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The experience of third-generation tyrosine kinase inhibitor ponatinib treatment in Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph'+ ALL) patients post-allogeneic transplantation is limited. We retrospectively collected data on 25 Ph'+ ALL patients who were started on ponatinib after allogeneic transplantation between July 2015 and July 2019 from nine transplantation centers in Italy. Ponatinib was given in prophylaxis in five (20%), as pre-emptive treatment in seven (28%), and as salvage therapy in thirteen (52%) patients. It was combined with donor leukocyte infusions in ten patients. Half of the patients (12/25) harbored T315I mutation of BCR/ABL1, while in the remaining mutational analysis was negative or not performed. Among the 20 patients who received ponatinib as pre-emptive/salvage treatment, complete molecular response was achieved in 15 (75%) patients. Estimated overall survival at 2-year post-initiation of treatment in the whole cohort was 65% (respectively 60%, 60%, and 78% for the prophylaxis, pre-emptive, and salvage therapy groups). In patients with T315I-positive mutational status, the estimated 2-year survival was 40%. Fourteen patients (56%) experienced toxicity, requiring temporary or definitive suspension of treatment. In conclusion, treatment of Ph'+ ALL patients with ponatinib after transplantation is effective, although the question of adequate drug dose and treatment duration remains unanswered. [ABSTRACT FROM AUTHOR]

Abstract: This retrospective study of the thrombocythemia Italian registry (RIT) documented that 71 (30.6%) out of 232 ET patients experienced 88 cardiovascular adverse events (CV-AEs) during anagrelide treatment (522 pt-y). The rate of CV-AEs was: 24.1% for palpitations, 4.3% for angina, 3.5% for arterial hypertension, 3.0% for congestive heart failure, 1.8% for arrhythmia, 0.9% for AMI, 0.4% for pericardial effusion. CV-AEs led to treatment discontinuation in nine (3.9%) patients, while in the remaining cases they were managed by pharmacological intervention and/or patient life style improvement. CV-AEs had no relationship with patient characteristics (including older age). A significant relationship was found only with a higher anagrelide induction dose. In the absence of any agreed protocol, a cardiovascular instrumental evaluation (CV-IE) was performed in 102 (44%) patients before commencement of anagrelide (with higher rate after the anagrelide/Xagrid EMA approval of 2004), and in 84 (36%) patients during treatment. Patients with and without CV-IEs, who resulted completely balanced for all their characteristics, did not significantly differ in the occurrence of CV-AEs. In conclusion, this study on ET patients treated with anagrelide shows that CV-AEs, equally distributed in younger and older subjects, were mostly mild and easily manageable, allowing safe treatment continuation in the majority of cases. Moreover, routinely performing a CV-IE did not appear to anticipate the occurrence of CV-AEs. [Copyright &y& Elsevier]