Chimeric antigen receptor T-cell (CAR-T) therapy has transformed treatment paradigms for relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) in children and younger adults. We performed a systematic review to investigate the published literature on efficacy and toxicity of CAR-T therapy in adults with r/r B-ALL. We searched MEDLINE, Embase and Cochrane Library for prospective, interventional studies and included published studies of ≥5 patients with median age at enrollment of ≥ 18 years. Risk of bias was assessed using a modified Institute of Health Economics tool. A total of 2566 records were assessed; 16 studies involving 489 patients were included in the final analysis. The mean CR rate was 81% and MRD negative remission rate was 81% at 4 weeks post CAR-T infusion. With median follow-up across studies of 24 months the cumulative 12-month probability of PFS and OS were 37% (95% CI 26-48%) and 57% (95% CI 49-65%), respectively. Relapse occurred in 40.3%; target antigen was retained in 73.2% of relapses. Across studies, any grade of CRS occurred in 82% (95% CI 61-95%) and grade 3 or higher CRS in 27% (95% CI 18-36%). Neurotoxicity of any grade occurred in 34% (95% CI 24-47%) and grade 3 or higher in 14% (95% CI 1-25%). In summary, CAR-T therapy achieves high early remission rates in adults with r/r B-ALL and represents a significant improvement over traditional salvage chemotherapy. Relapses are common and durable response remains a challenge.

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A 65-year-old man with a 14-year history of well-controlled HIV infection presented to the emergency department with three weeks of nausea, abdominal pain and confusion. His medical history included chronic obstructive pulmonary disease with features of asthma and infrequent exacerbations, allergic rhinitis, hypertension, dyslipidemia, chronic kidney disease (estimated glomerular filtration rate [eGFR] 30 mL/min/m 2 ), osteopenia, gastresophageal reflux disease, and a remote history of depression. His viral load had been undetectable, with a CD4 count above 400 (normal range 356-1573) cells/µL for many years on a ritonavir-containing antiretroviral regimen. He was also taking intranasal budesonide (total daily dose 128 µg), as well as inhaled budesonide (total daily dose 800 µg) in combination with formoterol. In response to a decline in his bone mineral density, recent progressive renal dysfunction (eGFR had decreased from 60 to 30 mL/min/m 2 over the course of the year) and worsening dyslipidemia, his antiretroviral therapy was changed to abacavir, lamivudine and dolutegravir eight weeks before he presented to the emergency department.Following this change in treatment, the patient was seen in the chronic viral illness clinic, and he reported asthenia, anorexia, nausea and intermittent episodes of crampy epigastric abdominal pain. He was afebrile, his seated blood pressure was 110/70 mm Hg, with a pulse rate at 100 beats/min. The remainder of the physical exam was unremarkable. A contrast-enhanced computed tomography (CT) scan of the abdomen did not show a cause for his abdominal pain.The patient's new antiretroviral regimen was put on hold, and genetic testing for a predisposition to abacavir hypersensitivity was conducted as a possible explanation for his symptoms. Because the patient was volume depleted, treatment with intravenous saline was started. After receiving 3 L of crystalloid, he felt better and was discharged home, with all antiretroviral treatments suspended and follow-up scheduled in clinic.Two weeks after discharge, the patient presented to the emergency department. In addition to intermittent epigastric pain, he now reported five days of headache, worsening fatigue, diffuse arthralgias, myalgias and fever. His wife also reported that he had been having difficulty with difficulty with planning and organizing his daily tasks, short-term memory and finding words. Upon physical examination, his body temperature was 38.9°C, and he had sinus tachycardia of 110 beats/min and a blood pressure of 100/60 mm Hg, which fell to 90/50 mm Hg after one minute of standing. Jugular venous pressure was 0 cm above the sternal angle. The remainder of the physical examination was normal. His Montreal Cognitive Assessment was 14/30, indicating substantially impaired cognitive function.The patient had a CD4 count of 350 cells/µL, and his plasma HIV RNA level had risen from previously undetectable to 1.5 million copies /mL. A plain CT scan of his head was unremarkable. A lumbar puncture was performed and showed an iso...

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Cord blood (CB) transplantation is hampered by low cell dose and high non-relapse mortality (NRM). A phase I-II trial of UM171-expanded CB transplants demonstrated safety and favourable preliminary efficacy. The aim of the current analysis was to retrospectively compare results of the phase I-II trial to those after unmanipulated CB and matched unrelated donor (MUD) transplants. Data from recipients of CB and MUD transplants were obtained from the Center for International Blood and Marrow Transplant Research (CIBMTR) database. Patients were directly matched for the number of prior allogeneic hematopoietic stem cell transplants (alloHCT), disease and refined Disease Risk Index. Patients were further matched by propensity score for age, comorbidity index and performance status. Primary endpoints included NRM, progression-free survival (PFS), overall survival (OS) and graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) at 1- and 2-years post alloHCT. Overall, 137 CIBMTR (67 CB, 70 MUD) and 22 UM171-expanded CB patients were included. NRM at 1 and 2 years was lower, PFS and GRFS at 2 years and OS at 1 year were improved for UM171-expanded CBs compared to CB controls. Compared to MUD controls, UM171 patients had lower 1- and 2-year NRM, higher 2-year PFS, and higher 1- and 2-year GRFS. Furthermore, UM171-expanded CB recipients experienced less grades III-IV acute GVHD and chronic GVHD compared to MUD graft recipients. Compared to real-world evidence with CB and MUD alloHCT, this study suggests that UM171-expanded CB recipients may benefit from lower NRM and higher GRFS.

Introduction: Patients with T-cell lymphoma have variable clinical manifestations and outcomes depending on the histology and their response to therapies. However, the overall outcomes are not as good as their B-cell lymphoma counterpart with induction chemotherapy alone. Therefore, autologous transplant is often used as consolidation in first remission or at relapse because of the poor outcomes with conventional therapy. We have reported previously on Stanford experience of these patients who underwent autologous transplant before 2007 (BBMT 2008, 14:741). Here, we reported a retrospective review of patients in the modern era (2008-2018) with emphasis on the impact of pre-transplant disease status on outcomes and post-transplant relapse management. Method: Between July 1, 2008 and July 31, 2018, 102 consecutive patients with T-cell lymphoma received high dose chemotherapy/autologous hematopoietic cell rescue at Stanford and constitute the study cohort (Figure 1). This study cohort was selected for adequate follow-up (>2 years) after transplant. Progression free survival (PFS) and overall survival (OS) was estimated from the date of transplant using the Kaplan-Meier method. PFS and OS were compared between groups with different pre-transplant disease status based on response to the last pre-transplant therapies (CR1 vs. PR1 vs. CR2). Result: This study cohort included patients with peripheral T-cell lymphoma, non-specified (n=21), angioimmunoblastic T-cell lymphoma (n=50), ALK-negative anaplastic large-cell lymphoma (n=14), ALK-positive anaplastic large-cell lymphoma (n=5), extranodal NK/T cell lymphoma (n=9), enteropathy-type T-cell lymphoma (n=1), adult T-cell leukemia/lymphoma (n=1) and hepatosplenic T-cell lymphoma (n=1). It had a male/female ratio of 61/41, and a median age of 58 years (range 23-71). At diagnosis the majority of the patients had stage III/IV disease (70%) and B symptoms (56%). The median time from diagnosis to transplant was 8.1 months (range 4-176). The majority of patients were in first complete remission (CR1, n=79) at the time of transplant, while others were in PR1 (n=11) or in CR2 (n=12) from last pre-transplant therapies. Ninety-one (89%) patients received high dose cyclophosphamide/carmustine/etoposide(CBV) and 11 patients received high dose carmustine/etoposide/cytarabine/melphalan (BEAM) prior to autograft infusion. Median follow-up post-transplant was 36.8 months (range 0.7-130) for the entire cohort. The estimated 3-year PFS and OS were 60% (95% CI 49-68%) and 75% (95% CI 65-82%), respectively (Figure 2A). Patients who were in CR1 had significantly better median PFS compared to patients in PR1 or CR2 (7.04 vs 1.19 years, p=0.039; 7.04 vs 0.48 years p=0.004, Figure 2B). The estimated 3-year PFS were 67% (95% CI 55-76%), 36% (95% CI 11-63%), and 29% (95% CI 8-56%) for the CR1, PR1 and CR2 groups respectively. Patients who were in CR1 also had significantly better median OS compared to patients in PR1 or CR2 (not reached vs 2.30 years, p=0.018; not reached vs 3.76 years p=0.045, Figure 2C).The estimated 3-year OS were 82% (95% CI 71-89%), 44% (95% CI 14-70%), and 53% (95% CI 21-78%) for the CR1, PR1 and CR2 groups respectively. In this cohort, there were no significant differences in either PFS or OS between different histology. Forty patients experienced disease relapse after transplant. The majority (n=28, 70%) of these patients received additional therapies including chemotherapy (n=13), brentuximab vedotin (n=12), HDAC inhibitor (n=7), and radiation (n=3) with a median systemic therapy of 2 (range 1-5). Thirteen patients eventually underwent allogeneic hematopoietic cell transplantation. The median OS after post-transplant relapse was 21.3 months (Figure 3). Both brentuximab vedotin and allogeneic transplant seemed to provide prolonged survival for these relapsed patients, with estimated 2-year post-relapse OS were 75% (95% CI 13-96%) and 63% (95% CI 28-84%) for the two groups respectively. Conclusion: Autologous transplant remains to be a good option as consolidation for patients with T-cell lymphoma, mostly in patients with first complete remission. While close to 40% of the patients experienced relapse after autologous transplant, additional therapies such as brentuximab vedotin or/and allogeneic transplant can provide long-term benefit for these patients. Disclosures Shizuru: Jasper Therapeutics, Inc: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees. Shiraz:Kite, a Gilead Company: Research Funding; ORCA BioSystems: Research Funding. Muffly:Servier: Research Funding; Amgen: Consultancy; Adaptive: Research Funding. Sidana:Janssen: Consultancy. Meyer:Orca Bio: Research Funding. Rezvani:Pharmacyclics: Research Funding. Miklos:Novartis: Consultancy, Other: Travel support, Research Funding; Pharmacyclics: Consultancy, Other: Travel support, Patents & Royalties, Research Funding; Allogene Therapeutics Inc.: Research Funding; Kite-Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Juno-Celgene-Bristol-Myers Squibb: Consultancy, Other: Travel support, Research Funding; Janssen: Consultancy, Other: Travel support; Miltenyi Biotec: Research Funding; Adaptive Biotech: Consultancy, Other: Travel support, Research Funding. Negrin:Magenta Therapeutics: Consultancy, Current equity holder in publicly-traded company; Biosource: Current equity holder in private company; Amgen: Consultancy; BioEclipse Therapeutics: Current equity holder in private company; UpToDate: Honoraria; KUUR Therapeutics: Consultancy.