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Prognosis in myeloma.

OBJECTIVE: To review biologic factors that may be useful in determining prognosis in patients with myeloma. DESIGN: The currently available clinical variables and staging systems were assessed for their predictive value in myeloma, and newly proposed prognostic factors were summarized. RESULTS: Because some patients with myeloma may potentially benefit by new, more intensive therapies such as stem cell transplantation or may have prolonged survival with standard therapy, determining factors that would distinguish such patients is important. Independent prognostic factors such as the plasma cell labeling index and beta 2-microglobulin have repeatedly outperformed other prognostic clinical variables and can be combined into a system that identifies poor, intermediate, and good prognostic groups of patients with myeloma. New factors are needed to improve on the predictive value of these two variables. Studies of the biologic features of myelomas have led to the discovery of soluble interleukin 6 receptor (sIL 6R) in the serum. sIL 6R enhances the myeloma cell response to interleukin 6, a central growth factor that affects myeloma cell proliferation. Preliminary studies by the Eastern Cooperative Oncology Group show that sIL 6R predicts survival independent of the plasma cell labeling index and beta 2-microglobulin. Other proposed independent prognostic factors include cytokines and their soluble receptors, regulatory T cells, circulating myeloma cells, myeloma cell precursors, and markers of proliferation, apoptosis, and drug resistance. CONCLUSION: Because of wide variation in duration of survival, the prognosis of patients with myeloma, a fatal bone marrow plasma cell neoplasm, cannot yet be adequately predicted. Better prognostic factors are needed for stratification in clinical trials, counseling of patients, and designing of new therapeutic trials.

Humans↗

Third International Conference on Biology, Prevention and Treatment of Gastrointestinal Malignancies. Cologne, 23-26 September 1998.

R. Mayer (USA), summarizing the data presented during the three-day conference, stressed the importance of the development of new cytotoxic drugs and -- particularly -- biological therapies as forms of treatment for patients with gastrointestinal malignancies. He also acknowledged the increasing application of molecular biology to gastrointestinal cancer through the identification of genetically-defined high-risk patients who merit costly screening techniques and the increased use of molecular 'markers' to serve as prognostic indicators and criteria for stratification in future clinical trials. Dr Mayer cautioned against allowing long-term frustration over poor surgical outcomes in patients with T3-4 esophageal cancer and enthusiasm derived from uncontrolled (i.e., phase II) trials to lead to the premature acceptance of preoperative chemoradiation therapy as standard treatment for such patients in the absence of properly controlled, adequately powered randomized studies. Dr Mayer reinforced the progress that has been made in the adjuvant treatment of colon cancer and noted the increasing number of new randomized studies that have been proposed to further enhance the likelihood for cure, particularly in patients with stage III disease. Dr Mayer concluded by presenting a series of hypothetical agenda items for the Fourth International Conference on Biology, Prevention, and Treatment of Gastrointestinal Malignancies to be held in the new millennium which he hoped would demonstrate the incorporation of biological agents into clinical trials, would document more concerted efforts to study the biology and improve the treatment for pancreatic cancer, and would begin to consider the use of 'risk-adapted' management strategies into clinical trials, based on such preclinical biological markers as intratumoral thymidylate synthase levels, apoptotic indices, allelic deletions, and the like.

Antineoplastic Combined Chemotherapy Protocols↗

Preoperative elevation of serum C--reactive protein is predictive for prognosis in myeloma bone disease after surgery.

We investigated whether preoperative levels of serum C-reactive protein (CRP) and its correlation with tumour clinicopathological findings adds prognostic information beyond the time of diagnosis in patients with myeloma bone disease (MM) to facilitate the surgical decision-making process. Six hundred and fifty-eight myeloma patients were evaluated retrospectively for surgery. Clinicopathological variables of patients who underwent surgery (n=71) were compared between patients with preoperative CRP>or=6 mg l-1 and those with CRP<6 mg l-1. Univariate and multivariate analyses were performed to identify prognostic factors after surgery. Patients with an increase of CRP prior to surgery showed inferior survival compared to patients with normal levels. Patients with normal CRP levels at diagnosis but elevations prior to surgery do seem to have a similar unfavourable overall survival (OS) than patients with an increase both, at diagnosis and at surgery. Conversely, patients with normal CRP levels prior to surgery still have the best OS, irrespective of their basic values. Multivariate analysis revealed preoperative CRP levels above 6 mg l-1 Lactate dehydrogenase (LDH) above normal, and osteolyses in long weight bearing bones as independent predictors of survival. These findings suggest that in patients with MM serum levels of CRP increase during disease activity and might be significantly correlated with specific disease characteristics including adverse prognostic features such as osteolyses in long weight bearing bones. Thus, preoperative elevated CRP serum levels might be considered as independent predictor of prognosis and could provide additional prognostic information for the risk stratification before surgical treatment in patients with myeloma bone disease.

Adult↗

[Flow cytophotometry parameters, hormone receptors and axillary lymph node status as prognostic factors in primary breast cancer].

The prognostic significance of DNA flow cytometric examinations of 247 patients (mean age 57 years; 27-84) with operable breast cancer was analyzed. The findings were compared with biochemically determined steroid-hormone receptors and lymph node status. Forty-two percent of the tumors were diploid and 58% aneuploid; 32% of them had a high S-phase portion (greater than 5%; definition by the crit-level method). S-phase fractions were lower in diploid than in aneuploid tumors (2.5 +/- 2.2% versus 5.5 +/- 3.4%). Both with diploid tumors as well as tumors with a low S-phase fraction (less than 5%), recurrence-free survival was better than with aneuploid tumors (p = 0.02) and tumors with a high S-phase fraction (p = 0.004). A direct proportional relationship was found between the S-phase fraction and the mean recurrence-free interval. As regards overall survival, no significant differences have been detected so far, either for diploid and aneuploid tumors or tumors with low and high S-phase fractions. Using the Cox regression model, the prognostic significance of ploidy status and S-phase, as new factors, independent of age, lymph node and steroid-hormone receptor status, is shown. DNA flow cytometry is suitable for routine clinical use and should be used in particular as an independent prognostic factor for planning and stratification in adjuvant therapeutic studies.

Adult↗

The association between the proximal extension of the clot and the severity of pulmonary embolism (PE): a proposal for a new radiological score for PE.

BACKGROUND: The aim of the study was to investigate the association between the proximal level of the clot and the severity of pulmonary embolism (PE). METHODS: The cohort consisted of 99 consecutive patients with PE diagnosed by multi-detector computed tomography. A new score was constructed by calculating the mean value of the largest affected vessel [sub-segmental = 1, segmental = 2, lobar = 3, main pulmonary artery (MPA) = 4] in each lung. RESULTS: A significant association was found between the most proximal level of PE and pulmonary artery obstruction index (PAOI) (P < 0.0001), right ventricular (RV)/left ventricular (LV) ratio (P < 0.0001), and PaO(2) (P = 0.004). No significant association was found between systolic blood pressure and the level of PE. Troponin-T was elevated in none of the sub-segmental, 5% of segmental, 20% of lobar, and in 56% of PEs in the MPA (P = 0.001). Significant association was found between the proposed score and PAOI (P < 0.0001), RV/LV ratio (P < 0.0001), PaO(2) (P < 0.008). Troponin-T was elevated in 10% of level 1, 0% of level 2, 43% level of 3, 66% of level 4 PE (P < 0.0001). Cut-off level score 4 yielded a sensitivity of 84% and a specificity of 74% for the detection of elevated troponin-T. CONCLUSIONS: In conclusion, the study indicates that both the most proximal level of PE and the proposed score are related to the severity of PE as determined by blood oxygenation, biochemical and radiological parameters and could therefore be of value for rapid risk stratification of PE. However, the prognostic value of these classifications and their clinical significance needs to be evaluated in properly designed studies.

Carbon Dioxide↗

Effects of single-nucleotide polymorphisms in MTHFR and MTRR on mortality and allograft loss in kidney transplant recipients.

BACKGROUND: Plasma total homocysteine (tHcy) is associated with cardiovascular outcomes in kidney transplant recipients (KTR). The methylenetetrahydrofolate-reductase (MTHFR) 677C>T polymorphism, an important determinant of plasma tHcy concentrations, could therefore constitute an important prognostic marker. METHODS: We prospectively followed 710 KTR over >6 years. The MTHFR677C>T, MTHFR1298A>C, MTHFR1793G>A, and MTRR66A>G polymorphisms were analyzed. Demographic, clinical, and transplant-related information was obtained, and patients were followed-up using the Austrian Dialysis and Transplant Registry. Using Cox regression, we established the independent relations of each genotype to the risk of death from any cause, and/or kidney allograft loss. RESULTS: During a median follow-up of 6.1 years, 154 participants died and 260 kidney allografts were lost. Compared to patients with the MTHFR677CC genotype, patients with MTHFR677CT had an adjusted relative mortality risk of 1.02 (95%CI 0.70-1.47), and those with MTHFR677TT of 0.98 (95%CI 0.52-1.85). Compared to MTHFR677CC, the relative risks of kidney allograft loss were 0.93 (95%CI 0.70-1.23; MTHFR677CT) and 0.78 (95%CI 0.47-1.30; MTHFR677TT), respectively. None of the other genotypes were associated with the risks studied, either. These findings did not depend on whether we controlled for tHcy levels. CONCLUSION: This study does not support the routine use of MTHFR or MTRR genotyping for prognostic evaluation or risk-stratification in kidney transplant recipients.

Adult↗

Loss of breast cancer metastasis suppressor 1 protein expression predicts reduced disease-free survival in subsets of breast cancer patients.

PURPOSE: This study aims to determine the effect of loss of breast cancer metastasis suppressor 1 (BRMS1) protein expression on disease-free survival in breast cancer patients stratified by estrogen receptor (ER), progesterone receptor (PR), or HER2 status, and to determine whether loss of BRMS1 protein expression correlated with genomic copy number changes. EXPERIMENTAL DESIGN: A tissue microarray immunohistochemical analysis was done on tumors of 238 newly diagnosed breast cancer patients who underwent surgery at the Cleveland Clinic between January 1, 1995 and December 31, 1996, and a comparison was made with 5-year clinical follow-up data. Genomic copy number changes were determined by array-based comparative genomic hybridization in 47 breast cancer cases from this population and compared with BRMS1 staining. RESULTS: BRMS1 protein expression was lost in nearly 25% of cases. Patients with tumors that were PR negative (P=0.006) or HER2 positive (P=0.039) and <50 years old at diagnosis (P=0.02) were more likely to be BRMS1 negative. No overall correlation between BRMS1 staining and disease-free survival was observed. A significant correlation, however, was seen between loss of BRMS1 protein expression and reduced disease-free survival when stratified by either loss of ER (P=0.008) or PR (P=0.029) or HER2 overexpression (P=0.026). Overall, there was poor correlation between BRMS1 protein staining and copy number status. CONCLUSIONS: These data suggest a mechanistic relationship between BRMS1 expression, hormone receptor status, and HER2 growth factor. BRMS1 staining could potentially be used in patient stratification in conjunction with other prognostic markers. Further, mechanisms other than genomic deletion account for loss of BRMS1 gene expression in breast tumors.

Adult↗

Plasma brain natriuretic peptide as an indicator of left ventricular systolic function and long-term survival after acute myocardial infarction. Comparison with plasma atrial natriuretic peptide and N-terminal proatrial natriuretic peptide.

BACKGROUND: Elevated plasma levels of atrial natriuretic peptide (ANP) and the N-terminal fragment of the ANP prohormone (N-ANP) are associated with decreased left ventricular function and decreased long-term survival after acute myocardial infarction (AMI). Previous data suggest that plasma brain natriuretic peptide (BNP) may increase proportionally more than plasma ANP after AMI and in chronic heart failure. The diagnostic and prognostic value of plasma BNP as an indicator of left ventricular dysfunction and long-term survival after AMI, relative to that of ANP and N-ANP, remain to be established. METHODS AND RESULTS: Venous blood samples for analysis of ANP, N-ANP, and BNP were obtained on day 3 after symptom onset from 131 patients with documented AMI. Left ventricular ejection fraction was determined by echocardiography in a subsample of 79 patients. Twenty-eight cardiovascular and 3 noncardiovascular deaths occurred during the follow-up period (median, 1293 days). All three peptides proved to be powerful predictors of cardiovascular mortality by univariate Cox proportional hazards regression analyses (ANP: P < .0001; N-ANP: P = .0002; BNP: P < .0001). In a multivariate model, plasma BNP (P = .021) but not ANP (P = .638) or N-ANP (P = .782) provided additional prognostic information beyond left ventricular ejection fraction. Logistic regression analysis showed that ANP (P = .003) and N-ANP (P = .027) but not BNP (P = .14) were significantly associated with a left ventricular ejection fraction < or = 45%. CONCLUSIONS: These results suggest that plasma BNP determination provides important, independent prognostic information after AMI. Although plasma ANP appears to be a better predictor of left ventricular dysfunction, plasma BNP may have greater potential to complement standard prognostic indicators used in risk stratification after AMI because of its strong, independent association with long-term survival, enhanced in vitro stability, and simplicity of analysis.

Aged↗

Value of stress myocardial perfusion single photon emission computed tomography in patients with normal resting electrocardiograms: an evaluation of incremental prognostic value and cost-effectiveness.

BACKGROUND: The incremental value and cost-effectiveness of stress single photon emission computed tomography (SPECT) is of unclear added value over clinical and exercise treadmill testing data in patients with normal resting ECGs, a patient subset known to be at relatively lower risk. METHODS AND RESULTS: We identified 3058 consecutive patients who underwent exercise dual isotope SPECT, who on follow-up (mean, 1.6+/-0.5 years; 3.6% lost to follow-up) were found to have 70 hard events (2.3% hard-event rate). Survival analysis used a Cox proportional hazards model, and cost-effectiveness was determined by the cost per hard event identified by strategies with versus without the use of SPECT. In this cohort, a normal study was associated with an exceedingly low hard-event rate (0.4% per year) that increased significantly as a function of the SPECT result. After adjusting for pre-SPECT information, exercise stress SPECT yielded incremental value for the prediction of hard events (chi2 52 to 85, P<0.001) and significantly stratified patients. In patients with intermediate to high likelihood of coronary artery disease after exercise treadmill testing, a cost-effectiveness ratio of $25 134 per hard event identified and a cost of $5417 per reclassification of patient risk were found. Subset analyses revealed similar prognostic, and cost results were present in men, women, and patients with and without prior histories of coronary artery disease. CONCLUSIONS: Stress SPECT yields incremental prognostic value and enhanced risk stratification in patients with normal resting ECGs in a cost-effective manner. These findings are opposite those of previous studies examining anatomic end points in this same population and thus, if confirmed, have significant implications for patient management.

Cohort Studies↗

Cytogenetics and age are major determinants of outcome in intensively treated acute myeloid leukemia patients older than 60 years: results from AMLSG trial AML HD98-B.

To assess the prognostic impact of cytogenetics in elderly patients with acute myeloid leukemia (AML) receiving intensive induction and consolidation treatment according to a single protocol specifically designed for patients above age 60, pretreatment samples from 361 patients registered for the AML HD98-B trial of the German-Austrian AML Study Group were analyzed by chromosome banding and fluorescence in situ hybridization, and cytogenetic findings were correlated with outcome. Using a proportional hazards model with backward selection, 3 prognostic subgroups were identified based on the influence of cytogenetic abnormalities on overall survival (OS): low-risk, t(15;17), and inv(16) in 25 of 361 patients (7%); standard-risk, normal karyotype, t(8;21), t(11q23), +8 within a noncomplex karyotype, and +11 within a noncomplex karyotype in 208 of 361 patients (58%); high-risk, all other aberrations in 128 of 361 patients (35%). On multivariate analysis, high-risk cytogenetics (hazard ratio [HR], 2.24) and age above 70 years (HR, 2.34) were independent prognostic factors affecting OS, and stratification according to these parameters demonstrated that a large subgroup of patients (55%), characterized by age 70 or older or high-risk cytogenetics, or both, had very unfavorable treatment results despite intensive chemotherapy. Thus, karyotype and age are major determinants of outcome in elderly patients with AML.

Acute Disease↗

Factors predictive of tumor-positive nonsentinel lymph nodes after tumor-positive sentinel lymph node dissection for melanoma.

PURPOSE: Approximately 20% of sentinel node (SN) positive melanoma patients have additional non-SN (NSN) metastasis. The rationale for this study was to identify the factors associated with additional nodal disease, as a method to determine which patients may most benefit from completion lymph node dissection (CLND). PATIENTS AND METHODS: During 1990 to 2002, 1,599 patients have undergone SN biopsy at our institute. 19.5% underwent CLND for tumor-positive SN. One hundred ninety-one of these patients had clinicopathologic information available for review. Univariate analyses used chi2 test, Wilcoxson rank sum test, and chi2 test for trend. Multivariate analyses used logistic regression and Wald test. RESULTS: Forty-six (24%) patients had tumor-positive NSN. Univariate analyses showed that primary thickness (Breslow and Clark), primary site, SN tumor size, and number of tumor-positive SNs were significantly associated with tumor-positive NSN. Multivariate analysis (167 patients), confirmed that Breslow and SN tumor size were independently predictive. Sex, histology, ulceration, mitotic index, and SN basin location were not predictive. Risk stratification by the number of prognostic factors present (Breslow > or = 3 mm and SN tumor size > or = 2 mm) showed that probability of finding tumor-positive NSN was 12.3% in the low-risk group (0 factors), 30.9% in the intermediate-risk group (1 factor), and 41.9% in the high-risk group (2 factors). CONCLUSION: Thicker primary and larger SN tumor size are factors that correlate best with tumor-positive NSN. Although none of these factors are absolutely predictive of residual nodal disease, these factors must be strongly considered if the SN contains metastasis, as they provide enhanced risk assessment for NSN tumor-positivity.

Adolescent↗

Cardiovascular disease in U.S. patients with metabolic syndrome, diabetes, and elevated C-reactive protein.

OBJECTIVE: C-reactive protein (CRP) independently predicts cardiovascular disease (CVD); whether it can stratify risk in those with metabolic syndrome and diabetes is not well documented. We evaluated whether elevated CRP levels modify the relationship of metabolic syndrome and diabetes with CVD in U.S. adults. RESEARCH DESIGN AND METHODS: In a cross-sectional study of 3,873 subjects (weighted to 156 million) aged >/=18 years participating in the National Health and Nutrition Examination Survey 1999-2000, subjects were classified as having diabetes, metabolic syndrome according to modified National Cholesterol Education Program criteria, or neither condition by low (<1 mg/l), intermediate (1-3 mg/l), or high (>3 mg/l) CRP levels. Logistic regression examined the odds of CVD by disease condition and CRP group. RESULTS: After adjusting for age, sex, smoking, and total cholesterol, compared with those with neither metabolic syndrome nor diabetes and low CRP levels, the odds of CVD were 1.99 (95% CI 1.10-3.59) for those with no disease and high CRP levels and 2.67 (1.30-5.48) for those with metabolic syndrome and intermediate CRP. Persons with metabolic syndrome but high CRP had an odds ratio (OR) of 3.33 (1.80-6.16), similar to those with diabetes and low CRP (3.21 [1.27-8.09]). The likelihood of CVD was highest in those with diabetes who had intermediate CRP levels (6.01 [2.54-14.20]) and in those with diabetes and high CRP (7.73 [3.99-14.95]). CONCLUSIONS: In this cross-sectional analysis, CVD is more common in those with metabolic syndrome or diabetes who have elevated CRP. Stratification by CRP may add prognostic information in patients with metabolic syndrome or diabetes.

Adult↗

The effect of sentinel lymph node biopsy on the Nottingham Prognostic Index in breast cancer patients.

The Nottingham Prognostic Index (NPI) is a prognostic variable suitable for the stratification of breast cancer patients for adjuvant systemic treatment. The impact of sentinel node biopsy (SNB) and of the assessment of nodal involvement was evaluated in 136 successful SNB procedures completed by axillary dissection (AD). The three strategies assessed included SNB and AD in all cases, AD only in SN-positive cases, and AD only if the SN contained macrometastases. Isolated tumour cells in lymph nodes were regarded either as metastases or as negative findings. The success rate and accuracy of SNB were 90% and 96%, respectively. The NPI was influenced by variations in the surgical staging strategy and the definition of nodal involvement, in at most, five patients. Adjuvant systemic treatment, indicated on the basis of the NPI is less influenced by staging strategies and definitions of metastases than that given on the basis of nodal status alone.

Adult↗

Quantitation of left ventricular mass and function: balancing evidence with dreams.

The quantitative evaluation of the echocardiographic geometry and function for non-ischemic, symmetrically contracting left ventricles is increasingly requested, even when the request is not clinically fully justified and does not take into account the feasibility and reliability of measurements. The general opinion is that, despite a number of technical limitations, the overall information gained from left ventricular (LV) quantitation has a crucial importance for risk stratification, mainly due to the prognostic impact of echocardiographically evaluated LV hypertrophy. This trend tends to automatically transfer epidemiological evidence into clinical application, without consideration of the consequences of the transition of standard errors into single cases. Two recent studies, through differently designed, have demonstrated that the test-retest intraobserver variability of LV mass performs well enough to allow, in most circumstances, the identification of patients with LV hypertrophy. In contrast, the variability of nominal, individual values is high. Tables are available to weight the probability of true biological change when comparing values in the same patient. To a lesser extent, the same conclusions as for LV mass can be applied to measures of systolic function. The technical reliability for measures of diastolic filling is generally good or very good, but the intrapatient variability is probably higher than with measures of LV geometry and systolic function. Moreover, the utility in clinical practice of measures of diastolic filling should be proven. In general, the accurate quantitation of LV geometry and function implies reliable methods and appropriate learning procedures in every echo lab, according to the procedures and the achievements recommended in the current literature. The development of new echocardiographic techniques and the adoption of the procedure of off-line revision of echocardiographic studies might further reduce the variability in the quantitation of measures of LV geometry and function.

Echocardiography↗

[Comorbidity in the elderly: a sample of 2373 hospitalized elderly patients].

The aim of this study was to discuss about prevalence and clinical rilevance of comorbidity in the elderly patients. Our sample included 2373 (mean age 77.8 +/- 8.5; 1302 men and 1071 woman) consecutively admitted to the University Department of Geriatric Medicine of Torino. We examined some demographic variables, cognitive and functional status, main pathologies. Severity of illness was assessed using the C.I.R.S. The coexistence of two or more diseases was 83%: cardiovascular and chronic pulmonary diseases were the most frequently recorded (respectively 68% and 27%). The comorbidity and severity indexes of C.I.R.S. were associated respectively with mortality (O.R. 1.78; C.I. 1.36 - 2.33) and length of hospital staying (O.R. 2.35; C.I. 1.19 - 4.65). Comorbidity is an important specific prognostic indicator for reliable risk stratification of older patients.

Aged↗

Non-Q-wave myocardial infarction: incidence, pathophysiology, and clinical course compared with Q-wave infarction.

Acute myocardial infarction can be stratified into electrocardiographic subsets based on the presence or absence of new Q waves. This stratification has important clinical and prognostic utility. Coronary angiography during acute non-Q-wave compared with Q-wave infarction shows much higher infarct-related artery patency rates (about 75 vs. 10%) and increased coronary collateralization. Culprit legion morphology in non-Q-wave infarction commonly is complex. The frequent demonstration of recurrent clinical ischemia, or residual thallium-201 uptake abnormalities, and metabolic activity on persistent emission tomography suggest the presence of viable myocardium in the distribution of the non-Q-wave infarction usually represents 20-25% of acute myocardial infarctions. The University of California San Diego Collaborative Postinfarction Database and other large studies have found non-Q-wave infarctions to be more common in patients with a history of previous infarction and congestive heart failure, although their mortality during acute hospitalization is lower. However, in long-term followup to one year and beyond, non-Q-wave infarct mortality rates equal those of Q-wave infarction. Patients at low early and late risk of mortality include those with a first infarction who are under age 70, whereas patients with evidence of residual ischemia postinfarction are at increased risk of events. It is interesting to speculate that the settings of unstable angina pectoris, non-Q-wave infarction, and perhaps the picture after thrombolysis for acute myocardial infarction, have pathophysiologic similarities which may carry implications for future research and therapy.

Electrocardiography↗

AML: immunophenotypic heterogeneity and prognostic significance of c-kit expression.

Antigenic profiles in AML that have generally accepted prognostic significance, and allow treatment stratification, have not yet been defined. In a previous report of Ashman et al., the proto-oncogene c-kit defined by binding of the moab YB5.B8 was expressed on about one third of AML cases, mainly of the undifferentiated FAB-subtypes and associated with poor prognosis and overall survival. In this study, the moab 17F11 also directed against the c-kit structure stained 41/47 AML and 6/8 CML blast specimens, whereas all investigated 40 ALL samples were c-kit negative. c-kit was not restricted to any particular, undifferentiated FAB-subtype, but found in 9/9 AML-M0/M1, 18/19 AML-M2, 0/1 AML-M3, 11/13 AML-M4 and 3/5 AML-M5 subtypes. Immunophenotypical analysis showed no restriction of c-kit expression to immature, CD34+ precursors, but c-kit was also expressed on CD4+ CD34- precursor cells differentiating towards the monocyte lineage. In addition, multi-color labelings revealed an extraordinary heterogeneity of concomitant antigen expression on c-kit+ cells 10/36 c-kit+ CD34+ samples expressing CD56 and 16/36 c-kit+ CD34+ samples being CD7 positive; two c-kit+ CD34+ specimens carried the B-cell antigen CD19. In correlation to clinical outcome c-kit expression as single parameter was not predictive for poor response to therapy and short survival as previously suggested.

Aged↗

Estimate of expected survival at diagnosis in Hodgkin's disease: a means of weighting prognostic factors and a tool for treatment choice and clinical research. A report from the International Database on Hodgkin's Disease (IDHD).

PURPOSE: The aim was to identify a mathematical model that, when fitted with the survival time distribution of a Hodgkin's disease population, would provide a reliable estimate of expected survival at diagnosis for any new Hodgkin patient. This model would be based upon a multivariable selection of the best prognostic factors evaluable at diagnosis and its forecast could be of assistance in the choice of treatment. METHODS: The study sample consisted of the 5,023 patients whose basic clinical information was collected into the IDHD. These were people treated with standard protocols over the last two decades in 18 institutions. Several survival time distributions (exponential, Weibull, Gompertz, log-logistic and log-normal) were investigated to find the one that best fit the data and to relate its parameters to patient prognostic characteristics. RESULTS: The log-normal model provided the best fit for the data. The most statistically significant prognostic covariates were stage, age, histotype, B symptoms, serum albumin, sex and involved area distribution. Mediastinal, extranodal or bone marrow involvement, erythrocyte sedimentation rate, hemoglobin, serum alkaline phosphatase and lactate dehydrogenase did not add significant information. An equation containing these seven variables was derived to estimate median survival. Five distinct prognostic classes were identified by four cut-off values for this estimate. CONCLUSIONS: Direct use of estimated median survival or allocating each patient into one of the five prognostic classes allows better tailoring of clinical strategies according to prognostic characteristics, more accurate patient stratification and evaluation of results in clinical trials and metaanalyses. Instructions are given for using this tool for both clinical and investigational purposes.

Adolescent↗