***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: New treatments are needed for B-cell malignancies persisting after allogeneic hematopoietic stem cell transplantation ( alloHSCT ) . We conducted a clinical trial of allogeneic T cells genetically modified to express a chimeric antigen receptor ( CAR ) targeting the B-cell antigen CD19 . T cells for genetic modification were obtained from each patient 's alloHSCT donor . All patients had malignancy that persisted after alloHSCT and st and ard donor lymphocyte infusions ( DLIs ) . Patients did not receive chemotherapy  prior to the CAR T-cell infusions and were not lymphocyte depleted at the time of the infusions . The 10 treated patients received a single infusion of allogeneic anti-CD19-CAR T cells . Three patients had regressions of their malignancies . One patient with chronic lymphocytic leukemia ( CLL ) obtained an ongoing complete remission after treatment with allogeneic anti-CD19-CAR T cells , another CLL patient had tumor lysis syndrome as his leukemia dramatically regressed , and a patient with mantle cell lymphoma obtained an ongoing partial remission . None of the 10 patients developed graft-versus-host disease ( GVHD ) . Toxicities included transient hypotension and fever . We detected cells containing the anti-CD19-CAR gene in the blood of 8 of 10 patients . These results show for the first time that donor-derived allogeneic anti-CD19-CAR T cells can cause regression of B-cell malignancies resistant to st and ard DLIs without causing GVHD We conducted a clinical trial to assess adoptive transfer of T cells genetically modified to express an anti-CD19 chimeric Ag receptor ( CAR ) . Our clinical protocol consisted of chemotherapy followed by an infusion of anti-CD19-CAR-transduced T cells and a course of IL-2 .  Six of the 8 patients treated on our protocol obtained remissions of their advanced , progressive B-cell malignancies . Four of the 8 patients treated on the protocol had long-term depletion of normal polyclonal CD19(+ ) B-lineage cells . Cells containing the anti-CD19 CAR gene were detected in the blood of all patients . Four of the 8 treated patients had prominent elevations in serum levels of the inflammatory cytokines IFNγ and TNF . The severity of acute toxicities experienced by the patients correlated with serum IFNγ and TNF levels . The infused anti-CD19-CAR-transduced T cells were a possible source of these inflammatory cytokines because we demonstrated peripheral blood T cells that produced TNF and IFNγ ex vivo in a CD19-specific manner after anti-CD19-CAR-transduced T-cell infusions . Anti-CD19-CAR-transduced T cells have great promise to improve the treatment of B-cell malignancies because of a potent ability to eradicate CD19(+ ) cells in vivo ; however , reversible cytokine-associated toxicities occurred after CAR-transduced T-cell infusions Outcomes for patients with refractory diffuse large B cell lymphoma ( DLBCL ) are poor . In the multicenter ZUMA-1 phase 1 study , we evaluated KTE-C19 , an autologous CD3ζ/CD28-based chimeric antigen receptor ( CAR ) T cell therapy , in patients with refractory DLBCL . Patients received low-dose conditioning chemotherapy with concurrent cyclophosphamide ( 500 mg/m2 ) and fludarabine ( 30 mg/m2 ) for 3 days followed by KTE-C19 at a target dose of 2 × 106 CAR T cells/kg . The incidence of dose-limiting toxicity ( DLT ) was the primary endpoint . Seven patients were treated with KTE-C19 and one patient experienced a DLT of grade 4 cytokine release syndrome ( CRS ) and neurotoxicity . Grade ≥3 CRS and neurotoxicity were observed in 14 % ( n = 1/7 ) and 57 % ( n = 4/7 ) of patients , respectively . All other KTE-C19-related grade ≥3 events resolved within 1 month . The overall response rate was 71 % ( n = 5/7 ) and complete response ( CR ) rate was 57 % ( n = 4/7 ) . Three patients have ongoing CR ( all at 12 + months ) . CAR T cells demonstrated peak expansion within 2 weeks and continued to be detectable at 12 + months in patients with ongoing CR . This regimen of KTE-C19 was safe for further study in phase 2 and induced durable remissions in patients with refractory DLBCL PURPOSE Salvage chemotherapy followed by high-dose therapy and autologous stem-cell transplantation ( ASCT ) is the st and ard treatment for relapsed diffuse large B-cell lymphoma ( DLBCL ) . Salvage regimens have never been compared ; their efficacy in the rituximab era is unknown . PATIENTS AND METHODS Patients with CD20(+ ) DLBCL in first relapse or who were refractory after first-line therapy were r and omly assigned to either rituximab , ifosfamide , etoposide , and carboplatin ( R-ICE ) or rituximab , dexamethasone , high-dose cytarabine , and cisplatin ( R-DHAP ) . Responding patients received high-dose chemotherapy and ASCT . RESULTS The median age of the 396 patients enrolled ( R-ICE , n = 202 ; R-DHAP , n = 194 ) was 55 years . Similar response rates were observed after three cycles of R-ICE ( 63.5 % ; 95 % CI , 56 % to 70 % ) and R-DHAP ( 62.8 % ; 95 CI , 55 % to 69 % ) . Factors affecting response rates ( P < .001 ) were refractory disease/relapse less than versus more than 12 months after diagnosis ( 46 % v 88 % , respectively ) , International Prognostic Index ( IPI ) of more than 1 versus 0 to 1 ( 52 % v 71 % , respectively ) , and prior rituximab treatment versus no prior rituximab ( 51 % v 83 % , respectively ) . There was no significant difference between R-ICE and R-DHAP for 3-year event-free survival ( EFS ) or overall survival . Three-year EFS was affected by prior rituximab treatment versus no rituximab ( 21 % v 47 % , respectively ) , relapse less than versus more than 12 months after diagnosis ( 20 % v 45 % , respectively ) , and IPI of 2 to 3 versus 0 to 1 ( 18 % v 40 % , respectively ) . In the Cox model , these parameters were significant ( P < .001 ) . CONCLUSION In patients who experience relapse more than 12 months after diagnosis , prior rituximab treatment does not affect EFS . Patients with early relapses after rituximab-containing first-line therapy have a poor prognosis , with no difference between the effects of R-ICE and R-DHAP BACKGROUND Treatment of B cell malignancies with adoptive transfer of T cells with a CD19-specific chimeric antigen receptor ( CAR ) shows remarkable clinical efficacy . However , long-term persistence of T cells targeting CD19 , a pan-B cell marker , also depletes normal B cells and causes severe hypogammaglobulinemia . Here , we developed a strategy to target B cell malignancies more selectively by taking advantage of B cell light Ig chain restriction . We generated a CAR that is specific for the κ light chain ( κ . CAR ) and therefore recognizes κ-restricted cells and spares the normal B cells expressing the nontargeted λ light chain , thus potentially minimizing humoral immunity impairment . METHODS We conducted a phase 1 clinical trial and treated 16 patients with relapsed or refractory κ+ non-Hodgkin lymphoma/chronic lymphocytic leukemia ( NHL/CLL ) or multiple myeloma ( MM ) with  autologous T cells genetically modified to express κ . CAR ( κ . CARTs ) . Other treatments were discontinued in 11 of the 16 patients at least 4 weeks prior to T cell infusion . Six patients without lymphopenia received 12.5 mg/kg cyclophosphamide 4 days before κ . CART infusion ( 0.2 × 108 to 2 × 108 κ . CARTs/m2 ) . No other lymphodepletion was used . RESULTS κ . CART expansion peaked 1 - 2 weeks after infusion , and cells remained detectable for more than 6 weeks . Of 9 patients with relapsed NHL or CLL , 2 entered complete remission after 2 and 3 infusions of κ . CARTs , and 1 had a partial response . Of 7 patients with MM , 4 had stable disease lasting 2 - 17 months . No toxicities attributable to κ . CARTs were observed . CONCLUSION κ . CART infusion is feasible and safe and can lead to complete clinical responses . TRIAL REGISTRATION Clinical Trials.gov NCT00881920 . FUNDING National Cancer Institute ( NCI ) grants 3P50CA126752 and 5P30CA125123 and Leukemia and Lymphoma Society ( LLS ) Specialized Centers of Research ( SCOR ) grant 7018 Immunotherapeutic ablation of lymphoma is a conceptually attractive treatment strategy that is the subject of intense translational research . Cytotoxic T lymphocytes ( CTLs ) that are genetically modified to express CD19- or CD20-specific , single-chain antibody-derived chimeric antigen receptors ( CARs ) display HLA-independent antigen-specific recognition/killing of lymphoma targets . Here , we describe our initial experience in applying CAR-redirected autologous CTL adoptive therapy to patients with recurrent lymphoma . Using plasmid vector electrotransfer/drug selection systems , cloned and polyclonal CAR(+ ) CTLs were generated from autologous peripheral blood mononuclear cells and exp and ed in vitro to cell numbers sufficient for clinical use . In 2 FDA -authorized trials , patients with recurrent diffuse large cell lymphoma were treated with cloned CD8(+ ) CTLs expressing a CD20-specific CAR ( along with NeoR ) after autologous hematopoietic stem cell transplantation , and patients with refractory follicular lymphoma were treated with polyclonal T cell preparations expressing a CD19-specific CAR ( along with HyTK , a fusion of hygromycin resistance and HSV-1 thymidine kinase suicide genes ) and low-dose s.c . recombinant human interleukin-2 . A total of 15 infusions were administered ( 5 at 10(8)cells/m(2 ) , 7 at 10(9)cells/m(2 ) , and 3 at 2 x 10(9)cells/m(2 ) ) to 4 patients .  Overt toxicities attributable to CTL administration were not observed ; however , detection of transferred CTLs in the circulation , as measured by quantitative polymerase chain reaction , was short ( 24 hours to 7 days ) , and cellular antitransgene immune rejection responses were noted in 2 patients . These studies reveal the primary barrier to therapeutic efficacy is limited persistence , and provide the rationale to prospect ively define T cell population s intrinsically programmed for survival after adoptive transfer and to modulate the immune status of recipients to prevent/delay antitransgene rejection responses Myeloablative autologous hematopoietic stem cell transplantation ( HSCT ) is a mainstay of therapy for relapsed intermediate- grade B-cell non-Hodgkin lymphoma ( NHL ) ; however , relapse rates are high . In phase 1 studies design ed to improve long-term remission rates , we administered adoptive T-cell immunotherapy after HSCT , using ex vivo-exp and ed autologous central memory-enriched T cells ( TCM ) transduced with lentivirus expressing CD19-specific chimeric antigen receptors ( CARs ) . We present results from 2 safety/feasibility studies , NHL1 and NHL2 , investigating different T-cell population s and CAR constructs . Engineered TCM-derived CD19 CAR T cells were infused 2 days after HSCT at doses of 25 to 200 × 10(6 ) in a single infusion . In NHL1 , 8 patients safely received T-cell products engineered from enriched CD8(+ ) TCM subsets , expressing a first-generation CD19 CAR containing only the CD3ζ endodomain ( CD19R : ζ ) . Four of 8 patients ( 50 % ; 95 % confidence interval [ CI ] : 16 - 84 % ) were progression free at both 1 and 2 years . In NHL2 , 8 patients safely received T-cell products engineered from enriched CD4(+ ) and CD8(+ ) TCM subsets and expressing a second-generation CD19 CAR containing the CD28 and CD3ζ endodomains ( CD19R:28ζ ) . Six of 8 patients ( 75 % ; 95 % CI : 35 - 97 % ) were progression free at 1 year . The CD4(+)/CD8(+ ) TCM-derived CD19 CAR T 
    Output:
    
Although the CRS and neurotoxicity incidences were high , most were reversible with minimal risk of death .