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G Longton

Publications and source records attributed to G Longton.

At least 19 recordsLinked to original sources
PubMed2001

p16(INK4a) lesions are common, early abnormalities that undergo clonal expansion in Barrett's metaplastic epithelium.

Barrett's esophagus (BE) is the only known precursor to esophageal adenocarcinoma, a cancer of which the incidence has been increasing at an alarming rate in Western countries. p16(INK4a) lesions occur frequently in esophageal adenocarcinomas but their role in neoplastic progression is not well understood. We detected 9p21 loss of heterozygosity, p16 CpG island methylation, and p16 mutations in biopsies from 57%, 61%, and 15%, respectively, of 107 patients with BE. In contrast, no mutations were found in p14(ARF) or p15, and methylation was found in only 4% and 13%, respectively. >85% of Barrett's segments had clones with one (p16+/-) or two (p16-/-) p16 lesions. Both p16+/- and p16-/- clones underwent extensive expansion involving up to 17 cm of esophageal mucosa. The prevalence of established biomarkers in BE, such as 17p (p53) loss of heterozygosity, aneuploidy, and/or increased 4N (tetraploid) populations, increased from 0% to 20% to 44% in patients whose biopsies were p16+/+, p16+/-, and p16-/-, respectively (P < 0.001). Barrett's segment lengths also increased with change in p16 status with a median of 1.5, 6.0, and 8.0 cm for patients with p16+/+, p16+/-, and p16-/- biopsies, respectively (P < 0.001). We conclude that most Barrett's metaplasia contains genetic and/or epigenetic p16 lesions and has the ability to undergo clonal expansion, creating a field in which other abnormalities can arise that can lead to esophageal adenocarcinoma.

Adult↗
PubMed2001

Effect of choice of reference equation on analysis of pulmonary function in cystic fibrosis patients.

Pulmonary function is an important measure of disease severity and prognosis in cystic fibrosis (CF). It is generally expressed as a percentage of a predicted value, calculated using regression equations derived from a reference population. A number of reference equations are in widespread use. The purposes of this study were to determine: 1) the extent to which, for a given absolute FEV(1) value, percent of predicted (PPFEV(1)) values vary when derived by different reference equations; and 2) whether these differences affect conclusions of longitudinal and cross-sectional analyses. Subjects were all Caucasians 6-18 years old in the 1990 Cystic Fibrosis Foundation Registry. We found clinically important discrepancies in PPFEV(1) when calculated by the methods of Dockery et al. [Am Rev Respir Dis 1983;128:405-412] and Wang et al. [Pediatr Pulmonol 1993;15:75-78] as compared to Knudson et al. [Am Rev Respir Dis 1983;127:725-734] or Polgar and Promadhat [Pulmonary Function Testing in Children 1971; Philadelphia: W.B. Saunders]. In longitudinal analyses, the choice of reference equation resulted in varying apparent rates of decline in FEV(1). For example, among subjects ages 12-14 years in 1990, the decline in PPFEV(1) from 1990-1995 varied between 2-11%, depending on the choice of reference equation. In cross-sectional analyses, the choice of reference equation affected the distribution of subjects classified as having mild, moderate, or severe lung disease. CF physicians should be aware of the impact of choice of reference equation in both clinical care and research.

Adolescent↗
PubMed2001

Bone density loss after allogeneic hematopoietic stem cell transplantation: a prospective study.

The incidence and course of bone density abnormalities following hematopoietic stem cell transplantation are poorly understood and complicated by the impact of multiple factors. Hip, spine, and wrist bone mineral densities (BMDs) were measured in 104 adults (54 women, 54 men; mean age, 40 years [range, 18-64 years]) at 3 and 12 months after allogeneic transplantation. Clinical and laboratory variables were evaluated using univariate and multivariate analyses to determine risk factors for osteoporosis, fracture, and avascular necrosis. At 3 months posttransplantation, combined (male and female) hip, spine, and wrist z scores were -0.35, -0.42, and +0.04 standard deviations, respectively. At 12 months both men and women experienced significant loss of hip BMD (4.2%, P < .0001); changes in the spine and wrist were minimal. The cumulative dose and number of days of glucocorticoid therapy and the number of days of cyclosporine or tacrolimus therapy showed significant associations with loss of BMD; age, total body irradiation, diagnosis, and donor type did not. Nontraumatic fractures occurred in 10.6% of patients and avascular necrosis in 9.6% within 3 years posttransplantation. The decrease in height between pretransplantation and 12 months posttransplantation was significant (P = .0001). Results indicate that loss of BMD after allogeneic stem cell transplantation is common and accelerated by the length of immunosuppressive therapy and cumulative dose of glucocorticoid. An increased incidence of fracture and avascular necrosis may adversely impact long-term quality of life. Prevention of bone demineralization appears warranted after stem cell transplantation.

Adolescent↗
PubMed2001

Predictors of progression in Barrett's esophagus II: baseline 17p (p53) loss of heterozygosity identifies a patient subset at increased risk for neoplastic progression.

OBJECTIVES: Most patients with Barrett's esophagus do not progress to cancer, but those who do seem to have markedly increased survival when cancers are detected at an early stage. Most surveillance programs are based on histological assessment of dysplasia, but dysplasia is subject to observer variation and transient diagnoses of dysplasia increase the cost of medical care. We have previously validated flow cytometric increased 4N fractions and aneuploidy as predictors of progression to cancer in Barrett's esophagus. However, multiple somatic genetic lesions develop during neoplastic progression in Barrett's esophagus, and it is likely that a panel of objective biomarkers will be required to manage the cancer risk optimally. METHODS: We prospectively evaluated endoscopic biopsies from 325 patients with Barrett's esophagus, 269 of whom had one or more follow-up endoscopies, by a robust platform for loss of heterozygosity (LOH) analysis, using baseline 17p (p53) LOH as a predictor and increased 4N, aneuploidy, high-grade dysplasia, and esophageal adenocarcinoma as outcomes. RESULTS: The prevalence of 17p (p53) LOH at baseline increased from 6% in negative for dysplasia to 57% in high-grade dysplasia (p < 0.001). Patients with 17p (p53) LOH had increased rates of progression to cancer (relative risk [RR] = 16, p < 0.001), high-grade dysplasia (RR = 3.6, p = 0.02), increased 4N (RR = 6.1, p < 0.001), and aneuploidy (RR = 7.5, p < 0.001). CONCLUSIONS: Patients with 17p (p53) LOH are at increased risk for progression to esophageal adenocarcinoma as well as high-grade dysplasia, increased 4N, and aneuploidy. 17p (p53) LOH is a predictor of progression in Barrett's esophagus that can be combined with a panel of other validated biomarkers for risk assessment as well as intermediate endpoints in prevention trials.

Adenocarcinoma↗
PubMed2001

Predictors of progression in Barrett's esophagus III: baseline flow cytometric variables.

OBJECTIVES: Barrett's esophagus develops in 5-10% of patients with gastroesophageal reflux disease and predisposes to esophageal adenocarcinoma. We have previously shown that a systematic baseline endoscopic biopsy protocol using flow cytometry with histology identifies subsets of patients with Barrett's esophagus at low and high risk for progression to cancer. In this report, we further examined cytometric variables to better define the characteristics that best enable DNA cytometry to help predict cancer outcome. METHODS: Patients were prospectively evaluated using a systematic endoscopic biopsy protocol, with baseline histological and flow cytometric measurements as predictors and with cancer as the outcome. RESULTS: A receiver operating curve analysis demonstrated that a 4N fraction cut point of 6% was optimal to discriminate cancer risk (relative risk [RR] = 11.7, 95% CI = 6.2-22). The 4N fractions of 6-15% were just as predictive of cancer as were fractions of >15%. We found that only aneuploid DNA contents of >2.7N were predictive of cancer (RR = 9.5, CI = 4.9-18), whereas those patients whose sole abnormality was an aneuploid population with DNA content of < or =2.7 had a low risk for progression. The presence of both 4N fraction of >6% and aneuploid DNA content of >2.7N was highly predictive of cancer (RR = 23, CI = 10-50). S phase was a predictor of cancer risk (RR = 2.3, CI = 1.2-4.4) but was not significant when high-grade dysplasia was accounted for. CONCLUSIONS: Flow cytometry is a useful adjunct to histology in assessing cancer risk in patients with Barrett's esophagus. Careful examination of cytometric variables revealed a better definition of those parameters that are most closely associated with increased cancer risk.

Barrett Esophagus↗
PubMed2000

Predictors of progression to cancer in Barrett's esophagus: baseline histology and flow cytometry identify low- and high-risk patient subsets.

OBJECTIVE: Barrett's esophagus develops in 5-20% of patients with gastroesophageal reflux disease and predisposes to esophageal adenocarcinoma. The value of endoscopic biopsy surveillance is questioned because most patients do not develop cancer. Furthermore, observer variation in histological diagnosis makes validation of surveillance guidelines difficult because varying histological interpretations may lead to different estimated rates of progression. Thus, objective biomarkers need to be validated for use with histology to stratify patients according to their risk for progression to cancer. METHODS: We prospectively evaluated patients using a systematic endoscopic biopsy protocol with baseline histological and flow cytometric abnormalities as predictors and cancer as the outcome. RESULTS: Among patients with negative, indefinite, or low-grade dysplasia, those with neither aneuploidy nor increased 4N fractions had a 0% 5-yr cumulative cancer incidence compared with 28% for those with either aneuploidy or increased 4N. Patients with baseline increased 4N, aneuploidy, and high-grade dysplasia had 5-yr cancer incidences of 56%, 43%, and 59%, respectively. Aneuploidy, increased 4N, or HGD were detected at baseline in all 35 patients who developed cancer within 5 yr. CONCLUSIONS: A systematic baseline endoscopic biopsy protocol using histology and flow cytometry identifies subsets of patients with Barrett's esophagus at low and high risk for progression to cancer. Patients whose baseline biopsies are negative, indefinite, or low-grade displasia without increased 4N or aneuploidy may have surveillance deferred for up to 5 yr. Patients with cytometric abnormalities merit more frequent surveillance, and management of high-grade dysplasia can be individualized.

Adult↗
PubMed1998

The development of chronic graft-versus-host disease: an analysis of screening studies and the impact of corticosteroid use at 100 days after transplantation.

The value of routine chronic graft-versus-host disease (GVHD) screening studies performed between 70 and 120 days after allogeneic marrow transplantation was retrospectively evaluated among 241 patients. All patients received methotrexate and cyclosporine for GVHD prophylaxis and survived without relapse more than 4 months after transplant. Ninety-one patients (38%) developed clinical extensive chronic GVHD requiring systemic therapy. Data on patients who developed clinical extensive chronic GVHD were compared with those on patients without chronic GVHD to determine which of the following screening tests predicted the subsequent development of clinical extensive chronic GVHD: skin biopsy, oral exam, lip biopsy, Schirmer's test, serum alkaline phosphatase, aspartate transaminase, immunoglobulin level and platelet count. In a univariable analysis, a positive oral examination and a low platelet count were predictive of chronic extensive GVHD development. In a multivariable analysis which adjusted for the contribution of other chronic GVHD risk factors, such as age and a history of acute GVHD none of the screening tests were predictive of chronic GVHD development. The risk factors in this multivariable analysis which had the strongest association with the development of chronic GVHD was a history of acute GVHD and use of corticosteroids at day 100 (RR = 3.9, P = 0.001). The use of corticosteroids for acute GVHD at day 100 had a predictive effect on chronic GVHD development independent of the grade of acute GVHD (RR = 2.1, P = 0.004). Based on these study results, the use of chronic GVHD screening tests may not be of value in predicting who will develop this complication. Patients on corticosteroids at day 100 should be considered for clinical trials to determine the efficacy of new immunosuppressive agents in preventing chronic GVHD.

Adrenal Cortex Hormones↗
PubMed1997

A marginal regression modelling framework for evaluating medical diagnostic tests.

Technological advances continue to develop for early detection of disease. Research studies are required to define the statistical properties of such screening or diagnostic tests. However, statistical methodology currently used to evaluate diagnostic tests is limited. We propose the use of marginal regression models with robust sandwich variance estimators to make inference about the sensitivity and specificity of diagnostic tests. This method is more flexible than standard methods in that it allows comparison of sensitivity between two or more tests even if all tests are not carried out on all subjects, it can accommodate correlated data, and the effect of covariates can be evaluated. This last feature is important since it allows researchers to understand the effects on sensitivity and specificity of various environmental and patient characteristics. If such factors are under the control of the clinician, it provides the opportunity to modify the diagnostic testing program to maximize sensitivity and/or specificity. We show that the marginal regression modelling methods generalize standard statistical methods. In particular, when we compare two screening tests and we test each subject with both screens, the method corresponds to McNemar's test. We describe data from an ongoing audiology screening study and we analyse a simulated version of the data to illustrate the methodology. We also analyse data from a longitudinal study of PCR as a diagnostic test for cytomegalovirus.

Adult↗
PubMed1997

Design of a study to improve accuracy in reading mammograms.

This paper is concerned with the design and analysis of mammography reading studies. In particular we consider studies aimed at evaluating interventions to improve the accuracy with which mammograms are read. A simple randomized design is suggested in which a relatively large group of readers read sets of mammograms before and after an intervention phase. We propose solutions to three difficult statistical issues that arise in the context of such studies: (i) the choice of primary outcome measure; (ii) the data analysis technique to be employed; and (iii) the methodology for calculating sample sizes for readers and images to be read. First, we argue in favor of using sensitivity and specificity as the primary outcome measures rather than receiver operating characteristic (ROC) curves in mammography studies, although the latter are considered state of the art for many types of radiology reading studies. We argue that sensitivity and specificity are more clinically relevant and conceptually more straightforward than ROC curves. Second, we suggest a bivariate approach to data analysis for evaluating intervention effects on sensitivity and specificity. This accommodates the correlations inherent between these measures and allows for estimation of joint effects on them. Finally we propose a method for power calculations that uses computer simulation techniques. Simple formulas for sample size calculations are not available in part because variability in accuracy amongst readers and variation in difficulty among images introduce complexity into power calculations. The simulation method that we propose accommodates such complexity and is easy to implement. The methodology was motivated by a study funded by the Department of Defense to evaluate the potential efficacy of an educational intervention. In the context of this study we illustrate the steps involved in power calculations and apply the data analytic techniques to the sort of data expected to result from this study. Though the proposed methods were motivated by this particular study, the statistical considerations are relevant more broadly in mammography and indeed in other types of radiologic imaging studies. Standards for the conduct of radiologic reading studies are not yet well developed, as they are for randomized clinical trials and for case-control studies. We hope that the discussion in this paper will add to the dialogue necessary for development of such standards.

Breast Neoplasms↗
PubMed1997

Evaluation of pretransplant donor anti-recipient cytotoxic and helper T lymphocyte responses as correlates of acute graft-vs.-host disease and survival after unrelated marrow transplantation.

We analyzed pretransplant donor anti-recipient cytotoxic and helper T lymphocyte (CTL and HTL) responses separately in two cohorts of unrelated marrow transplant recipients. Donors and recipients were typed for HLA-A and -B antigens by serologic methods, and for HLA-DRB1 by molecular methods. A single mismatch for a cross-reactive HLA-A or -B antigen or the -DRB1 allele was accepted in patients younger than 36 years if an HLA-A, -B, or -DRB1-matched donor could not be identified. The combination of methotrexate and cyclosporine was used for graft-vs.-host disease (GVHD) prophylaxis, and marrows were not T cell depleted. Donor anti-recipient CTL precursor frequencies showed no correlation with the severity of acute GVHD or with survival after transplantation. HTL responses were detected in the presence of HLA-class II disparity and showed weak correlations with the severity of acute GVHD (p = 0.054) and with survival after transplantation (p = 0.08). These results suggest that testing donor anti-recipient CTL responses before unmodified marrow transplantation does not predict clinically important events and is not likely to help select unrelated donors. With the current availability of molecular genetic methods for assessing HLA-class II compatibility, testing donor anti-recipient HTL responses is not likely to add information that would help select unrelated donors.

Acute Disease↗
PubMed1996

Marrow transplantation for Fanconi anaemia: conditioning with reduced doses of cyclophosphamide without radiation.

Nine patients with Fanconi anaemia (FA) were conditioned for HLA-identical sibling bone marrow transplant (BMT) with reduced dose of cyclophosphamide (Cy) without radiation or antithymocyte globulin (ATG). The total dose of Cy was 140 mg/kg (n = 2) or 120 mg/kg (n = 7). The median patient age was 8 years (range 4-19). Graft-versus-host disease (GVHD) prophylaxis was with methotrexate and cyclosporine (n = 8) or cyclosporine alone (n = 1). All patients had sustained engraftment and two developed grade>/= II acute GVHD. Cy toxicity included grade >/= 2 mucositis seen in all evaluable patients and haemorrhagic cystitis in two patients. The Kaplan-Meler survival estimate is 89% with a median follow-up of 285 d (range 56-528). For the purpose of comparison, this report also reviews and updates long-term follow-up data on 32 previously reported FA patients conditioned with 140-200 mg Cy/kg without radiation. The lowest dose of Cy (without radiation or ATG) after which HLA-identical sibling marrow transplant can be successfully performed in FA patients has yet to be determined, but it appears that uniform and sustained engraftment can be achieved with a Cy dose of as low as 120 mg/kg.

Adolescent↗
PubMed1996

Evaluation of the mixed lymphocyte culture (MLC) assay as a method for selecting unrelated donors for marrow transplantation.

The utility of the MLC assay as a test of HLA-D region matching and predictor of graft-versus-host disease (GvHD) was evaluated in 435 patients receiving marrow grafts from unrelated donors. Donors and recipients were phenotyped for HLA-A, B and DR antigens by serology, tested in MLC, and retrospectively genotyped for DRB1, B3, B4, B5, DQB1 and DPB1 alleles by PCR/SSOP. Of the 244 HLA-A, B, DR-identical donor-recipient pairs with valuable MLC and DRB1 typing results available, 208 were matched for HLA-A, B and DRB1, while 36 were matched for HLA-A and B and mismatched for a DRB1 allele. Donor anti-recipient relative responses (RR) in MLC, corresponding to the GvHD vector in marrow transplantation, ranged from 7.2 to 100%, with a median of 4.0%. A comparison of reactivity in MLC between pairs matched versus mismatched for DRB1 alleles showed a significant overlap in the distribution of RRs. Using optimally-defined RR cutoffs of 4 and 16%, no correlation between MLC results and risk of developing clinically significant grades III-IV GvHD (p=0.6 and 0.5, respectively) was found when the contribution of DRB1 mismatch was accounted for. Matching for DRB1 alleles, in contrast, was a better predictor of clinically significant GvHD, with DRB1-matched transplant recipients less likely to develop grades III-IV GvHD than DRB1-mismatched recipients (p=0.14). Among the 208 patients and donors matched for DRB1 alleles, the MLC, although reactive (RR > 4.0%) in 45% of cases, did not predict GvHD. Overall, these results underscore the limitations in using the MLC to predict DRB1 matching or risk of clinically significant GvHD among patients receiving unrelated marrow grafts. The availability of DRB1 allele matching by sequence-specific oligonucleotide probes (SSOP) or by direct sequencing provides a method for donor matching that is rapid, precise and superior to the MLC for predicting clinically relevant outcome.

Acute Disease↗
PubMed1996

Treatment of malignant mesothelioma with methotrexate and vinblastine, with or without platinum chemotherapy.

STUDY OBJECTIVE: To determine the efficacy of methotrexate, vinblastine, and platinum chemotherapy in patients with diffuse unresectable malignant mesothelioma. DESIGN: Patients with histologically confirmed malignant mesothelioma were evaluated for treatment with methotrexate, vinblastine, and cisplatin chemotherapy. If the patient had preexisting hearing loss or neuropathy, or was significantly disabled (eg, spending greater than half of the day in bed or a chair), cisplatin therapy was withheld. SETTING: All patients were initially evaluated at the University of Washington Medical Center and received chemotherapy at the University of Washington or in the community. INTERVENTIONS: Between 1990 and 1994, 17 patients received this chemotherapy. Ten patients received cisplatin, 100 mg/m2 IV on day 1, methotrexate, 30 mg/m2 IV on days 8, 15, and 22, and vinblastine, 3 mg/m2 IV on days 8, 15, and 22, in 28-day cycles. One patient had carboplatin substituted for cisplatin due to preexisting hearing loss. Six patients received weekly methotrexate and vinblastine at the same doses without platinum. MEASUREMENTS AND RESULTS: Nine of the 17 (53%; 95% confidence interval [CI], 28 to 77%) patients responded, including two complete remissions, two partial remissions, and five regressions. Median time to progression is 8 months. The median survival time for all patients is 14 months. Projected 2-year survival is 35% (95% CI, 12 to 60%). CONCLUSIONS: Although the number of the patients in this study is small, the response rate and projected 2-year survival of 35% are better than those typically reported for unresectable malignant mesothelioma. Further investigation is warranted in confirmatory trials.

Aged↗
PubMed1996

A controlled trial of long-term administration of intravenous immunoglobulin to prevent late infection and chronic graft-vs.-host disease after marrow transplantation: clinical outcome and effect on subsequent immune recovery.

To determine whether intravenous immunoglobulin (IVIg) given monthly from day 90 to day 360 posttransplantation decreased the incidence of late infection, chronic graft-vs.-host disease (GVHD), and obliterative bronchiolitis after marrow transplantation, patients were assigned randomly to receive either IVIg (500 mg/kg/month) or no IVIg prophylaxis. Participants were registered before transplantation, and 250 patients (123 IVIg and 127 control) were evaluable for events after day 100. The two groups were balanced for age, marrow source, cytomegalovirus (CMV) seropositivity, pretransplantation conditioning, and prophylaxis for infection and GVHD. Between days 100 and 365 posttransplantation, the incidence of bacteremia or septicemia per 100 patient-days of risk was 0.10 in the IVIg group and 0.12 in the controls (p = not significant). During the same period, the incidence of localized infection was marginally higher in control patients than in IVIg recipients (0.44 vs. 0.24, respectively; relative risk [RR] 1.46, p < 0.07). Administration of IVIg prophylaxis had no effect on survival, the incidence of obliterative bronchiolitis, severity of airflow obstruction, or the incidence or mortality of chronic GVHD. After discontinuing IVIg prophylaxis at day 360, subsequent recovery of endogeneous humoral immunity was impaired (serum IgG1 and IgA levels were significantly lower than controls at day 730), and total infections were less common in the second year in control patients than in former IVIg recipients (0.12 vs 0.19, respectively; RR 0.61, p = 0.03). We conclude that in the absence of hypogammaglobulinemia, monthly administration of IVIg given from day 90 to 360 does not reduce late complications and may impair long-term humoral immune recovery after marrow transplantation.

Adolescent↗
PubMed1994

Increased risk of infection in marrow transplant patients receiving methylprednisolone for graft-versus-host disease prevention.

One hundred forty-seven patients with hematologic diseases and treated by allogeneic marrow transplants received graft-versus-host disease (GVHD) prevention with methotrexate and cyclosporine. In addition, 73 of the 147 patients were randomized to receive methylprednisolone during the first 35 days after transplant to improve GVHD prevention, whereas 74 patients were randomized not to receive methylprednisolone. The randomized trial enabled us to examine whether methylprednisolone increased the risk of infection after marrow grafting. Charts of study patients were analyzed retrospectively for infection events including bacteremia, septicemia, and fungemia. The randomization was stratified by diagnosis, patient age, genotypic HLA identity, and assignment to laminar airflow room isolation. All patients were given a short course of methotrexate (no longer than 11 days) and cyclosporine for no longer than 180 days after marrow transplantation. Methylprednisolone was begun on the day of marrow grafting at a dose of 1 mg/kg body weight intravenously in divided AM and PM doses through day 22. Methylprednisolone was administered at a dose of 0.5 mg/kg in divided doses from days 22 through 35, and then discontinued. Infections were analyzed for the time interval ending on day 65 after transplantation, which included the period of methylprednisolone administration and 1 month thereafter. Seventy-one episodes of first infection events were observed in patients receiving methylprednisolone compared with 47 episodes in patients not receiving the drug. Predominant infections were bacteremias, followed in descending order by fungemias and septicemias. The most prevalent organisms cultured were gram-positive bacteria, especially coagulase-negative Staphylococcus and Streptococcus species. Pseudomonas species were the most common gram negative bacteria, and the most prevalent fungus was Candida albicans. Multivariable Cox regression analysis showed that patients receiving methylprednisolone had a 1.5 times higher risk of infection (P = .03), with acute GVHD being another independent risk factor for infections (P = .005). Methylprednisolone, when added to GVHD prevention by methotrexate and cyclosporine, increases the risk of infection during the early posttransplantation period.

Anemia, Aplastic↗
PubMed1993

Summarizing data on survival, relapse, and chronic graft-versus-host disease after bone marrow transplantation: motivation for and description of new methods.

Kaplan-Meier curves are frequently used to summarize survival, relapse, and chronic graft-versus-host disease (GVHD) data in the bone marrow transplant setting. Some fundamental problems with the use of Kaplan-Meier curves for the summary of relapse and GVHD are described. Alternatively, the use of simple probability and conditional probability curves for summarizing relapse incidence and transplant-related mortality is illustrated with previously published data from a randomized clinical trial. Prevalence curves provide an appropriate alternative for the summary of a transient condition such as chronic GVHD. When combined with Kaplan-Meier curves for survival and/or relapse-free survival, these methods provide a more accurate and comprehensive summary of the various marrow transplant outcomes. These methods of display are also applicable to other settings where more than one type of treatment failure can occur and where follow-up time may be variable.

Bone Marrow Transplantation↗
PubMed1993

Acute graft-versus-host disease and the risks for idiopathic pneumonia after marrow transplantation for severe aplastic anemia.

The risks for the development of idiopathic pneumonia after allogeneic BMT were assessed in a case-series review at a single marrow transplantation center. All allogeneic marrow recipients (n = 299) (age range 1-60 years) with severe aplastic anemia (SAA) transplanted from family member donors after conditioning with CY were evaluated. Post-grafting immunosuppression consisted of MTX alone in 205 patients (69%), CY alone in 16 (5%) and a combination of the two in 78 (26%). The incidence estimate for any pneumonia within the first 200 days after transplant was 18% (95% confidence interval = 14-24%). Of 48 cases of pneumonia, CMV infection was documented in 44%, 21% were idiopathic and the remainder were either due to other infections or were not evaluated. The effect of acute GVHD on the incidence of pneumonia was examined using multivariate Cox proportional hazards models which included covariates for potential confounding factors. Consistent with previous reports, acute GVHD was associated with an increased incidence of any pneumonia (relative risk (RR) = 3.5, 95% Cl = 1.9-6.9; p < 0.001). Specifically, acute GVHD also was associated with the largest risk of idiopathic pneumonia (RR = 5.0, 95% Cl = 1.1-22; p = 0.04). In conclusion, recognition of acute GVHD as a risk factor for idiopathic pneumonia suggests that mechanisms in addition to chemoradiation damage are responsible for non-infectious lung injury after BMT.

Acute Disease↗