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Biomedical subjects

C Canning

Publications and source records attributed to C Canning.

At least 19 recordsLinked to original sources
PubMed2006

Bevacizumab: a new way of doing business?

This review highlights the history of the development of treatments for choroidal neovascularization (wct AMD). It examines how drug therapies have evolved for the management of age-related macular degeneration (AMD) and the value of randomised clinical trials in determining efficacy. Finally it examines the emerging practice of utilising bevacizumab for the treatment of choroidal neovascularization despite the lack of any phase III clinical trial data.

Angiogenesis Inhibitors↗
PubMed2006

Patterns of cardiovascular risk in rheumatoid arthritis.

BACKGROUND: Although it is known that rheumatoid arthritis is associated with an increased risk of cardiovascular disease (CVD), the pattern of this risk is not clear. This study investigated the relative risk of myocardial infarction, stroke and CVD mortality in adults with rheumatoid arthritis compared with adults without rheumatoid arthritis across age groups, sex and prior CVD event status. METHODS: We conducted a cohort study among all residents aged >or=18 years residing in British Columbia between 1999 and 2003. Residents who had visited the doctor at least thrice for rheumatoid arthritis (International Classification of Disease = 714) were considered to have rheumatoid arthritis. A non-rheumatoid arthritis cohort was matched to the rheumatoid arthritis cohort by age, sex and start of follow-up. The primary composite end point was a hospital admission for myocardial infarction, stroke or CVD mortality. RESULTS: 25 385 adults who had at least three diagnoses for rheumatoid arthritis during the study period were identified. During the 5-year study period, 375 patients with rheumatoid arthritis had a hospital admission for myocardial infarction, 363 had a hospitalisation for stroke, 437 died from cardiovascular causes and 1042 had one of these outcomes. The rate ratio for a CVD event in patients with rheumatoid arthritis was 1.6 (95% confidence interval (CI) 1.5 to 1.7), and the rate difference was 5.7 (95% CI 4.9 to 6.4) per 1000 person-years. The rate ratio decreased with age, from 3.3 in patients aged 18-39 years to 1.6 in those aged >or=75 years. However, the rate difference was 1.2 per 1000 person-years in the youngest age group and increased to 19.7 per 1000 person-years in those aged >or=75 years. Among patients with a prior CVD event, the rate ratios and rate differences were not increased in rheumatoid arthritis. CONCLUSIONS: This study confirms that rheumatoid arthritis is a risk factor for CVD events and shows that the rate ratio for CVD events among subjects with rheumatoid arthritis is highest in young adults and those without known prior CVD events. However, in absolute terms, the difference in event rates is highest in older adults.

Adolescent↗
PubMed2006

A randomized controlled trial of mailed osteoporosis education to older adults.

INTRODUCTION: Osteoporosis represents a growing public health concern; however, current rates of management are sub-optimal. The aim of our study was to assess, in a randomized controlled trial, the effect of a mailed educational intervention on older adults' knowledge, attitudes, and preventive behaviors regarding osteoporosis. The setting was a large publicly funded state pharmacy benefits program. The patients were 31,715 Medicare beneficiaries from Pennsylvania who participated in a drug benefits program for low-to-moderate income elderly people. METHODS: All women aged over 65 years, and all men and women with a history of fracture or long-term oral use of glucocorticoid, were included. Approximately half of the participants (intervention group) were randomly selected to receive three mailings aimed at improving knowledge of osteoporosis and enhancing preventive activities, such as using calcium and vitamin D, reducing fall risks in the home, obtaining a bone mineral density (BMD) test, and taking medications when necessary. The other participants did not receive the intervention mailings and served as controls. We surveyed a sample of intervention and control subjects to determine the effects of the intervention on knowledge, attitudes, self-efficacy (confidence in one's ability to perform specific activities), and behavior regarding osteoporosis prevention and treatment. Six hundred randomly selected participants in the intervention group and an equal number in the control group were invited to participate. RESULTS: Twenty-six had died and 636 of the remaining 1,185 (54%) completed the survey. Respondents and non-respondents did not differ significantly with respect to measured sociodemographic factors. All scales had good reliability (all Cronbach's alphas>0.65). Knowledge of osteoporosis was generally very good and did not differ between intervention (mean=65% correct responses) and control subjects (mean=67% correct; P=0.4). Perceived susceptibility to osteoporosis was relatively high and similar across groups (P=0.4). Self-efficacy for participating in osteoporosis prevention and treatment was very strong in both the intervention (mean=4.3 on a 0-5 scale) and control (mean=4.2, P=0.03) groups . On average, subjects in the intervention group reported participating in 3.5 of 6 preventive osteoporosis activities compared with 3.4 in the control group (P=0.5). CONCLUSIONS: Compared with the controls, a mailed educational intervention for osteoporosis was not associated with better knowledge, higher perceived susceptibility, or performance of preventive measures among the at-risk older adults that we studied. The intervention group demonstrated a small increase in self-efficacy. More intensive patient interventions or intervention aimed at other aspects of the care process may be required to bring about changes that lead to a reduction in fractures.

Aged↗
PubMed2005

Supportive devices for preventing and treating subluxation of the shoulder after stroke.

BACKGROUND: Supportive devices such as slings, wheelchair attachments and orthoses have been used to treat subluxation of the shoulder after stroke. OBJECTIVES: To investigate the effect of supportive devices in preventing subluxation, re-positioning the head of humerus in the glenoid fossa, decreasing pain, increasing function and adversely increasing contracture in the shoulder after stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched on 22 March 2004). In addition, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 2004), MEDLINE (1966 to March 2004), CINAHL (1982 to March 2004), EMBASE (1974 to March 2004), AMED (1985 to March 2004) and the Physiotherapy Evidence Database (PEDro, March 2004). We also handsearched conference proceedings and contacted authors for additional information. SELECTION CRITERIA: Studies were included if they were: randomised, quasi-randomised or controlled trials; participants had a stroke; intervention was supportive devices; and subluxation, pain, function or contracture were measured. DATA COLLECTION AND ANALYSIS: Two independent reviewers examined the identified studies which were assessed for methodological quality and analysed as (1) supportive devices versus no supportive devices or (2) two supportive devices. MAIN RESULTS: Four trials (one on slings, three on strapping - 142 participants) met the inclusion criteria. One trial testing a hemisling versus no device reported that no participants had subluxation greater than 10 mm, the same number had lost more than 30 degrees of shoulder external rotation (Peto odds ratio (OR) = 1.00, 95% confidence interval (CI) 0.1 to 9.3), and more participants in the hemisling group had pain (Peto OR = 8.7, 95% CI 1.1 to 67.1). The other three showed that strapping was effective in delaying the onset of pain (weighted mean difference (WMD) = 14 days, 95% CI 9.7 to 17.8), but was ineffective in reducing pain severity (WMD = -0.7 cm on a visual analogue scale, 95% CI -2.0 to 0.7), increasing upper limb function (WMD = 0.8, 95% CI -1.5 to 3.1) or affecting the degree of contracture (WMD = -1.4 degrees, 95% CI -10.9 to 8.1) at the shoulder. AUTHORS' CONCLUSIONS: There is insufficient evidence to conclude whether slings and wheelchair attachments prevent subluxation, decrease pain, increase function or adversely increase contracture in the shoulder after stroke. There is some evidence that strapping the shoulder delays the onset of pain but does not decrease it, nor does it increase function or adversely increase contracture.

Braces↗
PubMed2004

CD8+ cell depletion of donor lymphocyte infusions using cd8 monoclonal antibody-coated high-density microparticles (CD8-HDM) after allogeneic hematopoietic stem cell transplantation: a pilot study.

A CD8 murine monoclonal antibody-coated high-density microparticle (HDM) has been developed, which allows for the rapid depletion of CD8+ T cells from apheresis products by gravity sedimentation. We conducted a study to determine the efficacy and safety of CD8 depletion of donor lymphocyte infusions (DLI) to treat relapse after stem cell transplantation using the Eligix CD8-HDM Cell Separation System. Patients were targeted to receive 3 x 10(7) CD4+ T cells/kg. Nine patients were enrolled, three with CML, three myeloma, two CLL, and one NHL. A median of 1 x 10(10) mononuclear cells were obtained by apheresis and processed. The median depletion of CD8+ cells was 99.3% (97.8->99.5%). CD8 depletion was highly specific, with a median recovery of CD4+ cells of 75%. A median of 2.9 x 10(7) CD4+ cells/kg was infused. No infusional toxicity was noted. All CML patients achieved a complete molecular remission. A CLL patient demonstrated a complete response. One patient developed GVHD (grade II acute GVHD and subsequently chronic GVHD). The CD8-HDM Cell Separation System appears to be highly selective and effective in depleting CD8+ T cells from DLI apheresis products, and CD8-depleted DLI is capable of mediating a graft-versus-leukemia effect while minimizing GVHD.

Adult↗
PubMed2003

Outcome after autologous and allogeneic stem cell transplantation for patients with multiple myeloma: impact of graft-versus-myeloma effect.

A total of 228 patients with multiple myeloma (MM), 166 patients receiving autologous transplantation (124 PBSC and 38 BM) and 66 patients receiving T-cell-depleted allogeneic transplantation were analyzed to compare overall survival (OS), progression-free survival (PFS) and risk of relapse. Patients receiving autologous transplantation had a significantly improved OS (P=0.006) and PFS (P=0.002) at 2 years with OS and PFS for autologous transplant 74% and 48%, respectively, compared with 51% and 28% for allogeneic transplantation. By 4 years after transplantation, outcome was similar with OS and PFS for autologous transplantation 41% and 23%, respectively, compared with 39% and 18% for allogeneic transplantation. The 4-year cumulative incidence of nonrelapse mortality was significantly higher in patients receiving allogeneic transplantation (24% vs 13%) (P=0.004). Relapse was the principle cause of treatment failure for both groups; however, there was a significantly reduced risk of relapse associated with allogeneic transplantation at 4 years: 46% for allograft vs 56% for autograft (P=0.02). Despite a lower risk of relapse after allogeneic transplantation, autologous transplantation is associated with improved OS and PFS compared with allogeneic transplantation in patients with MM. Strategies focused on reducing nonrelapse mortality in allogeneic transplantation may translate into an improved outcome for patients receiving allogeneic transplantation.

Adult↗
PubMed2002

The evaluation of screening policies for diabetic retinopathy using simulation.

AIMS: To develop a model for evaluating screening strategies and to use it to determine the cost effectiveness of varying the screening method and the screening interval. METHODS: A discrete event simulation was designed, validated and run for a population of 500000. Most parameters were derived from peer-reviewed publications. RESULTS: Standard methods of screening save up to 50% of the potential sight years lost. They give up to 85% of the sight years saved by an idealized gold standard programme using mydriatic seven-field photography reported by an ophthalmologist. The mobile camera, used for annual screening and 6-month follow-up after the detection of background retinopathy, had an estimated cost of pound 449200 per year with pound 2842 per sight year saved. It is less efficient to screen Type 2, rather than Type 1 diabetes mellitus patients, but they contributed to almost three-quarters of the sight years saved. CONCLUSIONS: The model can evaluate screening intervals and methods on a national or health authority basis. Results indicate that it appears more cost effective to continue to screen outside an ophthalmology clinic, until treatment is needed. Programmes with annual screening, and more frequent screening for those with background retinopathy, are robust to realistic fluctuations in compliance and screening sensitivity.

Computer Simulation↗
PubMed2001

A cohort study of possible risk factors for over-reporting of antihypertensive adherence.

BACKGROUND: The identification of poor medicinal adherence is difficult because direct observation of medication use is usually impractical. Up to 50% of individuals on chronic therapies may not be taking their medication as prescribed. This study is one of the first to explore possible risk factors for over-reporting of antihypertensive adherence using electronic medication monitoring. METHODS: The adherence of 286 individuals on single-drug antihypertensive therapy in a large managed care organization was electronically monitored for approximately three months. Questionnaires on socioeconomic background, adherence to therapy, health beliefs, and social support before and after adherence monitoring were completed. Over-reporting of antihypertensive adherence was assessed by comparing the self-reported frequency of noncompliance with that determined from electronic dosing records. Risk factors for over-reporting were identified by contingency table analysis and step-wise logistic regression. RESULTS: Although only 21% of participants acknowledged missing doses on one or more days per week, electronic monitoring documented nonadherence at this or a higher level in 42% of participants. The following variables were associated with over-reporting: >1 versus 1 daily dose (OR = 2.58; 95% CI = 1.50-4.41; p =.0006), lower perceived health risk from nonadherence (OR = 1.35; 95% CI = 1.10-1.64; p =.0035), and annual household income of <15,000 dollars versus >30,000 dollars (OR = 2.64; 95% CI = 1.13-6.18; p =.025). CONCLUSIONS: Over-reporting of adherence may be affected by factors related to dosing frequency, health beliefs and socioeconomic status. This topic deserves further investigation in other patient populations to elucidate possible underlying behavioral explanations.

Adolescent↗
PubMed2001

Quantitation of T-cell neogenesis in vivo after allogeneic bone marrow transplantation in adults.

Following myeloablative therapy, it is unknown to what extent age-dependent thymic involution limits the generation of new T cells with a diverse repertoire. Normal T-cell receptor gene rearrangement in T-cell progenitors results in the generation of T-cell receptor rearrangement excision circles (TRECs). In this study, a quantitative assay for TRECs was used to measure T-cell neogenesis in adult patients with leukemia who received myeloablative therapy followed by transplantation of allogeneic hematopoietic stem cells. Although phenotypically mature T cells had recovered by 1 to 2 months after bone marrow transplantation (BMT), TREC levels remained low for 3 months after BMT. T-cell neogenesis became evident by 6 months, and normal levels of adult thymic function were restored at 6 to 12 months after BMT. Subsequent leukemia relapse in some patients was associated with reduced TREC levels, but infusion of mature donor CD4(+) T cells resulted in rapid restoration of thymic function. These studies demonstrate that T-cell neogenesis contributes to immune reconstitution in adult patients and suggest that thymic function can be manipulated in vivo. (Blood. 2001;98:1116-1121)

Adult↗
PubMed2001

T-cell--depleted allogeneic bone marrow transplantation followed by donor lymphocyte infusion in patients with multiple myeloma: induction of graft-versus-myeloma effect.

Previous trials of allogeneic bone marrow transplantation (BMT) in patients with multiple myeloma (MM) have demonstrated high response rates but also high transplantation-related mortality (TRM) and high relapse rates. Exploitation of this strategy remains of interest because donor lymphocyte infusions (DLIs) can induce a potent graft-versus-myeloma (GVM) effect. CD6 T-cell--depleted allogeneic BMT was combined with prophylactic CD4(+) DLI administered 6 to 9 months after BMT in an effort to reduce TRM and to induce a GVM response after BMT. Twenty-four patients with matched sibling donors and chemotherapy-sensitive disease underwent BMT. CD6 T-cell depletion of donor bone marrow was the sole method of graft-versus-host disease (GVHD) prophylaxis. GVHD after BMT was minimal, 1 (4%) grade III and 4 (17%) grade II GVHD. Fourteen patients received DLI, 3 in complete response and 11 with persistent disease after BMT. Significant GVM responses were noted after DLI in 10 patients with persistent disease, resulting in 6 complete responses and 4 partial responses. After DLI, 50% of patients developed acute (> or = II) or extensive chronic GVHD. Two-year estimated overall survival and current progression-free survival (PFS) for all 24 patients is 55% and 42%, respectively. The 14 patients receiving DLI had an improved 2-year current PFS (65%) when compared with a historical cohort of MM patients who underwent CD6-depleted BMT survived 6 months with no GVHD and did not receive DLI (41%) (P =.13). Although this study suggests that prophylactic DLI induces significant GVM responses after allogeneic BMT, only 58% of patients were able to receive DLI despite T-cell--depleted BMT. Therefore, less toxic transplantation strategies are needed to allow a higher proportion of patients to receive DLI and the benefit from the GVM effect after transplantation. (Blood. 2001;98:934-939)

Actuarial Analysis↗
PubMed2001

CML66, a broadly immunogenic tumor antigen, elicits a humoral immune response associated with remission of chronic myelogenous leukemia.

This report describes a tumor-associated antigen, termed CML66, initially cloned from a chronic myelogenous leukemia (CML) cDNA expression library. CML66 encodes a 583-aa protein with a molecular mass of 66 kDa and no significant homology to other known genes. CML66 gene is localized to human chromosome 8q23, but the function of this gene is unknown. CML66 is expressed in leukemias and a variety of solid tumor cell lines. When examined by Northern blot, expression in normal tissues was restricted to testis and heart, and no expression was found in hematopoietic tissues. When examined by quantitative reverse transcription-PCR, expression in CML cells was 1.5-fold higher than in normal peripheral blood mononuclear cells. The presence of CML66-specific antibody in patient serum was confirmed by Western blot and the development of high titer IgG antibody specific for CML66 correlated with immune induced remission of CML in a patient who received infusion of normal donor lymphocytes for treatment of relapse. CML66 antibody also was found in sera from 18-38% of patients with lung cancer, melanoma, and prostate cancer. These findings suggest that CML66 may be immunogenic in a wide variety of malignancies and may be a target for antigen-specific immunotherapy.

Amino Acid Substitution↗
PubMed2001

A CD4+ T cell clone selected from a CML patient after donor lymphocyte infusion recognizes BCR-ABL breakpoint peptides but not tumor cells.

BACKGROUND: In patients with chronic myelocytic leukemia (CML), the breakpoint cluster region and fusion between the BCR and the c-ABL genes (BCR-ABL) oncogen product is a potential tumor-specific antigen. Previous studies have shown that T cells specific for the junctional region peptides of the BCR-ABL oncoprotein can be detected in healthy individuals as well as in patients with CML in chronic phase. We assessed whether BCR-ABL- specific T cells could be found in a patient achieving a complete cytogenetic remission after CD4+ donor lymphocyte infusion. METHODS: Using dendritic cells pulsed with BCR-ABL breakpoint peptides as antigen-presenting cells, we stimulated patient peripheral blood lymphocytes to isolate peptide-specific T cell clones present at the time of the cytogenetic response. T cell clones were isolated and the cellular specificity of these cells was examined. RESULTS: A CD3+ CD4+ T cell clone (1F7) that recognizes overlapping p210 junctional peptides presented by HLA-DR molecules was identified and expanded in vitro. Clone 1F7 failed to recognize autologous tumor cells as well as dendritic cells derived from patient CML cells. Clone 1F7 did not inhibit the growth and differentiation of CML precursor cells in a standard colony formation assay. Finally, using a clone-specific probe, 1F7 cells could not be detected in patient peripheral blood at the time of the donor lymphocyte infusion response. CONCLUSIONS: These results suggest that clone 1F7 was selected in vitro using highly potent peptide pulsed dendritic cells but was not representative of the anti-leukemia immune response in vivo. Based on these findings, CD4+ T cells with BCR-ABL specificity do not appear to be mediators of the anti-leukemia response in vivo after donor lymphocyte infusion.

Adult↗
PubMed2001

Derivation of adherence metrics from electronic dosing records.

Numerous adherence variables have been created from electronic dosing records hindering synthesis of the vast body of adherence research. To elucidate the mathematical foundation for electronic adherence monitoring and to understand how diverse electronic adherence metrics are related to each other and the underlying construct of adherence behavior. Several representative adherence metrics are derived mathematically and their relationship to the underlying consumption (or dosing event) rate analyzed. Data from a 3-month study of 286 individuals on single-drug antihypertensive therapy are then used to empirically study the statistical properties of several of these electronic adherence metrics. As suggested by their common link to the consumption (or dosing event) rate, the analyzed electronic adherence metrics were generally strongly correlated (r <- .6 and > .4). The lowest correlation (r = .15) involved the ratio of the observed number of doses to the recommended number (called average adherence), which tended to emphasize quantity consumed, and the ratio of the observed to maximum mean squared rate deviation (MSRD ratio), which focused more on dose timing. Despite their different formulations, electronic adherence variables are generally closely correlated. Adherence metrics that average the consumption rate over multiple doses (by summing up the number of doses and dividing by the monitored time) may be less sensitive to short-term fluctuations in medication intake. Metrics that are more sensitive to timing variability may thus be preferable when timing as well as quantity of dosing are of interest.

Adult↗
PubMed2001

UK survey of attitudes to local anaesthesia for vitreoretinal surgery.

BACKGROUND: The use of local anaesthesia (LA) for vitreoretinal (VR) surgery is growing although surgeons in the UK traditionally use general anaesthesia. PURPOSE: To assess the use and attitudes towards local anaesthesia for VR surgery among the members of the British and Eire Association of Vitreo-retinal Surgeons (BEAVRS). METHODS: A questionnaire was sent to members of BEAVRS. Use of LA was assessed for the following procedures: macular hole; diabetic vitrectomy; vitrectomy; cryopexy and gas; buckling and re-buckling procedures. Attitudes of surgeons generally using LA for primary retinal detachment surgery (> 50% of cases) were compared with those generally using general anaesthesia (GA) (> 50% of cases). RESULTS: 33.6% of surgeons preferred LA for macular hole; 26.2% for diabetic vitrectomy; 23.3% for vitrectomy, cryopexy and gas; 21.4% for buckling procedures; and 9.35% for re-buckling procedures. When surgeons routinely using LA were compared with those regularly using GA they considered LA less stressful for patients and surgeon, patients tolerant to longer operations, and buckling or redo surgery no more difficult under LA. However, both groups considered surgery on young patients and teaching relatively more difficult under LA. CONCLUSION: The use of LA may convey benefits for VR surgery and faster rehabilitation for patients. However, we identified wide variations in the use of and attitudes to LA for VR surgery in British surgeons.

Adult↗
PubMed2000

Corneal opacities after cataract surgery with hypromellose.

26 cases of corneal opacity after cataract surgery occurred in a period of 2 weeks in one surgical unit. Cases occurred after a change in source of intraocular hypromellose solution and only among patients in whom the new product had been used.

Cataract Extraction↗
PubMed2000

Conversion to full donor chimerism following donor lymphocyte infusion is associated with disease response in patients with multiple myeloma.

Donor lymphocyte infusions (DLIs) have been demonstrated to induce clinical responses in patients with relapsed multiple myeloma after allogeneic bone marrow transplantation, but the immunologic mechanisms involved have not been well characterized. In patients with chronic myelocytic leukemia (CML), remissions following DLI are invariably associated with conversion to complete donor hematopoiesis, suggesting that the target antigens of this response are expressed on both normal and CML-derived hematopoietic stem cells. In the present study, we examined hematopoietic chimerism and the complexity of the T-cell receptor (TCR) repertoire in 4 patients with relapsed multiple myeloma who received infusions of donor CD4+ lymphocytes. Three of 4 patients had a clinical response that began 1 to 2 months after DLI. All 3 responding patients developed lymphocytosis at the initiation of response that was due to a 2- to 4.5-fold increase in the number of CD3+ T cells. In 1 patient, this was due primarily to increases in CD3+ and CD8+ cells; in 2 patients, to increased numbers of CD3+ and CD8+ and CD3+ and CD4+ T cells. In all responding patients, conversion to complete donor hematopoiesis occurred in the first 2 months after DLI. The single nonresponding patient remained it 100% recipient hematopoiesis. The TCR repertoire complexity was examined by polymerase chain reaction amplification of complementary-determining region 3 (CDR3) derived from 24 Vbeta gene subfamilies. In 2 patients, the initiation of myeloma response and conversion to complete donor hematopoiesis was associated with normalization of TCR complexity. Complete donor chimerism and normal TCR complexity remained stable in all patients and did not change with subsequent relapse or development of graft-versus-host disease (GVHD). Thus, conversion to full donor chimerism was temporally associated with the antimyeloma effect of DLI but not with the development of GVHD. Nevertheless, the maintenance of stable donor hematopoiesis did not prevent disease relapse and was not associated with prolonged remission. The selective relapse of myeloma cells without concomitant return of mixed hematopoietic chimerism suggests that myeloma tumor cells in some patients develop resistance to immune destruction.

Animals↗
PubMed2000

Changes in T cell receptor repertoire associated with graft-versus-tumor effect and graft-versus-host disease in patients with relapsed multiple myeloma after donor lymphocyte infusion.

Recent reports of clinical responses following donor lymphocyte infusions (DLI) in patients with relapsed multiple myeloma (MM) after allogeneic BMT have demonstrated the ability of allogeneic cells to mediate a graft-versus-myeloma (GVM) effect, but the mechanisms involved have not been determined. To identify changes in the T cell compartment associated with DLI, we performed a molecular analysis of the T cell receptor (TCR) repertoire in four patients with relapsed MM who received infusions of CD4+ lymphocytes from HLA-identical sibling donors. Three of the four patients demonstrated a clinical anti-myeloma response following DLI but also developed graft-versus-host disease (GVHD). The TCR repertoire was examined after PCR amplification of 24 Vbeta gene subfamilies. This method determines the relative utilization of each Vbeta gene subfamily and also allows the identification of clonal and oligoclonal T cell populations through analysis of CDR3 regions for each TCR Vbeta gene subfamily. Serial blood samples were obtained over at least a 1 year period before and after DLI and results compared to 10 normal donors. Serial analysis of CDR3 size profiles demonstrated the appearance of clonal T cell populations after DLI in each of the three responding patients. The appearance of some clones was noted within the first 3 months after DLI and coincided with decreasing levels of monoclonal paraprotein indicating an ongoing GVM response. Other T cell clones appeared at later time points and coincided with the development of GVHD. These findings demonstrate that T cell clones with different patterns of onset can be identified in the peripheral blood of MM patients following DLI. Further functional characterization of these distinct clonal expansions will be required to determine whether these T cell clones are mediators of either anti-myeloma or anti-host activity.

Adult↗