Is rituximab (R) the optimal therapeutic intervention (TI) for post-transplant lymphoproliferative disorder (PTLD) following solid organ transplant (SOT)?

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8074-8074
Author(s):  
R. E. Tsao ◽  
T. Jin ◽  
B. Richendollar ◽  
E. Hsi ◽  
B. Pohlman
Keyword(s):  
De Novo ◽  
Univariate Analysis ◽  
Cleveland Clinic ◽  
Organ Transplant ◽  
Clinical Information ◽  
Initial Study ◽  
Solid Organ ◽  
Younger Age ◽  
Study Results

8074 Background: PTLD is a rare, often fatal, complication of SOT. Most are derived from CD20+ B-cells. Historically, patients (pts) received a variety of TIs ranging from decreased immunosuppression to chemotherapy (CT). Based on promising initial study results, most pts now receive rituximab (R) without CT as part of 1st TI. Methods: We searched the Cleveland Clinic pathology archives for SOT pts, who were diagnosed with PTLD between 1987 and 2006; reviewed the medical records; extracted clinical information and outcomes; and analyzed the data by Cox proportional univariate and multivariate analyses. Results: We identified 55 SOT pts (heart, 18; lung, 16; kidney 14; liver, 6; pancreas, 1), who were diagnosed with PTLD at median age 47 years (range 7–66). The median time from SOT to PTLD was 1.7 years (range .2–20.9). 1st TI (usually >1) included “complete” resection (4), decreased immunosuppresion (53), acyclovir or ganciclovir (28), interferon (4), radiation therapy (6), CT (12), and/or R (17). Response to 1st TI was CR (30) or PR (10). The median follow-up among surviving pts is 5.0 years (range .1–11.4). 29 (including 5 CT and 5 R) pts have died; only 2 CT but all 5 R pts died from PTLD. On univariate analysis, younger age+, <2 prior rejection episodes+*, PS <2+*, normal LDH+*, <2 extranodal sites+, lower IPI+*, >1 1st TI+, and 1st TI with CT* were associated with an improved overall survival (OS)+ and/or PTLD-specific survival (PSS)*. On multivariate analysis, only PS <2 (HR 0.04 [CI 0.01–0.14], p<0.001) and >1 1st TI (HR 0.43 [CI 0.19–0.97], p=0.041) were associated with improved OS while PS <2 (HR 0.04 [0.01- 0.16], p<0.001) and 1st TI with CT (HR 0.19 [CI 0.04–0.84], p<0.028) were associated with improved PSS. Conclusions: A significant minority of SOT pts that receive R without CT as part of 1st TI still die from PTLD. PS is the most important predictor of outcome. In conjunction with the improved survival observed in de novo B-cell NHL pts treated with R+CT (compared to CT alone), this retrospective analysis suggests that some SOT PTLD pts should receive R+CT as part of 1st TI. No significant financial relationships to disclose.

Prognostic Value of Tumor-Infiltrating TIA-1+ Cytotoxic T Cells (TIA1-CTCs) and FOXP3+ Regulatory T Cells (Tregs) in Post-Transplant Lymphoproliferative Disorder (PTLD) Following Solid Organ Transplant (SOT).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 54-54
Author(s):  
Raymond E. Tsao ◽  
Bill Richendollar ◽  
Tony Jin ◽  
Eric Hsi ◽  
Brad Pohlman
Keyword(s):  
T Cells ◽  
Prognostic Value ◽  
Multivariate Analyses ◽  
Cytotoxic T Cells ◽  
Univariate Analysis ◽  
Single Agent ◽  
Cleveland Clinic ◽  
Organ Transplant ◽  
Progression Free Survival ◽  
Solid Organ

Abstract Background: PTLD is a rare, often fatal, complication of SOT. Several studies have identified clinical prognostic factors in PTLD. However, no published studies to our knowledge have yet correlated outcome with the number (#) or type of tumor infiltrating T-cells, which in other types of lymphoma may have prognostic value. We hypothesized that tumor infiltrating T-cells, including TIA1-CTCs and Tregs, would predict survival in SOT PTLD. Methods: We searched the Cleveland Clinic pathology archives for SOT patients (pts), who were diagnosed with PTLD between 1987 and 2007; reviewed the medical records and extracted clinical information and outcomes; performed immunohistochemical (IHC) studies for CD3, TIA-1, and FOXP3; and analyzed the data by Cox proportional univariate and multivariate analyses. Results: We identified 62 SOT pts (heart, 22; lung, 17; kidney 15; liver, 7; pancreas, 1), who were diagnosed with PTLD at median age of 51 years (range 7–73). The median time from SOT to PTLD was 1.8 years (range 0.2–20.9). 1st therapeutic intervention (1st TI) (usually >1) included “complete” resection (4), decreased immunosuppression (51), acyclovir or gancyclovir (32), rituximab (R) (18), “CHOP” chemotherapy (11), radiation therapy (7), and interferon (4). Response to 1st TI was CR (34) or PR (10). The median follow-up among surviving pts is 3.6 years (range 0.1–11.7). 35 (including 4 CHOP and 9 R) pts have died; only 2 CHOP but all 9 R pts died from PTLD. IHC studies in 42 evaluable cases showed the following median # (and range) of cells /10 hpf: CD3 525 (8–2451), TIA1-CTCs 304 (6–1238) and FOXP3 13 (1–338). On univariate analysis, younger age, prior rejection episodes <2, PS <2, LDH normal, extranodal sites (ENS) <2, IPI <4, 1st TI >1, 1st TI with CHOP, # of CD3 cells >550/10 hpf, and # of TIA1-CTCs >300/10 hpf were associated with an improved overall survival (OS), PTLD-specific survival (PSS), and/or progression-free survival (PFS). On multivariate analyses, only PS <2, ENS <2, and 1st TI with CHOP remained independent predictors of outcome. Among the subset of 47 pts with monomorphic B-cell (MMBC) PTLD, these same clinical factors were also independently statistically significant. Conclusions: High #s of infiltrating T cells and TIA1-CTCs are associated with a favorable outcome and may reflect a relatively intact local anti-tumor response. Tregs, which may potentially antagonize such a response, are uniformly low and do not correlate with outcome in PTLD. In this analysis, a significant minority of SOT pts treated initially with single agent R still died from PTLD while pts treated initially with CHOP (with or without R) appeared to have a better outcome, arguing for its early use - at least in a subset of pts. Future studies should attempt to identify biological factors that predict which MMBC PTLD pts might benefit from the addition of CHOP to standard R as part of 1st TI.

scholarly journals Disease course of Neurofibromatosis Type 2; a 30-year follow-up study of 353 patients seen at a single institution

2020 ◽  
Author(s):  
Claire Forde ◽  
Andrew T King ◽  
Scott A Rutherford ◽  
Charlotte Hammerbeck-Ward ◽  
Simon K Lloyd ◽  
...  
Keyword(s):  
De Novo ◽  
Radiation Treatment ◽  
Univariate Analysis ◽  
Age At Onset ◽  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
Disease Course ◽  
Number Of Patients

Abstract Background Limited data exists on the disease course of Neurofibromatosis Type 2 (NF2) to guide clinical trial design. Methods A prospective database of patients meeting NF2 diagnostic criteria, reviewed between 1990–2020, was evaluated. Follow-up to first vestibular schwannoma (VS) intervention and death was assessed by univariate analysis and stratified by age at onset, era referred and inheritance type. Interventions for NF2-related tumours were assessed. Cox regression was performed to determine the relationship between individual factors from time of diagnosis to NF2-related death. Results Three-hundred-and-fifty-three patients were evaluated. During 4643.1 follow-up years from diagnosis to censoring 60 patients (17.0%) died. The annual mean number of patients undergoing VS surgery or radiotherapy declined, from 4.66 and 1.65 respectively per 100 NF2 patients in 1990-1999 to 2.11 and 1.01 in 2010-2020, as the number receiving bevacizumab increased (2.51 per 100 NF2 patients in 2010-2020). Five patients stopped bevacizumab to remove growing meningioma or spinal schwannoma. 153/353 (43.3%) had at least one neurosurgical intervention/radiation treatment within 5 years of diagnosis. Patients asymptomatic at diagnosis had longer time to intervention and better survival compared to those presenting with symptoms. Those symptomatically presenting &lt;16 and &gt;40 years had poorer overall survival than those presenting at 26-39 years (P=0.03 and P=0.02 respectively) but those presenting between 16-39 had shorter time to VS intervention. Individuals with de novo constitutional variants had worse survival than those with de novo mosaic or inherited disease (P=0.004). Conclusion Understanding disease course improves prognostication, allowing for better informed decisions about care.

Characteristics and Survival Patterns of Solid Organ Transplant Patients Developing De Novo Colon and Rectal Cancer

2004 ◽  
Vol 47 (11) ◽  
pp. 1898-1903 ◽  
Author(s):  
Harry T. Papaconstantinou ◽  
Bradford Sklow ◽  
Michael J. Hanaway ◽  
Thomas G. Gross ◽  
Thomas M. Beebe ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
De Novo ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Transplant Patients ◽  
Colon And Rectal Cancer ◽  
Survival Patterns

scholarly journals Sustained Trichodysplasia Spinulosa Polyomavirus Viremia Illustrating a Primary Disseminated Infection in a Kidney Transplant Recipient

2021 ◽  
Vol 9 (11) ◽  
pp. 2298
Author(s):  
Marie-Céline Zanella ◽  
Damien Pastor ◽  
Mariet C. W. Feltkamp ◽  
Karine Hadaya ◽  
Samuel Cordey ◽  
...  
Keyword(s):  
Kidney Transplant Recipient ◽  
Organ Transplant ◽  
High Viral Load ◽  
Skin Lesions ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Viral Loads ◽  
Anal Swab ◽  
Solid Organ Transplant Recipients

Novel human polyomaviruses (HPyV) have been recently identified in solid organ transplant recipients. Trichodysplasia spinulosa (TS) is a rare disease associated with immunosuppression and induced by a polyomavirus (TSPyV). We report here a case of primary and disseminated TSPyV infection after kidney transplantation with extensive skin lesions, sustained viremia, and high viral loads in urine specimens, anal, nasal and throat swabs, assessed via specific real-time PCR for TSPyV during a follow-up period of 32 months after transplantation. The detection of TSPyV with a high viral load in respiratory and anal swab samples is compatible with viral replication and thus may suggest potential respiratory and oro-fecal routes of transmission.

The Immunocompromised Surgical Patient and Opportunistic Infections

2017 ◽  
Author(s):  
Kiran Gajurel ◽  
Aruna K Subramanian
Keyword(s):  
De Novo ◽  
Opportunistic Infections ◽  
Organ Transplant ◽  
Surgical Excision ◽  
Suppressive Therapy ◽  
Surgical Patient ◽  
Solid Organ ◽  
Fungal Sinusitis ◽  
Delay In Diagnosis ◽  
Immunosuppressive Medications

Immunosuppressive medications used to prevent allograft rejection render solid-organ transplant recipients vulnerable to various opportunistic infections. These infections include bacteria, viruses, fungi, and parasites and occur either via reactivation of previously acquired latent infection or de novo acquisition from the donor organ itself or the environment after the transplantation. The type and clinical course of the infection depend on various factors, including the transplanted organ, nature of immunosuppressive regimens, timing of infection relative to the organ transplant, and type and duration of prophylaxis. Proper donor and recipient screening for preventable infections and posttransplantation prophylaxis are instrumental in preventing morbid infections. Posttransplantation infections may present with subtle findings and thus may cause a delay in diagnosis and treatment, resulting in a poor outcome. Appropriate pathogen-specific tests should be requested promptly for early diagnosis. Since these infections may have overlapping clinical and radiologic features, tissue biopsy, if feasible, should be done to establish a definitive diagnosis. Surgical excision or débridement should be attempted in patients presenting with abscesses or invasive fungal sinusitis along with antimicrobial therapy. After the completion of treatment, suppressive therapy may be required in certain infections to prevent a relapse as long as the patient remains immunosuppressed. This review contains 3 tables, and 82 references. Key words: allograft, donor, immunocompromised, infection, opportunistic, organ, transplant 

A Multisite Study on Using Symptom-Targeted Interventions to Improve Mental Health Outcomes of Solid Organ Transplant Patients

2020 ◽  
Vol 30 (2) ◽  
pp. 132-139
Author(s):  
Gracie Moore Greene ◽  
Joseph R. Merighi ◽  
Patricia Voorhes ◽  
Melissa McCool
Keyword(s):  
Psychosocial Adjustment ◽  
Organ Transplant ◽  
Clinical Intervention ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Depression And Anxiety ◽  
General Anxiety Disorder ◽  
Targeted Interventions ◽  
Transplant Patients

Introduction: Depression and anxiety are common affective experiences during the first year following a solid organ transplant. This study examined the degree to which an evidenced-based clinical intervention implemented by social workers—Symptom Targeted Intervention—can alter self-reported depression and anxiety in heart, kidney, liver, and lung transplant recipients. Research Questions: This investigation explored 2 questions: (1) Can symptom-targeted interventions significantly reduce posttransplant recipients’ self-reported depression and anxiety at the conclusion of treatment and at 1-month follow-up? and (2) Does the response differ by gender? Design: A 1-group pretest–posttest design with a 1-month follow-up was used to test for changes in anxiety and depression after transplantation. Forty-eight patients at 2 US transplant centers were enrolled between January 2016 and May 2017. Data were collected using an online platform and analyzed to assess for differences over time and by gender. Results: Anxiety decreased significantly between pretest and posttest using the General Anxiety Disorder-2 ( P < .05). Comparisons by gender indicated that women had a significant decrease in anxiety between pretest and posttest ( P < .001); however, there was no significant decrease in anxiety for men. Analyses by gender and time yielded no significant differences for depression. Discussion: Symptom-targeted interventions have the potential to reduce anxiety in solid organ transplant patients and enhance their psychosocial adjustment after surgery.

Addition of Rituximab (R) to CHOP Improves Survival in the Non-GCB Subtype of Diffuse Large B Cell Lymphoma (DLBCL).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 816-816 ◽  
Author(s):  
Pedro Farinha ◽  
Laurie Sehn ◽  
Brian Skinnider ◽  
Joseph M. Connors ◽  
Randy D. Gascoyne
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
De Novo ◽  
Univariate Analysis ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Chop Chemotherapy ◽  
Entire Study ◽  
Survival Difference

Abstract Background: The cell of origin (COO) distinction provides a prognostic and biologically relevant subclassification of DLBCL. Germinal center B cell (GCB) and non-GCB subtypes were originally characterized by gene expression studies and subsequently validated at the protein level by Hans et al., Blood 193: 275–82 (2004). The addition of R to CHOP chemotherapy has been shown to improve the outcome of patients with DLBCL. The underlying mechanism(s) responsible for this effect is largely unknown. However, it is known that R may preferentially prevent chemotherapy failure in DLBCLs that express Bcl-2 protein or fail to express Bcl-6 (Mounier et al., Blood101: 4279–84 2003, Winter et al., Blood107: 4207–13 2006). Bcl-2 over-expression and absence of Bcl-6 is more common in the non-GCB subtype. Thus, R may benefit mostly non-GCB lymphomas. To test this hypothesis we assessed the clinical impact of CHOP-R vs CHOP in DLBCL distinguished by COO subtypes. Method: We identified 163 patients with DLBCL treated with either CHOP or CHOP-R with available paraffin blocks and interpretable immuno-staining. All were de novo DLBCL cases diagnosed between 1999 and 2002 at the BCCA. The two treatment cohorts represent consecutive eras of therapy (Sehn et al., JCO2005; 23: 5027–33), and thus the median follow-up of living patients was 5.1 and 4.0 y for CHOP and CHOP-R, respectively. HIV+ patients or those with active secondary malignancies were excluded. Tissue microarrays (TMA) were built using duplicate 0.6mm cores from paraffin embedded formalin fixed (FFPE) tissues and stained with antibodies against CD10, Bcl-6, MUM1, and Bcl-2. The COO distinction was determined using the method of Hans. Results: Patients were treated with either CHOP (81) or CHOP-R (82). Their clinical characteristics, including the IPI, were evenly matched. The median follow-up of living patients was 4.4 y. The IPI was predictive of overall survival (OS) (p&lt;0.0001) for the entire study population. Six cases had uninterpretable immunostains resulting in 74 cases with a GCB phenotype and 83 with a non-GCB phenotype (n = 157). Overall, 71% and 75% of the cases over-expressed Bcl-2 and Bcl-6, respectively. Bcl-2 protein was expressed in 70% GCB cases and 73% non-GCB (p= 0.72). Bcl-6 was expressed in 96% GCB cases and 63% non-GCB cases (p&lt;0.0001). In univariate analysis, the addition of R was associated with a better prognosis in the non-GCB cases (p=0.02), but not in the GCB cases (p=0.3). This survival difference was not solely explained by either Bcl-2 or Bcl-6 expression. The addition of R to CHOP chemotherapy and IPI were independent predictors of OS in non-GCB DLBCL (p=0.02; p=0.016, respectively). The addition of R was also of prognostic importance in the lymphomas over-expressing Bcl-2 (p=0.0081). Conclusion: Immuno-chemotherapy using CHOP-R is associated with better OS in DLBCL, due largely to its effect on the non-GCB subgroup. Although Bcl-2 expression does not contribute to the determination of COO distinctions, the OS of Bcl-2-positive DLBCL patients is significantly improved by the addition of R. These results provide insight into the possible mechanisms by which R exerts its beneficial therapeutic effect. Overall Survival for 157 DLBCL Based on Cell of Origin Overall Survival for 157 DLBCL Based on Cell of Origin

High Rate of Survival in Transformed Lymphoma after Autologous Stem Cell Transplant (ASCT): Pathologic Analysis and Comparison with De Novo DLBCL.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1137-1137
Author(s):  
Stephen S. Smith ◽  
Brian Bolwell ◽  
Anjali Advani ◽  
Steven Andresen ◽  
Josephine Chan ◽  
...  
Keyword(s):  
De Novo ◽  
Cleveland Clinic ◽  
B Cell Lymphoma ◽  
Rank Test ◽  
P Value ◽  
Cell Transplant ◽  
Transformed Lymphoma ◽  
Baseline Characteristics ◽  
Pathologic Analysis

Abstract Introduction: Survival gains in follicular lymphoma (FL) have been variably attributed to improved first line and salvage therapies, and a decreasing frequency of histologic transformation (HT). Although ASCT is often used in patients (pts) with transformed lymphoma (TL), optimal pt selection and factors predictive of outcome are unclear. Although immunohistochemistry (IHC) has been applied to prognostication in de novo DLBCL, few studies have investigated IHC as a prognostic factor in TL. The purpose of this analysis was to review outcomes using ASCT for TL at the Cleveland Clinic Taussig Cancer Insitute (CCTCI) in light of modern IHC-based pathologic analysis. Methods: All pts undergoing ASCT for diffuse large B-cell lymphoma from 2003–2008 at CCTCI (n=130) were identified. IHC analysis for markers CD10, BCL2, BCL6, and MUM-1 was available for 56 pts, who were analyzed further. Pts with TL (n=25) were compared as a group to de novo cases (n=31). Baseline characteristics were compared using Fisher’s exact and Wilcoxon rank-sum tests. Relapse-free and overall survival (RFS and OS) were estimated with the Kaplan-Meier method and compared via log-rank test. Cox proportional hazards analysis was used to examine features predicting outcome after ASCT. Results: Median age was 57 years. Of 25 TL pts, 16 had prior FL, 1 each had small lymphocytic lymphoma and nodular LP Hodgkin lymphoma, and 7 presented with coexistent DLBCL and FL in the same biopsy specimen. Among 18 TL pts with metachronous presentation, HT occurred at a median of 26 months (range, 8–198 months). Pathologic characteristics (%) are: Group CD10 BCL6 MUM-1 BCL2 GCB phenotype* MedianKI67 index t(14;18) *Criteria from Hans et al, Blood2004;103(1):275–82 TL 84 95 38 84 92 70 8/10 de novo 61 88 43 63 71 80 1/8 P value .08 .62 1.0 .18 .09 .63 .02 Age and disease status at time of transplant were similar between groups. Three de novo pts and 2 TL patients underwent ASCT during first remission; all others underwent ASCT for relapsed/refractory disease. With a median follow-up of 25 months, 4 year RFS was 64% vs. 59% (p=.82) and OS 63% vs. 59% (p=.68) for TL and de novo pts, respectively (see Figures 1 and 2). No IHC feature predicted RFS or OS. Elevated LDH at time of ASCT predicted poor RFS (HR 4.6, p=.008) and OS (HR 6.3, p=.005) on multivariate analysis, and increasing number of prior regimens predicted poor RFS only (HR 1.4, p=.003). Conclusions: TL resembled de novo DLBCL in terms of IHC characteristics, but a higher proportion of TL cases bore the t(14;18) translocation. ASCT was effective in treating TL, with a 4-year RFS and OS exceeding 60%. This was indistinguishable from outcomes for de novo DLBCL pts treated with ASCT over the same period. Baseline characteristics were similar between TL and de novo pts. Survival in FL may be improving in part due to good outcomes using ASCT for TL. Confirmation of our observed RFS/OS among TL pts requires longer follow-up, given the ongoing risk of relapse of indolent disease. Outcome after ASCT cannot be predicted by IHC, and novel approaches are needed to improve pt selection and elucidate the biology of HT. Figure 1: RFS Figure 1:. RFS Figure 2: OS Figure 2:. OS

Effect of chemotherapy on survival of patients with recurrent pancreatic ductal adenocarcinoma (PDAC) following surgical therapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15748-e15748
Author(s):  
Olumide B. Gbolahan ◽  
Yan Tong ◽  
Bert H. O'Neil ◽  
Safi Shahda
Keyword(s):  
Adjuvant Therapy ◽  
Metastatic Disease ◽  
Survival Benefit ◽  
De Novo ◽  
Univariate Analysis ◽  
Ductal Adenocarcinoma ◽  
Tumor Characteristics ◽  
Curative Therapy ◽  
Kaplan Meier

e15748 Background: Patients with recurrent PDAC are treated similarly to patients with de novo metastatic disease. The aim of this study is to report the outcome of patients with recurrent PDAC following initial definitive resection and adjuvant therapy. Methods: Patients were identified from an IRB approved, retrospective database at Indiana University that contained patient and tumor characteristics, adjuvant therapy and all treatment for metastatic disease. Follow-up was updated as of 6/2014. Overall survival (OS) from recurrence until death or last follow up was estimated using the Kaplan Meier method. Results: Between 2008-2014, 451 patients with resectable PDAC and available follow up data were identified, of whom 234 had documented relapse. Patient/tumor characteristics were as follows: median age: 64.2 years (25-89), 54% male, 76% LN+, 24% positive margins, 66% and 85% with lymphovascular and perineural invasion respectively. 69% of patients received adjuvant gemcitabine (GEM). Median time to relapse was 10 months. 60% of patients received at least 1 line of systemic therapy and 18% received 2 lines. Chemotherapy was GEM-based: 33%, 5FU-based 33%, or both 33% and 1% other treatment. Median OS from time of relapse was significantly improved following chemotherapy compared to no chemotherapy (10 months vs 3 months, P < 0.0001). Median OS for 5FU based and GEM based treatment was 6 and 8 months, respectively (P = 0.09). Those who received both had mOS of 14 months (95% C.I 10-17months, P < 0.0001). On univariate analysis, chemotherapy, regardless of type was associated with a survival benefit. Conclusions: Chemotherapy appears to be associated with survival benefit for patients with relapsed PDAC following initial curative therapy. Survival in our retrospective study appears similar to reported literature for de novo metastatic disease.

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