Long-term health outcomes of allogeneic hematopoietic stem cell transplantation

BackgroundFifty years of hematopoietic cell transplantation (HCT) has ushered in an exciting era of cellular therapy and has led to enormous progress in improving the outcomes of patients with both malignant and non-malignant hematologic disease. As the survival of transplanted patients has increased, so has the recognition of long-term complications related to this therapy.PurposeThe goal of this review is to highlight some of the most common long-term complications of HCT.Data sourcesTo this end, we have conducted a review of the published literature on the long-term complications of HCT encompassing the past 50 years.Study selectionWe have endeavored to include long-term complications reported in research articles, case series and case reports, reviews, and abstracts. We have focused primarily on adult allogeneic HCT, but have included some data from studies of pediatric allogeneic HCT as well. We have also prioritized the literature published in the last 15 years.Data extractionKey data supporting the onset and prevalence of the most common long-term complications was extracted.LimitationsWhile the list of long-term complications extracted and reported was comprehensive, it was not exhaustive.ConclusionsWe have endeavored to highlight some of the most common long-term complications of HCT, the recognition and management of which constitutes an important part of HCT survivorship care

Characteristics of post hoc subgroup analyses of oncology clinical trials: A systematic review

BACKGROUND: Subgroup analyses in clinical trials assess intervention effects on specific patient subgroups, ensuring generalizability. However, they are usually only able to generate hypotheses rather than definitive conclusions. This study examined the prevalence and characteristics of post hoc subgroup analysis in oncology. METHODS: We systematically reviewed published subgroup analyses from 2000 to 2022. We included articles presenting secondary, post hoc, or subgroup analyses of interventional clinical trials in oncology, cancer survivorship, or cancer screening, published separately from the original clinical trial publication. We collected cancer type, year of publication, where and how subgroup analyses were reported, and funding. RESULTS: Out of 16 487 screened publications, 1612 studies were included, primarily subgroup analyses of treatment trials for solid tumors (82%). Medical writers contributed to 31% of articles, and 58% of articles reported conflicts of interest. Subgroup analyses increased significantly over time, with 695 published between 2019 and 2022, compared to 384 from 2000 to 2014. Gastrointestinal tumors (25%) and lymphoid lineage tumors (39%) were the most frequently studied solid and hematological malignancies, respectively. Industry funding and reporting of conflicts of interest increased over time. Subgroup analyses often neglected to indicate their secondary nature in the title. Most authors were from high-income countries, most commonly North America (45%). CONCLUSIONS: This study demonstrates the rapidly growing use of post hoc subgroup analysis of oncology clinical trials, revealing that the majority are supported by pharmaceutical companies, and they frequently fail to indicate their secondary nature in the title. Given the known methodological limitations of subgroup analyses, caution is recommended among authors, readers, and reviewers when conducting and interpreting these studies

Trends in volumes and survival after hematopoietic cell transplantation in racial/ethnic minorities

ABSTRACT: There has been an increase in volume as well as an improvement in overall survival (OS) after hematopoietic cell transplantation (HCT) for hematologic disorders. It is unknown if these changes have affected racial/ethnic minorities equally. In this observational study from the Center for International Blood and Marrow Transplant Research of 79 904 autologous (auto) and 65 662 allogeneic (allo) HCTs, we examined the volume and rates of change of autoHCT and alloHCT over time and trends in OS in 4 racial/ethnic groups: non-Hispanic Whites (NHWs), non-Hispanic African Americans (NHAAs), and Hispanics across 5 2-year cohorts from 2009 to 2018. Rates of change were compared using Poisson model. Adjusted and unadjusted Cox proportional hazards models examined trends in mortality in the 4 racial/ethnic groups over 5 study time periods. The rates of increase in volume were significantly higher for Hispanics and NHAAs vs NHW for both autoHCT and alloHCT. Adjusted overall mortality after autoHCT was comparable across all racial/ethnic groups. NHAA adults (hazard ratio [HR] 1.13; 95% confidence interval [CI] 1.04-1.22; P = .004) and pediatric patients (HR 1.62; 95% CI 1.3-2.03; P < .001) had a higher risk of mortality after alloHCT than NHWs. Improvement in OS over time was seen in all 4 groups after both autoHCT and alloHCT. Our study shows the rate of change for the use of autoHCT and alloHCT is higher in NHAAs and Hispanics than in NHWs. Survival after autoHCT and alloHCT improved over time; however, NHAAs have worse OS after alloHCT, which has persisted. Continued efforts are needed to mitigate disparities for patients requiring alloHCT

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Cancer in the Time of Coronavirus: A Call for Crisis Oncology Standards of Care

Since the Coronavirus Disease 2019 (COVID-19) was identified as a global pandemic, health systems have been severely strained, particularly affecting vulnerable populations such as patients with cancer. In response to the COVID-19 pandemic, a variety of oncology specialty societies are making recommendations for standards of care. These diverse standards and gaps in standards can lead to inconsistent and heterogeneous care among governments, cancer centers, and even among oncologists within the same practice. These challenges highlight the need for a common nomenclature and crisis guidelines. For times of increased scarcity of resources, the National Academy of Medicine developed Crisis Standards of Care, defined as fairness, duty to care, duty to steward resources, transparency, consistency, proportionality, and accountability. However, we believe there is an urgent need to develop cancer-specific guidelines by convening a panel of experts from multiple specialties. These would be Crisis Oncology Standards of Care (COSCs) that are sensitive to both the individual cancer patient and to the broader health system in times of scarce resources, such as pandemic, natural disaster, or supply chain disruptions

Impact of the COVID-19 Pandemic on Colorectal and Prostate Cancer Screening in a Large U.S. Health System

During the first year of the coronavirus disease 2019 (COVID-19) pandemic, prevention measures included quarantining and facility closures. Because cancer screening is dependent on interventions in facilities, the extent of the COVID-19 impact on screening was questioned. A claims registry from a large health system was queried for colorectal and prostate cancer screening. A screening gap and screening loss ratio were calculated by comparing 2020 screening to historical reference years. All cancer screenings decreased in the first four months of the pandemic. Colorectal cancer screening returned to baseline in the latter six months of 2020. Prostate cancer screening exceeded baseline in the latter six months, but with a lesser gain than previous years. Populations disproportionately affected by decreased cancer screening included men and black people. To catch-up after the initial deficit in screening, it is estimated that the rate of colorectal cancer screening needs to increase by 50%

Impact of the COVID-19 Pandemic on Colorectal and Prostate Cancer Screening in a Large U.S. Health System

During the first year of the coronavirus disease 2019 (COVID-19) pandemic, prevention measures included quarantining and facility closures. Because cancer screening is dependent on interventions in facilities, the extent of the COVID-19 impact on screening was questioned. A claims registry from a large health system was queried for colorectal and prostate cancer screening. A screening gap and screening loss ratio were calculated by comparing 2020 screening to historical reference years. All cancer screenings decreased in the first four months of the pandemic. Colorectal cancer screening returned to baseline in the latter six months of 2020. Prostate cancer screening exceeded baseline in the latter six months, but with a lesser gain than previous years. Populations disproportionately affected by decreased cancer screening included men and black people. To catch-up after the initial deficit in screening, it is estimated that the rate of colorectal cancer screening needs to increase by 50%

Cryptococcemia in an HIV-negative patient with decompensated liver cirrhosis

Background: Cryptococcal infections have been mostly associated with immunocompromised individuals, 80–90% of whom have been HIV-positive patients. Increasingly, cryptococcal infections are being reported in cirrhotic patients who are HIV-negative. The underlying immunologic defects in cirrhotic patients seem to play an important role in predisposing them to cryptococcosis and affecting their morbidity and mortality. Case presentation: We present a case of disseminated cryptococcosis in an HIV-negative patient with underlying cirrhosis, who had rapid worsening of his hyponatremia with renal failure and was unable to recover, despite aggressive measures. Conclusion: Cryptococcus is a more common culprit of infections seen in cirrhotic patients than what it was previously known, and a high index of suspicion is required to diagnose these patients. Identification of poor prognostic factors, early diagnosis and intervention is crucial in the management of these patients