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1.
J Hematol Oncol ; 17(1): 2, 2024 01 07.
Article in English | MEDLINE | ID: mdl-38185663

ABSTRACT

The use of peripheral blood (PB) or bone marrow (BM) stem cells graft in haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis remains controversial. Moreover, the value of adding anti-thymoglobulin (ATG) to PTCy is unknown. A total of 1344 adult patients received an unmanipulated haploidentical transplant at 37 centers from 2012 to 2019 for hematologic malignancy. We compared the outcomes of patients according to the type of graft, using a propensity score analysis. In total population, grade II-IV and III-IV acute GVHD (aGVHD) were lower with BM than with PB. Grade III-IV aGVHD was lower with BM than with PB + ATG. All outcomes were similar in PB and PB + ATG groups. Then, in total population, adding ATG does not benefit the procedure. In acute leukemia, myelodysplastic syndrome and myeloproliferative syndrome (AL-MDS-MPS) subgroup receiving non-myeloablative conditioning, risk of relapse was twice greater with BM than with PB (51 vs. 22%, respectively). Conversely, risk of aGVHD was greater with PB (38% for aGVHD II-IV; 16% for aGVHD III-IV) than with BM (28% for aGVHD II-IV; 8% for aGVHD III-IV). In this subgroup with intensified conditioning regimen, risk of relapse became similar with PB and BM but risk of aGVHD III-IV remained higher with PB than with BM graft (HR = 2.0; range [1.17-3.43], p = 0.012).


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Adult , Humans , Bone Marrow , Retrospective Studies , Hematopoietic Stem Cell Transplantation/adverse effects , Cyclophosphamide/therapeutic use , Graft vs Host Disease/etiology , Graft vs Host Disease/prevention & control , Recurrence , Hematopoietic Stem Cells
2.
Lancet ; 401(10392): 1941-1950, 2023 06 10.
Article in English | MEDLINE | ID: mdl-37105210

ABSTRACT

BACKGROUND: Advanced-stage cutaneous T-cell lymphomas (CTCLs) are rare, usually refractory, and fatal diseases. Case series have suggested that allogeneic haematopoietic stem cell transplantation (HSCT) might improve the prognosis of advanced-stage CTCLs. The objective of this study was to investigate the effect of allogeneic HSCT compared with non-HSCT therapy on the outcome of individuals with advanced-stage CTCLs. METHODS: In this prospective, multicentre, matched controlled trial, conducted at 30 hospitals, participants with advanced CTCLs were allocated treatment: if they had an available compatible related donor they were assigned to allogeneic HSCT, or if not they were allocated to non-allogeneic HSCT therapy. Key inclusion criteria were participants aged 18-70 years, with advanced stage mycosis fungoides or Sézary syndrome, and at least one poor prognostic criteria. Participants were excluded if they were not in complete or partial remission of the disease. Propensity score 1:1 matching with replacement (ie, that each participant treated with HSCT was matched to the participant with the closest propensity score treated with non-HSCT therapy, even if they had already been matched) was used to handle confounding factors, with the balance of covariate distribution between HSCT and non-HSCT groups assessed using standardised mean differences. The primary endpoint was progression-free survival in the matched intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02520908), and is currently active but not recruiting. FINDINGS: From June 1, 2016, to March 3, 2022, total of 99 participants were enrolled at 17 centres in France. Participants with a sibling or matched unrelated donor were assigned to allogeneic HSCT (HSCT group, n=55 [56%]) and participants without a donor were assigned to non-allogeneic HSCT treatment (non-HSCT group, n=44 [44%]). The median follow-up among survivors was 12·6 months (IQR 11·0-35·2). In the HSCT group, 51 participants (93%) were 1:1 matched to participants from the non-HSCT group. In the intention-to-treat analysis, median progression-free survival was significantly longer in the HSCT group (9·0 months [95% CI 6·6-30·5]) than in the non-HSCT group (3·0 months [2·0-6·3]), with a hazard ratio of 0·38 (95% CI 0·21-0·69; p<0·0001). In the per-protocol population, 40 participants (78%) in the HSCT group had 101 serious events and 29 participants (67%) in the non-HSCT group had 70 serious adverse events. The most common serious adverse event other than graft-versus-host disease in both groups was infections, occurring in 30 participants (59%) in the HSCT group and in 19 participants (44%) in the non-HSCT group. INTERPRETATION: Allogeneic HSCT was associated with significantly longer progression-free survival in participants with advanced-stage CTCLs. These results indicate that allogeneic HSCT treatment should be made available to individuals with high-risk, advanced-stage mycosis fungoides or Sézary syndrome who achieve pre-transplant disease remission. FUNDING: French Ministry of Health, National Cancer Institute, Programme Hospitalier de Recherche Clinique en Cancérologie.


Subject(s)
Hematopoietic Stem Cell Transplantation , Lymphoma, T-Cell, Cutaneous , Mycosis Fungoides , Sezary Syndrome , Skin Neoplasms , Humans , Prospective Studies , Sezary Syndrome/therapy , Sezary Syndrome/etiology , Propensity Score , Lymphoma, T-Cell, Cutaneous/therapy , Lymphoma, T-Cell, Cutaneous/etiology , Transplantation, Homologous , Hematopoietic Stem Cell Transplantation/methods , Mycosis Fungoides/etiology , Mycosis Fungoides/pathology , Skin Neoplasms/therapy , Skin Neoplasms/etiology
3.
Int J Clin Exp Hypn ; 71(1): 79-88, 2023.
Article in English | MEDLINE | ID: mdl-36622325

ABSTRACT

The insertion of a nasogastric (NG) tube is often a difficult experience for both patients and caregivers. This often results in a high failure rate of NG insertion. This pilot study aimed to evaluate the effectiveness, tolerance, and acceptability of hypnoanalgesia to assist self-insertion of an NG tube. Patients undergoing high-dose chemotherapy for autologous or allogeneic hematopoietic stem cell transplantation (HSCT) or acute leukemia and with high risk of aplasia were included in the study. A total of 38 patients were included during 6 consecutive months. They all achieved successful NG tube self-insertion. The NG tube remained in place during hospitalization in 32 cases for an average duration of 15 days. Six patients rejected the NG tube during vomiting but they all voluntarily attempted it again later on and succeeded. The discomfort related to NG-tube insertion was mild. This pilot study suggests that NG tube self-insertion assisted by hypnoanalgesia may be effective, well-accepted, and well-tolerated in patients. These promising findings will need further confirmation.


Subject(s)
Antineoplastic Agents , Hypnosis , Humans , Pilot Projects , Intubation, Gastrointestinal/adverse effects , Intubation, Gastrointestinal/methods , Hypnosis, Anesthetic
5.
Eur J Haematol ; 107(1): 111-121, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33765335

ABSTRACT

In this randomized phase 3 study, the FILO group tested whether the addition of 6 mg/m2 of gemtuzumab ozogamycin (GO) to standard chemotherapy could improve outcome of younger patients with de novo acute myeloid leukemia (AML) and intermediate-risk cytogenetics. GO arm was prematurely closed after 254 inclusions because of toxicity. A similar complete remission rate was observed in both arms. Neither event-free survival nor overall survival were improved by GO in younger AML patients (<60 years) ineligible for allogeneic stem-cell transplantation. (P = .086; P = .149, respectively). Using unsupervised hierarchical clustering based on mutational analysis of seven genes (NPM1, FLT3-ITD, CEBPA, DNMT3A, IDH1, IDH2, and ASXL1), six clusters of patients with significant different outcome were identified. Five clusters were based on FLT3-ITD, NPM1, and CEBPA mutations as well as epigenetic modifiers (DNMT3A, IDH1/2, ASXL1), whereas the last cluster, representing 25% of patients, had no mutation and intermediate risk. One cluster isolated FLT3-ITD mutations with higher allelic ratio and a very poor outcome. The addition of GO had no impact in these molecular clusters. Although not conclusive for GO impact in AML patients <60 years, this study provides a molecular classification that distinguishes six AML clusters influencing prognosis in younger AML patients with intermediate-risk cytogenetic.


Subject(s)
Gemtuzumab/pharmacology , Gene Expression Regulation, Leukemic , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/drug therapy , Adolescent , Adult , Cluster Analysis , Cytogenetic Analysis , Cytogenetics , DNA Mutational Analysis , Disease-Free Survival , Female , Gene Expression Profiling , Hematopoietic Stem Cell Transplantation , Humans , Karyotyping , Male , Middle Aged , Mutation , Prognosis , Remission Induction , Risk , Young Adult
7.
Eur J Haematol ; 106(6): 859-867, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33733520

ABSTRACT

OBJECTIVES: The impact of conventional treatment for acute myeloid leukemia (AML) on the nutritional, cognitive, and functional status of elderly patients is seldom studied. This assessment was performed in the context of the LAMSA 2007 trial. METHODS: The trial enrolled 424 patients with de novo AML. Among them, 316 benefited from geriatric assessment (GA) including nutritional, cognitive, and functional status and were scored according to Eastern Cooperative Oncology Group (ECOG) and sorror for the prediction of treatment toxicity, morbidity, and mortality. Patients were investigated at diagnosis for three times during follow-up. RESULTS: This study showed that AML and its treatment have no impact on cognitive (P = .554) nor functional status (P = .842 for Activity of Daily Living and P = .087 for Instrumental Activities of Daily Living). The nutritional status improved over time (P = .041). None of these three parameters at baseline, associated or not with ECOG and sorror scores, impacted survivals or toxicities. CONCLUSIONS: The cognitive, functional, and nutritional status had no impact in this cohort of fit elderly AML patients without unfavorable cytogenetics. The GA tools used provided no additional information compared with ECOG and sorror scores, to predict toxicity, morbidity, or mortality due to intensive chemotherapy.


Subject(s)
Activities of Daily Living , Antineoplastic Agents , Cognition/drug effects , Leukemia, Myeloid, Acute/drug therapy , Nutritional Status/drug effects , Aged , Aged, 80 and over , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Female , Follow-Up Studies , Geriatric Assessment , Humans , Male , Middle Aged , Prospective Studies
8.
Leukemia ; 35(5): 1291-1300, 2021 05.
Article in English | MEDLINE | ID: mdl-32943750

ABSTRACT

We previously reported the benefit of lomustine addition to conventional chemotherapy in older acute myeloid leukemias with nonadverse chromosomal aberrations in the LAM-SA 2007 randomized clinical trial (NCT00590837). A molecular analysis of 52 genes performed in 330 patients included in this trial, 163 patients being treated with lomustine in combination with idarubicin and cytarabine and 167 without lomustine, identified 1088 mutations with an average of 3.3 mutations per patient. NPM1, FLT3, and DNMT3A were the most frequently mutated genes. A putative therapeutic target was identified in 178 patients (54%). Among five molecular classifications analyzed, the ELN2017 risk classification has the stronger association with the clinical evolution. Patients not treated with lomustine have an expected survival prognosis in agreement with this classification regarding the overall and event-free survivals. In strong contrast, lomustine erased the ELN2017 classification prognosis. The benefit of lomustine in nonadverse chromosomal aberrations was restricted to patients with RUNX1, ASXL1, TP53, and FLT3-ITDhigh/NPM1WT mutations in contrast to the intermediate and favorable ELN2017 patients. This post-hoc analysis identified a subgroup of fit elderly AML patients with intermediate cytogenetics and molecular markers who may benefit from lomustine addition to intensive chemotherapy.


Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Lomustine/therapeutic use , Biomarkers, Tumor/genetics , Chromosome Aberrations/drug effects , Cytarabine/therapeutic use , Cytogenetics/methods , Female , Humans , Idarubicin/therapeutic use , Karyotype , Karyotyping/methods , Leukemia, Myeloid, Acute/genetics , Male , Middle Aged , Mutation/drug effects , Nucleophosmin , Prognosis
9.
Infez Med ; 29(4): 618-622, 2021.
Article in English | MEDLINE | ID: mdl-35146373

ABSTRACT

We report a case of severe refractory hepato-splenic candidiasis confirmed following splenectomy in an immunocompromised 54-year-old woman treated for acute lymphoblastic leukemia. Liver biopsies did not contribute to identifying the etiology of the multiple hepato-splenic lesions. In view of the lack of improvement after several lines of antifungal treatments, a splenectomy was performed and confirmed splenic candidiasis. PET/CT scan was used to monitor the evolution of hepato-splenic hypermetabolism. Splenectomy can be envisaged to establish fungal infection in immuno-compromised patients, to exclude relapse, and to guide the choice of antifungal agents.

10.
Geriatrics (Basel) ; 5(4)2020 Sep 27.
Article in English | MEDLINE | ID: mdl-32992602

ABSTRACT

(1) Background: COVID-19 has become a global pandemic and older patients present higher mortality rates. However, studies on the characteristics of this population set are limited. The objective of this study is to describe clinical characteristics and outcomes of older patients hospitalized with COVID-19. (2) Methods: This retrospective cohort study was conducted from March to May 2020 and took place in three acute geriatric wards in France. Older patients hospitalized for COVID-19 infections were included. We collected clinical, radiological, and laboratory outcomes. (3) Results: Ninety-four patients were hospitalized and included in the final analysis. Mean age was 85.5 years and 55% were female. Sixty-four (68%) patients were confirmed COVID-19 cases and 30 (32%) were probable. A majority of patients were dependent (77%), 45% were malnourished, and the mean number of comorbidities was high in accordance with the CIRS-G score (12.3 ± 25.6). The leading causes of hospitalization were fever (30%), dyspnea (28%), and geriatric syndromes (falls, delirium, malaise) (18%). Upon follow-up, 32% presented acute respiratory failure and 30% a geriatric complication. Frailty and geriatric characteristics were not correlated with mortality. Acute respiratory failure (p = 0.03) and lymphopenia (p = 0.02) were significantly associated with mortality. (4) Conclusions: Among older patients hospitalized with COVID-19, clinical presentations were frequently atypical and complications occurred frequently. Frailty and geriatric characteristics were not correlated with mortality.

12.
BMC Fam Pract ; 20(1): 14, 2019 Jan 17.
Article in English | MEDLINE | ID: mdl-30654761

ABSTRACT

Following publication of the original article [1], the authors reported an error to one of the 'study groups' in the authorship section.

13.
J Clin Oncol ; 36(32): 3203-3210, 2018 Nov 10.
Article in English | MEDLINE | ID: mdl-30260758

ABSTRACT

PURPOSE: Acute myeloid leukemia (AML) in elderly patients has a poor prognosis. In an attempt to improve outcome for these patients, the prospective open-label phase III LAM-SA 2007 (Adding Lomustine to Chemotherapy in Older Patients With Acute Myelogenous Leukemia (AML), and Allogeneic Transplantation for Patients From 60 to 65 Years Old) trial randomly assigned patients to a standard induction regimen with lomustine added or to a consolidation regimen with cytarabine and idarubicin. PATIENTS AND METHODS: Adults age 60 years or older with previously untreated AML who were fit to receive intensive chemotherapy and who were without unfavorable cytogenetics received standard chemotherapy with lomustine (idarubicin, cytarabine, and lomustine [ICL]) or without (idarubicin and cytarabine [IC]). The primary objective of the study was overall survival (OS); secondary objectives were response rate, cumulative incidence of relapse (CIR), event-free survival (EFS), and safety. RESULTS: From February 2008 to December 2011, 459 patients were enrolled. Comparing patients in the IC and ICL arms, complete response or complete response with incomplete recovery was achieved in 74.9% versus 84.7% (P = .01). The proportional hazards assumption was rejected for OS (P = .02), which led us to consider two separate time intervals: during and after induction. There was no significant difference between the two arms during induction, although induction deaths were 3.7% versus 7.7%, respectively (P = .11). However, significantly better results were observed after induction with an improved 2-year OS of 56% in the ICL arm versus 48% in the IC arm (P = .02). At 2 years, EFS was improved at 41% in the ICL arm versus 26% in the IC arm (P = .01). The CIR at 2 years was 41.2% in the ICL arm versus 60.9% in the IC arm (P = .003). Grade 3 and 4 toxicities, mostly hematologic, were significantly higher in the ICL arm (P = .04), and fewer patients required a second treatment after ICL. CONCLUSION: Adding lomustine to standard chemotherapy significantly improved the outcome of elderly patients with AML.

14.
JAMA ; 318(6): 557-566, 2017 08 08.
Article in English | MEDLINE | ID: mdl-28787506

ABSTRACT

Importance: Bronchiolitis obliterans syndrome has been associated with increased morbidity and mortality after allogeneic hematopoietic stem cell transplant (HSCT). Previous studies have suggested that azithromycin may reduce the incidence of post-lung transplant bronchiolitis obliterans syndrome. Objective: To evaluate if the early administration of azithromycin can improve airflow decline-free survival after allogeneic HSCT. Design, Setting, and Participants: The ALLOZITHRO parallel-group trial conducted in 19 French academic transplant centers and involving participants who were at least 16 years old, had undergone allogeneic HSCT for a hematological malignancy, and had available pretransplant pulmonary function test results. Enrollment was from February 2014 to August 2015 with follow-up through April 26, 2017. Interventions: Patients were randomly assigned to receive 3 times a week either 250 mg of azithromycin (n = 243) or placebo (n = 237) for 2 years, starting at the time of the conditioning regimen. Main Outcomes and Measures: The primary efficacy end point was airflow decline-free survival at 2 years after randomization. Main secondary end points were overall survival and bronchiolitis obliterans syndrome at 2 years. Results: Thirteen months after enrollment, the independent data and safety monitoring board detected an unanticipated imbalance across blinded groups in the number of hematological relapses, and the treatment was stopped December 26, 2016. Among 480 randomized participants, 465 (97%) were included in the modified intention-to-treat analysis (mean age, 52 [SD, 14] years; 75 women [35%]). At the time of data cutoff, 104 patients (22%; 54 azithromycin vs 50 placebo) had experienced an airflow decline; 138 patients (30%) died (78 azithromycin vs 60 placebo). Two-year airflow decline-free survival was 32.8% (95% CI, 25.9%-41.7%) with azithromycin and 41.3% (95% CI, 34.1%-50.1%) with placebo (unadjusted hazard ratio [HR], 1.3; 95% CI, 1.02-1.70; P = .03). Of the 22 patients (5%) who experienced bronchiolitis obliterans syndrome, 15 (6%) were in the azithromycin group and 7 (3%) in the placebo group (P = .08). The azithromycin group had increased mortality, with a 2-year survival of 56.6% (95% CI, 50.2%-63.7%) vs 70.1% (95% CI, 64.2%-76.5%) in the placebo group (unadjusted HR, 1.5; 95% CI, 1.1-2.0; P = .02). In a post hoc analysis, the 2-year cumulative incidence of hematological relapse was 33.5% (95% CI, 27.3%-39.7%) with azithromycin vs 22.3% (95% CI, 16.4%-28.2%) with placebo (unadjusted cause-specific HR, 1.7; 95% CI, 1.2-2.4; P = .002). Conclusions and Relevance: Among patients undergoing allogeneic HSCT for hematological malignancy, early administration of azithromycin resulted in worse airflow decline-free survival than did placebo; these findings are limited by early trial termination. The potential for harm related to relapse requires further investigation. Trial Registration: clinicaltrials.gov Identifier: NCT01959100.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Azithromycin/therapeutic use , Bronchiolitis Obliterans/prevention & control , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Adult , Anti-Bacterial Agents/adverse effects , Azithromycin/adverse effects , Bronchiolitis Obliterans/etiology , Disease-Free Survival , Double-Blind Method , Female , Hematologic Neoplasms/mortality , Humans , Intention to Treat Analysis , Male , Middle Aged , Recurrence , Respiratory Function Tests , Transplantation Conditioning , Transplantation, Homologous , Treatment Failure
15.
BMC Fam Pract ; 18(1): 78, 2017 Aug 03.
Article in English | MEDLINE | ID: mdl-28774265

ABSTRACT

BACKGROUND: Anal disorders are largely underestimated in general practice. Studies have shown patients conceal anal symptoms leading to late diagnosis and treatment. Management by general practitioners is poorly described. The aim of this study is to assess the prevalence of anal symptoms and their management in general practice. METHODS: In this prospective, observational, national study set in France, all adult patients consulting their general practitioner during 2 days of consultation were included. Anal symptoms, whether spontaneously revealed or not, were systematically collected and assessed. For symptomatic patients, the obstacles to anal examination were evaluated. The general practitioner's diagnosis was collected and a proctologist visit was systematically proposed in case of anal symptoms. If the proctologist was consulted, his or her diagnosis was collected. RESULTS: From October 2014 to April 2015, 1061 patients were included by 57 general practitioners. The prevalence of anal symptoms was 15.6% (95% CI: 14-18). However, 85% of these patients did not spontaneously share their symptoms with their doctors, despite a discomfort rating of 3 out of 10 (range 1-5). Although 65% of patients agreed to an anal examination, it was not proposed in 45% of cases with anal symptoms. Performing the examination was associated with a significantly higher diagnosis rate of 76% versus 20% (p < 0.001). Proctologist and general practitioner diagnoses were consistent in 14 out of 17 cases. CONCLUSIONS: Patients' concealed anal symptoms are significant in general practice despite the impact on quality of life. Anal examination is seldom done. Improved training of general practitioners is required to break the taboo.


Subject(s)
Anus Diseases/epidemiology , General Practice/statistics & numerical data , Adult , Aged , Anus Diseases/diagnosis , France/epidemiology , Humans , Male , Middle Aged , Physical Examination , Prevalence , Prospective Studies
16.
Eur J Haematol ; 98(5): 443-449, 2017 May.
Article in English | MEDLINE | ID: mdl-28122150

ABSTRACT

OBJECTIVES: Anthracyclines and cytarabine are cornerstones for intensive chemotherapy in acute myeloid leukemia (AML). The goals of this study were to comprehensively assess deviations from theoretical doses and the impact of body-surface area (BSA) on patients' characteristics, physicians' strategy, dose adjustment, and clinical outcome. METHODS: The GOELAMS 2001 phase III trial included 823 AML patients below 60 years of age. In the course of treatment, anthropomorphic parameters and chemotherapy doses were prospectively registered. RESULTS: Very high BSA (≥2.15 m2 ) was the factor most significantly associated with the physician's decision to reduce chemotherapy doses during induction and postremission therapy. Despite similar AML characteristics and therapeutic strategies, the very high BSA group exhibited a significantly worse survival (5-years OS of 27%) compared to the low (BSA≤1.5 m2 ), intermediate (1.5 m2

Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Body Surface Area , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/mortality , Adult , Age Factors , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Body Weights and Measures , Clinical Trials, Phase III as Topic , Female , Humans , Leukemia, Myeloid, Acute/diagnosis , Male , Multicenter Studies as Topic , Recurrence , Remission Induction , Survival Analysis , Treatment Outcome , Young Adult
17.
Haematologica ; 101(7): 884-90, 2016 07.
Article in English | MEDLINE | ID: mdl-27056924

ABSTRACT

Unrelated allogeneic transplantation for severe aplastic anemia is a treatment option after immunosuppressive treatment failure in the absence of a matched sibling donor. Age, delay between disease diagnosis and transplantation, and HLA matching are the key factors in transplantation decisions, but their combined impact on patient outcomes remains unclear. Using the French Society of Bone Marrow Transplantation and Cell Therapies registry, we analyzed all consecutive patients (n=139) who underwent a first allogeneic transplantation for idiopathic severe aplastic anemia from an unrelated donor between 2000 and 2012. In an adjusted multivariate model, age over 30 years (Hazard Ratio=2.39; P=0.011), time from diagnosis to transplantation over 12 months (Hazard Ratio=2.18; P=0.027) and the use of a 9/10 mismatched unrelated donor (Hazard Ratio=2.14; P=0.036) were independent risk factors that significantly worsened overall survival. Accordingly, we built a predictive score using these three parameters, considering patients at low (zero or one risk factors, n=94) or high (two or three risk factors, n=45) risk. High-risk patients had significantly shorter survival (Hazard Ratio=3.04; P<0.001). The score was then confirmed on an independent cohort from the European Group for Blood and Marrow Transplantation database of 296 patients, with shorter survival in patients with at least 2 risk factors (Hazard Ratio=2.13; P=0.005) In conclusion, a simple score using age, transplantation timing and HLA matching would appear useful to help physicians in the daily care of patients with severe aplastic anemia.


Subject(s)
Anemia, Aplastic/diagnosis , Anemia, Aplastic/therapy , Bone Marrow Transplantation , Unrelated Donors , Adolescent , Adult , Aged , Anemia, Aplastic/mortality , Bone Marrow Transplantation/adverse effects , Bone Marrow Transplantation/methods , Child , Child, Preschool , Female , France , Graft vs Host Disease/etiology , Humans , Infant , Lymphocyte Depletion , Male , Middle Aged , Prognosis , Severity of Illness Index , Survival Analysis , Transplantation Conditioning/adverse effects , Transplantation Conditioning/methods , Transplantation, Homologous , Treatment Outcome , Young Adult
18.
Haematologica ; 101(4): 466-73, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26768687

ABSTRACT

Brentuximab vedotin was reported to be effective and safe against refractory/relapsed Hodgkin lymphoma in cohorts of between 12 to 102 patients. Herein we report our retrospective analysis of the French experience with brentuximab vedotin used alone to treat 240 refractory/relapsed Hodgkin lymphoma patients enrolled in a named patient program between 2011 and 2013. All patients had histologically documented CD30+ Hodgkin lymphoma; 74% had refractory disease or early relapses. After a median of 3 lines of chemotherapy, brentuximab vedotin was infused intravenously (1.8 mg/kg every 3 weeks). The primary endpoint was best response. Response at the end of treatment, its duration, survival data and toxicity profile were secondary endpoints. Patients received a median of 6 cycles; 68 underwent a consolidation thereafter. The best response was observed after a median of 4 cycles in 145 (60.4%) patients: 33.8% complete response/unconfirmed complete response, 26.7% partial response. Objective responses were observed as decreased (39.3%) in the 28 patients >60 years. The median response duration was 8.4 months. With median follow-up at 16.1 months, median progression-free survival was 6.8 months and this was significantly longer for patients transplanted after brentuximab vedotin (a median of 18,8 months); median overall survival was not reached. No death has been linked to brentuximab vedotin toxicity. The most common adverse events were peripheral sensory neuropathy (29.3%) and hematological toxicity. The results of this analysis support the previously reported brentuximab vedotin efficacy with manageable toxicity. Because of the short-term responses in most patients, a high-dose therapy with stem cell transplantation for responders should be considered as quickly as possible.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Biomarkers, Tumor/genetics , Hodgkin Disease/drug therapy , Immunoconjugates/administration & dosage , Adolescent , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Brentuximab Vedotin , Drug Administration Schedule , Drug Resistance, Neoplasm , Female , France , Gene Expression , Hodgkin Disease/genetics , Hodgkin Disease/mortality , Hodgkin Disease/pathology , Humans , Immunoconjugates/adverse effects , Injections, Intravenous , Ki-1 Antigen/genetics , Male , Middle Aged , Nausea/diagnosis , Nausea/etiology , Nausea/pathology , Neoplasm Staging , Peripheral Nervous System Diseases/diagnosis , Peripheral Nervous System Diseases/etiology , Peripheral Nervous System Diseases/pathology , Recurrence , Remission Induction , Retrospective Studies , Survival Analysis , Treatment Outcome
19.
PLoS One ; 8(9): e73993, 2013.
Article in English | MEDLINE | ID: mdl-24069261

ABSTRACT

PURPOSE: We designed a gene profiling experiment to identify genes involved in secondary drug resistance in mantle cell lymphomas (MCL). EXPERIMENTAL DESIGN: We obtained paired tissue samples collected from the same patients before treatment and after relapse or progression. Variations in gene expression between the 2 samples were estimated for 5 patients. For each gene, the mean variation was estimated for patients with a refractory primary tumor and for responders who developed secondary drug resistance. Nine genes of interest were selected on the basis of the magnitude and statistical significance of the variation of expression in responders and non-responders. RESULTS: BMP7 was the only one with significantly increased expression at relapse in patients who developed secondary resistance. Validation of BMP7 as a key gene involved in secondary resistance was performed using cultures of cell line. Incubation of BMP7 with MCL cell lines increased their resistance to bortezomib and cytarabine, while inhibition of BMP7 expression by siRNA correlated with increased cell death linked to drug application. CONCLUSION: Variations in gene expression after treatment point out BMP7 as a key gene involved in secondary resistance in mantle cell lymphoma.


Subject(s)
Bone Morphogenetic Protein 7/genetics , Drug Resistance, Neoplasm/genetics , Gene Expression , Lymphoma, Mantle-Cell/genetics , Adult , Aged , Antineoplastic Agents/pharmacology , Antineoplastic Agents/toxicity , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Base Sequence , Bone Morphogenetic Protein 7/chemistry , Bone Morphogenetic Protein 7/metabolism , Boronic Acids/pharmacology , Boronic Acids/toxicity , Bortezomib , Cell Line, Tumor , CpG Islands , DNA Methylation , Female , Gene Expression Regulation, Neoplastic , Humans , Lymphoma, Mantle-Cell/drug therapy , Lymphoma, Mantle-Cell/pathology , Male , Middle Aged , Molecular Sequence Data , Neoplasm Staging , Pyrazines/pharmacology , Pyrazines/toxicity , RNA Interference , Recurrence , Treatment Outcome
20.
Haematologica ; 98(9): 1467-75, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23539540

ABSTRACT

The role of reduced intensity allogeneic stem cell transplantation for the treatment of relapsed/refractory Hodgkin's lymphoma remains controversial. We retrospectively analyzed 191 patients who underwent reduced intensity allogeneic stem cell transplantation between 1998 and 2008 for relapsed or refractory Hodgkin's lymphoma and whose data were reported to the French registry. The median follow-up was 36 months. The estimated 3-year overall survival rate, progression-free survival rate, cumulative incidence of relapse and cumulative incidence of non-relapse mortality were 63%, 39%, 46%, and 16%, respectively. There was no difference in outcome between patients in complete response and in partial response at the time of transplantation with regards to overall survival (70% versus 74%, no significant difference) and progression-free survival (51% versus 42%, no significant difference). Patients with chemoresistant disease had a shorter overall survival (39% at 3 years; P=0.0003) and progression-free survival (18% at 3 years; P=0.001) than patients in complete remission. The use of umbilical cord blood as the source of stem cells was associated with a poor outcome with an increased risk of death with a hazard ratio of 3.49 (95% confidence interval: 1.26 to 9.63; P=0.016). The use of peripheral blood was associated with a better outcome for patients who where alive 1 year after transplantation with a hazard ratio of 0.38 (95% confidence interval: 0.17 to 0.83; P=0.016). Disease status at transplantation remains the most important risk factor for outcome. Our data suggest that the use of peripheral blood should be preferred whereas umbilical cord blood should be used with caution.


Subject(s)
Cord Blood Stem Cell Transplantation/methods , Hodgkin Disease/diagnosis , Hodgkin Disease/surgery , Peripheral Blood Stem Cell Transplantation/methods , Societies, Medical , Transplantation Conditioning/methods , Adolescent , Adult , Bone Marrow Transplantation/adverse effects , Bone Marrow Transplantation/methods , Cohort Studies , Cord Blood Stem Cell Transplantation/adverse effects , Disease-Free Survival , Female , Follow-Up Studies , France , Hodgkin Disease/epidemiology , Humans , Male , Middle Aged , Peripheral Blood Stem Cell Transplantation/adverse effects , Retrospective Studies , Transplantation Conditioning/adverse effects , Transplantation, Homologous , Young Adult
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