The cover image is based on the Clinical Message Chronic lymphocytic leukemia with progressive anemia secondary to development of composite lymphoma by Habib Moshref Razavi, James England, Jeffrey Craig et al., https://doi.org/10.1002/ccr3.2656.
A 78-year-old male with a history of polycythemia vera (PV) presented with bilateral foot ulcerations (a) limiting his ability to exercise or wear shoes. His PV had been managed for the previous 5 years with aspirin 81 mg per os (PO) daily, intermittent phlebotomy, and hydroxycarbamide (hydroxyurea [HU]) 1500 mg PO daily. At the time of presentation, his hemoglobin was 138 g/L, hematocrit 0.41, white blood cell count 14.5 × 109/L, and platelet count 695 × 1012/L. Cultures from the right toe ulcer grew Pseudomonas aeruginosa and Streptococcus pyogenes; scintigraphy bone scan demonstrated evidence of osteomyelitis of the right first phalanx. The HU was held and the patient was started on a 6-week course of ciprofloxacin and doxycycline. Ruxolitinib 10 mg PO BID was initiated for management of PV. Follow-up 3 months later demonstrated significant improvement of the cutaneous ulcerations (b). Cutaneous toxicity can occur in 5%–12.5% of myeloproliferative neoplasm patients treated with HU, and can lead to significant complications such as the secondary osteomyelitis seen in this case. Etiology of ulcers is multifactorial with microvascular disturbance from reduced red blood cell deformability and reduced wound healing due to cytotoxic effects on keratinocytes and basal cells of the epidermis and endothelium. European Leukemia NET (ELN) criteria for HU intolerance includes development of lower extremity ulcers and should prompt the use of alternative cytoreductive therapy. Patient counselling and clinician recognition of HU cutaneous adverse events may allow for rapid therapy change and prevention of complications. Patient provided written consent for photographs to be used for publication and education purposes. Data sharing is not applicable to this article as no new data were created or analyzed in this study.
Abstract Otitis externa and chronic otitis media often present to the otolaryngologist with a discharging ear. The conventional method of treatment is to perform regular aural toilet and insert medicated dressings into the external auditory canal. This treatment is either performed by trained nurses or medical staff, but in either case is time consuming. This study compares the efficacy of the above standard regimen with a novel treatment where a single aural toilet is carried out and medicated ointment instilled into the ear. Both regimens were evaluated at three weeks. Our results shows that there was no significant difference between the two treatment regimens with regard to the resolution of either of the conditions studied or the improvement in the symptom status of the patients. On the basis of this it would seem that a single aural toilet and instillation of medicated ointment is a valid treatment option, cuts down hospital attendance and could be performed in the community by general medical practitioners or trained practice nurses.
Ruxolitinib is the most commonly used JAK-inhibitor (JAKi) for the management of symptoms related to splenomegaly and cytokine-mediated inflammation in patients with myelofibrosis (MF), but is limited by variable durability of response with most patients experiencing failure after 2-3 years. Long-term data on other approved JAKi, fedratinib and pacritinib, are not available due to the clinical hold put on pivotal trials for toxicity concerns.Following the initial hold for concern of Wernicke's encephalopathy, fedratinib was approved by the Food and Drug Administration (FDA) in 2019 for MF. We review the data available from early, and late phase critical trials, outline a role for fedratinib in the current treatment landscape of MF, and highlight the knowledge gaps in optimizing use of fedratinib.The JAKARTA and JAKARTA2 trials established efficacy in spleen volume response (SVR) and symptom reduction in JAKi-naïve and ruxolitinib-exposed MF patients, respectively. Further trials, FREEDOM and FREEDOM2, are in progress to understand long-term effects of fedratinib; and include strategies to mitigate gastrointestinal toxicity, monitor thiamine levels and surveil for encephalopathy. We use fedratinib for symptomatic MF following ruxolitinib failure in patients without significant cytopenias; with practical strategies for monitoring and managing potential toxicity.
Lymphoproliferative disorders are prevalent in HIV-positive patients and the majority are aggressive [1]. The success of highly active antiretroviral therapy (HAART) has resulted in a substantial i...
Abstract Deterioration of hematologic parameters in lymphoma patients is often attributed to disease progression, comorbidities, or treatment effects. Second primary malignancies occur at increased frequency in CLL and must also be considered.
Myelofibrosis (MF) is an acquired clonal hematopoietic stem cell disorder associated with debilitating constitutional symptoms, extramedullary hematopoiesis resulting in splenomegaly, and a propensity to transform to a blast phase/acute myeloid leukemia (AML).The discovery of JAK inhibitors (JAKi) has been pivotal in the treatment of symptomatic MF by reducing spleen size, and alleviating cytokine-related symptom burden [1].Despite this, up to 50% of MF patients discontinue JAKi by 2-3 years and only one quarter of patients remain on treatment at 5 years [2,3].Prospective trials of JAKi therapy provide little information after patients discontinue therapy and safety specific follow up is completed.Although survival following ruxolitinib cessation is poor, in the range 13-16 months, the clinical course and reasons for JAKi failure in MF patients are not well characterized [4][5][6][7].Criteria for JAKi failure are variably defined in retrospective studies and second-line JAKi therapy trials [8][9][10].JAKi therapy may fail for a variety of reasons including sub-optimal/loss of spleen response, severe cytopenias, progression to an accelerated or blast phase (AP/BP) of disease, secondary malignancies other than AML, recurrent severe infections, or other non-hematological toxicities.Recognition of patterns of failure is important to accurately characterize, and plan treatment strategies in these patients.We conducted a retrospective study analyzing a molecularly annotated, mature dataset of MF patients treated with JAKi followed in a prospective MPN registry (NCT02760238) at Princess Margaret Cancer Centre.We evaluated the impact of baseline clinical and molecular factors on clinical outcomes and therapy failure.We characterized different patterns of JAKi failure according to consensus criteria of the Canadian MPN Group (Supp.Table S1) [11] and its impact on survival.In a sub-set of patients with paired samples we evaluated the impact of clonal evolution on outcomes following JAKi failure.Cohort selection, study definitions, molecular, and statistical analysis are summarized in Appendix.
