Intensive consolidation therapy compared with standard consolidation and maintenance therapy for adults with acute myeloid leukaemia aged between 46 and 60 years: final results of the randomized phase III study (AML 8B) of the European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) Leukemia Cooperative Groups.

The most effective post-remission treatment to maintain complete remission (CR) in adults aged between 46 and 60 years with acute myeloid leukaemia (AML) is uncertain. Previously untreated patients with AML in CR after induction chemotherapy with daunorubicin and cytarabine were randomized between two intensive courses of consolidation therapy containing high-dose cytarabine, combined with amsacrine or daunorubicin and a standard consolidation and maintenance therapy containing standard dose cytarabine and daunorubicin. One hundred fifty-eight CR patients were assigned to the intensive group and 157 patients to the standard group. After a median follow-up of 7.5 years, the 4-year survival rate was 32 % in the intensive group versus 34 % in the standard group (P = 0.29). In the intensive group, the 4-year relapse incidence was lower than in the standard group: 55 and 75 %, respectively (P = 0.0003), whereas treatment-related mortality incidence was higher: 22 versus 3 % (P < 0.0001). Two intensive consolidation courses containing high-dose cytarabine as post-remission treatment in patients with AML aged between 46 and 60 years old did not translate in better long-term outcome despite a 20 % lower relapse incidence. Better supportive care and prevention of treatment-related complications may improve the overall survival after intensified post-remission therapy in this age group.

[Continuous sedation until death. A French way for the end-of-life care?]. / La sédation continue jusqu'à la mort. Une voie française pour les soins de fin de vie ?

Continuous sedation until death (CSUD) is a practice which has developed recently in several countries, appearing more acceptable than euthanasia and medically assisted suicide, since more close to a "natural death". The French parliament has just adopted a law which stipulates CSUD on request of the patient in a definite number of circumstances, especially in incurable diseases near to the terminal stage with suffering refractory to treatments. Thus France has adopted a unique international position for the end-of-life care. However several ethical problems raised by CSUD, which corresponds to a psycho-social death preceding the biological one, have been raised in the literature. The legitimacy of CSUD, especially if sedation is deep and not proportional to the degree of suffering, or if it is performed in case of a purely existential distress, is a matter of discussion. The primacy allocated to autonomy is questionable for the more vulnerable patients, who deserve mainly a social solidarity. The double-effect principle is replaced actually in CSUD by a co-intention both to relieve suffering and meanwhile eventually to hasten death, especially when stopping nutrition and hydration. CSUD is thus located in a grey zone between palliative care and euthanasia.

Allogeneic stem cell transplantation in acute lymphoblastic leukemia and non-Hodgkin's lymphoma for patients

BACKGROUND AND OBJECTIVES: In the EORTC ALL-3 trial, the efficacy of allogeneic transplantation was compared with that of autologous marrow transplantation and maintenance chemotherapy in patients

Ethical and clinical aspects of intensive care unit admission in patients with hematological malignancies: guidelines of the ethics commission of the French society of hematology.

Admission of patients with hematological malignancies to intensive care unit (ICU) raises recurrent ethical issues for both hematological and intensivist teams. The decision of transfer to ICU has major consequences for end of life care for patients and their relatives. It also impacts organizational human and economic aspects for the ICU and global health policy. In light of the recent advances in hematology and critical care medicine, a wide multidisciplinary debate has been conducted resulting in guidelines approved by consensus by both disciplines. The main aspects developed were (i) clarification of the clinical situations that could lead to a transfer to ICU taking into account the severity criteria of both hematological malignancy and clinical distress, (ii) understanding the process of decision-making in a context of regular interdisciplinary concertation involving the patient and his relatives, (iii) organization of a collegial concertation at the time of the initial decision of transfer to ICU and throughout and beyond the stay in ICU. The aim of this work is to propose suggestions to strengthen the collaboration between the different teams involved, to facilitate the daily decision-making process, and to allow improvement of clinical practice.

[Distress during end-of-life: Ethical questions about sedation]. / Détresse en fin de vie : questionnement éthique sur la sédation.

Distress and suffering are words currently used in the medical vocabulary, the first carrying a more acute and dramatic feature, while suffering is more subjective. They may concern the somatic, psychic, social, and spiritual domains, with interactions such as excrutiating and unrelieved pain causing psychological distress. Distress during the end of life is induced by the threatening of an unavoidable death, more or less foreseen by the patient. It may correspond to an existential distress, with loss of the meaning of life, and of the social role, along with metaphysical anxiety. Patient's next of kin and carers can also be involved by the distress, either by empathic transmission, or due to specific factors. Palliative care and anticipation should allow to prevent or relieve distress and suffering. This imply to ask for palliative care on due time, and to anticipate the foreseeable situations, trying meanwhile to identify the patient's preferences. Pharmacologic sedation is becoming a frequent practice during terminal phase of diseases, raising ethical questioning on its motives and aims. Deep continuous sedation maintained until death may be viewed as a psychic and social euthanasia, ethically questionable, and should be foreseen only in case of intractable distress. A controlled and reversible sedation, when needed, should be preferred, always with the agreement of the patient or his/her proxy. Existential distress by itself should not justify a deep continuous sedation.

Daunorubicin versus mitoxantrone versus idarubicin as induction and consolidation chemotherapy for adults with acute myeloid leukemia: the EORTC and GIMEMA Groups Study AML-10.

PURPOSE: To compare the antitumor efficacy of three different anthracyclines in combination with cytarabine and etoposide in adult patients with newly diagnosed acute myeloid leukemia (AML). PATIENTS AND METHODS: We randomly assigned 2,157 patients (age range, 15 to 60 years) to receive intensive induction-consolidation chemotherapy containing either daunorubicin, idarubicin, or mitoxantrone. After achieving complete remission (CR), patients were assigned to undergo either allogeneic or autologous stem-cell transplantation (SCT), depending on the availability of a sibling donor. RESULTS: The overall CR rate (69%) was similar in the three groups. Autologous SCT was performed in 37% of cases in the daunorubicin arm versus only 29% and 31% in mitoxantrone and idarubicin, respectively (P < .001). However, the disease-free survival (DFS) and survival from CR were significantly shorter in the daunorubicin arm: the 5-year DFS was 29% versus 37% and 37% in mitoxantrone and idarubicin, respectively. The proportion of patients who underwent allogeneic SCT (22%) was equivalent in the three treatment groups, and the outcome was similar as well. The [corrected] 5-year overall survival rates were 31%, 34%, and 34%, [corrected] respectively. CONCLUSION: In adult patients with AML who do not receive an allogeneic SCT, the use of mitoxantrone or idarubicin instead of daunorubicin enhances the long-term efficacy of chemotherapy.

Allogeneic compared with autologous stem cell transplantation in the treatment of patients younger than 46 years with acute myeloid leukemia (AML) in first complete remission (CR1): an intention-to-treat analysis of the EORTC/GIMEMAAML-10 trial.

In the European Organization for Research and Treatment of Cancer Leukemia Group and Gruppo Italiano Malattie Ematologiche dell' Adulto (EORTC-LG/GIMEMA) acute myeloid leukemia (AML)-10 trial, patients in first complete remission (CR1) received a single intensive consolidation (IC) course. Subsequently, those patients younger than 46 years with an HLA-identical sibling donor were assigned to undergo allogeneic (allo) stem cell transplantation (SCT), and patients without such a donor were planned for autologous (auto) SCT. Between November 1993 and December 1999, of 1198 patients aged younger than 46 years, 822 achieved CR. The study group constituted 734 patients who received IC: 293 had a sibling donor and 441 did not. Allo-SCT and auto-SCT were performed in 68.9% and 55.8%, respectively. Cytogenetic determination was successfully performed in 446 patients. Risk groups were good (t(8;21), inv16), intermediate (NN or -Y only), and bad/very bad (all others). Median follow-up was 4 years; 289 patients relapsed, 66 died in CR1, and 293 died. Intention-to-treat analysis revealed that the 4-year disease-free survival (DFS) rate of patients with a donor versus those without a donor was 52.2% versus 42.2%, P =.044; hazard ratio = 0.80, 95% confidence interval (0.64, 0.995), the relapse incidence was 30.4% versus 52.5%, death in CR1 was 17.4% versus 5.3%, and the survival rate was 58.3% versus 50.8% (P =.18). The DFS rates in patients with and without a sibling donor were similar in patients with good/intermediate risk but were 43.4% and 18.4%, respectively, in patients with bad/very bad risk cytogenetics. In younger patients (15-35 years), the difference was more pronounced. The strategy to perform early allo-SCT led to better overall results than auto-SCT, especially for younger patients or those with bad/very bad risk cytogenetics.