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Both intravenous and subcutaneous immunoglobulins are therapeutic modalities approved in various conditions, including primary and secondary immune deficiencies and autoimmune disorders. To date, immunoglobulins have more often been considered as a safe medication, with minor adverse effects such as hypertension, fever and chills, nausea, myalgia or headache. However, with the wider use of immunoglobulins in the treatment of autoimmune diseases, severe side effects have also been reported to occur in immunoglobulin-treated patients, especially anaphylaxis, aseptic meningitis, acute renal impairment, thrombotic events as well as haematological manifestations. This paper reviews all the potential adverse events related to immunoglobulin therapy and establishes a comprehensive guideline for the management of these events.

Introduction Le syndrome de bronchiolite obliterant (BOS) est une des complications pulmonaires tardives non infectieuses la plus grave dans l’allogreffe. Il persiste encore de nombreuses incertitudes notamment sur son etiologie et sa prise en charge. Afin d’ameliorer les connaissances et le pronostic de la BOS, l’American Society of Blood and Marrow Transplantation a recommande un suivi pneumologique systematique en post-allogreffe. Mais nous n’avons pas la preuve a ce jour de son benefice. Nous avons evalue sa mise en place aux hospices civils de Lyon a partir de janvier 2013. Methodes Les patients allogreffes entre janvier 2013 et juillet 2016 vivant a 3 mois de la greffe ont ete inclus retrospectivement. Le diagnostic de BOS suivait les recommandations de la National Institut of Health (NIH). Une suspicion de syndrome bronchiolaire debutant (hors critere NIH) par le pneumologue etait traitee par corticoide inhale. Le suivi en pneumologie etait defini par la realisation d’une epreuve fonctionnelle respiratoire (EFR) en pre-greffe et d’au moins une consultation pneumologique avec EFR dans la premiere annee post-greffe. Resultats Au total, 225 patients ont ete analyses avec un suivi median de 23 mois (IQR : 25–75 % : 13–33). Le taux de suivi en pneumologie etait de 14 % (n = 8/59) en 2013 puis 72 % (21/29) en 2016. La prevalence de BOS etait de 14 % en 2013 (8/59) versus 7 % (2/29) en 2016 et la prevalence totale de 10,2 % (n = 23). En analyse multivariee, les facteurs de risque de BOS etaient le mismatch HLA donneur–receveur (OR = 2,9 ; IC95 % : 1–8,4) et le nombre d’organes atteints par une reaction chronique du greffon contre l’hote (GvHc) extrapulmonaire (OR = 8,21, IC95 % : 2,42–27,9 si au moins 2 organes atteints). La mediane de diagnostic de la BOS en absence du suivi est de 14 mois (IQR : 25–75 % : 11–17) versus 7 mois (IQR : 25–75 % : 5,3–10,5) en cas de suivi. Un syndrome bronchiolaire debutant a ete traite chez 22 patients. On observait au diagnostic une baisse de −6 % du VEMS (IQR : 25–75 % : −8 a 2) par rapport aux valeurs pre-greffe et un VR/CPT a 118 (IQR : 25–75 % : 107–140) et au moins une GvHc extrapulmonaire chez 7 patients (32 %). Conclusion Nous avons mis en evidence dans cette etude en vrai vie un taux de suivi en pneumologie de plus de 70 % sur la derniere annee de l’etude. Nous avons retrouve une association forte entre la BOS et la GvHc. Le suivi pneumologique met en evidence l’existence de syndrome bronchiolaire debutant en post-allogreffe dont il sera interessant d’etudier le lien possible avec une BOS debutante.

International audience; Toxoplasmosis (TXP) is a life-threatening complication of allogeneic haematopoietic stem cell transplantation (AHSCT). Little is known about the risk factors and there is no consensus on prophylactic measures. To investigate the risk factors, we conducted a single-centre, retrospective matched case-control study among adults who underwent AHSCT from January 2006 to March 2015 in our hospital. TXP cases were identified from the prospectively maintained hospital's database. The 1:2 control population consisted of the two patients who received an AHSCT immediately before and after each case with similar donor relationship (related, unrelated) but who did not develop TXP. Risk factors were identified by conditional logistic regression. Clinical features and outcome of TXP were examined. Twenty-three (3.9%) cases of TXP (20 diseases, three infections) were identified among 588 AHSCT recipients. Twenty (87%) cases had a positive pre-transplant Toxoplasma gondii serology. In comparison with 46 matched control patients, risk factors were the absence of effective anti-Toxoplasma prophylaxis (odds ratio (OR) 11.95; 95% CI 3.04-46.88; p \textless0.001), high-grade (III-IV) acute graft-versus-host-disease (OR 3.1; 95% CI 1.04-9.23; p 0.042) and receipt of the tumour necrosis factor-alpha blocker etanercept (OR 12.02; 95% CI 1.33-108.6; p 0.027). Mortality attributable to TXP was 43.5% (n = 10). Non-relapse mortality rates during the study period of cases and controls were 69.6% (n = 16) and 17.4% (n = 8), respectively. Lung involvement was the dominant clinical feature (n = 14). Two cases were associated with graft failure, one preceded by haemophagocytic syndrome. Given TXP-related morbidity and attributable mortality, anti-Toxoplasma prophylaxis is essential for optimized management of seropositive AHSCT recipients

Both intravenous and subcutaneous immunoglobulins are therapeutic modalities approved in various conditions, including primary and secondary immune deficiencies and autoimmune disorders. To date, immunoglobulins have more often been considered as a safe medication, with minor adverse effects such as hypertension, fever and chills, nausea, myalgia or headache. However, with the wider use of immunoglobulins in the treatment of autoimmune diseases, severe side effects have also been reported to occur in immunoglobulin-treated patients, especially anaphylaxis, aseptic meningitis, acute renal impairment, thrombotic events as well as haematological manifestations. This paper reviews all the potential adverse events related to immunoglobulin therapy and establishes a comprehensive guideline for the management of these events.

L’allogreffe de cellules souches hematopoietiques a longtemps represente la seule therapeutique curatrice de la leucemie myeloide chronique (LMC), malgre des comorbidites et un taux de mortalite importants. Elle reste neanmoins a ce jour un outil toujours en vigueur dans l’arsenal therapeutique de la LMC qui est maintenant domine par les inhibiteurs de tyrosine-kinase de premiere puis de deuxieme generation. Cependant, certains patients restent en echec de ces therapeutiques utilisees seules ou combinees, et de nouvelles alternatives interessantes peuvent etre representees par l’omacetaxine ou le ponatinib. Nous reprenons ici les donnees cles de la litterature concernant ces outils therapeutiques anciens ou innovants.

To illustrate methodological issues, we compared donor vs no-donor to transplant vs no-transplant comparisons in a cohort of 107 patients aged ⩽50 years with adverse karyotype AML in first CR. Adverse karyotypes were defined as −7, del(7q), −5, del(5q), t(9;22), 11q23, 3q26 or complex abnormalities. Mantel–Byar estimations and hematopoietic SCT (HSCT) as a time-dependent variable were used to compare transplant vs no-transplant cumulative incidence of relapse (CIR), relapse-free survival (RFS) and OS. In all, 52 patients had a sibling donor, but only 35 of them were transplanted in first CR, whereas 9 patients received HSCT from alternative stem cell sources. Donor-based analysis showed lower CIR in the donor group, not translating in prolonged RFS or OS. Conversely, transplant-based analysis showed that HSCT in the first CR improved the three CIR (multivariate hazard ratio (HR), 0.31; P

Resume La greffe allogenique de cellules souches hematopoietiques est la forme d’immunotherapie cellulaire la plus employee grâce aux cellules allogeniques etrangeres au patient porteur du cancer, qui reconnaissent et eliminent les cellules tumorales. La curabilite par allogreffe de cellules souches hematopoietiques est basee sur deux mecanismes d’action : le conditionnement myelo-ablatif ou non myelo-ablatif et immunosuppresseur induisant une cytoreduction importante des cellules tumorales ou l’induction de tolerance et le controle antitumoral immunologique assure par des effecteurs immuns allogeniques appele effet GVL ou GVT (effet du greffon contre la leucemie ou la tumeur). Cette strategie est actuellement en phase de mutation importante en raison de developpements technologiques et medicamenteux recents avec : (a) les greffes de cellules souches hematopoietiques sanguines obtenues apres mobilisation par des facteurs de croissance hematopoietiques et les greffes de sang placentaire ; (b) l’augmentation des greffes a partir de donneurs volontaires et le developpement des greffes haplo-identiques ; (c) l’immunomodulation guidee par la documentation du chimerisme et de la maladie residuelle apres la greffe avec reinjection de lymphocytes du donneur ; (d) les conditionnements d’intensite reduite visant a reduire la toxicite en limitant l’intensite chimiotherapique du conditionnement et en favorisant l’effet antitumoral immunologique ; (e) la chimiotherapie sequentielle suivie d’allogreffe apres conditionnement non myelo-ablatif dans le cas d’hemopathies refractaires ou a tres mauvais pronostique. L’experience acquise montre indeniablement que cette strategie doit etre developpee et affinee du fait du benefice potentiel attendu chez certains patients et ainsi l’allogreffe de cellules souches hematopoietiques veritable immunotherapie devrait etre positionnee dans le cadre d’une strategie therapeutique globale en onco-hematologie.

50 patients with a median age of 41 years (range 29–54) underwent allogeneic bone marrow transplantation for multiple myeloma. 35 patients were on second-line treatment, and 15 on first-line treatment. 24 patients were considered refractory to previous treatment. 45 patients received marrow from HLA-matched sibling donors (3 of these from twin donors), and 5 from unrelated or related non-sibling donors. 21 patients entered complete remission, while 15 had persistent disease following repopulation of the marrow. 14 patients were not evaluable for remission status because of early transplantation-related death. The overall median survival from bone marrow transplantation was 27 months, with a projected long-term survival of 34%. Patients who were 40 yr of age or older had a survival that was not different from that of patients between 29 and 40 yr of age. The median disease-free survival of patients who entered complete remissions was 41 months. These patients tended to have a longer survival than patients with persistent disease following repopulation of the marrow. Allogeneic bone marrow transplantation appears to be a promising method for treatment of certain patients with multiple myeloma.

Summary Paroxysmal nocturnal haemoglobinuria is a rare but serious disease. It is treated today with eculizumab, a humanized monoclonal antibody, that blocks the complement activation of C5. Six patients were treated, with blood collection at each eculizumab infusion; intravascular haemolysis remained with a sharp drop in the haptoglobin level in all patients and a fairly high level of total biliburin in at least 50% of patients despite a significant decrease in the lactate dehydrogenase level. In two patients, the direct antiglobulin test was positive for the complement only (C3d) after a treatment period of two weeks and eight months without associated blood transfusion. The percentage of deficient red blood cells (CD59 negative) increases either rapidly or slowly or may remain steady as seen through flow cytometry. In the six patients of our study, the size of deficient granulocytes and monocytes clones remained unchanged.

International audience; OBJECTIVES: Human herpes virus 6 (HHV-6) can reactivate after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and may be associated with significant clinical manifestations. METHODS: Case control study of HHV-6 infections after allo-HSCT. Chromosomal integration (ciHHV-6) for viral loads \\textgreater/= 5.5-log10 copies/mL was investigated. Viral co-infections, T-cell recovery, risk factors and outcome were compared in HHV-6- and non-HHV-6-infected patients. Antiviral treatment strategies were reviewed. RESULTS: Among 366 adult allo-HSCT recipients, 75 HHV-6 infections occurred. Three (4%) recipients were ciHHV-6. HHV-6 infections were associated with CMV (p = 0.05; sdHR 1.73, CI 0.99-3.02) and/or BKV infections (p \\textless 0.0001; sdHR 4.63, CI 2.04-10.53) but not EBV reactivation (p = 0.34). A slower CD8+ T-cells recovery was observed until 6 months after allo-HSCT in the HHV-6-infected group (p \\textless 0.001), independently of acute and/or chronic graft-versus-host disease. The overall probability of survival after allo-HSCT was diminished for active HHV-6-infected patients (p = 0.0326). Cord blood unit recipients had a higher risk of developing HHV-6 infection compared to bone marrow recipients (p = 0.0007; sdHR 3.82, CI 1.76-8.27). Anti-HHV-6 treatment achieved complete response in only 2/3 of the cases. CONCLUSIONS: In this series of allo-HSCT recipients, 4% were ciHHV-6, active HHV-6 infection was likely associated with CMV and BKV co-reactivations, delayed CD8+ T-cell recovery and poorer outcome

Introduction: In a developing country like Algeria, such expensive therapy is not available. Alternative approaches are needed to help these adult. In Algeria ‘imatib’ (CIPLA-India) was introduced in 2006; but no study has been published yet in the North Africa region regarding response and outcome of this copy in CML patients. The goal of this multicenter study is to characterize newly adult CML in the western region of Algeria and to assess the effectiveness and safety of imatib (IM, copy) as frontline therapy for patients with CML. Patients and Methods: The study was carried out in 7 hematology centers in the western Algeria. Patients, who were diagnosed to be suffering from CML between January 1 st , 2007 and December 31 st , 2014 were selected for data analysis. All patients received a copy preparation, consisting of the alpha crystal form of imatinib, (IM, copy) at a oral dose of 400 mg daily and monitored for tolerance and side effects while on therapy. Results: Between January 2007 and December 2014, 355 patients with CML were treated with imatib (Copy). The median follow- up of the study was 46 months (range: 13–107 months). Complete hematological response (CHR) was seen in 83% of patients within 3 months. According to the Sokal score, 72% patients with low, 78% with intermediate and 69% with high risk disease achieved a CHR in 3 months (p=0.26) and according to the EUTOS score, 81% of patients with low and 70% with high risk disease achieved a CHR in 3 months (p=0.08). The major molecular response (MMR) at six months (M6), M9, M12, M18 and M24 was 21%, 38%, 35%, 51% and 67% respectively and 34% of patients achieved a complete molecular response (CMR). The projected 5-year overall survival (OS) rate was 83%. Side effects of imatib (copy) in this study were similar to those reported previously for the entire imatinib mesylate treatment study and only 8% of patients were intolerant to imatib (copy) and treated with a second generation of BCR-ABL inhibitor. Conclusion: This study reflects real world experience treating patients with CML in a developing country and thus sheds light on differences in this population compared to Western countries. In conclusion, imatib (copy) is effective and safe in treating patients with CML in chronic phase and proves to have a durable outcome. To our knowledge this is the first study reporting the response to imatib (copy) in a Algerian population.

Haploidentical allogeneic stem cell transplantation (CST) has globally taken off in the past decade. It appears to be a valid alternative to other sources of stem cells; however, further research is necessary to validate the use of this approach in standard patient care. In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) set up its fourth annual series of workshops which brought together practitioners from all of its member centers. These workshops took place in September 2013 in Lille. This is part one of the recommendations regarding allogeneic stem cell transplantation from an HLA-haploidentical related donor.

Haploidentical allogeneic stem cell transplantation (CST) has globally taken off in the past decade. It appears to be a valid alternative to other sources of stem cells; however, further research is necessary to validate the use of this approach in standard patient care. In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) set up its fourth annual series of workshops which brought together practitioners from all of its member centers. These workshops took place in September 2013 in Lille. This is part two of the recommendations regarding allogeneic stem cell transplantation from an HLA-haploidentical related donor.

The role of anti-HLA antibodies in allogeneic stem cell transplantation setting is still unclear. In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) set up its fourth annual series of workshops which brought together practitioners from all of its member centers. These workshops took place in September 2013 in Lille. This article offers the recommendations of the group that considered the impact that have anti-HLA antibodies on outcomes in allogeneic stem cell transplantation.

Item does not contain fulltext Out of 690 allogeneic matched sibling donor transplants for multiple myeloma reported to the European Group for Blood and Marrow Transplantation (EBMT) registry, 334 were performed during the period 1983-93 (all with bone marrow) and 356 during 1994-98 [223 with bone marrow and 133 with peripheral blood stem cells (PBSCs)]. The median overall survival was 10 months for patients transplanted during the earlier time period and 50 months for patients transplanted with hone marrow during the later period. The use of PBSCs was associated with earlier engraftment but no significant survival benefit compared to bone marrow transplants during the same time period. The improvement in survival since 1994 with the result of a significant reduction in transplant-related mortality, which was 38%, 21% and 25% at 6 months and 46%, 30% and 37% at 2 years during the earlier period, and the later period with bone marrow and PBSCs respectively. Reasons for the reduced transplant-related mortality appeared to be fewer deaths owing to bacterial and fungal infections and interstitial pneumonitis, in turn a result of earlier transplantation and less prior chemotherapy. Better supportive treatment and more frequent use of cytokines may also play a role. The improvement in survival was not directly related to the increased use of PBSCs.

In order to assess the place of HLA-identical allogeneic bone marrow transplantation (BMT) and to compare it to other post-induction therapies, we analyzed patient outcome in intention-to-treat based on the presence or not of an HLA-identical familial donor in young adults with de novo acute myeloid leukemia (AML) in first complete remission (CR). Between 1985 and 1998, 152 consecutive AML patients aged less than 41 years old, seen in our institution, were treated according to 3 different successive protocols (LYLAM85, LAM90, AML10). 144/152 patients entered our prospective study in which they were registered at time of diagnosis for presence or absence of HLA-identical donor and analyzed in intention-to-treat. In this study, 52 patients (36%), who had at least one identical sibling donor (group 1), were offered allogeneic BMT after CR achievement. The 92 patients without donor were allocated to group 2 and were assigned to receive chemotherapy or autologous transplantation as post-remission according to the protocol they were initially included in. Patients from both groups had similar disease characteristics at diagnosis. Karyotypes at diagnosis were defined as low risk (t(8;21) or t(15;17) or chromosome 16 abnormalities(, intermediate risk (normal karyotypes), or high risk (other abnormalities). Overall, 114/152 patients (75%) achieved a CR. Of the 144 eligible patients, 46/52 (88%) with a donor and 68/92 (74%) without a donor achieved a CR. The median follow-up duration of the 144 patients was 21.2 months. The relapse rate was higher in group 2 (56%) than in group 1 (31%). However, the overall survival was not different between patients with and without donor (median survival respectively at 16.7 months and 26.6 months with estimated survival at 5 years respectively at 32% and 34%). Thirty-four patients from group 1 (65%) were actually transplanted in first CR. The probability of 5-year survival for patients receiving effectively allogeneic BMT was 44% and was not significantly better than that of patients who did not. In univariate as in multivariate analysis, karyotypic status was the main prognostic factor for CR achievement (p = 0.002), CR duration (p < 0.0001), and overall survival (p < 0.0001). There were no significant differences between group 1 and group 2 when survivals were compared with adjustment for karyotypes.

Introduction Les pneumopathies aigues infectieuses sont des causes frequentes et majeures de morbimortalite chez les patients d’hematologie. Le lavage broncho-alveolaire (LBA) fait partie de la strategie diagnostique mais reste a risque chez des patients qui sont en plus sous anti-infectieux de large spectre. L’objectif etait de rechercher des facteurs predictifs de positivite des LBA realises pour pneumopathie aigue en contexte infectieux chez les patients immunodeprimes d’hematologie afin de mieux definir les patients pour lesquels cet examen sera rentable. Methodes Cette etude etait retrospective, observationnelle, unicentrique et s’interessait aux LBA consecutifs realises devant l’association d’une nouvelle image scannographique pulmonaire et d’une fievre chez des patients atteints de leucemie aigue et/ou allogreffes de moelle. Les LBA etaient classes en 2 groupes (LBA positifs et LBA negatifs) qui etaient compares. Resultats Entre octobre 2011 et juin 2014 sur 141 LBA realises chez 114 patients dans cette indication 69 etaient positifs et 72 negatifs. Il n’y avait pas de difference entre les deux groupes sur les anti-infectieux (proportion de patients sous anti-infectieux, nombre de lignes, duree) pris avant la realisation du LBA, le statut d’immunosuppression des patients, les caracteristiques de l’episode infectieux aigu et les conditions de realisation de l’examen. Le pronostic a 30 jours des patients n’etait pas different entre les groupes sur la survie, la proportion de passages en reanimation et de retour a domicile. A plus long terme, avec un suivi moyen de 312 jours, 61 patients sur 114 patients sont morts pendant notre etude (53,5 %). Conclusion Notre etude n’a pas permis de retrouver de facteurs predictifs de rentabilite du LBA realise pour pneumopathie aigue infectieuse chez les patients immunodeprimes d’hematologie mais confirme les donnees de la litterature et en particulier la rentabilite du LBA dans cette indication meme chez des patients sous traitement anti-infectieux large spectre prealable.

In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here we report our results and recommendations regarding the choice of optimal unrelated cord blood unit in terms of cell dose, HLA-matching and other characteristics.

Summary. Itraconazole, a new triazole antifungal agent, has marked in vitro activity against filamentous fungi, particularly Aspergillus. We studied three groups of patients suffering from aspergillosis (16 cases): six affected with aspergilloma, three with allergic bronchopulmonary aspergillosis and seven with invasive aspergillosis. The survey consisted in clinical, radiological, mycological and serological evaluations with respect to drug plasma levels. Itraconazole was given at a dosage of 200–400 mg day-1 for periods ranging from 14 to 488 days. Out of the 16 patients, nine responded to therapy (recovery or improvement) and one failed to respond. Three patients improved but experienced relapses and three others could not be evaluated because of liver function disorders, so that treatment had to be stopped prematurely. Zusammenfassung. Itraconazol, ein neues antimykotisches Triazol hat eine in vitro nachgewiesene Wirkung gegen Fadenpilze, im besonderen Aspergillus. Wir untersuchten 3 Patientengruppen, die an Aspergillose litten (16 Falle); 6 davon waren von einem Aspergillom betroffen, 3 Falle mit allergischer bronchopulmonarer Aspergillose und 7 Falle mit invasiver Aspergillose. Die Uberwachung bestand aus klinischen, radiologischen, mykologischen und serologischen Untersuchungen mit Berucksichtigung der Medikamentenspiegel im Plasma. Itraconazol wurde in einer Dosis von 200–400 mg/Tag fur die Dauer von 14–488 Tagen gegeben. Von 16 Patienten reagierten 9 mit Heilung oder Besserung, 1 Patient reagierte nicht auf die Therapie. Der Zustand von 3 weiteren Patienten bessertc sich, sie erlitten jedoch Ruckfalle. Drei andere Falle konnten wegen Storungen der Leberfunktion nicht berucksichtigt werden, so das die Behandlung in diesen Fallen sofort beendet werden muste.

Allogeneic hematopoietic stem cell transplantation is the most widely used form of immunotherapy. The allogeneic immune effectors infused with the graft can recognize and eradicate the patients' tumoral cells. The curative potential of allogeneic hematopoietic stem cell transplantation is classically based on two mechanisms: the conditioning myelo-ablative or immunosuppressive inducing either the cytoreduction of tumoral cells or tolerance and the immune control mediated by allogeneic immune effectors (graft-versus-leukemia or tumor effect, GVL or GVT). Allogeneic hematopoietic stem cell transplantation is currently under important mutations because of better understanding of the GVT mechanisms and the development of new treatment techniques with: (a) allo-hematopoietic stem cell transplantation of peripheral blood stem cells after mobilization with G-CSF and allotransplant of cord blood cells; (b) increase number of allogeneic hematopoietic stem cell transplantation from unrelated and haplo-identical donors; (c) immunomodulation according to the chimerism and residual disease documentation with donor lymphocyte infusion (DLI); (d) development of reduced intensity conditioning regimens aiming to reduce the toxicity while favoring the immune component of the anti-tumoral effect; (e) development of sequential chemotherapy followed by allogeneic hematopoietic stem cell transplantation after reduced intensity conditioning in case of refractory diseases. In addition the present experience shows clearly that the allogeneic hematopoietic stem cell transplantation strategy should be developed and refined because of the potential benefit that can be expected in some patients' sub-groups and then allogeneic hematopoietic stem cell transplantation, real immunotherapy should be included in the global therapeutic strategy in onco-hematology.

Preferential sensitivity of hematopoietic (HPs) and mesenchymal (MPs) progenitors to fludarabine suggests impaired bone marrow niche and HP mobilization

Le traitement des leucemies aigues myeloblastiques (LAM) comprend la prise en charge transfusionnelle de thrombopenies profondes. Le choix d’une attitude transfusionnelle (AT) prophylactique (sur chiffre plaquettaire) vs therapeutique (sur signes cliniques) evoque par l’etude de Slichter (2004) reste encore discute. Nous avons compare retrospectivement l’AT de l’institut Paoli-Calmettes (IPC) ayant opte jusqu’en 2012 pour une AT therapeutique, a celle du centre d’hematologie de Lyon (CHU E. Herriot, CEH), ayant opte pour une AT prophylactique. L’analyse compare chez les patients (Pts) adultes induits pour une LAM de 2001 a 2010, le nombre de deces par hemorragie et la consommation de produits sanguins durant l’induction (45 jours) et durant les 6 premiers mois de traitement. Au total, 885 Pts ont ete induits a l’IPC (âge my 59 ans, 45 % > 60 ans) et 524 au CHE (âge my 52 ans, 31 % > 60 ans). Durant l’induction, puis les 6 premiers mois, les Pts IPC et CEH ont recu en my 5,1 vs 10,3, puis 9 vs 20 CP. Durant ces 6 mois, a l’IPC et au CEH, 21 vs 6 Pts sont decedes d’hemorragie, a j18 et j130 en mediane, dont 8 vs 4 dans un contexte d’etat refractaire aux transfusions plaquettaires. A l’IPC, 4 Pts sont decedes dans un contexte de CIVD persistante, 8 dans un contexte de sepsis de grade ≥ 3. En conclusion, dans un contexte d’AT therapeutiques vs prophylactique, les TP ont ete 2 fois moins eleves mais plus de Pts sont decedes d’hemorragies, precoces et en contexte de sepsis. Ces resultats indiqueraient que le choix d’une AT prophylactique (consensus actuel), pourrait etre adapte aux facteurs de risque : pendant l’induction plutot qu’en consolidation ou lors de sepsis.

Background: OTX015 (Oncoethix) is a small molecule that specifically binds to BRDs 2, 3 and 4, thereby inhibiting binding to acetylated histones, resulting in downregulation of several oncogenes driven by super-enhancers. The therapeutic potential of BRD inhibitors has been demonstrated in several preclinical models including hematologic malignancies. Methods: The primary end point of this dose escalation study (3 + 3 design) was to establish the Phase 2 recommended dose (P2RD) and schedule in two independent cohorts of patients (pts) with either relapsed/refractory acute leukemia (AL) or other hematologic malignancies (OHM). OTX015 was given orally, daily (qd), with 1 bidaily (bid) dose level (DL) explored, continuously in OHM or for 14 days ON/7 days OFF in AL. Results: From January 2013 to August 2014, 41 pts with AL (AML 37; ALL 3) or high-risk myelodysplastic syndrome (HR-MDS 1) and 45 pts with OHM (22 diffuse large B-cell lymphoma [DLBCL], 11 other lymphomas, 12 multiple myeloma) were enrolled over 7 DLs from 10 to 160 mg. Dose-limiting toxicities (DLT) during the first treatment cycle were observed at doses >120 mg in AL (diarrhea, asthenia) and doses >80 mg in OHM (primarily thrombocytopenia). Additionally, both AL and OHM pts treated at >80 mg experienced grade 1-2 gastrointestinal events (diarrhea, dysgueusia) that hampered compliance, though not meeting DLT criteria. PK showed dose-proportional OTX015 exposure (AUC0-24h) up to 120 mg qd; trough plasma concentrations at 80 mg qd reached the GI50 cut-off of 500 nM for sensitive tumor cell lines in vitro. Two complete remissions (CR) and 1 CR with incomplete recovery (CRi) were observed in pts with relapsed/refractory HR-MDS or AML secondary to MDS and 2 CR and 1 partial response in DLBCL pts. OTX015 P2RD was determined as 80 mg qd with a 14 days ON/7days OFF schedule, based on kinetics of platelet nadir and recovery. Conclusion: OTX015 is an orally available molecule showing dose-proportional exposure up to 120 mg qd with a favorable tolerance profile, and evidence of clinical activity in refractory DLBCL and AML/HR-MDS. Expansion cohorts in AML secondary to MDS, de novo AML and DLBCL at the P2RD are ongoing.

Over the past decade, great progress has been made in the treatment of adult acute lymphoblastic leukemia (ALL). Improvements in the quality and availability of broad-spectrum antibacterial antibiotics, antifungal agents, and platelet transfusions, as well as greater understanding of the optimal use of a variety of antineoplastic agents, have resulted in gradual improvements in CR rates and the identification of a significant fraction of patients achieving long-term disease free survival [6, 9, 11, 12, 13, 16, 17]. Stem cell transplantation (SCT) is one of the postremission strategies for the eradication of residual disease in ALL. Long-term disease-free survival for patients with ALL after management with chemotherapy plus SCT is now widely accepted [7, 8, 20]. However, little data is still available on long-term survival beyond 3 years.

The approval of epoetin biosimilars in the European Union requires extensive scientific evaluation and stringent regulatory procedures, including post-marketing studies. The ORHEO (place of biOsimilaRs in the therapeutic management of anaemia secondary to chemotherapy in HaEmatology and Oncology) study was an observational, longitudinal, multicentre study performed in France to evaluate the efficacy and safety of biosimilar epoetins for the treatment of CIA in the clinical setting. Patients >18 years with CIA (haemoglobin [Hb] 2310 patients (mean age 66.5 years) from 232 centres were included, of whom 79.6% had solid tumours, 13.0% had lymphoma and 7.4% myeloma. Of those patients with solid tumours, 30.1% of patients had a stage III and 21.6% had a stage IV tumour. Almost all patients received the biosimilar epoetin zeta (Retacrit®, Hospira UK Ltd., median dose 30,000 IU/week). Mean baseline Hb level across all patients was 9.6 g/dL, with 35.6% of patients having moderate anaemia (Hb 8–9.5 g/dL). Following treatment, Hb response was achieved in 81.6% and 86.5% of patients at 3 and 6 months, respectively. The overall mean change in Hb level was 1.5 ± 1.6 g/dL at 3 months and 1.72 ± 1.61 g/dL at 6 months. Transfusion rates were 9.4% and 5.8%, while the rate of thromboembolic events was 2.4% and 1.5%, at 3 and 6 months respectively. In conclusion, Retacrit was effective and well tolerated in the management of CIA in patients with solid tumours, lymphoma and myeloma. Disclosure M. Michallet: I received honoraria from Hospira for advisory boards and consulting, P. Soubeyran: I received honoraria from Hospira for advisory boards and consulting, H. Albrand: Employed by Hospira, E. Luporsi: I received honoraria from Hospira for advisory boards and consulting.

The timing of transplantation in chronic myeloid leukaemia is still debated and previous treatment with interferon (IFN) alpha has been reported to be deleterious. We have analysed the outcome of 438 allogeneic transplants performed between 1984 and 1995 and reported to the Société Française de Greffe de Moelle (SFGM) registry. One hundred and two patients (group I) received IFN for more than 6 weeks (median = 9 months) before transplant. Their outcome was compared with 336 other patients (group II) not pretreated with IFN. There were no significant differences between the groups for engraftment and chronic graft-versus-host disease (GVHD) incidence. However, other significant differences included the incidence of acute GVHDor = 2 at 3 months which was higher in group I (65 +/- 10%) than in group II (38 +/- 5%; P = 0.01). Moreover, disease-free survival (DFS) and overall survival (OS) at 5 years were significantly shorter for group I than for group II (33 +/- 10% vs. 41 +/- 6%; P = 0.005)(95% CI) and (41 +/- 10% vs. 55 +/- 6%; P = 0.002)(95% CI) respectively. After adjustment for patient and transplant covariables in a multivariate analysis, prior IFN was not found to adversely affect transplant outcome.

Cent quarante-cinq concentres de granulocytes obtenus par apherese (CGA) ont ete transfuses chez 37 patients immunodeprimes (mediane d’âge : 54 ans). Tous les patients ont ete hospitalises en secteur protege et en aplasie (neutrophiles E. coli (9), staphyloccoque coagulase negatif (6), Pseudomonas aeruginosa (5), Fusarium (3), Candida albicans (2), virus respiratoire para influenzae (1), Steptophomonas (1). Dans 10 cas, aucun agent infectieux n’a ete retrouve. Le nombre de CGA par patient variait de 1 a 10 culots (mediane : 3). Neuf patients ont egalement eu recours a un geste chirurgical (6 mises a plat, 1 ablation de PAC, 2 drainages cutanes), 18 ont recu des facteurs de croissance et 8 une corticotherapie. Aucun effet indesirable lies aux CGA n’a ete rapporte. La mediane de duree d’aplasie etait de 27 jours (10–120) pour une mediane de duree d’hospitalisation de 39 jours. L’infection a ete totalement maitrisee dans 70 % des cas. Deux patients sont decedes. La transfusion de CGA represente un complement therapeutique utile dans un contexte infectieux severe chez les immunodeprimes. Son indication doit cependant rester limitee aux formes majeures et, une fois initiee, doit etre repetee jusqu’a la maitrise de l’infection.

Allogeneic transplantation of hematopoietic stem cells (HSC) is a curative treatment for hematological malignancies aiming to eradicate the malignant clone using the immunological conflict inherent to donor HSC installation in the recipient. The different possible sources of HSCs (bone marrow, blood, and cord blood) and better knowledge of HLA typing has led to the development of new transplantation techniques and modalities (transplantations after non-myeloablative conditioning, haploidentical transplantations, etc.), which should improve patient survival and extend allograft indications. HSC allografting is subject to immunological reactions stemming from the histocompatibility discrepancy between donor and recipient. For the most part, these are reactions of the graft against the host (graft-versus-host disease: GVHD) and graft rejection (host-versus-graft: HVG). This immunological conflict can also be responsible for recognizing and destroying the recipient's residual tumor cells, which carry specific tumor antigens and/or minor antigens of histocompatibility (graft-versus-leukemia effect, GVL or graft-versus-malignancy effect, GVM). The posttransplantation period can also be riddled with various complications such as veno-occlusive disease, endocrine complications, as well as complications arising from infections and secondary neoplasms because of a more or less substantial and durable immune deficiency. Acute and chronic leukemias are the major indications for HSC allogeneic transplantation, for which the results are variable and closely related to the patient status, the hematological disease, and the transplant procedure. Other hematological diseases are also indications for allogeneic transplantation but are rarer, for which allogeneic transplantation remains nevertheless the only curative treatment, despite an overly high level of toxicity. Improvement in the results of unrelated transplantations, use of peripheral HSC or cord blood cells, development of non-myeloablative conditioning regimens, and techniques of ex vivo manipulation of the graft have allowed HSC allogeneic transplantation indications to be extended. The antitumor efficacy of donor lymphocytes infusion for relapses after transplantation mirrors the GVL effect and is the first stage in a targeted cellular immunotherapy using sensitized lymphocytes or dendritic cells.

There is now convincing evidence that minor histocompatibility antigens (mHag) may play a significant role in the pathogenesis of graft-versus-host disease after HLA-identical bone marrow transplantation. Indeed, in this clinical situation, T cells specific for mHag have been isolated. Here, we addressed whether one can generate mHag-specific T cells in vitro, without any in vivo immunization, among healthy blood donors.We used monocyte-derived dendritic cells (Mo-DCs) as antigen presenting cells to induce primary responses between healthy HLA-identical siblings, in mixed lymphocyte dendritic cell reactions (MLDCRs).We show that CD4+ T-cell clones, specific for the mHag H-Y, can be generated in vitro. These clones were derived from a gender-mismatched positive MLDCR pair of HLA-identical siblings and were restricted by the HLA DQB1*0502 molecule. In addition, these CD4+ T clones were also able to lyse allogeneic targets with the same pattern of restriction and specificity than helper function. Finally, acute myeloid leukemia (AML) blast cells were susceptible to lysis by these clones.Altogether, these results predict that Mo-DCs could help to generate class II-associated, mHag-specific, T-cell lines or clones in vitro, between healthy blood donors, without any need of transplantation-mediated immunization.

Treatment of adult acute lymphoblastic leukemia (ALL) remains unsatisfactory [1-4]. Different strategies such as allogenic, autologous transplantation or more intensive chemotherapy may improve the outcome. Their exact place is still controversial according to the stage (first or second remission) or to the aggressiveness of the disease (high or standard risk).

To test the value of the combination of pefloxacin and vancomycin as gastro-intestinal tract decontamination for the prevention of infections in patients with chemotherapy-induced neutropenia.Oral pefloxacin plus vancomycin (48 patients), pefloxacin alone (51 patients), or placebo (52 patients) were administered in a randomized double-blind study. Evaluation was done by determining site and documentation of infections, organisms responsible for bacteriologically documented infections, organisms acquired in surveillance cultures and number of days with fever during aplasia.Patients receiving pefloxacin had significantly fewer episodes of bacteremia with enterobacteriacae. No differences were noted between patients treated by pefloxacin and those who received a combination of pefloxacin with vancomycin regarding gram-positive (Gram+) infections and infections with gram-negative (Gram-) organisms usually resistant to pefloxacin. However, placebo gave similar results. There was no induction of resistance to pefloxacin during the study. Tolerance of treatment was excellent. Only a prolonged aplasia has been observed in patients receiving pefloxacin.Thus, the combination of vancomycin with pefloxacin was not more efficacious than pefloxacin only for the prevention of Gram+ infections in the neutropenic patient. The systematic use of antibiotics as gastrointestinal tract decontamination for the prevention of infections in patients with aplasia may be questionable.

The aims of our study performed in myeloma were to evaluate the performance and the safety of Systemix's high-speed clinical cell sorter, to assess the safety and efficacy of deescalating cell dose cohorts of CD34+Thyl+ hematopoietic stem cells (HSCs) as autologous grafts by determining engraftment, and to assess the residual tumor cell contamination using polymerase chain reaction (PCR) amplification assays of patient-specific complementarity determining region III (CDR III) analysis for residual myeloma cells.The clinical trial was performed in 31 multiple myeloma patients, using purified human CD34+Thyl+ HSCs mobilized from peripheral blood with cyclosphosphamide and granulocyte-macrophage colony-stimulating factor to support a single transplant after high-dose melphalan 140 mg/m2 alone (cohort 1) and with total body irradiation (TBI) (cohorts 2-5) after an HSC transplant cell dose de-escalation/escalation design.Twenty-three patients were transplanted. Engraftment data in the melphalan + TBI cohorts confirmed that HSC doses above the threshold dose of 0.8 x 10(6) CD34+Thy1+ HSCs/ kg provided prompt engraftment (absolute neutrophil count0.5 x 10(9)/L day 10; platelet count50 x 10(9)/L day 13). A higher rate of infections was observed in the early and late follow-up phases than usually reported after CD34+ selected or unselected autologous transplantation, which did not correlate with the CD34+Thy1+ HSC dose infused. Successful PCR for CDR III could only be performed in five patients on initial apheresis product and final CD34+Thy1+ HSC product and showed a median tumor log reduction3.12.CD34+Thy1+ HSCs are markedly depleted or free of detectable tumor cells in multiple myeloma and are capable of producing fast and durable hematopoietic reconstitution at cell doses0.8 x 10(6) CD34+Thy1+ HSCs/kg. The delayed immune reconstitution observed is not different from that described in unselected autologous bone marrow and peripheral blood mononucleated cells transplants in multiple myeloma and may be corrected by addition of T cells either to the graft or to the patient in the posttransplant phase.

Immunological control of acute leukemia may be achieved after allogeneic transplant. Despite promising preliminary results, the impact of immunotherapy with interleukin-2 (r-IL-2) on patients with acute leukemia (AL), in first complete remission (CR1) remains unclear. We conducted a prospective multicenter randomized trial to compare outcome in patients with AL in CR1, treated with autologous bone marrow transplantation (BMT) with or without postgraft r-IL-2. One hundred and thirty patients with AL in CR1 (myeloblastic (AML): N = 78; lymphoblastic (ALL): N = 52) were randomized at time of BMT to receive (N = 65) or not (N = 65) r-IL-2. r-IL-2 (RU 49637 from Roussel Uclaf) was started after hematological recovery, as a five cycle regimen (12 M IU/m2/day continuous infusion on day 1-5, 15-17, 29-31,43-45 and 57-59). The two groups were balanced for patient and transplant characteristics. Analysis was based on an intent to treat. Thirty-eight (59%) of the 65 patients randomized into the study group started r-IL-2 at a median of sixty-eight days (23-140) after transplant and received 77% (16-100) of the scheduled dosage. They received a median of 120 x 10(6) IU/m2 (25-156) over 10 (3-13) days during a total median period of 56 (3-78) days. With a median follow-up of 7 years (5.4-8.1 years), 79 patients relapsed (study group: 43 (66%); control group: 36 (55%): p = NS). Survival and leukemia-free survival estimates were 33% (23-45) versus 43% (22-52) and 29% (19-41) versus 36% (24-51) respectively for study and control groups (all p = NS). These results show that leukemic control after autologous BMT is not increased by r-IL-2 therapy. Further studies should investigate more appropriate r-IL-2 schedules and the possibilities offered by better antigen recognition and activated effector cells.

The place of allogeneic bone marrow transplantation (BMT) in the treatment of aggressive non-Hodgkin's lymphoma (NHL) remains controversial. We conducted a retrospective study of French experience in allografting NHL between 1984 and 1994. To improve the homogeneity of the study population, cases of low-grade, Burkitt and lymphoblastic NHL were excluded. 73 patients were included in the analysis. Median age at transplantation was 35 years (range 9-61 years); 64 patients were in stage IV and 45 had bone marrow involvement at diagnosis. At the time of transplantation, 46 patients had sensitive disease (25 in complete remission; CR). The overall survival (OS) and progression-free survival (PFS) rates were 41% and 40% respectively at 5 years (median follow-up of survivors 90 months). The probability of disease progression was 30% at 5 years, and only one relapse occurred after 15 months. 32 patients died of transplantation-related complications. In multivariate analysis, pretransplant complete remission was the main factor associated with longer survival (OS at 60 months of 76% among the 25 patients in CR at transplant and of 23% among the 48 patients not in CR at transplant). Neither acute nor chronic graft-versus-host disease (GvHD) influenced the relapse rate. In conclusion, in this high-risk population the overall results of allogeneic BMT were encouraging, despite a high transplant-related mortality rate. We believe this procedure should be studied further in prospective controlled trials.

Resting energy expenditure (REE) was measured by indirect calorimetry during allogeneic and autologous bone marrow transplantation in order to evaluate the evolution in allogeneic and autologous recipient patients. REE values obtained with indirect calorimetry and compared with values using the Harris-Benedict formula were different. Evolution of REE during aplasia were significantly different in autologous and allogeneic recipients with an increase 11.5 ' 10.8 cent for autologous and a decrease of - 7.3 ' 8.9 cent in allogeneic bone marrow transplantation (BMT) patients. There were no differences in nutritional status and REE before BMT, at discharge and 1 month after discharge between the two groups but all patients had inflicted damage on their nutritional status at discharge from hospital after BMT. However, these patients differed because of the decrease in oral nutritional intake and an increase in the length of aplasia and hospital stay in allogeneic patients. Currently, there is no proof that recommendations for nutritional interventions or results of nutritional investigations in allogeneic BMT can be extrapolated in autologous patients. Harris-Benedict formula does not estimate the energy expenditure of patients submitted to massive chemotherapy and BMT with enough precision because of the great differences in individuals.

The effectivness of interferon alpha (IFN) for the treatment of chronic myelogenous leukemia (CML) during the chronic phase is now well established. Several studies have shown that IFN produces hematologic remission in 60% to 80% of patients [1]. In some studies the achievement of complete hematologic response within 3 months seems to represent a significant factor which correlates with a cytogenetic response [2]. Also, the treatment with IFN resulted in suppression of the Ph-positive cells population which was complete in 7% to 25% of the patients [3, 4]. A major cytogenetic response (i.e., less than 35% Ph-positive cells) was noted in 35 to 45% of the patients. Such cytogenetic response was not only complete but also prolonged for periods ranging between 2 and 8 years [5].

Treatment with interferon prolongs survival in chronic myelogenous leukemia. We conducted a clinical trial to assess the efficacy of treatment with a combination of interferon and cytarabine.Previously untreated patients with chronic myelogenous leukemia were randomly assigned to receive either hydroxyurea (50 mg per kilogram of body weight per day) and interferon alfa-2b (5 million units per square meter of body-surface area per day), or hydroxyurea and interferon in the same dosages plus monthly courses of cytarabine (20 mg per square meter per day, for 10 days). The end points were overall survival, complete hematologic remission at 6 months, and major cytogenetic response (less than 35 percent Philadelphia chromosome-positive cells in the bone marrow) at 12 months.The trial was stopped when a sequential analysis showed a benefit of interferon and cytarabine. A significant improvement in survival was observed in the interferon-cytarabine group (360 patients) as compared with the interferon group (361 patients) (P=0.02; relative risk of death, 0.64; 95 percent confidence interval, 0.44 to 0.93). After three years, the survival rate was 85.7 percent with interferon and cytarabine and 79.1 percent with interferon alone. The rate of hematologic response was higher in the interferon-cytarabine group than in the interferon group (P=0.003). Major cytogenetic responses were observed 12 months after randomization in 126 of 311 patients treated with interferon and cytarabine (41 percent) and in 75 of 314 patients treated with interferon only (24 percent, P0.001).The combination of interferon and cytarabine, as compared with interferon alone, increases the rate of major cytogenetic response and prolongs survival in patients with the chronic phase of chronic myelogenous leukemia.

Allogeneic BMT for patients with acute myeloid leukemia (AML) is presently a reference therapy. The indications for this therapy mainly rely upon prognostic factors, and their importance is constantly reassessed. To examine the impact of time from diagnosis to transplant on survival and leukemia-free survival (LFS), we analyzed 109 patients from the database of the SFGM comprising patients who had all received an HLA-identical allogeneic BMT for a diagnosis of AML in first complete remission (CR1) between January 1987 and December 1992. All patients were conditioned with cyclophosphamide (CY) and total body irradiation (TBI) (CYTBI), and methotrexate (MTX) + cyclosporin A (CsA) were used as graft-versus-host disease (GVHD) prophylaxis. Patient characteristics were: age = 33 +/- 9, M/F = 64/45, white blood cell count (WBC) at diagnosis = 27 +/- 42 x 10(9)/l, FAB distribution: M1 and M2 = 55; M3 = 15, M4 and M5 = 33, M0, M6 and M7 = 6. Karyotyping was carried out for 64 patients: 32 had a normal karyotype, 16 had good prognosis abnormalities (t(8;21), t(15;17), inv 16) and 16 patients had other abnormalities. Eleven patients needed two courses of induction to achieve CR. Time between diagnosis and BMT was 120 (64-287) days. Forty-nine patients developed gradeor = 2 acute GVHD (actuarial probability = 46%). With a median follow-up of 50 months (27-100), the 5-year probabilities for transplant-related mortality (TRM), relapse, overall survival and LFS are respectively 25%, 26%, 59% and 55%. A multivariate analysis showed that survival is adversely influenced by three independent factors: time to transplant (120 days vsor = 120 days), acute GVHD (grade 2-4 vs grade 0-1) and age (33 vsor = 33). LFS is only influenced by the first two of these factors. The favorable impact of a shorter time from diagnosis to transplant should lead to performing the transplant as early as possible. Practically speaking, this means that when such therapy is chosen for a patient with CR1 AML, the search for an allogeneic donor should begin immediately and transplant be performed as soon as possible.

older. Previous studies have suggested that taking into account selected geriatric parameters extracted from the comprehensive geriatric assessment may improve both prognosis and chemotherapy tolerance. However they were heterogeneous consisting of patients with different tumor types and treatment regimens. A simplified scale would be a helpful tool for oncologist to predict chemotherapy feasibility. Objectives: The aim of the prospective OLD cohort study was to identify geriatric predictors of chemotherapy feasibility in chemonaive elderly cancer patients (NCT00664911). Methods: Inclusion criteria: ≥ 75 years, solid tumour, patient planned to receive≥ 2/3 of standard dose of first cycle of standard chemotherapy. Ten selected geriatric parameters were recorded at baseline by the oncologist: 1. 3 words test, 2. date and address (cognitive function), 3. Instrumental Activities of Daily Living, 4. monopodal stand-up test, 5.hospitalization during previous year, 6. number ofmedicines taken for co morbidities, 7.creatinine clearance, 8. albumin serum level, 9. selfrated depressive mood and 10. presence of a caregiver. The main outcome was chemotherapy feasibility defined by the ability to deliver at least 3 months of the planned regimen therapy, using a multivariate logistic regression Results: From 2008 to 2012, 576 patients were included in 49 centers. 516 (89.6%) were eligible for analysis. Patients’ characteristics: mean age 81 years; main tumour type, colorectal (51%); advanced stage, 70%; PS 0-1, 84%. Chemotherapy feasibility as defined per protocol was reached in 298 (57.8%) patients. Grade 3-4 toxicity occurred in 26.2%. In multivariate analysis, only 2 factors were significantly associated with failure to deliver chemotherapy: albuminemia b 30 g/L (adjusted OR =2.34 CI95% [1.43-3.83]) and depressive mood (adjusted OR= 1.55 CI95% [1.02-2.35]). Conclusion: Albuminemia and self rated depressive mood status are independent predictive factors for chemotherapy feasibility in elderly patients with solid tumour adding question to the relevant selection of geriatric factors to be used in the baseline assessment before chemotherapy administration. A focus on the colorectal subgroup will be presented at the meeting.

In 204 adult patients with de novo acute myeloid leukemia (AML), we prospectively compared allogeneic bone marrow transplantation (alloBMT), autologous stem cell transplantation (ASCT) and chemotherapy (Chemo). 162 patients (79.4%) achieved a complete remission (CR). Of the 135 patients who were still in CR after consolidation, 96 patients were less than 46 years of age: 36 patients had an HLA-identical sibling donor and were allocated for alloBMT (group I); they were compared to the 60 other patients who did not have an HLA-identical sibling donor and were treated with either ASCT or chemotherapy (group II). The 3-year disease-free survival was higher for group I patients (66.5 +/- 16%) than for the 60 group II patients (42.4 +/- 13%) (P0.05). The actuarial risk of relapse at 3 years was significantly lower for group I patients (24 +/- 15%) than for the other 60 group II patients (56 +/- 13%; P0.009). By multivariate analysis, the disease-free survival and risk of relapse were influenced by the initial WBC count (P0.02 and P0.006), the number of chemotherapy courses for CR (P0.001 and P0.01) and the type of post-induction treatment (alloBMT vs no alloBMT; P0.1 and P0.02). The 99 patients who did not fulfill the inclusion criteria for alloBMT were given intensive chemotherapy including high-dose aracytine. When they were still in CR (n = 77), these patients were then randomized for either ASCT (n = 39) or Chemo (n = 38). We were unable to detect any statistical difference between ASCT and Chemo for either disease-free survival, risk of relapse or survival. These results indicate that alloBMT seems to produce results which are at least superior to those of other therapeutic modalities. The results of either ASCT or Chemo look similar.

Bone marrow transplantation (BMT) is a potentially curative therapy in selected patients with hematologic disorders (acute leukemia, chronic myelogenous leukemia, lymphoma) or solid tumors (testicular or breast cancer). Pulmonary complications occur in 40 to 60% of patients receiving BMT, and are related to various mechanisms: chemotherapy-induced neutropenia, pulmonary toxicity of radiotherapy or chemotherapy, graft-versus-host disease. Bacterial or fungal pneumonia occurring during the initial period of neutropenia, and interstitial pneumonia (related to cytomegalovirus or of unknown origin) are the major respiratory complications of the first 100 days. Bacterial sinusitis and pulmonary infections, and obstructive airways disease related to bronchiolitis are the main late-onset respiratory disorders. No single risk factor can predict the development of these complications, which result from a sequence of events including infections, pulmonary injuries related to chemotherapy or radiotherapy, and inappropriate immunological reaction after transplantation. Antimicrobial prevention has been shown to reduce the mortality of these complications, but they still result in both important morbidity and mortality. They are the most frequent non relapse cause of death among long term surviving patients. Better understanding of their pathogenesis, and early recognition and treatment of respiratory complications of BMT should improve the efficacy of this therapy.

A prospective randomized study was conducted comparing the efficacy and toxicity of two anthracyclines for the treatment of patients with acute myeloid leukemia (AML) between 55 and 75 years. A total of 220 patients were randomized to receive as induction chemotherapy cytosine arabinoside (Ara-C: 100 mg/m2/day; continuous infusion for 7 days) combined with either daunorubicin (DNR: 50 mg/m2/day, i.v. bolus for 3 days) (n=108) or idarubicin (IDA: 8 mg/m2/day, i.v. bolus for 5 days) (n=112). The complete remission (CR) rate was similar (P=0.296) after IDA (76/112; 68%) and DNR (66/108; 61%) (P=0.3). For patients aged 55-65, the CR rate was significantly higher after IDA (39/47; 83%) than after DNR (29/50; 58%) (P=0.007). Persistent leukemia was more frequent after DNR (26/108) than after IDA (13/112; P=0.015). Hematological and extra-hematological toxicities were similar. The CR patients were given a consolidation course of chemotherapy with Ara-C: 50 mg/m2/12 h, subcutaneously for 5 days, combined with either DNR:30 mg m2/day, i.v. bolus for 3 days or IDA:8 mg/m2/day i.v. bolus for 3 days according to the initial randomization, and then received a continuous maintenance treatment for 2 years. The survival and disease-free survival (DFS) were similar in both groups; there was no difference in the risk of relapse. However, there was a trend for a longer event-free survival (EFS) in the IDA group than for the DNR patients (P=0.07). Our results seem to indicate that IDA is probably more efficient than DNR for AML patients between 55 and 75 years, and confirm the data published in other studies comparing prospectively IDA and DNR in adults.