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A prognostic-factor risk index in advanced non-small-cell lung cancer treated with cisplatin-containing combination chemotherapy.

Prognostic factors for response and survival were retrospectively evaluated in 192 previously untreated patients with advanced non-small-cell lung cancer (NSCLC) who had received either vindesine plus cisplatin or mitomycin plus vindesine plus cisplatin as initial treatment. Univariate analysis demonstrated that squamous-cell histology, early stage, and a small number of metastatic sites were favorable prognostic factors for response to chemotherapy. Multivariate analysis using Cox's proportional hazard model indicated that the number of metastatic sites was the only significant pretreatment factor for response (P = 0.0005). Multivariate regression analysis revealed that the number of metastatic sites (P = 0.0002), sex (P = 0.0009), serum albumen levels (P = 0.0018), performance status (P = 0.0026) and lactic dehydrogenase values (P = 0.0026) contributed independently to survival. On the basis of these five prognostic factors, a prognostic index for survival was used to define three prognostic groupings (good, intermediate, and poor) for survival (median survival, 16.5 vs 9.4 vs 4.6 months; P = 0.0001). This particular regression model should aid in the design and analysis of new treatment strategies and may be useful for indirect comparisons of different studies carried out in similar patient populations.

Adenocarcinoma↗

At convenience and systematic random sampling: effects on the prognostic value of nuclear area assessments in breast cancer patients.

This study compares the influence of two different nuclear sampling methods on the prognostic value of assessments of mean and standard deviation of nuclear area (MNA, SDNA) in 191 consecutive invasive breast cancer patients with long term follow up. The first sampling method used was 'at convenience' sampling (ACS); the second, systematic random sampling (SRS). Both sampling methods were tested with a sample size of 50 nuclei (ACS-50 and SRS-50). To determine whether, besides the sampling methods, sample size had impact on prognostic value as well, the SRS method was also tested using a sample size of 100 nuclei (SRS-100). SDNA values were systematically lower for ACS, obviously due to (unconsciously) not including small and large nuclei. Testing prognostic value of a series of cut off points, MNA and SDNA values assessed by the SRS method were prognostically significantly stronger than the values obtained by the ACS method. This was confirmed in Cox regression analysis. For the MNA, the Mantel-Cox p-values from SRS-50 and SRS-100 measurements were not significantly different. However, for the SDNA, SRS-100 yielded significantly lower p-values than SRS-50. In conclusion, compared with the 'at convenience' nuclear sampling method, systematic random sampling of nuclei is not only superior with respect to reproducibility of results, but also provides a better prognostic value in patients with invasive breast cancer.

Biopsy↗

The important prognostic value of Ki-67 expression as determined by image analysis in breast cancer.

A series of 191 female breast carcinomas (with long-term follow-up) were analysed immunohistochemically (with a monoclonal MIB1 antibody) for Ki-67 (a proliferation marker) expression with special reference to well-established prognostic factors and patient survival. Expression of Ki-67 was directly related to the S-phase fraction (P < 0.0001), the volume-corrected mitotic index (P < 0.0001), histological grade (P < 0.0001), the apoptotic index (P < 0.0001), oestrogen and progesterose receptor content (P < 0.0001 for both) and p53 accumulation (P = 0.001). No correlation was found between Ki-67 expression and lymph node status (P = 0.25), metastasis at operation (n = 0.81) or tumour size (n = 0.38). The proliferation rate, as measured by image analysis of Ki-67 expression, predicted survival in the entire cohort (P = 0.001) and in axillary-lymph-node-negative (ANN) patients (P = 0.003). The difference in recurrence-free survival between the high- and low-expression groups was greatest in ANN tumours, 40% (P = 0.008). In axillary-lymph-node-positive tumours, the Ki-67 expression was not significantly related to recurrence-free survival (P = 0.723). The results of multivariate survival analysis showed that tumour size, axillary lymph node status, and mitotic index were independent prognostic factors in the entire series whereas, in ANN cases, tumour size and Ki-67 labelling were independent prognostic factors. These findings imply that Ki-67 expression could be an important prognostic determinant in breast cancer. Because of the evident loss of the predictive power of tumour size in the 1990s, the prognostic value of Ki-67 expression may even be accentuated in the currently diagnosed small breast carcinomas.

Breast Neoplasms↗

Confirmation and improvement of Sokal's prognostic classification of Ph+ chronic myeloid leukemia: the value of early evaluation of the course of the disease. The Italian Cooperative Study Group on Chronic Myeloid Leukemia.

A simple prognostic classification of Ph+ chronic myeloid leukemia (CML) was proposed in 1984 by an international study Group and is now widely used for clinical purposes. That study was retrospective, and was based on disease features at diagnosis. To test prospectively and to check the value of the classification, and to investigate if additional information on the early course of leukemia can help in refining the prognosis, 505 Ph+, nonblastic and nontransplanted patients first registered between 1984 and 1986 were followed up to June 1990. It was found that the prognostic formulation predicted survival in that series exactly the same way as in the original series (median survival: greater than 60 months for low-risk patients, 46 months for intermediate-risk patients, and 32 months for high-risk ones). It was also found that several objective or subjective assessments of disease course during the first 8 months after diagnosis were significantly related to survival length within any risk group. This study provides full confirmation of Sokal's international prognostic classification, and shows that the definition of prognosis can be improved some months after diagnosis by taking into account the course of the disease and the response to therapy. These conclusions apply to patients receiving conventional treatment. The course of Ph+ chronic myeloid leukemia (CML) is rigidly programmed to progress to an acute phase, which is called blastic metamorphosis (BM) and which can develop either suddenly (blastic crisis) or by a slow progression (accelerated phase). In all recent series, 2-year survival ranged between 65% and 80%, median survival was slightly shorter than 4 years, and the proportion of patients who were still alive after 10 years was less than 10%. However, a number of prognostic variables were identified and a prognostic formulation that was elaborated by an international study was shown to provide a reliable estimate of survival length and is currently used for that purpose. The value of that formulation, and the formulation itself, require periodical controls and revisions. For that purpose, the Italian Cooperative Study Group on CML registered and followed up all CML patients who were first seen between 1984 and 1986. A very preliminary analysis of that cohort of patients has already been performed, but it was limited to the first 2 years after diagnosis.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans↗

Prognostic factors and natural history in lymph node-negative breast cancer patients.

The prognostic significance of clinical and histological factors as well as hormone receptors was analyzed in a population of 3,064 lymph node-negative breast cancer patients operated in the Stockholm region between 1976 and 1988. None of these patients received systemic adjuvant treatment. Multivariate analysis showed that only histological tumor size, number of examined axillary lymph nodes, and progesterone receptors were independent prognostic factors in terms of recurrence-free interval. An individual risk of recurrence was calculated taking into account these three factors to discriminate between three groups of patients with a risk of less than 15%, 15-25%, and more than 25% of recurrence at 5 years. Similar results were obtained taking into account only the first two factors. The prognostic information added by the knowledge of progesterone receptors only changed the recurrence rate in approximately 3%. This study showed that conventional prognostic factors permit the identification of high risk lymph node-negative breast cancer patients. Results obtained by the use of new more sophisticated factors should be compared with those obtained analyzing strong conventional prognostic factors.

Breast Neoplasms↗

The importance of neural invasion (NI) as a prognostic factor in diffuse invasive gastric cancer.

The relationship between histological factors, including neural invasion (NI), and survival rates in patients with Borrmann type IV diffuse invasive gastric cancer was examined to determine the significance of NI as a prognostic factor. NI was studied histochemically in 75 patients who underwent resection after 1982, 37 of whom underwent curative resection. The 3-year and 5-year survival rates of the 37 patients who underwent curative resection were 37.2% and 12.7%, respectively. Recurrence was detected as peritoneal dissemination in 19 of those patients (82.6%), and the most significant prognostic factor was the depth of wall invasion (P < 0.01). While NI (P = 0.06) and lymph node metastasis (P = 0.09) appeared to be prognostic factors, there were no significant differences. Therefore, the depth of wall invasion was classified as T2 and T3 or 4 to examine the association of NI and lymph node metastasis with prognosis, whereby NI was shown to be a significant prognostic factor in T2. In conclusion, NI may be a significant prognostic factor in patients with wall invasion of T2 without serosal invasion, as it provides a pathway for the progression to peritoneal dissemination.

Disease Progression↗

Prognostic factors including neoadjuvant chemotherapy in Mexican children with neuroblastoma.

INTRODUCTION: There are several prognostic factors in children with neuroblastoma that have been outlined in the international literature. MATERIAL AND METHODS: A retrospective study was carried out analysing the medical records of patients with the pathological diagnosis of neuroblastoma seen at the Department of Oncology from the Instituto Nacional de Pediatriá (Mexico) between January 1984 to January 1997. A total of 32 clinical prognostic factors were assess in our population. RESULTS: Fifty five patients whose age ranged from 1 to 168 months old, mean of 35 months were included. Out of 32 prognostic factors only 6 including sex (p= 0.0039), metastatic disease to bone (p= 0.003), bone marrow involvement (p= 0.0027), staging system (p= 0.000015), surgical treatment (p 0,0022) and neoadjuvant chemotherapy (p.005) were the most significant. CONCLUSIONS: It was concluded that besides the prognostic factors outlined, neoadjuvant chemotherapy is of utmost importance. It decreases tumor volume and allows surgery to be more successful, therefore believing that this variable represents a specific prognostic factor in cases of advanced neuroblastoma.

Adolescent↗

Prognostic value of myocardial hypoperfusion indexes in patients with suspected or known coronary artery disease.

BACKGROUND: We evaluated the prognostic value of exercise 201Tl indexes of myocardial hypoperfusion in patients with suspected or known coronary artery disease. METHODS AND RESULTS: Patients were divided into two groups: group I consisted of 332 patients with diagnostic electrocardiographic stress test results and group II consisted of 144 patients with nondiagnostic (inadequate or uninterpretable) stress electrocardiograms. At the 2-year follow-up, 20 hard events (16 cardiac deaths and 4 nonfatal myocardial infarctions) and 80 soft events (coronary revascularization procedures) occurred in group I. Considering total events, thallium imaging provided significant prognostic information in addition to clinical and exercise stress test data in the total study population (p < 0.001) and in patients with previous myocardial infarction (p < 0.001); in patients without previous infarction, thallium imaging added incremental prognostic value only in those with positive electrocardiographic stress test results (p < 0.01). When only hard events were considered, thallium variables added further information only in patients with previous myocardial infarction (p < 0.05). In group II at the end of follow-up, 15 hard and 39 soft events had occurred. In these patients occurrence of total (p < 0.001), hard (p < 0.05), and soft (p < 0.001) events was higher in those with abnormal thallium scintigraphic results than in those without. Moreover, no clinical and exercise variable, except history of myocardial infarction, was significantly related to outcome, whereas both indexes of extent and severity of hypoperfusion were significant. CONCLUSIONS: The results of this study demonstrate that scintigraphic indexes of myocardial hypoperfusion obtained by qualitative planar thallium imaging give unique prognostic information in patients with nondiagnostic electrocardiographic stress test results. Thallium imaging provides incremental prognostic information even in patients with diagnostic electrocardiographic stress test results but not in the low-risk subset of patients without previous infarction who have negative electrocardiographic stress test results.

Adult↗

Immunohistochemical Detection of p53 and c-erbB-2 Proteins: Prognostic Significance in Operable Breast Cancer.

We examined the associations of p53 expression and/or c-erbB-2 expression with Ag-NOR counts and clinicopathologic variables in 111 breast cancer patients, and assessed whether expression of either p53or c-erbB-2 would be useful prognostic indicators. There was no significant association between p53 expression and c-erbB-2 expression, but p53 expression and c-erbB-2 expression, especially in combination, were shown to be significantly associated with Ag-NOR counts and axillary lymph node metastasis. Although p53 expression and c-erbB-2 expression were significant prognostic factors by univariate analysis, they did not appear to be independent prognostic factors by multivariate analysis, in which nodal status was introduced using the Cox model. When nodal status was excluded from the model, however, concurrent p53 and c-erbB-2 expression did have a significant prognostic value. Therefore, it was suggested that concurrent p53 and c-erbB-2 expression provides valuable prognostic information for breast cancer patients in whom axillary lymph node dissection has not been performed.

Journal Article↗

Prognostic factors in glioblastoma multiforme. 10 years experience of a single institution.

BACKGROUND: To analyze prognostic factors in patients with a glioblastoma multiforme treated in an academic institute over the last 10 years. PATIENTS AND METHOD: From 1988 to 1998, 198 patients with pathologically confirmed glioblastoma multiforme were analyzed. Five radiation schedules were used mainly based on pretreatment selection criteria: 1. 60 Gy in 30 fractions followed by an interstitial iridium-192 (Ir-192) boost for selected patients with a good performance and a small circumscribed tumor, 2. 66 Gy in 33 fractions for good performance patients, 3. 40 Gy in eight fractions or 4. 28 Gy in four fractions for poor prognostic patients and 5. no irradiation. RESULTS: Median survival was 16 months, 7 months, 5.6 months, 6.6 months and 1.8 months for the groups treated with Ir-192, 66 Gy, 40 Gy, 28 Gy and the group without treatment, respectively. No significant improvement in survival was encountered over the last 10 years. At multivariate analysis patients treated with a hypofractionated scheme showed a similar survival probability and duration of palliative effect compared to the conventionally fractionated group. The poor prognostic groups receiving radiotherapy had a highly significant better survival compared to the no-treatment group. Patients treated with an Ir-192 boost had a better median survival compared to a historical group matched on selection criteria but without boost treatment (16 vs 9.7 months, n.s.). However, survival at 2 years was similar. Analysis on pretreatment characteristics at multivariate analysis revealed age, neurological performance, addition of radiotherapy, total resection, tumor size post surgery and deterioration before start of radiotherapy (borderline) as significant prognostic factors for survival. CONCLUSION: Despite technical developments in surgery and radiotherapy over the last 10 years, survival of patients with a glioblastoma multiforme has not improved in our institution. The analysis of prognostic factors corresponded well with data from the literature. A short hypofractionated scheme seems to be a more appropriate treatment for patients with intermediate or poor prognosis as compared to a conventional scheme. The benefit in median survival for patients treated with an interstitial boost is partly explained by patient selection. Since there were no long-term survivors with this boost treatment, its clinical value, if there is one, is still limited.

Actuarial Analysis↗

Prognostic value of DNA ploidy in 653 Japanese women with node-negative breast cancer.

BACKGROUND: The prognostic value of DNA ploidy has been extensively studied in breast cancer; however, the results remain controversial. Flow cytometry (FCM) studies of DNA ploidy on frozen sections have not yet been performed in a large series of Japanese women with node-negative breast cancer. METHODS: An FCM analysis of DNA ploidy was performed on frozen sections of node-negative breast cancer from 653 Japanese women, with a mean follow-up duration of 46 months. RESULTS: Three hundred and twenty-four (49.6%) patients showed a diploid tumor, while 329 (50.4%) showed an aneuploid tumor. There was a significant correlation between DNA ploidy and estrogen receptor (ER) status. Patients with an aneuploid tumor had a significantly worse outcome in terms of both disease-free survival (DFS; P = 0.0116) and overall survival (OS: P = 0.0492) than those with a diploid tumor, while the same effect, in terms of DFS, was also seen in ER-positive breast cancer. Multivariate analyses indicated DNA ploidy to be an independent prognostic factor for DFS, while DNA ploidy and tumor size were found to be independent prognostic factors for OS. DNA ploidy was also shown to be an independent prognostic factor for DFS in ER-positive breast cancer. CONCLUSION: Our findings demonstrated DNA ploidy, based on FCM, to have an important prognostic value in Japanese women with node-negative breast cancer.

Adult↗

Prognostic factors in 2230 Korean colorectal cancer patients: analysis of consecutively operated cases.

To define the prognostic factors in Korean colorectal cancer patients, univariate and multivariate analysis were performed on data from 2230 consecutive patients who underwent resection for colorectal cancer at the Seoul National University Hospital. The prognostic variables used for the analysis included patient's age, gender, bowel obstruction, bleeding, symptom duration, preoperative leukocyte count, preoperative serum carcinoembryonic antigen (CEA) level, Dukes' stage, tumor location, tumor size, depth of bowel wall invasion, number of lymph node metastases, histologic differentiation, and gross morphology of tumor. The overall 5-year survival rate was 62%. In the univariate analysis, all the factors except sex, symptom duration, and tumor size were associated with prognosis. Among the factors significant in the univariate analysis, Dukes' stage (p < 0.001), number of lymph node metastasis (p < 0.001), CEA level (p < 0.001), tumor location (p = 0.003), gross morphology of tumor (p = 0.017), and depth of bowel wall invasion (p = 0.031) were significant in the multivariate analysis. Several differences in prognostic factors between colon cancer and rectal cancer were observed. In the multivariate analysis, gross tumor morphology was significant only for colon cancer, and histologic differentiation was significant only for rectal cancer. Lymph node metastasis was an independent prognostic variable for both colon and rectal cancer, but its significance was more prominent for rectal cancer. Although Dukes' stage is the most reliable prognostic predictor, this study shows that other factors (preoperative CEA level, gross morphology of tumor, location of tumor, nodal status) also provide important information for the outcome of the patient.

Adult↗

Hemoglobin as an independent prognostic factor in the radiotherapy of head and neck tumors.

PURPOSE: The purpose of this study was to analyze the prognostic value of baseline hemoglobin levels before radiotherapy in patients with head and neck tumors. PATIENTS AND METHODS: In a retrospective study with a median follow-up of 43 months, we analyzed the results of 214 patients irradiated for head and neck cancer between January 1, 1990 and January 1, 1998 (180 men and 34 women; median age 58 years). The treatment concept consisted in adjuvant radiotherapy in 58 patients, 77 patients received definitive radiochemotherapy, 42 patients definitive radiotherapy, and 37 patients reirradiation for in-field recurrence. Baseline hemoglobin values were divided in four groups of the same patient number (quartiles). Several known prognostic factors like sex, age, tumor stage, histologic grading, performance status, and treatment scheme were analyzed for their influence on overall and event-free survival and correlated with pretreatment hemoglobin values (Kaplan-Meier method). In addition, univariate und multivariate logistic regression analyses were carried out to evaluate the effect of baseline hemoglobin on response rates. RESULTS: The median survival (event-free survival) of all patients amounted to 15 months (10 months). 25%, 50%, and 75% of patients had hemoglobin values < 11.2 g/dl, < 12.7 g/dl, and < 13.9 g/dl, respectively. In the univariate analysis, the following variables were significant prognostic factors for overall/event-free survival (log-rank test): treatment concept (p < 0.001/p < 0.001), tumor stage (p < 0.001/p < 0.001), general condition (p < 0.001/p < 0.001), and pretreatment hemoglobin (p = 0.014/p = 0.05). Multivariate analysis (Cox) proved these parameters to be independent of each other. In addition, response rate after radiation showed a strong association between hemoglobin and local control probability (p = 0.02). CONCLUSION: In this retrospective analysis, baseline hemoglobin level was shown to be an independent significant prognostic factor in radiotherapy of head and neck cancer patients. Therefore, the value of tumor anemia as a prognostic factor should be emphasized more.

Adult↗

Prognostic factors for brain metastases after whole brain radiotherapy. Data from a single institution.

PURPOSE: Prognostic factors for overall survival of patients treated for brain metastases with whole brain radiotherapy (WBRT) at a single institution were retrospectively evaluated, and the validity of the RTOG recursive partitioning analysis (RPA) for prognostic classes was assessed. PATIENTS AND METHODS: The data of all patients (n = 268) with brain metastases from solid tumors homogeneously treated between 01/1997 and 09/1999 at the University of Heidelberg, Germany, with WBRT without surgery or radiosurgery were reviewed. 13 different patient- and therapy-related variables were evaluated for prognosis. Second, a grouping of the study cohort was performed according to the RTOG RPA prognostic classes. RESULTS: Median survival of the whole population after the start of WBRT was 3.8 months. The 1-year survival rate was 19%. Multivariate analysis revealed that only the Karnofsky performance status, control of the primary and no extracranial disease were independent prognostic factors for overall survival. These are also the main determinants of the RTOG RPA classes. Applying the RTOG RPA classes to the authors' data set revealed three subgroups with significantly different prognosis. CONCLUSION: Based on this analysis, prognostic factors for survival after WBRT in patients with brain metastases could be identified. A total of 19% (n = 44/232) survived > or = 1 year, whereas overall survival was poor. The potential value of the RPA classes in estimating the patient's prognosis could be confirmed.

Adolescent↗

11C-methionine PET as a prognostic marker in patients with glioma: comparison with 18F-FDG PET.

PURPOSE: The purpose of this study was to compare the prognostic value of 11C-methionine (MET) and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in glioma patients. METHODS: The study population comprised 47 patients with gliomas (19 glioblastoma, 28 others). Pretreatment magnetic resonance imaging, MET PET and FDG PET were performed within a time interval of 2 weeks in all patients. The uptake ratio and standard uptake values were calculated. Univariate and multivariate analyses were done to determine significant prognostic factors. Ki-67 index was measured by immunohistochemical staining, and compared with FDG and MET uptake in glioma. RESULTS: Among the several clinicopathological prognostic factors, tumour pathology (glioblastoma or not), age (> or =60 or <60 years), Karnofsky performance status (KPS) (> or =70 or <70) and MET PET (higher uptake or not compared with normal cortex) were found to be significant predictors by univariate analysis. In multivariate analysis, tumour pathology, KPS and MET PET were identified as significant independent predictors. The Ki-67 proliferation index was significantly correlated with MET uptake (r=0.64), but not with FDG uptake. CONCLUSION: Compared with FDG PET in glioma, MET PET was an independent significant prognostic factor and MET uptake was correlated with cellular proliferation. MET PET may be a useful biological prognostic marker in glioma patients.

Brain Neoplasms↗

Dual-phase 18F-fluoro-2-deoxy-D-glucose positron emission tomography as a prognostic parameter in patients with pancreatic cancer.

PURPOSE: Recently, dual-phase 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) was shown to be useful in the differentiation between malignant and benign pancreatic lesions. The aim of this prospective study was to evaluate the value of dual-phase FDG-PET as a prognostic parameter in patients with pancreatic cancer. METHODS: Sixty-five consecutive patients with pancreatic cancer underwent dual-phase FDG-PET. Standardised uptake values at 1 h (SUV1) and 2 h (SUV2) following the injection of FDG were determined, and the retention index (RI) was calculated by dividing the difference between SUV2 and SUV1 by SUV1. The prognostic value of SUV1, SUV2 and RI was analysed, along with the various clinical and biochemical parameters. RESULTS: Multivariate analysis showed that only three factors had an independent association with longer patient survival: female gender (p<0.01), TNM stage I-III (p<0.05) and RI>10% (p<0.01). Neither SUV1 nor SUV2 showed any prognostic significance. Combination of tumour stage and RI allowed more accurate prognostic evaluation. Patients at stage I-III with RI>10% survived longer than did patients at the same stage with RI<10% (15.3 vs 11.5 months, p<0.01). Patients at stage IV with RI>10% had an intermediate prognosis, with a median survival of 9.5 months; patients at stage IV with RI<10% showed the worst prognosis, with a median survival of 4.9 months (p<0.05). CONCLUSION: RI calculated with dual-phase FDG-PET can be used not only as a tool for initial diagnosis and staging of pancreatic cancer but also as a strong independent prognostic parameter that can allow accurate identification of those patients who will benefit from intensive anticancer treatment at different stages of the disease.

Female↗

Salvage by timed sequential chemotherapy in primary resistant acute myeloid leukemia: analysis of prognostic factors.

Primary resistant acute myeloid leukemia (AML) has a very poor prognosis. Etoposide-mitoxantrone-cytarabine (EMA) timed sequential chemotherapy including a first sequence combining mitoxantrone (12 mg/m(2) per day over 3 days) with cytarabine (500 mg/m(2) per day over the same period), and a second sequence consisting in etoposide (200 mg/m(2) per day for 3 days) and cytarabine as in the first sequence, has been proposed as a salvage regimen. Over a 10-year period, 66 primary resistant AML patients have been treated by EMA salvage chemotherapy. All patients displayed intermediate- or high-risk karyotypic abnormalities. Of the 66 patients, 24 [36%, 95% confidence interval (CI): 25-49%] achieved complete remission (CR). Thirty-eight patients were resistant to EMA chemotherapy and four patients died from toxicity during aplasia. After CR achievement, 18 patients received consolidation therapy. Five patients with an HLA-identical sibling donor underwent allogeneic stem cell transplantation (SCT), one patient received autologous SCT, two patients received a second course of EMA chemotherapy, and ten were scheduled for 6-monthly maintenance courses (mini-EMA). Median follow-up was 7.3 years. At the time of analysis, 21 of the 24 patients (87%) who achieved CR have relapsed. Median disease-free survival (DFS) was 5 months (95% CI: 4.3-7.7 months). Median overall survival (OS) was 5 months (95% CI: 3.8-6.7 months). There were only two long-term remitters (3%). In the univariate analysis, CR achievement was mainly related to white blood cell (WBC) count at the time of starting salvage therapy with poorer outcome for patients with more aggressive leukemia (WBC count > or =10 x 10(9)/l) (CR rates: 50% vs 10%, p<0.001). Overall survival was also influence by WBC count (median OS: 7.2 months vs 2.8 months, respectively, for WBC or =10 x 10(9)/l, p<0.0001). Initial karyotype was not a significant prognostic factor either for CR achievement or for DFS or OS when comparing patients with normal karyotype and those with chromosomal abnormality. In multivariate analysis, WBC count less than 10 x 10(9)/l with the absence of circulating blasts at the time of starting salvage therapy appeared to be of favorable prognostic value for CR achievement ( p=0.002), while WBC count less than 10 x 10(9)/l appeared to be of favorable prognostic value for survival ( p<0.0001). Using these two objective parameters of proven significance, we devised a prognostic system of immediate clinical utility for prognostic stratification and risk-adapted therapeutic choices. Patients with both factors (WBC count <10 x 10(9)/l and no circulating blasts) or with at least one at the time of starting salvage therapy had a CR rate of 50% and were therefore candidates for intensified post-remission therapy. All other patients displayed a very poor outcome and must be oriented after failure of first-line therapy to alternate therapeutic programs based on investigational drugs.

Adolescent↗

Modern diagnostics in chronic myeloproliferative diseases (CMPDs).

According to the new WHO classification a group of chronic myeloproliferative diseases (CMPDs) were defined: chronic myeloid leukemia (CML), chronic neutrophilic leukemia (CNL), chronic eosinophilic leukemia and hypereosinophilic syndrome (CEL/HES), polycythemia vera (PV), chronic idiopathic myelofibrosis (with extramedullary hematopoiesis, CIMF), essential thrombocythemia (ET), and so called CMPD/unclassifiable. As clinical features and laboratory findings differ widely between these diseases several diagnostic approaches are mandatory at diagnosis for classification and are needed also for follow up studies, especially for the measurement of minimal residual disease (MRD). We here outline the laboratory set up at diagnosis and during follow up in CMPDs with specific focus on the respective therapeutical consequences. Only by using a comprehensive diagnostic panel including cytomorphology, cytogenetics, and molecular genetic methods establishing the correct diagnosis, optimizing treatment as well as evaluating treatment response is possible in CMPDs today.

Blood Cell Count↗