The antibody response of haematological malignancies to COVID-19 infection and vaccination

SummaryCancer patients with COVID-19 have reduced survival. While most cancer patients, like the general population, have an almost 100% rate of seroconversion after COVID-19 infection or vaccination, patients with haematological malignancies have lower seroconversion rates and are far less likely to gain adequate protection. This raises the concern that patients with haematological malignancies, especially those receiving immunosuppressive therapies, may still develop the fatal disease when infected with COVID-19 after vaccination. There is an urgent need to develop Guidelines to help direct vaccination schedules and protective measures in oncology patients, differentiating those with haematological malignancies and those in an immunocompromised state.

The Role of the CREB Protein Family Members and the Related Transcription Factors in Radioresistance Mechanisms

In the framework of space flight, the risk of radiation carcinogenesis is considered a “red” risk due to the high likelihood of occurrence as well as the high potential impact on the quality of life in terms of disease-free survival after space missions. The cyclic AMP response element-binding protein (CREB) is overexpressed both in haematological malignancies and solid tumours and its expression and function are modulated following irradiation. The CREB protein is a transcription factor and member of the CREB/activating transcription factor (ATF) family. As such, it has an essential role in a wide range of cell processes, including cell survival, proliferation, and differentiation. Among the CREB-related nuclear transcription factors, NF-κB and p53 have a relevant role in cell response to ionising radiation. Their expression and function can decide the fate of the cell by choosing between death or survival. The aim of this review was to define the role of the CREB/ATF family members and the related transcription factors in the response to ionising radiation of human haematological malignancies and solid tumours.

A comprehensive systematic review and meta-analysis of the global data involving 61,532 cancer patients with SARS-CoV-2 infection.

Background SARS-CoV-2 have been shown to be associated with more severe disease and death in cancer patient. A systematic review and meta-analysis was conducted to determine the risk by age, tumour type and treatment of infection with SARS-CoV-2 in cancer patients. Methods Systematic review by searching PubMed, Web of Science, and Scopus for articles published in English up to June 14, 2021 of SARS-CoV-2 infection in >10 patients with malignant disease. Outcomes included factors in patients with malignant disease that may predict a poor outcome from COVID-19 compared to patients without malignant disease, including patient demographics, tumour subtype and cancer treatments. A meta-analysis was performed using random effects model. Results 81 studies were included, totalling 61,532 cancer patients. Haematological malignancies comprised 22.1% (9,672 of 43,676) of cases. Relative risk (RR) of mortality when age and sex matched was 1.69 (95% CI, 1.46-1.95; p<0.001; I2=51%). RR of mortality, versus non-cancer patients, was associated with decreasing age (exp(b)0.96; 95% CI, 0.922-0.994; p=0.028) but not male sex (exp(b)1.89; 95% CI, 0.222-6.366; p=0.83). RR of mortality in those with haematological malignancies versus non-cancer control was 1.81 (95% CI, 1.53-2.95; I2=0.0%). Compared to other cancers, increased risk of death was seen for lung (RR 1.68, 95% CI, 1.45-1.94; p<0.001), genitourinary (RR 1.11; 95% CI, 1.00-1.24; p=0.059) and haematological malignancies (RR 1.42; 95% CI, 1.31-1.54; p<0.001). Breast (RR 0.51; 95% CI, 0.36-0.71; p<0.001) and gynaecological cancers (RR 0.76; 95% CI, 0.62-0.93; p=0.009) had lower risk of death. Receipt of chemotherapy had greatest overall pooled mortality risk of 30% (95% CI, 25-36%; I2=86.97%) and endocrine therapy the lowest at 11% (95% CI, 6-16%; I2=70.7%). Conclusions Cancer patients, particularly younger cancer patients, appear at increased risk of mortality from COVID-19 compared to non-cancer patients. Differences in outcomes were seen based on tumour types and treatment.

Antibody response after vaccination against SARS-CoV-2 in adults with haematological malignancies: a systematic review and meta-analysis

Vaccines against SARS-CoV-2 have shown remarkable efficacy and thus constitute an important preventive option against COVID-19, especially in fragile patients. We aimed to systematically analyse the outcomes of patients with haematological malignancies who received vaccination and to identify specific groups with differences in outcomes. The primary end point was antibody response after full vaccination (two doses of mRNA or one dose of vector-based vaccines). We identified 49 studies comprising 11086 individuals. Overall risk of bias was low. The pooled response for haematological malignancies was 64% (95% confidence interval [CI], 59-69; I²=93%) vs 96% (95% CI, 92-97; I²=44%) for solid cancer and 98% (95% CI, 96-99; I²=55%) for healthy controls (P<0.001). Outcome was different across haematological malignancies (P<0.001). The pooled response was 50% (95% CI, 43-57; I²=84%) for chronic lymphocytic leukaemia, 76% (95% CI, 67-83; I²=92%) for multiple myeloma, 83% (95% CI, 69-91; I²=85%) for myeloproliferative neoplasms, 91% (95% CI, 82-96; I²=12%) for Hodgkin’s lymphoma, and 58% (95% CI, 44-70; I²=84%) for aggressive and 61% (95% CI, 48-72; I²=85%) for indolent non-Hodgkin’s lymphoma. The pooled response for allogeneic and autologous haematopoietic cell transplantation was 82% and 83%, respectively. Being in remission and prior COVID-19 showed significantly higher responses. Low pooled response was identified for active treatment (35%), anti-CD20 therapy ≤1 year (15%), Bruton kinase inhibition (23%), venetoclax (26%), ruxolitinib (42%), and chimeric antigen receptor T-cell therapy (42%). Studies on timing, value of boosters, and long-term efficacy are needed. This study is registered with PROSPERO (CRD42021279051).

Rehabilitation after Allogeneic Haematopoietic Stem Cell Transplantation: A Special Challenge

The general population is getting older and suffer more haematological malignancies despite being physically fit. These malignancies are mainly only curable via an alloHCT, and they are now carried out more frequently. Patients benefit from intensive rehabilitation earlier and may need it repeatedly in cases of severe side effects (e.g., graft-versus-host disease). They can suffer many problems that other cancer patients do not experience, such as severe infections, continued immunosuppression, nutritional restrictions, acute or chronic GvHD, or organ impairments (e.g., lung, eyes). They may also encounter various associated psychological problems, e.g., feeling like a chimera. Rehabilitation centres willing to care for patients after alloHCT should have an experienced multidisciplinary team and should work in close co-operation with the primary transplant centre.

Sudden Unexpected Death Caused by Cardiac Metastasization from Histiocytic Sarcoma

Background: Haematological malignancies, such as lymphoma and leukaemia, can have a variety of clinical manifestations. The most frequent cause of death from haematological malignancies is multiple organ failure due to neoplastic organ infiltration and/or septic shock. Histiocytic sarcoma (HS) is a rare malignant nodal or extranodal tumour with histiocytic immunophenotype that originates from a lymphohematopoietic precursor. The patients with HS usually have a poor prognosis due to its aggressive clinical behaviour. Rare cases of undiagnosed sudden HS death have been described in the literature. Methods: A forensic autopsy of a 46-year-old white male who died at home suddenly and unexpectedly without warning conditions or known diseases. Gross analysis, histology and toxicology were also performed. Results: The diagnosis of HS of the ileum with secondary nodal and cardiac metastatization was made. Conclusions: A prompt diagnosis of HS in life is paramount because it can make a difference in prognostic outcomes.

Beta-D-Glucan in Patients with Haematological Malignancies

(1-3)-beta-D-glucan (BDG) is an almost panfungal marker (absent in zygomycetes and most cryptococci), which can be successfully used in screening and diagnostic testing in patients with haematological malignancies if its advantages and limitations are known. The aim of this review is to report the data, particularly from the last 5 years, on the use of BDG in haematological population. Published data report mainly on the performance of the Fungitell™ assay, although several others are currently available, and they vary in method and cut-off of positivity. The sensitivity of BDG for invasive fungal disease (IFD) in haematology patients seems lower than in other populations, possibly because of the type of IFD (lower sensitivity was found in case of aspergillosis compared to candidiasis and pneumocystosis) or the use of prophylaxis. The specificity of the test can be improved by using two consecutive positive assays and avoiding testing in the case of the concomitant presence of factors associated with false positive results. BDG should be used in combination with clinical assessment and other diagnostic tests, both radiological and mycological, to provide maximum information. Good performance of BDG in cerebrospinal fluid (CSF) has been reported. BDG is a useful diagnostic method in haematology patients, particularly for pneumocystosis or initial diagnosis of invasive fungal infections.