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10.5-kb homozygote of tumor necrosis factor-beta gene is associated with a better prognosis in gastric cancer patients.

BACKGROUND: In NcoI restriction fragment length polymorphism analysis of tumor necrosis factor-beta (TNF-beta) gene, the frequency of 10.5-kb homozygote is low in patients with lung cancer and is associated with a better prognosis. These results should be examined in other malignancies. METHODS: Using polymerase chain reaction, the authors performed NcoI restriction fragment length polymorphism analysis in 152 patients with gastric cancer, in 69 patients with benign gastric lesion, and in 141 healthy volunteers. RESULTS: In 3-year survival, the 10.5-kb homozygote showed a better prognosis (87.1%) than other alleles (5.5-kb homozygote, 52.5%; heterozygote, 79.1%), and there was a statistically significant difference between the 10.5-kb homozygote and the 5.5-kb homozygote. In 3-year survival for Stages III and IV, the 10.5-kb homozygote also showed a better prognosis (64.9%) than other alleles (5.5-kb homozygote, 16.7%; heterozygote, 41.4%). There were statistically significant differences (10.5-kb homozygote vs. 5.5-kb homozygote, P < 0.01; heterozygote vs. 5.5-kb homozygote, P < 0.05). There was a statistical difference between all patients and Stages III and IV (P < 0.05). CONCLUSIONS: The 10.5-kb homozygote of TNF-beta gene is associated with a prolonged survival in patients with gastric cancer, as has been shown in the patients with lung cancer.

Aged↗

Nuclear morphometry for improved prediction of the prognosis of human bladder carcinoma.

BACKGROUND: Histologic grade and clinical stage generally are used for estimating the prognosis of bladder carcinoma. However, both methods have been reported to have a rather low reproducibility and to be unsatisfactory for predicting the recurrence and progression of superficial bladder carcinoma. Recently, nuclear morphometry was used to quantitate the malignant potential of cancer cells in a more objective and reproducible manner. The authors quantitatively analyzed the malignant potential of bladder carcinoma at initial presentation using a combination of several nuclear morphometric variables. METHODS: The subjects were 156 patients with previously untreated bladder carcinoma. Three morphometric variables were measured in each subject: the mean nuclear volume (MNV), the nuclear roundness factor (NRF), and the variation of nuclear area (VNA). RESULTS: Univariate analysis showed that MNV and NRF were significant prognostic indicators for survival (MNV, P < 0.0001; NRF, P = 0.008). In addition, MNV was a prognostic indicator for tumor recurrence (P = 0.001), whereas MNV and NRF were prognostic indicators for invasive progression (MNV, P = 0.02; NRF, P = 0.009). For accurate prediction of the prognosis of patients with bladder carcinoma, a prognostic score, a recurrence score, and a progression score were designed using the coefficients of MNV and NRF in a proportional hazards model. The prognostic score clearly divided the patients into two different groups with 5-year survival rates of 88% and 64% (P = 0.0002). In addition, patients with superficial bladder carcinoma and a low recurrence score had a significantly higher 5-year recurrence free rate than those with a high recurrence score (40% vs. 23%, P = 0.0004), and the 5-year progression free rate of patients with a low progression score was significantly higher than that of those with a high progression score (98% vs. 73%, P = 0.0006). CONCLUSIONS: These findings suggest that nuclear morphometry is a reliable technique with which to identify prognostic indicators for human bladder carcinoma. A combination of several nuclear morphometric variables provides a more accurate indication of prognosis than any single parameter.

Adult↗

Does the early detection of lung carcinoma improve prognosis? The Turku Study.

BACKGROUND: The prognosis of lung carcinoma patients is better when the diagnosis is made early, the disease is localized, and radical surgery is possible. Screening for lung carcinoma with mass radiography or sputum cytology should contribute to a more favorable prognosis. To the author's knowledge to date, large-scale screening studies have shown improved survival but no reduction in mortality. METHODS: The histologic tumor type, disease stage, treatment, and survival rates were studied in 93 men who were found to have lung carcinoma during a single chest X-ray screening of > 33,000 smoking men ages 50-69 years and in 239 men of the same age range whose lung carcinoma was detected either through symptomatic presentation or through chest X-ray obtained for other purposes. RESULTS: The histologic distribution was similar in the two groups but screening detected more early stage tumors that more often were resectable (37% vs. 19%). The 5-year survival rate for the patients detected by screening was 19% and that of the other patients was 10%, with a relative risk 0.65 (95% confidence interval, 0.50-0.84). CONCLUSIONS: The results of the current study demonstrate that chest X-ray screening might improve the prognosis of patients with lung carcinoma. However, these results are subject to many factors that were only partially controlled and should be interpreted cautiously.

Aged↗

Expression of angiomodulin (tumor-derived adhesion factor/mac25) in invading tumor cells correlates with poor prognosis in human colorectal cancer.

Angiomodulin (tumor-derived adhesion factor/mac25/insulin-like growth factor binding protein-7), a cell-adhesive glycoprotein, is secreted by cancer cells and vascular endothelial cells. It may be involved in angiogenesis and modulation of the vascular functions necessary for tumor development. Although angiomodulin is expressed in colon cancer, there is limited information on it concerning cancer progression. In the present immunohistochemical study, we examined expression of angiomodulin in human colorectal cancer and its relationship with prognosis. A group of 89 surgically resected colorectal cancers was investigated immunohistochemically. In 37 cases (41.6%), angiomodulin was expressed in invading cancer cells. Early recurrence within 12 months after surgery was higher in patients with angiomodulin-expressing cancer than in those without (p < 0.05). The Kaplan-Meier life table revealed that patients with angiomodulin-positive tumor cells had a shorter survival time than those with negative cells (p < 0.01). The prognosis of patients with Dukes' C and angiomodulin-positive cells was apparently worse than that of patients with Dukes' D and angiomodulin-negative cells. Multivariate analysis with logistic regression indicated that only angiomodulin expression in cancer cells, lymph node metastasis and age remained significant prognostic variables for survival (p < 0.05). Angiomodulin showed correlations with poor prognosis, indicating that it may be a useful prognostic marker in patients with colorectal cancer.

Adult↗

Evaluation of chemotherapy response using technetium-99M-sestamibi scintigraphy in untreated adult malignant lymphomas and comparison with other prognosis factors: a preliminary report.

The purpose of this study was to predict chemotherapy response using technetium-99m methoxyisobutylisonitrile (Tc-MIBI) scintigraphy in untreated adult malignant lymphomas (ML) and compare the response with other prognosis factors. Before chemotherapy, 25 adult patients with ML were enrolled in this study. Tc-MIBI scintigraphy was performed 10 min after intravenous injection of Tc-MIBI to calculate tumor-to-background (T/B) uptake ratio and interpret the results visually. Chemotherapy response was evaluated in the first 1 to 2 years after completion of treatment by clinical and radiological methods. The mean T/B uptake ratio of the 15 patients with good response (3.3 +/- 0.6) was significantly higher than that of the 10 patients with poor response (1.2 +/- 0.1). All of the 15 patients with good response had positive Tc-MIBI scintigraphic results. All of the 10 patients with poor response had negative Tc-MIBI scintigraphic results. However, there were no significant differences in the incidences of good and poor responses for other prognosis factors. In our preliminary study, when compared with other prognosis factors, Tc-MIBI scintigraphy was the best tool to predict chemotherapy response in adult patients with ML.

Adult↗

Treatment of poor-prognosis early rheumatoid arthritis. A randomized study of treatment with methotrexate, cyclosporin A, and intraarticular corticosteroids compared with sulfasalazine alone.

OBJECTIVE: To determine whether a regimen of methotrexate, cyclosporin A, and corticosteroids introduced at onset in poor-prognosis rheumatoid arthritis (RA) can produce a significant improvement in outcome compared with standard monotherapy with sulfasalazine (SSZ). METHODS: Eighty-two consecutive patients presenting with new, untreated RA of less than 12 months' duration who fulfilled criteria for poor long-term outcome were randomized to receive either combination therapy (n = 40) or SSZ alone (n = 42). The primary outcome measures were remission and American College of Rheumatology (ACR) criteria for 20% improvement at 48 weeks. RESULTS: After 48 weeks, the numbers of patients who met the ACR criteria for 20% improvement were not significantly different between the two groups (combination 58% versus SSZ 45%), and similar numbers of patients had persisting clinical remission (approximately 10% both groups). During the first 3 months, there were significantly greater reductions in parameters of disease activity in the combination group. By 24 weeks, the swollen and tender joint counts, C-reactive protein levels, and erythrocyte sedimentation rates had fallen significantly in both groups, with a greater improvement in the swollen and tender joint count in the combination group. At 48 weeks, the radiographic damage score had increased by a median of 1 (range 0-42.5) in the combination group and 1.25 (range 0-72.5) in the SSZ group (P = 0.28; although there were significant differences in the scores for the right hand). There were significantly fewer withdrawals due to lack of efficacy in the combination group than in the SSZ group (1 of 40 versus 10 of 42; P = 0.007). In the combination group, dose reduction was needed in 22.5% because of hypertension and in 22.5% because of elevated creatinine levels. Over 48 weeks, serum creatinine increased in both groups, but particularly in the combination arm. CONCLUSION: In poor-prognosis RA patients, "aggressive" combination therapy led to more rapid disease suppression but did not result in significantly better ACR response or remission rates. This suggests that in poor-prognosis disease, an approach based on identifying patients with poor treatment responses before extra therapy is added ("step-up" approach) may be more appropriate than the use of combination therapy in all patients from the outset.

Adrenal Cortex Hormones↗

Biological characteristics of newly diagnosed poor prognosis acute myelogenous leukemia.

A pilot study was conducted of the biological characteristics of the leukemia cells of newly diagnosed patients with poor prognosis acute myelogenous leukemia (AML). This study included measurements of the pretherapy proliferative rate of the leukemia cells in vivo, assessment of differentiation in vivo during remission induction therapy, and the level of expression of the fms, myc, and IL1 beta genes in pretherapy leukemia cells. Short cell cycle times were characteristic of the best prognostic category and were associated with a rapid reduction in marrow leukemia cells in cytosine arabinoside (araC)-sensitive patients. Expression of c-fms was associated with rapid reduction in marrow leukemia cells during araC therapy and with a successful treatment outcome. Expression of the IL1 beta gene was associated with short remissions. These studies suggest that when compared to newly diagnosed standard prognosis AML, the leukemia of poor prognosis patients is more likely to exhibit long cell cycle times, low levels of fms expression, and is less likely to be associated with myeloid differentiation during remission induction therapy.

Aged↗

Cortical blindness: etiology, diagnosis, and prognosis.

We examined 15 patients with cortical blindness, reviewed the records of 10 others, and compared these 25 patients to those in previous studies of cortical blindness. Although cerebrovascular disease was the most common cause in our series, surgery, particularly cardiac surgery, and cerebral angiography were also major causes. Only 3 patients denied their blindness, although 4 others were unaware of their visual loss. Electroencephalograms (EEGs) were performed during the period of blindness in 20 patients and all recordings were abnormal, with absent alpha rhythm. Visual evoked potentials recorded during blindness were abnormal in 15 of 19 patients, but did not correlate with the severity of visual loss or with outcome. Bioccipital lucencies were found in computed tomographic (CT) scans of 14 patients; none of the 14 regained good vision. Recovery of vision was poor in all 8 patients who had a spontaneous stroke, but fair or good in 11 of the other 17 patients. Prognosis was best in patients under the age of 40 years, in those without a history of hypertension or diabetes mellitus, and in those without associated cognitive, language, or memory impairments. We conclude that the prognosis in cortical blindness is poor when caused by stroke; EEGs are more useful than visual evoked potentials for diagnosis; and bioccipital abnormalities shown on CT scan are associated with a poor prognosis.

Blindness↗

Intracerebral hemorrhage versus infarction: stroke severity, risk factors, and prognosis.

The purpose of this study was to compare stroke severity, risk factors, and prognosis in patients with intracerebral hemorrhage versus infarction. We prospectively studied 1,000 unselected patients with acute stroke of a verified type in the Copenhagen Stoke Study. Neurological deficits and functional disabilities were evaluated weekly from the time of acute admission throughout the rehabilitation period. Eighty-eight (9%) had intracerebral hemorrhage. The relative frequency of intracerebral hemorrhage rose exponentially with increasing stroke severity. In multivariate analyses, stroke type had no influence on mortality, neurological outcome, functional outcome, or the time course of recovery. Initial stroke severity was the all-important prognostic factor. The relative importance of hypertension and blood pressure on admission was not greater for intracerebral hemorrhage than for infarction. No preponderance was found between type of stroke and sex, age, and smoking. Diabetes, ischemic heart disease, and elevated serum total cholesterol level all favored cerebral infarction as opposed to intracerebral hemorrhage. We conclude that the type of stroke per se has no influence on stroke prognosis in general; the extent of the injury is decisive. The poorer prognosis in patients with intracerebral hemorrhage is due to the increase in frequency of intracerebral hemorrhage with increasing stroke severity. The likelihood of cerebral infarction occurring as opposed to intracerebral hemorrhage seems increased fivefold in stroke patients with diabetes. Hypertension and blood pressure on admission were not predictors of stroke type.

Aged↗

Fear avoidance and prognosis in back pain: a systematic review and synthesis of current evidence.

OBJECTIVE: Fear of pain, which is hypothesized to result in avoidance behavior, has been described as an obstacle to recovery in populations of patients with low back pain. However, the evidence to support the link between high levels of fear at early stages of pain and poor prognosis has yet to be systematically assessed. We undertook this review to explore current evidence and to propose further development of theoretical models. METHODS: We performed a systematic literature review of all prospective inception cohorts of patients with acute low back pain that measured fear of pain (often described as fear avoidance) at baseline. RESULTS: We reviewed 9 studies reported between 2001 and 2006. Several of these had acceptable/good methodology. Three studies, of which at least 1 had excellent methodology, showed no link between measures of fear at baseline and poor prognosis in the short term (3 months) or the long term (12 months). Three studies with acceptable methodology showed weak evidence for such a link, but the effect sizes were small. The only study with acceptable methodology to find a clear link suggested that fear of movement was linked to long-term pain. CONCLUSION: Despite the prevalent focus on fear of pain at early stages of back pain, there is little evidence to link such fear states with poor prognosis. There is some evidence to suggest that fear may play a role when pain has become persistent. There is a growing consensus that distress/depression plays an important role at early stages, and clinicians should focus on these factors.

Avoidance Learning↗

Effect of initial biopsy procedure on prognosis in Stage 1 invasive cutaneous malignant melanoma: review of 1086 patients.

After treatment for primary clinical Stage 1 invasive cutaneous malignant melanoma, 1086 patients were followed for a minimum of 5 years from initial operation. Patient data were retrieved from the unit's melanoma registry; 96 (8.8 per cent) were treated initially by incisional biopsy, 292 (26.9 per cent) by narrow margin excision biopsy and 698 (64.3 per cent) by wide margin excision. Logistic regression analysis was performed to assess the statistical significance of the association between the various factors. The method of initial biopsy was related to maximal tumour thickness, age, and sex. Incisional biopsy rendered 38 out of 96 (40 per cent) lesions not fully assessable on current histopathological criteria, significantly higher than for the other biopsy techniques (P less than 0.0001). Incisional biopsy did not adversely affect prognosis in terms of local recurrence and mortality. Prognosis was related to tumour thickness, age and sex of the patient, and not to biopsy technique. We recommend that all suspicious lesions should be submitted to excisional rather than incisional biopsy to avoid compromising the histological assessment, given the importance of maximal tumour thickness in determining treatment and prognosis.

Adolescent↗

Incidence and prognosis of Krukenberg tumour in Northern Ireland.

The case notes of 15 patients with Krukenberg tumours were studied to determine the incidence, presentation, clinical findings and prognosis of the disease in Northern Ireland. Patients tended to be young and premenopausal. A short history of abdominal pain was the most frequent presenting complaint, abdominal swelling being second. Menstrual irregularities occurred infrequently and no patient was virilized. Tumours tended to be large, bilateral and associated with ascites. The stomach was the commonest primary site. The overall prognosis was poor, especially if the primary tumour remained covert at the time of diagnosis. The prognosis was unaffected by subsequent discovery of the primary source; extensive investigation is inconvenient for the patient and wasteful of resources. The incidence of the tumour in Northern Ireland was 0.16 per 100,000 per annum: it will be rarely encountered by general surgeons.

Adult↗

Predictability and prognosis of PTCA-induced coronary artery aneurysms.

The natural history of coronary aneurysms, defined as local dilatations exceeding the diameter of the normal adjacent vessel segments by at least 1.5 times, is not significantly different from the natural history of nonaneurysmal coronary disease. However, little is known about the prognosis of percutaneous transluminal coronary angioplasty (PCTA)-induced coronary aneurysms. Therefore, we investigated the occurrence and the medium long-term prognosis of such aneurysms in 728 patients who, after successful PTCA, underwent repeat coronary angiography at mean 4.5 months post-PTCA. A coronary aneurysm at the site of PTCA ws noted in 3.9% of patients (n = 28). Of the potentially predictive factors analyzed, only a coronary dissection at the time of PTCA had statistically significant influence. The long-term prognosis of PTCA-induced coronary aneurysms was excellent. One patient underwent (unrelated) cardiac surgery, all other 27 patients remained eventfree. We conclude that the same benign nature of coronary aneurysmal disease holds true for those aneurysms that develop after PTCA.

Angioplasty, Balloon, Coronary↗

Risk indicators for death and prognosis among patients in whom acute myocardial infarction was not confirmed in relation to prescription of beta blockers at discharge.

A large number of studies have shown the prognosis after acute myocardial infarction (AMI) to be favorably affected by treatment with beta blockers. Whether such treatment also will have a favorable effect on the prognosis in patients in whom AMI was not confirmed has not been shown. A study was undertaken at Sahlgren's Hospital, Göteborg, to determine risk indicators for death and prognosis among 1,443 patients in whom AMI was not confirmed and who survived hospitalization in relation to whether or not beta blockers were prescribed at discharge. One-year mortality was determined and p values were corrected for differences at baseline. Of the 1,443 patients who participated in the analyses, 44% were prescribed beta blockers. They differed from the remaining patients by younger age, predominance of men, a more frequent history of AMI, angina pectoris, and hypertension, and a less frequent history of congestive heart failure. Patients in whom beta blockers were prescribed had a 1-year mortality of 6% compared with 16% in those not on beta blockers (p < 0.001). The difference was similar in various subgroups according to clinical history.

Adrenergic beta-Antagonists↗

Prognosis following acute myocardial infarction in patients with ST-T abnormalities on electrocardiograms obtained before myocardial infarction.

BACKGROUND: Many studies have examined the relationship between prognosis after myocardial infarction (MI) and electrocardiographic (ECG) findings at the time of or after the onset of MI. However, little work has been done concerning the association between ECG findings obtained before the onset of MI (pre-MI) and the prognosis after MI. HYPOTHESIS: The study was undertaken to determine whether ST-T segment and T-wave morphology on pre-MI ECGs provides useful information for prognosis after acute MI. METHODS: Pre-MI ECGs of 212 patients recorded within the 6-month period before MI were studied for the presence of high-voltage R waves, ST-segment depression, and negative T waves. The Kaplan-Meier method and multivariate analysis were used to determine the relationship between these ECG findings and in-hospital cardiac death. RESULTS: In-hospital cardiac death occurred in 32 (15.1%) patients. The in-hospital mortality rate was 38.5% (5/13) for the patients with high-voltage R waves, 54.5% (6/11) for patients with ST-segment depression, and 45.6% (15/33) for patients with negative T waves. The in-hospital mortality rate was 13.6% (27/199) for patients without high-voltage R waves, 12.9% (26/201) for patients without ST-segment depression, and 9.5% (17/179) for those without negative T waves. Multivariate analysis identified age and negative T waves as independent risk factors for cardiac death, with a hazard ratio for negative T waves of 3.1. CONCLUSION: Negative T waves on pre-MI ECGs represent an independent predictor of in-hospital cardiac death in patients with MI.

Age Factors↗

Hepatocyte growth factor is associated with poor prognosis of malignant gliomas and is a predictor for recurrence of meningioma.

BACKGROUND: Hepatocyte growth factor (HGF) is a cytokine that participates in multiple cell functions; it promotes proliferation, motility, and morphogenesis of epithelial cells. Some malignant tumors, such as breast carcinoma, bronchogenic carcinoma, and multiple myeloma, overexpress it and its receptor. Hepatocyte growth factor is also present in normal astrocytes; therefore, it is important to investigate whether HGF participates in the pathophysiology of malignant gliomas and other brain tumors. Intratumoral concentration of HGF in human intracranial neoplasms was measured and correlated with prognosis, tumor recurrence, vasogenic edema, cell proliferation index, and vascular density. METHODS: Hepatocyte growth factor concentration was measured in 62 intracranial tumors, including 16 anaplasic astrocytomas (AA), 16 glioblastoma multiformes (GM), 11 meningiomas, 9 hypophyseal adenomas, 7 oligodendrogliomas, and 3 cordomas, and in 4 samples of nonneoplastic brain tissue. The following parameters were correlated with HGF values: survival and tumor recurrence, cell proliferation index and vascular density as determined by immunohistopathologic analysis, and peritumoral edema as seen by magnetic resonance imaging. RESULTS: Hepatocyte growth factor concentration (pg/mL) was significantly higher in malignant gliomas (AA and GM) than in adenomas, oligodendrogliomas, and nonneoplastic brain tissue, but it was similar to that of meningiomas. Mean survival of patients with AA was 16.5 +/- 3.6 months and for patients with GM 12.3 +/- 1.3 months. Hepatocyte growth factor concentration was higher in GM than in AA (15,844 +/- 2504 vs. 7499 +/- 1703, P = 0.0375) and was correlated with the cell proliferation index and with poor prognosis. Likewise, mean tumoral concentration of HGF was higher in meningiomas that relapsed than in those without recurrence (22,887 +/- 6489 vs. 2090 +/- 497, P = 0.008). CONCLUSIONS: Intratumoral concentration of HGF in gliomas is associated with malignancy and poor prognosis. High HGF is also found in meningiomas and is related with long term recurrence. The current findings suggest that the routine measurement of HGF may be used as a predictive factor for planning therapeutic strategies in both malignant gliomas and meningiomas. The potential use of HGF inhibitors or antagonists for therapy of these tumors should be explored.

Adult↗

Association of hypoxia-inducible factors 1alpha and 2alpha with activated angiogenic pathways and prognosis in patients with endometrial carcinoma.

BACKGROUND: Hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha are essential regulatory proteins for the adaptation of tumor cells to hypoxia, and they stimulate angiogenesis through activation of the vascular endothelial growth factor (VEGF) gene. METHODS: HIF-1alpha and HIF-2alpha proteins were studied immunohistochemically in a group of 81 patients with Stage I endometrial adenocarcinoma of the endometrioid cell type. The results were correlated with intratumoral angiogenesis, the expression of the angiogenic factors VEGF and thymidine phosphorylase (TP), and the VEGF/receptor (VEGF/KDR) complex. Relations also were sought with estrogen receptor (ER) and progesterone receptor (PR), with the apoptosis-related proteins bcl-2 and p53, with several histopathologic parameters, and with patient prognosis. In addition, a sample of 25 normal endometria at various phases of the menstrual cycle was studied for the presence of HIF-1alpha and HIF-2alpha. RESULTS: HIF-1alpha expression was detected in 49% of endometrial carcinomas. The expression was cytoplasmic or mixed nuclear/cytoplasmic. HIF-1alpha expression was associated with up-regulation of the VEGF pathway and with increased standard microvessel density (sMVD) and activated VEGF/KDR microvessel density (aMVD). It also was associated with a poor prognosis in both univariate and multivariate analyses. HIF-2alpha protein showed a pattern of expression similar to the pattern seen in HIF-1alpha, but expression of HIF-2alpha protein occurred in only 17% of endometrial carcinomas, and it was associated with increased TP reactivity. There also was a relation of HIF-1alpha expression with well-differentiated endometrial neoplasms, and there was a marginal association of HIF-1alpha and HIF-2alpha with ER expression. With reference to normally cycling tissues, HIF-1alpha nuclear/cytoplasmic expression was particularly strong in the samples of early proliferative phase endometrium compared with HIF-2alpha protein expression, which showed a constant reaction throughout the menstrual cycle. CONCLUSIONS: The up-regulation of HIF-1alpha and, to a lesser extent, of HIF-2alpha is a common event in Stage I endometrial adenocarcinomas. In these tumors, HIF-1alpha expression is related to increased angiogenesis, through activation of the VEGF angiogenic pathway, and to an unfavorable prognosis. HIF-2alpha accumulation is associated with increased expression of the angiogenic factor TP.

Adenocarcinoma↗

Complete cytogenetic and molecular responses to interferon-alpha-based therapy for chronic myelogenous leukemia are associated with excellent long-term prognosis.

BACKGROUND: Little is known regarding long-term prognosis among patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) who achieve a complete cytogenetic response (0% Ph-positive cells) after treatment with interferon-alpha. METHODS: The authors analyzed 512 patients with Ph-positive, early chronic-phase CML who were treated with interferon-based therapies between 1981-1995 for the incidence and durability of complete cytogenetic response, and in relation to long-term prognosis. RESULTS: One hundred forty patients (27%) achieved a complete cytogenetic response. Their 10-year survival rate was 78%. At the time of last follow-up, 44 patients (31%, 9% of the total) were alive, 21 in first and 23 in second durable complete cytogenetic response (median, 127 months; range, 88-191 months); 39 patients had not received any therapy for a median of 50 months (range, 11-139 months). Analysis by reverse transcriptase-polymerase chain reaction in 78 patients during complete cytogenetic response showed 46 who had achieved at least 1 complete molecular response. Five of these 78 patients had died by the time of last follow-up, but only 2 had died of disease-specific causes. Recurrence rates were significantly lower and cytogenetic response durations were significantly longer among patients who achieved at least one complete molecular response. CONCLUSIONS: Achieving a complete cytogenetic or molecular response after therapy with interferon-alpha appears to be associated with excellent long-term prognosis. Approximately 10% of patients reportedly can achieve durable complete cytogenetic response, with or without continuation of interferon. This finding emphasizes the potential of long-term event-free survival in CML patients outside the context of allogeneic stem cell transplantation, which may be improved with new therapies such as imatinib mesylate.

Female↗