Priapismo y leucemia mieloide crónica en adolescente. Debut poco frecuente. Reporte de caso / Priapism and chronic myeloid leukemia in an adolescent. Rare debut presentation. A case report

El priapismo es una erección dolorosa y persistente acompañada o no de estímulo sexual. Una causa poco frecuente de esta anormalidad es la leucemia mieloide crónica. Se han reportado pocos casos de priapismo como manifestación inicial de una leucemia de este tipo en pacientes adolescentes. A continuación, se informa el caso de un paciente de 16 años de edad que presentó priapismo como manifestación inicial de una leucemia mieloide crónica. Durante su evolución, no se realizó aspiración de los cuerpos cavernosos. Se inició tratamiento hematológico específico y, ante la persistencia del priapismo, fue necesario realizar un shunt de cuerpos cavernosos en dos ocasiones, tratamiento a pesar del cual existen altas probabilidades de secuelas.

Priapism is a painful and persistent erection, with or without sexual stimulation. A rare cause of such abnormality is chronic myeloid leukemia. Few cases of priapism as an initial manifestation of this type of leukemia have been reported in adolescent patients. Here we describe the case of a 16-year-old patient who presented with priapism as the initial manifestation of chronic myeloid leukemia. No cavernosal aspiration was performed. A specific hematological treatment was started and, given the persistence of priapism, the patient required 2 corpora cavernosa shunt procedures; despite this treatment, there is a high probability of sequelae.

High Efficacy and Safety of Asciminib in a Chronic Myeloid Leukemia Patient with Chronic Kidney Disease Following Renal Transplantation.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm driven by the BCR::ABL1 tyrosine kinase. Tyrosine kinase inhibitors (TKIs) have been established as standard therapies for CML. However, some CML patients experience TKI intolerance. Asciminib was approved for CML patients either intolerant or refractory to TKI therapy. We herein report a 63-year-old CML patient who underwent renal transplantation and exhibited TKI intolerance. He was switched to asciminib, which achieved a deep molecular response without exacerbation of the renal function. Our experience revealed that asciminib is effective and safe for CML patients complicated with chronic kidney disease.

Association of Nilotinib With Cardiovascular Diseases in Patients With Chronic Myelogenous Leukemia: A National Population-Based Cohort Study.

BACKGROUND: Tyrosine kinase inhibitor (TKI) treatment has been identified to be a risk factor for metabolic syndrome and cardiovascular diseases (CVDs) in patients diagnosed with chronic myeloid leukemia (CML). However, the specific contribution of post-TKI metabolic syndrome and the individual TKIs, including imatinib, nilotinib, and dasatinib, contribute to the development of CVDs remains unclear. METHODS: We conducted a nationwide database to investigate the incidence of post-TKI metabolic syndrome, including diabetes, hyperlipidemia, and hypertension, as well as their association with CVDs. To compare the risk of post-TKI comorbidities and CVDs among TKIs, we utilized the incidence rate ratio (IRR), and subdistribution hazard ratio (SHR) calculated from multiple Fine-Gray models. RESULTS: A total of 1211 patients without diabetes, 1235 patients without hyperlipidemia, and 1074 patients without hypertension were enrolled in the study. The incidence rate of post-TKI diabetes and hyperlipidemia was the highest in patients treated with nilotinib compared to imatinib and dasatinib (IRRs ≥ 3.15, Ps ≤ .047). After adjusting for confounders, nilotinib remained a significant risk factor for post-TKI diabetes and hyperlipidemia at an SHR of 3.83 (P < .001) and 5.15 (P < .001), respectively. Regarding the occurrence of CVDs, patients treated with nilotinib were more likely to develop CVDs than those treated with imatinib in non-hyperlipidemic group (IRR = 3.21, P = .020). Pre-existing and post-TKI hyperlipidemia were found to have a stronger association with CVDs, with SHR values of 5.81 (P = .034) and 13.21 (P = .001), respectively. CONCLUSION: The findings of this study indicate that nilotinib treatment is associated with increased risks of diabetes and hyperlipidemia, with hyperlipidemia being the most significant risk for CVDs. Therefore, we recommend that CML patients receiving nilotinib should undergo screening for diabetes and hyperlipidemia prior to initiating TKI treatment. Additionally, regular monitoring of lipid profiles during TKI therapy and implementing effective management strategies to control hyperlipidemia are crucial.

Spontaneous tumor lysis syndrome in a patient with chronic myeloid leukemia treated successfully with allopurinol.

BACKGROUND: Tumor Lysis Syndrome (TLS) is an oncologic emergency that may occur in any patient with a hematologic malignancy, even prior to initiation of chemotherapy. Spontaneous TLS massive tumor cell destruction with intracellular electrolyte release prior to the initiation of chemotherapy. Spontaneous tumor lysis syndrome is a rare presentation, mainly occurring in Acute Leukemia and non-Hodgkin Lymphoma. Chronic Myeloid Leukemia (CML) is a low-risk disease based on TLS risk stratification. To the best of our knowledge, spontaneous TLS in the chronic phase of CML successfully treated with allopurinol and aggressive hydration has yet to be reported in the literature. A case report is described regarding a 67 year old Jamaican female with a history of hypertension who presented to the emergency department with abdominal pain, nausea, and vomiting for 1 day. The patient was found to have leukocytosis to 344,000 with 4% Blasts, hyperuricemia, and acute kidney injury. A peripheral blood smear confirmed the diagnosis of CML. Bone marrow biopsy was performed with evidence of the chronic phase of CML. The patient met clinical criteria for spontaneous tumor lysis syndrome. The patient was started on aggressive intravenous hydration, allopurinol, hydroxyurea and imatinib. Creatinine and uric acid level improved on this regimen within 48 h of initiation.

Priapism and chronic myeloid leukemia in an adolescent. Rare debut presentation. A case report. / Priapismo y leucemia mieloide crónica en adolescente. Debut poco frecuente. Reporte de caso.

Priapism is a painful and persistent erection, with or without sexual stimulation. A rare cause of such abnormality is chronic myeloid leukemia. Few cases of priapism as an initial manifestation of this type of leukemia have been reported in adolescent patients. Here we describe the case of a 16-year-old patient who presented with priapism as the initial manifestation of chronic myeloid leukemia. No cavernosal aspiration was performed. A specific hematological treatment was started and, given the persistence of priapism, the patient required 2 corpora cavernosa shunt procedures; despite this treatment, there is a high probability of sequelae.

El priapismo es una erección dolorosa y persistente acompañada o no de estímulo sexual. Una causa poco frecuente de esta anormalidad es la leucemia mieloide crónica. Se han reportado pocos casos de priapismo como manifestación inicial de una leucemia de este tipo en pacientes adolescentes. A continuación, se informa el caso de un paciente de 16 años de edad que presentó priapismo como manifestación inicial de una leucemia mieloide crónica. Durante su evolución, no se realizó aspiración de los cuerpos cavernosos. Se inició tratamiento hematológico específico y, ante la persistencia del priapismo, fue necesario realizar un shunt de cuerpos cavernosos en dos ocasiones, tratamiento a pesar del cual existen altas probabilidades de secuelas.

Cardiovascular Adverse Events of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia: Clinical Relevance, Impact on Outcome, Preventive Measures and Treatment Strategies.

OPINION STATEMENT: The introduction of TKIs into the therapeutic armamentarium of CML has changed the disease paradigm, increasing long-term survival from 20% to over 80%, with a life expectancy now approaching that of the general population. Although highly effective, TKIs also have a toxicity profile that is often mild to moderate, but sometimes severe, with multiple kinases involved in the development of adverse events (AEs). Among others, cardiovascular AEs observed in TKI-treated CML patients may represent a significant cause of morbidity and mortality, and their pathogenesis is still only partially understood. In view of the recent introduction into daily clinical practice of new TKIs, namely the STAMP inhibitor asciminib, with a distinct safety profile, hematologists now more than ever have the opportunity to select the most suitable TKI for each patient, an aspect that will be fundamental in terms of personalized preventive and therapeutic strategies. Furthermore, physicians should be aware of the feasibility of TKI dose modifications at all stages of the patients' treatment journey, both at diagnosis for frail or elderly subjects or with multiple comorbidities, and during follow-up for those patients who experience toxicity, as well as to prevent it, with the main objective of reducing side effects while maintaining the response. Consequently, preserving the cardiovascular health of CML patients will likely be a more urgent topic in the near future, with specific measures aimed at controlling cardiovascular risk factors through a multidisciplinary approach involving a panel of healthcare professionals together with the hematologist.

Chronic myeloid leukemia with sleep-related painful erections as a first symptom: a case report.

BACKGROUND: Sleep-related painful erections are characterized by deep penile pain that occurs during erections in the rapid eye movement stage of sleep. CASE PRESENTATION: This case presents a 43-year-old Chinese Han patient with sleep-related painful erections. Turgid painful erections (4-5 episodes of tumescence) during the sleep hours caused pain. Further, blood testing revealed an abnormal increase in white blood cells (123 × 109/L). The patient was diagnosed with chronic myeloid leukemia by bone marrow biopsy, BCR::ABL1 fusion gene testing, and Philadelphia chromosome. However, the sleep-related painful erections have dramatically decreased in frequency of erectile pain after chemotherapy for Chronic myeloid leukemia in our case. CONCLUSION: We considered that the occurrence of sleep-related painful erections was related to chronic myeloid leukemia and the case might be secondary sleep-related painful erections.

Acquired Factor VII Deficiency Associated With Chronic Myeloid Leukemia Blast Crisis.

Factor VII (FVII) is an important, vitamin K-dependent clotting factor. Acquired FVII deficiency is a rare entity that is associated with serious bleeding complications. We report a case of acquired FVII deficiency in a patient with recurrent chronic myeloid leukemia in blast crisis who developed bilateral retinal hemorrhages. The coagulopathy was corrected with the initiation of chemotherapy and subsequent reduction in peripheral blast count.

COVID-19 Infection in Chronic Myeloid Leukemia Patients Receiving Tyrosine Kinase Inhibitor in Makassar, Indonesia: A Six-Case Report and Literature Review.

Management of chronic myeloid leukemia (CML) in patients who are infected with COVID-19 is a challenging task due to disease-related or treatment-related factors that place such patients at a higher risk of complications. However, a low-infectivity-rate mechanism has been proposed by some researchers. In CML patients with COVID-19 infection, the most important treatment-related factor involves tyrosine kinase inhibitors (TKIs). In this case report, six patients with chronic-phase CML who experienced COVID-19 of mild-moderate severity all continued to receive TKI treatment for CML concurrently with COVID-19 treatment. All patients fully recovered. In the present study, we also review four other cases of COVID-19 infection in CML patients. Outcomes for TKI-treated CML patients who contract COVID-19 are influenced by many factors. Tyrosine kinase inhibitor therapy may benefit CML patients due to its antiviral effect, but the interaction between TKIs and drugs used for COVID-19 treatment requires careful monitoring. An individual approach is needed in every case.

Clinical Outcomes of Patients with Chronic Myeloid Leukemia and COVID-19 Infection-A Single Center Survey.

Background: Previous research has shown different effects of hematological malignancies on the outcome of patients with COVID-19 infection depending on the type of disease and the treatment received. This research was aimed at examining the clinical outcome of COVID-19 infection in positive patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors. Methods: We collected retrospective information on chronic myeloid leukemia patients who were treated and monitored in our institution during the pandemic period. Within this cohort, we recorded COVID-19 positive symptomatic patients and analyzed their basic characteristics, symptoms, severity, and outcome. Results: In the study cohort when COVID-19 was diagnosed, 86.7% of patients were on first-generation tyrosine kinase inhibitors therapy-imatinib. At the time of infection, 70% of patients were in molecular remission, 23.4% in complete cytogenetic remission, and 3.3% in complete hematological response. Most patients had symptomatic disease. Within the analyzed group, 56.7% of patients had asymptomatic/mild COVID-19 infection, 23.3% of patients had moderate symptoms which did not require hospitalization, and 20% of patients had severe/critical symptoms that required admission to the intensive care unit. More than half of the patients interrupted treatment with tyrosine kinase inhibitors temporarily during COVID-19. There were no deaths due to COVID-19 infection. Conclusions: In compliance with other larger clinical studies, analysis of the clinical outcome of COVID-19 infection in patients with chronic myeloid leukemia on tyrosine kinase inhibitors therapy in this study showed that they do not have an increased risk for COVID-19 infection and that they have a mild course of the disease with recovery.

High sensitivity c-reactive protein and circulating biomarkers of endothelial dysfunction in patients with chronic myeloid leukemia receiving tyrosine kinase inhibitors.

Tyrosine kinase inhibitors (TKIs) have revolutionized the management of patients with chronic myelogenous leukemia (CML); however, they may cause cardiovascular (CV) toxicities. In this cross-sectional study, we explored whether high-sensitivity C-reactive protein (hsCRP) and novel markers of vascular dysfunction were associated with exposure to specific TKIs, in 262 CML patients. Hs-CRP level was not associated with CML disease activity or treatment with a specific TKI. Body mass index (OR: 1.15, 95% CI: 1.108-1.246; p < 0.001) and CML duration (OR: 1.004, 95% CI: 1.001-1.008; p = 0.024) were independently associated with higher hs-CRP. In exploratory analyses, novel endothelial-centric markers (e.g. ET-1 and VCAM-1) were differential across the various TKIs, particularly amongst nilotinib- and ponatinib-treated patients. While Levels of hs-CRP do not appear to be correlated with specific TKIs, circulating markers of vascular dysfunction were altered in patients treated with specific TKIs and should be explored as potential markers of TKI-associated CV risk.

Patients with chronic myeloid leukemia and coronavirus disease 2019 in the Omicron era.

To explore the prevalence and severity of COVID-19 and the mental health during the Omicron pandemic in patients with chronic myeloid leukemia (CML), a cross-sectional survey from 2609 respondents with CML was performed. A total of 1725 (66%) reported that they had COVID-19 during this period. Among them, 1621 (94%) were mild; 97 (6%), moderate; 7 (0.4%), severe; and 0, critical or death. Four hundred three (15%), 199 (8%), and 532 (20%) had moderate to severe depression, anxiety, and distress, respectively. Eight hundred ninety (34%), 667 (26%), and 573 (22%), avoidance, intrusion, and hyper-arousal, respectively. In multivariate analyses, longer TKI-therapy duration was significantly associated with a lower prevalence of COVID-19 (odds ratio [OR] = 0.98; 95% confidence interval [CI], 0.95, 0.99; p = 0.043); however, living in urban areas (OR = 1.6 [1.3, 2.0]; p < 0.001) and having family members with COVID-19 (OR = 18.6 [15.1, 22.8]; p < 0.001), a higher prevalence of COVID-19. Increasing age (OR = 1.2 [1.1, 1.4]; p = 0.009), comorbidity(ies) (OR = 1.7 [1.1, 2.7]; p = 0.010), and multi-TKI-resistant patients receiving 3rd-generation TKIs or investigational agents (OR = 2.2 [1.2, 4.2]; p = 0.010) were significantly associated with moderate or severe COVID-19. Female, comorbidity(ies), unvaccinated, and moderate or severe COVID-19 were significantly associated with almost all adverse mental health consequences; increasing age or forced TKI dose reduction because of various restriction during the pandemic, moderate to severe distress, avoidance, or intrusion; however, mild COVID-19, none or mild anxiety, distress, avoidance, or intrusion. In conclusion, shorter TKI-therapy duration, increasing age, comorbidity(ies), or multi-TKI-resistant patients receiving 3rd-generation TKIs or investigational agents had a higher prevalence of COVID-19 or higher risk of moderate or severe disease in patients with CML; increasing age, female, comorbidity(ies), forced TKI dose reduction due to the pandemic, moderate or severe COVID-19, unvaccinated, a higher likelihood of worse mental health.

SARS-CoV-2 Omicron BA.5.2-infection and COVID-19 in persons with chronic myeloid leukaemia.

OBJECTIVE: A SARS-CoV-2 Omicron (BA.5.2) epidemic began in China in December, 2022 following stopping the zero COVID policy. METHODS: We studied features of the epidemic in 1,121 persons with chronic myeloid leukaemia (CML). RESULTS: 1103 (98%) were in chronic, 10 in accelerated and 8 in acute phases. 834 (74%) became infected almost all of whom met criteria for COVID-19. The most common symptoms were fever (91%), cough (90%) and fatigue (82%). 42 infected persons were asymptomatic. Most people quarantined at home and self-medicated. 22 were hospitalized for COVID-19. At admission 5 had mild, 14, moderate and 3, severe/critical disease according to World Health Organization (WHO) criteria. 5 received respiratory assistance, 3 were admitted to the intensive care unit (ICU) and 1 in accelerated phase died from COVID-19. Co-variates associated with a risk of COVID-19 in SARS-CoV-2-infected subjects include age ≥ 65 years, higher education level and imatinib therapy. CONCLUSION: In conclusion, most SARS-CoV-2 Omicron BA.5.2 infections in persons with CML resulted in COVID-19 most of which cases are mild with only 1 death.

Patient-Specific Pharmacokinetics and Dasatinib Nephrotoxicity.

BACKGROUND: Dasatinib has been associated with nephrotoxicity. We sought to examine the incidence of proteinuria on dasatinib and determine potential risk factors that may increase dasatinib-associated glomerular injury. METHODS: We examined glomerular injury through urine albumin-creatinine ratio (UACR) in 82 patients with chronic myelogenous leukemia who were on tyrosine-kinase inhibitor therapy for at least 90 days. t tests were used to compare mean differences in UACR, while regression analysis was used to assess the effects of drug parameters on proteinuria development while on dasatinib. We assayed plasma dasatinib pharmacokinetics using tandem mass spectroscopy and further described a case study of a patient who experienced nephrotic-range proteinuria while on dasatinib. RESULTS: Participants treated with dasatinib ( n =32) had significantly higher UACR levels (median 28.0 mg/g; interquartile range, 11.5-119.5) than participants treated with other tyrosine-kinase inhibitors ( n =50; median 15.0 mg/g; interquartile range, 8.0-35.0; P < 0.001). In total, 10% of dasatinib users exhibited severely increased albuminuria (UACR >300 mg/g) versus zero in other tyrosine-kinase inhibitors. Average steady-state concentrations of dasatinib were positively correlated with UACR ( ρ =0.54, P = 0.03) and duration of treatment ( P = 0.003). There were no associations with elevated BP or other confounding factors. In the case study, kidney biopsy revealed global glomerular damage with diffuse foot process effacement that recovered on termination of dasatinib treatment. CONCLUSIONS: Exposure to dasatinib was associated with a significant chance of developing proteinuria compared with other similar tyrosine-kinase inhibitors. Dasatinib plasma concentration significantly correlated with higher risk of developing proteinuria while receiving dasatinib. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_09_08_CJN0000000000000219.mp3.