Has the Incidence of Extramedullary Disease Changed with the New Therapeutic Approaches? Analysis of a Cohort of 965 Multiple Myeloma (MM) Patients (pts).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4749-4749
Author(s):  
Marzia Varettoni ◽  
Alessandro Corso ◽  
Gianmatteo Pica ◽  
Patrizia Zappasodi ◽  
Silvia Mangiacavalli ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Time ◽  
Response To Therapy ◽  
Response To Treatment ◽  
High Dose ◽  
Solitary Plasmacytoma ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Over Time

Abstract Extramedullary myeloma (EMM) at diagnosis or during the course of the disease is rare and often anecdotal. We reviewed the records of 965 consecutive MM pts diagnosed and followed from 1969 to July 2007 in order to evaluate: the overall incidence of EMMs and the changes over time clinical presentation, response to treatment and outcome of EMM pts divided into two subgroups according to the time of appearance, at diagnosis or during the course of the disease. We considered three periods: 1969–1989 (conventional chemotherapy, CCT); 1990–1999 (introduction of high-dose therapy, HDT); 2000–2007, (era of novel agents). The overall incidence of EMM was of 13% (129/965 pts), 87/42 M/F, median age 58 (31–80) years. A prior MGUS was present in 24 pts and a solitary plasmacytoma in 10 (8%). Characteristics at the time of EMM were: 77 pts IgG (60%), 23 IgA (18%), 2 IgM (2%), 16 light chain (12%), 11 not secretory (8%); 29 pts were in stage I, 14 in stage II, 86 in stage III; 30/129 pts (23%) were asymptomatic. More frequently involved sites were: paravertebral (40%), rib cage (32%), pelvis (10%). Multiple localizations were present in 27 pts (21%). A plasmacytic leukemia was observed during the follow-up in 9 pts (7%). The overall median follow-up was 24.4 (2.5–148) months. Seventy-three pts presented EMM at the time of diagnosis with different incidences in the 3 periods: 1969–1989 4.5%, 1990–99 4.3%, 2000–07 12.7%. These pts were treated with HDT in 43 cases (59%) and CCT in 30 (41%). Radiotherapy (RT) was associated in 38 pts (52%). A partial response (PR) was achieved in 49 pts (67%). Progression or relapse were observed in 46 pts (63%) and the median time to progression (TTP) and overall survival (OS) in this subgroup of pts were 17.3 and 21.5 months respectively. The other 56 pts showed an EMM during the course of the disease after a median time of 20 (2–144) months from diagnosis. EMM incidence varied as follows: 1969–1989 2.7%, 1990–99 7.2%, 2000–07 7.4%. Median number of previous lines of therapy was 1 (range: 1–7), including HDT in 22 pts (39%), thalidomide or lenalidomide in 18 (32%), bortezomib in 5 (9%). The median time from HDT to EMM was 17 (2–125) months. Treatment of these pts consisted of CCT in 36 cases (64%), thalidomide in 3 (5%) and bortezomib in 8 (14%). RT was given in 29 cases (52%). Response rate in this subgroup was low, only 30% of pts obtained a PR. The median TTP and OS from the time of appearance of EMM were 4.7 and 6.5 months respectively and the overall survival from the diagnosis was 29.9 months. The two groups of EMM pts were also compared for all the clinical characteristics, response to therapy and outcome. EMM pts at diagnosis showed higher levels of monoclonal component and haemoglobin, and lower bone marrow plasmacytosis with respect to the others. OS from diagnosis was similar in the two groups. In conclusion, our study shows an increased incidence of EMM over time. The more recent increase of EMM at diagnosis might be due to the wider use of more sensitive imaging techniques as CT scan and magnetic resonance, while during the course of the disease after 1990 could be related to the longer survival of pts thanks to the new therapeutic approaches. Anyway, the presence of EMM whether at diagnosis or at progression seems to negatively affect the outcome of pts since the OS is shorter than MM pts without EMM.

scholarly journals Clinical Characteristics, Treatment Patterns and Outcomes of Solitary Plasmacytoma - a Multicenter Retrospective Cohort Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3180-3180
Author(s):  
Svetlana Trestman ◽  
Chezi Ganzel ◽  
Shai Levi ◽  
Moshe E. Gatt ◽  
Noa Lavi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Time ◽  
Real World ◽  
Clinical Characteristics ◽  
Treatment Patterns ◽  
High Dose ◽  
Solitary Plasmacytoma ◽  
Fdg Uptake ◽  
Post Therapy

Background: Solitary plasmacytoma (SPC) is a rare plasma cells disorder, which may present as a single bone lesion or an extramedullary plasmacytoma. High dose radiotherapy may be curative, yet most patients eventually develop Multiple Myeloma (MM). Due to rarity of the disease, there is uncertainty regarding the optimal treatment strategy, especially in patients that present with known risk factors. The role of adjuvant anti-myeloma therapy is still under debate, whereas few studies have reported efficacy of novel agents. We aimed to explore clinical characteristics and treatment patterns and to identify predictors for relapse and progression to myeloma in a real world setting. Methods: Consecutive patients, diagnosed and treated for solitary plasmacytoma in 13 centers, between 2008 and 2019 (defined by the IMWG criteria) were identified, based on medical centers patient registries and pathological reports. Patient's medical charts were reviewed, and data regarding patient and disease characteristics, treatment regimen, and clinical endpoints, focusing on response to treatment and time to disease progression were documented. The treatment response categories were defined according to the IMWG criteria. Results: 62 patients (pts) were identified. Baseline characteristics and workup are detailed in the table. Median follow-up was 39 months (mo) (IQR: 13.5, 63.3). Fifty nine pts (95.2%) were treated with radiotherapy, with a median dose of 45.0 Gy (range: 30-54 Gy); radiotherapy dose was 45-54 in 31 pts, < 45Gy in 11 pts. Twenty pts (33.9%) underwent surgery in addition to radiotherapy, 3 more pts underwent a surgery alone. The median time to radiotherapy since diagnosis was 2.7 months (range: 1day-18.2 months), 8 pts received any anti-myeloma therapy for treatment of plasmacytoma including Melphalan/dexamethasone (n=1), bortezomib based induction followed by ASCT (n=2), VD/VTD (n=2) and KRD (n=1). Among 25 patients with evaluable post-therapy PET-CT response (performed 12 months post radiotherapy), 26% had no remaining FDG uptake, 20% had a 50% or greater decrease in FDG uptake. Among 40 patients with CT or MRI post therapy assessment, 20% had disappearance of SPC, 27% had ≥50% reduction, 7% had <50% reduction and 25% remained without change. Non-bone SPC were more likely to achieve CR than bone SPCs, 86% vs 29%, respectively, p=0.021. During the follow-up period, 16 pts (25.8%) experienced evolution to MM (15 pts had bony and 1 soft tissue plasmacytoma in diagnosis). Among patients with bone SPC (n=49), 30.5% evolved to MM. A total of 6 pts had a recurrence of SPC (5 pts had a bony and 1 patient upper aerodigestive plasmacytoma in diagnosis). 5 pts died (3 without recurrence or evolution to MM). Median time to plasmacytoma recurrence in pts that achieved CR was 36.7 mo (range: 3 -67.9 mo); Median time of evolution to MM was 37.5 mo (range: 6.7-87.2 mo). Progression free survival (PFS) was 67.7 mo for all pts (Fig1A), 48 mo for bone SPC and was not reached for non-bone SPC (p=0.11) (Fig1B). Median overall survival was not reached. Overall survival at median follow-up was 93.6%. Notably, all 8 pts who were treated with anti-myeloma therapy had a bony plasmacytoma and received radiotherapy in addition. None of these pts had recurrence of plasmacytoma or evolution to MM. Of the 11 pts that had SPC in an upper aerodigestive tract site, none evolved to MM; 10 of these pts were treated with only radiotherapy, one had a plasmacytoma recurrence in the same site. Conclusions: We present real world data of a multicenter patient cohort with SPC. As previously suggested, prognosis is more favorable for none bone SPCs. Though numbers are modest, our analysis suggests a benefit of the early addition of systemic therapy to standard radiotherapy for patients with solitary bone plasmacytoma. Disclosures Yael: Janssen: Consultancy; Amgen: Consultancy, Research Funding; Neopharm: Consultancy; Takeda: Consultancy; Madison: Consultancy; VBL Therapeutics: Employment.

Durable Remission with Salvage Autotransplants in Patients with Multiple Myeloma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1227-1227
Author(s):  
Nina Shah ◽  
Khawaja Fraz Ahmed ◽  
Sofia Qureshi ◽  
Jatin Shah ◽  
Robert Z Orlowski ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Median Time ◽  
Chromosomal Abnormalities ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Remission Duration

Abstract Abstract 1227 Poster Board I-249 Background In comparison with single autologous hematopoietic stem cell transplantation (auto HCT), tandem autologous HCT has resulted in longer event-free and overall survival in randomized trials for patients with newly diagnosed multiple myeloma (MM). Most myeloma patients, however, only receive a single auto HCT. Many of these patients are eligible for a second auto HCT as salvage at the time of relapse. We evaluated the outcome of salvage auto HCT for MM patients treated at our institution. Methods We performed a retrospective chart review and identified 62 MM patients (38 males, 24 females) who received a second auto HCT as salvage between 1/3/1992 and 11/4/2008.. Preparative regimen was high-dose melphalan alone or in combination with other chemotherapy agents, including busulfan, topotecan and bortezomib. Three patients received a combination of thiotepa, busulfan and cyclophosphamide. Results Median interval between the first and salvage auto HCT was 21 months (range 2-81). Median age at salvage HCT was 55 years (37-73) and median prior treatment regimens were 4 (range 2-16). Twelve patients had chromosomal abnormalities on conventional cytogenetic studies. Patients received a median CD34 cell dose of 4 ×106 / kg (range 2.3-11.2). Fourteen patients (22%) experienced grade 3 or higher toxicity after the salvage auto HCT. Two patients died within 100 days with a TRM of 3%. Median time to neutrophil engraftment was 10 days (8-38). Responses after salvage auto HCT were as follows: CR+ near CR 15%, PR 48%, with an overall response rate of 63%. Twenty-seven (44%) patients received post auto HCT maintenance therapy. Median follow-up from salvage HCT was 25 months. Kaplan-Meier estimates of median progression-free survival and overall survival (OS) were 15.5 and 43.3 months, respectively. Median time to progression after the first and salvage auto HCT was 20 and 12 months, respectively, with total remission duration of 32 months from two HCTs. Median OS from the time of diagnosis was 72 months, comparable to reported results with tandem auto HCT. At last follow up, 20 patients were alive and in remission. Conclusions In selected MM patients a second auto HCT for salvage therapy is well tolerated with acceptable toxicity. The combined remission duration and overall survival are comparable to outcomes with tandem autotransplants. Disclosures Qazilbash: Cephalon: Speakers Bureau.

scholarly journals Japan Scar Workshop (JSW) Scar Scale (JSS) for Assessing Keloids and Hypertrophic Scars

2020 ◽  
pp. 133-140
Author(s):  
Rei Ogawa
Keyword(s):  
Hypertrophic Scar ◽  
Assessment Tool ◽  
Treatment Method ◽  
Response To Therapy ◽  
Assessment Scale ◽  
Response To Treatment ◽  
Hypertrophic Scars ◽  
Scar Assessment ◽  
Appropriate Treatment

AbstractThe Vancouver scar scale, the Manchester scar scale, and the Patient and Observer Scar Assessment Scale (POSAS) are all very well-known scar evaluation methods. These tools are based on a number of scar variables, including color, height, and pliability. However, since all were mainly developed to evaluate burn scars, they are difficult to use in clinical practice for keloids and hypertrophic scars. This is because these pathological scars require both differential diagnosis and a way to evaluate their response to therapy. The Japan Scar Workshop (JSW) has sought to develop a scar assessment scale that meets these clinical needs. The first version of this scar assessment tool was named the JSW scar scale (JSS), and it was reported in 2011. In 2015, the revised second version was reported. The JSS consists of two tables. One is a scar classification table that is used to determine whether the scar is a normal mature scar, a hypertrophic scar, or a keloid. This grading system helps the user to select the most appropriate treatment method for the scar. The other table in the JSS is an evaluation table that is used to judge the response to treatment and for follow-up. Both tables contain sample images of each subjective keloid/hypertrophic scar item that allow the user to evaluate each item without hesitation.

scholarly journals Survival in Patients Who Underwent HLA-Haploidentical Stem Cell Transplantation in Two Centers in Colombia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 32-32
Author(s):  
Lisbeth Ramirez ◽  
Juan Manuel Herrera ◽  
Angela María Peña ◽  
Maria Luna-Gonzalez ◽  
Claudia Marcela Chalela ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Retrospective Study ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Median Time ◽  
Clinical Characteristics ◽  
High Dose ◽  
Post Transplantation ◽  
Hematopoietic Stem

Introduction: Allogeneic hematopoietic stem cell transplantation (HCT) is a potentially curative treatment for several malignant and non-malignant hematological diseases. However, sometimes it is challenging to find human leukocyte antigen (HLA)-matched related or unrelated donors, especially in minority populations such as Hispanics. Transplantation of T cell replete HLA haploidentical graft (HaploHCT) followed by a high dose post-transplantation cyclophosphamide (PTCy) to eradicate alloreactive T cells is an option for populations with low donor availability. HaploHCT has emerged as an effective and safe strategy in this population (Luznik L et al. BBMT 2008), but data in Hispanics is scarce. Objective: The aim of our study was to describe the clinical characteristics and assess overall survival at 100 days, 1- and 3-years of patients who underwent haploHCT in two Colombian reference centers. Methods: An observational retrospective study was conducted at two tertiary referral centers in Colombia. Patients who underwent haploHCT at Clinica FOSCAL and Centro Medico Imbanaco between January 2013 and January 2020 were selected. Demographic and clinical characteristics where analyzed using descriptive statistics. The Kaplan-Meier method was used to assess overall survival (OS) rates and the log-rank test was used to compare survival rates between groups. All data were analyzed using R statistical software®. Results: Seventy-six patients were included. Mean age at transplantation was 34 years (range 18-60). Forty-two (57.89%) patients were female. Average body mass index was 19.86kg/m2. The majority of patients (57%) had a pre-transplantation ECOG performance status of 2. The most common indication for haploHCT was acute lymphoblastic leukemia (55.26%), followed by acute myeloid leukemia (23.64%). A sibling was the donor in 69.74% of the cases. Forty-seven (61.84%) patients were ABO-matched group. Peripheral blood stem cells were the graft source in 96% of the patients. The average number of infused CD34+ cells was 11.15 x 106/kg. Fludarabine-melphalan was the most commonly used conditioning regimen (57%), followed by fludarabine-busulfan-thiotepa (39%). Graft-versus-host disease (GVHD) prophylaxis consisted of PTCy (50 mg/kg/day) on days 3 and 4 after HCT and a calcineurin inhibitor plus mycophenolate mofetil from day 5 to day 35 post-HCT. Median time to neutrophil engraftment (neutrophils &gt; 0,5x109/L) was 15 days (range 10-33), while platelet engraftment, defined as as the second day of unsupported platelet count of ≥20 × 109, occurred at a median time of 13 days (range 5-38) post-transplantation. On day 28 post-HSCT, 93.4% of the patients had achieved 100% chimerism. OS was 91% (95%CI 84-97.5) at 100 days, 81% (95%CI 72-90) at 1-year, and 77% (95%CI 68-88) at 3-years after HaploHCT. C onclusion: The results of our haploHCT retrospective study in a Hispanic population are comparable to several other cohorts that have reported similar outcomes of haploHCT compared to HLA-matched HCT. The OS rates reported in our study suggest that haploHCT is a viable option in patients without an HLA-matched related or unrelated donor available, especially in populations with lower rates of suitable donors. Acknowledgements: We deeply thank Gonzalo Gutiérrez García, M.D. for his leadership and guidance implementing the haploHCT program in Clinica FOSCAL. Disclosures Peña: Roche: Honoraria. Salazar:Janssen: Honoraria; Novartis: Honoraria. Sandoval-Sus:MorphoSys US: Consultancy; Janssen: Consultancy; Massive Bio: Consultancy; Celgene: Speakers Bureau. Sossa:Novo: Honoraria; Takeda: Honoraria; Astellas: Honoraria; Roche: Honoraria.

Clinical, Endocrine and Imaging Characteristics of Patients with Primary Hypophysitis

2018 ◽  
Vol 50 (04) ◽  
pp. 296-302 ◽  
Author(s):  
Anna Angelousi ◽  
Carolina Cohen ◽  
Soledad Sosa ◽  
Karina Danilowicz ◽  
Lina Papanastasiou ◽  
...  
Keyword(s):  
Natural History ◽  
Immunosuppressive Agents ◽  
Hormonal Treatment ◽  
Response To Treatment ◽  
High Dose ◽  
Partial Recovery ◽  
Gonadal Dysfunction ◽  
Imaging Characteristics ◽  
Primary Hypophysitis

AbstractPrimary hypophysitis (PH) is a rare disease with a poorly-defined natural history. Our aim was to characterise patients with PH at presentation and during prolonged follow-up. Observational retrospective study of 22 patients was conducted from 3 centres. In 14 patients, PH was confirmed histologically and in the remaining 8 clinically, after excluding secondary causes of hypophysitis. All patients had hormonal and imaging investigations before any treatment. Median follow up was 48 months (25–75%: 3–60). There was a female predominance with a female/male ratio: 3.4:1. Eight out of 22 patients had another autoimmune disease. Headaches and gonadal dysfunction were the most common symptoms. Five patients presented with panhypopituitarism; 17 patients had anterior pituitary deficiency, and 7 had diabetes insipidus. At presentation, 9 patients were treated surgically, 5 received replacement hormonal treatment, and 8 high-dose glucocorticoids from whom 5 in association with other immunosuppressive agents. Six patients showed complete recovery of pituitary hormonal deficiencies while 6 showed a partial recovery during a 5-year follow-up period. No difference was found between patients treated with surgery and those treated medically. The overall relapse rate was 18%. PH can be manifested with a broad spectrum of clinical and hormonal disturbances. Long-term follow-up is required to define the natural history of the disease and response to treatment, since pituitary hormonal recovery or relapse may appear many years after initial diagnosis. We suggest that surgery and immunosuppressive therapy be reserved for exceptional cases.

Final overall survival in the phase 3 NETTER-1 study of lutetium-177-DOTATATE in patients with midgut neuroendocrine tumors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4112-4112
Author(s):  
Jonathan R. Strosberg ◽  
Martyn E Caplin ◽  
Pamela L. Kunz ◽  
Philippe B Ruszniewski ◽  
Lisa Bodei ◽  
...  
Keyword(s):  
Overall Survival ◽  
Neuroendocrine Tumors ◽  
High Dose ◽  
Radioligand Therapy ◽  
Phase 3 ◽  
Long Term Follow Up ◽  
Long Acting ◽  
Safety Signals

4112 Background: As demonstrated in the primary analysis of the phase 3 NETTER-1 trial, 177Lu-DOTATATE significantly prolonged progression-free survival (PFS) versus high-dose long-acting octreotide, with a HR of 0.18 (95% CI: 0.11, 0.29; p < 0.0001), in patients with advanced, progressive, well-differentiated, somatostatin receptor-positive midgut neuroendocrine tumors (NETs). Here we report final overall survival (OS) for NETTER-1. Methods: In this international open-label trial, eligible patients were randomized to receive either four cycles of 177Lu-DOTATATE 7.4 GBq (200 mCi) every 8 ± 1 weeks plus long-acting octreotide 30 mg or high-dose long-acting octreotide 60 mg every 4 weeks (control arm), both on top of best supportive care. After disease progression on randomized treatment or completion of an 18-month treatment period, patients in both arms entered long-term follow-up and could receive further anti-cancer treatment as recommended by their physicians. The primary endpoint was PFS per RECIST 1.1 and OS was a key secondary endpoint. Primary intention-to-treat analysis of OS was prespecified to take place after 158 deaths or 5 years after the last patient was randomized, whichever occurred first. Results: Of 231 randomized patients, 101/117 (86.3%) in the 177Lu-DOTATATE arm and 99/114 (86.8%) in the control arm entered long-term follow-up. Final analysis occurred 5 years after the last patient was randomized, following 142 deaths, with a median follow-up of more than 76 months. During long-term follow-up, 41/114 (36%) of patients in the control arm received subsequent radioligand therapy (“cross-over”), the majority (22.8%) within 24 months. Median OS was 48.0 months (95% CI: 37.4, 55.2) in the 177Lu-DOTATATE arm and 36.3 months (95% CI: 25.9, 51.7) in the control arm. HR was 0.84 (95% CI: 0.60, 1.17) with p = 0.30 (unstratified 2-sided log-rank test). A total of 2/112 (1.8%) 177Lu-DOTATATE treated patients in the study developed myelodysplastic syndrome (MDS). No new cases of MDS or acute leukemia were reported in the long-term follow-up. Overall, no new safety signals emerged during long-term follow-up. Conclusions: Median OS was 48.0 months in the 177Lu-DOTATATE arm of the NETTER-1 trial and 36.3 months in the control arm. This difference was not statistically significant, potentially impacted by a high rate (36%) of cross-over of patients in the control arm to radioligand therapy after progression. In overall conclusion, the NETTER-1 study demonstrated that 177Lu-DOTATATE yielded a clinically and statistically significant improvement in PFS as a primary endpoint (HR: 0.18, p < 0.0001) as well as a clinically meaningful trend towards improvement in median OS of 11.7 months. No new safety signals emerged during the 5-year long-term follow-up. Clinical trial information: NCT01578239.

scholarly journals Clinicopathological Features, Risk Factors and Predispositions, and Response to Treatment of Eosinophilic Oral Disease in 24 Dogs (2000-2016)

2019 ◽  
Vol 36 (1) ◽  
pp. 25-31
Author(s):  
Danielle Mendelsohn ◽  
John R. Lewis ◽  
Kristin Iglesias Scott ◽  
Dorothy C. Brown ◽  
Alexander M. Reiter
Keyword(s):  
Risk Factors ◽  
Body Weight ◽  
Clinicopathological Features ◽  
Response To Therapy ◽  
Oral Disease ◽  
Response To Treatment ◽  
Inclusion Criteria ◽  
Lesion Location ◽  
Referral Practice

The objectives of this study were to retrospectively describe clinicopathological features of eosinophilic oral disease in dogs, to identify possible risk factors or predispositions to the condition, and to report overall treatment response. Canine medical records from a veterinary teaching hospital and private referral practice over a 17-year period were reviewed for a diagnosis of eosinophilic oral disease. Twenty-four dogs with 26 lesions met the inclusion criteria. Patient mean age and body weight were 6.8 (3.8) years and 13.4 kg, respectively. Fifteen breeds were represented including Cavalier King Charles spaniel (16.7%), Labrador retriever (12.5%), and West Highland white terrier (12.5%). Eosinophilic lesions were found in the palate (65.4%), tongue (26.9%), and other oral locations (7.7%). Median follow-up time was 5 months. Analysis revealed statistically significant associations between lesion location and body weight (palatal and tongue lesions were more likely in smaller dogs, whereas lesions in the other category [lip or mucosa] were more likely in larger dogs). There was a correlation in lesion location and resolution (all dogs with palatal lesions became asymptomatic at their last recheck), and resolution and the use of antibiotics plus prednisone (greater likelihood of resolution without the use of this combination). Seventy percent of asymptomatic dogs resolved without medication or with allergen therapy alone, suggesting that asymptomatic dogs may respond well to conservative management. No associations were found between lesion location and breed, signalment and response to therapy, lesion resolution and the use of glucocorticoids, or significance of peripheral eosinophilia.

scholarly journals P1795ASSOCIATION BETWEEN T CELL INFILTRATION IN BIOPSY PROVEN ACUTE T CELL MEDIATED REJECTION AND RESPONSE TO THERAPY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Nooshin Dalili ◽  
Pedram Ahmadpoor ◽  
Behzad Einollahi ◽  
Hamed Azhdari Tehrani
Keyword(s):  
T Cell ◽  
Graft Function ◽  
Stable Condition ◽  
Response To Therapy ◽  
Response To Treatment ◽  
P Value ◽  
Organ Rejection ◽  
Graft Outcome ◽  
Significant Difference

Abstract Background and Aims Renal transplantation is considered as the best replacement therapy for advanced ESRD patients. An allograft rejection happens as a result of post transplant immune reactions, which change the outcome of the organ transplantation. Today a major challenge in the field of transplantation is the identification of easy, reliable and non-invasive markers or methods that being able to predict the probability of organ rejection. One of the possible methods is looking for type of infiltrated cells in tissue obtaining by biopsy stained with specific cellular markers and assesses the infiltration of these cells in different types of rejection. Here the severity of CD3, CD20, Th17 and FOXP3 infiltration in patients with biopsy proven acute cellular rejection was evaluated based on IHC staining, whether these specific infiltrations can show an association with graft outcome or not. Method 50 patients with biopsy proven Acute T Cell Mediated Rejection (ATCMR) recruited. Previous clinical data and 1 year clinical follow up collected. The entire specimen assessed for infiltration of CD3, CD20, FOXP3 Tregs and Th17 with IHC. Patients divided into subgroups: stable graft function versus impaired graft function based on serum creatinine course in one year follow up after rejection therapy and appropriate response to treatment versus failure to response, based on allograft function throughout the course of admission. Results In impaired graft function arm, FOXP3 (7.88 vs. 8.02 with P-value 0.96) and Th17 cells were higher (5.01 vs. 10.2 with P-value 0.24) but with non-significant values. FOXP3/Th17 ratio was higher in stable group (1.4 vs. 1.12 with P-value 0.22). In failure to response to therapy group both FOXP3 (9.95 vs. 6.63 with P-value 0.1) and Th17 (11.3 vs. 8.3 with P-value 0.15) cells were higher. FOXP3/Th17 ratio was higher in proper response group (1.19 vs. 1.15 with P-value 0.8). No significant difference was obtained between CD3 and CD20 infiltration in these two groups. Conclusion Final results showed that Th17 has more important role in predicting the graft outcome and response to treatment and FOXP3 infiltration had a minor part. This may be in controversial with previous facts about the role of FOXP3 cells, which drive the allograft into stable condition.

Sarcomatoid Renal Cell Carcinoma: Biologic Behavior, Prognosis, and Response to Combined Surgical Resection and Immunotherapy

1999 ◽  
Vol 17 (2) ◽  
pp. 523-523 ◽  
Author(s):  
Thomas Cangiano ◽  
Joseph Liao ◽  
John Naitoh ◽  
Frederick Dorey ◽  
Robert Figlin ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Cell Carcinoma ◽  
Surgical Resection ◽  
Median Duration ◽  
Renal Cell ◽  
High Dose ◽  
Risk Of Death

PURPOSE: Sarcomatoid variants of renal cell carcinoma (RCC) are aggressive tumors that respond poorly to immunotherapy. We report the outcomes of 31 patients with sarcomatoid RCC treated with a combination of surgical resection and immunotherapy. PATIENTS AND METHODS: Patients were identified from the database of the University of California Los Angeles Kidney Cancer Program. We retrospectively reviewed the cases of 31 consecutive patients in whom sarcomatoid RCC was diagnosed between 1990 and 1997. Clinical stage, sites of metastasis, pathologic stage, and type of immunotherapy were abstracted from the medical records. The primary end point analyzed was overall survival, and a multivariate analysis was performed to distinguish any factors conferring an improved survivorship. RESULTS: Twenty-six percent of patients were male and 74% were female, and the median age was 59 years (range, 34 to 73 years). Length of follow-up ranged from 2 to 77 months (mean, 21.4 months). Twenty-eight patients (84%) had known metastases at the time of radical nephrectomy (67% had lung metastases and 40% had bone, 21% had liver, 33% had lymphatic, and 15% had brain metastases). Twenty-five patients (81%) received immunotherapy, including low-dose interleukin (IL)-2–based therapy (five patients), tumor-infiltrating lymphocyte–based therapy plus IL-2 (nine patients), high-dose IL-2–based therapy (nine patients), dendritic cell vaccine–based therapy (one patient), and interferon alpha–based therapy alone (one patient). Two patients (6%) achieved complete responses (median duration, 46+ months) and five patients (15%) achieved partial responses (median duration, 36 months). One- and 2-year overall survival rates were 48% and 37%, respectively. Using a multivariate analysis, age, sex, and percentage of sarcomatoid tumor (< or > 50%) did not significantly correlate with survival. Improved survival was found in patients receiving high-dose IL-2 therapy compared with patients treated with surgery alone or any other form of immunotherapy (P = .025). Adjusting for age, sex, and percentage of sarcomatoid tumor, the relative risk of death was 10.4 times higher in patients not receiving high-dose IL-2 therapy. Final pathologic T stage did not correlate significantly with outcome, but node-positive patients had a higher death rate per year of follow-up than did the rest of the population (1.26 v 0.76, Cox regression analysis). CONCLUSION: Surgical resection and high-dose IL-2–based immunotherapy may play a role in the treatment of sarcomatoid RCCs in select patients.

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