Incidence of symptomatic Covid-19 infections in patients with mastocytosis and chronic myeloid leukemia: A comparison with the general Austrian population.

BACKGROUND: The SARS-COV-2 (Covid-19) pandemic has impacted the management of patients with hematologic disorders. In some entities, an increased risk for Covid-19 infections was reported, whereas others including chronic myeloid leukemia (CML) had a lower mortality. We have analyzed the prevalence of Covid-19 infections in patients with mastocytosis during the Covid-19 pandemic in comparison to data from CML patients and the general Austrian population. MATERIALS AND METHODS: The prevalence of infections and PCR-proven Covid-19 infections was analyzed in 92 patients with mastocytosis. As controls, we used 113 patients with CML and the expected prevalence of Covid-19 in the general Austrian population. RESULTS: In 25% of the patients with mastocytosis (23/92) signs and symptoms of infection, including fever (n = 11), dry cough (n = 10), sore throat (n = 12), pneumonia (n = 1), and dyspnea (n = 3) were recorded. Two (8.7%) of these symptomatic patients had a PCR-proven Covid-19 infection. Thus, the prevalence of Covid-19 infections in mastocytosis was 2.2%. The number of comorbidities, subtype of mastocytosis, regular exercise, smoking habits, age, or duration of disease at the time of interview did not differ significantly between patients with and without Covid-19 infections. In the CML cohort, 23.9% (27/113) of patients reported signs and symptoms of infection (fever, n = 8; dry cough, n = 17; sore throat, n = 11; dyspnea, n = 5). Six (22.2%) of the symptomatic patients had a PCR-proven Covid-19 infection. The prevalence of Covid-19 in all CML patients was 5.3%. The observed number of Covid-19 infections neither in mastocytosis nor in CML patients differed significantly from the expected number of Covid-19 infections in the Austrian population. CONCLUSIONS: Our data show no significant difference in the prevalence of Covid-19 infections among patients with mastocytosis, CML, and the general Austrian population and thus, in mastocytosis, the risk of a Covid-19 infection was not increased compared to the general population.

Ponatinib-Associated Cutaneous Eruptions-A Case Series and Review of Clinicopathologic Findings.

ABSTRACT: Ponatinib is a third-generation tyrosine kinase inhibitor used to treat chronic myeloid leukemia and Philadelphia-positive acute lymphoblastic leukemia. Cutaneous toxicities are a commonly reported side effect of ponatinib treatment with "rash" being one of the most common. Specific subtypes are infrequently reported, but include hyperkeratotic, folliculocentric, ichthyosiform, and pityriasis rubra pilaris-like eruptions. Herein, we highlight the clinicopathologic features of 2 cases of ponatinib-induced pityriasis rubra pilaris-like eruptions. We also classify the clinical and histopathologic features of all previously reported ponatinib-associated eruptions in the literature and discuss treatment and potential diagnostic pitfalls.

Single-center study on SARS-CoV-2 infection in patients affected by CML: Vaccination status and bosutinib therapy as possible protective factors for hospitalization.

INTRODUCTION: COVID-19 pandemic had a considerable impact among haematological patients. On the other hand, the effect of this disease on patients (pts) affected by Chronic Myeloid Leukemia (CML) is not clearly defined. OBJECTIVES: The primary objective of this study was to evaluate mortality-hospitalization rates and possible protective factors for hospitalization in CML pts affected by COVID. METHODS: We collected data from CML patients followed at our institution whotested positive for SARS-CoV-2 infection. The following variables were assessed: demographical data, type of TKI therapy, vaccination status, presence of cardiovascular disease (CVD), period of infection, COVID-19 presenting symptoms, severity and mortality. Data were collected retrospectively and then analysed in univariate and multivariate analysis. RESULTS: Out of a total of 325 CML pts treated at our institution, we recorded 72 SARS-CoV-2pts (22%) who tested positive with a SARS-CoV-2 PCR assay. Twenty two were infected in 2020 (30%), 16 patients in 2021 (22%) and 34 in 2022 (46%); with a hospitalization rate of 27%, 25% and 3% respectively. Of the 72 confirmed infections, 13 pts (18%; (CI) 10-28) were asymptomatic and 48 (66%; CI: 55-76) had mild symptoms. A total of 11 pts were admitted to hospital and 3 of these required ICU admission. No deaths were recorded. The probability of hospitalization was significantly reduced if patients were vaccinated (odds ratio OR 0.037 with CI: 0-0.33 p 0.002) or treated with Bosutinib (OR 0.06 with CI: 0-0.5 p 0.008). CONCLUSION: In the present study, no significant increase in mortality was noted among patients with CML as compared to the general population inItaly. Vaccination and treatment with bosutinib were identified as baseline characteristics that were associated with a decreased risk of hospitalitazion resulting from COVID-19 infection.

Treatment of blast phase chronic myeloid leukaemia: A rare and challenging entity.

Despite the success of BCR-ABL-specific tyrosine kinase inhibitors (TKIs) such as imatinib in chronic phase (CP) chronic myeloid leukaemia (CML), patients with blast phase (BP)-CML continue to have a dismal outcome with median survival of less than one year from diagnosis. Thus BP-CML remains a critical unmet clinical need in the management of CML. Our understanding of the biology of BP-CML continues to grow; genomic instability leads to acquisition of mutations which drive leukaemic progenitor cells to develop self-renewal properties, resulting in differentiation block and a poor-prognosis acute leukaemia which may be myeloid, lymphoid or bi-phenotypic. Similar advances in therapy are urgently needed to improve patient outcomes; however, this is challenging given the rarity and heterogeneity of BP-CML, leading to difficulty in designing and recruiting to prospective clinical trials. This review will explore the treatment of BP-CML, evaluating the data for TKI therapy alone, combinations with intensive chemotherapy, the role of allogeneic haemopoietic stem cell transplantation, the use of novel agents and clinical trials, as well as discussing the most appropriate methods for diagnosing BP and assessing response to therapy, and factors predicting outcome.

Effectiveness of digital care platform CMyLife for patients with chronic myeloid leukemia: results of a patient-preference trial.

BACKGROUND: Two most important factors determining treatment success in chronic myeloid leukemia (CML) are adequate medication compliance and molecular monitoring albeit still being suboptimal. The CMyLife platform is an eHealth innovation, co-created with and for CML patients, aiming to improve their care, leading to an increased quality of life and the opportunity of hospital-free care. OBJECTIVE: To explore the effectiveness of CMyLife in terms of information provision, patient empowerment, medication compliance, molecular monitoring, and quality of life. METHODS: Effectiveness of CMyLife was explored using a patient-preference trial. Upon completion of the baseline questionnaire, participants actively used (intervention group) or did not actively use (questionnaire group) the CMyLife platform for at least 6 months, after which they completed the post-intervention questionnaire. Scores between the intervention group and the questionnaire group were compared with regard to the within-subject change between baseline and post-measurement using Generalized Estimating Equation models. RESULTS: At baseline, 33 patients were enrolled in the questionnaire group and 75 in the intervention group. Online health information knowledge improved significantly when actively using CMyLife and patients felt more empowered. No significant improvements were found regarding medication compliance and molecular monitoring, which were already outstanding. Self-reported effectiveness showed that patients experienced that using CMyLife improved their medication compliance and helped them to oversee their molecular monitoring. Patients using CMyLife reported more symptoms but were better able to manage these. CONCLUSIONS: Since hospital-free care has shown to be feasible in time of the COVID-19 pandemic, eHealth-based innovations such as CMyLife could be a solution to maintain the quality of care and make current oncological health care services more sustainable. TRIAL REGISTRATION: ClinicalTrials.gov NCT04595955 , 22/10/2020.

Role of tyrosine kinase inhibitor in chronic myeloid leukemia patients with SARS-CoV-2 infection: A narrative Review.

Severe acute respiratory syndrome (SARS) caused by a novel coronavirus-2 (CoV-2), also known as COVID-19, has spread rapidly worldwide since it is recognized as a public health emergency and has now been declared a pandemic on March 11, 2020, by the World Health Organization. The genome of SARS-CoV-2 comprises a single-stranded positive-sense RNA approximately 27 to 30 kb in size. The virus is transmitted through droplets from humans to humans. Infection with the SARS virus varies from asymptomatic to lethal, such as fever, cough, sore throat, and headache, but in severe cases, pneumonia and acute respiratory distress syndrome. Recently, no specific and effective treatment has been recommended for patients infected with the SARS virus. However, several options can be investigated to control SARS-CoV-2 infection, including monoclonal antibodies, interferons, therapeutic vaccines, and molecular-based targeted drugs. In the current review, we focus on tyrosine kinase inhibitor management and their protective role in SARS-CoV-2 patients with chronic myelogenous leukemia.

A clinician perspective on the treatment of chronic myeloid leukemia in the chronic phase.

Tyrosine kinase inhibitors (TKIs) have vastly improved long-term outcomes for patients with chronic myeloid leukemia (CML). After imatinib (a first-generation TKI), second- and third-generation TKIs were developed. With five TKIs (imatinib, dasatinib, bosutinib, nilotinib, and ponatinib) targeting BCR::ABL approved in most countries, and with the recent approval of asciminib in the USA, treatment decisions are complex and require assessment of patient-specific factors. Optimal treatment strategies for CML continue to evolve, with an increased focus on achieving deep molecular responses. Using clinically relevant case studies developed by the authors of this review, we discuss three major scenarios from the perspective of international experts. Firstly, this review explores patient-specific characteristics that affect decision-making between first- and second-generation TKIs upon initial diagnosis of CML, including patient comorbidities. Secondly, a thorough assessment of therapeutic options in the event of first-line treatment failure (as defined by National Comprehensive Cancer Network and European LeukemiaNet guidelines) is discussed along with real-world considerations for monitoring optimal responses to TKI therapy. Thirdly, this review illustrates the considerations and importance of achieving treatment-free remission as a treatment goal. Due to the timing of the writing, this review addresses global challenges commonly faced by hematologists treating patients with CML during the COVID-19 pandemic. Lastly, as new treatment approaches continue to be explored in CML, this review also discusses the advent of newer therapies such as asciminib. This article may be a useful reference for physicians treating patients with CML with second-generation TKIs and, as it is focused on the physicians' international and personal experiences, may give insight into alternative approaches not previously considered.

Definition of factors associated with negative antibody response after COVID-19 vaccination in patients with hematological diseases.

COVID-19 in patients with hematological diseases is associated with a high mortality. Moreover, preventive vaccination demonstrated reduced efficacy and the knowledge on influencing factors is limited. In this single-center study, antibody levels of the SARS-CoV-2 spike protein were measured ≥ 2 weeks after 2nd COVID-19 vaccination with a concentration ≥ 0.8 U/mL considered positive. Between July and October 2021, in a total of 373 patients (median age 64 years, 44% women) with myeloid neoplasms (n = 214, 57%), lymphoid neoplasms (n = 124, n = 33%), and other diseases (n = 35, 10%), vaccination was performed with BNT162b2 (BioNTech), mRNA-1273 (Moderna), ChADOx1 (AstraZeneca), or a combination. A total of 229 patients (61%) were on active therapy within 3 months prior vaccination and 144 patients (39%) were previously treated or treatment naïve. Vaccination-related antibody response was negative in 56/373 patients (15%): in 39/124 patients with lymphoid neoplasms, 13/214 with myeloid neoplasms, and 4/35 with other diseases. Active treatment per se was not correlated with negative response. However, rituximab and BTK inhibitor treatment were correlated significantly with a negative vaccination response, whereas younger age and chronic myeloid leukemia (CML) disease were associated with positive response. In addition, 5 of 6 patients with myeloproliferative neoplasm (MPN) and negative vaccination response were on active treatment with ruxolitinib. In conclusion, a remarkable percentage of patients with hematological diseases had no response after 2nd COVID-19 vaccination. Multivariable analysis revealed important factors associated with response to vaccination. The results may serve as a guide for better protection and surveillance in this vulnerable patient cohort.

The new HFA/ICOS risk assessment tool to identify patients with chronic myeloid leukaemia at high risk of cardiotoxicity.

AIMS: Tyrosine kinase inhibitors (TKIs) used to treat chronic myeloid leukaemia (CML) can cause cardiovascular adverse events. So far, the Systematic Coronary Risk Evaluation (SCORE) charts of the European Society of Cardiology (ESC) have been used to identify cancer patients at increased cardiovascular risk. The primary aim of our study was to evaluate the usefulness of the new cardiovascular risk assessment model proposed by the Cardio-Oncology Study Group of the Heart Failure Association (HFA) of the ESC in collaboration with the International Cardio-Oncology Society (ICOS) to stratify the cardiovascular risk in CML patients, compared with SCORE risk charts. The secondary aim was to establish the incidence of adverse arterial events (AEs) in patients with CML treated with TKIs and the influence of preventive treatment with aspirin. METHODS AND RESULTS: A retrospective single-centre observational study was carried out on 58 patients (32 men and 26 women; mean age ± SD: 59 ± 15 years) with CML treated with TKIs for a median period of 43 ± 31 months. Cardiological evaluation was performed and cardiovascular risk was estimated with SCORE risk charts and with the new risk assessment tool proposed by HFA/ICOS. AEs were recorded. According to SCORE charts and the new HFA/ICOS risk stratification tool, respectively, 46% (Group A1) and 60% (Group A2) of patients were at high-very high risk, and 54% (Group B1) and 40% (Group B2) at low-moderate risk. AEs were significantly more frequent in Group A1 than Group B1 (P value < 0.01) when considered overall; they were significantly more frequent in Group A2 than Group B2 either overall or considered individually. HFA/ICOS risk stratification tool was significantly more sensitive than SCORE (P < 0.01) in identifying patients at higher risk of cardiovascular toxicity. In addition, we did not find AEs in patients pretreated with aspirin. CONCLUSIONS: The new HFA/ICOS risk stratification model allows a more tailored cardiovascular risk stratification in patients with CML and it is more sensitive than SCORE charts.

ACUTE GVHD TRIGGERED BY COVID-19 IN A BONE MARROW RECIPIENT (preprint)

Introduction: There are few reports regarding risk of COVID-19-associated complications in bone marrow recipients. We report a patient who had graft-versus-host disease triggered by COVID-19. Results The patient was a 17-year-old boy who underwent HSCT from matched sibling donor for CML. He had complete donor chimerism at day +30. Cyclosporine was tapered and stopped at day +65. Until day +93, he had no complaints. The patient started to suffer from cutaneus and gastro-intestinal grade III GVHD after the diagnossis of CIVID-19. Discussion In the absence of any other condition to explain this clinical picture and the good response to GVHD treatment indicate that the triggering factor in the development of GVHD may be COVID-19 in the era of TLR, which plays a common role in the pathogenesis of both GVHD and COVID-19.

What Do We Currently Know About Chronic Myeloid Leukemia (CML) and COVID-19?

PURPOSE OF REVIEW: COVID-19 is highly contagious; since it was first identified, the virus has rapidly spread to more than 100 countries and was declared a pandemic on March 11, 2020, by the World Health Organization (WHO). This disease presents several challenges when managing patients with leukemia. We review the information about chronic myeloid leukemia (CML) and COVID-19: risk factors, prognosis, and the role of tyrosine kinase inhibitors (TKIs). RECENT FINDINGS: At present, we find no data suggesting that patients with CML-chronic phase (CML-CP) are at higher risk of infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than the general healthy population. TKIs had been proposed to fight the SARS-CoV-2-related disease (COVID-19). CML patients should continue receiving their TKIs if they have COVID-19 disease. The role of TKIs as protective factors against SARS-CoV-2 infection in patients with CML should be confirmed by large-scale epidemiologic studies.

COVID-19 infection in chronic myeloid leukaemia after one year of the pandemic in Italy. A Campus CML report.

Limited information is available on the impact of the COVID-19 pandemic on the management of chronic myeloid leukaemia (CML). The Campus CML network collected retrospective information on 8 665 CML patients followed at 46 centres throughout Italy during the pandemic between February 2020 and January 2021. Within this cohort, we recorded 217 SARS-CoV-2-positive patients (2·5%). Most patients (57%) were diagnosed as having SARS-CoV-2 infection during the second peak of the pandemic (September 2020 to January 2021). The majority (35%) was aged between 50 and 65 years with a male prevalence (73%). Fifty-six percent of patients presented concomitant comorbidities. The median time from CML diagnosis to SARS-CoV-2 infection was six years (three months to 18 years). Twenty-one patients (9·6%) required hospitalization without the need of respiratory assistance, 18 (8·2%) were hospitalized for respiratory assistance, 8 (3·6%) were admitted to an intensive care unit, while 170 (78%) were only quarantined. Twenty-three percent of patients discontinued tyrosine kinase inhibitor (TKI) therapy during the infection. Twelve patients died due to COVID-19 with a mortality rate of 5·5% in the positive cohort and of 0·13% in the whole cohort. We could also document sequelae caused by the SARS-CoV-2 infection and an impact of the pandemic on the overall management of CML patients.

The serological prevalence of SARS-CoV-2 infection in patients with chronic myeloid leukemia is similar to that in the general population.

BACKGROUND: Patients with hematological malignancies are at an increased risk of SARS-CoV-2 disease (COVID-19) and adverse outcome. However, a low mortality rate has been reported in patients with chronic myeloid leukemia (CML). Preclinical evidence suggests that tyrosine kinase inhibitors (TKIs) may have a protective role against severe COVID-19. METHODS: We conducted a cross-sectional study of 564 consecutive patients with CML who were tested for anti-SARS-CoV-2 IgG/IgM antibodies at their first outpatient visit between May and early November 2020 in five hematologic centers representative of three Italian regions. RESULTS: The estimated serological prevalence of SARS-CoV-2 infection in patients with CML after the first pandemic wave was similar to that in the general population (about 2%), both at national and regional levels. CML patients with positive anti-SARS-CoV-2 serology were more frequently male (p = 0.027) and active workers (p = 0.012), while there was no significant association with TKI treatment type. Only 3 out of 11 IgG-positive patients had previously received a molecular diagnosis of COVID-19, while the remainders were asymptomatic or with mild symptoms. CONCLUSIONS: Our data confirm that the course of SARS-CoV-2 infection in patients with CML is generally mild and reassure about the safety of continuing TKIs during the COVID-19 pandemic. Furthermore, we suggest that patients with CML succeed to mount an antibody response after exposure to SARS-CoV-2, similar to the general population.

COVID-19 in chronic myeloid leukemia patients in Latin America.

This observational, multicenter study aimed to report the clinical evolution of COVID-19 in patients with chronic myeloid leukemia in Latin America. A total of 92 patients presented with COVID-19 between March and December 2020, 26% of whom were severe or critical. The median age at COVID-19 diagnosis was 48 years (22-79 years), 32% were 60 years or older, and 61% were male. Thirty-nine patients presented with at least one comorbidity (42.3%). Eighty-one patients recovered (88%), and 11 (11.9%) died from COVID-19. There was one case of reinfection. Patients with a major molecular response presented superior overall survival compared to patients with no major molecular response (91 vs. 61%, respectively; p = 0.004). Patients in treatment-free remission and receiving tyrosine kinase inhibitors showed higher survival rates than patients who underwent hematopoietic stem cell transplantation and those who did not receive tyrosine kinase inhibitors (100, 89, 50, and 33%, respectively; p < 0.001).