In order to improve the outcome observed with azacitidine (AZA) in higher‐risk Myelodysplastic syndrome (MDS), its combination with other drugs in MDS must be evaluated. So far, no combination has ...not been shown to be more effective than AZA alone. AZA‐PLUS was a phase II trial that, in a “pick a winner” approach, randomly assigned patients with higher‐risk MDS, CMML and low blast count AML to: AZA; AZA plus lenalidomide; AZA plus Valproic Acid or AZA plus Idarubicin. 322 patients were included. After six cycles, 69 (21.4%) CR + PR were observed with no benefit from any combination. Median EFS and OS were 17.2 and 19.7 months in the whole cohort, respectively, with no difference across randomised arms. Infection and rates of hospitalisation during the first six cycles were higher in the AZA‐LEN And AZA‐IDA arm, related to increased myelosuppression. Factors associated with better response were IPSS, favourable or intermediate karyotype, haemoglobin, lower circulating blast count, fibrinogen level and lower LDH, while poorer survival was seen in therapy‐related MDS and, in the case of TP53, PTPN11 or CSF3R mutation. The combinations used did not improve the outcome obtained with AZA alone. However, our “pick a winner” randomised strategy may remain useful with potentially more active drugs to be tested in combination with AZA.
Abstract Objective Few studies have evaluated the nutritional status in acute myeloid leukemia (AML) patients during induction treatment. The aim of this retrospective study was to describe ...nutritional status of newly-diagnosed adult AML patients at admission and during induction chemotherapy. Research Methods & Procedures We included consecutive newly-diagnosed adult AML patients admitted in the Department of Hematology (Limoges University Hospital) from April 2010 to January 2014. Nutritional assessment included body mass index (BMI) and weight loss to diagnose undernutrition. Weekly laboratory tests were collected and total energy expenditure calculated to adapt food intake. Results Out of 95 patients, 14 (15%) presented undernutrition at admission: low BMI values (p<0.001) and weight loss >5% for 9.5% patients. After chemotherapy induction, 17 patients (18%) were undernutrition (p=0.05). Patients without undernutrition had a significantly lower median weight, BMI and serum albumin level at discharge compared with admission values (p<0.05) whereas their serum transthyretin levels were higher (p=0.03). They also had shorter hospital stays than patients with undernutrition (31 vs. 39 days; p=0.03)) and longer survival at 12 months (89.9% vs. 58.3% ( p= 0.002)). Conclusions AML patients with good nutritional status undergoing induction chemotherapy have shorter hospital stays and longer survival.
Abstract
In order to improve the outcome observed with azacitidine (AZA) in higher‐risk Myelodysplastic syndrome (MDS), its combination with other drugs in MDS must be evaluated. So far, no ...combination has not been shown to be more effective than AZA alone. AZA‐PLUS was a phase II trial that, in a “pick a winner” approach, randomly assigned patients with higher‐risk MDS, CMML and low blast count AML to: AZA; AZA plus lenalidomide; AZA plus Valproic Acid or AZA plus Idarubicin. 322 patients were included. After six cycles, 69 (21.4%) CR + PR were observed with no benefit from any combination. Median EFS and OS were 17.2 and 19.7 months in the whole cohort, respectively, with no difference across randomised arms. Infection and rates of hospitalisation during the first six cycles were higher in the AZA‐LEN And AZA‐IDA arm, related to increased myelosuppression. Factors associated with better response were IPSS, favourable or intermediate karyotype, haemoglobin, lower circulating blast count, fibrinogen level and lower LDH, while poorer survival was seen in therapy‐related MDS and, in the case of
TP53
,
PTPN11
or
CSF3R
mutation. The combinations used did not improve the outcome obtained with AZA alone. However, our “pick a winner” randomised strategy may remain useful with potentially more active drugs to be tested in combination with AZA.
Acquired thrombotic thrombocytopenic purpura is still associated with a 10-20% death rate. It has still not been possible to clearly identify early prognostic factors of death. This study involved ...thrombotic thrombocytopenic purpura patients with acquired severe (<10% of normal activity) ADAMTS13 deficiency and aimed to identify prognostic factors associated with 30-day death.
The study involved a prospective cohort of patients and was carried out between October 2000 and August 2010. A validation cohort of patients was set up from September 2010 to August 2011. Altogether, 281 (analysis cohort) and 66 (validation cohort) consecutive adult thrombotic thrombocytopenic purpura patients with acquired severe ADAMTS13 deficiency were enrolled. The study evaluated 30-day mortality after treatment initiation according to characteristics at inclusion.
Non-survivors (11%) were older (P=10(-6)) and more frequently presented arterial hypertension (P=5.10(-4)) and ischemic heart disease (P=0.013). Prognosis was increasingly poor with age (P=0.004). On presentation, cerebral manifestations were more frequent in non-survivors (P=0.018) and serum creatinine level was higher (P=0.008). The most significant independent variables determining death were age, severe cerebral involvement and LDH level 10 N or over. A 3-level risk score for early death was defined and confirmed in the validation cohort using these variables, with higher values corresponding to increased risk of early death.
A risk score for early death was defined in patients with thrombotic thrombocytopenic purpura and validated on an independent cohort. This score should help to stratify early treatment and identify patients with a worse prognosis.
Objectives Cytomegalovirus (CMV) drug resistance is a therapeutic challenge in the transplant setting. No longitudinal cohort studies of CMV resistance in a real-life setting have been published in ...the valganciclovir era. We report findings for a French multicentre prospective cohort of 346 patients enrolled at initial diagnosis of CMV infection (clinical trial registered at clinicaltrials.gov: NCT01008540). Patients and methods Patients were monitored for detection of CMV infection for ≥2 years. Real-time detection of resistance by UL97 and UL54 gene sequencing and antiviral phenotyping was performed if viral replication persisted for >21 days of appropriate antiviral treatment. Plasma ganciclovir assays were performed when resistance was suspected. Results Resistance was suspected in 37 (10.7%) patients; 18/37 (5.2% of the cohort) had virological resistance, associated with poorer outcome. Most cases involved single UL97 mutations, but four cases of multidrug resistance were due to UL54 mutations. In solid organ transplant recipients, resistance occurred mainly during primary CMV infection (odds ratio 8.78), but also in two CMV-seropositive kidney recipients. Neither CMV prophylaxis nor antilymphocyte antibody administration was associated with virological resistance. Conclusions These data show the feasibility of surveying resistance. Virological resistance was frequent in patients failing antiviral therapy. More than 1/5 resistant isolates harboured UL54 mutations alone or combined with UL97 mutations, which conferred a high level of resistance and sometimes were responsible for cross-resistance, leading to therapeutic failure.
Human cytomegalovirus (HCMV) and human herpesvirus-6 (HHV-6) are two closely related viruses, which belong to the Herpesviridae family. Following primary infection, they are thought to persist for ...life as latent forms in mononuclear cells. HCMV and HHV-6 can cause considerable morbidity in immunocompromised individuals, such as transplant patients. A sensitive and specific LightCycler multiplex real-time PCR assay based on fluorescence energy transfer (known as FRET) was developed. This assay, by using two sets of hybridization probes specific for HHV-6 (A and B) and HCMV, can differentiate reliably and quantify simultaneously both viruses in order to diagnose reactivation processes. The assay was optimized and the lower limit of detection for both viruses was determined to be 10 viral genome copies per reaction. Both viruses were quantified in 83 peripheral blood mononuclear cells (PBMCs) and 87 polymorphonuclear leukocytes (PMNLs) collected from 32 transplant recipients. This multiplex real-time quantitative PCR was finally compared with two other quantitation and detection assays used daily in laboratory (PCR DIG detection and antigenemia for HCMV, TaqMan Assay for HHV-6). This technique can be useful for the differentiation and quantitation of HCMV and HHV-6 for monitoring transplant patients.
Posttransplantation lymphoproliferative disorder (PTLD) is a well-known complication of immunosuppression associated with solid organ transplantation. The donor or host origin of PTLD may influence ...the outcome of the disease as it has been reported that a donor origin may be associated with a better prognosis. The aim of the study was to determine the origin (recipient or donor) of 12 PTLD occurring in kidney transplant recipients and to correlate the results with clinical findings.
Origin of PTLD was determined using HLA DRB1 molecular typing, analysis of multiple short-tandem repeat microsatellite loci, and HLA class I antigen expression by immunohistochemistry.
Combining the three techniques, we found that eight cases originated from the recipient and four cases originated from the donor. The results of the three techniques were concordant and altogether assigned the origin of the tumors. All the donor-origin PTLD were strictly localized to the kidney graft, developed after a mean time of 5 months after transplantation, and regressed after reduction of immunosuppression. In contrast, seven of the eight recipient-origin PTLD presented as multisystemic disease, occurred a mean time of 75.7 months after the transplantation, and had a worse outcome (mortality, five deaths of eight patients, 62.5%).
These results suggest that PTLD originating from the donor arise in the first year after transplantation into the graft, and that recipient-origin PTLD develop later as an invasive disease. Because it permits simultaneously the analysis of cell morphology and tumor origin, immunohistochemistry is a more reliable technique in the case of graft tumors associated with allograft rejection. The determination of the origin of the tumors seems to be of value in the management of PTLD to predict the outcome and to adapt therapy.
Background: Extranodal natural killer (NK)/T-cell lymphoma, nasal type, and aggressive NK-cell leukemia are highly aggressive diseases with a poor outcome.
Patients and methods: We report a ...multicentric French retrospective study of 15 patients with relapsed, refractory, or disseminated disease, treated with L-asparaginase-containing regimens in seven French centers. Thirteen patients were in relapse and/or refractory and 10 patients were at stage IV.
Results: All but two of the patients had an objective response to L-asparaginase-based treatment. Seven patients reached complete remission and only two relapsed.
Conclusion: These data, although retrospective, confirm the excellent activity of L-asparaginase-containing regimens in refractory extranodal NK/T-cell lymphoma and aggressive NK-cell leukemia. Therefore, L-asparaginase-based regimen should be considered as a salvage treatment, especially for patients with disseminated disease. First-line L-asparaginase combination therapy for extranodal NK/T-cell lymphoma and aggressive NK-cell leukemia should be tested in prospective trials.
La transfusion plaquettaire (plq) ABO incompatible (plq non ABO) des patients (pts) est en augmentation en situation d’allogreffe (G). La HAS (niveau preuve 2) incite à éviter ces incompatibilités. ...Nous déterminons l’incidence du signalement d’effets indésirables (EIR) dans cette situation.
Les pts allogreffés à Limoges (couple D/R O/O) transfusés en plq non ABO (pré et/ou post G) sont inclus de façon rétrospective, à partir du logiciel Traceline (Mak-system). L’étude est descriptive (test statistique de comparaison χ2).
Entre 2005 et 2016, 47 G ont été réalisées pour 46 pts (34H, 12F) et un âge médian de 54 ans. Il y a plus de O+/O+ (n=35). Trente et un G (65,9 %) ont reçues des plq non ABO en pré-/post- G, une majorité de CPA A (pré G : n=63, post G : n=50). En moyenne, 61,6 PSL ont été transfusés dans le groupe plq non ABO et 20 PSL pour l’autre groupe. Un ratio de 12/47 G (25,5 %) ont une EIR (grade 1) : 3 anti-HLA (3 anti-RH3 dont un avec un anti-RH 1), 1 anti-JK2 (G sans plq non ABO), 2 allergies, 2 RFNH et 1 hyperthermie avant CSH. Un ratio de 11/12 EIR (91,7 %) concernent des G avec plq non ABO, dont 7/11 en pré-G. Il existe significativement plus d’EIR avec les plq non ABO, p=0,002, sans différence significative entre CPA et MCP.
Les EIR sont surtout des immunisations anti-érythrocytaires. Leur origine principale est la transfusion de plq (CGR phénotypés RH-KELL), et nécessitent des CGR phénotypés et compatibilisés avec un risque d’impasse transfusionnelle. Le nombre de PSL transfusés est significatif, à corréler avec le contexte de G. Une étude prospective est nécessaire, la transfusion plq en incompatibilité ABO est plus à risque d’EIR.
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