B J Boughton’s research while affiliated with Queen Elizabeth Hospital Birmingham and other places

Thirteen adults with acute myeloblastic leukaemia (AML) in early 2nd complete remission (CR) were treated with recombinant interleukin-2 (IL-2) and autologous IL-2-activated peripheral blood lymphocytes (LAK cells). All 13 developed IL-2-induced in vitro lymphocytoxicity against K562 and Daudi target cells. After seven years' follow-up, there was no overall improved survival compared with a historical control group treated with chemotherapy alone. However 7/13 patients developed T-cel-associated cutaneous graft-versus-host disease (GVHD), and 4/4 of these tested showed in vitro evidence of a T-cell-mediated graft-versus-leukaemia (GVL) effects. These had significantly longer 2nd CRs and survived longer. More lymphocytes were harvested and more LAK cells were reinfused in these seven cases. Since these patients also had longer 1st CRs, their GVL response to IL-2/LAK cells could be a feature of slowly progressive disease.

This report examines perceptions of social support and family dynamics in bone marrow transplant (BMT) long-term survivors, as part of a larger study examining issues of quality of life and psychosocial adjustment in this patient group. Ninety one BMT survivors participated in the study. Their responses were compared with those of a matched control group of 73 patients receiving maintenance chemotherapy (MC). The results indicated that the BMT group received more social support than the MC group. Main sources of support were the patients' immediate family members. No significant differences in the typology and dynamics of family environments were observed between groups. However, the groups were significantly different compared with healthy, non-distressed families in cohesion, control and conflict. It was of importance to note that a considerable number of BMT subjects reported at least one nurse as a person who provides support to them, indicating the potential important role of nurses in the psychosocial adjustment of BMT long-term survivors. Strong family relationships were associated in both the BMT and MC groups with significantly better adjustment with respect to their domestic, extended family or social environment, and psychological distress. Social support and family relationships might be two of the main spheres of life contributing to higher levels of quality of life, and their important role as a stressor-filter is highlighted.

A retrospective descriptive study was designed to assess the quality of life (QoL) and psychosocial adjustment in long-term BMT survivors compared with a group of patients with haematological malignancies receiving maintenance chemotherapy (MC), matched for age, post-treatment time, sociodemographic and disease characteristics. The sample consisted of 91 long-term BMT survivors and 73 MC patients from three teaching hospitals in the UK. The results indicated that most of the BMT subjects had a good to excellent quality of life and, in some domains, even better adjustment than the MC patients. However, 20% of the BMT subjects had failed to return to full-time employment at a mean post-BMT time of almost 40 months. A significant number of BMT subjects were also identified with symptoms of anxiety and depression. The physical symptomatology had an association with psychological status. Impotence-related difficulties, decreased sexual satisfaction and altered body image were the main characteristics of psychosexual dysfunction in the BMT group. Poorer quality of life was predicted by the presence of depressive symptoms, low affirmation, and impoverished social adjustment.

This prospective study was designed to measure changes in the psychological status, self-esteem, dependence on other people, physical symptom distress and coping during isolation for bone marrow transplantation (BMT). A sample of 26 BMT patients was assessed at four different points in time. Results indicated that high psychological morbidity was present the day before the transplant, which remained elevated throughout hospitalisation and even a month after discharge. Main distressing symptoms included changes in bowel patterns, fatigue, insomnia, poor appetite and poor concentration. Tension-anxiety and depression showed a non-significant decrease throughout hospitalisation, but anger-hostility and fatigue were increased, especially in the last assessment about a month after discharge from hospital. Activity levels declined over time. Dependence on others and self-esteem have shown no significant changes over time, although pre-transplant assessment showed low self-esteem and a high degree of dependence on others. Main coping mechanisms during isolation identified in the study were hope, directing attention, maintaining control over the situation and acceptance. Psychological disturbance during isolation had a ‘carry-over effect’ even a month after discharge from hospital. Higher symptom distress was associated with higher mood disturbance. Different types of isolation during BMT were not associated with differential amounts of psychomorbidity. Finally, patients who received professional psychological support during BMT demonstrated significantly lower mood disturbance compared with patients who did not receive psychological support.

Fifty long-term survivors of bone marrow transplant (mean post-transplant time = 42.4 months) participated in a study examining their psychosocial adjustment and quality of life. Differences between patients who received an autologous marrow transplant and those who received an allogeneic marrow transplant were identified. Patients with an autologous transplant had mainly psychological difficulties in their post-transplant adaptation, whereas patients with allogeneic transplant developed more physical problems. Overall, their psychosocial adjustment was similar and comparable with other medical groups of patients. A quarter of both groups had failed to return to work/education and up to 9.5% had difficulty in carrying out daily tasks. Twenty per cent of the patients with autologous transplant had clinical signs of anxiety and 10% clinical signs of depression, whereas there was an incidence of 10% of patients with allogeneic transplant with anxiety, but no cases with clinical depression. Family relationships were found to be more integrated and lower in conflict compared with normal families. Quality of life has been described as good to excellent in most of the patients. Multiple regression analysis showed that physical symptomatology, vocational adjustment and depression are predictors of the degree of the patients' quality of life.

Gonadal function and psychosexual adjustment were evaluated in 29 male patients after autologous and allogeneic BMT (mean post-BMT time 35.6 months). Patients were divided into groups according to their interval from transplant in order to evaluate gonadal function throughout the post-BMT years. Thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were normal throughout the post-BMT years. Follicle-stimulating hormone (FSH) and luteinising hormone (LH) were increased throughout the years after BMT, suggesting moderate compensated hypogonadism. Hyperprolactinaemia was observed only in the 2nd year post-BMT and testosterone levels were normal, suggesting that Leydig cells can withstand alkylating agents or TBI. Psychosexual functioning in BMT survivors was compared with that of a group of mixed-diagnosis cancer patients (n = 30) and a group of healthy young subjects (n = 119). Long-term BMT survivors had similar psychosexual adjustment to that of other cancer patients who had received less intensive chemotherapy. Half the patients were dissatisfied with their current sex life. Major problems included impotence/erectile difficulties (37.9%), low sexual desire (37.9%) and altered body image (20.7%). However, both BMT survivors and cancer patients had significantly higher psychosexual dysfunction compared with healthy subjects. The type of chemotherapy, TBI (either single-dose or fractionated), type of transplant and post-BMT time did not correlate with either gonadal or psychosexual functioning.

A 48-year-old man was treated by allogeneic bone marrow transplantation (BMT) in first remission of M4 acute myelogenous leukaemia (AML). He experienced no graft-versus-host disease (GVHD) and 7 months later he relapsed. Following further chemotherapy, he entered a second complete remission; however, he refused a further allogeneic or autologous BMT but agreed to immunotherapy with interleukin-2 and autologous lymphokine-activated killer (LAK) cells. He tolerated this treatment well but went on to develop grade II skin GVHD. Polymerase chain reaction studies of DNA microsatellites of the autologous LAK cells showed that they were of donor origin. The patient remained well for 9 months until, immediately following the introduction of prednisolone for his persistent GVHD, he relapsed. He declined further active treatment and died 5 months later. The case shows that IL-2/LAK cells can be safely given to patients who have experienced no GVHD following allo-BMT and are likely to be effective through an ongoing graft-versus-leukaemia effect.

Forty-two patients with chronic lymphocytic leukaemia (CLL), serum IgG levels < 5.5 milligrams and a history of two or more recent infections, were randomized to receive infusions of 18 g human intravenous immunoglobulin (IVIg) or human albumin placebo every three weeks. During the 12 month study 122 infections were documented but only four were associated with neutropenia. Ten patients (24%) with IgG levels < 3.0 milligrams experienced 65% of the infections. In response to IVIg there were immediate and accumulative increases in serum IgG levels and an associated decrease in total and serious infections. If three further infections occurred, placebo patients were commenced on 18 g IVIg, and IVIg patients were increased to 24 g IVIg. Approximately 50% of these cases subsequently remained infection free. The study shows the usefulness of prophylactic Sandoglobulin in CLL patients with hypogammaglobulinaemia, and suggests that this may be justified in those with recurrent infections and serum IgG levels < 3 milligrams.

There were 129 nurses and 26 doctors from 16 BMT centres in the UK who responded to a mailed survey of their job satisfaction, their psychological difficulties at work, the sources and effects of working stress, and any stress-reducing techniques they found useful. Half were emotionally exhausted, and 80% reported feelings of low personal accomplishment. A significant proportion, particularly medical staff, had marked feelings of depersonalisation. All aspects of job satisfaction were thought to be unsatisfactory (namely professional support or training). Signs of clinical anxiety were seen in > 10% of staff, and overt depression was present in 0.8% of nurses and 3.8% of doctors. Emotionally burnout developed because of work-related and personality factors. Sources of stress were found in regular work with dying patients excessive responsibility, rapid advances in transplant technology, and excessive personal demands of patient and families. The majority of staff had experienced difficulties in their personal lives which were directly linked to stress at work. The implications for both the patients and staff are discussed, and stress management techniques are suggested.

Thalidomide is now widely used to treat chronic graft-versus-host disease, but its use is associated with non-teratogenic side effects such as peripheral neuropathy. To examine the value of monitoring plasma concentrations of the drug in such patients, we have developed a high-performance liquid chromatographic (HPLC) assay. The method uses 0.5 mL plasma, is linear to 10 mg/L and had a detection limit of 0.2 mg/L. Thalidomide in plasma specimens was unstable at physiological pH but could be stabilized for several weeks by simple acidification. We describe a protocol for monitoring patients treated with thalidomide which permits convenient transportation and storage of specimens and report, provisionally, that plasma concentrations in the range 1-7 mg/L are therapeutically effective in chronic graft-versus-host disease without adverse side effects.