scholarly journals Nasalis típusú extranodalis natural killer T-sejtes lymphoma hazai előfordulása és kezelésével szerzett tapasztalatok

2017 ◽  
Vol 158 (41) ◽  
pp. 1635-1641
Author(s):  
Annamária Bakos ◽  
Árpád Szomor ◽  
Tamás Schneider ◽  
Zsófia Miltényi ◽  
Imelda Marton ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
Treatment Strategies ◽  
Second Line ◽  
Upper Aerodigestive Tract ◽  
Second Line Therapy ◽  
Hematopoietic Stem ◽  
Non Hodgkin Lymphoma ◽  
Line Therapy ◽  
Natural Killer T

Abstract: Introduction: Extranodal natural killer/T (NK/T) cell lymphoma, nasal type (ENKTL) represents a rare subtype of T-cell lymphomas with aggressive clinical behavior according to WHO 2016 classification. Aim: ENKTL has distinctive geographic distribution with higher incidence in Asia and Latin America (10% of all non-Hodgkin lymphoma cases), than in Europe and North America (<1%). ENKTL tipically origins from nasopharynx and upper aerodigestive tract. Anthracycline-based chemotherapy regimens are largely ineffective in the treatment of ENKTL. Method: Our aims were to evaluate the incidence and treatment strategies of ENKTL patients in Hungarian Haematological Centres between 2003 and 2015. Altogether 20 patients with ENKTL were treated in the 4 haematological hospitals (male:female ratio 12:8, with median 49.5 years of age). Results: Ten patients had localized (stage I–II) disease at the time of the diagnosis. Seventeen patients were treated with chemotherapy (11/CHOP, CHOP-like, 2/HyperCVAD, 1/ProMACECytaBom, 1/SMILE, 2/others), which was completed with involved-field radiation therapy (IFRT) (40–46 Gy) in 6 cases were used. After first-line therapy 9 patients achieved complete remission (CR), 3 patients had partial remission (PR), 3 patients had progressive disease (PD), and 2 patients had stable disease (SD). Median follow-up was 32 (3–113) months. Five patients received second-line therapy for progressive or recurrent disease [2/DHAP, 1/VIM, 1/HyperCVAD, 1/ProMACECytaBom]. None of the patients achieved CR after second-line therapy. Two patients have undergone autologous hematopoietic stem cell transplantation (HSCT) after the first CR. Conclusion: ENKTL treatment is more effective with nonanthracycline-containing regimens. L-asparaginase containing chemotherapy and concurrent or sequential chemo-radiotherapy improves survival and CR rates. Orv Hetil. 2017; 158(41): 1635–1641.

Primary cardiac natural killer/T-cell lymphoma, a very rare form of lymphoma

2018 ◽  
Vol 27 (3) ◽  
pp. 210-212 ◽  
Author(s):  
Frank Farfán-Leal ◽  
Amparo Esteban ◽  
Rocío Hinojar ◽  
Mónica García-Cosío ◽  
Francisco Contreras
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
Cell Lymphoma ◽  
Clinical Manifestations ◽  
T Cell Lymphoma ◽  
Lower Survival Rate ◽  
Natural Killer T Cell ◽  
Non Hodgkin Lymphoma ◽  
Killer T Cell ◽  
Natural Killer T

Extranodal natural killer/T-cell lymphoma is a rare non-Hodgkin lymphoma that is divided into nasal, non-nasal, and aggressive/leukemia subtypes, according to anatomic origin and clinical manifestations, with each subtype carrying a different prognosis. We present a case of primary cardiac natural killer/T-cell lymphoma with extension to other organs in a 38-year-old man, to highlight the role of imaging in categorizing nasal versus non-nasal types. This distinction has relevant implications for patient care because the non-nasal type has a much lower survival rate.

Allogeneic Myeloablative Hematopoietic Stem Cell Transplantation for Chronic Myelogenous Leukemia in the Imatinib Era.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 970-970
Author(s):  
Jiri Pavlu ◽  
Matthias Klammer ◽  
Ian Gabriel ◽  
Richard Szydlo ◽  
Eduardo Olavarria ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Scoring System ◽  
Chronic Phase ◽  
Myelogenous Leukemia ◽  
Prognostic Scores ◽  
Second Line ◽  
Second Line Therapy ◽  
Hematopoietic Stem ◽  
Line Therapy

Abstract Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is no longer the first treatment option for patients with chronic myelogenous leukemia (CML) but there is a considerable debate about its use as a second line therapy. When used in this indication the second-generation tyrosine kinase inhibitors (2G-TKI) induce complete cytogenetic responses (CCyR) in 40–50% of patients in chronic phase but those without CCyR are unlikely to benefit in long term. It is therefore important to identify groups of patients with a good outcome after transplantation so that this may be offered as second line therapy where appropriate. The outcome of allo-SCT has improved over time so we restricted our analysis to the most recent 8 years to coincide with the introduction of imatinib into clinical practice. 131 patients received myeloablative transplants from January 2000 till December 2007. 67 patients were transplanted in chronic phase (14 in second and 2 in third chronic phase), 46 in accelerated phase and 2 in blastic phase. Forty-nine patients received imatinib at some point prior to transplantation and 30 of these experienced failure of imatinib therapy (as defined by European LeukemiaNet criteria). Conditioning consisted of cyclophosphamide and total body irradiation for 51 recipients of sibling stem cells. In addition in vivo T cell depletion with anti CD52 antibody (Campath 1H) was used for 80 unrelated donor transplants. The median age of the patients was 33.4 (15 to 56) years and the median disease duration at transplant was 13 (2 to 105) months. The probability of overall survival (OS) at 3 and 5 years was 64.8% and 62.6% respectively. We confirmed the prognostic value of the EBMT risk assessment score (Gratwohl) and pretransplant level of the C-reactive protein (CRP) and developed a combined additive pretransplant scoring system based on these predictive factors (EBMT risk assessment score plus 0 for CRP <2 mg/L, 1 for CRP from 2 to 10 mg/L, and 2 for CRP >10 mg/L). This identified 5 prognostic groups (Figure 1) with 3yr probabilities of survival of 92.6% (N= 27, score 0–1), 86.2% (N=29, score 2), 58.2% (N=29, score 3), 47.5% (N=20, score 4) and 30.8% (N=26, score 5 or more). The patients who failed imatinib (N=30) had significantly higher prognostic scores on the above described pre-transplant scoring system compared to the rest of patients transplanted (p=0.001). However, in a multivariate analysis adjusted for prognostic scores, their OS was significantly better (p=0.032). The OS in the best prognostic group is comparable with that of unselected patients treated with imatinib and it is possible that their long-term survival might be better. Allogeneic transplantation is unlikely to be preferred as the first line therapy even in selected patients due to its higher early mortality but our data support its use as second line therapy in patients in chronic phase who failed imatinib and have poor pre-2G-TKI predictive factors for CCyR as determined previously at our institution (namely Sokal risk score at diagnosis, the best cytogenetic response obtained on imatinib, G-CSF requirement during imatinib therapy and time from detection of imatinib failure to onset of 2G-TKI therapy) but achieved good score on the pre-transplant scoring system. It should also be used for those whose disease is more advanced where the 2G-TKI do not offer durable remissions. Figure 1 Figure 1.

Genes Influencing the Development and Severity of Chronic ITP Identified through Whole Exome Sequencing

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 73-73 ◽  
Author(s):  
Jenny M. Despotovic ◽  
Linda M. Polfus ◽  
Jonathan M. Flanagan ◽  
Carolyn M. Bennett ◽  
Michele P Lambert ◽  
...  
Keyword(s):  
T Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Second Line ◽  
Second Line Therapy ◽  
Advisory Committees ◽  
Chronic Itp ◽  
Line Therapy ◽  
Whole Exome ◽  
Phenotype Data

Abstract Background: Chronic immune thrombocytopenia (ITP) is a complex autoimmune disease characterized by antibody mediated platelet destruction and impaired production. Sustained autoimmunity in chronic ITP appears to be due to generalized immune dysregulation including altered T cell balance with a shift toward immune activation (increased Th1/Th2 ratio) as well as decreased number and impaired function of regulatory T cells (Treg). The cause of these abnormalities has not been fully elucidated and is likely multifactorial, but genetic factors may be involved in ITP pathogenesis. Improved understanding of genetic influences could lead to novel therapeutic approaches. Aim: To identify genetic variants that may be involved in chronic ITP susceptibility and severity. Methods: Whole exome sequencing (WES) was performed on 262 samples with robust phenotype data on children with chronic ITP from the North American Chronic ITP Registry (NACIR, n= 173) and the Platelet Disorders Center at the Weill-Cornell Medical Center (n=89). All but three patients were ≤19 years old at diagnosis; 83% had primary ITP, 10% had Evans syndrome, 7% had other autoimmune disorders. Sequencing data for ITP cases of European American (EA) ancestry were compared to EA controls with platelets >150 x 109/L sequenced in the Atherosclerosis Risk in Communities (ARIC) Study (N=5664) to identify candidate genes associated with ITP susceptibility. Analyses filtered variants on a minor allele frequency (MAF) <0.01 as well as functionality of nonsynonymous, stop gain, splicing, stop loss, and indel variants. Both Fisher-Exact tests of single variants and Firth logistic regression for gene-based tests, accounting for an unequal proportion of cases compared to controls, were used. A Bonferroni corrected threshold based on 16,532 genes was calculated at 3.0x10-6. In a separate analysis, phenotype data for ITP cases were reviewed and cases stratified by disease severity according to second line treatment needed (Yes =139, No=113) and compared to ARIC EA controls with platelet count >150 x 109/L (N=5664). Results: Several damaging variants identified in genes involved in cellular immunity had a significantly increased frequency in the EA ITP cohort (Table). The most significant associations were detected in the IFNA17 gene, which is involved in TGF-β secretion and could affect number and function of the Treg compartment. IFNA17 rs9298814 (9:21227622 A>C) was identified in 26% of cases in the EA ITP cohort compared to <0.01% of EA controls, and other low frequency but presumed deleterious variants were also identified in IFNA17. IFNA17 gene variants remained significant in the most severely affected patients, specifically those requiring second line therapy, providing further evidence for this gene's functional relevance in the pathogenesis and pathophysiology of ITP. Other genes with known impact on T cell number or function, including DGCR14, SMAD2 and CD83 also contained variants with increased frequency in the EA ITP cohort. IFNLR1 and REL genes were also significantly associated with need for second line ITP therapy. Analysis of this large cohort did not validate any of over 20 variants that have been previously published as candidates for ITP susceptibility or evolution to chronic ITP. Conclusion: Damaging variants in genes associated with cellular immunity have an increased frequency in children with chronic ITP compared to controls, providing further evidence for the role of T cell abnormalities in the pathophysiology of ITP. The IFNA17 and IFNLR1 genes maintained significance when the ITP cohort was stratified according to disease severity, and may be important candidate genes involved in immune regulation and sustained autoimmunity associated with chronic ITP. Table. Genes identified through WES analysis of children with chronic ITP. Gene Function Relevant to ITP Pathophysiology Minor Allele Count (MAC)Cases Controls p value EA Chronic ITP vs. EA ARIC (non-ITP) controls N=172 N=5664 IFNA17 Treg, TGF-β signaling 91 17 3.97x10-13 DGCR14 IL-17 induction 14 3 1.27x10-10 SMAD2 TGF-β signaling 1 0 5.62x10-22 CD83 Th17/Treg balance 2 3 1.67x10-6 EA Chronic ITP requiring Second Line Therapy vs. EA ARIC (non-ITP) controls N=139 N=5664 IFNLR1 Class II cytokine receptor 2 1 3.95x10-15 IFNA17 Treg, TGF-β signaling 75 17 3.40x10-7 REL T and B cell function, inflammation 2 0 1.39x10-14 Disclosures Off Label Use: Off-label use of CliniMACS purified CD34+ cells. Lambert:GSK: Consultancy; NovoNordisk: Honoraria; Hardin Kundla McKeon & Poletto: Consultancy. Recht:Baxalta: Research Funding; Kedrion: Consultancy. Bussel:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; protalex: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; rigel: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cangene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals Extranodal natural killer T cell lymphoma of the oropharyx: case report

2021 ◽  
Vol 37 (1) ◽  
Author(s):  
Ashraf Saad Abou-Halawa ◽  
Ibrahim Hassan Ibrahim ◽  
Mahmoud Hassan Eid ◽  
Mohamed Rifaat Ahmed
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
Cell Lymphoma ◽  
Early Response ◽  
T Cell Lymphoma ◽  
Upper Aerodigestive Tract ◽  
Natural Killer T Cell ◽  
Painful Ulcer ◽  
Killer T Cell ◽  
Natural Killer T

Abstract Background T cell lymphoma of the upper aerodigestive tract is a rare entity usually presenting as midfacial ulcerative lesion. It is extremely rare to present as non-healing erosive lesion of the oropharynx. Case presentation A 29-year-old female patient presented with odynophagia and trismus for several months. An “inflammatory” oropharyngeal ulcer was diagnosed and she was treated with repeated courses of antibiotics and corticosteroids without response. Recently, she had some blood stained saliva and vomited fresh blood. When seen, she had extensive painful ulcer eroding the right side of the soft palate and right tonsillar area. The ulcer had a whitish floor and ragged border without any tendency to heal. A second biopsy was taken and proved the lesion to be extranodal natural killer T cell lymphoma (ENKTL). The patient was treated with a modified SMILE (steroid, methotrexate, ifosfamide, l-asparaginase, and etoposide) protocol. Conclusions Extranodal natural killer T cell lymphoma can manifest first in the oropharynx. If left untreated it may lead to deep erosive lesion and major oral bleeding. SMILE chemotherapy protocol was used in our patient with good early response.

scholarly journals Extracorporeal Photopheresis As Second Line Therapy for Steroid Refractory Acute Gvhd: Retrospective Study of Long-Term Outcomes

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1944-1944
Author(s):  
Rohini Radia ◽  
Emma Das-Gupta ◽  
Guillermo Orti ◽  
Donal McLornan ◽  
Majid A. Kazmi ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
Performance Status ◽  
Chronic Gvhd ◽  
Second Line ◽  
Extracorporeal Photopheresis ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Gvhd Prophylaxis

Abstract Introduction Up to 50% of patients with acute GVHD (aGVHD) have a suboptimal response to first line therapy with corticosteroids. Extracorporeal photopheresis (ECP) is one of the recommended second line options. Overall response rates of 60-77% have been reported with ECP as second line therapy for aGVHD. Factors associated with lower response and survival were Grade >II at onset and number of organs involved. In a large retrospective study of ECP as second line therapy, 19.5% of patients developed chronic GVHD (cGVHD). Previous studies have included small numbers of patients with aGVHD post T cell depleted transplants or Donor Lymphocyte Infusion (DLI). Methods We conducted a retrospective analysis of outcomes in 40 patients treated with ECP for steroid refractory or steroid dependent aGVHD at 2 UK transplant centres. The aim was to analyse overall survival and long-term outcomes. All patients received 2-3 treatments per week for 8 weeks after which schedules differed according to centre, cessation or gradual taper. Results Between 2006 and 2014, 44 patients had received ECP as second line therapy, 4 were excluded from analysis as they had received less than 4 treatments. The median age was 51years (21-67years). Table 1 illustrates details of conditioning and GVHD prophylaxis. Thirty percent of patients were post DLI: 5 (12.5%) for disease relapse and 7 (17.5%) for mixed chimerism. Transplant conditioning included T cell depletion in 24 (60%): alemtuzumab n=17, ATG n=7. The median duration of steroids pre-starting ECP was 18 days (range 5-56). Using Modified Glucksberg crtieria at the onset of ECP, 5 patients (12.5%) had Grade II, 30 (75%) Grade III (including 6 with stage 4 gut) and 5 (12.5%) Grade IV aGVHD. Nine patients (22.5%) had 1 organ involvement and 31 (77.5%) had 2 or more organs involved. The dominant organ was gut in 21 (52.5%), liver in 10 (25%)and skin in 9 (22.5%). Maximal response rates were CR 57.5%, PR 27.5% and NR 15%. A number of patients received additional immunosuppressive therapy, predominantly anti-TNF antibodies: 14 patients (35%) (etanercept n=11, infliximab n=3). Using Kaplan-Meier analysis, censoring at last follow up, the overall survival from start of ECP at 5 years was 45.1% (95% CI 31.85-63.04%) Figure 1. The median survival was 2 years (27days-7.8yrs). In the DLI group, the 5 year overall survival was 59.8%. In a subgroup log rank Mantel-Cox analysis no significant difference was observed in the 5 year overall survival according to dominant organ involved: 53% skin, 40.6% gut and 50% liver (p=0.77) Figure 2. The cumulative incidence of death was 57.5% (23patients). The leading cause of death was infection 13/23 deaths (56.5%) followed by 5 deaths due to GVHD, 4 due to relapse, 1 from unrelated causes. The incidence of chronic GVHD was 55%. Treatment for cGVHD varied with 8 patients continuing ECP >12 weeks on a tapering schedule, 2 patients restarting ECP for cGVHD and the others receiving a variety of therapies including MMF, tacrolimus, Rituximab and imatinib. At last follow up, 17 patients were alive, 9 were off immunosuppression (2 of whom had not developed cGVHD) and 8 were still on immunosuppression. The performance status in the 17 surviving patients was ECOG 0= 8, 1=8 and 2=1. Discussion Our study shows an encouraging 5 year overall survival of 45.1% in a cohort with predominantly severe Grade III aGVHD. The 5 year survival was higher in the DLI group at 59.8%. Fifty three percent had stage 3-4 gut involvement, which is a recognised poor risk feature. Infection was the leading cause of death, which is of particular relevance in the T deplete setting. Whilst 55% developed cGVHD, over a long follow up period (median of 4years), the cGVHD resolved and performance status was preserved in most of the surviving patients. The incidence of cGVHD was higher than in other studies but the patients had higher grade of aGVHD at onset, were older and had multi-organ involvement. These findings need to be confirmed in prospective studies. Table 1. Pretransplant Characteristics No. of patients (%) Conditioning Regimes Myeloablative 10 (25%) Non-myeloablative 18 (45%) Total post DLI 12 (30%) T cell depletion 24 (60%) Alemtuzumab 17 (42.5%) ATG 7 (17.5%) GVHD prophylaxis CsA 20 (50%) CsA/MTX 9 (22.5%) CsA/MMF Tacro/MMF 8 (20%) 3 (7.5%) Donor Source Matched sibling Matched unrelated donor 10/10 9/10 8/10 Double Cord 9 (22.5%) 21 (52.5%) 3 (7.5%) 1 (2.5%) 6 (15%) Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Radia: Therakos: Other: ASH travel expense, Speakers Bureau. Off Label Use: Extracorporeal Photopheresis (ECP) is not licensed for use in GVHD but is recommended in international guidelines as a therapeutic option.. McLornan:Novartis: Research Funding, Speakers Bureau. Russell:Therakos: Other: shares.

Outcome of Risk Adapted Therapy for Relapsed/Refractory Acute Lymphoblastic Leukemia in Children: Results From a Single Institution

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4237-4237
Author(s):  
Asim F Belgaumi ◽  
Asem Bukhari ◽  
Mohammed Al-Mahr ◽  
Amal Al-Seraihy ◽  
Hazem Mahmoud ◽  
...  
Keyword(s):  
Overall Survival ◽  
Induction Therapy ◽  
Late Relapse ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Hematopoietic Stem ◽  
First Line Therapy ◽  
Line Therapy ◽  
Significant Difference

Abstract Abstract 4237 Although the outcome of first line therapy for childhood ALL has improved significantly, the results of second line therapy remains suboptimal. The most important predictive factors identified for second line therapy are timing and site of relapse; early relapse and bone marrow (BM) involvement invoking poorer outcomes. At our institution we have utilized a risk stratified therapeutic strategy for relapsed/refractory ALL which includes these factors. Re-induction for patients with first remission (CR1) duration of <18 months or those with remission failure was with high dose cytarabine (HDAraC) containing regimens, most often with idarubicin (Ida). For patients with CR1 >18 months, we utilized a standard 4-drug (prednisone, vincristine, daunomycin, asparaginase [PVDA]) induction regimen. Patients who relapsed in the BM while on chemotherapy or within 1 year of being off therapy were eligible for hematopoietic stem cell transplantation (SCT) after achieving CR, as were patients with isolated extra-medullary relapse with CR1 <18 months. Patients with late relapse were treated with post consolidation maintenance chemotherapy alone. Data collected prospectively in our database were reviewed. ALL patients who relapsed after receiving first line therapy at our institution and those who were referred to us at first relapse were included in this analysis. Only overall survival (OS) is presented as all patients who failed to achieve a CR or relapsed after achieving CR eventually died regardless of further therapeutic interventions. Fifty-nine patients with ALL failed their first line therapy between January 1, 2005 and May 31, 2011. There were four induction failures and 55 relapses. These 59 patients included 39 males; 53 of the patients had B-cell ALL and 6 had T-cell ALL. The age at original diagnosis ranged from 0.55 to 13.8 years (mean 6; median 4.8; SEM 0.50) whereas the age at first failure ranged from 0.68 to 16.4 years (mean 8.0; median 7.8; SEM 0.50). 36/55 (65.5%) relapses occurred on first line chemotherapy, 17 (30.9%) after completion of therapy and 2 (3.6%) following SCT. For the relapsed patients, the duration of CR1 ranged from 0.09 to 9 years (mean 2.0; median 1.7; SEM 0.22); 24 (44.4%) patients relapsed less than 18 months from CR1. 36 (61%) patients had isolated BM relapse, 13 (22.1%) had isolated extra-medullary (7 CNS; 6 testicular) and the remaining 10 had BM with other sites. Twenty four patients (40.7%) were re-induced with HDAraC/Ida (HIda), 28 (47.5%) with PVDA, 4 (6.8%) Fludarabine/AraC (FA) and 3 did not receive any second line therapy. For those who were treated 37 (62.7%) achieved a CR; 13 of the 19 patients who did not achieve CR with second-line therapy received third-line induction therapy (9 FA; 1 HIda; 1 VM26/AraC; 1 PVDA; 1 VP/CTX) and 7 (53.8%) achieved CR. The overall survival for all 59 patients at 2 years is 45.3%; for those who achieved CR the overall survival at 2 years is 64.7%. When we compared those patients who had CR1 durations >18 months with those who were induction failures or had CR1 duration <18 months, we found no significant difference in CR2 induction rates (76.7% v. 80%; p=1.0), nor in OS (56.9% v. 34.5% at 2 years; p=0.14). CR induction rates did not change when we further categorized CR1 duration into 18 months, 18–36 months and >36 months (80% v. 72.2% v. 80%; p=0.74). However, the OS was significantly higher for the >36 month group (83.3%; p=0.023) when compared to the other 2 groups (38.7% and 38.4%, respectively). In patients with <36 months of CR1, HSCT resulted in a significantly improved OS as compared to chemotherapy alone (51.4% v. 30.9 at 2 years; p=0.05). For those patients who achieved a CR2 there was no difference in the OS between those who underwent HSCT v. those who continued on chemotherapy (68% v. 58.5% at 2 years; p=0.33). Patients who achieved a CR after 2nd line therapy fared much better than those who achieved a CR after 3rd line therapy (25/36 [69.4%] alive v. 2/7 [28.6%] alive; OS at 2 years 68.3% v. 29.2%; p=0.06). In conclusion, we believe that this risk stratified approach to the treatment of relapsed/refractory ALL in children is effective. While the majority of the patients can be re-induced into remission, maintenance of the remission is dependent on the duration of CR1; patients with late relapse do as well as treatment naïve patients. Increased intensity induction therapy for early relapses and SCT for patients with <36 months of CR1 may be beneficial. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Differential Outcome of Patients with Primary Refractory Vs. Relapsed Peripheral T-Cell Lymphoma: Analysis from a Prospective Multicenter US Cohort Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4150-4150 ◽  
Author(s):  
Frederick Lansigan ◽  
Steven M Horwitz ◽  
Lauren C Pinter-Brown ◽  
Kenneth R Carson ◽  
Andrei R Shustov ◽  
...  
Keyword(s):  
T Cell ◽  
Research Funding ◽  
Single Agent ◽  
Novel Agents ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Multi Agent ◽  
Equity Ownership ◽  
Frontline Therapy

Abstract Introduction: Outcomes for patients with aggressive T cell lymphomas who are not cured by frontline therapies are poor. A Canadian retrospective analysis showed median overall survival (OS) to be 6.5 months combined for peripheral T-cell lymphoma (PTCL) patients in first relapse (Rel) and patients with primary refractory (Ref) disease (Mak, et al. JCO 2013). There have been no prospective studies that have examined the differences between Rel and Ref patients. In this analysis, we examined clinical features and outcomes for 285 patients prospectively enrolled in the COMPLETE Registry who completed frontline therapy and identified 119 patients with either Rel or Ref disease. We describe differences in clinical features, treatment, and outcomes between Rel and Ref patients. Methods: Patients with all subtypes of PTCL from 72 sites in the US were prospectively enrolled in the COMPLETE registry at initial diagnosis. Clinical and histopathologic features, treatment regimens, goals of therapy, toxicities, and outcomes were recorded. For this analysis, Ref disease was defined as no response to initial treatment or progression during or within 1 month of completing frontline therapy. Rel disease was defined as progression at least 1 month from completion of frontline therapy in patients who achieved a complete response (CR) or partial response (PR). Results: Of 285 patients in COMPLETE who had locked treatment and follow-up records required for this analysis, 50 met the criteria for Rel and 69 for Ref PTCL. Demographics (age, gender, race) and key clinical characteristics at initial diagnosis (histology [Table 1], bone marrow involvement, LDH, ECOG performance status) did not significantly differ between Rel and Ref patients. According to the treating physician, the primary goal of second-line therapy was cure in over half of both groups (52% for Rel, 60% for Ref); the remainder were managed with palliative intent. Rel patients received novel therapies (see Table 2 for definition) more frequently than Ref patients (58% vs. 28%) (P = 0.005) and were less likely to receive multi-agent regimens (24% vs. 45%; P = 0.04) [Table 2]. In the 55 Rel and Ref patients who received single-agent therapy, the most common agents were brentuximab vedotin (20%), romidepsin (15%), pralatrexate (9%) and gemcitabine (7%). In the 30 patients who received multi-agent therapy, the most common regimens were ICE (ifosfamide, carboplatin and etoposide) (17%), GemOx (gemcitabine and oxaliplatin) (17%), and CHOP or CHOP-like plus etoposide (13%). Despite similar frontline therapy with combination chemotherapy regimens, more Rel patients underwent high dose therapy and transplant compared to the Ref group (30% vs. 4%; P = 0.0005). Although single agent versus combination therapy showed similar objective response rates (ORR= CR+PR), the ORR of novel vs. traditional chemotherapy showed a trend favoring novel agents for the entire cohort (57% vs. 38%; P = 0.07). The ORR to second-line therapy was higher in Rel patients (63% vs. 38%; P = 0.02) as was the proportion achieving a CR (38% vs. 15%; P = 0.02). Further, Rel patients had longer OS compared Ref patients, with a median OS of 31 months (95% CI: 22.1 months to not reached) versus 10.2 months (95% CI: 6.5 - 15.9 months) from first diagnosis (Figure 1a) and 14.6 months versus 6.1 months (P = 0.048) from the time of relapse or progression (Figure 1b). For both Rel and Ref patients, there was no difference in survival by PTCL subtype. In both the Rel group and Ref groups, survival was significantly longer in patients treated with curative vs. palliative (as determined by the treating physician) intent (P = 0.01). Conclusions: Our analysis of real world outcomes in patients with aggressive T cell lymphomas demonstrates that outcomes are significantly worse for patients with Ref compared to those with Rel disease. Interestingly, novel single agent therapies were used most often as second-line therapy in Rel patients while multi-agent chemotherapy was used more frequently in Ref patients, despite the demonstration of activity of novel single agents in the Ref setting in other studies. The high proportion of patients with Rel or Ref disease in COMPLETE, and the demonstrated activity of novel agents in the Rel and Ref settings, supports initiatives to incorporate novel agents into frontline therapy for PTCL. Disclosures Lansigan: Spectrum: Consultancy, Research Funding; Pharmacyclics: Consultancy; Teva: Research Funding; Celgene: Consultancy. Horwitz:Huya: Consultancy; Celgene: Consultancy; Takeda: Consultancy, Research Funding; Infinity: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy; Kyowa Hakka Kirin: Consultancy, Research Funding; Spectrum: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; ADCT Therapeutics: Research Funding. Pinter-Brown:Celgene: Consultancy; Spectrum Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy. Carson:American Cancer Society: Research Funding. Pro:Seattle Genetics: Honoraria; Takeda: Honoraria; Celegene: Honoraria. Hsi:Onyx Pharmaceuticals: Honoraria; Seattle Genetics: Honoraria; Eli Lilly: Research Funding; Cellerant: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; HTG Molecular Diagnostics: Consultancy. Federico:MedNet Solutions: Consultancy. Gisselbrecht:Roche/Genentech: Research Funding, Speakers Bureau. Schwartz:MedNet Solutions: Employment. Bellm:Merck: Equity Ownership; Johnson & Johnson: Equity Ownership; BMS: Equity Ownership; MedNet Solutions: Consultancy, Other: Reimbursement of travel-related expenses. Acosta:Spectrum Pharmaceuticals: Employment, Equity Ownership. Foss:Celgene: Consultancy, Research Funding, Speakers Bureau; Seattle Genetics: Consultancy, Speakers Bureau; Spectrum Pharmaceuticals: Consultancy; Eisai: Consultancy.

scholarly journals Outcomes Following Salvage Therapy in Primary Refractory Peripheral T-Cell Lymphoma (PTCL)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4152-4152
Author(s):  
Janie Y Zhang ◽  
Robert Briski ◽  
Sumana Devata ◽  
Mark S Kaminski ◽  
Tycel Phillips ◽  
...  
Keyword(s):  
T Cell ◽  
Salvage Therapy ◽  
Cell Lymphoma ◽  
Initial Therapy ◽  
Refractory Disease ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Multi Agent ◽  
Systemic Therapies

Abstract Background: Resistance to conventional anthracycline-based regimens (CHOP/CHOEP) and the emergence of primary refractory disease remains a clinical challenge in PTCL, and is observed in ≈25% of patients. Outcomes in the setting of primary refractory disease, particularly for those patients who fail to achieve a remission with second-line chemotherapy, are poorly described and the optimal therapeutic strategy for these patients remains uncertain. Patients and Methods: We identified 159 patients with PTCL who received multi-agent, anthracycline-based treatment from 1988 to 2011 in the PTCL database at our institution. Primary refractory disease, defined as disease progression during initial therapy or relapse within 6 months of its completion, was observed in 58 (36%) of patients. Results: The median age at diagnosis with primary refractory PTCL was 49 years (range, 18.8-77.1). Median follow up was 2.7 years among surviving patients (95% CI, 1.2-6.3). Median overall survival (OS) was 1.1 years (95% CI, 0.7-1.9). The median number of lines of therapy underwent by patients was 3 (range, 1-9). PTCL, NOS (n=24), angioimmunoblastic T-cell lymphoma (n=6), and ALK-positive anaplastic large cell lymphoma (n=7) accounted for the majority (63.8%) of these patients. No difference in OS was observed between patients who failed to respond to initial therapy and those who relapsed within 6 months after a first remission (median OS 0.9 [95% CI, 0.6-1.9] vs. 1.3 [95% CI, 0.5-6.3], p=0.6). After developing primary refractory disease, 48.3% of patients received aggressive, multi-agent salvage regimens (ICE, n=16; DHAP, n=3; ESHAP, n=6; other, n=3), 29.3% of patients received other systemic therapies (HDAC inhibitor, n=1; gemcitabine-based therapies, n=5; pralatrexate, n=3; other, n=8), and 22.4% of patients received no systemic therapies. Patients who received no systemic salvage therapy had reduced OS compared to both patients who received aggressive regimens and patients who received other types of systemic therapies (median OS 0.3 [95% CI, 0.2-1.1] vs. 1.7 [95% CI, 0.8-11.7] vs. 1.3 [95% CI, 0.4-8.6], respectively, p<0.001), but the difference in OS observed between patients who received conventional salvage regimens and other systemic therapies was not significant (p=0.3). Patients receiving aggressive, multi-agent salvage regimens were more likely to undergo autologous or allogeneic stem cell transplantation (SCT) compared to those receiving non-traditional regimens or no systemic therapy (53.6% vs. 23.5% vs. 0%, respectively, p=0.0003). Following second-line therapy, 32.8% of patients underwent high dose therapy followed by autologous SCT (ASCT) (n=5) or allogeneic SCT (allo-SCT) (n=15). Not surprisingly, consolidation with either ASCT or allo-SCT was associated with improved OS (median OS 2.3 [95% CI, 0.9-11.4] vs. 0.6 [95% CI, 0.4-1.3], p=0.0012). Among patients who underwent allo-SCT, 26.7% (n=4) relapsed; among those who underwent ASCT, 60% (n=3) relapsed. A median OS of 0.6 years (95% CI, 0.4-1.1) was observed in patients who failed to achieve a remission with first salvage therapy and did not undergo ASCT or allo-SCT (n=25). Overall, 77.6% of patients with primary refractory PTCL failed to achieve a remission following second-line therapy or relapsed within 3 months of transplant. Among patients who did not achieve remission with the first salvage therapy, a median of 1 subsequent line of therapy (range, 0-7) was utilized. Among these patients who did not achieve a remission with initial salvage therapy, 20.6% (n=7) achieved a partial or complete remission with further therapy. Conclusion: Primary refractory PTCL is associated with dismal outcomes. The likelihood of achieving a remission and proceeding to transplant is ≈30% and with transplant, only 11 (19% of patients with primary refractory disease) achieved a durable remission. Improved understanding of resistance mechanisms in PTCL and the development of improved therapeutic strategies are needed. A significant survival benefit was not observed for patients receiving traditional salvage regimens compared to other systemic second-line regimens, with median survival <20 months. Therefore, participation in well-designed clinical trials should be encouraged in these patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Extranodal Natural Killer/T-Cell Lymphoma of the Nasal Type with Skin Metastases

2016 ◽  
Vol 9 (1) ◽  
pp. 1-5
Author(s):  
Fadi Al Akhrass ◽  
Brooklyn Hensley ◽  
Lillian Thomas ◽  
Raymond Elsoueidi
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Upper Aerodigestive Tract ◽  
Nasal Type ◽  
Natural Killer T Cell ◽  
Skin Metastases ◽  
Killer T Cell ◽  
Natural Killer T

Extranodal natural killer/T-cell lymphoma (ENKL) of the nasal type is a rare, clinically aggressive disease. ENKL of the nasal type is often localized in the upper aerodigestive tract, including the nasal cavity, nasopharynx, paranasal sinuses, tonsils, hypopharynx and larynx, and usually presents as stage I/II. Extranasal involvement can occur, and a common site of extranasal involvement or metastatic disease includes the skin. Identifying skin metastases is important for the appropriate staging and treatment. We report a case of ENKL of the nasal type that presented with localized disease and subsequent skin lesions that were consistent with skin metastases.

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