Nota: todavía estamos traduciendo partes del sitio web al español.

Here’s a list of research we’ve produced.

Scope and Consistency of Cancer Outcomes Reported in Randomized Trials in Kidney Transplant Recipients

Eric H Au…Christopher D Blosser…Jonathan C Craig
Kidney International Reports
Original Work
DOI: 10.1016/j.ekir.2022.10.032
PMID: 36815120

Cancer is an important outcome in kidney transplantation, but the scope and consistency of how cancer is defined and reported in trials involving kidney transplant recipients has not been evaluated. This study aimed to assess the range and variability of cancer outcomes in trials involving kidney transplant recipients.

The database was searched from February 2000 to July 2021 to identify all randomized controlled trials (RCTs) in adult kidney transplant recipients, and which included cancer as a specified outcome. The definition of cancer, types of cancer (if any), timepoint(s) of measurement and method of aggregation were extracted for each cancer outcome. Of the 819 trials in kidney transplantation, only 84 (10%) included 1 or more cancer outcomes. Of these, 72 of 84 (86%) trials included cancer as a secondary outcome and 12 of 84 (14%) considered cancer as a primary outcome. The most frequent description of cancer was “malignancy” (n = 44, 43%), without reference to diagnostic criteria, histology, grade, or stage. The 2 most common cancer types were posttransplant lymphoproliferative disorder (PTLD) (n = 20, 20%) and nonmelanoma skin cancer (n = 10, 10%). Several methods of aggregation were identified, including incidence or rate (n = 47, 46%), frequency or proportion (n = 30, 29%), and time to event (n = 5, 5%). Approximately half the cancer outcomes were measured at a single time point (n = 44, 52%). Cancer is an infrequently reported outcome and is inconsistently defined in trials of kidney transplant recipients. Consistent reporting of cancer outcomes using standardized definitions would provide important information on the impact of cancer in patients after kidney transplantation.

Evaluation of the Modified Oxford Score in Recurrent IgA Nephropathy in North American Kidney Transplant Recipients: The Banff Recurrent Glomerulonephritis Working Group Report

Nada Alachkar…Christopher D Blosser…Serena M Bagnasco
Original Work
DOI: 10.1097/TP.0000000000004640
PMID: 37202854

The modified Oxford classification mesangial and endocapillary hypercellularity, segmental sclerosis, interstitial fibrosis/tubular atrophy, and the presence of crescents (MEST-C) of immunoglobulin A nephropathy (IgAN) was recently shown to be a predictor of graft failure in Asians with recurrent IgAN. We aimed to validate these findings in a cohort from North American centers participating in the Banff Recurrent Glomerulopathies Working Group.

We examined 171 transplant recipients with end-stage kidney disease because of IgAN; 100 of them with biopsy-proven recurrent IgAN (57 of them had complete MEST-C scores) and 71 with no recurrence. IgAN recurrence, which was associated with younger age at transplantation ( P = 0.012), strongly increased the risk of death-censored graft failure (adjusted hazard ratio, 5.10 [95% confidence interval (CI), 2.26-11.51]; P < 0.001). Higher MEST-C score sum was associated with death-censored graft failure (adjusted hazard ratio, 8.57 [95% CI, 1.23-59.85; P = 0.03] and 61.32 [95% CI, 4.82-779.89; P = 0.002] for score sums 2-3 and 4-5 versus 0, respectively), and so were the single components endocapillary hypercellularity, interstitial fibrosis/tubular atrophy, and crescents ( P 0.05). Our findings may validate the prognostic usefulness of the Oxford classification for recurrent IgAN and support the inclusion of the MEST-C score in allograft biopsies diagnostic reports.

Transplant Onconephrology: An Update

Christopher D Blosser, Andrew J Portuguese, Cecilia Santana, Naoka Murakami
Seminars in Nephrology
DOI: 10.1016/j.semnephrol.2023.151348
PMID: 37209580

Transplant onconephrology is a growing specialty focused on the health care of kidney transplant recipients with cancer. Given the complexities associated with the care of transplant patients, along with the advent of novel cancer therapies such as immune checkpoint inhibitors and chimeric antigen-receptor T cells, there is a dire need for the subspecialty of transplant onconephrology. The management of cancer in the setting of kidney transplantation is best accomplished by a multidisciplinary team, including transplant nephrologists, oncologists, and patients. This review addresses the current state and future opportunities for transplant onconephrology, including the roles of the multidisciplinary team, and related scientific and clinical knowledge.

Anti-HLA antibodies in recipients of CD19 versus BCMA-targeted CAR T-cell therapy

Joshua A Hill…Christopher D Blosser…Shaun W Jackson
American Journal of Transplantation
Original Work
DOI: 10.1016/j.ajt.2022.11.001
PMID: 36748802

Antibodies against foreign human leukocyte antigen (HLA) molecules are barriers to successful organ transplantation. B cell-depleting treatments are used to reduce anti-HLA antibodies but have limited efficacy. We hypothesized that the primary source for anti-HLA antibodies is long-lived plasma cells, which are ineffectively targeted by B cell depletion. To study this, we screened for anti-HLA antibodies in a prospectively enrolled cohort of 49 patients who received chimeric antigen receptor T-cell therapy (CARTx), targeting naïve and memory B cells (CD19-targeted, n = 21) or plasma cells (BCMA-targeted, n = 28) for hematologic malignancies. Longitudinal samples were collected before and up to 1 year after CARTx. All individuals were in sustained remission.

We identified 4 participants with anti-HLA antibodies before CD19-CARTx. Despite B cell depletion, anti-HLA antibodies and calculated panel reactive antibody scores were stable for 1 year after CD19-CARTx. Only 1 BCMA-CARTx recipient had pre-CARTx low-level anti-HLA antibodies, with no follow-up samples available. These data implicate CD19neg long-lived plasma cells as an important source for anti-HLA antibodies, a model supported by infrequent HLA sensitization in BCMA-CARTx subjects receiving previous plasma cell-targeted therapies. Thus, plasma cell-targeted therapies may be more effective against HLA antibodies, thereby enabling improved access to organ transplantation and rejection management.

CD19 CAR-T therapy in solid organ transplant recipients: case report and systematic review

Andrew J. Portuguese, Jordan Gauthier, Scott S. Tykodi, Evan T. Hall, Alexandre V. Hirayama, Cecilia C. S. Yeung, Christopher D. Blosser
Bone Marrow Transplantation
Original Work
DOI: 10.1038/s41409-022-01907-z

Post-transplant lymphoproliferative disorder (PTLD) is a leading cause of cancer death in solid organ transplant recipients (SOTRs). Relapsed or refractory (R/R) PTLD portends a high risk of death and effective management is not well established. CD19-targeted CAR-T cell therapy has been utilized, but the risks and benefits are unknown. We report the first case of diffuse large B-cell lymphoma (DLBCL) PTLD treated with lisocabtagene maraleucel and present a systematic literature review of SOTRs with PTLD treated with CD19 CAR-T therapy.

Our patient achieved a complete response (CR) with limited toxicity but experienced a CD19+ relapse 8 months after infusion despite CAR-T persistence. Literature review revealed 14 DLBCL and 2 Burkitt lymphoma PTLD cases treated with CD19 CAR-T cells. Kidney (n = 12), liver (n = 2), heart (n = 2), and pancreas after kidney (n = 1) transplant recipients were analyzed. The objective response rate (ORR) was 82.4% (14/17), with 58.5% (10/17) CRs and a 6.5-month median duration of response. Among kidney transplant recipients, the ORR was 91.7% (11/12). Allograft rejection occurred in 23.5% (4/17). No graft failure occurred. Our analysis suggests that CD19 CAR-T therapy offers short-term effectiveness and manageable toxicity in SOTRs with R/R PTLD. Further investigation through larger datasets and prospective study is needed.

Epidemiology of Renal Cell Carcinoma: 2022 Update

Laura Bukavina…Christopher D Blosser…Sarah P Psutka
European Urology
Original Work
DOI: 10.1016/j.eururo.2022.08.019
PMID: 36100483

International variations in the rates of kidney cancer (KC) are considerable. An understanding of the risk factors for KC development is necessary to generate opportunities to reduce its incidence through prevention and surveillance.

To retrieve and summarize global incidence and mortality rates of KC and risk factors associated with its development, and to describe known familial syndromes and genetic alterations that represent biologic risk factors. A systematic review was conducted via Medline (PubMed) and Scopus to include meta-analyses, reviews, and original studies regarding renal cell carcinoma, epidemiology, and risk factors. Our narrative review provides a detailed analysis of KC incidence and mortality, with significant variations across time, geography, and sex. In particular, while KC incidence has continued to increase, mortality models have leveled off. Among the many risk factors, hypertension, obesity, and smoking are the most well established. The emergence of new genetic data coupled with observational data allows for integrated management and surveillance strategies for KC care. KC incidence and mortality rates vary significantly by geography, sex, and age. Associations of the development of KC with modifiable and fixed risk factors such as obesity, hypertension, smoking, and chronic kidney disease (CKD)/end-stage kidney disease (ESKD) are well described. Recent advances in the genetic characterization of these cancers have led to a better understanding of the germline and somatic mutations that predispose patients to KC development, with potential for identification of therapeutic targets that may improve outcomes for these at-risk patients. We reviewed evidence on the occurrence of kidney cancer (KC) around the world. Currently, the main avoidable causes are smoking, obesity, and high blood pressure. Although other risk factors also contribute, prevention and treatment of these three factors provide the best opportunities to reduce the risk of developing KC at present.

Immune checkpoint inhibitor use in solid organ transplant recipients: a systematic review

Andrew J. Portuguese, Scott S. Tykodi, Christopher D. Blosser, Ted A. Gooley, John A. Thompson, Evan T. Hall
Journal of the National Comprehensive Cancer Network
Invited Review
DOI: 10.6004/jnccn.2022.7009

Chronic immunosuppression in solid organ transplant recipients (SOTRs) leads to an increased risk of a wide variety of cancers. Immune checkpoint inhibitor (ICI) therapy is indicated for many of these; however, the risks and benefits of ICI use in the SOTR population have not been well characterized. We performed a systematic literature review identifying 119 reported cases of ICI use among SOTRs. Treatments used included PD-1 inhibition (75.6%), CTLA-4 inhibition (12.6%), PD-L1 inhibition (1.7%), and combination and/or sequential ICI therapy (10.1%). The most common cancers included cutaneous melanoma (35.3%), hepatocellular carcinoma (22.7%), and cutaneous squamous cell carcinoma (18.5%).

The overall objective response rate (ORR) was 34.5%, with a median duration of response of 8.0 months. Ongoing response was seen in 21.0%. Cutaneous squamous cell carcinoma had significantly better ORR compared with other cancer types (68.2% vs 26.8%; odds ratio [OR], 5.85; P =.0006). Factors associated with improved ORR included increasing time from transplant to ICI (OR, 1.09; P =.008) and preemptive reduction in intensity of the graft maintenance immunosuppressive regimen (50.0% vs 18.5%; OR, 4.40; P =.0088). Rejection occurred in 41.2%, graft failure in 23.5%, and immune-related adverse events in 18.5%. Factors significantly associated with allograft rejection included allograft PD-L1 positivity (100% vs 0%; P<.0001) and absence of tacrolimus in the immunosuppressive regimen (48.7% vs 25.6%; OR, 0.36; P =.019). The most common cause of death was progressive malignancy (64.0%), followed by graft failure (24.0%). Our analysis provides current benchmark data to help inform management of SOTRs with advanced cancers that are reflected by our patient cohort. Biomarker development, more robust datasets, and prospective study of concomitant immunosuppression management may help refine decision-making in this complex scenario in the future. Close coordination of care between the medical oncologist and transplant specialist is encouraged to help optimize treatment outcomes.

Kidney recipients with allograft failure, transition of kidney care (KRAFT): a survey of contemporary practices of transplant providers

Tarek Alhamad, … Christopher D. Blosser, … Darshana M. Dadhania
American Journal of Transplantation
Original Work
DOI: 10.1111/ajt.16523

Kidney allograft failure and return to dialysis carry a high risk of morbidity. A practice survey was developed by the AST Kidney Pancreas Community of Practice workgroup and distributed electronically to the AST members. There were 104 respondents who represented 92 kidney transplant centers. Most survey respondents were transplant nephrologists at academic centers. The most common approach to immunosuppression management was to withdraw the antimetabolite first (73%), while only 12% responded they would withdraw calcineurin inhibitor (CNI) first.

More than 60% reported that the availability of a living donor is the most important factor in their decision to taper immunosuppression, followed by risk of infection, risk of sensitization, frailty, and side effects of medications. More than half of respondents reported that embolization was either not available or offered to less than 10% as an option for surgical intervention. Majority reported that ≤50% of failed allograft patients were re-listed before dialysis, and less than a quarter of transplant nephrologists performed frequent visits with their patients with failed kidney allograft after they return to dialysis. This survey demonstrates heterogeneity in the care of patients with a failing allograft and the need for more evidence to guide improvements in clinical practice related to transition of care.

Immune checkpoint inhibitors in kidney transplant patients: a multi-center study

Naoka Murakami, … Christopher D. Blosser, … Kenar D. Jhaveri
Kidney International
Original Work
DOI: 10.1016/j.kint.2020.12.015

Immune checkpoint inhibitors (ICIs) are widely used for various malignancies. However, their safety and efficacy in patients with a kidney transplant have not been defined. To delineate this, we conducted a multicenter retrospective study of 69 patients with a kidney transplant receiving ICIs between January 2010 and May 2020. For safety, we assessed the incidence, timing, and risk factors of acute graft rejection. For efficacy, objective response rate and overall survival were assessed in cutaneous squamous cell carcinoma and melanoma, the most common cancers in our cohort, and compared with stage-matched 23 patients with squamous cell carcinoma and 14 with melanoma with a kidney transplant not receiving ICIs.

Following ICI treatment, 29 out of 69 (42%) patients developed acute rejection, 19 of whom lost their allograft, compared with an acute rejection rate of 5.4% in the non-ICI cohort. Median time from ICI initiation to rejection was 24 days. Factors associated with a lower risk of rejection were mTOR inhibitor use (odds ratio 0.26; 95% confidence interval, 0.09-0.72) and triple-agent immunosuppression (0.67, 0.48-0.92). The objective response ratio was 36.4% and 40% in the squamous cell carcinoma and melanoma subgroups, respectively. In the squamous cell carcinoma subgroup, overall survival was significantly longer in patients treated with ICIs (median overall survival 19.8 months vs. 10.6 months), whereas in the melanoma subgroup, overall survival did not differ between groups. Thus, ICIs were associated with a high risk of rejection in patients with kidney transplants but may lead to improved cancer outcomes. Prospective studies are needed to determine optimal immunosuppression strategies to improve patient outcomes.

Changes in cancer incidence and outcomes among kidney transplant recipients in the United States over a thirty-year period (1987-2016)

Christopher D. Blosser, Gregory Haber, Eric A. Engels
Kidney International
Original Work
DOI: 10.1016/j.kint.2020.10.018

Recipients of kidney transplants have elevated cancer risk compared with the general population. Improvements over time in transplant care and cancer treatment may have affected incidence and outcomes of cancer among recipients of kidney transplant. To evaluate this, we used linked United States transplant and cancer registry data to study 101,014 adult recipients of kidney transplants over three decades (1987-1996, 1997-2006, 2007-2016). Poisson regression was used to assess trends in incidence for cancer overall and seven common cancers. Associations of cancer with risk of death-censored graft failure (DCGF) and death with functioning graft (DWFG) were evaluated with Cox regression. We also estimated absolute risks of DCGF and graft failure following cancer for recipients transplanted in 2007-2016.

There was no significant change in the incidence of cancer overall or for six common cancers in recipients across the 1987-2016 period. Only the incidence of prostate cancer significantly decreased across this period after multivariate adjustment. Among recipients of kidney transplants with non-Hodgkin lymphoma, there were significant declines over time in elevated risks for DCGF and DWFG but no significant changes for other combined cancers. For recipients transplanted in the most recent period (2007-2016), risks following cancer diagnosis remained high, with 38% experiencing DWFG and 14% graft failure within four years of diagnosis. Absolute risk of DWFG was especially high following lung cancer (78%), non-Hodgkin lymphoma (38%), melanoma (35%), and colorectal cancer (49%). Thus, across a 30-year period in the United States, there was no overall change in cancer incidence among recipients of kidney transplants. Despite improvements for non-Hodgkin lymphoma, cancer remains a major cause of morbidity and mortality.

Cancer & Transplantation — comprehensive review series

Christopher D. Blosser
American Journal of Transplantation Supplement
Series Editorship

A curated series of invited reviews of topics related to cancer and transplantation published in the American Journal of Transplantation.

Audio interview series on cancer in transplantation

Christopher D. Blosser, Germaine Wong, Tarek Alhamed, Scott Tykodi, Kirsten Wentlandt
American Journal of Transplantation

Dr. Christopher Blosser created and hosted a four-part series on cancer and organ transplant, covering unmet needs, cancer recurrence monitoring, immunotherapy, and palliative conversations with Drs. Germaine Wong, Tarek Alhamed, Scott Tykodi, and Kirsten Wentlandt.