaks induced by X-irradiation led to the proposal that the natural ends of chromosomes are capped by a specialized structure, the telomere. Telomeres prevent end-to-end fusions and exonucleolytic degradation, enable the end of the linear DNA molecule to replicate, and function in cell division. Human telomeric DNA comprises approximately 2-20 kilobases (kb) of the tandemly repeated sequence (TTAGGG)n oriented 5'----3' in towards the end of the chromosome, interspersed with variant repeats in the proximal region. Immediately subtelomeric lie families of unrelated repeat motifs (telomere-associated sequences) whose function, if any, is unknown. In lower eukaryotes the formation and maintenance of telomeres may be mediated enzymatically (by telomerase) or by recombination; in man the mechanisms are poorly understood, although telomerase has been identified in HeLa cells. Here we describe an alpha thalassaemia mutation associated with terminal truncation of the short arm of chromosome 16 (within band 16p13-3) to a site 50 kb distal to the alpha globin genes, and show that (TTAGGG)n has been added directly to the site of the break. The mutation is stably inherited, proving that telomeric DNA alone is sufficient to stabilize the broken chromosome end. This mechanism may occur in any genetic disease associated with chromosome truncation.

Sheehan's syndrome presenting with type III hyperlipoproteinaemia.

A patient is described in whom the presenting feature of hypopituitarism was the development of palmar xanthomata associated with type III hyperlipoproteinaemia. Treatment of her secondary hypothyroidism with thyroxine caused resolution of the xanthomata and hyperlipidaemia, but the underlying compositional abnormality of the lipoproteins could still be observed.

Rhesus Du incompatibility in a newborn with high levels of anti D and a benign clinical course.

The Rhesus variant Du is regarded as a weak form of the Rhesus D antigen, but haemolytic disease of the newborn may occur if the maternal serum contains Anti-D [5]. We describe the case of an infant with Rhesus Du incompatibility and high levels of Anti-D in the maternal serum, but without clinical evidence of haemolytic disease of the newborn.

Primary acquired sideroblastic anaemia and myeloproliferative disease: a report on three cases.

Three patients who presented with primary acquired sideroblastic anaemia (PASA) later developed myelofibrosis (MF). As both are clonal disorders a second mutation is suggested.

Lymph node imprint cytology for the rapid assessment of axillary node metastases in breast cancer.

Lymph node imprint cytology was performed on 86 nodes from 13 consecutive patients with breast cancer undergoing simple mastectomy with axillary node sampling, and a prospective comparison with paraffin section was made. The results showed a diagnostic sensitivity and specificity of 0.93 and 0.98 respectively. The predictive value of a positive result was 0.98. This technique can be used to identify patients with Stage I disease rapidly, thereby allowing their exclusion from treatment with peri-operative chemotherapy.

Prospects for social workers in health planning.

The nature and extent of social worker's involvement in regional health planning agencies was the subject of the nationwide study reproted here. Social work proved to be more heavily represented on the professional staffs of these agencies than any other discipline. This was just one of the findings that can help shape the profession's response to the possibilities this new field represents.