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PubMed2005

Predictors of depression after stroke: a systematic review of observational studies.

BACKGROUND AND PURPOSE: Although depression is common after stroke, there is uncertainty over its etiology and risk factors, which complicates management. Knowledge of the predictors of depression associated with stroke may allow for the better targeting of therapy, both prevention and treatment. METHODS: We undertook a systematic review of all published, nonexperimental, population-, hospital-, and rehabilitation-based stroke studies (to June 2004) with prospective, consecutive patient recruitment undertaken to identify variables associated with depressive symptoms (or "illness") after stroke. Assessments were made of the quality of studies including the validity of prognostic models. RESULTS: Data were available from 3 population-based studies including 492 patients, 8 hospital-based studies including 15,272 patients, and 9 rehabilitation-based studies including 2170 patients. Physical disability, stroke severity and cognitive impairment were consistently associated with depression. In addition to the common problem of selection bias, major limitations of these studies included variable selection and poor statistical quality and reporting; small sample sizes meant that only a limited range of variables were analyzed in multivariate models. CONCLUSIONS: There is a paucity of well-designed studies of sufficient size to allow stable multivariate predictive models of depression after stroke to be developed. Other than showing that depression is associated with more severe strokes, current evidence does not allow for ready identification of patients most at risk of developing this important complication of stroke.

Aged↗

PubMed2005

Do we have reliable biochemical markers to predict the outcome of critical illness?

Current outcome prediction in critically ill patients relies on the art of clinical judgement and/or the science of prognostication using illness severity scores. The biochemical processes underlying critical illness have increasingly been unravelled. Several biochemical markers reflecting the process of inflammation, immune dysfunction, impaired tissue oxygenation and endocrine alterations have been evaluated for their predictive power in small subpopulations of critically ill patients. However, none of these parameters has been validated in large populations of unselected ICU patients as has been done for the illness severity and organ failure scores. A simple biochemical predictor of ICU mortality will probably remain elusive because the processes underlying critical illness are very complex and heterogeneous. Future prognostic models will need to be far more sophisticated.

Biomarkers↗

PubMed1999

Editorial

Remarkable advances have occurred in wound healing during the past decade in both basic wound biology, as well as applied research into novel treatments of chronic wounds. Newly developed therapies have included the use of growth factors to enhance wound epithelialization, and the use of bioengineered dressings, including skin substitutes. These advances were recently highlighted in the December 1998 JCMS supplement on Wound Care. The lead article in this current issue of JCMS focuses on potential mechanisms to establish quantifiable end points during wound healing, and speculates on the potential relevance to the development of novel therapies. Palenske and Morhenn have found that measurement of skin capacitance is a useful tool in determining endpoints in wound healing. While our ultimate goal in wound healing is to completely re-epithelialize and heal a wound, sometimes interventions are less successful. In evaluating wound healing agents in preclinical or early clinical studies, surrogate markers may be necessary. Skin capacitance may serve as such a marker. In our Point Counterpoint Section, Drs Goldhar and Gratton address the controversial issue of whether dermatologists should promote treatment products. There are strong opinions on both sides of this question, and these two practitioners have concisely addressed the respective sides of this issue. The Grand Rounds Section features an article by Bergman and co-authors in which they describe a case of crusted scabies in association with HTLV-1. Dermatologists are frequently faced with individuals with generalized pruritic eruptions, where scabies is frequently in the differential diagnosis. Indeed, scabies is quite common worldwide. However, crusted scabies, or Norwegian scabies, is much less common, and one clearly has to consider immune deficiencies. This report highlights the association of crusted scabies with immune deficiency. In our CME sections of this issue, we have two important articles. The first, by Dr. Sherri Bale, is a continuation of our Genetic Studies in skin disease research, and the article reviews the area of mapping of hereditary skin disease by focusing on the gene for pseudoxanthoma elasticum. In our day-to- day clinical practice, we frequently discuss the clinical diseases we see in terms of prognosis that is often based on our own individual experience. Evidence based prognostic modelling may provide a very important technique to more accurately assess our patients' outcomes. Drs. Kantor and Margolis review the models and enhance our understanding of these techniques. In this issue of the Journal we introduce a new section of structured book reviews. Two books, Morphologic Diagnosis of Skin Disease and Handbook of Dermatology for Primary Care are reviewed. The structured review provides a concise analysis of these books to allow readers to determine application of these publications to their needs. I hope that each and every one of our readers had a very happy holiday season and I wish you the best for the new year.

Journal Article↗

PubMed2003

Performance of a new clinical grading system for chronic graft-versus-host disease: a multicenter study.

We recently reported 3 risk factors (RFs) at diagnosis of chronic graft-versus-host disease (cGVHD) that were significantly associated with increased nonrelapse mortality. These included extensive skin involvement (ESI), thrombocytopenia (TP), and progressive type of onset (PTO). The hazard ratio (HR) for mortality of the patients with prognostic score (PS) between 0 and 2 (intermediate-risk; 1 RF) compared to those with PS 0 (favorable-risk; 0 RF) was 3.7 (95% CI, 1.4, 9.3); the HR for patients with PS equal to or more than 2 (high-risk; > 1 RF) compared with intermediate-risk group was 6.9 (3.8, 12.4). A rare presentation of TP and PTO without ESI yielded a PS of 1.8 (intermediate-risk). This paper reports the performance of the prognostic model and the individual RFs using data from an additional 1105 patients from University of Nebraska (n = 60), International Bone Marrow Transplantation Registry (n = 708), Fred Hutchinson Cancer Research Center (n = 188), and University of Minnesota (n = 149). The extent of skin involvement was quantified in 3 cohorts using the available data collected in different formats before the analysis. Although the HR for mortality of the patients in the intermediate-risk group versus those in the favorable-risk group ranged from 2.3 to 8.9 across the centers, it was between 1.6 to 6.9 for patients in the high-risk group versus those in the intermediate-risk group. Although TP itself was uniformly associated with increased risk of mortality across all test samples, ESI and PTO showed statistically significant associations with mortality in 1 and 2 cohorts, respectively. In conclusion, the model was predictive of cGVHD-specific survival, but the mortality hazard associated with ESI was lower in each of these test samples compared with the learning sample. Although the new clinical grading based on the model is promising because of its utility across multiple independent data sets, prospective validation is needed.

Adolescent↗

PubMed2005

Advances in the biology and therapy of diffuse large B-cell lymphoma: moving toward a molecularly targeted approach.

Diffuse large B-cell lymphoma (DLBCL) displays striking heterogeneity at the clinical, genetic, and molecular levels. Clinical prognostic models can define a population at high risk for relapse following empiric chemotherapy, although such models do not account for underlying biologic differences among tumors. Commonly observed genetic abnormalities that likely contribute to pathogenesis include translocations of BCL6, BCL2, cMYC, and FAS(CD95) mutations, and aberrant somatic hypermutation. Despite recent advances in empiric chemotherapy, including interval reduction of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and the incorporation of anti-CD20 monoclonal antibodies, a significant proportion of patients still die of their disease. Gene expression profiling has shed light on the molecular heterogeneity within DLBCL by highlighting similarities between subsets of tumors and normal B cells, identifying features associated with unfavorable responses to empiric combination chemotherapy, and defining robust subtypes with comprehensive transcriptional signatures. Such strategies have suggested distinct routes to lymphomagenesis and have identified promising rational therapeutic targets. Additional novel therapies under investigation include those targeting BCL6 and BCL2, as well as development of novel monoclonal antibody-based therapies. Our increasing molecular understanding of the heterogeneous subsets within DLBCL will likely improve the current empiric therapy of DLBCL by identifying rational therapeutic targets in specific disease subtypes.

Antineoplastic Agents↗

PubMed2007

Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome.

Acquired genomic aberrations have been shown to significantly impact survival in several hematologic malignancies. We analyzed the prognostic value of the most frequent chromosomal changes in a large series of patients with newly diagnosed symptomatic myeloma prospectively enrolled in homogeneous therapeutic trials. All the 1064 patients enrolled in the IFM99 trials conducted by the Intergroupe Francophone du Myélome benefited from an interphase fluorescence in situ hybridization analysis performed on purified bone marrow plasma cells. They were systematically screened for the following genomic aberrations: del(13), t(11;14), t(4;14), hyperdiploidy, MYC translocations, and del(17p). Chromosomal changes were observed in 90% of the patients. The del(13), t(11;14), t(4;14), hyperdiploidy, MYC translocations, and del(17p) were present in 48%, 21%, 14%, 39%, 13%, and 11% of the patients, respectively. After a median follow-up of 41 months, univariate statistical analyses revealed that del(13), t(4;14), nonhyperdiploidy, and del(17p) negatively impacted both the event-free survival and the overall survival, whereas t(11;14) and MYC translocations did not influence the prognosis. Multivariate analyses on 513 patients annotated for all the parameters showed that only t(4;14) and del(17p) retained prognostic value for both the event-free and overall survivals. When compared with the currently used International Staging System, this prognostic model compares favorably. In myeloma, the genomic aberrations t(4;14) and del(17p), together with beta2-microglobulin level, are important independent predictors of survival. These findings have implications for the design of risk-adapted treatment strategies.

Adolescent↗

PubMed2004

Underweight is independently associated with mortality in post-operative and non-operative patients admitted to the intensive care unit: a retrospective study.

BACKGROUND: Low and high body mass index (BMI) have been recently shown to be associated with increased and decreased mortality after ICU admission, respectively. The objective of this study was to determine the impact of BMI on mortality and length of stay in patients admitted to the intensive care unit (ICU). METHODS: In this retrospective cohort study, the Acute Physiology and Chronic Health Evaluation (APACHE) III database of patients admitted to the ICUs of a tertiary academic medical center, from January 1997 to September 2002, was crossed with a Hospital Rule-based Systems database to obtain the height and weight of the patients on admission to the ICU. The cohort was divided in post-operative and non-operative groups. We created the following five subgroups based on the BMI: <18.5, 18.5 to 24.9, 25 to 29.9, 30.0 to 39.9, >/= 40.0 Kg/m2. A multiple logistic regression analysis was used to determine the independent impact of BMI on hospital mortality. The ICU length of stay ratio was defined as the ratio of the observed to the predicted LOS. P-value < 0.05 was considered significant. The 95% confidence interval (CI) was calculated for the odds ratio (OR). RESULTS: BMI was available in 19,669 of the 21,790 patients in the APACHE III database; 11,215 (57%) of the patients were admitted post-operatively. BMI < 18.5 was associated with increased mortality in both post-operative (OR = 2.14, 95% CI, 1.39 to 3.28) and non-operative (OR = 1.51, 95% CI, 1.13 to 2.01) patients. Post-operative patients with a BMI between 30.0 to 39.9 had a lower mortality rate (OR = 0.68, 95% CI, 0.49 to 0.94). Post-operative patients with BMI <18.5 or BMI >/= 40 had an ICU length of stay ratio significantly higher than patients with BMI between 18.5 to 24.9. The addition of BMI < 18.5 did not improve significantly the accuracy of our prognostic model in predicting hospital mortality. CONCLUSIONS: Low BMI is associated with higher mortality in both post- and non-operative patients admitted to the ICU. LOS is increased in post-operative patients with low and high BMIs.

Journal Article↗

PubMed2004

Risk management in patients with severe acute pancreatitis.

Primary or secondary infection of necrotized areas by enteral bacteria is considered a primary cause of mortality in patients with severe acute pancreatitis (SAP). Indeed, 20-30% of patients die during the course of the disease from multiple organ dysfunction after infection. This is why strategies such as antibiotic prophylaxis and early surgical intervention are appealing, but the controlled data that support these measures are insufficient. On the other hand, environmental risk factors (e.g. smoking, alcohol) and genetic predisposition have been identified; together, these led to SAP being considered a 'multifactorial' disease. However, this description does not help the intensivist to assess risk in the individual patient. A number of prognostic factors in SAP have been identified, and different scoring systems have been developed that include therapy-associated and patient-related factors. Nevertheless, at present no prognostic model is available that takes into account all of these predictors. Moreover, despite several attempts to create guideline-based strategies, SAP is still characterized by rapidly progressive multiple organ failure and high mortality, and both surgical and conservative therapies yield poor outcomes. This brief commentary highlights the most recent developments in risk management for patients with SAP.

Critical Illness↗

PubMed2025

Bioinformatics identification and validation of pyroptosis-related gene for ischemic stroke.

BACKGROUND: Ischemic stroke (IS) is one of the common and frequent diseases with extremely high lethality and disability in the world, and there is no effective treatment at present. This study aimed to screen hub genes involved in cerebral ischemia/reperfusion injury (CIRI) and pyroptosis, and explore promising intervention targets. METHODS: CIRI-related genes (GSE202659 and GSE131193) and pyroptosis-related genes (PRGs) in mice were obtained from the Gene Expression Omnibus (GEO) and GeneCards database. We screened for LASSO regression to construct a prognostic model of GSE131193 and PRGs and examined by GSE137482. The functional enrichment analysis of Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) were performed on pyroptosis-related differentially expressed genes (PRDEGs) of GSE202659.The key modules for CIRI and pyroptosis were identified by Weight Gene Co-expression Network Analysis (WGCNA). Subsequently, Protein-protein Interaction (PPI) network and the Cytoscape was constructed to screen out hub genes. Used the starBase to predict miRNA interacting with hub genes and constructed mRNA-miRNA-lncRNA interaction networks. CIRI-related Molecular Subtypes were constructed for hub genes. The relationship between immune cells and hub genes was verified via CIBERSORT. Finally, we selected C57BL/6 mice to construct models to confirm hub genes by enzyme linked immunosorbent assay (ELISA), reverse transcription-polymerase chain reaction (RT-PCR), western blot, and Immunofluorescence. RESULTS: A total of 272 PRGs and 35 PRDEGs were screened. An eight-gene risk prediction models were established (AUC = 0.868). GO, KEGG, GSEA and GSVA analyses revealed that PRDEGs were mainly involved in positive regulation of cytokine production, and NOD-like receptor signaling pathway. And then, seven hub genes (Irf1, Icam1, Tlr2, Tnf, Cebpb, Il1rn, and Casp8) were identified by PPI. Icam1, Tnf, Cebpb, Il1rn, and Casp8 had high expression profiles in Cluster2 by hierarchical clustering. The immune infiltration analysis results showed that among the hub genes, Cebpb, Il1rn, and Casp8, showed a significant positive correlation with the degree of NK.Actived, and Icam1 showed a significant negative correlation with B.Cells.Memory. The results of animal experiments significantly demonstrated an upregulation of Irf1, Icam1, Tlr2, Cebpb, and Il1rn. CONCLUSION: Our finding indicated that Irf1, Icam1, Tlr2, Cebpb, and Il1rn are hub genes associated with pyroptosis, and these genes are all associated with different immune cells, so as to provide new targets for the prevention and treatment of IS from the perspective of pyroptosis.

Pyroptosis↗

PubMed1990

Cellular DNA content and prognosis of high-grade soft tissue sarcoma: the Scandinavian Sarcoma Group experience.

The nuclear DNA content of 148 high-grade soft tissue sarcomas of the extremities and trunk was determined by flow cytometry, using tumor material from paraffin-embedded tissue. The patients were part of a prospective randomized clinical trial on the efficacy of adjuvant single-agent chemotherapy with doxorubicin. Chemotherapy did not improve the metastasis-free survival (MFS). After a median follow-up time of 48 months (range, 2 to 97), a multivariate analysis of prognostic factors for developing metastatic disease was performed. DNA aneuploidy was found to be an independent prognostic risk factor in addition to histologic malignancy grade IV, intratumoral vascular invasion, tumor size over 10 cm, and male sex. Patients with none or one risk factor had a 5-year MFS of 79%, with two risk factors 65%, with three risk factors 43%, and with four and five risk factors 0%. About one half (78 of 148) of the patients with three factors or less belonged to a group with a MFS over 60%. The combination of different risk factors, including DNA aneuploidy, seems to be a useful prognostic model for soft tissue sarcomas, which could be of value to select high-risk patients for further trials with adjunctive therapy.

Adolescent↗

PubMed1994

ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study.

PURPOSE: This study attempted to determine the efficacy of the combination of etoposide (VP-16), methyl-prednisolone, and cytarabine (Ara-C) with or without cisplatin in relapsing and refractory adult lymphoma patients. PATIENTS AND METHODS: The first 63 patients were randomized to receive VP-16 40 mg/m2/d for 4 days, methylprednisolone 500 mg intravenously daily for 5 days, and Ara-C 2 g/m2 intravenously over 2 to 3 hours on day 5 with or without cisplatin 25 mg/m2 IV administered by 24-hour infusion for 4 days (ESHA +/- P). Markedly different responses between ESHA (33%) and ESHAP (75%) led to deletion of the ESHA arm. A total of 122 patients on the ESHAP regimen were studied. RESULTS: Forty-five patients (37%) attained a complete remission (CR) and 33 (27%) attained a partial remission (PR), for a total response rate of 64%. The median duration of CR was 20 months, with 28% of remitters still in CR at 3 years. The overall median survival duration was 14 months; the survival rate at 3 years was 31%. Overall time to treatment failure (TTF) showed 10% of all patients to be alive and disease-free at 40 months. Response and survival rates were similar in patients with low-grade (n = 34), intermediate-grade (n = 67), transformed (n = 18), and high-grade (n = 3) lymphoma. The most significant factors for response and survival by multivariate analysis were the serum lactic dehydrogenase (LDH) level, tumor burden, and age (when analyzed as a continuous variable), while prior CR was highly significant by univariate analysis. A significant difference in survival was noted for patients with normal LDH levels and low- or intermediate-tumor burden or patients with low tumor burden and elevated LDH levels (55% 3-year survival rate) versus patients with elevated LDH levels and intermediate or high tumor burden (< 20%). Major toxicities included myelosuppression, with a median granulocyte count of 500/microL and platelet count of 70,000/microL. CONCLUSION: ESHAP was found to be an active, tolerable chemotherapy regimen for relapsing and refractory lymphoma. Applying a prognostic model based on tumor burden and serum LDH level shows significant differences in survival in this patient population.

Adolescent↗

PubMed1996

High-dose chemotherapy as salvage treatment in germ cell tumors: a multivariate analysis of prognostic variables.

PURPOSE: To identify prognostic variables for response and survival in male patients with relapsed or refractory germ cell tumors treated with high-dose chemotherapy (HDCT) and hematopoietic progenitor cell support. PATIENTS AND METHODS: Three hundred ten patients treated with HDCT at four centers in the United States and Europe were retrospectively evaluated. Univariate and multivariate analysis of patient, disease, and treatment characteristics were used for comparisons of response rates and failure-free survival (FFS). RESULTS: The actuarial FFS rate was 32% at 1, 30% at 2, and 29% at 3 years. Multivariate analysis identified progressive disease before HDCT, mediastinal nonseminomatous primary tumor, refractory or absolute refractory disease to conventional-dose cisplatin, and human chorionic gonadotropin (HCG) levels greater than 1,000 U/L before HDCT as independent adverse prognostic variables for FFS after HDCT. These variables were used to identify patients with good, intermediate, and poor prognoses. In the good-risk category, the predicted FFS rate at 2 years was 51%, compared with 27% and 5% in the intermediate-risk and poor-risk categories (P < .001). The increased risk for treatment failure was due to both a significantly lower rate of favorable responses and a significantly higher rate of relapses. Within the prognostic categories, the particular HDCT regimen or higher dosages of carboplatin or etoposide did not have a significant influence on treatment outcome. CONCLUSION: Prognostic variables for treatment response after HDCT can be identified. The proposed prognostic model might help to optimize the use of HDCT in germ cell tumors and warrants validation in future trials.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

Fertility after chemotherapy for testicular germ cell cancers.

PURPOSE: To analyze the probability of recovery of spermatogenesis after orchidectomy and cisplatin-based chemotherapy (CT) for testicular germ cell cancer. PATIENTS AND METHODS: One hundred seventy-eight patients treated between 1979 and 1991 were selected by the requirement of sperm count both pre-CT and post-CT. Counts were classified as normospermic (NS) if more than 10 x 10(6)/mL, oligospermic (OS) if 1 to 9 x 10(6)/mL, and azoospermic (AS) if less than 1 x 10(6)/mL. The median follow-up time after CT before sperm analysis was 30 months. RESULTS: Analysis of 170 patients whose spermatogenesis was reassessed at least 1 year after CT showed that of 89 patients whose pre-CT counts were NS, the post-CT count was NS in 64%, OS in 16%, and AS in 20%. There was clear evidence for continued recovery beyond 1 year; the probability of spermatogenesis increased to 48% by 2 years and 80% by 5 years. There was a significantly higher probability of recovery to OS and NS count levels in the 54 patients treated with carboplatin-rather than cisplatin-based therapy. There was an independent and similar effect of normal pre-CT count. There was a reduced probability to recover to OS in the 26 patients treated with more than four cycles of CT. A prognostic model identified three groups with 25%, 45%, and 82% probabilities of recovering spermatogenesis by 2 years after CT. CONCLUSION: Analysis of pre-CT sperm count together with details of planned treatment can be used to predict recovery of spermatogenesis following germ cell CT.

Adolescent↗

PubMed1998

Suppression of cytogenetic clonal evolution with interferon alfa therapy in patients with Philadelphia chromosome-positive chronic myelogenous leukemia.

PURPOSE: To investigate whether cytogenetic clonal evolution can be suppressed with interferon alfa (IFN-alpha) therapy in patients with chronic myelogenous leukemia (CML). PATIENTS AND METHODS: Ninety patients with CML and cytogenetic clonal evolution who received IFN-alpha-based regimens were analyzed. Clonal evolution was defined as the presence of karyotypic abnormalities in addition to the Philadelphia (Ph) chromosome. Patients were evaluated for the suppression of cytogenetic clonal evolution after therapy, the cytogenetic response, and survival. RESULTS: The median age of the population was 39 years (range, 15 to 70 years), median time from diagnosis to clonal evolution 14 months (range, 0 to 145 months), and median percentage of abnormal metaphases 18% (range, 4% to 100%). Fifty six patients (62%) achieved some suppression of cytogenetic clonal evolution; in 41 patients (46%), the suppression was complete. The overall median survival was 51 months, with 43% alive at 5 years. Patients who achieved a complete suppression of cytogenetic clonal evolution had a median survival of 66 months, with 51% alive at 5 years. Characteristics associated with a better response include a lower percentage of abnormal metaphases, time to cytogenetic clonal evolution of 24 months or less, and absence of other features of accelerated disease. A prognostic classification for cytogenetic clonal evolution defined three groups with complete response (CR) rates of 85%, 34%, and 0% (P < .0001) and median survival times of 58, 31, and 30 months, respectively (P=.02). CONCLUSION: Patients with cytogenetic clonal evolution can respond to IFN-alpha therapy, and this response is associated with longer survival. A previously described prognostic model separates patients into subsets with different probabilities of response to IFN-alpha and survival.

Adolescent↗

PubMed1999

Prognostic factors in children with localized malignant nonseminomatous germ cell tumors.

PURPOSE: Prognostic factors were studied in children older than 1 year who were treated with chemotherapy for extracranial localized malignant non seminomatous germ cell tumors. PATIENTS AND METHODS: Data from two consecutive protocols were pooled. The TGM 85 (1985-1989) protocol consisted of alternating courses of cyclophosphamide, dactinomycin and vinblastine, bleomycin, and cisplatin at a dose of 100 mg/m(2) per course. The TGM 90 (1990-1994) protocol was initiated with carboplatin 400 mg/m(2) substituted for cisplatin as the only modification to the previous protocol. RESULTS: We examined alpha-fetoprotein (AFP) levels, disease stage, and primary site and identified three prognostic groups. Patients with a poor prognosis had either an AFP level >/= 10,000 ng/mL or stage III disease and a sacrococcygeal or mediastinal primary site; such patients represented 46% of the patient population and experienced a 43% 3-year failure-free survival rate and a 77% overall survival rate. Patients with a good prognosis had an AFP level less than 10,000 ng/mL, stage I or II disease, and a testicular, ovarian, perineal, or retroperitoneal primary site; such patients represented 22% of the patient population and experienced no treatment failures. The other patients were classified in the intermediate prognosis group and represented 37% of the patient population, with an 81% 3-year failure-free survival rate and a 92% overall survival rate. CONCLUSION: Initial AFP level, disease stage, and primary site are the most important prognostic factors in this analysis. Prognostic models for pediatric germ cell tumors should allow the stratification of patients for a risk-adapted approach to treatment.

Adolescent↗

PubMed2000

Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia.

PURPOSE: To evaluate the efficacy and toxicity of Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone), a dose-intensive regimen, in adult acute lymphocytic leukemia (ALL). PATIENTS AND METHODS: Adults with newly diagnosed ALL referred since 1992 were entered onto the study; treatment was initiated in 204 patients between 1992 and January 1998. No exclusions were made because of older age, poor performance status, organ dysfunction, or active infection. Median age was 39.5 years; 37% were at least 50 years old. Mature B-cell disease (Burkitt type) was present in 9%, T-cell disease in 17%. Leukocytosis of more than 30 x 10(9)/L was found in 26%, Philadelphia chromosome-positive disease in 16% (20% of patients with assessable metaphases), CNS leukemia at the time of diagnosis in 7%, and a mediastinal mass in 7%. Treatment consisted of four cycles of Hyper-CVAD alternating with four cycles of high-dose methotrexate (MTX) and cytarabine therapy, together with intrathecal CNS prophylaxis and supportive care with antibiotic prophylaxis and granulocyte colony-stimulating factor therapy. Maintenance in patients with nonmature B-cell ALL included 2 years of treatment with mercaptopurine, MTX, vincristine, and prednisone (POMP). RESULTS: Overall, 185 patients (91%) achieved complete remission (CR) and 12 (6%) died during induction therapy. Estimated 5-year survival and 5-year CR rates were 39% and 38%, respectively. The incidence of CNS relapse was low (4%). Compared with 222 patients treated with vincristine, doxorubicin, and dexamethasone (VAD) regimens, our patients had a better CR rate (91% v 75%, P <.01) and CR rate after one course (74% v 55%, P <.01) and better survival (P <.01), and a smaller percentage had more than 5% day 14 blasts (34% v 48%, P =.01). Previous prognostic models remained predictive for outcome with Hyper-CVAD therapy. CONCLUSION: Hyper-CVAD therapy is superior to our previous regimens and should be compared with established regimens in adult ALL.

Adolescent↗

PubMed2001

Circulating neuroblastoma cells detected by reverse transcriptase polymerase chain reaction for tyrosine hydroxylase mRNA are an independent poor prognostic indicator in stage 4 neuroblastoma in children over 1 year.

PURPOSE: In this prospective, multicenter study, the independent prognostic power of neuroblastoma cells detected by reverse transcriptase polymerase chain reaction (RT-PCR) for tyrosine hydroxylase (TH) mRNA was evaluated. PATIENTS AND METHODS: The clinical significance of disease detected by RT-PCR in peripheral blood from children at diagnosis was compared with established prognostic markers [ie, age, lactate dehydrogenase (LDH), neuron-specific enolase, ferritin, and MYCN gene amplification] by multivariate analysis. The value of disease detection by RT-PCR during treatment and follow-up was also examined. RESULTS: TH mRNA was detected in peripheral blood from 33 of 49 (67%) children with stage 4 neuroblastoma > 1 year old at diagnosis and was a significant predictive factor for overall survival [hazard ratio (HR) = 2.40, 95% confidence interval (CI) 1.19 to 4.84, P =.014) and event-free survival (HR = 2.09, 95% CI 1.06 to 4.17, P =.034) in a multivariate analysis. Detection of disease in blood from clinically disease-free children was related to increased risk of death (HR 2.54, 95% CI 1.42 to 4.55, P =.0014). CONCLUSION: TH mRNA in peripheral blood of children with neuroblastoma is a poor prognostic indicator, reflecting the propensity for dissemination via the bloodstream. When combined with a serum LDH > 1500 IU/L, this is the most powerful poor prognostic model at diagnosis for children > 1 year old with stage 4 disease. The detection of TH mRNA in peripheral blood from clinically disease-free children is related to increased risk of relapse and death.

Age Factors↗

PubMed2002

Nomogram for overall survival of patients with progressive metastatic prostate cancer after castration.

PURPOSE: To develop a pretreatment prognostic model for survival of patients with progressive metastatic prostate cancer after castration using parameters that are measured during routine clinical management. PATIENTS AND METHODS: Pretreatment clinical and biochemical determinants from 409 patients enrolled onto 19 consecutive therapeutic protocols from June 1989 through January 2000 were evaluated. The factors selected were age, Karnofsky performance status (KPS), hemoglobin (HGB), prostate-specific antigen (PSA), lactate dehydrogenase (LDH), alkaline phosphatase (ALK), and albumin. These factors were combined in an accelerated failure time regression model to produce a nomogram to predict median, 1-year, and 2-year survival. The nomogram was validated internally and externally using data from a multicenter randomized trial of suramin plus hydrocortisone versus hydrocortisone alone. RESULTS: The median survival of the entire group was 15.8 months (range, 0.9 to 77.8 months); 87% have died. In multivariable analysis, KPS, HGB, ALK, albumin, and LDH were significantly associated with survival (P <.05), whereas age and PSA were not. All seven factors were included in the nomogram. When applied to the external validation data set, the nomogram achieved a concordance index of 0.67. Calibration plots suggested that the nomogram was well calibrated for all predictions. CONCLUSION: A nomogram derived from pretreatment parameters that are measured on a routine basis was constructed. It can be used to predict the median, 1-year, and 2-year survival of patients with progressive castrate metastatic disease with reasonable accuracy. The information is useful to assess prognosis, guide treatment selection, and design clinical trials.

Adult↗