CD30 as a therapeutic target in adult haematological malignancies: Where are we now?

CD30 is a transmembrane protein from the tumour necrosis factor receptor superfamily. It is expressed on a small subset of activated T and B lymphocytes, and various lymphoid neoplasms. CD30 is a particularly interesting treatment target because its levels are high in tumours but low in healthy tissues. Several therapeutic strategies targeting CD30 have been developed, including monoclonal antibodies, conjugated antibodies (combination of brentuximab vedotin with chemotherapy or immunotherapy), bispecific antibodies and cell and gene therapies, such as anti-CD30 CAR-T cells in particular. We briefly review the biology of CD30 which makes it a good therapeutic target, and we describe all of the anti-CD30 therapies that have emerged to date.

Role of up-front autologous stem-cell transplantation in peripheral T-cell lymphoma for patients in response after induction: an analysis of patients from LYSA centers.

Background: Peripheral T-cell lymphoma (PTCL) remains a therapeutic challenge. Due to the rarity and the heterogeneity of PTCL, no consensus has been achieved regarding even the type of first-line treatment. The benefit of autologous stem-cell transplantation (ASCT) is, therefore, still intensely debated. Patients and methods: In the absence of randomized trials addressing the role of ASCT, we performed a large multicentric retrospective study and used both a multivariate proportional hazard model and a propensity score matching approach to correct for sample selection bias between patients allocated or not to ASCT in intention-to-treat (ITT). Results: Among 527 patients screened from 14 centers in France, Belgium and Portugal, a final cohort of 269 patients ≤65 years old with PTCL-not otherwise specified (NOS) (N = 78, 29%), angioimmunoblastic T-cell lymphoma (AITL) (N = 123, 46%) and anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK-ALCL) (N = 68, 25%) with partial (N = 52, 19%) or complete responses (N = 217, 81%) after induction was identified and information about treatment allocation was carefully collected before therapy initiation from medical records. One hundred and thirty-four patients were allocated to ASCT in ITT and 135 were not. Neither the Cox multivariate model (HR = 1.02; 95% CI: 0.69-1.50 for PFS and HR = 1.08; 95% CI: 0.68-1.69 for OS) nor the propensity score analysis after stringent matching for potential confounding factors (logrank P = 0.90 and 0.66 for PFS and OS, respectively) found a survival advantage in favor of ASCT as a consolidation procedure for patients in response after induction. Subgroup analyses did not reveal any further difference for patients according to response status, stage disease or risk category. Conclusions: The present data do not support the use of ASCT for up-front consolidation for all patients with PTCL-NOS, AITL, or ALK-ALCL with partial or complete response after induction.

[Agrypnia (organic insomnia)]. / Les agrypnies.

The word agrypnia, ie, organic insomnia, was first used to describe a patient with a Morvan fibrillary chorea, which is an ill-delineated syndrome. This review considers the experimental insomnia created by raphe nuclei, anterior hypothalamic, or thalamic lesions. There are some papers reporting REM and non-REM sleep reduction in man after vascular, traumatic or degenerative lesion of the pons. There is only one case of agrypnia due to a bilateral stereotatic thalamic injury. Infectious agrypnia (trypanosomiasis, Von Economo) may exist but has not been documented by polygraphic means. Fatal familial insomnia induces a precocious agrypnia and leads to death with vegetative and motor disturbances. It is associated with an abnormal prion-protein which may interfere with gabaergic synapses. Finally agrypnia in humans corresponds to either lesionnal or infra microscopic synaptic prion linked disorders.

[Early and middle latency auditory evoked potentials in vertebrobasilar strokes]. / Potentiels évoqués auditifs précoces et de latence moyenne dans les accidents vasculaires vertébrobasilaires.

Brainstem auditory evoked potentials (BAEPs) and middle-latency auditory evoked potentials (MLAEPs) have been recorded in 67 patients who had a stroke in well-defined territories of the vertebral and basilar arteries. Either CT scan or MRI have been performed in all cases. BAEPs were abnormal in 41/67 patients and MLAEPs were abnormal in 25/39 patients. BAEPs abnormalities were either bilateral (29/41 cases) or unilateral (12/41 cases). All components of BAEPS were unilaterally absent in four cases and bilaterally in one case. Pa component of MLAEPs was unilaterally delayed or reduced in five cases and bilaterally in 20 cases. Considering the topography of the infarct as shown by CT scan or MRI: medulla oblongata (13 cases): BAEPSs were normal in nine cases; pons (24 cases): BAEPs were abnormal in 16 cases; MLAEPs were abnormal in ten of 15 patients whose BAEPs were abnormal as well; mesencephalon (seven cases): BAEPs were abnormal in only two cases, and MLAEPs were abnormal in two cases one of which BAEPs were normal; in patients with diffuse infarctions either BAEPs or MLAEPs or both were abnormal in all cases. Stimulation of the ear ipsilateral to the lesion disclosed more BAEPs or MLAEPs abnormalities than stimulation of the contralateral ear.

[Progressive supranuclear paralysis. Quantification of dopamine D2 receptors using radionuclide tomography]. / Paralysies supra-nucléaires progressives. Quantification des récepteurs dopaminergiques D2 par tomoscintigraphie.

Progressive supranuclear palsy (PSP) may sometimes be misdiagnosed as Parkinson's disease in its early stages, hence an early positive diagnosis of PSP based on dopamine D2 receptor density could be extremely valuable. In the present case report, the absence of dopamine D2 receptors was clearly demonstrated in the striatum using 123I-iodobenzamide (IBZM) tomoscintigraphy. This illustrates the potential use of IBZM tomoscintigraphy to identify Parkinson-like's disease presenting with decreased dopamine D2 receptor density; and hence to predict L-Dopa effectiveness. Further studies are needed to evaluate the vaue of IBZM tomoscintigraphy in the different Parkinson's like diseases.

Randomised double blind trial of the safety and efficacy of two gadolinium complexes (Gd-DTPA and Gd-DOTA).

The main difference between macrocyclic Gd-DOTA and linear Gd-DTPA complexes is the greater stability of the former which theoretically might reduce biological interactions in man. To evaluate the clinical relevance of this property, 300 unselected neurological patients were included in a randomised double-blind comparison involving five European centres, focused mainly on the tolerance of these two contrast media. Clinical tolerance was assessed immediately after the procedure and 24 h later. Adverse events were found with a similar frequency in the two groups (17.3% for Gd-DOTA and 19.3% for Gd-DTPA). Minor neurological symptoms were the most frequent (48.6%) headache being the most common (29.2% of adverse events). No difference in efficacy was found.

MRI anatomy of the acoustic-facial bundle in vivo.

In this study performed on 5 healthy volunteers the authors used oblique axial, coronal and sagittal MRI sections suitable to be anatomical configuration of the acoustic-facial bundle and were able to individualize the nerves forming this bundle throughout their course, with the sole exception of the intermediate nerve (VII2). They also analysed the relations of these nerves between themselves and with the other elements of the cerebellopontine angle. In addition, a proton-density sequence (SE, 6,000/30 ms) made it possible to differentiate in vivo between the grey matter and the white matter sufficiently to individualize the principal nuclei and tracts of the brain stem, and in particular the main vestibulo-cochlear central pathways.

[The new imaging technics: theoretical principles, limitations and some ideas on costs]. / Les nouvelles techniques d'imagerie: principes théoriques, limites, notions de coût.

The new imaging techniques modify the diagnostic, or even sometimes therapeutic, decision lines. Their efficiency is much greater than that of the old techniques, while pretium doloris and side-effects are considerably reduced. Such advances are not without a major disadvantage: the ever increasing cost of imaging explorations. Radiological guidance (with conventional radiology, ultrasounds and computerized tomography) facilitates percutaneous procedures for diagnostic (biopsy) or therapeutic purposes (emptying of abscesses, chemonucleolysis of herniated lumbar disc, etc.).

[Non-traumatic vertebro-epidural radiculo-spinal cord compressions: value of x-ray computed tomography coupled with myelography for lesion evaluation and therapeutic indications]. / Compressions médullo-radiculaires vertébro-épidurales non traumatiques: intérêt de l'étude tomodensitométrique couplée à la myélographie pour le bilan lésionnel et les indications thérapeutiques.

About 37 cases of non-traumatic spinal cord and cauda-equina compression, the authors emphasize the value of CT-scan study after intra-thecal injection of water-soluble contrast-medium. This exploration gives accurate informations about the involvement of both spinal and para-spinal spaces. These data are helpful diagnosis purpose and for the choice of therapeutic especially when surgical procedure is decided.

Cerebral toxoplasmosis in acquired immuno deficiency syndrome. A comparative assisted tomographic and neuropathological study of a case.

Authors report a case of fatal CNS toxoplasmosis in a young homosexual man suffering from Kaposi angio-sarcoma. This paper is principally concerned with CT scan and neuropathological correlations.