In recent years, the introduction of chimeric antigen receptor (CAR) T-cell therapies into clinics has been a breakthrough in treating relapsed or refractory malignancies in hematology and oncology. To date, Food and Drug Administration (FDA) has approved six CAR-T therapies for specific non-Hodgkin lymphomas, B-cell acute lymphoblastic leukemia, and multiple myeloma. All registered treatments and most clinical trials are based on so-called 2nd generation CARs, which consist of an extracellular antigen-binding region, one costimulatory domain, and a CD3z signaling domain. Unfortunately, despite remarkable overall treatment outcomes, a relatively high percentage of patients do not benefit from CAR-T therapy (overall response rate varies between 50 and 100%, with following relapse rates as high as 66% due to limited durability of the response). Moreover, it is associated with adverse effects such as cytokine release syndrome and neurotoxicity. Advances in immunology and molecular engineering have facilitated the construction of the next generation of CAR-T cells equipped with various molecular mechanisms. These include additional costimulatory domains (3rd generation), safety switches, immune-checkpoint modulation, cytokine expression, or knockout of therapy-interfering molecules, to name just a few. Implementation of next-generation CAR T-cells may allow overcoming current limitations of CAR-T therapies, decreasing unwanted side effects, and targeting other hematological malignancies. Accordingly, some clinical trials are currently evaluating the safety and efficacy of novel CAR-T therapies. This review describes the CAR-T cell constructs concerning the clinical application, summarizes completed and ongoing clinical trials of next-generation CAR-T therapies, and presents future perspectives.

The number of allogeneic hematopoietic stem cell transplantations conducted worldwide is constantly rising. Together with that, the absolute number of complications after the procedure is increasing, with graft-versus-host disease (GvHD) being one of the most common. The standard treatment is steroid administration, but only 40–60% of patients will respond to the therapy and some others will be steroid-dependent. There is still no consensus regarding the best second-line option, but fecal microbiota transplantation (FMT) has shown encouraging preliminary and first clinically relevant results in recent years and seems to offer great hope for patients. The reason for treatment of steroid-resistant acute GvHD using this method derives from studies showing the significant immunomodulatory role played by the intestinal microbiota in the pathogenesis of GvHD. Depletion of commensal microbes is accountable for aggravation of the disease and is associated with decreased overall survival. In this review, we present the pathogenesis of GvHD, with special focus on the special role of the gut microbiota and its crosstalk with immune cells. Moreover, we show the results of studies and case reports to date regarding the use of FMT in the treatment of steroid-resistant acute GvHD.

Oral mucositis (OM) is one of the most frequent adverse events of high-dose conditioning chemotherapy with melphalan prior to autologous hematopoietic stem cell transplantation (AHSCT). It significantly reduces the patients’ quality of life. One of the preventive strategies for OM is cryotherapy. We retrospectively analyzed whether commercially available ice-cream could prevent OM during the melphalan infusion. We retrospectively analyzed 74 patients after AHSCT to see whether there is any correlation between OM and cryotherapy (ice-cream), melphalan dose (140 mg/m² or 200 mg/m²). The incidence of OM in our study inversely correlated with cryotherapy in the form of ice-cream. Out of 74 patients receiving conditioning chemotherapy with high-dose melphalan, 52 received cryotherapy. Fifteen patients in the cryotherapy group (28.84%) developed OM, whereas 13 patients (59.09%) developed it in the group without cryotherapy. In a multiple linear regression test cryotherapy remained a significant protective factor against OM (p = 0.02) We have also seen the relationship between melphalan dose with OM (p < 0.005). Cryotherapy in the form of ice-cream is associated with a lower rate of OM and, therefore, could potentially be used as a cost-effective, less burdensome, and easy to implement method in prevention of oral mucositis.

Not available Keywords: vision loss chronic myeloid leukemia leukostasis

DOI: 10.20452/pamw.16588, Published online: October 24, 2023, Authors: Magdalena Rajner, Marcin Jasiński, Ewa Karakulska-Prystupiuk, Urszula Ambroziak, Wiesław W. Jędrzejczak, Grzegorz W. Basak

Lymphomas remain a significant cause of morbidity and mortality among patients living with HIV. Although the introduction of antiretroviral therapy has led to a reduction in the incidence of AIDS-related lymphomas (ARL) and an overall improvement in prognosis, these malignancies continue to pose a considerable clinical challenge. Beyond the inherent complexity of lymphoma treatment itself, the management of comorbidities, particularly infections, represents a therapeutic obstacle. Here, we review the published evidence on ARL complicated by COVID-19. Despite the fact that nearly 800 million confirmed cases of SARS-CoV-2 infection have been reported so far, only five cases of ARL and COVID-19 have been published, among whom most patients experienced a mild course of SARS-CoV-2 infection, with only one case progressing to severe COVID-19 that required oxygen therapy and prolonged hospitalization. Additionally, we present another case of a 49-year-old male patient with newly diagnosed ARL, Epstein–Barr virus (EBV)-positive, diffuse large B-cell lymphoma, not otherwise specified, complicated by prolonged SARS-CoV-2 infection. Although initially asymptomatic, the patient subsequently experienced transient respiratory failure. Despite administration of molnupiravir, both SARS-CoV-2 antigen and RT-qPCR tests remained positive for a minimum of 113 days. The prolonged SARS-CoV-2 infection, in conjunction with other opportunistic infections, impeded the delivery of adequate chemotherapy dose intensity and contributed to disease progression and ultimately the patient’s death. This case and review of the literature underscores the diversity of the clinical course of SARS-CoV-2 infection in patients with ARL and highlights the associated challenges in delivering optimal anti-lymphoma therapy in those patients.