Summary:Using a prospective, repeated measures design, this study investigated the psychosocial functioning of patients and a close relative pre-and post-allogeneic and autologous bone marrow transplantation (BMT). All patients (n = 28) undergoing BMT in a 1 year period, and their relatives, were interviewed 1 week pre-transplant and at 3, 6 and 12 months post-BMT, using quantitative and qualitative measures. Pre-transplant data revealed a high level of anxiety (61% with moderate to severe anxiety), and a low level of depression (14% with moderate to severe depression). Twelve patients died in the study period. For the surviving patients there was a statistically significant improvement in physical, psychological and social functioning. Most relatives (88%) reported considerable psychological distress pretransplant and at 3 months post-transplant, but this was largely resolved by 12 months post-transplant. Significant correlations between the relative's distress and patient's physical and psychological wellbeing were observed at 3 months post-transplant, but not at the other assessment points. The findings from this study will help in counselling patients and their relatives as to what to expect in the year following BMT. Keywords: psychosocial; outcome; BMT; families It has been well documented that bone marrow transplantation (BMT) is physically and psychologically demanding for patients. [1][2][3][4][5][6][7] The effects of BMT on donors 8 and on other family members has received less attention, 9 although evidence suggests considerable disruption to families. 10 Prospective longitudinal research that includes baseline assessments is required, 11 with greater emphasis on the process of psychosocial adjustment in both patients and families. 9,11 One of the first prospective studies of psychosocial functioning in BMT showed that functioning was most impaired at 90 days post-transplant, with most aspects of physical and psychosocial functioning restored after 1 year. 12 A further prospective study reported similar findings, with little difference in physical and psychosocial status when assessed at pre-BMT and 1 year post-BMT. 13 While mean differences on pre-BMT and 1 year scores were not sig- nificant, the use of means obscures possible significant changes that individual patients may experience. 13 An analysis of change scores between pre-and post-transplant for individual patients suggests many experience substantial changes between these two assessments, 13 although detailed longitudinal studies of individual adaptation are scarce. 11 Qualitative research methods have rarely been used when studying BMT patients, particularly in a prospective longitudinal manner. Qualitative research is often viewed as the antithesis of quantitative research, 14 being somehow 'unscientific' and unreliable. 15 However, quantitative and qualitative methods are better viewed as complementary, 14 especially when health and illness issues are being examined in small numbers of patients, 16 and offer a useful addition to the usual...
The influence of mixed hematopoietic chimerism (MC) after allogeneic bone marrow transplantation remains unknown. Increasingly sensitive detection methods have shown that MC occurs frequently. We report a highly sensitive novel method to assess MC based on the polymerase chain reaction (PCR). Simple dinucleotide repeat sequences called microsatellites have been found to vary in their repeat number between individuals. We use this variation to type donor-recipient pairs following allogeneic BMT. A panel of seven microsatellites was used to distinguish between donor and recipient cells of 32 transplants. Informative microsatellites were subsequently used to assess MC after BMT in this group of patients. Seventeen of the 32 transplants involved a donor of opposite sex; hence, cytogenetics and Y chromosome-specific PCR were also used as an index of chimerism in these patients. MC was detected in bone marrow aspirates and peripheral blood in 18 of 32 patients (56%) by PCR. In several cases, only stored slide material was available for analysis but PCR of microsatellites or Y chromosomal material could be used successfully to assess the origin of cells in this archival material. Cytogenetic analysis was possible in 17 patients and MC was detected in three patients. Twelve patients received T-cell-depleted marrow and showed a high incidence of MC as revealed by PCR (greater than 80%). Twenty patients received unmanipulated marrow, and while the incidence of MC was lower (44%), this was a high percentage when compared with other studies. Once MC was detected, the percentages of recipient cells tended to increase. However, in patients exhibiting MC who subsequently relapsed, this increase was relatively sudden. The overall level of recipient cells in the group of MC patients who subsequently relapsed was higher than in those who exhibited stable MC. Thus, while the occurrence of MC was not indicative of a poor prognosis per se, sudden increases in the proportions of recipient cells may be a prelude to graft rejection or relapse.
Summary:Chronic myeloid leukaemia (CML) can be treated sucAllogeneic bone marrow transplantation (BMT) is a successful treatment modality for patients with chronic myeloid leukaemia (CML). Sixty to 80 percent of patients cessfully with allogeneic bone marrow transplantation transplanted with unmanipulated BM in first chronic phase (BMT) leading to long-term disease-free survival. Leu-(CP) achieve long-term disease-free survival. 1 However, kemia relapse, however, remains a significant clinical relapse rates of 10-20% are still the most frequent cause problem. Relapse following BMT presumably results of treatment failure. 2,3 Leukaemia relapse following BMT from the expansion of small numbers of recipient leupresumably results from the inability of the conditioning kaemic cells which have survived the conditioning therregimen to eliminate all recipient leukaemic cells. Ideally, apy. In order to define patients who are at a high risk following BMT, the recipient's bone marrow should be of leukaemia relapse, a variety of techniques have been completely ablated by the conditioning regimen, facilitating employed to detect persistence of host haemopoiesis the engraftment of donor haemopoietic stem cells giving (mixed chimaerism, MC) or residual leukaemia rise to a complete donor haemopoietic chimaera. 4(minimal residual disease, MRD). However, the precise The true incidence and significance of the detection of relationship between the detection of MC and MRD mixed haemopoietic chimaerism (MC) post-BMT remains post-BMT is unknown. We have investigated chimaerunclear. 4,5 MC was initially thought to indicate an impendism and MRD status in 22 patients who were in clinical ing relapse, however, using more sensitive molecular techand haematological remission post-allogeneic BMT for niques it has become clear that MC post-BMT is not chronic phase CML. Chimaerism was assessed using uncommon, with varying percentages of recipient cells short tandem repeat PCR (STR-PCR) while BCR-ABL being detected in different study groups. [6][7][8][9][10] This variation mRNA detection using reverse transcriptase polymerase in the degree of MC is influenced by a number of factors chain reaction (RT-PCR) was performed to detect the including the sensitivity and timing of the assay, the disease presence of MRD. Seventeen patients received unmanindication for BMT, the stage of disease at time of BMT ipulated marrow (non-TCD) while in five patients a T and the choice of conditioning regimen. Several studies cell-depleted transplant (TCD) was performed as indicated that low levels of persisting recipient cells are not additional GVHD prophylaxis. Chimaerism was evaluassociated with an increased risk of leukaemic relapse. 7-10ated in 18 patients (14 non-TCD, four TCD). Mixed However, increasing levels of recipient cells over time chimaerism was an uncommon finding in recipients of (progressive mixed chimaerism) appear to predict relapse, unmanipulated BMT (21%) when compared to TCD especially in recipients of a T cell-depleted (TCD) trans-BMT (100...
Summary. Peripheral blood stem cell (PBSC) mobilization using idarubicin and cytarabine was investigated in 40 patients with chronic myeloid leukaemia in first chronic phase (CML CP1). Disease contamination was evaluated in harvests from 41/44 (93%) mobilization episodes. Using cytogenetics, 22/37 (59%) showed a complete or major response; Southern blot analysis demonstrated a complete or major response in 9/17 (53%). No harvests were RT-PCR negative. In the 41 evaluable episodes, more complete or major responses were seen when PBSC mobilization occurred within 24 months [17/23 (74%) versus 6/18 (33%); P ¼ 0 : 02] and within 12 months of diagnosis [10/11 (91%) versus 13/30 (43%); P ¼ 0 : 018]. 20 patients underwent PBSC transplantation and 18/20 successfully engrafted. Post-transplant cytogenetic analysis was available on 15 cases, of whom five achieved a major cytogenetic response at 1-3 months, with five partial cytogenetic remissions. Two of 40 patients died during mobilization therapy (5%) and three of 20 after the transplant (15%). Overall mortality was high at five of 40 patients, and the procedural mortality was 20%. This study demonstrates that Ph-negative PBSCs can be mobilized in a significant proportion of patients with CML CP1, with the best results observed within a year of diagnosis. These cells can subsequently be used for autologous transplantation, however, the impact on long-term survival requires longer follow-up, and potential benefits may be compromised by the high mortality.
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