Long-term outcome after allogeneic hematopoietic stem cell transplantation for advanced stage acute myeloblastic leukemia: a retrospective study of 379 patients reported to the Société Française de Greffe de Moelle (SFGM)

To assess the place of allogeneic hematopoietic stem cell transplantation (HSCT) in the advanced stage of acute myeloid leukemia (AML), we retrospectively analyzed 379 consecutive patients who underwent allogeneic HSCT for advanced AML. The median follow-up of the entire cohort was 7.5 years. Sixty-nine patients (18%) were transplanted with primary resistant disease. Three hundred and ten (82%) were relapsed patients, 94 (30%) of whom were in untreated relapse, 67 (22%) in refractory relapse and 149 (48%) in 2nd or 3rd complete remission at time of transplantation. The 5-year probabilities of overall survival (OS), disease-free survival (DFS), and transplant-related mortality (TRM) were 22 +/- 4%, 20 +/- 4%, 45 +/- 6%, respectively. In multivariate analysis, we demonstrated the favorable impact on OS, DFS and TRM of two factors over which we have no control (age <15 years, complete remission achievement) and three factors over which we have some control (female donor, acute and chronic graft-versus-host disease). The results of this study suggest that the graft-versus-leukemia effect is important in advanced AML and that new HSCT modalities are needed for some patients with this indication.     

Prevalence of factor V Leiden (APCR) and other inherited thrombophilias in young patients with myocardial infarction and normal coronary arteries

Objective—To investigate the role of activated protein C resistance (APCR, factor V Leiden) in coronary artery thrombosis.
Methods—The prevalence of APCR and of congenital deficiencies of antithrombin III, protein C, protein S, plasminogen, and factor XII was investigated in adult patients under 45 years of age with acute myocardial infarction. The results were compared with those of a group of 53 age and sex matched control subjects.
Results—Among 75 patients under the age of 45 years who were admitted from November 1994 to April 1996 for acute myocardial infarction, 22 (29.3%) had normal coronary arteriography (group I) and 53 (70.7%) had significant coronary artery disease (group II). Inherited thrombophilia was more often found in group I (4/22, 18.2%) than in group II (4/53, 7.5%) but the difference was not significant (F test: p = 0.22). The prevalence of APCR was 9.1% (2/22) in group I, 3.8% (2/53) in group 2 (p = 0.57), and 3.8% (2/53) in the normal control group (p = 0.57).
Conclusions—The prevalence of congenital thrombophilias, including APCR, does not seem to be increased in young patients with myocardial infarction and normal coronary angiograms, compared with young patients with coronary atherosclerosis and with normal control subjects. However, the statistical power of the study is too low to detect a significant difference and these results are published to allow a meta-analysis of this problem in the future.

Keywords: myocardial infarction; factor V Leiden; coagulation factors; inherited thrombophilia     

Combination of quinine as a potential reversing agent with mitoxantrone and cytarabine for the treatment of acute leukemias: a randomized multicenter study

A phase III prospective randomized multicenter study was performed to determine whether quinine could improve the response rate of poor-risk acute leukemias (ALs) to standard chemotherapy including a multidrug resistance (MDR)-related cytotoxic agent. The rationale of the study was based on the negative prognostic value of MDR phenotype in ALs and the ability of quinine to reverse this phenotype both in vitro and ex vivo. Three hundred fifteen patients (median age, 49 years; range, 16 to 65) with relapsed (n = 108) or refractory (n = 32) acute myeloblastic leukemia (AML), relapsed (n = 27) or refractory (n = 9) acute lymphoblastic leukemia (ALL), secondary AL (n = 22) or blastic transformation of myelodysplastic syndrome ([MDS] n = 74) or myeloproliferative syndrome ([MPS] n = 43) were randomly assigned to receive mitoxantrone ([MXN] 12 mg/m2/d, days 2 to 5) and cytarabine ([Ara-C] 1 g/m2/12 h, days 1 to 5) alone or in combination with quinine (30 mg/kg/d, days 1 to 5; continuous intravenous infusion beginning 24 hours before MXN infusion). Side effects of quinine were observed in 56 of 161 quinine-treated patients and disappeared in all but four cases after one or two 20% dose decreases. Sera from quinine-treated patients showed increased MXN uptake in an MDR-positive cell line compared with matched sera obtained before quinine infusion. Quinine induced a significant increase in the incidence of nausea, vomiting, mucositis, and cardiac toxicity. A complete response (CR) was observed in 85 of 161 patients (52.8%) from the quinine-treated group versus 70 of 154 patients (45.5%) in the control group (P = .19). The most important differences between quinine and control group CR rates were observed in patients with refractory AMLs and blastic transformation of MDS and MPS. The CR rate was higher in P-glycoprotein-positive cases, although the difference was not significant. Failure of the regimen due to blastic persistence or blast number increase was higher in the control group (61 of 154 patients) than in the quinine group (45 of 161, P = .04). Early death was observed in eight cases (four in each arm) and death in aplasia in 27 cases (20 in quinine group v seven in control group, P = .01). The significant increase of toxicity in the quinine arm could have masked the clinical benefit of MDR reversion in poor- risk ALs.     

Sideroblastic anaemia during fusidic acid treatment

OBJECTIVES AND METHODS: To describe cases of fusidic acid-associated sideroblastic anaemia from the French Pharmacovigilance database. RESULTS: Six cases of sideroblastic anaemia associated with oral fusidic acid treatment were retrieved. Four females and two males (mean age 65.3 yr) developed severe anaemia (mean haemoglobin level: 6.9 g/dL) within 32-190 d (mean: 81 d) of treatment. Bone marrow aspirates showed dyserythropoiesis and ringed sideroblasts in all patients. Four patients required repeated blood transfusions. After fusidic acid discontinuation in five patients, complete recovery was obtained. In one patient, rechallenge with fusidic acid resulted in recurrence of anaemia that resolved after definitive discontinuation of the drug. CONCLUSION: Our data indicate that fusidic acid should be added to the list of drugs that can cause sideroblastic anaemia.     

Myélome multiple de novo : faut-il proposer une prophylaxie antithrombotique ?

The incidence of venous thromboembolism in multiple myeloma depends on the disease characteristics that include recent diagnosis, persistent or recurrent multiple myeloma, patient characteristics, and the type of treatment received such as thalidomide or lenalidomide especially in combination with high-dose dexamethasone, or combined chemotherapy. Currently, recommendations could be challenged by the results of the first randomized study evaluating aspirin, low molecular weight heparins and vitamin K antagonists in the antithrombotic prophylaxis. The recent data from the literature show that it is not possible to propose a therapeutic management for venous thromboembolism prophylaxis in multiple myeloma and that the use of antithrombotic prophylaxis may not be mandatory.     

Management of bone marrow biopsy related bleeding risks: a retrospective observational study

Journal of Thrombosis and Thrombolysis - Bone marrow biopsies are largely used for the diagnosis and prognostic of various hematological diseases. Complications are rare but can be as serious as...     

Presurgical Assessment of the Sensorimotor Cortex Using Resting-State fMRI

BACKGROUND AND PURPOSE:The functional characterization of the motor cortex is an important issue in the presurgical evaluation of brain lesions. fMRI noninvasively identifies motor areas while patients are asked to move different body parts. This task-based approach has some drawbacks in clinical settings: long scanning times and exclusion of patients with severe functional or neurologic disabilities and children. Resting-state fMRI can avoid these difficulties because patients do not perform any goal-directed tasks.MATERIALS AND METHODS:Nineteen patients with diverse brain pathologies were prospectively evaluated by using task-based and resting-state fMRI to localize sensorimotor function. Independent component analyses were performed to generate spatial independent components reflecting functional brain networks or noise. Three radiologists identified the motor components and 3 portions of the motor cortex corresponding to the hand, foot, and face representations. Selected motor independent components were compared with task-based fMRI activation maps resulting from movements of the corresponding body parts.RESULTS:The motor cortex was successfully and consistently identified by using resting-state fMRI by the 3 radiologists for all patients. When they subdivided the motor cortex into 3 segments, the sensitivities of resting-state and task-based fMRI were comparable. Moreover, we report a good spatial correspondence with the task-based fMRI activity estimates.CONCLUSIONS:Resting-state fMRI can reliably image sensorimotor function in a clinical preoperative routine. It is a promising opportunity for presurgical localization of sensorimotor function and has the potential to benefit a large number of patients affected by a wide range of pathologies.

Mapping of cerebral function in neurosurgery patients aims to predict the efficacy of the neurosurgical treatment, estimate the operation risk, and avoid neurologic deficits. Several techniques have been used to identify brain activity in tissue surrounding the regions planned for resection, including neuronavitaged transcranial magnetic stimulation,¹ magnetoencephalography,² and fMRI,³ each having advantages and drawbacks over the others.The clinical criterion standard for localization of functional brain areas is intraoperative electrical stimulation in the awake patient.⁴ Although electrical stimulation provides unique assistance during surgery, it is an invasive technique that requires expertise of the surgical team and a cooperative and motivated subject. It also adds considerable time to the surgical procedure for an investigation limited to a few cortical areas. Therefore, fMRI has been seen as very promising for clinical applications. However, its integration into preoperative surgical planning has been relatively slow because of several practical constraints: the dedicated experimental setup, long scanning time, and a high cognitive demand on the patient. Moreover, localizing the sensorimotor cortex with fMRI at the individual level can be challenging in some cases when the patient has paresis or paralysis. Furthermore, >1 acquisition is necessary whenever the lesion is bordering on several motor representations.Techniques measuring functional connectivity can address several of the limitations faced by stimulus-driven or task-based fMRI (tb-fMRI). Resting-state fMRI (rs-fMRI) uses slow, spontaneous fluctuations in the blood oxygen level–dependent signal to characterize networks of distant brain regions.⁵ The subject simply “rests” in the scanner without any specific task to perform. rs-fMRI has been successfully applied in groups of healthy volunteers,⁶ provides a means of mapping several functional networks in a single acquisition, appears robust across individuals,⁷ and is less-demanding than tb-fMRI because it requires less cooperation from the patient and can be used in individuals with neurologic deficits or cognitive dysfunction or in children. Additionally, spontaneous activity continues in the primary sensory and motor cortices even when subjects are asleep⁸ or anesthetized.⁹ This feature suggests that complete patient compliance may not be necessary. Resting-state networks have been extensively explored in recent years at the group level in populations of healthy subjects and patients. In the case of neurosurgery patients with brain damage,¹⁰ precise functional network estimation at the individual level is essential for surgery planning and/or intraoperative navigation. The conclusions of previous pioneering studies were limited to the feasibility of rs-fMRI for presurgical mapping by using small patient samples.^11–15In this study, we investigated the sensitivity of extracting the sensorimotor network from rs-fMRI at the individual level in patients with brain damage scheduled for surgery. Because brain lesions can appear at any segment of the motor cortex, we divided our investigations into 3 portions of the somatotypy (foot, hand, and face). rs-fMRI was then compared with tb-fMRI acquired when corresponding body parts were moved.     

Clinical and pathological impact of an optimal assessment of brain invasion for grade 2 meningioma diagnosis: lessons from a series of 291 cases

Brain invasion has not been recognized as a standalone criterion for atypical meningioma by the WHO classification until 2016. Since the 2007 edition suggested that meningiomas harboring brain invasion could be classified as grade 2, brain invasion study was progressively strengthened in our center, based on a strong collaboration between neurosurgeons and neuropathologists regarding sample orientation and examination. Practice changes were considered homogeneous enough in 2011. The aim of the present study was to evaluate the impact of gross practice change on the clinical and pathological characteristics of intracranial meningiomas classified as grade 2.

The characteristics of consecutive patients with a grade 2 meningioma surgically managed before (1998–2005, n?=?125, group A) and after (2011–2014, n?=?166, group B) practices changed were retrospectively reviewed.

Sociodemographical and clinical parameters were comparable in groups A and B, and the median age was 62 years in both groups (p?=?0.18). The 5-year recurrence rates (23.2% vs 29.5%, p?=?0.23) were similar. In group A, brain invasion was present in 48/125 (38.4%) cases and was more frequent than in group B (14/166, 8.4%, p?<?0.001). In group A, 33 (26.4%) meningiomas were classified as grade 2 solely based on brain invasion (group A_SBI), and 92 harbored other grade 2 criteria (group A_OCA). Group A_SBI meningiomas had a similar median progression-free survival compared to groups A_OCA (68 vs 80 months, p?=?0.24) and to A_OCA and B pooled together (n?=?258, 68 vs 90 months, p?=?0.42).

An accurate assessment of brain invasion is mandatory as brain invasion is a strong predictor of meningioma progression.

     

Mucormycosis after allogeneic haematopoietic stem cell transplantation: a French Multicentre Cohort Study (2003-2008)

Clin Microbiol Infect 2012; 18: E396-E400 ABSTRACT: We conducted a nationwide retrospective study to evaluate clinical characteristics and outcome of mucormycosis among allogeneic haematopoietic stem cell transplant recipients. Twenty-nine patients were diagnosed between 2003 and 2008. Mucormycosis occurred at a median of 225?days after allogeneic haematopoietic stem cell transplant, and as a breakthrough infection in 23 cases. Twenty-six patients were receiving steroids, mainly for graft-versus-host disease treatment, while ten had experienced a prior post-transplant invasive fungal infection. Twenty-six patients received an antifungal treatment; surgery was performed in 12. Overall survival was 34% at 3?months and 17% at 1?year.     

Porphyria cutanea tarda after allogeneic bone marrow transplantation for chronic myelogenous leukemia

A case of porphyria cutanea tarda (PCT) occurring after bone marrow transplantation (BMT) is reported. A 43-year-old male with chronic myelogenous leukemia received an human leukocyte antigen (HLA)-identical allogeneic transplantation with T-cell depleted marrow. Because of graft rejection, a second transplant was performed 4 months later. A grade II acute graft- vs.-host disease and a cytomegalovirus (CMV) infection were subsequently observed. Two years after the second transplant, cutaneous symptoms of PCT with typical biochemical abnormalities developed. Liver biopsy revealed signs of hepatitis with iron overload. CMV was isolated from liver tissue. The possible roles of underlying disease, BMT, and CMV liver disease are discussed in view of the recently reported cases of PCT in patients with AIDS or hematological disorders.