Clonal architecture and evolutionary history of Waldenström's macroglobulinemia at the single-cell level.

To provide insight into the subclonal architecture and co-dependency patterns of the alterations in Waldenström's macroglobulinemia (WM), we performed single-cell mutational and protein profiling of eight patients. A custom panel was designed to screen for mutations and copy number alterations at the single-cell level in samples taken from patients at diagnosis (n=5) or at disease progression (n=3). Results showed that in asymptomatic WM at diagnosis, MYD88L265P was the predominant clonal alteration; other events, if present, were secondary and subclonal to MYD88L265P. In symptomatic WM, clonal diversity was more evident, uncovering combinations of alterations that synergized to promote clonal expansion and dominance. At disease progression, a dominant clone was observed, sometimes accompanied by other less complex minor clones, which could be consistent with a clonal selection process. Clonal diversity was also reduced, probably due to the effect of treatment. Finally, we combined protein expression with mutational analysis to map somatic genotype with the immunophenotype. Our findings provide a comprehensive view of the clonality of tumor populations in WM and how clonal complexity can evolve and impact disease progression.

Impact of atrial fibrillation in onco-hematological patients in Europe: a targeted literature review.

INTRODUCTION: Atrial fibrillation (AF) is a common complication in cancer patients, and the increased risk associated with certain therapies poses a major challenge. The objective was to determine the clinical and economic burden of AF in onco-hematological patients in Europe. AREAS COVERED: A targeted literature review was completed for observational, retrospective and case studies, and reviews on AF in onco-hematology published between January 2010 and 2022 in PubMed, Science Direct, Medes and IBECS. The search was based on epidemiology, cost, health-related quality of life (HRQoL), disease burden and management, and patient journey. Thirty-one studies fulfilled eligibility criteria. Annual incidence of AF during treatment varies up to 25%, and increased with first-generation Bruton tyrosine kinase inhibitors (BTKi). Risk factors include age ≥65, prior AF or hypertension, hyperlipidemia and ibrutinib use. Complications are managed with anticoagulants and/or antiarrhythmics, and regular monitoring. When AF is no longer controllable, dose reduction or discontinuation is recommended. No data on costs, HRQoL and patient journey were identified. EXPERT OPINION: There is scarce and heterogeneous information on AF in onco-hematology in Europe. Available evidence reports a higher risk of AF associated with first-generation BTKi. Further studies are needed to understand the burden of AF in these patients.

Platelet-derived growth factors from a single donor by apheresis and one freeze-thaw cycle for treating medication-related osteonecrosis of the jaw.

Aim: To assess whether the use of allogeneic platelet-derived growth factors could serve as a feasible, effective and safe biological therapy for the treatment of medication-related osteonecrosis of the jaw (MRONJ). Materials & methods: Patients with multiple myeloma and MRONJ were included and treated with allogeneic platelet-rich plasma, continued for between 6 and 18 weeks (mean: 9). Results: We observed a treatment success rate of 87.5% (p < 0.05). Assessing the association between healing and treatment duration, we observed a statistically significant relationship (χ2 = 8.00; p = 0.018; Cramer's V = 1), confirming that healing was very closely related to the duration of the treatment. Conclusion: Allogeneic platelet-rich plasma could be a recommended treatment for MRONJ. Future research with a large sample to validate our findings is required.

Healing of Chronic Wounds with Platelet-Derived Growth Factors from Single Donor Platelet-Rich Plasma following One Freeze-Thaw Cycle. A Cross-Sectional Study.

Chronic non-healing wounds (CNHWs) may be associated with trauma or idiopathic in nature and are difficult to treat. Our objective was to assess the use of platelet-derived growth factor (PDGF) from single-donor platelets (al-PRP), using one freeze-thaw cycle, for treating CNHWs. We conducted a cross-sectional study. A total of 23 CNHWs being treated with al-PRP. The al-PRP treatment can be considered successful in well over half (n = 13, 56.5%) of the wounds. We found that all the wounds treated for up to 7 weeks showed partial or complete healing, while those treated for between 8 and 12 weeks did not show healing, healing again being successful in cases in which treatment was extended to more than 13 weeks (85.7%). Using chi-square tests, this relationship was found to be highly significant (p < 0.001, chi2 = 19.51; p value = 0.00006). Notably, Cramer's V coefficient was very high (0.921), indicating that the effect size of PRP treatment duration on healing is very large (84.8%). We could suggest that the use of al-PRP in the healing of CNHWs is a promising approach. Further studies with larger sample sizes and long follow-ups are needed to obtain multivariate models to explain which factors favour the healing of ulcers treated with PRP.

Recommendations for the treatment of invasive fungal infection caused by filamentous fungi in the hematological patient

El tratamiento antifúngico del paciente hematológico ha alcanzado una gran complejidad con la llegada de nuevos antifúngicos y pruebas diagnósticas que han dado lugar a diferentes estrategias terapéuticas. La utilización del tratamiento más adecuado en cada caso es fundamental en infecciones con tanta mortalidad. La disponibilidad de recomendaciones como éstas, realizadas con la mejor evidencia por un amplio panel de 48 expertos, en las que se intenta responder a cuándo está indicado tratar y con qué hacerlo considerando diferentes aspectos del paciente (riesgo de infección fúngica, manifestaciones clínicas, galactomanano, TC de tórax y profilaxis realizada), puede ayudar a los clínicos a mejorar los resultados(AU)

Antifungal treatment in the hematological patient has reached a high complexity with the advent of new antifungals and diagnostic tests, which have resulted in different therapeutic strategies. The use of the most appropriate treatment in each case is essential in infections with such a high mortality. The availability of recommendations as those here reported based on the best evidence and developed by a large panel of 48 specialists aimed to answer when is indicated to treat and which agents should be used, considering different aspects of the patient (risk of fungal infection, clinical manifestations, galactomanann test, chest CT scan and previous prophylaxis) may help clinicians to improve the results(AU)