Gordon Cook

Outcomes for patients with hematologic malignancy infected with COVID-19 have not been aggregated. The objective of this study was to perform a systematic review and meta-analysis to estimate the risk of death and other important outcomes for these patients. We searched PubMed and EMBASE up to 20 August 2020 to identify reports of patients with hematologic malignancy and COVID-19. The primary outcome was a pooled mortality estimate, considering all patients and only hospitalized patients. Secondary outcomes included risk of intensive care unit admission and ventilation in hospitalized patients. Subgroup analyses included mortality stratified by age, treatment status, and malignancy subtype. Pooled prevalence, risk ratios (RRs), and 95% confidence intervals (CIs) were calculated using a random-effects model. Thirty-four adult and 5 pediatric studies (3377 patients) from Asia, Europe, and North America were included (14 of 34 adult studies included only hospitalized patients). Risk of death among adult patients was 34% (95% CI, 28-39; N = 3240) in this sample of predominantly hospitalized patients. Patients aged ≥60 years had a significantly higher risk of death than patients <60 years (RR, 1.82; 95% CI, 1.45-2.27; N = 1169). The risk of death in pediatric patients was 4% (95% CI, 1-9; N = 102). RR of death comparing patients with recent systemic anticancer therapy to no treatment was 1.17 (95% CI, 0.83-1.64; N = 736). Adult patients with hematologic malignancy and COVID-19, especially hospitalized patients, have a high risk of dying. Patients ≥60 years have significantly higher mortality; pediatric patients appear to be relatively spared. Recent cancer treatment does not appear to significantly increase the risk of death.

By a method using sealed envelopes a series of patients with active chronic hepatitis who had not received corticosteroids or adrenocorticotrophic hormone was divided into two groups; one was given prednisolone and the other was used as a control. Fifty-four patients were initially included in the study over a period of 48 months, but five were subsequently withdrawn when it became clear that the diagnosis was incorrect. The corticosteroid group then contained 22 and the control group 27 patients. The two groups were reasonably well matched; the corticosteroid group, however, contained rather more females of a lower age. Although the mean serum bilirubin was higher in the control group, the mean serum aspartate aminotransferase and total globulin were higher in the corticosteroid group, indicating that that group contained more patients with a high degree of ‘activity’ of the hepatic lesion. The mean erythrocyte sedimentation rate was also higher in the corticosteroid group. An initial dose of 15 mg prednisolone daily was used in the corticosteroid group, and this was reduced whenever biochemical tests of liver function became normal or when there was evidence of severe side-effects of corticosteroids. It was subsequently stopped altogether in eight patients. During the first two to three years after inclusion to the study, the mean serum bilirubin, total globulin and albumin in the corticosteroid group showed a significant trend to normal when compared with the control group. The most significant and unexpected finding was a marked rise in serum albumin. After the investigation had been in progress for 72 months, three patients in the corticosteroid group and 15 in the control group had died at a mean of 11 (4 to 17) and 23 (1 to 63) months respectively. The difference between the mortality in the two groups is significant (P<0·01). The survivors in the two groups had been in the study for 53 (25 to 72) and 52 (29 to 72) months respectively. Four patients in the corticosteroid group had illnesses which were probably severe complications of corticosteroid therapy, and several others had minor complications. It is concluded that corticosteroid therapy should he used during the early-active phase (usually two to three years) of active chronic hepatitis and is of value in increasing life expectancy in patients with the condition. The mode of action is not clear, but it is probably related both to its immuno-suppressive properties and also an ability to stimulate albumin synthesis. The dose should be kept as low as possible, based on serum globulin and albumin concentrations, and be withdrawn when all biochemical tests of liver function return to normal.

PURPOSE: At the molecular level, myeloma is characterized by copy number abnormalities and recurrent translocations into the immunoglobulin heavy chain locus. Novel methods, such as massively parallel sequencing, have begun to describe the pattern of tumor-acquired mutations, but their clinical relevance has yet to be established. METHODS: We performed whole-exome sequencing for 463 patients who presented with myeloma and were enrolled onto the National Cancer Research Institute Myeloma XI trial, for whom complete molecular cytogenetic and clinical outcome data were available. RESULTS: We identified 15 significantly mutated genes: IRF4, KRAS, NRAS, MAX, HIST1H1E, RB1, EGR1, TP53, TRAF3, FAM46C, DIS3, BRAF, LTB, CYLD, and FGFR3. The mutational spectrum is dominated by mutations in the RAS (43%) and nuclear factor-κB (17%) pathways, but although they are prognostically neutral, they could be targeted therapeutically. Mutations in CCND1 and DNA repair pathway alterations (TP53, ATM, ATR, and ZNFHX4 mutations) are associated with a negative impact on survival. In contrast, those in IRF4 and EGR1 are associated with a favorable overall survival. We combined these novel mutation risk factors with the recurrent molecular adverse features and international staging system to generate an international staging system mutation score that can identify a high-risk population of patients who experience relapse and die prematurely. CONCLUSION: We have refined our understanding of genetic events in myeloma and identified clinically relevant mutations that may be used to better stratify patients at presentation.