Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has rapidly become an unprecedented pandemic that has impacted society, disrupted hospital functions, strained health care resources, and ...impacted the lives of transplant professionals. Despite this, organ failure and the need for transplant continues throughout the United States. Considering the perpetual scarcity of deceased donor organs, Kates et al present a viewpoint that advocates for the utilization of coronavirus disease 2019 (COVID‐19)–positive donors in selected cases. We present a review of the current literature that details the potential negative consequences of COVID‐19–positive donors. The factors we consider include (1) the risk of blood transmission of SARS‐CoV‐2, (2) involvement of donor organs, (3) lack of effective therapies, (4) exposure of health care and recovery teams, (5) disease transmission and propagation, and (6) hospital resource utilization. While we acknowledge that transplant fulfills the mission of saving lives, it is imperative to consider the consequences not only to our recipients but also to the community and to health care workers, particularly in the absence of effective preventative or curative therapies. For these reasons, we believe the evidence and risks show that COVID‐19 infection should continue to remain a contraindication for donation, as has been the initial response of donation and transplant societies.
After reviewing current literature regarding SARS‐CoV‐2 organ involvement and impact on the healthcare system, the authors detail why COVID‐19 positive individuals should not be considered for organ donation at this time. See related article by Kates et al on page 1787.
Certain population groups are known to have higher than average anal cancer risk, namely persons living with HIV (PLHIV), men who have sex with men (MSM), women diagnosed with human papillomavirus ...(HPV)‐related gynecological precancerous lesions or cancer, solid organ transplant recipients (SOTRs) and patients with autoimmune diseases. Our aim was to provide robust and comparable estimates of anal cancer burden across these groups. Summary incidence rates (IRs), as cases per 100 000 person‐years (py), were calculated by fixed‐effects meta‐analysis. IRs were 85 (95% confidence interval CI = 82‐89) for HIV‐positive MSM (n = 7 studies; 2 229 234 py), 32 (95% CI = 30‐35) for non‐MSM male PLHIV (n = 5; 1626 448 py) and 22 (95% CI = 19‐24) for female PLHIV (n = 6; 1 472 123 py), with strong variation by age (eg, from 16.8 < 30 years to 107.5 ≥ 60 years for HIV‐positive MSM). IR was 19 (95% CI = 10‐36) in HIV‐negative MSM (n = 2; 48 135 py). Anal cancer IRs were much higher after diagnosis of vulvar (IR = 48 95% CI = 38‐61; n = 4; 145 147 py) than cervical (9 95% CI = 8‐12; n = 4; 779 098 py) or vaginal (IR = 10 95% CI = 3‐30; n = 4; 32 671) cancer, with equivalent disparity after respective precancerous lesions. IR was 13 (95% CI = 12‐15) in SOTRs (n = 5; 1 946 206 py), reaching 24.5 and 49.6 for males and females >10 years after transplant. Anal cancer IRs were 10 (95% CI = 5‐19), 6 (95% CI = 3‐11) and 3 (95% CI = 2‐4) for systemic lupus erythematosus, ulcerative colitis and Crohn's disease, respectively. In conclusion, a unifying anal cancer risk scale, based upon comprehensive meta‐analysis, can improve prioritization and standardization in anal cancer prevention/research initiatives, which are in their public health infancy.
What's new?
Anal cancer (AC) is quite rare in the general population. However, some groups are known to be at higher risk. In this meta‐analysis, the authors identified these groups (e.g., HIV‐positive status, other HPV‐related cancers, etc.), and were then able to develop an AC‐risk scale based on incidence estimates. Because there is currently no consensus regarding standardized screening for AC, this risk scale can help clinicians to prioritize and compare risk profiles for AC research and prevention initiatives. These can then be guided by similar principles of management for populations with similar absolute risk.
Summary Background Post-transplantation lymphoproliferative disorder (PTLD) develops in 1–10% of transplant recipients and can be Epstein–Barr virus (EBV) associated. To improve long-term efficacy ...after rituximab monotherapy and to avoid the toxic effects of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy seen in first-line treatment, we initiated a phase 2 trial to test whether the subsequent use of rituximab and CHOP would improve the outcome of patients with PTLD. Methods In this international multicentre open-label phase 2 trial, treatment-naive adult solid-organ transplant recipients diagnosed with CD20-positive PTLD who had failed to respond to upfront immunosuppression reduction received four courses of rituximab (375 mg/m2 intravenously) once a week followed by 4 weeks without treatment and four cycles of CHOP every 3 weeks. In case of disease progression during rituximab monotherapy, CHOP was started immediately. Supportive therapy with granulocyte-colony stimulating factor after chemotherapy was mandatory and antibiotic prophylaxis was recommended. The primary endpoint was treatment efficacy measured as response rates in all patients who completed treatment with rituximab and CHOP, per protocol, and response duration, in all patients who completed all planned therapy and responded. Secondary endpoints were frequency of infections, treatment-related mortality, and overall survival. This study is registered at ClinicalTrials.gov , number NCT01458548. Findings 74 patients were enrolled between Dec 12, 2002 and May 5, 2008, of whom 70 patients were eligible to receive treatment. PTLD was of late type in 53 (76%) of 70 patients, monomorphic in 67 (96%) of 70, and histologically EBV associated in 29 (44%) of 66 cases. Four of 70 patients did not receive CHOP. 53 of 59 patients had a complete or partial response (90%, 95% CI 79–96), of which 40 (68%, 55–78) were complete responses. At data cutoff (June 1, 2011) median response duration in the 53 patients who had responded to treatment had not yet been reached (>79·1 months). The main adverse events were grade 3–4 leucopenia in 42 of 62 patients (68%, 55–78) and infections of grade 3–4 in 26 of 64 patients (41%, 29–53). Seven of 66 patients (11%, 5–21) had CHOP-associated treatment-related mortality. Median overall survival was 6·6 years (95% CI 2·8–10·4; n=70). Interpretation Our results support the use of sequential immunochemotherapy with rituximab and CHOP in PTLD. Funding F Hoffmann-La Roche, Amgen Germany, Chugaï France.
China's aims are to develop an ethical and sustainable organ transplantation system for the Chinese people and to be accepted as a responsible member of the international transplantation community. ...In 2007, China implemented the Regulation on Human Organ Transplantation, which was the first step towards the establishment of a voluntary organ donation system. Although progress has been made, several ethical and legal issues associated with transplantation in China remain, including the use of organs from executed prisoners, organ scarcity, the illegal organ trade, and transplantation tourism. In this Health Policy article we outline the standards used to define cardiac death in China and a legal and procedural framework for an organ donation system based on voluntary donation after cardiac death that adheres to both China's social and cultural principles and international transplantation standards.
Summary
Burkitt lymphoma arising in paediatric post‐solid‐organ transplantation‐Burkitt lymphoma (PSOT‐BL) is a clinically aggressive malignancy and a rare form of post‐transplant lymphoproliferative ...disorder (PTLD). We evaluated 35 patients diagnosed with PSOT‐BL at 14 paediatric medical centres in the United States. Median age at organ transplantation was 2.0 years (range: 0.1–14) and age at PSOT‐BL diagnosis was 8.0 years (range: 1–17). All but one patient had late onset of PSOT‐BL (≥2 years post‐transplant), with a median interval from transplant to PSOT‐BL diagnosis of 4.0 years (range: 0.4–12). Heart (n = 18 51.4%) and liver (n = 13 37.1%) were the most frequently transplanted organs. No patients had loss of graft or treatment‐related mortality. A variety of treatment regimens were used, led by intensive Burkitt lymphoma‐specific French–American–British/Lymphomes Malins B (FAB/LMB), n = 13 (37.1%), and a low‐intensity regimen consisting of cyclophosphamide, prednisone and rituximab (CPR) n = 12 (34.3%). Median follow‐up was 6.7 years (range: 0.5–17). Three‐year event‐free and overall survival were 66.2% and 88.0%, respectively. Outcomes of PSOT‐BL patients receiving BL‐specific intensive regimens are comparable to reported BL outcomes in immunocompetent children. Multi‐institutional collaboration is feasible and provides the basis of prospective data collection to determine the optimal treatment regimen for PSOT‐BL.
Donor origin cancer (DOC) in transplant recipients may be transmitted with the graft (donor-transmitted cancer DTC) or develop subsequently from the graft (donor-derived cancer DDC).
Recipients with ...DOC between January 1, 2001, and December 31, 2010, were identified from the United Kingdom Transplant Registry and database search at transplantation centers.
Of 30,765 transplants from 14,986 donors, 18 recipients developed DOC from 16 donors (0.06%): 3 were DDC (0.01%) and 15 were DTC (0.05%). Of the 15 DTCs, 6 were renal cell cancer; 5, lung cancer; 2, lymphoma; 1, neuroendocrine cancer; and 1, colon cancer. Recipients with DTC underwent explant/excision (11), chemotherapy (4), and radiotherapy (1). Of 15 recipients, 3 (20%) recipients with DTC died as a direct consequence of cancer. Early DTC (diagnosed ≤6 weeks of transplantation) showed a better outcome (no DTC-related deaths in 11 cases) as opposed to late DTC (DTC-related deaths in 3 of 4 cases). Five-year survival was 83% for kidney recipients with DTC compared with 93% for recipients without DTC (P=0.077). None of the donors resulting in cancer transmission was known to have cancer at donation.
DTC is rare but frequently results in graft loss and death. The risk of cancer transmission cannot be eliminated because, in every case, the presence of cancer was not known at donation. This information will allow informed consent for prospective recipients. Explantation/excision is likely to benefit recipients with localized cancer, but in transplants other than kidney/pancreas, the benefits should be balanced against the risks of retransplantation.
Vaccine‐induced SARS‐CoV‐2 antibody responses are attenuated in solid organ transplant recipients (SOTRs) and breakthrough infections are more common. Additional SARS‐CoV‐2 vaccine doses increase ...anti‐spike IgG in some SOTRs, but it is uncertain whether neutralization of variants of concern (VOCs) is enhanced. We tested 47 SOTRs for clinical and research anti‐spike IgG, pseudoneutralization (ACE2 blocking), and live‐virus neutralization (nAb) against VOCs before and after a third SARS‐CoV‐2 vaccine dose (70% mRNA, 30% Ad26.COV2.S) with comparison to 15 healthy controls after two mRNA vaccine doses. We used correlation analysis to compare anti‐spike IgG assays and focused on thresholds associated with neutralization. A third SARS‐CoV‐2 vaccine dose increased median total anti‐spike (1.6‐fold), pseudoneutralization against VOCs (2.5‐fold vs. Delta), and neutralizing antibodies (1.4‐fold against Delta). However, neutralization activity was significantly lower than healthy controls (p < .001); 32% of SOTRs had zero detectable nAb against Delta after third vaccination compared to 100% for controls. Correlation with nAb was seen at anti‐spike IgG >4 Log10(AU/ml) on the Euroimmun ELISA and >4 Log10(AU/ml) on the MSD research assay. These findings highlight benefits of a third vaccine dose for some SOTRs and the need for alternative strategies to improve protection in a significant subset of this population.
Neutralizing antibodies against SARS‐CoV‐2 variants of concern increase in solid organ transplant recipients after a third dose of SARS‐CoV2 vaccine but remain significantly lower iin comparison to healthy controls.
Psychosocial factors may significantly affect post-transplant outcomes. The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) was developed as an assessment tool to enhance the ...pre-transplant psychosocial evaluation.
We identified heart, lung, liver, or kidney transplant recipients assessed with the SIPAT pre-transplantation and transplanted between June 1, 2008, and July 31, 2011, at our institution. We analyzed prospectively accumulated psychosocial and medical outcomes at 1 year of follow-up.
217 patients were identified and included in the analysis. The primary outcomes of organ failure and mortality occurred in 12 and 21 patients, respectively, and were not significantly associated with the pre-transplant SIPAT scores. On the other hand, SIPAT scores were significantly correlated with the probability of poor medical and psychosocial outcomes (secondary outcomes). In fact, higher SIPAT scores predicted higher rates of rejection episodes (Spearman ρ = 0.15, 95% 95% confidence interval CI = 0.02-0.28, p = .023), medical hospitalizations (ρ = 0.29, 95% CI = 0.16-0.41, p < .001), infection rates (p = .020), psychiatric decompensation (p = .005), and support system failure (area under the curve = 0.70, 95% CI = 0.60-0.79, p < .001). The relationship with nonadherence suggested a trend, but no statistical significance was observed (area under the curve = 0.60, 95% CI = 0.50-0.71, p = .058).
Study outcomes suggest that SIPAT is a promising pre-transplantation assessment tool that helps identify candidate's areas of psychosocial vulnerability and whose scores are associated with both psychosocial and medical outcomes after transplantation.
Depression and anxiety are common mental health problems in transplant populations. There is mixed evidence concerning whether they increase morbidity and mortality risks after transplantation. If ...such associations exist, additional risk reduction strategies may be needed.
Four bibliographic databases were searched from 1981 through September 2014 for studies prospectively examining whether depression or anxiety (determined with diagnostic evaluations or standardized symptom scales) affected risk for posttransplant mortality, graft loss, acute graft rejection, chronic rejection, cancer, infection, and rehospitalization.
Twenty-seven studies (10 heart, total n = 1738; 6 liver, n = 1063; 5 kidney, n = 49515; 4 lung, n = 584; 1 pancreas, n = 80; 1 mixed recipient sample, n = 205) were identified. In each, depression and/or anxiety were typically measured before or early after transplantation. Follow-up for outcomes was a median of 5.8 years (range, 0.50-18.0). Depression increased the relative risk (RR) of mortality by 65% (RR, 1.65; 95% confidence interval 95% CI, 1.34-2.05; 20 studies). Meta-regression indicated that risk was stronger in studies that did (vs did not) control for potential confounders (P = .032). Risk was unaffected by type of transplant or other study characteristics. Depression increased death-censored graft loss risk (RR, 1.65; 95% CI, 1.21-2.26, 3 studies). Depression was not associated with other morbidities (each morbidity was assessed in 1-4 studies). Anxiety did not significantly increase mortality risk (RR, 1.39; 95% CI, 0.85-2.27, 6 studies) or morbidity risks (assessed in single studies).
Depression increases risk for posttransplant mortality. Few studies considered morbidities; the depression-graft loss association suggests that linkages with morbidities deserve greater attention. Depression screening and treatment may be warranted, although whether these activities would reduce posttransplant mortality requires study.
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