Survey of Alternative Medicine Use among Organ Transplant Patients

Herbal medicine and health food supplements have become increasingly popular. However, many of these pharmacologically active compounds remain poorly understood. Patients with chronic and life-threatening conditions often use alternative therapies while receiving conventional medical care, and this population is at increased risk for complications and adverse drug interactions due to poor health and complex drug regimens. Patients awaiting or who had received solid organ transplants were surveyed about their use of herbal medicines and health food supplements. Twenty percent of respondents acknowledged experience with these products, which they used to prolong the function of a failing organ or to obtain relief from fatigue and insomnia. Transplant staff often were unaware of their patients' use of these treatments, despite patients' claims to the contrary. The potential for unexpected drug interactions, toxicity, and other adverse reactions resulting from the use of herbal medicines or supplements must be recognized and identified by transplant teams.

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JC Polyomavirus and Transplantation: Implications for Virus Reactivation after Immunosuppression in Transplant Patients and the Occurrence of PML Disease

Transplantology ◽

10.3390/transplantology2010004 ◽

2021 ◽

Vol 2 (1) ◽

pp. 37-48

Author(s):

James E. K. Hildreth ◽

Donald J. Alcendor

Keyword(s):

Inflammatory Responses ◽

Rare Complication ◽

Organ Transplant ◽

Solid Organ ◽

Virus Reactivation ◽

Jc Polyomavirus ◽

Hematological Disorders ◽

Transplant Patients ◽

Immunosuppressed Patients ◽

Life Threatening

The JC polyomavirus (JCPyV/JCV) is a member of the Polyomaviridae family and is ubiquitious in the general population, infecting 50–80% of individuals globally. A primary infection with JCV usally results in an asymptomatic, persistent infection that establishes latency in the renourinary tract. Reactivation from latency via iatrogenic immununosuppression for allograft transplantation may result in organ pathology and a potential life-threatening neuropathological disease in the form of progressive multifocal leukoencephalopathy (PML). Currently, no treatment exists for PML, a rare complication that occurs after transplantation, with an incidence of 1.24 per 1000 persons a year among solid organ transplant patients. PML is also observed in HIV patients who are immununosuppressed and are not receiving antiretroviral therapy, as well as individuals treated with biologics to suppress chronic inflammatory responses due to multiple sclerosis, Crohn’s disease, non-Hodgkin’s lymphoma, rheumatoid arthritis, and other autoimmune-mediated hematological disorders. Here, we describe the proposed mechanisms of JCV reactivation as it relates to iatrogenic immunosuppression for graft survival and the treatment of proinflammatory disease, such as biologics, proposed trafficking of JCV from the renourinary tract, JCV central nervous system dissemination and the pathology of PML in immunosuppressed patients, and potential novel therapeutics for PML disease.

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Incidence and risk factors for mucormycosis in renal transplant patients

Journal of Investigative Medicine ◽

10.1136/jim-2021-001933 ◽

2021 ◽

pp. jim-2021-001933

Author(s):

Melissa Rachel Downey ◽

Varsha Taskar ◽

Daniel F Linder ◽

Stephanie L Baer ◽

Jennifer L Waller ◽

...

Keyword(s):

Risk Factors ◽

Renal Transplant ◽

Iron Overload ◽

Organ Transplant ◽

Deceased Donor ◽

Solid Organ ◽

Hispanic Ethnicity ◽

Transplant Patients ◽

Increased Risk ◽

Renal Transplant Patients

AbstractBackgroundRenal transplant patients are at increased risk for mucormycosis. Diabetes, neutropenia, deferoxamine therapy, and immunosuppressive medications have been associated with increased risk of mucormycosis in studies of solid organ transplant recipients. To focus on renal transplant patients, the US Renal Data System (USRDS) was queried to determine the incidence and risk factors for mucormycosis.MethodsAll renal transplant patients in the USRDS from 1988 to 2015 were queried for a diagnosis of mucormycosis after the first transplant date using ICD-9 and ICD-10 codes. The International Classification of Diseases (ICD) codes, which currently exist in the ninth and tenth revisions, are a global system of classification used to code diagnoses, procedures, and symptoms. We defined proven mucormycosis by a histopathologic or fungal stain procedure code within 7 days of the diagnosis code. Logistic regression controlling for person-years at risk was used to examine demographic and clinical diagnosis risk factors for mucormycosis.ResultsOf the 306,482 renal transplant patients, 222 (0.07%) had codes consistent with proven mucormycosis. The incidence of mucormycosis increased from 1990 to 2000 (peak 17.6 per 100,000 person-years) and subsequently demonstrated more variability. Hispanic ethnicity (OR=1.45), age 65 years or greater (OR=1.64), other or black race compared with white race (OR=1.96 and 1.74), cadaver or other donor type (OR=2.41), and receiving tacrolimus (OR=2.09) were associated with increased risk. Comorbidities associated with decreased risk of mucormycosis included female sex (OR=0.68), iron overload (OR=0.56), and receiving mycophenolate mofetil (OR=0.67) or azathioprine (OR=0.53).ConclusionsIn renal transplant patients, age, deceased donor graft transplant, tacrolimus administration, race other than white, and Hispanic ethnicity were associated with increased risk of mucormycosis. Unexpectedly, iron overload was protective. Mucormycosis is a rare infection in renal transplant patients which should be considered in patients with the above risk factors after more common infections have been ruled out.

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Clinical Pharmacokinetic and Pharmacodynamic Monitoring for Mycophenolate Mofetil

Journal of Pharmacy Practice ◽

10.1177/0897190005282360 ◽

2005 ◽

Vol 18 (6) ◽

pp. 422-431 ◽

Cited By ~ 1

Author(s):

Yi-Min Ku ◽

Megan McCartan ◽

Dean Collier

Keyword(s):

Mycophenolate Mofetil ◽

Drug Interactions ◽

Immunosuppressive Agents ◽

Organ Transplant ◽

Clinical Monitoring ◽

Solid Organ ◽

Inosine Monophosphate Dehydrogenase ◽

Dosing Regimen ◽

Time Curve ◽

Transplant Patients

The use of mycophenolate mofetil (MMF), in combination with cyclosporine (CsA) or tacrolimus (FK) and corticosteroids, has been shown to improve clinical outcomes through significant reduction in the incidence of acute rejection in solid organ transplant patients. A fixed oral dosing regimen of 1 or 1.5 g MMF twice daily received Food and Drug Administration approval in 1995 with no recommendations for concentration monitoring at that time. Subsequent evidence has generated substantial debate on the need of clinical monitoring for MMF. This article summarizes the rationale, evidence, and approaches of clinical monitoring for MMF. Mycophenolic acid (MPA), the active moiety of MMF, noncompetitively inhibits the enzyme inosine monophosphate dehydrogenase (IMPDH), which is the target enzyme for MPA. Pharmacokinetic monitoring, by use of MPA predose or MPA area under the concentration-time curve (AUC) values, and pharmacodynamic monitoring by analysis of inhibition of IMPDH have been evaluated in organ transplant patients. The possibility of drug interactions between other immunosuppressive agents has also received attention recently. The clinical implications of drug interactions are discussed in this article.

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Effects of Monoclonal Gammopathy of Undetermined Significance (MGUS) on Outcomes after Solid Organ Transplant

Blood ◽

10.1182/blood.v124.21.3507.3507 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3507-3507

Author(s):

Teresa E Goebel ◽

Nicholas K Schiltz ◽

Aiswarya Chandran Pillai ◽

Paolo Caimi ◽

Siran M Koroukian ◽

...

Keyword(s):

Conflicts Of Interest ◽

Hematologic Malignancy ◽

Organ Transplant ◽

Solid Organ Transplant ◽

Lymphoproliferative Disease ◽

Solid Organ ◽

Transplant Patients ◽

Diagnosis Codes ◽

Increased Risk ◽

Increase Risk

Abstract Background: MGUS is a precancerous condition which can progress to multiple myeloma (MM) or other hematologic malignancy. MGUS increases the risk of developing MM approximately 25-fold, and increases lifetime risk of infection, venous thromboembolism (VTE), and skeletal related events (SRE). Solid organ transplant requires immunosuppression, which is associated with overlapping risks, including hematologic malignancy such as post transplant lymphoproliferative disease (PTLD). Hypothesizing that MGUS would further increase risk of PTLD and other complications after transplant, we described risk of these outcomes in patients with MGUS prior to solid organ transplant (MGUS+) compared to those without MGUS (MGUS-). Methods: We used the 2005-2011 California State Inpatient, Emergency, and Ambulatory Databases. MGUS and complications were identified by ICD-9 diagnosis codes, and solid organ transplant by ICD-9 procedure codes. Patients with the ICD-9 diagnosis code 273.1 documented on or before the day of solid organ transplant surgery were defined as MGUS+. We used logistic regression to analyze complications in MGUS+ versus MGUS- transplant patients. Results: Of 24,358,669 patients, we identified 22,062 solid organ transplant patients. Transplant patients were 8.8% African American, 29.5% Hispanic, 43.4% White, 15.1% other, and 3.2% had data missing. 72 were MGUS+ prior to solid organ transplant. Median age of MGUS+ was 61.5 years versus 51 years for MGUS-. Outcomes are shown in table 1. Table 1. Transplant Patients Outcome MGUS + N=72 MGUS – N=21,990 Odds Ratio (95% CI) PTLD 0 161 n/a MM ≤10 37 34.90 (12.11, 100.61) Lymphoma 0 193 n/a VTE 20 3,202 2.26(1.35, 3.79) SRE 18 2,320 2.83(1.66, 4.83) Infection 50 11,612 2.03(1.23, 3.36) *Frequencies ≤10 are reported as such per the data use agreement. Conclusions: Compared to MGUS-, MGUS+ solid organ transplant patients had higher risk of VTE, SRE, and infection, but did not have higher risk of PTLD or other lymphomas. MGUS+ transplant patients are more likely to develop MM than MGUS-; however, this risk is similar to that historically attributed to MGUS, in patients who have not undergone transplant. These data show increased risk of certain complications in MGUS+ patients, and do not support screening for MGUS to assess risk of PTLD prior to solid organ transplant. Disclosures No relevant conflicts of interest to declare.

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2646. Incidence of Myelosuppression Related to Valganciclovir Prophylaxis in Solid-Organ Transplant Recipients at High Risk of CMV Disease

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.2324 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S925-S926

Author(s):

Sara Belga ◽

Cristina Hernandez ◽

Dima Kabbani ◽

Carlos Cervera

Keyword(s):

Complete Blood Count ◽

Organ Transplant ◽

Solid Organ Transplant ◽

First Year ◽

Solid Organ ◽

Transplant Patients ◽

Increased Risk ◽

Cmv Disease ◽

The Impact

Abstract Background Valganciclovir (VGCV) prophylaxis in solid-organ transplant patients (SOT) is limited by myelotoxicity. We aimed to analyze the impact of VGCV prophylaxis on myelotoxicity and risk factors for its occurrence. Methods Retrospective single-center cohort study of adult CMV-seronegative recipients transplanted between July 2005 and November 2017. CMV D+/R− recipients received 3 to 6 months of VGCV prophylaxis whereas CMV D-/R- received no VGCV. Definitions: leukopenia < 3.5 × 109/L, significant neutropenia < 1.0 × 109/L and significant thrombocytopenia < 50 × 109/L. Results A total of 363 SOT recipients were included, 169 (47%) CMV D+/R− and 194 (53%) CMV D−/R−, with a mean age of 49.5 years and 275 (76%) males; types of organ transplant: 133 (37%) liver, 181 (50%) kidney, 37 (10%) simultaneous kidney-pancreas and 12 (3%) other. Although there was no difference in the incidence of significant neutropenia or thrombocytopenia per transplant type, leukopenia in the first year was more common in liver transplant patients (P < 0.001). New onset leukopenia post-SOT, significant neutropenia (Figure 1) and significant thrombocytopenia in the first year were more common in patients receiving VGCV: 116 D+/R− (69%) vs. 52 D−/R− (31%), P < 0.001; 86 (91%) vs. 9 (9%), P < 0.001; 8 (80%) vs. 2 (20%), P = 0.050; respectively. G-CSF was used more frequently in patients receiving prophylaxis (60% CMV D+/R− vs. 10% CMV D−/R−, P < 0.001). Significant neutropenia had no impact on long-term mortality adjusted by age and transplant type (HR 1.1, 95% CI 0.6–2.1, P = 0.709). Significant neutropenia led to decrease immunosuppression in 90% of patients (vs. 46%, P < 0.001) and was associated with increased risk of rejection (HR 8.5, P < 0.001). In multivariate analysis for significant neutropenia in the first year, VGCV prophylaxis was the only predictor of this outcome after adjusting for confounders (HR 15.1, 95% CI 7.5–30.1, P < 0.001). Conclusion VGCV prophylaxis increased the risk of significant neutropenia by 15-fold post-SOT. No other clinical variables were useful to predict this complication. Therefore, complete blood count monitoring is still needed for all SOT recipients receiving VGCV prophylaxis. Disclosures All authors: No reported disclosures.

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The Effect of Tacrolimus on Time to Development of Post-Transplant Lymphoproliferative Disorder (PTLD).

Blood ◽

10.1182/blood.v116.21.4500.4500 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4500-4500

Author(s):

Hillary S Maitland ◽

George Stukenborg ◽

Michael E. Williams

Keyword(s):

B Cell ◽

Lymphoproliferative Disorder ◽

Organ Transplant ◽

Solid Organ Transplant ◽

Reactive Lymphoid Hyperplasia ◽

Solid Organ ◽

Post Transplant ◽

Transplant Patients ◽

Increased Risk ◽

The Relationship

Abstract Abstract 4500 Background: Post Transplant Lymphoproliferative Disorder (PTLD) is a rare but potentially fatal complication occurring after solid organ transplant. PTLD is divided pathologically into three subgroups: early lesions, polymorphic PTLD, and monomorphic PTLD. The severity of these complications ranges from reactive lymphoid hyperplasia to aggressive non-Hodgkin lymphoma and Hodgkin-like lymphoma. Most PTLD are of B cell lineage associated with infection or reactivation of Epstein Barr virus (EBV). Post-transplant patients on immunosuppressive therapy may lack sufficient cytotoxic T cells to clear EBV-infected B cells, allowing unchecked polyclonal B cell proliferation and infection of other cells with EBV. Immunosuppression with cyclosporine and tacrolimus has been associated with a higher risk for development of PTLD. This study examines the relationship between tacrolimus and PTLD among solid-organ transplant patients. Methods: Differences in time to PTLD between patients with and without exposure to tacrolimus were assessed using a retrospective, case-control design. University of Virginia Health System registry records were searched to identify all patients in the post- solid organ transplant population diagnosed with malignancy in the years 1998–2009. Bone marrow transplant patients were excluded. Following IRB approval, data was collected on the type of transplant, immunosuppressive regimen, time from transplant to development of PTLD, and lymphoma treatment; from electronic charts and pathology reports were reviewed. Results: A total of 2841 patients with solid organ transplants were identified, including1486 patients who received tacrolimus for immunosuppression. There were 26 cases of PTLD: 19 with exposure to tacrolimus (1.3%), and 8 without exposure (0.6%). The mean time to PTLD was 2.52 years (SD = 0.65) in the tacrolimus group, and was 6.75 years (SD = 1.80) among those not exposed. This difference in time to event was stat istically significant (Log-Rank = 5.347, p = .0208). Conclusion: In our population of post solid organ transplant patients with PTLD, exposure to tacrolimus was associated with significantly shorter time to development. Prospective studies are needed to better elucidate the relationship between type of immunosuppression and development of PTLD. These results suggest that immunosuppressive regimens using tacrolimus may be associated with increased risk of developing PTLD. Disclosures: No relevant conflicts of interest to declare.

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Contraception for Solid Organ Transplant Patients: Utilizing Social Media

Case Medical Research ◽

10.31525/ct1-nct03979950 ◽

2019 ◽

Author(s):

Keyword(s):

Social Media ◽

Organ Transplant ◽

Solid Organ Transplant ◽

Solid Organ ◽

Transplant Patients

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Angiogenesis Inhibitors as Anti-Cancer Therapy Following Renal Transplantation: A Case Report and Review of the Literature

Current Oncology ◽

10.3390/curroncol28010064 ◽

2021 ◽

Vol 28 (1) ◽

pp. 661-670

Author(s):

Lawrence Kasherman ◽

Jeffrey Doi ◽

Katherine Karakasis ◽

Jeffrey Schiff ◽

Abhijat Kitchlu ◽

...

Keyword(s):

Renal Transplantation ◽

Organ Transplant ◽

Angiogenesis Inhibitors ◽

Solid Organ ◽

Transplant Recipients ◽

Immunosuppressive Medication ◽

Increased Risk ◽

Anti Cancer ◽

Solid Organ Transplant Recipients

Solid organ transplant recipients on long-term immunosuppressive medication are at increased risk of developing malignancy, and treatment of advanced cancers with angiogenesis inhibitors in this context has not been widely studied. We present a case of recurrent high-grade serous ovarian carcinoma treated with paclitaxel and bevacizumab in the context of prior renal transplantation where the patient responded well to treatment with controlled toxicities, discussing the potential for increased rates of adverse events and drug interactions in this select population.

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Exploring the Epidemiology of Cancer after Solid Organ Transplantation (EpCOT): an observational cohort study

BMJ Open ◽

10.1136/bmjopen-2020-043731 ◽

2021 ◽

Vol 11 (4) ◽

pp. e043731

Author(s):

Adnan Sharif ◽

Javeria Peracha ◽

David Winter ◽

Raoul Reulen ◽

Mike Hawkins

Keyword(s):

Organ Transplantation ◽

Record Linkage ◽

Solid Organ Transplantation ◽

Organ Transplant ◽

Solid Organ Transplant ◽

Study Cohort ◽

Solid Organ ◽

Post Transplantation ◽

Increased Risk ◽

Risk Of Cancer

IntroductionSolid organ transplant patients are counselled regarding increased risk of cancer (principally due to their need for lifelong immunosuppression) and it ranks as one of their biggest self-reported worries. Post-transplantation cancer is common, associated with increased healthcare costs and emerging as a leading cause of post-transplant mortality. However, epidemiology of cancer post-transplantation remains poorly understood, with limitations including translating data from different countries and national data being siloed across different registries and/or data warehouses.Methods and analysisStudy methodology for Epidemiology of Cancer after Solid Organ Transplantation involves record linkage between the UK Transplant Registry (from NHS Blood and Transplant), Hospital Episode Statistics (for secondary care episodes from NHS Digital), National Cancer Registry (from cancer registration data hosted by Public Health England) and the National Death Registry (from NHS Digital). Deterministic record linkage will be conducted by NHS Digital, with a fully anonymised linked dataset available for analysis by the research team. The study cohort will consist of up to 85 410 solid organ transplant recipients,who underwent a solid organ transplant in England between 1 January 1985 and 31 December 2015, with up-to-date outcome data.Ethics and disseminationThis study has been approved by the Confidentiality Advisory Group (reference: 16/CAG/0121), Research Ethics Committee (reference: 15/YH/0320) and Institutional Review Board (reference: RRK5471). The results of this study will be presented at national and international conferences, and manuscripts with results will be submitted for publication in high-impact peer-reviewed journals. The information produced will also be used to develop national evidence-based clinical guidelines to inform risk stratification to enable risk-based clinical follow-up.Trial registration numberNCT02991105.

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