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PubMed2000

Ethical guideposts for allelic variation databases.

Basically, a mutation database (MDB) is a repository where allelic variations are described and assigned within a specific gene locus. The purposes of an MDB may vary greatly and have different content and structure. The curator of an electronic and computer-based MDB will provide expert feedback (clinical and research). This requires ethical guideposts. Going to direct on-line public access for the content of an MDB or to interactive communication also raises other considerations. Currently, HUGO's MDI (Mutation Database Initiative) is the only integrated effort supporting and guiding the coordinated deployment of MDBs devoted to genetic diversity. Thus, HUGO's ethical "Statements" are applicable. Among the ethical principles, the obligation of preserving the confidentiality of information transferred by a collaborator to the curator is particularly important. Thus, anonymization of such data prior to transmission is essential. The 1997 Universal Declaration on the Human Genome and Human Rights of UNESCO addresses the participation of vulnerable persons. Researchers in charge of MDBs should ensure that information received on the testing of children or incompetent adults is subject to ethical review and approval in the country of origin. Caution should be taken against the involuntary consequences of public disclosure of results without complete explanation. Clear and enforceable regulations must be developed to protect the public against misuse of genetic databanks. Interaction with a databank could be seen as creating a "virtual" physician-patient relationship. However, interactive public MDBs should not give medical advice. We have identified new social ethical principles to govern different levels of complexity of genetic information. They are: reciprocity, mutuality, solidarity, and universality. Finally, precaution and prudence at this early stage of the MDI may not only avoid ethically inextricable conundrums but also provide for the respect for the rights and interests of all those involved.

Adult↗
PubMed1984

Glottic carcinoma. The roles of surgery and irradiation.

The treatment of 336 patients with squamous cell carcinoma of the glottic larynx seen at the University of Virginia Medical Center from 1960 through 1977 was reviewed. Two hundred eighty-five patients form the basis of this report. Patients were grouped by stage and by other prognostic factors. Five-year actuarial survival, recurrences, salvage therapy, complications, second primaries, and incidence in patients younger than 45-years-old were examined. The actuarial 5-year survivals are Stage I, 96%; Stage II, 88%; Stage III, 65%; and Stage IV, 57%. Early glottic carcinoma responded equally well to radiation therapy or surgery, and mortality from intercurrent disease was more common than death from glottic carcinoma. Anterior commissure involvement was not found to significantly decrease prognosis in Stage I disease. Within Stage II, patients with impaired true cord mobility had a significantly decreased survival, 71%, versus 93% for Stage II carcinoma with mobile cords. Surgery was superior to irradiation when cord mobility was impaired or fixed. Surgical salvage was successful in 70% of cases when the cords were originally mobile but 11% when cord motion had been impaired or fixed. Patients younger than age 45 years presented with more advanced disease, but by stage, treatment response did not differ from the remaining older group. Based on this review and from data reported in the literature, the authors recommend curative radiation therapy in patients with glottic carcinoma where the vocal cords are fully mobile. When cord mobility is impaired or fixed, the inclusion of surgery in the initial management results increased survival over irradiation alone. Recognizing that glottic carcinoma is often part of a multisystem disease, individualization of treatment is especially important in these advanced tumors.

Actuarial Analysis↗
PubMed2001

Advent of occupational health services research.

After lagging behind health services research in general health care, research is now examining health services provided to workers suffering occupational injuries and illnesses. The National Institute for Occupational Safety and Health, the Robert Wood Johnson Foundation Workers' Compensation Health Initiative, the Agency for Health Care Policy and Research (now the Agency for Healthcare Research and Quality), and the Canadian Institute for Work and Health co-sponsored a June, 1999, conference to explore research needs in this area. Fundamental tenets for advancing occupational health services research include: adopting the goal of improving occupational health care, including better integration of preventive and curative care; creating standardized interstate occupational health care data sets that include medical, economic, and patient perspectives; better defining quality in occupational care and developing appropriate performance measures; in addition to medical costs, assessing social, economic, medical and functional outcomes of care; considering the connections between work and health, including general health services; and addressing the need to train qualified occupational health services researchers. Am. J. Ind. Med. 40:291-294, 2001. Published 2001 Wiley-Liss, Inc.

Health Services Research↗
PubMed1992

Primary malignant lymphoma of the spleen.

We treated two patients with primary splenic malignant lymphoma. One was a 63-year-old man with diffuse histiocytic non-Hodgkin's lymphoma accompanied by multiple liver metastases which were composed of necrotic tissue probably due to preoperative transarterial chemoembolization (TAE). He eventually died of liver failure two years and six months after splenectomy. The autopsy revealed that a large part of the cirrhotic liver had been occupied by a diffuse-type hepatocellular carcinoma, but no recurrence of the malignant lymphoma was found in the liver or other organs. The second patient was a 40-year-old woman with a massive invasion of the stomach, colon, pancreas, and diaphragm by a splenic tumor. The splenic tumor and the adjacent involved organs were resected. Pathologically, well-differentiated diffuse lymphocytic non-Hodgkin's malignant lymphoma was evident. No recurrence has been found for six years and two months. Based on an evaluation of the 71 patients with primary splenic malignant lymphoma reported to data in Japan, the patients treated by a curative resection in an early clinical stage have a more favorable prognosis.

Adult↗
PubMed1998

Perioperative blood transfusions reduce long-term survival following surgery for colorectal cancer.

PURPOSE: The aim of the study contained herein was to investigate the association between blood transfusion and long-term outcome for patients treated for colorectal cancer, controlling for the effect of other prognostic factors. We also wanted to study whether blood storage time influenced the prognosis. METHODS: Cox's proportional hazards regression analysis was used to analyze data from 336 patients who survived resection with curative intent. Median follow-up was 5.8 (2-16.8) years or until death. RESULTS: Local recurrences and distant metastases were significantly more frequent when more than two units of blood had been transfused. In the multivariate Cox's analysis, with backward elimination of nonsignificant factors at the 10 percent level, the following risk factors were significantly related to death by colorectal cancer: tumor stage (T stage and N stage), perforation of tumor, age, and the need for a blood transfusion. Transfusions of more than two units of blood were independently and significantly associated with death from colorectal cancer (relative hazard, 2.7; 95 percent confidence intervals, 1.4-5.2). Time of blood storage had no effect on the prognoses. In patients dying from diseases unrelated to colorectal cancer, age and American Society of Anesthesiologists group were significantly related to death, whereas blood transfusion was not. CONCLUSION: We found an independent and significant association between perioperative blood transfusion and poor prognosis in colorectal cancer patients. Blood storage time was not a prognostic factor.

Age Factors↗
PubMed1986

A comparison of stapled and handsewn anastomoses in patients undergoing resection for Dukes' B and C colorectal cancer. An analysis of disease-free survival and survival from the NSABP prospective clinical trials.

This study was to assess the effect of stapled colorectal anastomoses on local recurrence, disease-free survival, and survival following curative resection for Dukes' B and C adenocarcinoma. Data were derived from two randomized prospective trials of the National Surgical Adjuvant Breast and Bowel Project designed to evaluate the efficacy of adjuvant therapy in colorectal cancer. Of 1111 patients with colonic anastomoses, 255 were stapled mechanically. There were no significant differences in disease-free survival, survival, or local tumor recurrence among patients subjected to stapled or handsewn anastomoses. Of the 181 patients undergoing anterior resection for rectal cancer, 82 anastomoses were fashioned with staples. No significant disadvantage in disease-free survival, survival, or local recurrence could be attributed to use of the mechanical stapling devices. Twelve percent of patients undergoing stapled rectal anastomoses developed a local recurrence as a first sign of treatment failure compared with 19 percent for the handsewn group. No significant differences in the length of distal margins were detectable. The average time on study was 41 months. The use of stapled anastomoses for carcinoma of the colon or rectum is not associated with an adverse effect on long-term outcome.

Adenocarcinoma↗
PubMed2004

[RFA of bone and soft tissue tumors].

Radiofrequency ablation (RFA) of primary and secondary liver malignancies is a promising and rapidly evolving technique, which increasingly gains importance. A new field of RFA is the minimal invasive therapy of osseous and soft tissue tumors. In the management of osteoid-osteoma, RFA is a well established treatment option. Basic principles, indications, complications and results of RFA will be presented. A careful evaluation of indications for RFA in osseous or soft tissue neoplasms is mandatory. In patients who are neither candidates for surgical tumor resection nor respond to chemotherapy, there is a need for alternative treatment options. In these preselected patients a substantial improvement in quality of life with low associated morbidity can be provided by RFA. In malignancies of bone and soft-tissue tumors, RFA is a palliative treatment option. Therefore, the results can not be compared to those of surgical resection or chemotherapy which essentially are employed with curative intention. Our own experiences as well as data published in the literature indicate that RFA is a helpful tool in preserving patient's quality of life. The high technical and clinical success together with a low complication rate makes RFA of osseous and soft tissue neoplasms a valuable supportive tool for patients not referable for surgery or systemic therapy.

Bone Neoplasms↗
PubMed2006

Improved long-term survival after liver resection for hepatocellular carcinoma in the modern era: retrospective study from HCV-endemic areas.

INTRODUCTION: It remains unclear whether recent progress in perioperative management and treatment for recurrent hepatocellular carcinoma (HCC) has improved patient outcomes in hepatitis C virus-endemic areas. METHODS: The clinicopathologic and follow-up data of 218 consecutive HCC patients who underwent curative resection between 1982 and 2003 were analyzed. Patients were assigned to one of two groups: before 1992 (early group; n=82) and 1992 and later (late group; n=136). Factors influencing survival rates were investigated by multivariate analysis. The effects of the period during which the hepatic resection was done on the patients' outcome were examined with respect to tumor size. RESULTS: The 5-year cancer-related and disease-free survival rates were 51.4% and 20.4%, respectively. The late group showed better 5-year cancer-related survival than the early group (64.1% vs. 33.8%), but disease-free survival did not differ significantly between the groups. On multivariate analysis, the period of the hepatic resection was identified as an independent prognostic factor for cancer-related survival (relative risk 0.70, P<0.01) but not disease-free survival. There were no differences in the cancer-related and disease-free survival rates between the two groups for patients with tumors 50 mm, both cancer-related and disease-free survival rates were better in patients in the late group. CONCLUSIONS: During the past two decades, improvements in the treatment of recurrent HCC tumors have contributed to controlling large HCCs but not to controlling the multicentric development of HCCs. It may be important to control multicentric recurrence of HCC to improve patient survival in areas where the hepatitis C virus is endemic.

Adult↗
PubMed2006

Extent of disease at presentation and outcome for adrenocortical carcinoma: have we made progress?

BACKGROUND: Adrenocortical carcinoma (ACC), a rare and aggressive malignancy, accounts for up to 14% of adrenal incidentalomas. The only chance of cure for ACC is diagnosis at an early stage; therefore, a main indication for adrenalectomy in patients with adrenal incidentaloma has been the potential risk of ACC. Recent studies suggest that this has led to earlier stage of ACC at diagnosis, more curative operations, and better survival. METHODS: We analyzed data on ACC from The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. Four equal time quartiles (1973-1979, 1980-1986, 1987-1993, and 1994-2000) were compared for changes in demographics, pathology, treatment, and cause-specific mortality. RESULTS: The average age was 51.2 years (range: 1-97), and 45.9% of patients were men. The average tumor size was 12 cm (range: 2-36 cm), and only 4.2% were < or = 6 cm. Most (88%) patients had surgical resection of their tumor, and external beam radiotherapy was used in only 12% of patients. Between the time quartiles compared (as well as annually), there was no significant difference at presentation in age at diagnosis, sex, race/ethnicity, tumor size, tumor grade, the frequency of distant metastasis, and overall TNM stage. Low tumor grade, lower stage of ACC, later time quartile, and surgical resection were associated with a lower cause-specific mortality by univariate analysis (P < or = 0.002) and by multivariate analysis (P < or = 0.031). CONCLUSIONS: Although adrenal incidentalomas have become a common indication for adrenalectomy, this has not resulted in patients with ACC being diagnosed earlier or treated at a lower stage of disease at the national level. The most important predictors of survival in these patients are tumor grade, tumor stage, and surgical resection.

Adolescent↗
PubMed1990

Metastases after fractionated radiation therapy of three murine tumor models.

The incidence of lung metastases after fractionated radiation therapy was compared to single dose irradiation in a retrospective analysis of three murine tumor models. For FSaII and SCCVII 5 or 15 fractions over 5 days were given using curative and subcurative doses and photons and neutrons. Data were pooled from different experiments. In mice with locally controlled FSaII the incidence of lung metastases was the same after all treatments, whereas in mice with locally controlled SCCVII, metastases were enhanced after 15 fractions. Photon and neutron irradiations yielded similar results. Local recurrences were followed by increased metastases. MCaIV was subcuratively irradiated with 9 equal fractions followed by a top-up dose to achieve local control. Metastases were high if doses per fraction were low and interfraction time intervals long. The data on MCaIV indicate increased metastases if clonogenic cells during treatment represent a large proportion of the integral tumor burden. The results on FSaII and SCCVII indicate that fractionated treatments might differently influence distant metastasis in different tumor models.

Animals↗
PubMed2005

Design, synthesis and evaluation of 5-substituted amino-2,4-diamino-8-chloropyrimido-[4,5-b]quinolines as novel antimalarials.

Novel 5-substituted amino-2,4-diamino-8-chloropyrimido-[4,5-b]quinolines were designed based on a pharmacophore developed for potent antimalarial activity using Chem-X and MOE softwares. The designed molecules were synthesized by following a novel route and were evaluated by Rane's test for blood schizonticidal activity in mice infected by Plasmodium berghei. Based on the Mean Survival Time (MST) data, of the nine compounds evaluated, three had curative potential when compared with chloroquine.

Animals↗
PubMed2005

Stage migration influences on stage-specific survival comparison between D1 and D3 gastric cancer surgeries.

AIMS: We evaluate the influency stage migration in a randomised trial comparing D1 (N 1 lymphadenectomy) and D3 (N 1, 2 and 3 lymphadenectomy) dissections. METHODS: Two hundred and thirteen curatively resected patients were analysed, with this TNM data. RESULTS: After applying D3 patients' data according to simulated D1 staging, D3 resections were associated with up-staging to N2-3 levels in 8% of patients according to the N stage. The likelihood of N-status migration increased with increasing depth of invasion into the gastric wall. The increases in the calculated survival rate after stage migration on known 5-year survival rates were: 2% in stage IB, 1% in stage II, 4% in stage IIIA, and 1% in stage IIIB. CONCLUSIONS: Stage migration secondary to meticulous lymph node dissection affects stage-specific survival rates. True therapeutic survival benefit of D3 resection can only be assessed in this context.

Gastrectomy↗
PubMed1994

Early androgen ablation for stage D1 (N1 to N3, M0) prostate cancer: prognostic variables and outcome.

To elucidate the outcome for patients with stage D1 (N1 to N3, M0) prostate cancer we reviewed 179 patients with lymphadenectomy proved pelvic nodal metastases who underwent immediate androgen ablation as the only initial treatment. With a median followup of 43 months, the 5 and 8-year actuarial rates of freedom from disease progression were 55% and 25%, respectively, and the median interval to disease progression was 67 months. The 5 and 8-year survival rates were 85% and 57%, respectively. Median survival after disease progression was 36 months. Local and distant disease progression was equally important. At 5 and 8 years the incidence of local progression was 32% and 51%, respectively, while metastatic rates at the same intervals wer 22% and 44%, respectively. Multivariate regression revealed that tumor grade and transurethral resection in preoperative stage C disease correlated with disease progression. Pretreatment prostate specific antigen (PSA) levels were not predictive of outcome. The fact that transurethral resection predicted for local as well as distant failure suggests that the procedure selects for rather than aggravates adverse disease. Posttreatment PSA levels were a sensitive index of response to treatment and of subsequent outcome. All patients who failed to achieve undetectable PSA levels had relapse by 8 years, whereas those whose levels became undetectable experienced only a 5% incidence of disease progression. These data show that androgen ablation alone is not curative for node positive disease but is associated with significant disease control and good short-term (5-year) survival. The primary tumor is an important source of androgen insensitive cells and comprehensive treatment strategies for this stage of disease require attention to the primary tumor as well as microscopic metastases.

Adenocarcinoma↗
PubMed2004

Laparoscopic resection of rectosigmoid carcinoma: prospective randomised trial.

BACKGROUND: Although laparoscopic resection of colorectal carcinoma improves post-operative recovery, long-term survival and disease control are the determining factors for its application. We aimed to test the null hypothesis that there was no difference in survival after laparoscopic and open resection for rectosigmoid cancer. METHODS: From Sept 21, 1993, to Oct 21, 2002, 403 patients with rectosigmoid carcinoma were randomised to receive either laparoscopic assisted (n=203) or conventional open (n=200) resection of the tumour. Survival and disease-free interval were the main endpoints. Patients were last followed-up in March, 2003. Perioperative data were recorded and direct cost of operation estimated. Data were analysed by intention to treat. FINDINGS: The demographic data of the two groups were similar. After curative resection, the probabilities of survival at 5 years of the laparoscopic and open resection groups were 76.1% (SE 3.7%) and 72.9% (4.0%) respectively. The probabilities of being disease free at 5 years were 75.3% (3.7%) and 78.3% (3.7%), respectively. The operative time of the laparoscopic group was significantly longer, whereas postoperative recovery was significantly better than for the open resection group, but these benefits were at the expense of higher direct cost. The distal margin, the number of lymph nodes found in the resected specimen, overall morbidity and operative mortality did not differ between groups. INTERPRETATION: Laparoscopic resection of rectosigmoid carcinoma does not jeopardise survival and disease control of patients. The justification for adoption of laparoscopic technique would depend on the perceived value of its effectiveness in improving short-term post-operative outcomes.

Aged↗
PubMed1997

Salvage radiotherapy for Hodgkin's disease following chemotherapy failure.

PURPOSE: This study aims to: 1) assess failure-free survival (FFS), overall survival (OS), and failure pattern after salvage radiotherapy (SRT) for patients with Hodgkin's disease (HD) who fail chemotherapy (CT); 2) identify patients suitable for SRT as an alternative to more aggressive salvage regimens. METHODS AND MATERIALS: Between 1978 and 1992, 52 patients with relapsed/refractory HD following 26 CT received SRT at the Peter MacCallum Cancer Institute. Patient characteristics at diagnosis were: median age (range 12-63); male-31, female-21; Stage I-4, II-16, III-25, or IV-7. Prior to SRT 27 patients had received the equivalent of both MOPP and ABV(D). The duration of initial complete response (CR) from CT was greater than 12 months in 22 patients. SRT (dose 34-42 Gy) was given to active disease sites. RESULTS: Five-year FFS and OS rates following SRT were 26 and 57%, respectively. Five-year FFS and OS rates of 36 and 75%, respectively, were achieved in patients who relapsed in supradiaphragmatic nodal sites without B symptoms; in a subset of patients with initial Stage I-II disease the FFS and OS rates were 50 and 86%, respectively. On multivariate analysis significant factors for FFS were B symptoms at the time of SRT (p = 0.003), extranodal involvement (p = 0.011) and histology (p = 0.018). For OS significant factors were B symptoms (p = 0.0007), age (p = 0.014) and number of prior CT regimens (p = 0.03). CONCLUSION: The relatively poor results of SRT in terms of FFS justify the use of alternative salvage strategies for most patients with Hodgkin's disease who fail CT. However, SRT offers a low morbidity, potentially curative option for a subset of patients. Our data suggest that patients most suitable for SRT are those with relapse in supradiaphragmatic nodal sites and no B symptoms.

Adolescent↗
PubMed1998

Pulmonary resection for malignancy in the elderly: is age still a risk factor?

OBJECTIVE: There is an increasing number of elderly patients presenting with potentially-resectable lung malignancy. The objective of this study is to evaluate the modern perioperative morbidity and mortality in patients undergoing oncologic lung resection and to analyse the trend over a 26-year period in our experience. METHODS: Between 1971 and 1996, 1506 patients underwent lung resection for malignancy. We reviewed the 30-day perioperative risk in a group of 385 (25.6%) patients aged 70 years and older operated on for intended cure of lung malignancy. Operations included 293 (77%) lobectomies, 24 pneumonectomies (6%), 16 bilobectomies (4%) and 52 wedge or segmental resections (13%). The pathology was bronchogenic carcinoma in 89% and metastasis or other tumours in 11% of patients. We compared the 30-day perioperative risk between the elderly group (age 70 or greater) and a cohort of 180 patients (control) 69 years and younger. RESULTS: The mortality for all resections in elderly group was 4.2% (16/385) and was 1.6% for the control group. Mortality in the octogenarian group was 2.8%. Female gender correlated with a decreased risk of death, with only two of 16 deaths in females (P < 0.005). Overall morbidity was higher in the study than in control patients (34% vs. 25%, n.s.), although major morbidity was similar in both groups (13.2% vs. 13%). Abnormal pulmonary-function testing and positive cardiac history did not correlate with increase overall or specific risk. Pneumonectomy carried a higher risk for death, with three of 24 deceased (12.5%; P < 0.05). Changes in outcome were analysed over two time periods: the mortality in the early period (1971-1982), 11.1% (8/72), was significantly elevated above the control group, while mortality in the modern period (1983-1994) was not, with a rate of 2.6% (8/313). CONCLUSIONS: In our series, mortality associated with operative treatment for lung malignancy in the elderly declined, so age alone no longer appears to be a risk factor. Age remains a risk factor for overall, but not major, morbidity. Pneumonectomy should undertaken cautiously in this age group. Based on this data, functional elderly patients should not be denied curative lung resection based on age alone.

Adenocarcinoma↗
PubMed2004

[Strategies for the diagnosis and treatment of prenatal toxoplasmosis - a survey].

Today, a decreasing number of infants with prenatal toxoplasmosis present with clinical signs of severe, generalised infection and cerebral involvement. The favourable clinical outcome - mild or subclinical infection - is considered to be an effect of early maternofetal treatment with spiramycin and pyrimethamine/sulfadiazine (PS). However, a Cochrane Review and a recently published European multicentre study on congenital toxoplasmosis did not only question this positive effect but also the efficiency of a postnatal long-term therapy. Both studies caused much confusion among neonatologists and paediatricians. The new setting requires an update of the diagnostic possibilities and different therapeutic strategies for prenatal toxoplasmosis. Only few prospective studies are available to compare the efficiency of different drug regimens in infected infants. However, clinical data demonstrate that the available therapeutics are not curative and cannot prevent late sequelae. Follow-up studies in pregnant women and their offspring show that prenatal parasite detection does not predict an unfavourable clinical outcome when treatment is initiated early after diagnosis. In Germany, prenatal screening is not obligatory. In case of primary maternal infection, materno-fetal therapy is recommended. A combination therapy consisting of PS is considered more effective than a spiramycin monotherapy. Treatment is recommended for all infected newborns with different strategies for infants with or without clinical symptoms. The treatment strategies of different European countries are discussed. This paper provides recommendations for the diagnosis and treatment of newborn toxoplasmosis and materno-fetal infection as well as recommendations for the clinical management of infected neonates and their follow-up, including drug monitoring.

Coccidiostats↗
PubMed2001

A systematic overview of chemotherapy effects in acute myeloid leukaemia.

A systematic review of chemotherapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for the evaluation of the scientific literature are described separately (Acta Oncol 2001; 40: 155-65). This synthesis of the literature on chemotherapy in patients with acute myeloid leukaemia (AML) is based on 129 scientific articles: one meta-analysis, 51 randomised trials, 39 prospective and 18 retrospective studies, and 20 other articles. Altogether, 39,557 patients were included in these studies. The conclusions reached can be summarized into the following points: Standard induction therapy for patients with AML, consisting of daunorubicin and ara-C in conventional doses, results in a complete remission (CR) rate of 50-60% in an unselected population and a long-term survival of about 10-20%. The total doses of both ara-C and daunorubicin are of importance for remission duration and in some studies also for survival. High-dose ara-C in the induction therapy prolongs remission duration in randomised trials, but has not been proven to affect long-term survival. It also increases toxicity and is not generally recommended. Idarubicin, another anthracyclin, has been compared with daunorubicin in conjunction with ara-C, resulting in a higher CR rate, especially in younger patients. In a meta-analysis of the five-randomised trials performed, a slight survival advantage was also seen with idarubicin. Yet, there is inconclusive evidence to conclude that idarubicin is superior to daunorubicin, and further trials are needed. Mitoxantrone improves the outcome of induction therapy in comparison with daunorubicin in some randomised studies, but conclusive evidence is still lacking. The addition of etoposide to daunorubicin or mitoxantrone and ara-C has improved CR rates, but has not convincingly improved survival and secondary leukaemias may be induced. New induction treatment strategies are defined by identification of prognostic subgroups. A risk stratification of AML patients as to chromosomal aberrations might be of importance for the choice of therapy. Moreover, the speed and the morphological response to the first induction course are predictive for relapse. However, no prospective randomised studies are as yet published regarding risk-adapted induction therapy. Post-remission dose-intensive chemotherapy prolongs the duration of remission, seemingly most in patients < 60 years. However, the data in support of these conclusions are sparse. A convincing effect on survival has not been shown. Limited data indicate that post-remission maintenance therapy with long-term attenuated chemotherapy prolongs time to recurrence, without evidence for prolongation of survival. Allogeneic bone marrow transplantation is an established practice for consolidation in first remission for young patients with an HLA-matched sibling. It is however not known which patients will really benefit from transplantation as no truly randomised comparison of allogeneic vs autologous transplantation or conventionally-dosed chemotherapy has been performed. Patients with and without an HLA-identical sibling have been compared on the basis of intention-to-treat principles ('genetic randomisation'). The disease-free survival seems to be prolonged in the donor group, due to a lower relapse rate with allogeneic transplantation. A higher procedure-related mortality makes the effects on total survival uncertain. Randomised trials with autologous transplantation vs conventional consolidation show a lower relapse rate and a trend for an improved disease-free survival. In one study, in which an autograft was added to four courses of intensive therapy, there was also a late survival advantage. Thus, the role for intensified post-remission treatment in first complete remission with high-dose chemotherapy followed by allogeneic or autologous marrow or stem cell transplantation requires further studies. Moreover, studies with stratification of therapy according to predictors for prognosis in the individual patient are needed. Allogeneic stem cell transplantation after minimal or reduced myeloablative conditioning ('mini-transplantation' or non-myelo stem cell transplantation) induces a host-vs-graft tolerance and an immune graft-vs-leukaemia effect. This new concept of immunotherapy seems to have a low procedure-related mortality, but long-term effects are unknown and evaluation in controlled clinical studies is required. Patients with relapsed AML can only infrequently achieve long-term remissions with chemotherapy in conventional doses. trolled data indicate that allogeneic transplantation can be a curative treatment for these patients a

Acute Disease↗