ABSTRACT
This retrospective national study compared the use of alemtuzumab-based conditioning regimens for hematopoietic SCT (HSCT) in acquired severe aplastic anemia with antithymocyte globulin (ATG)-based regimens. One hundred patients received alemtuzumab and 55 ATG-based regimens. A matched sibling donor (MSD) was used in 87 (56%), matched unrelated donor (MUD) in 60 (39%) and other related or mismatched unrelated donor (UD) in 8 (5%) patients. Engraftment failure occurred in 9% of the alemtuzumab group and 11% of the ATG group. Five-year OS was 90% for the alemtuzumab and 79% for the ATG groups, P=0.11. For UD HSCT, OS of patients was better when using alemtuzumab (88%) compared with ATG (57%), P=0.026, although smaller numbers of patients received ATG. Similar outcomes for MSD HSCT using alemtuzumab or ATG were seen (91% vs 85%, respectively, P=0.562). A lower risk of chronic GVHD (cGVHD) was observed in the alemtuzumab group (11% vs 26%, P=0.031). On multivariate analysis, use of BM as stem cell source was associated with better OS and EFS, and less acute and cGVHD; young age was associated with better EFS and lower risk of graft failure. This large study confirms successful avoidance of irradiation in the conditioning regimens for MUD HSCT patients.
Subject(s)
Anemia, Aplastic/therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Antilymphocyte Serum/therapeutic use , Bone Marrow Transplantation/methods , Peripheral Blood Stem Cell Transplantation/methods , Transplantation Conditioning/methods , Adolescent , Adult , Aged , Alemtuzumab , Bone Marrow Cells/cytology , Child , Child, Preschool , Female , Graft Survival , Graft vs Host Disease , Humans , Infant , Male , Middle Aged , Registries , Retrospective Studies , Risk Factors , Siblings , Tissue Donors , Treatment Outcome , United Kingdom , Young AdultABSTRACT
OBJECTIVES: To investigate short-term effects of Multi-Sensory Stimulation (MSS) on behaviour, mood and cognition of older adults with dementia, the generalization of effects to day hospital and home environments and the endurance of any effects over time. DESIGN: A randomized controlled trial comparing MSS with a credible control of one-to-one activities. METHODS: Fifty patients with diagnoses of moderate to severe dementia were randomized to either MSS or Activity groups. Patients participated in eight 30-minute sessions over a 4-week period. Ratings of behaviour and mood were taken before, during and after sessions to investigate immediate effects. Pre, mid, post-trial, and follow-up assessments were taken to investigate any generalization of effects on cognition, behaviour at the day hospital and behaviour and mood at home and endurance of effects once sessions had ceased. RESULTS: Immediately after MSS and Activity sessions patients talked more spontaneously, related better to others, did more from their own initiative, were less bored/inactive, and were more happy, active or alert. Both groups were more attentive to their environment than before, with a significantly greater improvement from the MSS group. At the day hospital, patients in the Activity group improved on their 'speech skills' (amount of speech; initiation of speech), whereas the MSS group remained unchanged during the trial. The MSS group showed a significant improvement in mood and behaviour at home compared to the Activity group whose behaviour deteriorated. No longer-term benefits were shown; indeed, behaviour declined sharply during the month follow-up period. CONCLUSIONS: Both MSS and Activity sessions appear to be effective and appropriate therapies for people with dementia.
Subject(s)
Acoustic Stimulation/methods , Alzheimer Disease/therapy , Photic Stimulation/methods , Affect , Aged , Alzheimer Disease/psychology , Cognitive Behavioral Therapy , Communication , Environment , Female , Generalization, Psychological , Humans , Male , Mental Disorders/psychology , Mental Disorders/rehabilitation , Relaxation TherapyABSTRACT
Glial cell line-derived neurotrophic factor (GDNF) has previously reduced motor deficits and preserved nigral dopamine neurones in rhesus monkeys with a unilateral MPTP-induced lesion of substantia nigra. We now report on the ability of GDNF to reverse motor deficits induced by parenteral administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to common marmosets resulting in bilateral degeneration of the nigrostriatal pathway. Prior to GDNF administration, all MPTP-treated animals showed akinesia or bradykinesia, rigidity, postural instability and tremor. Intraventricular injection of GDNF (10, 100 or 500 microg) at 9 and 13 weeks post MPTP treatment resulted in a concentration dependent improvement in locomotor activity and motor disability which became significant after administration of 100 and 500 microg of GDNF. The most prominent improvements were in alertness, checking movements, and posture. It is concluded that intraventricular GDNF administration improves bilateral Parkinsonian motor disability following MPTP treatment and this may reflect an action of GDNF on remaining nigral dopaminergic neurones.
Subject(s)
Motor Activity/drug effects , Motor Skills Disorders/drug therapy , Nerve Growth Factors , Nerve Tissue Proteins/therapeutic use , Neuroprotective Agents/therapeutic use , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine , Animals , Callithrix , Dopamine Agents , Drug Evaluation, Preclinical , Glial Cell Line-Derived Neurotrophic Factor , Motor Activity/physiology , Motor Skills Disorders/chemically induced , Nerve Tissue Proteins/pharmacology , Neuroprotective Agents/pharmacology , Parkinson Disease/drug therapy , Substantia Nigra/drug effects , Substantia Nigra/physiologyABSTRACT
One hundred and eighteen patients presenting with high-grade non-Hodgkin's lymphoma, undergoing autologous bone marrow transplantation (ABMT) in first complete remission (CR), have been reported to the European Group for Bone Marrow Transplantation (EBMT). Of these, 102 were eligible for inclusion in this study following review of registration forms. Patients with lymphoblastic lymphoma were excluded. Remission induction and high-dose regimens varied between contributing centres. A maintained CR was observed in 90% of patients. Early relapse was observed in 6%, and 4% suffered toxic deaths. With a median follow-up of 45 months (3-112 months), the 5-year actuarial overall and progression-free survivals are both 70%. Nineteen (18%) patients relapsed at a median of 3.5 months (0.25-52 months) after ABMT, only 1 achieving a further durable CR. The only factor with prognostic significance was histological subtype, with diffuse small noncleaved-cell lymphoma having a significantly worse outcome. High-dose therapy and ABMT has produced effective consolidation of first remission in this group of patients, even in those with poor prognostic features at presentation.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Marrow Transplantation , Lymphoma, Non-Hodgkin/therapy , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bleomycin/administration & dosage , Bone Marrow Purging , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Dexamethasone/administration & dosage , Doxorubicin/administration & dosage , Female , Humans , Leucovorin/administration & dosage , Life Tables , Lymphoma, Non-Hodgkin/classification , Lymphoma, Non-Hodgkin/drug therapy , Lymphoma, Non-Hodgkin/mortality , Lymphoma, Non-Hodgkin/pathology , Male , Methotrexate/administration & dosage , Middle Aged , Prednisone/administration & dosage , Remission Induction , Risk Factors , Survival Analysis , Treatment Outcome , Vincristine/administration & dosageABSTRACT
A case-controlled analysis was performed to assess the effect of stem-cell source on autograft in a group of patients with malignant lymphoma reported to the European Bone Marrow Transplant Group (EBMT). The study was performed matching 83 patients autografted with peripheral blood stem cells (PBSC) with 83 autologous bone marrow transplantation (ABMT) patients. The case-matching was carried out following selection of the main prognostic factors for progression-free survival by multivariate analysis. The progression-free survival was similar in both types of transplants (38.5% PBSCT vs. 36.4% ABMT). The overall relapse and progression rate for the PBSCT was 51.2% compared with 50.1% for the ABMT patients. The differences were not significant statistically. The transplant-related mortality was 6% for both groups. The neutrophil and leucocyte recovery occurred faster in the peripheral blood stem-cell transplantation (PBSCT); the platelet recovery was not significant. A higher number of interstitial pneumonitis and fungal infection episodes were observed in the ABMT group. In conclusion, in these closely matched groups, there is no difference in PFS between patients undergoing PBSCT and those undergoing ABMT. However, the patients autografted with PBSC have a more rapid engraftment and a lower toxicity.