Successful pregnancy following allogeneic bone marrow transplantation after conditioning by thoraco-abdominal irradiation

A 26-year-old woman delivered a normal child 5 years after bone marrow transplantation for severe aplastic anemia. The conditioning regimen comprised high dose cyclophosphamide and thoraco-abdominal irradiation (6 Gy). This and two previous cases demonstrate that normal pregnancy can follow total body or thoracoabdominal irradiation.     

Tentorial Meningiomas. Report on Twenty-Seven Cases

Summary ? Objective. Report our experience with 27 tentorial meningiomas (TM) surgically treated between 1985 and 1998.  Methods. The records of 27 patients with TMs were retrospectively reviewed for clinical presentation, neuroradiological evaluation, surgical treatment and long-term outcome. The extent of tumor resection was scored according to the Simpson's grading for tumor removal. Long-term results were evaluated according to the Glasgow Outcome Score (GOS).  Results. The average age was 53 years. Female predominance was 74%. The most common complaints at presentation were headaches (51%), gait ataxia (33%), memory disturbances (30%) and hypo-acousia (30%). A classification of TMs into 5 subgroups according to tumor site is proposed on the basis of imaging studies. A cerebrospinal fluid shunt was established prior to direct approach in 7 patients and as the sole procedure in one inoperable patient. Twenty-seven direct approaches were undertaken in 26 patients, including 17 infratentorial and 10 supratentorial approaches. Total tumor removal was achieved in 20 patients (77%) and subtotal removal in 6 (23%). Fifteen patients (55%) experienced 22 postoperative complications. One patient died three months after a subtotal resection (mortality=3,7%). With a mean follow-up of 54 months, all 26 survivors are currently alive with 23 having resumed their normal activities and 3 needing assistance. Five of 6 patients with subtotal resection survived and were followed for a period ranging from 72 to 132 months: none showed residual tumor progression and no re-operation was considered. An additional patient experienced a ?true? recurrence 6 years after total removal, with no tumor progression 2 years after his recurrence was recognized.  Discussion. The best surgical approach to TMs is still a controversial matter. The advantages and drawbacks of conventional versus transbasal approaches are reviewed. Our experience suggests that subtotal removal can be associated with long recurrence-free intervals and preserved quality of life. TMs located at the tentorial edge carried a definitely worse prognosis than peripheral forms.     

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...     

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.     

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.     

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.     

Potential utility of bone scan in cranial bone flap osteomyelitis

Annals of Nuclear Medicine - Currently, the diagnosis of bone flap osteomyelitis (BFO) remains a challenge for medical imaging. The present study aimed to identify predictive scintigraphic patterns...     

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.

     

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     

Results of a phase II trial of a combination of oral cytarabine ocfosfate (YNK01) and interferon alpha-2b for the treatment of chronic myelogenous leukemia patients in chronic phase.

Cytarabine ocfosfate (YNK01) is a prodrug analogue of cytarabine which is resistant to systemic deamination after oral administration. Following initial studies indicating significant anti-tumour activity of YNK01 a phase II trial was initiated in order to assess the tolerability and efficacy of a combination of this agent with interferon alpha-2b (IFN-alpha2b) in recently diagnosed chronic phase CML patients (n = 98). The treatment was subdivided into cycles consisting of 4 weeks of continuous administration of IFN-alpha-2b (3 MU/m(2)/day 1st week and then 5 MU/m(2)/day) and 14 days of oral YNK01 (600 mg/day 1st cycle). At the end of each cycle the dose of YNK01 was adjusted according to the blood count observed during the previous 4 weeks. The median time from diagnosis to inclusion in the trial was 2 months (range 6 days to 7.5 months). At 12 weeks, 62 patients (63%; 95% CI, 54-73) achieved a complete hematological response. At 24 weeks, of 98 patients, two achieved a complete cytogenetic response, 14 a partial response (16% major cytogenetic response rate; 95% CI, 9-24) and 34 a minor response; 19 patients were not evaluable for cytogenetic response. During the trial, 20 patients progressed to accelerated (6) or blastic phases (14). The median time to progression was 15 months (range 2-38 months). At 3 years the overall survival was 79% (95% CI, 70-88). Although the complete hematological response rate compared favorably with the 40% response rate previously obtained with the subcutaneous formulation of Ara-c, the cytogenetic response rate was less than expected. Most of the patients experienced side-effects and all permanently stopped YNK01. Although the combination seems attractive the initial dose of 600 mg per day is probably too high and should be reconsidered in further trials.