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Regarding management, it is important to focus on prevention, diagnosis, and treatment. [...]vaccines and anti-infective prophylaxis have improved survival rates for these patients. Having the best possible strategies for managing infections is fundamental for lowering the chances of illness and death for those who do get sick (2). [...]diverse novel aspects of the management and/or treatment of various infections, the validation of predictive risk models for infections in hematology, the COVID-19 behavior in certain populations, the optimal assessment of the response to some COVID-19 vaccinations, and atypical responses to treatments, e.g. antifungals such as voriconazole, are included here. Xie et al.present a rare case of a patient with systemic lupus erythematosus with a fungal infection who developed MDS-like adverse reactions after treatment with voriconazole. Because the patient's sputum culture showed Candida albicans infection, oral voriconazole was prescribed.

Recent advances in the treatment of hematologic malignancies have improved the overall survival rate, but the number of patients at risk of developing an invasive fungal infection (IFI) has increased. Invasive infections caused by non-Candida albicans species, non-Aspergillus molds, and azole-resistant Aspergillus fumigatus have been increasingly reported in recent years. We developed a cross-sectional multicenter survey which involved a total of 55 hematologists and infectious disease specialists from a total of 31 Spanish hospitals, to determine the most frequent strategies used for the management of IFIs. Data collection was undertaken through an online survey which took place in 2022. Regarding key strategies, experts usually prefer early treatment for persistent febrile neutropenia, switching to another broad-spectrum antifungal family if azole-resistant Aspergillus is suspected, broad-spectrum azoles and echinocandins as prophylactic treatment in patients receiving midostaurin or venetoclax, and liposomal amphotericin B for breakthrough IFIs after prophylaxis with echinocandins in patients receiving new targeted therapies. For antifungals failing to reach adequate levels during the first days and suspected invasive aspergillosis, the most appropriate strategy would be to associate an antifungal from another family.

Very few data exist on when a particular thrombopoietin-receptor agonist (TPO-RA) is favored in clinical practice for the treatment of patients with immune thrombocytopenia (ITP), about novel risk factors for vascular events (VE) with these drugs, nor about predictive factors for therapy free responses (TFR). We conducted an observational, retrospective, long-term follow-up multicenter study from November 2016 to January 2018 of 121 adult ITP patients initiating TPO-RA between January 2012 to December 2014. Data reflected that a platelet count ≤25 × 10 9 /l at the time when the TPO-RA was initiated was associated with a 2.8 higher probability of receiving romiplostim vs . eltrombopag ( P  = 0.010). VE on TPO-RA was related to previous neoplasia in patients over 65 years (50% vs . 2.2%, P  < 0.001), and to previous splenectomy in younger patients (100% vs . 33%, P  = 0.001). Receiving romiplostim as first TPO-RA with no subsequent TPO-RA switching was associated with a 50% likelihood of TFR after 2.9 years of therapy (3.3 years in chronic ITP patients). These real-world data help deciphering some areas of uncertainty, and offer insight into some of the most relevant challenges of ITP which may help clinicians make appropriate treatment decisions in the management of adult ITP patients with TPO-RA.

Despite the significant proportion of older patients with newly diagnosed multiple myeloma (MM), most clinical trials driving therapeutic decisions in routine practice include younger and presumably healthier patients than those in the real world. Furthermore, longitudinal studies suggest that elderly, transplant-ineligible patients with MM are not benefitting enough from new anti-MM agents. We retrospectively analyzed the profile of and treatment patterns and outcomes in 675 transplant-ineligible patients with MM who started frontline therapy in routine practice. The mean (SD) age was 75.6 (6.7) years; 152 (47.4%) had Eastern Cooperative Oncology Group performance status (ECOG PS) 2–4, and 73 (25.1%) had high cytogenetic risk. The most frequent frontline therapy was non-VMP bortezomib-based regimens (n=207; 30.7%), which were more frequent among patients with ECOG PS 0/1 and higher risk (e.g., international staging system (ISS) stage III, severely impaired glomerular filtrate rate (GFR), high lactate dehydrogenase (LDH), and high-risk cytogenetics); 185 patients (27.4%) started an attenuated (lite) VMP regimen, and 159 (23.6%) a VMP (VISTA) regimen. Median progression-free survival and overall survival (OS) were 15.3 months (95%CI 14.0–16.9) and 33.5 months (95%CI 29.1–37.2), respectively; 405 patients (78.2%) achieved partial response or better. Age, ECOG PS, ISS stage, serum LDH, GFR, cytogenetic risk, and treatment regimen significantly influenced OS. In this study, a remarkable proportion of transplant-ineligible patients with MM were older, frontline regimens were highly heterogeneous, and patients at higher risk often received less efficacious combinations. These findings suggest that clinicians have limited objective criteria for therapeutic decisions for this patient group.

Previous studies showed antitumor activity for plitidepsin plus dexamethasone (DXM) in relapsed/refractory multiple myeloma (r/r MM), and in vitro synergism with bortezomib (BTZ) or DXM against MM cells. This phase I trial evaluated plitidepsin (3‐h intravenous infusion Day 1 and 15), BTZ (subcutaneous bolus Day 1, 4, 8, and 11), and DXM (orally Day 1, 8, 15, and 22), every 4 weeks in 36 r/r MM patients. Twenty‐two patients were treated using a standard dose escalation design (10 at the recommended dose [RD] cohort), and 14 additional patients were treated to expand the RD cohort. No dose‐limiting toxicities (DLTs) occurred during dose escalation. The highest dose level evaluated (plitidepsin 5.0 mg/m2, BTZ 1.3 mg/m2, DXM 40.0 mg) was the RD for phase II studies. Results shown herein are focused on this RD. Two patients had DLTs (grade 3 diarrhea, and grade 3 nausea/vomiting refractory to antiemetic therapy). Grade ≥ 3 hematological toxicity (thrombocytopenia 46%, anemia 33%, and neutropenia 17%) was manageable and did not result in treatment discontinuation. Transient and manageable grade 3 ALT increase (26%) was the most common biochemical abnormality. At the RD cohort, overall response rate was 22.2% (95%CI, 6.4%–47.6%), including one stringent complete response, one very good partial response, and two partial responses in r/r patients to BTZ and/or lenalidomide. The clinical benefit rate was 77.8% (95%CI, 52.4–93.6%). No major pharmacokinetic drug–drug interaction was found. In conclusion, the triple combination of plitidepsin, BTZ, and DXM showed an acceptable safety profile and had moderate activity in adult patients with r/r MM. This phase I trial evaluated antitumor activity for plitidepsin plus bortezomib (BTZ) and dexamethasone (DXM) in relapsed/refractory multiple mieloma patients (r/r MM). This triple combination of plitidepsin, BTZ, and DXM showed an acceptable safety profile and had moderate activity in adult patients with r/r MM that have failed to standard common therapeutic options, including BTZ and lenalidomide.

The poor prognosis of refractory or relapsed (R/R) classical Hodgkin’s lymphoma (cHL) after autologous stem cell transplantation has improved greatly due to the introduction of brentuximab vedotin and PD-1 inhibitors. However, the duration of response achieved with these novel agents is too short. The information about the management of patients after anti-PD-1 therapy failure is very limited in cHL, although chemotherapy alone or combined with PD-1 inhibitors has shown encouraging results. We report three cases of heavily pretreated cHL, refractory to nivolumab monotherapy, successfully rescued with the addition of chemotherapy to nivolumab, as a bridge to allogeneic stem cell transplantation (allo-SCT). All three patients presented poor clinical features such as three to four previous lines including brentuximab vedotin and autologous stem cell transplantation, refractoriness to the last line of therapy previous to nivolumab, and rapid disease progression. Notwithstanding these characteristics and nivolumab failure, they achieved a complete response after the addition of chemotherapy, were consolidated with allo-SCT, and still remain in complete response. There are few studies concerning the combination of PD-1 inhibitors and chemotherapy after nivolumab failure, including one retrospective study and one phase II trial with nivolumab plus bendamustine. Therefore, only few patients are consolidated with allo-SCT. However, there are several ongoing trials investigating new combinations of chemotherapy and PD-1 inhibitors in R/R cHL, as well as in first line. All these data suggest that anti-PD-1 therapy may reprogram the immune system, activating and inhibiting effector and immunosuppressive cells, respectively, leading to overtake of chemorefractoriness. Allo-SCT can increase the immune-related events of patients treated with anti-PD-1 previously, consistent on acute graft-versus-host disease, sinusoidal obstruction syndrome, and noninfectious febrile syndrome. In conclusion, the combination of PD-1 inhibitor and chemotherapy may be a feasible therapy after anti-PD-1 treatment failure as a bridge to allo-SCT.

Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease with highly variable presentation, characteristics, and clinical course. Thrombocytopenia is a common complication of many viral infections, including SARS-CoV-2. In addition, both de novo ITP and exacerbation of ITP after vaccination against SARS-CoV-2 have been reported. Patients infected with SARS-CoV-2 develop a prothrombotic coagulopathy called COVID-19-associated coagulopathy (CAC). In addition, autoimmune hematological disorders secondary to SARS-CoV-2 infection, mainly ITP and autoimmune hemolytic anemia (AIHA), have been described. Furthermore, SARS-CoV-2 infection has been associated with exacerbation of autoimmune processes, including ITP. In fact, there is evidence of a high relapse rate in patients with preexisting ITP and COVID-19. As for vaccination against SARS-CoV-2, hematological adverse events (HAE) are practically anecdotal. The most common HAE is thrombocytopenia-associated thrombosis syndrome (TTS) linked to vectored virus vaccines. Other HAEs are very rare, but should be considered in patients with previous complement activation disease or autoimmunity. In patients with ITP who are vaccinated against SARS-CoV-2, the main complication is exacerbation of ITP and the bleeding that may result. In fact, this complication occurs in 12% of patients, with splenectomized and refractory patients with more than five lines of previous treatment and platelet counts below 50 × 10 9 /L being the most vulnerable. We conclude that, in general, there is no greater risk of severe SARS-CoV-2 infection in ITP patients than in the general population. Furthermore, no changes are advised in patients with stable ITP, the use of immunosuppressants is discouraged unless there is no other therapeutic option, and patients with ITP are not contraindicated for vaccination against COVID-19.

Twenty-six cases of Blastoschizomyces capitatus infection were diagnosed in 25 patients at 7 tertiary care hematology units in Spain over a 10-year period. Most patients (92%) had acute leukemia and developed infection during a period of severe and prolonged neutropenia. Two patients had esophagitis, and the rest had invasive infection. Fungemia (20 cases) was a common finding, with frequent visceral dissemination. The 30-day mortality associated with this infection was 52%, compared with 57% among patients with systemic infection. In a univariate analysis, the following 3 variables had a positive impact on 30-day survival: removal of the central venous catheter within 5 days after the onset of infection (P = .02), a good performance status (P = .003), and receipt of systemic prophylactic or empirical antifungal therapy before infection onset (P = .006). Outcome for neutropenic patients with B. capitatus infection is still poor. Rapid removal of the central venous catheter and novel antifungal therapies are recommended for treatment of this rare infection.

According to current guidelines, in chronic lymphocytic leukemia (CLL), only the TP53 molecular status must be evaluated prior to every treatment’s initiation. However, additional heterogeneous genetic events are known to confer a proliferative advantage to the tumor clone and are associated with progression and treatment failure in CLL patients. Here, we describe the implementation of a comprehensive targeted sequencing solution that is suitable for routine clinical practice and allows for the detection of the most common somatic single-nucleotide and copy number variants in genes relevant to CLL. We demonstrate that this cost-effective strategy achieves variant detection with high accuracy, specificity, and sensitivity. Furthermore, we identify somatic variants and copy number variations in genes with prognostic and/or predictive value, according to the most recent literature, and the tool provides evidence about subclonal events. This next-generation sequencing (NGS) capture-based target assay is an improvement on current approaches in defining molecular prognostic and/or predictive variables in CLL patients.