[Recognizing and managing side effects of tyrosine kinase inhibitors in chronic myeloid leukemia]. / Effets secondaires des inhibiteurs de tyrosine kinase dans la leucémie myéloïde chronique.

Tyrosine kinase inhibitors (TKI) have emerged as a paradigm-shifting therapeutic approach for the treatment of chronic myeloid leukemia (CML) following their regulatory approval in 2001. These agents have revolutionized the management of CML by significantly improving patient outcomes and enabling them to achieve near-normal life expectancies. Consequently, the utilization of TKI has become increasingly prevalent, accompanied by the recognition and management of their associated adverse effects. Given the expanding patient population receiving TKI therapy, it is imperative that hematologists, as well as general practitioners, assume the responsibility of closely and meticulously monitoring patients' treatment progress while effectively addressing the occurrence of any untoward effects.

Les inhibiteurs de tyrosine kinase (ITK) ont révolutionné la prise en charge de la leucémie myéloïde chronique (LMC) depuis leur autorisation de mise sur le marché en 2001, permettant aux patients d'obtenir une survie comparable à celle de la population générale. À ce jour, plusieurs générations d'ITK sont apparues, avec leurs effets secondaires respectifs. Leur prescription nécessite donc un suivi rapproché et pluridisciplinaire entre l'hématologue et l'interniste hospitalier, mais également le médecin généraliste, qui peut aussi être confronté à ces effets indésirables.

Mesenchymal stromal cells confer chemoresistance to myeloid leukemia blasts through Side Population functionality and ABC transporter activation.

Targeting chemoresistant malignant cells is one of the current major challenges in oncology. Therefore, it is mandatory to refine the characteristics of these cells to monitor their survival and develop adapted therapies. This is of particular interest in acute myeloid leukemia (AML), for which the 5-year survival rate only reaches 30%, regardless of the prognosis. The role of the microenvironment is increasingly reported to be a key regulator for blast survival. In this context, we demonstrate that contact with mesenchymal stromal cells promotes a better survival of blasts in culture in the presence of anthracycline through the activation of ABC transporters. Stroma-dependent ABC transporter activation leads to the induction of a Side Population (SP) phenotype in a subpopulation of primary leukemia blasts through alpha (α)4 engagement. The stroma-promoting effect is reversible and is observed with stromal cells isolated from either healthy donors or leukemia patients. Blasts expressing an SP phenotype are mostly quiescent and are chemoresistant in vitro and in vivo in patient-derived xenograft mouse models. At the transcriptomic level, blasts from the SP are specifically enriched in the drug metabolism program. This detoxification signature engaged in contact with mesenchymal stromal cells represents promising ways to target stroma-induced chemoresistance of AML cells.

Liposomal cytarabine in prophylaxis or curative treatment of central nervous system involvement in Burkitt leukemia/lymphoma.

In recent years, the outcome of Burkitt leukemia/lymphoma (BL) has improved significantly. Central nervous system (CNS) involvement continues to be a poor prognostic indicator. High doses of intravenous polychemotherapy, intrathecal chemotherapy, and cranio-spinal radiation therapy are used by numerous groups. Majority of patients are cured after this strategy. The next challenge is to decrease toxicities of treatment, including long-term toxicities secondary to cranio-spinal radiation therapy observed in these cured patients. Liposomal cytarabine could be a good alternative to cranio-spinal radiation therapy as already reported in acute lymphoblastic leukemia. We report here eleven patients treated in our center for BL, with liposomal cytarabine instead of cranio-spinal radiation therapy as prophylactic or curative treatment for CNS involvement. Treatment was safe with no short-term grade >3 adverse events. Moreover, no long-term side effects and no impact on outcome were observed. We conclude that LC could be a good option to decrease short/long-term side effects of cranio-spinal radiation therapy in BL and could be evaluated in a future clinical trial.

[Plasmacytoïd dendritic cells acute leukemia: a case report]. / Leucémie aiguë dérivée des cellules dendritiques plasmacytoïdes : à propos d'un cas.

We describe a case of a patient hospitalized in haematology unit for treatment to blastic plasmacytoid dendritic cell neoplasm. Apart skin lesions found at diagnosis in 83% of patients, few elements suggest the diagnosis. Cytology is not characteristic and no cytogenetic abnormality is specific to the LpDC, the karyotype shows generally at least three cytogenetic abnormalities. Definitive diagnosis rests to identification of a blastic population with immunophenotype CD4+ CD56+. This leukemia is chemosensitive but the relapse rate is important and the survival time is 16 months.