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Abstract: We report the case of a 54-year-old woman suspected of relapsing polychondritis who underwent a nasal septum biopsy under general anaesthesia. Tracheal intubation was unremarkable, but extubation attempts failed because of upper airway inspiratory collapse induced ventilatory distress. Definitive tracheostomy placement was mandatory. Cartilage biopsy confirmed severely developed relapsing polychondritis. Even though relapsing polychondritis is rare, anaesthesiologists should be aware of this pathology and preanaesthetic evaluation may focus on particular risks associated with upper airway cartilaginous structure anatomical and histological modifications. [Copyright &y& Elsevier]

During neurosurgery for hypophysary adenoma under general anaesthesia in a prone position, a 34 year-old-women received accidental 6 ml intramucosal injection of lidocaine with naphazoline. The patient presented a severe bradycardia associated with a major increase in arterial blood pression followed by a brief cardiac arrest. She also presented a prolonged awakening and a pulmonary oedema, which lead to mechanical ventilation. The patient rapidly recovered a normal clinical state. [Copyright &y& Elsevier]

L’allogreffe de CSH est l’unique traitement curatif de certaines hémopathies. L’absence de donneur compatible peut empêcher sa réalisation. A contrario, chacun a un donneur intra-familial ayant un haplotype commun. Nous rapportons le 1er cas français de greffe haploidentique après une déplétion CD3/CD19. Patient: Thomas 13 ans présente un tableau d’aplasie médullaire sévère idiopathique. En l’absence de donneur intrafamilial, il reçoit 2 cures de sérum antilymphocytaire, ciclosporine et stéroïdes, sans efficacité. En l’absence de donneur volontaire ou d’unité de sang placentaire, l’indication d’une allogreffe de CSH haploidentiques 7/10e à partir de son père est posée. Méthode: La double sélection négative CD3/CD19 tend à supprimer les lymphocytes T (responsables de GvH) et les lymphocytes B (responsables de PTLD) et à conserver les CSH et l’ensemble des CD34– dont PNN, monocytes- macrophages et NK, acteurs de l’immunité innée et d’une partie de la reconstitution immunitaire ultérieure. Le patient reçoit un RIC. La prophylaxie de la GVH est réalisée par mmF. Une prophylaxie antivirale, un monitoring viral pour ADV, cmV et EBV ainsi qu’un suivi du chimérisme sanguin hebdomadaires sont réalisés. Résultats: 17.106 CD34 +/kg sont collectées chez le père. 435.106CNT/kg dont 9.106 CD34 +/kg et 85.103 CD3/kg sont réinjectées. La sortie d’aplasie survient à J12 PG après une toxicité digestive de grade IV. Il n’y a pas eu d’épisode infectieux documenté. Aucune réactivation virale n’est observée jusqu’à ce jour. Le chimérisme sanguin est constamment 100 % donneur. Discussion et Conclusion: L’absence de greffon satisfaisant ou l’urgence relative de la greffe imposent le développement de techniques alternatives dont le recours à un donneur haplo-identique. En dépit de l’amélioration de la sélection positive des CD34 +, ces greffes demeurent grevées de taux de morbidité et mortalité élevés (infections sévères, rechutes). La double sélection négative CD3/CD19 associée à un suivi rapproché du chimérisme (pour ajustement rapide de l’immunosuppression) et à un RIC pourrait permettre de limiter ces écueils, ce que semblent démontrer les premiers résultats des équipes de Tübingen et Francfort. Cette première tentative française est également encourageante. [Copyright &y& Elsevier]

TYROSINE KINASE INHIBITORS FOR CHRONIC MYELOID LEUKEMIA. About 20 years ago, the discovery of imatinib, the first ATP-competitive inhibitor of BCR::ABL1 the driving oncoprotein of chronic myeloid leukemia (CML), revolutionized patients' outcome by transforming a fatal condition into a chronic one. Today, five more tyrosin kinase inhobitors (TKIs) have been approved, allowing to some extent individualization of drug therapy. The main therapeutic objective is to protect patients from progression towards a fatal blast crisis and to restore of a near-to-normal life expectancy on lifelong TKI treatment. Only a minority of patients manage to achieve a state called treatment-free remission. Research efforts must go on as some challenges remain such as improving scoring systems, increasing TKI safety profile, fighting against resistance and finding how to cure CML., Competing Interests: L’auteure déclare des liens d’intérêts avec Incyte, Novartis Pharma, Pfizer et Terns Pharma.

Tyrosine kinase inhibitors targeting the BCR-ABL1 oncoprotein represent an outstanding progress in chronic myeloid leukemia and long-term progression-free survival has become a reality for a majority of patients. However, tyrosine kinase inhibitors may at best chronicize rather than cure the disease thus current recommendation is to pursue treatment indefinitely. As a consequence, high quality treatment and care must integrate optimal disease control and treatment tolerability. Tyrosine kinase inhibitors have an overall favorable safety profile in clinical practice since most adverse events are mild to moderate in intensity. However, recent evidence has emerged that new generation tyrosine kinase inhibitors may sometimes damage vital organs and if not adequately managed, morbidity and mortality may increase. The 3rd generation tyrosine kinase inhibitor ponatinib is licensed for the treatment of chronic, accelerated or blast phase chronic myeloid leukaemia patients who are resistant to dasatinib or nilotinib; intolerant of dasatinib or nilotinib and for whom further treatment with imatinib is not clinically appropriate; or who express the T315I mutation. Ponatinib represents an important therapeutic option but it is associated with an increased risk of cardiovascular events. The purpose of this article by the France Intergroupe des Leucémies Myéloïdes Chroniques is to provide an overview of ponatinib efficacy and cardiovascular safety profile and to propose practical recommendations with the goal to minimize the risk and severity of cardiovascular events in ponatinib-treated patients., (Copyright © 2022 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

In the context of chronic myeloid leukemia (CML) resistant to tyrosine kinase inhibitors (TKIs), BCR-ABL1 tyrosine kinase domain (TKD) mutations still remain the sole biological marker that directly condition therapeutic decision. These recommendations aim at updating the use of BCR-ABL1 mutation testing with respect to new available therapeutic options and at repositioning different testing methods at the era of next generation sequencing (NGS). They have been written by a panel of experts from the French Study Group on CML (Fi-LMC), after a critical review of relevant publications. TKD mutation testing is recommended in case of treatment failure but not in case of optimal response. For patients in warning situation, mutation testing must be discussed depending on the type of TKI used, lasting of the treatment, kinetic evolution of BCR-ABL1 transcripts along time and necessity for switching treatment. The kind and the frequency of TKD mutations occasioning resistance mainly depend on the TKI in use and disease phase. Because of its better sensitivity, NGS methods are recommended for mutation testing rather than Sanger's. Facing a given TKD mutation, therapeutic decision should be taken based on in vitro sensitivity and clinical efficacy data. Identification by sequencing of a TKD mutation known to induce resistance must lead to a therapeutic change. The clinical value of testing methods more sensitive than NGS remains to be assessed., (Copyright © 2019 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Convincing clinical and experimental evidence is converging on the essential role of NK (Natural Killer) cells in the recognition and eradication of tumors. Recent studies emphasized the role of NK cells in the immune control of chronic myeloid leukemia (CML), a malignancy arising from hematopoietic stem cells, and the treatment of which has been revolutionized by the use of tyrosine kinase inhibitors (TKI). Three major findings are emerging: 1) the impairment of the numbers and function of NK cells at diagnosis, 2) the restoration of the NK cell function and numbers during remissions induced with TKI therapies and 3) the potential role of the more mature NK CD56 dim cell population in maintaining relapse-free survival after stopping TKI therapy. Immunological control of CML by NK cells which has been suspected for several decades is thus a new field of investigation for future therapies., (© 2018 médecine/sciences – Inserm.)

The development of tyrosine kinase inhibitors (TKI) has revolutionized management of patients with chronic myeloid leukemia (CML), transforming this fatal disease into a chronic disease with nearly normal life expectancy. Nilotinib is a second generation TKI targeting the oncoprotein BCR-ABL used in patients in the chronic phase of CML. Several research teams have suggested over recent years that nilotinib might be the causal agent in the development or aggravation of vascular disease, particularly in patients with cardiovascular risk factors or an established cardiovascular disease. We report here the case of a patient who developed severe peripheral arterial disease of the lower limbs that worsened despite optimal medical and surgical care, presenting recurrent re-stenoses after different revascularization techniques (bypass, angioplasty…) associated with aggravation of severe trophic disorders to the point of potentially requiring amputation. Discontinuation of nilotinib enabled a stabilization of the arterial lesions and complete healing of the trophic lesions. This case illustrates the importance of recognizing co-morbid conditions in patients with severe vascular disease and to examine the possibility of drug interactions leading to rapid aggravation of arterial disease with no other cause. Studying the pathophysiological impact of TKIs on the vascular system may open new avenues of research for the investigation of factors triggering arteriosclerosis., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Nilotinib (Tasigna) is a second-generation BCR-ABL kinase inhibitor, recently introduced and used for the treatment of chronic or accelerated phase CML patients, intolerant or resistant to imatinib. This treatment represents and important step forward for the disease control of such patients but can lead to side effects, sometimes serious, which can limit its optimal use. We propose here some guidelines that might be of help in daily practice, in order to manage properly these side effects.

We report the case of a 54-year-old woman suspected of relapsing polychondritis who underwent a nasal septum biopsy under general anaesthesia. Tracheal intubation was unremarkable, but extubation attempts failed because of upper airway inspiratory collapse induced ventilatory distress. Definitive tracheostomy placement was mandatory. Cartilage biopsy confirmed severely developed relapsing polychondritis. Even though relapsing polychondritis is rare, anaesthesiologists should be aware of this pathology and preanaesthetic evaluation may focus on particular risks associated with upper airway cartilaginous structure anatomical and histological modifications.