DA-R-EPOCH in Post Transplant Lymphoproliferative Disorders (PTLD) and EBV-Positive High Grade B-Cell Lymphomas with Rearrangements of MYC and BCL2 (HGBL)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1875-1875
Author(s):  
Patrick D. Ford ◽  
Alexandra E. Kovach ◽  
John P. Greer ◽  
David S. Morgan ◽  
Mahsa Sharifi Talbott ◽  
...  
Keyword(s):  
B Cell ◽  
Board Of Directors ◽  
Organ Transplant ◽  
B Cell Lymphoma ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Advisory Committees ◽  
Free Survival ◽  
Post Transplant ◽  
Number Of Patients

Abstract Introduction: Immunotherapy with rituximab alone or in combination with sequential chemotherapy such as CHOP, in addition to a reduction in immunosuppression (IST), has been shown to be effective in achieving long-term, disease-free survival in patients with B-cell PTLD. We have recently observed an increased incidence of HGBL in patients receiving IST following solid-organ transplant. Intensive induction regimens (ex: DA-R-EPOCH) in non-transplant HGBL has been associated with improved complete responses. Intensive regimens have not been previously evaluated in patients with PTLD. The aim of this study is to compare the tolerability of DA-R-EPOCH to R-CHOP in post-transplant patients with HGBL. Methods: Patients treated with either DA-R-EPOCH or R-CHOP were included in this study following IRB approval. Eligible patients were ≥18 years, had biopsy-confirmed B-cell PTLD, and were treated with at least one cycle of DA-R-EPOCH or R-CHOP. The primary outcome was progression-free survival (PFS); secondary outcomes were overall survival (OS), toxicities, and hospitalizations due to treatment-related toxicities. Statistical analysis was performed using SPSS.22 software Results: Sixty-three patients had biopsy-confirmed PTLD. Of these, 26 met inclusion criteria. Among these 26 patients, 19 (73.1%) were men; median age was 57 years (18-75 years); and transplants included 3 (11.5%) lung, 4 (15.4%) heart, 9 (34.6%) kidney, 8 (30.8%) liver, 2 (7.7%) pancreas, and 1 (3.8%) stem cell. All patients were receiving IST at the time of diagnosis of PTLD. Pathology reports found that 24 (92.3%) had diffuse large B-cell lymphoma (DLBCL)-like PTLD, and 11 (57.9%) had EBV-positive disease. HGBL was observed in 10 (38.5%) patients. Seven patients received DA-R-EPOCH, and 19 received R-CHOP. Baseline characteristics were similar between treatment groups. There was a significantly higher number of patients with HGBL in the DA-R-EPOCH arm compared with the R-CHOP arm (100% [7/7] vs. 15.8% [3/19]; 95% CI, -0.01-1.00; p=0.001). The median number of cycles administered was not significantly different between the groups (4.6 cycles vs. 5 cycles; 95% CI, 4.33-6.07; p=0.645). Dose intensification occurred in 8 of 32 cycles for patients who received DA-R-EPOCH. The median follow-up time for patients treated with DA-R-EPOCH was shorter (10 months) than for patients treated with R-CHOP (29 months). PFS was not found to be significantly different between the DA-R-EPOCH and R-CHOP arms (10.4 months vs. 61.4 months; 95% CI, 1.80-18.99; p=0.31). Patients with EBV-positive disease had inferior PFS compared with EBV-negative disease (7.37 months vs. NR; 95% CI, 1.02-10.2; p=0.046). In addition, OS, neutropenia, thrombocytopenia, hospitalizations, and hospitalizations due to febrile neutropenia were not significantly different between groups, though trends toward higher rates of grade 3 or 4 neutropenia, thrombocytopenia, and hospitalizations was observed in the DA-R-EPOCH group. Conclusion: To our knowledge, this is the first study evaluating the role of intensive induction therapy in patients with HGBL with MYC and BCL2 rearrangements observed in solid organ transplant recipients. In patients with PTLD, DA-R-EPOCH is a well-tolerated regimen with concurrent taper in IST. However, this strategy may not overcome the poor prognosis of HGBL. Dose adjustments beyond level 2 were limited by cytopenias. Figure Figure. Disclosures Reddy: KITE: Membership on an entity's Board of Directors or advisory committees; celgene: Membership on an entity's Board of Directors or advisory committees; GILEAD: Membership on an entity's Board of Directors or advisory committees; INFINITY: Membership on an entity's Board of Directors or advisory committees.

Abstract 1025: Risk of diffuse large B-cell lymphoma in solid organ transplant recipients

2012 ◽  
Author(s):  
Todd M. Gibson ◽  
Eric A. Engels ◽  
Christina A. Clarke ◽  
Ruth M. Pfeiffer ◽  
Charles F. Lynch ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Organ Transplant ◽  
B Cell Lymphoma ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Large B Cell Lymphoma ◽  
Solid Organ Transplant Recipients ◽  
Large B Cell

scholarly journals A Multi-Institutional Outcomes Analysis of Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma Treated with Ibrutinib

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1115-1115 ◽  
Author(s):  
Allison Marie Winter ◽  
Daniel J. Landsburg ◽  
Francisco J. Hernandez-Ilizaliturri ◽  
Nishitha Reddy ◽  
Stephen Smith ◽  
...  
Keyword(s):  
B Cell ◽  
Board Of Directors ◽  
De Novo ◽  
Molecular Subtype ◽  
Single Agent ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Advisory Committees ◽  
Free Survival ◽  
Large B Cell Lymphoma

Abstract Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with distinct survival differences according to molecular subtype with superior outcomes in patients with the germinal center B cell-like (GC) subtype as compared to those with the activated B cell-like (ABC) subtype. Efficacy data for single-agent ibrutinib in patients with relapsed/refractory (r/r) DLBCL are limited to a single clinical trial of 80 patients. In that study, higher response rates were observed for r/r ABC-DLBCL compared to GC-DLBCL (37% vs. 5%), when assigned by gene expression profiling (GEP). The response rate of those with unknown/unclassifiable DLBCL was 22%. Despite biologic rationale for selective cytotoxicity of ibrutinib for ABC-DLBCL, it is not clear that such preferential activity will be observed when subtyping based on immunohistochemical (IHC) staining is used, as the correlation with subtype determined by GEP and IHC is imperfect. Furthermore, GEP is time consuming and expensive so IHC is used in clinical practice to differentiate GC from non-GC, the latter of which includes both ABC and unclassifiable DLBCL. We retrospectively analyzed outcomes of patients with r/r DLBCL treated with ibrutinib at a number of large academic medical centers. Methods: We reviewed medical records of all patients with DLBCL treated with ibrutinib at five U.S. tertiary-care cancer centers from 2013 to 2016. We included patients with de novo DLBCL as well as those transformed from indolent lymphoma if the ibrutinib was given for the DLBCL histology. Patients were excluded if they received ibrutinib for ≤ 14 days. Molecular subtype (GC vs non-GC) was determined by local pathology findings and/or the investigator's application of the Hans algorithm. Categorical variables were compared between groups using the Chi-square test. Outcomes were calculated from the date of initiation of ibrutinib. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Results: Thirty five patients met inclusion criteria (27 de novo and 8 transformed DLBCL). The median age at diagnosis was 61 years (range 38-88) with 66% men.By Hans IHC criteria, there were 21 cases of non-GC, 9 GC and 5 were unknown.The median number of treatments prior to ibrutinib was 3 (range 1-8). 30% of patients had undergone prior autologous stem cell transplant. Characteristics including age, gender, transformed versus de novo, relapsed versus refractory, number of prior therapies, and prior use of transplant did not significantly differ between subgroups. The overall response rate (ORR) to ibrutinib was 29% with 4 patients achieving a complete response (CR) and 6 achieving a partial response (PR). When evaluated by subtype assigned by IHC, GC-DLBCL patients had an ORR of 44% and non-GC-DLBCL patients had an ORR of 19%. There was no significant difference in the rates of CR, PR, stable disease, or progressive disease between the subtypes (p=0.185) or between de novo ortransformed disease (P = 0.114). The median progression-free survival (PFS) was comparable for patients with the GC, non-GC, and unknown subtype (3.9, 2.2, and 4.1 months, respectively, P = 0.382, Figure). The median overall survival (OS) was longer for patients with the GC subtype (10.5 months) compared to 5.5 months for patients with the non-GC subtype, and 9.7 months for those with unknown subtype but this difference was not statistically significant (P=0.564). Figure: Progression Free Survival of r/r DLBCL Patients Treated with Ibrutinib, based on Hans Algorithm Subtype Conclusions: Responserates to single agent ibrutinib in the GC and non-GC subtypes of r/r DLBCL do not appear different when using Hans algorithm to assign subtypes. PFS and OS were modest in both groups and not statistically different. In conclusion, until GEP or other molecular technologies such as Nanostring are in more widespread use for routine subtyping of DLBCL, caution is advised when selecting patients for subtype-specific therapy, as clinical outcomes for patients receiving ibrutinib may not differ by cell of origin as determined by IHC. Figure Figure. Disclosures Reddy: celgene: Membership on an entity's Board of Directors or advisory committees; KITE: Membership on an entity's Board of Directors or advisory committees; GILEAD: Membership on an entity's Board of Directors or advisory committees; INFINITY: Membership on an entity's Board of Directors or advisory committees. Shadman:Pharmacyclics: Honoraria, Research Funding. Smith:Spectrum: Honoraria; Celgene: Honoraria; Abbvie: Research Funding; Genentech: Honoraria.

scholarly journals Post-Transplant Lymphoproliferative Disorder after Heart Transplant in the Pediatric Population: A Systematic Review

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 37-37
Author(s):  
Mobeen Zaka Haider ◽  
Muhammad Taqi ◽  
Hasan Mahmood Mirza ◽  
Zarlakhta Zamani ◽  
Hafsa Shahid ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
B Cell ◽  
Induction Therapy ◽  
Graft Rejection ◽  
Lymphoproliferative Disorder ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Post Transplant ◽  
Transplant Patients

Background: Post-transplant lymphoproliferative disorder (PTLD) is a B-cell proliferation disorder that results from disruption in the physiological mechanisms for proliferation in an immunocompromised host after a solid organ transplant. Our study aims to review the demographic characteristics and clinical outcomes after transplantation. We also aim to study the role of immunosuppression induction therapy, the effect of PTLD on survival, and the effective chemotherapy used for B-cell disorders leading to improved survival. Methods: Following the PRISMA guideline, we performed a comprehensive literature search on PubMed, Cochrane Library, Embase, and clinicaltrials.gov from the past decade on May 04, 2020. We used the MeSH terms of organ transplantation and lymphoproliferative disorders. 1741 articles were screened. We excluded all case reports, case series, pre-clinical trials, review articles, and meta-analysis and included three cohort studies and one prospective multicentric study. We extracted the data for baseline characteristics, the reason for transplantation, recipient & donor EBV status, immunosuppression used, type & stage of PTLD, organ system involved, duration between transplant and PTLD diagnosis, treatment, response to therapy, adverse effects of therapy and mortality. Results: We studied 9617 patients in the included four studies, out of which 499 patients developed PTLD. Data in these studies was collected over the last 20-26 years. Median follow-up of patients since transplant was 3-9 years (average 7.5y). Table 1 The age of the patients ranged from 3-18 years with a male: female gender ratio of 48:52% and around 50% of the patients were seronegative to EBV pretransplant. The following drugs were used for immunosuppression: cyclosporin, tacrolimus, azathioprine, mycophenolate, interleukin 2 receptor antagonist (basiliximab), corticosteroids, anti-thymocyte globulins(ATG). Kindel et al. narrated that the development of eosinophilic oesophagitis may be a marker for the development of PTLD.Gajarski et al. concluded that Post-transplant Immunosuppressive induction therapy with cytolytic drugs (e.g OKT3 monoclonal antibody, ATG, thymoglobulin Basiliximab and daclizumab) , lowers the rate of PTLD, graft rejections, and early infections in post-transplant patients as compared patients who did not receive induction therapy . This depends upon the type of induction e.g OKT3 monoclonal antibody was associated with increased PTLDs and graft rejection, while Thymoglobulin/IL-2R antagonists demonstrated to decrease both the outcomes. Claire et al. described that overall mortality is decreasing due to the ongoing better understanding of pathophysiology and treatment options related to solid organ transplant. The mortality of the post-transplant congenital heart disease group was higher as compared to the cardiomyopathy group due to high comorbidities and surgical complications. The study by Christopher et al. showed that EBV seronegativity before transplant is associated with an increased risk of PTLD. PTLD is associated with lower survival rates as compared to non-PTLD groups. Conclusion: Our review illustrates that pretransplant seronegativity, OKT3 monoclonal antibody, and the development of eosinophilic esophagitis during the immunosuppressive regime increase the risk of PTLD. This study demonstrates that with a better understanding of PTLD and tumor behavior, the all-cause mortality rates are falling significantly. PTLD is one of the leading causes of mortality in post-transplant patients. However, the immunosuppressive induction therapy, absence of eosinophilic esophagitis, thymoglobulin/IL-2R antagonists improve survival and outcomes in the post-transplant patient in terms of graft rejection, graft failure, and development of PTLD. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

scholarly journals Favorable Outcome of Primary Mediastinal Large B-Cell Lymphoma Patients Treated with Sequential R-CHOP/R- ICE Regimen Omitting Radiation

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3954-3954
Author(s):  
Neta Goldschmidt ◽  
Ora B. Paltiel ◽  
Dina Ben Yehuda ◽  
Geffen Kleinstern ◽  
Alexander Gural ◽  
...  
Keyword(s):  
B Cell ◽  
Board Of Directors ◽  
Clinical Laboratory ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Advisory Committees ◽  
Liver Uptake ◽  
Large B Cell Lymphoma ◽  
Number Of Patients ◽  
Large B Cell

Abstract Introduction: Progression-free (PFS) and overall survival (OS) rates for Primary mediastinal large B-cell lymphoma (PMBL) have risen to 84% and 92%, respectively, with the addition of rituximab to standard CHOP. Despite general acceptance of RCHOP as standard of care for Diffuse Large B-Cell lymphoma (DLBCL), many centers recommended alternative regimens for PMBL such as RMACOPB, RVACOPB, RCHOP-RICE and DA-EPOCH-R. The latter was adopted with great worldwide enthusiasm, despite its lack of proven superiority in randomized controlled trials (RCT). The benefits of DA-EPOCH-R include the omission of consolidation radiotherapy (RT), an attractive option in PMBL patients (pts), given their demographic profile-mainly females in their 3rd decade. We aimed to evaluate the PFS, the OS, the number of hospitalization days for treatment, and complications and the need for consolidation RT in a single center in the Rituximab era; where since 2007 over 80% of our pts were treated with the RCHOP-RICE regimen consisting of 4 courses of RCHOP followed by 3 courses of RICE. Methods: We reviewed the files of all PMBL pts who received 1st-line treatment in Hadassah Medical Center between 8/2002-10/2014, extracting clinical, laboratory and imaging data. Results: Of the 47 pts, 24 were treated with RCHOP-RICE (80% since 2007), 12 with RMACOPB, 3 with RVACOPB, 6 with RCHOP and 2 with DA-EPOCH-R. Pts were mainly female, with Stage I-II disease, and a high LDH level. Pt characteristics were comparable between the protocols (Table). In total, 21 (45%) of our pts received RT; only 3 pts (12%) treated with RCHOP-RICE compared to 18 pts (78%) treated with other protocols (p<0.01). A mean of 11+8 hospitalization days/pt were needed to administer the RCHOP-RICE regimen, significantly more than required for other treatments combined (p<0.01), except DA-EPOCH-R where the mean hospitalization days to administer 6 courses-=37+2 /pt (2 patients). Treatment-related toxicities did not differ between the groups. Late toxicity included advanced breast cancer in one pt who received RMACOPB and radiotherapy. The Deauville 5-point scale at interim was available for 39 pts, of whom 43% had an uptake </= to mediastinal blood pool, 33% had an uptake greater than the mediastinum and </= liver uptake and 23% had >liver uptake. At the end of therapy the numbers were 68%, 23% and 9% respectively, for 35 pts who were evaluated. The median 5-year PFS and OS were 93% and 98% respectively, with no difference between treatment regimens. Conclusion: The RCHOP-RICE regimen does not appear inferior to other regimens, allows to omit RT in PMBL and demonstrated no significant late toxicities. Published phase 2 data on DA-EPOCH-R (93% EFS and 95% OS) do not demonstrate an advantage compared to the simpler regimens described here. RCTs are required to establish the standard for efficacy, efficiency and safety of care in PMBL. Table 1. Characteristics RCHOP-RICE Others All patients Number of patients 24 23 47 Median age 34 34 34 Female n(%) 16 (67) 15 (65) 31 (66) Stage 1-2 n(%) 17 (71) 21 (91) 38 (81) Median tumor size (cm) 10.2 10.5 10.2 High LDH n(%) 21 (87) 17 (81) 38 (84) Effusion n(%) 10 (42) 9 (39) 19 (40) Median 5 year PFS 90% 95% 93% Median 5 year OS 100% 95% 98% Disclosures Lavie: Pfizer: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Safety and Clinical Activity of Temsirolimus in Combination with Rituximab and DHAP in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma - Report of the Prospective, Multicenter Phase II STORM Trial

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3028-3028
Author(s):  
Mathias Witzens-Harig ◽  
Andreas Viardot ◽  
Ulrich Keller ◽  
Christian Buske ◽  
Anne Crombé ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Advisory Committees ◽  
Free Survival ◽  
Multicenter Phase

Abstract Purpose. To evaluate the safety, tolerability and efficacy of the combination of the mTOR inhibitor Temsirolimus and a standard salvage regimen (R-DHAP) in patients with relapsed or refractory diffuse large cell B-Cell lymphoma (DLBCL). Methods. This is a prospective, multicenter, phase II, open-label study. Patients with relapsed or refractory DLBCL with a maximum of two prior treatment lines were eligible. The STORM regimen consisted of Rituximab 375 mg/m² (day 2) and DHAP (Dexamethasone 40mg day 3-6, Cisplatine 100 mg/m² day 3, Cytarabine 2x2 g/m² day 4) with Temsirolimus added on day 1 and 8 of a 21 d cycle, with 2-4 cycles planned. In part I, dose levels of 25, 50, 75 and 100 mg for Temsirolimus were predefined. Based on the observed toxicity profile, the independent data safety committee recommended a Temsirolimus dose of 25 mg given on day 1 and 8 for the part II extension cohort of the trial. Results. We here report on 46 patients (pts), 15 from part I and 31 from part II. Seven pts were not evaluable for response. Of the evaluable 39 patients, median age was 63 and median number of prior regimen was 1. Temsirolimus dose was 50 mg on day 1 and 8 in 7 pts from the part I of the trial and 25 mg in the remaining 39 pts. The overall response rate was 82% (32/39pts) with 22 partial and 10 complete responses. After a median follow up of 10 months for the total study population, median PFS and OS have not been reached (Figure 1A and 1B). Early safety analysis includes preliminary data of 22 pts. The most frequent non-hematologic side effects were nausea (14 pts, 64%), epistaxis (11 pts, 50%), fatigue (12 pts, 55%), fever (11 pts, 50%) and diarrhea (11 pts, 50%). Frequent grade 3/4 events (n>2) included leukopenia (21 pts, 95%), thrombocytopenia (20 pts, 91%), lymphopenia (11pts, 50%), anemia (8 pts, 36%), neutropenia (10 pts, 45%), renal failure (3 pts, 20%) and infections (7 pts, 32%, bladder infection, esophagus infection, central venous access infection, soft tissue infection, mucositis). Two therapy-related deaths occurred (one patient died from sepsis during neutropenia, another from cerebral bleeding, both events occurring after cycle 3). Conclusion. Temsirolimus can be safely added to DHAP and Rituximab with promising activity. Figure 1 Progression free survival Figure 1. Progression free survival Figure 2 Overall survival Figure 2. Overall survival Disclosures Witzens-Harig: Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Viardot:Pfizer: Honoraria; Takeda: Other: travel support; Roche: Honoraria; BMS: Consultancy; Janssen: Consultancy; Amgen: Consultancy. Keller:Roche: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Spectrum Pharmaceutical: Consultancy, Membership on an entity's Board of Directors or advisory committees. Buske:Celltrion, Inc.: Consultancy, Honoraria. Meissner:Amgen: Other: Travel Support; Takeda: Other: Travel Support; Teva: Other: Travel Support; Celgene: Other: Travel Support. LaRosee:Pfizer: Honoraria. Marks:Pfizer: Honoraria. Hess:Celgene: Honoraria; Roche, CTI, Pfizer, Celgene: Research Funding; Janssen: Honoraria; Roche: Honoraria; Pfizer: Honoraria; Novartis: Honoraria.

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.

IHC Analysis and Prognostic Factors in Post Transplant Lymphoproliferative Disorders after Solid Organ Transplantation: A Single Center Experience

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1443-1443
Author(s):  
Zohra Nooruddin ◽  
William Robinson ◽  
Daniel Pollyea ◽  
Jonathan A Gutman ◽  
Clayton Smith ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Board Of Directors ◽  
Median Time ◽  
Cell Lymphoma ◽  
Solid Organ ◽  
Advisory Committees ◽  
Post Transplant ◽  
Line Therapy ◽  
Poor Outcomes

Abstract Post Transplant Lymphoproliferative Disorder (PTLD) represents one of the most fatal complications following solid organ transplants (SOT). A multicenter analysis in 2010 reported a 3yr overall survival (OS) of 62%. In 2014 a single institutional study reported an improved median OS of 8 years in the rituximab era. Clinical studies have attempted to subdivide post transplant diffuse large B cell lymphomas (PT-DLBCL) into immunophenotypic subgroups with most reviews demonstrating a higher incidence of activated B-cell (ABC) subtype. Because of the rarity of PTLD, insight into disease development and progression is currently limited. We examined the clinical features and outcomes based on immunohistochemical (IHC) analysis in consecutive PTLD pts treated at the University of Colorado over a 25-year period. Methods: This retrospective analysis focused on 52 adult SOT pts who were treated for PTLD at our institution between Jan 1989 to April 2015. Results: 52 pts were analyzed. The median age at transplantation was 47.5 years (5-73yrs) and the median time from SOT to PTLD was 52.5 months (2.6 to 251). The most common transplanted organ included liver (46%), kidney (40%), heart (10%), lung (2%) and [kidney pancreas] (2 %). The grafted organ was involved in 10 pts (19%) Males comprised 67%, 63% were Stage III-IV, 69% were EBV positive, 23% had extranodal involvement, 19% had bone marrow involvement and 21% had CNS involvement. Of the 52 patients, 46 (88 %) had monomorphic histology. Amongst monomorphic PTLD 31 pts (60%) had DLBCL, 6 pts (14%) had Burkitt Lymphoma, 4 pts (9%) had CNS lymphoma, 1 pt (2%) had plasmablastic lymphoma, 1 pt (2%) had NK/T cell lymphoma and 1 pt (2%) had aggressive B cell lymphoma unclassifiable. Of the analyzed pts 85% were CD20 positive, 77 % had elevated LDH and 49% had an International Prognostic Index (IPI) > 1. Thirty Eight pts (73%) were on >1 immunosuppressive agent with a median immunosuppressive treatment duration of 36 months (range 0.25 to 23 yrs). All pts (100%) diagnosed within 12 months of SOT were EBV positive. Similarly all pts (100%) diagnosed 12 months after were EBV negative. Initial treatments included reduction in immunosuppression in 63% pts, rituximab monotherapy in 28% pts and chemotherapy in 53% pts. 67% of pts received rituximab either alone or in combination with chemotherapy. 48 of 52 pts were assessable for response; 4 pts were lost to follow up. 64% achieved a complete remission after first line therapy while 12% were refractory to front line therapy. 7 of 48 pts (14%) pts relapsed with a median time of 60 months (2yrs-15yrs). IHC staining utilizing the Hans Algorithm was applied on 20/31 pt samples with DLBCL. ABC subtype was identified in 70% (14/20) and GC (germinal center B-cell) subtype in 30% (6/20) samples. Median overall survival was 69 months (Figure 1). On univariate analysis CNS disease (HR 2.82, 95% CI 1.25- 6.3, p= 0.01), pts who received chemotherapy (HR 6.65, 95% CI 1.63-27.04, p= 0.008), graft involvement with PTLD (HR 2.63, 95% CI 1.01-6.86, p=0.04) and IPI > 1 (HR: 3.55; 95% CI: 1.47 - 8.57, p= 0.005) were associated with poor survival whereas EBV positivity (HR .25, 95% CI 0.10-0 .64, p= 0.005) was associated with improved survival. Advanced stage (Stage III-IV), high LDH, monomorphic histology, ABC DLBCL subtype, more than 1 immunosuppressive agents and rituximab treatment were not statistically significant parameters for survival. In multivariate analysis, EBV positivity was predictive of improved survival (p=0.006) while graft organ involvement (p=0.02) and chemotherapy administration (0.013) was associated with poor overall survival. Conclusion: In this consecutive series of PTLD after SOT from a single institution over a 25 year period, EBV positivity was associated with improved survival whereas graft organ involvement and chemotherapy was associated with poor outcomes. Similar to previously published data, in PT-DLBCL cases we were not able to demonstrate a definite association between histogenetic phenotype and prognosis. However we found 70% of PT-DLBCL samples to have an ABC subtype (Figure 2). The reason for this increased predilection is not fully understood. ABC subtype is known to have an inferior overall survival compared to GCB DLBCL which could explain the relatively poor outcomes in PT-DLBCL patients. This merits further studies in larger patient cohorts due to potential therapeutic implications. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Pollyea: Ariad: Consultancy; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; GlycoMimetics: Other: Member of data safety monitoring board; Karyopharm: Consultancy; Pfizer: Consultancy.

#74: Development of a Solid-Organ Transplant-Specific Antibiogram in a Tertiary Pediatric Hospital in Canada

2021 ◽  
Vol 10 (Supplement_1) ◽  
pp. S1-S1
Author(s):  
T Kitano ◽  
M Science ◽  
N Nalli ◽  
K Timberlake ◽  
U Allen ◽  
...  
Keyword(s):  
Treatment Guidelines ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Lower Sensitivity ◽  
Solid Organ ◽  
Pediatric Hospital ◽  
Post Transplant ◽  
Significant Difference ◽  
Organ Specific ◽  
Wide Population

Abstract Background Solid-organ transplant (SOT) patients are more vulnerable to infections by antimicrobial-resistant organisms (AROs) because of their hospital exposure, compromised immune systems, and antimicrobial exposure. Therefore, it may be useful for transplant facilities to create transplant-specific antibiograms to direct empirical antimicrobial regimens and monitor trends in antimicrobial resistance. Methods SOT (i.e., lung, liver, renal, and heart) antibiograms were created using antimicrobial susceptibility data on isolates from 2012 to 2018 at The Hospital for Sick Children, a tertiary pediatric hospital and transplant center in Toronto, Ontario. The Clinical Laboratory Standards Institute (CLSI) guidelines were followed to generate the antibiograms. The first clinical isolate of a species from a patient in each year was included irrespective of body site; duplicates were eliminated and surveillance cultures were excluded. Results from 2 years of data were pooled on a rolling basis to achieve an adequate sample size in both SOT and hospital-wide antibiogram. The SOT antibiogram was then compared with the hospital-wide antibiogram of the compatible 2 pooled years from 2012 to 2018. For subgroup analyses in the SOT population, organ-specific antibiograms and transplant timing-specific antibiograms (pretransplant, post-transplant &lt;1 year, and post-transplant ≥1 year) between transplant and sample collection dates were analyzed. All proportions were compared using the χ 2 test. Results The top 5 organisms in one (2 year) analysis period of the SOT antibiogram were Escherichia coli (n = 29), Staphylococcus aureus (n = 28), Pseudomonas aeruginosa (n = 20), Enterobacter cloacae complex (n = 18), and Klebsiella pneumoniae (n = 17). For E.coli, susceptibility in the SOT antibiogram was significantly lower than those in the hospital-wide antibiogram in 2017/2018 for ampicillin (27% vs. 48%; P = 0.015), piperacillin/tazobactam (55% vs. 87%; P &lt; 0.001), cefotaxime (59% vs. 88%; P &lt; 0.001), ciprofloxacin (71% vs. 87%; P = 0.007) and cotrimoxazole (41% vs. 69%; P &lt; 0.001), but not significantly different for gentamicin (94% vs. 91%; P = 0.490), tobramycin (88% vs. 90%; P = 0.701) and amikacin (100% vs. 99%; P = 0.558). These findings were consistent throughout the study period in E.coli. There was no statistically significant difference between the SOT and hospital-wide antibiograms for other organisms. There were no significant differences in susceptibility between organ-specific antibiograms or transplant timing-specific antibiograms in 2012–2018. Conclusions We found that E.coli from the SOT population had a significantly lower sensitivity to all antimicrobials, except aminoglycosides, compared with those from the hospital-wide population. Other organisms had similar susceptibility to the hospital-wide population. Developing a SOT antibiogram will assist in revising and improving empiric treatment guidelines for this population.

scholarly journals Does Post-Transplant Cytomegalovirus Increase the Risk of Invasive Aspergillosis in Solid Organ Transplant Recipients? A Systematic Review and Meta-Analysis

2021 ◽  
Vol 7 (5) ◽  
pp. 327
Author(s):  
Nipat Chuleerarux ◽  
Achitpol Thongkam ◽  
Kasama Manothummetha ◽  
Saman Nematollahi ◽  
Veronica Dioverti-Prono ◽  
...  
Keyword(s):  
Systematic Review ◽  
Invasive Aspergillosis ◽  
Meta Analysis ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Effect Estimate ◽  
Solid Organ ◽  
Post Transplant ◽  
Cmv Disease ◽  
The Impact

Background: Cytomegalovirus (CMV) and invasive aspergillosis (IA) cause high morbidity and mortality in solid organ transplant (SOT) recipients. There are conflicting data with respect to the impact of CMV on IA development in SOT recipients. Methods: A literature search was conducted from existence through to 2 April 2021 using MEDLINE, Embase, and ISI Web of Science databases. This review contained observational studies including cross-sectional, prospective cohort, retrospective cohort, and case-control studies that reported SOT recipients with post-transplant CMV (exposure) and without post-transplant CMV (non-exposure) who developed or did not develop subsequent IA. A random-effects model was used to calculate the pooled effect estimate. Results: A total of 16 studies were included for systematic review and meta-analysis. There were 5437 SOT patients included in the study, with 449 SOT recipients developing post-transplant IA. Post-transplant CMV significantly increased the risk of subsequent IA with pORs of 3.31 (2.34, 4.69), I2 = 30%. Subgroup analyses showed that CMV increased the risk of IA development regardless of the study period (before and after 2003), types of organ transplantation (intra-thoracic and intra-abdominal transplantation), and timing after transplant (early vs. late IA development). Further analyses by CMV definitions showed CMV disease/syndrome increased the risk of IA development, but asymptomatic CMV viremia/infection did not increase the risk of IA. Conclusions: Post-transplant CMV, particularly CMV disease/syndrome, significantly increased the risks of IA, which highlights the importance of CMV prevention strategies in SOT recipients. Further studies are needed to understand the impact of programmatic fungal surveillance or antifungal prophylaxis to prevent this fungal-after-viral phenomenon.

scholarly journals Impact of Interim FDG-PET (iPET) in the Outcomes of Patients with Aggressive B-Cell Lymphomas Receiving DA-EPOCH-R

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2898-2898
Author(s):  
Vania Phuoc ◽  
Leidy Isenalumhe ◽  
Hayder Saeed ◽  
Celeste Bello ◽  
Bijal Shah ◽  
...  
Keyword(s):  
B Cell ◽  
Board Of Directors ◽  
Fdg Pet ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Advisory Committees ◽  
End Of Treatment

Introduction: 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) remains the standard of care for baseline and end of treatment scans for aggressive non-Hodgkin lymphomas (NHLs). However, the role of interim FDG-PET remains not as well defined across aggressive NHLs, especially in the era of high-intensity chemoimmunotherapy. Interim FDG-PET (iPET) can serve as an early prognostic tool, and prior studies evaluating the utility of iPET-guided treatment strategies primarily focused on diffuse large B-cell lymphomas (DLBCL) and frontline R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Classification criteria systems assessing response also differ between studies with no clear consensus between use of Deauville criteria (DC), International Harmonization Project (IHP), and the ΔSUVmax method. Methods: This study evaluates our institutional experience with iPET during treatment with DA-EPOCH ± R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin with or without Rituximab) in aggressive NHLs. We retrospectively evaluated 70 patients at Moffitt Cancer Center who started on DA-EPOCH ± R between 1/1/2014 to 12/31/2018 for aggressive NHLs. Response on interim and end-of-treatment (EOT) scans were graded per DC, IHP, and ΔSUVmax methods, and progression free survival (PFS) probability estimates were calculated with chi-square testing and Kaplan Meier method. PFS outcomes were compared between interim negative and positive scans based on each scoring method. Outcomes were also compared between groups based on interim versus EOT positive or negative scans. Results: We identified 70 patients with aggressive NHLs who received DA-EPOCH ± R at our institute. The most common diagnoses were DLBCL (61%) followed by Burkitt's lymphoma (10%), primary mediastinal B-cell lymphoma (9%), plasmablastic lymphoma (7%), gray zone lymphoma (6%), primary cutaneous large B-cell lymphoma (1%), primary effusion lymphoma (1%), and other high-grade NHL not otherwise specified (3%). Of the 43 patients with DLBCL, 21/43 (49%) had double hit lymphoma (DHL) while 7/43 (16%) had triple hit lymphoma (THL), and 3/43 (7%) had MYC-rearranged DLBCL while 2/43 (5%) had double expressor DLBCL. Thirty nine out of 70 (56%) were female, and median age at diagnosis was 58.39 years (range 22.99 - 86.86 years). Most patients had stage IV disease (49/70, 70%), and 43/70 (61%) had more than one extranodal site while 45/70 (64%) had IPI score ≥ 3. Forty-six out of 70 (66%) received central nervous system prophylaxis, most with intrathecal chemotherapy (44/70, 63%). Fifty-five out of 70 (79%) had iPET available while 6/70 (9%) had interim computerized tomography (CT) scans. Fifty-six out of 70 (80%) had EOT PET, and 4/70 (6%) had EOT CT scans. Sustained complete remission occurred in 46/70 (66%) after frontline DA-EPOCH ± R (CR1), and 12/70 (17%) were primary refractory while 5/70 (7%) had relapse after CR1. Four of 70 (6%) died before cycle 3, and 3/70 (4%) did not have long-term follow-up due to transition of care elsewhere. Median follow-up was 15.29 months (range 0.85 - 60.09 months). There was significantly better PFS observed if iPET showed DC 1-3 compared to DC 4-5 (Χ2=5.707, p=0.0169), and PFS was better if iPET was negative by IHP criteria (Χ2=4.254, p=0.0392) or ΔSUVmax method (Χ2=6.411, p=0.0113). Comparing iPET to EOT PET, there was significantly better PFS if iPET was negative with EOT PET negative (iPET-/EOT-) compared to iPET positive with EOT negative (iPET+/EOT-), and iPET+/EOT+ and iPET-/EOT+ had worse PFS after iPET-/EOT- and iPET+/EOT- respectively. This pattern in iPET/EOT PFS probability remained consistent when comparing DC (Χ2=30.041, p<0.0001), IHP (Χ2=49.078, p<0.0001), and ΔSUVmax method (Χ2=9.126, p=0.0104). These findings fit clinical expectations with positive EOT scans indicating primary refractory disease. There was no significant difference in PFS when comparing DLBCL versus non-DLBCL (Χ2=3.461, p=0.0628) or DHL/THL versus non-DHL/THL diagnoses (Χ2=2.850, p=0.0914). Conclusion: Our findings indicate a prognostic role of iPET during treatment with DA-EPOCH ± R for aggressive NHLs. Significant differences in PFS were seen when graded by DC, IHP, and ΔSUVmax methods used in prior studies and when comparing interim versus EOT response. Larger studies are needed to confirm these findings. Disclosures Bello: Celgene: Speakers Bureau. Shah:Novartis: Honoraria; AstraZeneca: Honoraria; Spectrum/Astrotech: Honoraria; Adaptive Biotechnologies: Honoraria; Pharmacyclics: Honoraria; Jazz Pharmaceuticals: Research Funding; Incyte: Research Funding; Kite/Gilead: Honoraria; Celgene/Juno: Honoraria. Sokol:EUSA: Consultancy. Chavez:Janssen Pharmaceuticals, Inc.: Speakers Bureau; Genentech: Speakers Bureau; Kite Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees.

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