Total energy expenditure and body composition changes following peripheral blood stem cell transplantation and participation in an exercise programme

The purpose of this investigation was to assess changes in total energy expenditure (TEE), body weight (BW) and body composition following a peripheral blood stem cell transplant and following participation in a 3-month duration, moderate-intensity, mixed-type exercise programme. The doubly labelled and singly labelled water methods were used to measure TEE and total body water (TBW). Body weight and TBW were then used to calculate percentage body fat (%BF), and fat and fat-free mass (FFM). TEE and body composition measures were assessed pretransplant (PI), immediately post-transplant (PII) and 3 months post-PII (PIII). Following PII, 12 patients were divided equally into a control group (CG) or exercise intervention group (EG). While there was no change in TEE between pre- and post-transplant, BW (P

Quality of life changes following peripheral blood stem cell transplantation and participation in a mixed-type, moderate-intensity, exercise program

The purpose of this investigation was to evaluate the impact of undertaking peripheral blood stem cell transplantation (PBST) on quality of life (QoL), and to determine the effect of participating in a mixed-type, moderate-intensity exercise program on QoL. It was also an objective to determine the relationship between peak aerobic capacity and QoL in PBST patients. QoL was assessed via the CARES questionnaire and peak aerobic capacity by a maximal graded treadmill test, pretransplant (PI), post transplant (PII) and following a 12-week intervention period (PIII). At PII, 12 patients were divided equally into a control or exercise intervention group. Undergoing a PBST was associated with a statistically but not clinically significant decline in QoL (P < 0.05). Following the intervention, exercising patients demonstrated an improved QoL when compared with pretransplant ratings (P < 0.01) and nonexercising transplant patients (P < 0.05). Moreover, peak aerobic capacity and QoL were correlated (P < 0.05). The findings demonstrated that exercise participation following oncology treatment is associated with a reduction in the number and severity of endorsed problems, which in turn leads to improvements in global, physical and psychosocial QoL. Furthermore, a relationship between fitness and QoL exists, with those experiencing higher levels of fitness also demonstrating higher QoL.

Survival following mechanical ventilation of recipients of bone marrow transplants and peripheral blood stem cell transplants

Survival of bone marrow transplant recipients requiting mechanical ventilation is poor but improving. This study reports a retrospective audit of all haematopoietic stem cell transplant (HSCT) recipients requiring mechanical ventilation at an Australian institution over a period spanning 11 years from 1988 to 1998. Recipients of autologous transplants are significantly less likely to require mechanical ventilation than recipients of allogeneic transplants. Of 50 patients requiring mechanical ventilation, 28% survived to discharge from the intensive care unit, 20% to 30 days post-ventilation, 18% to discharge from hospital and 12% to six months post-ventilation. Risk factors for mortality in the HSCT recipient requiting mechanical ventilation include renal, hepatic and cardiovascular insufficiency and greater severity of illness. Mechanical ventilation of HSCT recipients should not be regarded as futile therapy.

Immunological changes after cancer treatment and participation in an exercise program

Purpose: The purpose of this investigation was to evaluate the impact of undertaking peripheral blood stem cell transplantation (PBST) on T-cell number and function, and to determine the role of a mixed type, moderate intensity exercise program in facilitating the recovery of T-cell number and function. Methods: Immunological measures of white blood cell, lymphocyte, CD3(+), CD4(+), and CD8(+) counts, and CD3(+) cell function were assessed pretransplant (PI), immediately posttransplant (PII), and 1 month (II), 2 months (12) and 3 months (PIII) posttransplant. After PII, 12 patients were divided equally into a control group (CG) or exercise intervention group (EG). Results: Lower total T-cell, helper T-cell, and suppressor T-cell counts (P < 0.01), as well as lower T-cell function (P < 0.01), when compared with normative data, were found at PI. More specifically, 88% of the group had CD3(+), CD4(+), and CD8(+) counts that were more than 40%, 20%, and 50% below normal at PI, respectively. Undertaking a PBST caused further adverse changes to the total leukocyte, lymphocyte, CD3(+), CD4(+) and CD8(+) count. and the helper/suppressor ratio. Although CD8(+) counts had returned to normal by PIII, CD3(+), CD4(+), and the CD4(+)/CD8(+) ratio remained significantly lower than normative data (P < 0.01), with 66%, 100%, and 100% of the subject group reporting counts and ratios, respectively, below the normal range. Conclusion: The PBST patients were immunocompromised before undertaking the transplant, and the transplant procedure imposed further adverse changes to the leukocyte and lymphocyte counts. The leukocyte and CD8(+) counts returned to normal within 3 months posttransplant; however, the other immunological parameters assessed demonstrated a delayed recovery. Although participation in the exercise program did not facilitate a faster immune cell recovery, neither did the exercise program hinder or delay recovery.

Granulocyte colony-stimulating factor modulates alpha-galactosylceramide-responsive human V alpha 24(+) V beta 11(+) NKT cells

Despite more than a 10-fold increase in T cell numbers in G-CSF-mobilized peripheral blood stem cell (PBSC) grafts, incidence and severity of acute graft-vs-host disease (GVHD) are comparable to bone marrow transplantation. As CD1d-restricted, Valpha24(+)Vbeta11(+) NKT cells have pivotal immune regulatory functions and may influence GVHD, we aimed to determine whether G-CSF has any effects on human NKT cells. In this study, we examined the frequency and absolute numbers of peripheral blood NKT cells in healthy stem cell donors (n = 8) before and following G-CSF (filgrastim) treatment. Effects of in vivo and in vitro G-CSF on NKT cell cytokine expression profiles and on responsiveness of NKT cell subpopulations to specific stimulation by alpha-galactosylceramide (alpha-GalCer) were assessed. Contrary to the effects on conventional T cells, the absolute number of peripheral blood NKT cells was unaffected by G-CSF administration. Furthermore, responsiveness of NKT cells to alpha-GalCer stimulation was significantly decreased (p < 0.05) following exposure to G-CSF in vivo. This hyporesponsiveness was predominantly due to a direct effect on NKT cells, with a lesser contribution from G-CSF-mediated changes in APC. G-CSF administration resulted in polarization of NKT cells toward a Th2, IL-4-secreting phenotype following alpha-GalCer stimulation and preferential expansion of the CD4(+) NKT cell subset. We conclude that G-CSF has previously unrecognized differential effects in vivo on NKT cells and conventional MHC-restricted T cells, and effects on NKT cells may contribute to the lower than expected incidence of GVHD following allogeneic peripheral blood stem cell transplantation.

Autologous hemopoietic stem cell transplantation in severe rheumatoid arthritis: A report from the EBMT and ABMTR

Objective. Since 1996, autologous hemopoietic stem cell transplantation (HSCT) has been used to treat severe rheumatoid arthritis (RA). To date, published reports have been individual cases or series containing small numbers. This study combined the worldwide experience in a single analysis. Methods. The Autoimmune Disease Databases of the European Group for Blood and Marrow Transplantation (EBMT) and the Autologous Blood and Marrow Transplant Registry (ABMTR) were used to identify patients with RA treated with autologous HSCT. Further information relating to patient and treatment-specific variables was obtained by questionnaire. Results. Seventy-six patients were registered from 15 centers. Seventy-three patients had received autologous HSCT, and in 3 patients hematopoietic stem cells (HSC) were mobilized but not transplanted. Transplanted patients (median age 42 yrs, 74% female, 86% rheumatoid factor positive) had been previously treated with a mean of 5 (range 2-9) disease modifying antirheumatic drugs (DMARD). Significant functional impairment was present, with a median Health Assessment Questionnaire (HAQ) score of 1.4 (range 1.1-2.0) and Steinbrocker score mean 2.39 (SD 0.58). The high dose treatment regimen was cyclophosphamide (CYC) alone in the majority of patients, mostly 200 mg/kg (n = 62). Seven patients received anti-thymocyte globulin (ATG) in addition to CYC, 2 patients busulfan and CYC (BuCYC), and one patient CYC with total body irradiation and ATG. One patient received fludarabine with ATG. Following treatment, one patient received bone marrow but the rest received chemotherapy and/or granulocyte colony-stimulating factor mobilized peripheral blood stem cells. The harvest was unmanipulated in 28 patients, the rest receiving some form of lymphocyte depletion, mostly through CD34+ selection. Median followup was 16 months (range 3-55). Responses were measured using the American College of Rheumatology (ACR) criteria. Forty-nine patients (67%) achieved at least ACR 50% response at some point following transplant. There was a significant reduction in the level of disability measured by the HAQ (p < 0.005). Most patients restarted DMARD within 6 months for persistent or recurrent disease activity, which provided disease control in about half the cases. Response was significantly related to seronegative RA (p = 0.02) but not to duration of disease, number of previous DMARD, presence of HLA-DR4, or removal of lymphocytes from the graft. There was no direct transplant related mortality, although one patient, treated with the BuCYC regimen, died 5 months post-transplant from infection and incidental non-small cell lung cancer. Conclusion. Autologous HSCT is a relatively safe form of salvage treatment in severe, resistant RA. In these open label studies significant responses were achieved in most patients, with over 50% achieving an ACR 50 or more response at 12 months. Although the procedure is not curative, recurrent or persistent disease activity may be subsequently controlled in some patients with DMARD. Clinical trials are necessary to develop this approach inpatients with aggressive disease who have failed conventional treatment including anti-tumor necrosis factor agents.

Granulocyte-colony-stimulating factor (G-CSF)-primed allogeneic bone marrow: significantly less graft-versus-host disease and comparable engraftment to G-CSF-mobilized peripheral blood stem cells

Prospective studies have shown rapid engraftment using granulocyte-colony-stimulating factor-mobilized peripheral blood stem cells (G-PBSCs) for allogeneic transplantation, though the risks for graft-versus-host disease (GVHD) may be increased. It was hypothesized that the use of G-CSF to prime bone marrow (GBM) would allow rapid engraftment without increased risk for GVHD compared with G-PBSC. Patients were randomized to receive G-BM or G-PBSCs for allogeneic stem cell transplantation. The study was designed (beta < .8) to detect a difference in the incidence of chronic GVHD of 33% ( < .05). The plan was to recruit 100 patients and to conduct an interim analysis when the 6-month follow-up point was reached for the first 50 patients. Fifty-seven consecutive patients were recruited (G-BM, n = 28; G-PBSC, n = 29). Patients in the G-PBSC group received 3-fold more CD34(+) and 9-fold more CD3(+) cells. Median times to neutrophil (G-BM, 16 days; G-PBSC, 14 days; P < .1) and platelet engraftment (G-BM, 14 days; G-PBSC, 12 days; P < .1) were similar. The use of G-PBSC was associated with steroid refractory acute GVHD (G-BM, 0%; G-PBSC, 32%; P < .001), chronic GVHD (G-BM, 22%; G-PBSC, 80%; P < .02), and prolonged requirement for immunosuppressive therapy (G-BM, 173 days; G-PBSC, 680 days; P < .009). Survival was similar for the 2 groups. Compared with G-PBSC the use of G-BM resulted in comparable engraftment, reduced severity of acute GVHD, and less subsequent chronic GVHD. (Blood. 2001;98:3186-3191) (C) 2001 by The American Society of Hematology.

Peripheral blood chimerism following human liver transplantation

The aim of this study was to prospectively investigate the peak levels and kinetics of donor leucocyte chimerism in human recipients following liver transplantation, The peak levels of chimerism mere observed within the first 48 hours following transplantation and ranged from 0.15% to 20% of total peripheral blood mononuclear cells, In all but one patient, who developed graft versus host disease, there was an early peak level of chimerism that declined over time such that donor leukocytes mere only intermittently detectable after 3 to 4 weeks. In 8 patients who had no episodes of graft rejection, the peak level of donor leukocyte chimerism ranged from 1.3% to 20% (mean +/- SEM; 5.5% +/- 2.1%). In 3 patients who were treated for episodes of acute graft rejection during the first four postoperative weeks, the peak level of donor leukocyte chimerism ranged from 0.15% to 0.2% (0.18 +/- 0.02, P = .012), The results demonstrate a marked variation in the total number of donor leukocytes detectable in the peripheral blood early after liver transplantation and also, that lower levels of chimerism may be associated with lower rates of initial graft acceptance and a higher incidence of acute rejection.

Cell-surface proteoglycan expression by lymphocytes from peripheral blood and Gingiva in health and periodontal disease

Cell-surface proteoglycans are involved in lymphocyte migration and activation. This study investigated the expression of syndecan-1, syndecan-4, and glypican in peripheral blood lymphocytes and by lymphocytes in variously inflamed periodontal tissues. Gingival specimens from healthy, gingivitis, or chronic periodontitis sites were stained by means of antibodies against B- and T-lymphocytes and also syndecan-1, syndecan-4, and glypican. Syndecan-1 expression by peripheral blood mononuclear cells (PBMC) from healthy, gingivitis, and chronic periodontitis subjects was assessed by flow cytometry. Syndecan-1 was expressed by B-cells/plasma cells but not T-cells in both gingivitis and chronic periodontitis lesions, Both B-cells/plasma cells and T-cells in gingivitis and chronic periodontitis expressed syndecan-4. Glypican was expressed only by macrophages. Stimulation of PBMC with mitogens and growth factors modulated syndecan-1 expression in both the T- and B-cells. Thus, cell-surface proteoglycan expression by lymphocytes in periodontal inflammation is cell-type-specific and may be modulated by inflammation.