COVID-19 vaccination and breakthrough infections in patients with cancer.

BACKGROUND: Vaccination is an important preventive health measure to protect against symptomatic and severe COVID-19. Impaired immunity secondary to an underlying malignancy or recent receipt of antineoplastic systemic therapies can result in less robust antibody titers following vaccination and possible risk of breakthrough infection. As clinical trials evaluating COVID-19 vaccines largely excluded patients with a history of cancer and those on active immunosuppression (including chemotherapy), limited evidence is available to inform the clinical efficacy of COVID-19 vaccination across the spectrum of patients with cancer. PATIENTS AND METHODS: We describe the clinical features of patients with cancer who developed symptomatic COVID-19 following vaccination and compare weighted outcomes with those of contemporary unvaccinated patients, after adjustment for confounders, using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19). RESULTS: Patients with cancer who develop COVID-19 following vaccination have substantial comorbidities and can present with severe and even lethal infection. Patients harboring hematologic malignancies are over-represented among vaccinated patients with cancer who develop symptomatic COVID-19. CONCLUSIONS: Vaccination against COVID-19 remains an essential strategy in protecting vulnerable populations, including patients with cancer. Patients with cancer who develop breakthrough infection despite full vaccination, however, remain at risk of severe outcomes. A multilayered public health mitigation approach that includes vaccination of close contacts, boosters, social distancing, and mask-wearing should be continued for the foreseeable future.

Posttraumatic growth and well-being among adolescents and young adults (AYAs) with cancer: a longitudinal study.

PURPOSE: This study examines posttraumatic growth (PTG) among adolescents and young adults (AYAs) with cancer, as well as its correlates and trajectories over time. The study also explores the buffering role of PTG on the associations between posttraumatic stress (PTS), health-related quality of life (HRQoL), and psychological distress. METHODS: A multicenter, longitudinal, prospective study was conducted among AYA cancer patients aged 14-39 years. One hundred sixty-nine patients completed a self-report measure of PTG (PTGI) and PTS (PDS) 6, 12, and 24 months after baseline (within the first 4 months of diagnosis). At 24-month follow-up, HRQoL (SF-36) and psychological distress (BSI-18) were also assessed. RESULTS: Among participants, 14% showed increasing PTG, 45% remained at a stable high PTG level, 14% showed decreasing PTG, and 27% remained at a stable low PTG level. AYAs who remained high on PTG were more often younger, female, and received chemotherapy. PTG level at 6-month follow-up was predictive of mental HRQoL (ß = 0.19; p = 0.026) and psychological distress (ß = -0.14; p = 0.043) at 24-month follow-up when corrected for PTS and sociodemographic and clinical covariates. No relationship between PTG and physical HRQoL was found. The interactive effects of PTS and PTG on outcomes were not significant, indicating that buffering did not take place. CONCLUSION: This study indicates that PTG is dynamic and predicts mental well-being outcomes but does not buffer the effects of PTS. Psychosocial interventions should focus on promoting PTG and reducing PTS in order to promote the adjustment of AYAs diagnosed with cancer.

Chronic GvHD-associated serositis and pericarditis.

Serositis is a rare manifestation of chronic GvHD (cGvHD). No risk factors or laboratory changes associated with this syndrome have been recognized to date, and outcomes have not been described in a large series. We searched our institutional database for patients undergoing allogeneic hematopoietic cell transplant identified as having serositis or pericarditis. Laboratory studies from prior to diagnosis, at diagnosis and post diagnosis of serositis, as well as outcomes from invasive procedures were included. Twenty patients met criteria for cGvHD-associated serositis, and all but three patients had a prior diagnosis of cGvHD. Fifteen were male, and the complication occurred in the setting of immunosuppressant taper in 12 cases. Ten patients required invasive interventions, including pericardial window or stripping. A significant increase in blood monocytes and decrease in serum albumin were identified at diagnosis compared with pre-diagnosis. Out of 20 patients, 17 were treated with steroids, with 12 demonstrating a complete response. These data suggest that cGvHD-associated serositis occurs mainly in the setting of treated as opposed to de novo cGvHD and biomarkers associated with the syndrome include a decrease in albumin and an increase in absolute monocyte count. Outcome data from larger series are required to better understand the optimal management of this rare complication.

Physician perceptions and practice patterns regarding fertility preservation in hematopoietic cell transplant recipients.

Physician practice variation may be a barrier to informing hematopoietic cell transplant (HCT) recipients about fertility preservation (FP) options. We surveyed HCT physicians in the United States to evaluate FP knowledge, practices, perceptions and barriers. Of the 1035 physicians invited, 185 completed a 29-item web-survey. Most respondents demonstrated knowledge of FP issues and discussed and felt comfortable discussing FP. However, only 55% referred patients to an infertility specialist. Most did not provide educational materials to patients and only 35% felt that available materials were relevant for HCT. Notable barriers to discussing FP included perception that patients were too ill to delay transplant (63%), patients were already infertile from prior therapy (92%) and time constraints (41%). Pediatric HCT physicians and physicians with access to an infertility specialist were more likely to discuss FP and to discuss FP even when prognosis was poor. On analyses that considered physician demographics, knowledge and perceptions as predictors of referral for FP, access to an infertility specialist and belief that patients were interested in FP were observed to be significant. We highlight variation in HCT physician perceptions and practices regarding FP. Physicians are generally interested in discussing fertility issues with their patients but lack educational materials.

Evolution in management of testicular seminoma: population-based outcomes with selective utilization of active therapies.

BACKGROUND: In this article, we report the evolution of treatment with increased use of active surveillance for stage I disease as well as risk-adapted chemotherapy for disseminated disease and associated outcomes of testicular seminoma in a contemporary population-based cohort. METHODS: All patients with histologically confirmed seminoma referred from 1999 to 2008 to the British Columbia Cancer Agency or Providence Cancer Center were retrospectively reviewed. Both institutions manage 90% of testicular cancers in their respective area. RESULTS: A total of 649 patients were included. Clinical stage (CS) distribution: CSI/II/III n=545/87/17. For CSI, there was a progressive and marked decrease in the utilization of prophylactic radiation (RT), and corresponding increase in the use of active surveillance. No deaths related to seminoma were reported in CSI patients. CSII or CSIII patients received RT or International Germ Cell Cancer Collaborative Group (IGCCCG) risk-appropriate chemotherapy with 101 of 104 patients being in long-term remission and 3 patients dying from treatment complications. For the entire seminoma population, <1% of patients died of seminoma or treatment after a median follow-up of 47 months (range 2-130 months). CONCLUSIONS: Progressive application of policies of active surveillance and earlier initiation of IGCCCG risk-adapted chemotherapy result in nearly universal control for all patients presenting with seminoma while reducing the burden of treatment.

Non-risk-adapted surveillance for patients with stage I nonseminomatous testicular germ-cell tumors: diminishing treatment-related morbidity while maintaining efficacy.

BACKGROUND: With treatment leading to nearly uniform cure in clinical stage I nonseminomatous testicular cancer (CSI-NSGCT), diminishing treatment-related morbidity has become the primary concern. This study examined feasibility and outcome of active surveillance as treatment in an unselected CSI patient population. MATERIALS AND METHODS: All patients with CSI-NSGCT referred from 1998 to 2007 to the British Columbia Cancer Agency and the Oregon Testis Cancer Program were retrospectively reviewed. A total of 233 patients were identified, of which 223 chose active surveillance. RESULTS: Vascular invasion (VI) was absent, present and unknown in 66%, 27% and 7% of cases, respectively. Overall, 49% of patients had embryonal predominant disease. Fifty-nine patients (26%) relapsed, all but one with good prognosis disease. VI was present in 30 relapsed patients. Most patients relapsed within 2 years (88%). Only 7 of 223 patients (3%) relapsed beyond 2 years. All relapses were in long-term remission following chemotherapy with or without retroperitoneal lymph node dissection (RPLND). Only 17 of 223 patients (8%) required postorchiectomy surgery. Disease-specific survival is 100% after a median follow-up of 52 months (3-136). No patient has required second-line chemotherapy. CONCLUSIONS: Active surveillance for all CSI-NSGCT patients is associated with excellent outcomes comparable with the best results reported with primary RPLND or adjuvant chemotherapy. Nearly 75% of patients are spared any therapy after orchiectomy.

Rescue from failed growth factor and/or chemotherapy HSC mobilization with G-CSF and plerixafor (AMD3100): an institutional experience.

Auto-SCT has been shown to be a potentially curative treatment for a variety of hematological malignancies. Auto-SCT is dependent on the successful mobilization and collection of hematopoietic stem cells to ensure engraftment. The inability to mobilize sufficient number of hematopoietic stem cells using standard cytokine-assisted mobilization strategies excludes eligible patients from potentially curative auto-SCT. Plerixafor (AMD3100; Mozobil), a novel bicyclam antagonist of the SDF-1alpha/CXCR4 complex, has been reported previously to augment PBSC mobilization in patients undergoing their first planned stem cell mobilization and collection attempt. In our experience, 17 of 20 patients otherwise eligible for auto-SCT who failed previous mobilization attempts had successful mobilization of CD34(+) hematopoietic stem cells with one apheresis procedure, and an additional patient required two aphereses procedures, when treated with the combination of plerixafor and G-CSF on a compassionate use protocol available at our institution.

Isolation in the allogeneic transplant environment: how protective is it?

Aggressive infection control measures that include isolating patients within protective hospital environments have become a standard practice during allogeneic stem cell transplantation. A wide range of interventions includes the management of ventilation systems, BMT unit construction and cleaning, isolation and barrier precautions, interactions with health-care workers and visitors, skin and oral care, infection surveillance, and the prevention of specific nosocomial and seasonal infections. However, many of these practices have not been definitively proven to provide patients the intended benefit of decreased infection rates or improved survival. Furthermore, each intervention comes with a financial and social cost. With institutional cost containment efforts and recent trials suggesting that patients may be safely cared for in the outpatient environment after allogeneic transplantation, many widely held practices in managing the transplant environment are being reconsidered. With changing practices, transplant teams are encouraged to review local patterns of infections and associated complications and communicate regularly with infection control committees for guidance on the evolution of isolation needs for the immunosuppressed patient.

Toxic megacolon: a life-threatening complication of high-dose therapy and autologous stem cell transplantation among patients with AL amyloidosis.

AL amyloidosis is a plasma cell disorder in which tissue deposition of immunoglobulin light chains leads to organ dysfunction. Recent reports of high-dose therapy with autologous stem cell transplantation for amyloidosis suggest higher response rates and extended survival compared to those seen with conventional chemotherapy. However, substantial treatment-related toxicity has been observed. This case series describes our institutional experience with autologous transplantation in four patients with amyloidosis with an emphasis on unique gastrointestinal toxicities, including toxic megacolon.

Allogeneic stem-cell transplantation in renal-cell carcinoma.

Metastatic renal-cell carcinoma (RCC) remains resistant to nearly all standard cytotoxic therapies, but immune-based cytokine therapies benefit a small minority of patients with advanced RCC. Nonmyeloablative allogeneic stem-cell transplantation is a novel approach to harnessing the immune system to combat this cancer. The strategy relies on a T-cell graft-versus-malignancy effect mediated by donor T cells. Preliminary work in using nonmyeloablative allogeneic stem-cell transplant in RCC has identified a graft-versus-RCC effect and yielded encouraging clinical responses.

Molecular analysis and polymorphism of the DLA-DQB genes.

Partial-length cDNA clones and full-length genomic clones corresponding to a complete canine DQB class II gene were isolated. Southern analyses suggested the presence of two DQB genes--one of which appeared to be a pseudogene lacking exon 2 called DQB2. The other DQB gene, called DQB1, was isolated from a genomic phage clone and contained six exons. The DQB1 clone was restriction mapped, and exon 2 was sequenced from 70 dogs. Twenty alleles were found. Most of the amino acid substitutions occurred at putative positions in the peptide binding site. Inheritance of these sequences showed Mendelian segregation with one or two alleles per dog. Cluster analysis of the nucleotide and predicted amino acid sequences subdivided the canine DQB1 alleles into four major allelic groups. The number of nonsynonymous changes was higher than the number of synonymous changes in the putative antigen recognition sites suggestive of positive selection.