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

Blood ◽  
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.

Lymphoproliferative Disease Risk in Patients with Autoimmune Disease: Clustering of Primary CNS Lymphoma with Drug Regimen and Disease Process

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1490-1490 ◽  
Author(s):  
Genevieve Marie Crane ◽  
Helen Powell ◽  
Rumen Kostadinov ◽  
Peter C. Burger ◽  
Richard F. Ambinder ◽  
...  
Keyword(s):  
T Cell ◽  
Autoimmune Disease ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Lymphoproliferative Disease ◽  
Tnf Alpha ◽  
Cell Phenotype ◽  
Solid Organ ◽  
Cns Involvement ◽  
Increased Risk

Abstract Introduction: While immunosuppression for solid organ transplant is associated with an increased risk of lymphoproliferative disease (LPD), this has been more difficult to establish in autoimmune disorders, even though patients are often treated with similar agents. One reason is that autoimmune disease may elevate baseline LPD risk. However, associations have been shown with certain rare types of LPD; most strikingly hepatosplenic lymphoma, now known to occur as a consequence of anti-TNF-alpha therapy in young men with inflammatory bowel disease (IBD) (J Ped Gast Nutr. 2007; 44:265-7). We have noticed a rise in the incidence of another rare lymphoma in autoimmune disease patients: primary central nervous system (PCNS) LPD. Six cases have been diagnosed at our institution since 2010, with none before that dating back to onset of electronic records in 1986. All of these patients were taking mycophenolate mofetil (MMF) and/or thiopurines. A similar rise in reported cases has been seen in the literature (Fig 1) with suggestion of but no direct association with drug treatment shown. We systematically investigated this trend. Methods: We searched our pathology database to identify all LPD cases diagnosed over a 28-year period in patients treated for autoimmune disease as well as all similar cases involving the CNS reported in the literature over the past 40 years. Statistical analyses were performed using the Fisher's exact test. Results: We identified 44 cases of LPD arising in patients treated for autoimmune disease, including 6 with PCNS disease (Table 1). Of LPDs in patients on anti-TNF-alpha agents, 4/5 had a T-cell phenotype, and 3 had IBD. By contrast, in patients who developed LPD while taking methotrexate, the majority for rheumatoid arthritis, only 1/18 had a T-cell phenotype. Instead they were categorized as polymorphous, Hodgkin or large B-cell morphologies, which were frequently EBV-positive (67%), but never involved the brain (0/18). The LPDs arising in patients on MMF and/or thiopurines showed a similar morphologic profile but were more likely to involve the CNS. In particular, MMF was significantly associated with PCNS compared to non-CNS disease (p<0.001), and the only patient on MMF that developed an LPD outside the CNS was taking MMF in combination with cyclosporine. The most common underlying disorders in PCNS disease were myasthenia gravis (MG) and IBD. We reviewed all cases of CNS LPD in patients treated for autoimmune disease reported in the literature (34 reports, 40 patients), including 32 with PCNS LPD and 8 with secondary CNS involvement. The vast majority of PCNS cases arose in patients taking MMF and/or thiopurines (29/32), but only MMF was significantly associated with primary compared to secondary CNS involvement (p<0.05). The most common underlying disease in PCNS patients was systemic lupus erythematosus (SLE) (10/32), followed by IBD and MG. No patients with secondary CNS involvement had SLE. Conclusions: While the overall risk of LPD in the context of autoimmune disease treatment has been controversial, the interaction between drug type and individual patient characteristics may dramatically increase risk for certain lymphomas. We now demonstrate a significant association between use of MMF and PCNS LPD, which appears to cluster in patients with a history of SLE, MG or IBD. Of interest, all 3 autoimmune patients in the JHH database who developed PCNS LPD following solid organ transplant (not shown) also had SLE. While methotrexate never produced a PCNS LPD in our series, it has been infrequently found in the literature. There is no evidence of an increased baseline risk of PCNS LPD in autoimmune patients; indeed, only one reported case in an untreated patient could be identified in the literature (J Rheum 1978; 5:75-78). In addition, EBV-associated PCNS lymphoma is virtually always seen in the context of immunosuppression. Further investigation into the increased risk of specific types of LPD with immunosuppressive treatment is warranted with significant implications for tailoring treatment options. Table 1. Demographics of JHH and Reported CNS Cases ('*' p<0.05). JHH All Reported CNS Cases (Literature) PCNS Non-CNS PCNS 2o CNS No. Cases 6 38 32 8 Age (range) 69(27-77) 61(18-77) 57(27-88) 62(15-71) % Male 50% 50% 32% 25% Deceased 17% 37% 45% 40% EBV 100% 69% 95% 100% MMF 80%* 3% 41%* 0 Thiopurines 40% 23% 72% 75% Methotrexate 0 58% 13% 38% SLE 0 9% 31%* 0 MG 33% 3% 19% 0 IBD 33% 24% 19% 38% Disclosures Borowitz: Becton Dickinson Biosciences, Medimmune: Research Funding.

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

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.

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

Blood ◽  
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.

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

BMJ Open ◽  
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.

Evaluation of Pulmonary Infections in Solid Organ Transplant Patients: 12 Years of Experience

2013 ◽  
Vol 45 (10) ◽  
pp. 3458-3461 ◽  
Author(s):  
F.Ö. Eyüboğlu ◽  
E. Küpeli ◽  
Ş.S. Bozbaş ◽  
Z.E. Özen ◽  
E.S. Akkurt ◽  
...  
Keyword(s):  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Years Of Experience ◽  
Pulmonary Infections ◽  
Transplant Patients
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