Management of patients with lymphoma and COVID-19: Narrative review and evidence-based practical recommendations

Patients with hematologic malignancies can be immunocompromized because of their disease, anti-cancer therapy, and concomitant immunosuppressive treatment. Furthermore, these patients are usually older than 60 years and have comorbidities. For all these reasons they are highly vulnerable to infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and have an increased risk of developing severe/critical Coronavirus disease 2019 (COVID-19) compared to the general population. Although COVID-19 vaccination has proven effective in reducing the incidence of severe/critical disease, vaccinated patients with lymphoma may not be protected as they often fail to develop a sufficient antiviral immune response. There is therefore an urgent need to address the management of patients with lymphoma and COVID-19 in the setting of the ongoing pandemic. Passive immunization with monoclonal antibodies against SARS-CoV-2 is a currently available complementary drug strategy to active vaccination for lymphoma patients, while monoclonal antibodies and antiviral drugs (remdesivir, ritonavir-boosted nirmatrelvir, and molnupiravir) have proven effective in preventing the progression to severe/critical COVID-19. In this narrative review we present the most recent data documenting the characteristics and outcomes of patients with concomitant lymphoma and COVID-19. Our ultimate goal is to provide practice-oriented guidance in the management of these vulnerable patients from diagnosis to treatment and follow-up of lymphoma. To this purpose, we will first provide an overview of the main data concerning prognostic factors and fatality rate of lymphoma patients who develop COVID-19; the outcomes of COVID-19 vaccination will also be addressed. We will then discuss current COVID-19 prophylaxis and treatment options for lymphoma patients. Finally, based on the literature and our multidisciplinary experience, we will summarize a set of indications on how to manage patients with lymphoma according to COVID-19 exposure, level of disease severity and former history of infection, as typically encountered in clinical practice

Reduced intensity conditioning allogeneic transplant for advanced chronic lymphocytic leukemia

We report the preliminary results of 12 patients with advanced stage chronic lymphocytic leukemia (CLL) transplanted following reduced intensity conditioning (RIC. With a median of 22 months of follow-up, 9 patients are alive and 3 have died of progressive disease, graft-versus-host disease (GVHD) or toxic hepatitis. Acute grade I-III GVHD occurred in 33% of patients and chronic GVHD in 50%. Eight of the 12 patients achieved a complete remission (CR) and 2 patients a partial remission (PR). Donor lymphocyte infusion was effective in 6 patients. Event-free survival, progression-free survival and non-relapse mortality at 3 years were 68%, 42% and 16%, respectively. Our results show successful immunomodulation and reduction in tumor burden in high risk CL

Efficacy of N-acetylcysteine and all-trans retinoic acid in restoring in vitro effective hemopoiesis in myelodysplastic syndromes

We evaluated the in vitro effect on clonogenic potential (CFU-GM) and apoptosis in myelodysplastic syndromes (MDS) progenitors of an anti-oxidant (N-acetylcysteine, NAC) and/or a differentiating (all-trans retinoic acid, ATRA) agent. NAC significantly reduced apoptosis, both NAC and ATRA induced an increase in CFU-GM, but NAC seemed to be particularly effective in the high risk (HR) MDS. NAC + ATRA conferred a significant advantage in terms of CFU-GM with respect to NAC and ATRA alone. Tumor Necrosis Factor-alpha (TNF-alpha) levels decreased after incubation with NAC in the MDS samples. This study shows that ineffective hemopoiesis in MDS could benefit from both NAC and ATRA, suggesting that anti-oxidant treatment may play a role in guaranteeing MDS cell survival, predisposing them towards differentiatio

Microenvironmental regulation of the IL-23R/IL-23 axis overrides chronic lymphocytic leukemia indolence

Although the progression of chronic lymphocytic leukemia (CLL) requires the cooperation of the microenvironment, the exact cellular and molecular mechanisms involved are still unclear. We investigated the interleukin (IL)-23 receptor (IL-23R)/IL-23 axis and found that circulating cells from early-stage CLL patients with shorter time-to-treatment, but not of those with a more benign course, expressed a defective form of the IL-23R complex lacking the IL-12R beta 1 chain. However, cells from both patient groups expressed the complete IL-23R complex in tissue infiltrates and could be induced to express the IL-12R. 1 chain when cocultured with activated T cells or CD40L(+) cells. CLL cells activated in vitro in this context produced IL-23, a finding that, together with the presence of IL-23 in CLL lymphoid tissues, suggests the existence of an autocrine/paracrine loop inducing CLL cell proliferation. Interference with the IL-23R/IL-23 axis using an anti-IL-23p19 antibody proved effective in controlling disease onset and expansion in xenografted mice, suggesting potential therapeutic strategies

Current concepts of laparoscopic splenectomy in elective patients

Formerly, open splenectomy represented the conventional surgical treatment for many hematologic diseases. Currently, thanks to permanent technical development and improved skills, also laparoscopic splenectomy (LS) has become a recognized procedure in the treatment of spleen diseases, even in case of splenomegaly. A systematic review was performed with the aim of recalling the proved concepts of this surgical treatment and to browse new devices and techniques and their impact on the surgical outcome. The literature search was initially conducted in PubMed by entering general queries related to LS. The record identified through PubMed searching (n = 1599) was then screened by applying several criteria (study published in English from 1991 to 2013 with abstract available, by excluding systematic/non-systematic reviews, meta-analysis, practice guidelines, case reports, and study involving animals). The articles assessed for eligibility (n = 160) were primarily evaluated by excluding studies that did not report operative time and conversion to open surgery. For articles that treated multiport LS we included only clinical trials with patients > 20. The studies included in qualitative synthesis were 23. The search strategy carried out in PubMed does not allow to obtain an overview of the items returned by the main queries. With this aim we replicated the search in the Web of ScienceTM database, only including the studies published in English in the period 1991-2013 with no other filter/selection criteria. The full records (n = 1141) and cited references returned by Web of ScienceTM were analyzed with the visualization of similarities (VOS) mapping technique. Maps of title/abstract text corpus and bibliographic coupling of authors obtained by applying the VOS approach were presented. If in normal-size or moderately enlarged spleens the laparoscopic approach is unquestionable, in massive splenomegaly the optimal technique remain to be determined. In this setting, prospective randomized trials to compare open vs LS are needed. Between the new techniques of LS the robotic single port splenectomy has the ability to join all the positive aspects of both techniques. Data about this topic are too initial and need to be confirmed with further studies

Laparoscopic Splenectomy Versus Open Splenectomy in Massive and Giant Spleens: Should we Update the 2008 EAES Guidelines?

The objective of this study was to derive some useful parameters to define the feasibility of laparoscopic splenectomy (LS) in massive [spleen longitudinal diameter (SLD)>20 cm] and giant spleens (SLD>25 cm). Between December 1996 and May 2017, 175 patients underwent an elective splenectomy. A laparoscopic approach was used in 133 (76%) patients. Massive spleens were treated in 65 (37.1%) patients, of which 24 were treated laparoscopically. In this subset of massive spleens, the results of laparoscopic splenectomy in massive spleens (LSM) and open splenectomy in massive spleens (OSM) were compared. The clinical outcome of a subgroup of patients with giant spleens was also analyzed. The LSM group resulted in significant longer operative times (143\ub131 vs. 112\ub140 min; P=0.001), less blood loss (278\ub1302 vs. 575\ub1583 mL; P=0.007), and shorter hospital stay (6\ub13 vs. 9\ub14 d; P=0.004). No conversions were experienced in the LSM group, and the morbidity rate was similar in both the LSM and OSM groups (16.6% vs. 20%; P=0.75). When considering the subset of 9 LSM patients and 26 OSM patients with giant spleens, the same favorable tendency of the laparoscopic group as regards surgical conversion, blood loss, and hospital stay was maintained. The laparoscopic approach can be successfully proposed in the presence of massive splenomegaly also after a careful preoperative evaluation of the expected abdominal "working space." In experienced hands, LS is safe, feasible, and associated with better outcomes than open splenectomy for the treatment of massive and giant spleen, with a maximum SLD limit of 31 cm