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Standard treatment for GVHD is glucocorticoids, but for glucocorticoid-refractory GVHD, no intervention has emerged as standard second-line treatment. This trial with 329 patients compared ruxolitinib with control (chosen from among 10 possible therapies) in patients with glucocorticoid-refractory chronic GVHD. Response at week 24 was 50% with ruxolitinib as compared with 26% with control therapy.

Approximately 50% of allogeneic hematopoietic stem cell transplantation (HSCT) Q6 recipients develop graft versus host disease (GVHD). Glucocorticoids (GC) are the first line of treatment for both acute and chronic GVHD. Failure to respond to GC [steroid-refractory (SR)] encompasses a very poor outcome with high mortality. Macrophage migration inhibitory factor (MIF) is released during transplantation and triggers enhanced and prolonged immune reactions. Persistently elevated levels of MIF have been shown to override both endogenous and exogenous antiinflammatory effects of GC. Two functional polymorphisms in the MIF gene, a -794 CATT5-8 microsatellite repeat and a -173 G/C single-nucleotide polymorphism, were analyzed in 86 patients who underwent allogeneic HSCT. We also measured MIF serum levels at different time points before and after HSCT. Frequencies of MIF high-expression -794 CATT7 containing genotypes were increased in patients with grade III-IV acute GVHD (aGVHD) (36.8%) compared with patients that did not develop aGVHD (5.8%) and patients with grade II aGVHD (0%), (p=0.0019, 0.0080 respectively). We also demonstrated that the frequencies of the MIF-794 CATT7 and -173 C containing genotypes, were significantly associated with steroid-refractory aGVHD (46.6%, 60% respectively) compared to steroid-responsive aGVHD (0%, 5.3% respectively), (p=0.0011, P=0.0007 respectively). We further showed that MIF circulating levels preceded onset of severe aGVHD. Our findings suggest that genetically controlled high expression MIF genotypes are associated with aGVHD worsening and could serve as a biomarker enhancing identification and treatment of steroid-refractory disease.

In patients with relapsed DLBCL in complete remission (CR), autologous hematopoietic cell transplantation (auto-HCT) and CAR-T therapy are both effective, but it is unknown which modality provides superior outcomes. We compared the efficacy of auto-HCT vs. CAR-T in patients with DLBCL in a CR. A retrospective observational study comparing auto-HCT (2015–2021) vs. CAR-T (2018–2021) using the Center for International Blood & Marrow Transplant Research registry. Median follow-up was 49.7 months for the auto-HCT and 24.7 months for the CAR-T cohort. Patients ages 18 and 75 with a diagnosis of DLBCL were included if they received auto-HCT ( n  = 281) or commercial CAR-T ( n  = 79) while in a CR. Patients undergoing auto-HCT with only one prior therapy line and CAR-T patients with a previous history of auto-HCT treatment were excluded. Endpoints included Progression-free survival (PFS), relapse rate, non-relapse mortality (NRM) and overall survival (OS). In univariate analysis, treatment with auto-HCT was associated with a higher rate of 2-year PFS (66.2% vs. 47.8%; p  < 0.001), a lower 2-year cumulative incidence of relapse (27.8% vs. 48% ; p  < 0.001), and a superior 2-year OS (78.9% vs. 65.6%; p  = 0.037). In patients with early (within 12 months) treatment failure, auto-HCT was associated with a superior 2-year PFS (70.9% vs. 48.3% ; p  < 0.001), lower 2-year cumulative incidence of relapse (22.8% vs. 45.9% ; p  < 0.001) and trend for higher 2-year OS (82.4% vs. 66.1% ; p  = 0.076). In the multivariable analysis, treatment with auto-HCT was associated with a superior PFS (hazard ratio 1.83; p  = 0.0011) and lower incidence of relapse (hazard ratio 2.18; p  < 0.0001) compared to CAR-T. In patients with relapsed LBCL who achieve a CR, treatment with auto-HCT is associated with improved clinical outcomes compared to CAR-T. These data support the consideration of auto-HCT in select patients with LBCL achieving a CR in the relapsed setting.

Abstract Acute lymphoblastic leukemia (ALL) is a malignant neoplasm of the blood stem cells, characterized by increased formation of immature lymphocytes. Ocular manifestations may vary with ocular, adnexal, and orbital involvement. In this case report, we describe the first case of extramedullary relapse of ALL limited to the anterior chamber of the eye treated with the novel chimeric antigen receptor T (CAR T)-cell therapy and provide a literature review of cases of ALL relapse in the anterior chamber. A 21-year-old male with a history of B-cell ALL presented with a unilateral blurry vision in his left eye. Ocular examination revealed the presence of cells +3 in the anterior chamber and a 1.5-mm hypopyon. Anterior chamber aspiration confirmed a B-ALL relapse. The patient was successfully treated with radiotherapy of his left eye and received CTL-019 transduced T cells (tisagenlecleucel; Novartis) with cytarabine as a bridging chemotherapy treatment. On the last examination, 18 months after the first presentation, the patient presented a complete ocular remission with no systemic or CNS involvement. ALL relapse may involve the anterior chamber of the eye, and an accurate diagnosis is crucial to enable a fast and appropriate treatment. Novel CAR T-cell immunotherapy, combined with ocular irradiation, may be considered in such cases.

BackgroundTisagenlecleucel, a CD19 chimeric antigen receptor T-cell therapy, is approved for adults with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBCL) after ≥2 lines of therapy. When used in real-world settings, tisagenlecleucel has shown similar efficacy and improved safety compared with previous clinical trials. However, long-term data on real-world outcomes are lacking.MethodsClinical data from a cohort of patients treated with tisagenlecleucel in a real-world setting were captured in the Center for International Blood and Marrow Transplant Research registry. The main clinical outcomes analysed included response rate, duration of response, survival, adverse events and clinicopathologic and treatment characteristics that may affect those outcomes.ResultsAs of May 2022, 1159 patients with R/R DLBCL/HGBCL received tisagenlecleucel. The overall response rate was 59.5%, and the complete response rate was 44.5%. With a median follow-up of 23.2 months in the efficacy set (n=968), the 24 month rates of progression-free survival, ongoing response and overall survival were 28.4%, 52.6% and 43.6%, respectively. Grade ≥3 cytokine release syndrome and neurotoxicity were reported in 6% and 7.4% of patients, respectively. Patients with DLBCL (vs HGBCL), complete response before infusion, prior autologous or allogeneic haematopoietic stem cell transplant and lactate dehydrogenase (LDH) within normal limits experienced more favourable efficacy outcomes, and those with Eastern Cooperative Oncology Group performance status of ≥2, ≥3 prior lines of therapy, elevated LDH and fludarabine-based lymphodepleting chemotherapy experienced less favourable safety outcomes.ConclusionsThis real-world study of tisagenlecleucel for patients with R/R DLBCL/HGBCL shows consistent efficacy and better safety outcomes than the pivotal trial. This study also identifies baseline disease characteristics and prior or concurrent treatments that may affect clinical outcomes.Tisagenlecleucel, a CD19 chimeric antigen receptor T-cell therapy, is approved for adults with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBCL) after ≥2 lines of therapy. When used in real-world settings, tisagenlecleucel has shown similar efficacy and improved safety compared with previous clinical trials. However, long-term data on real-world outcomes are lacking.Clinical data from a cohort of patients treated with tisagenlecleucel in a real-world setting were captured in the Center for International Blood and Marrow Transplant Research registry. The main clinical outcomes analysed included response rate, duration of response, survival, adverse events, and clinicopathologic and treatment characteristics that may affect those outcomes.As of May 2022, 1159 patients with R/R DLBCL/HGBCL received tisagenlecleucel. The overall response rate was 59.5%, and the complete response rate was 44.5%. With a median follow-up of 23.2 months in the efficacy set (n=968), the 24 month rates of progression-free survival, ongoing response, and overall survival were 28.4%, 52.6%, and 43.6%, respectively. Grade ≥3 cytokine release syndrome and neurotoxicity were reported in 6% and 7.4% of patients, respectively. Patients with DLBCL (vs HGBCL), complete response before infusion, prior autologous or allogeneic haematopoietic stem cell transplant, and lactate dehydrogenase (LDH) within normal limits experienced more favourable efficacy outcomes, and those with Eastern Cooperative Oncology Group performance status ≥2, ≥3 prior lines of therapy, elevated LDH, and fludarabine-based lymphodepleting chemotherapy experienced less favourable safety outcomes.In conclusion, this real-world study of tisagenlecleucel for patients with R/R DLBCL/HGBCL shows consistent efficacy and better safety outcomes than the pivotal trial. This study also identifies baseline disease characteristics and prior or concurrent treatments that may affect clinical outcomes.

COVID-19-related mortality among hematopoietic stem cell transplantation (HSCT) recipients in the pre-vaccine era ranged between 22 and 33%. The Pfizer/BioNTech BNT162b2 vaccine demonstrated significant immunogenicity and efficacy in the healthy population; however, its long-term effects on allogeneic HSCT recipients remained unclear. Our study longitudinally evaluated humoral and cellular responses to the BNT162b2 vaccine in adult allogeneic HSCT patients. A positive response was defined as antibody titers ≥ 150 AU/mL post-second vaccination. Among 77 included patients, 51 (66.2%) responded to vaccination. Response-associated factors were female gender, recent anti-CD20 therapy, and a longer interval between transplant and vaccination. Response rates reached 83.7% in patients vaccinated >12 months post-transplant. At 6 months post-second vaccination, antibody titers dropped, but were significantly increased with the booster dose. Moreover, 43% (6/14) of non-responders to the second vaccination acquired sufficient antibody titers after booster administration, resulting in an overall response rate of 79.5% for the entire cohort. The BNT162b2 vaccine was effective in allogeneic transplant recipients. Although antibody titers decreased with time, the third vaccination led to their significant elevation, with 93% of third-dose responders maintaining titers above 150 AU/mL at 3 months post-administration.

Patients with relapsed or refractory (r/r) primary central nervous system (CNS) lymphoma (PCNSL) or secondary central nervous system (CNS) lymphoma (SCNSL) face a dismal prognosis. They have been excluded from most clinical CAR T‐cell trials as investigators feared an increased risk for severe immune effector cell‐associated neurotoxicity (ICANS). To investigate the potential of anti‐CD19 CAR T‐cell therapy (CART) in such patients, we analyzed data of 100 patients with CNS manifestation treated with CART between January 2018 and July 2023 and reported to European Society for Blood and Marrow Transplantation. Median age was 62 years. Of patients, 58% had failed ≥3 treatment lines, and 40% had received autologous stem‐cell transplantation before CART. Fifty‐nine patients received axicabtagene ciloleucel, 38 patients were treated with tisagenlecleucel, three patients received other products. At the time of CART, 67 patients had active CNS disease. Overall and progression‐free survival (PFS) at 24 months were 37% and 28%. Relapse incidence (RI) at 24 months was 59%, whereas non‐relapse mortality at 1 year was 7%. Cytokine release syndrome (CRS) and ICANS of any grade occurred in 83% and 42% of patients, respectively. CRS grade 3 occurred in 11 and ICANS grades 3–4 in 17 patients. Two patients died of neurotoxicity. Elevated lactate dehydrogenase was an independent risk factor for RI and PFS (hazard ratio [HR] 2.4, p = 0.003; HR: 1.9, p = 0.016). Patients with ECOG 2–3 had a significantly increased risk for the development of ICANS (HR 2.68, p = 0.002). These data support the implementation of CART as treatment for patients with r/r PCNSL and SCNSL.

Background: Invasive mold infections (IMI) are leading infectious causes of mortality among patients with hematological malignancies. Objectives: To determine the relative contribution of host, disease, and treatment-related factors to patient survival. Methods: An observational, retrospective cohort study reviewing the medical records of patients with hematological malignancy and IMI (2006–2016). Causes of death were classified up to 90 days after diagnosis. Kaplan–Meier and Cox regression analyses were used to determine risk factors for early, late, and overall mortality. Results: Eighty-six patients with IMI were included; 29 (34%) and 41 (47%) died within 6 and 12 weeks of diagnosis, respectively. Death was attributed to IMI in 22 (53.6%) patients, all of whom died within 45 days of diagnosis. Risk factors for early mortality were elevated serum galactomannan, treatment with amphotericin B, IMI progression 3 weeks after diagnosis, and lymphoma undergoing HCT. Late mortality was associated with relapsed/refractory malignancy and elevated serum galactomannan. Conclusions: In this single-center study of patients with IMI, infections were the most frequent causes of death, and time-dependent risk factors for death were identified. These results may help direct risk-assessment and monitoring of patients undergoing treatment of IMI.