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Introduction: Chimeric antigen receptor positive T cell (CAR-T cell) treatment became standard therapy for relapsed or refractory hematologic malignancies, such as non-Hodgkin's lymphoma and multiple myeloma. Owing to the rapidly progressing field of CAR-T cell therapy and the lack of generally accepted treatment guidelines, we hypothesized significant differences between centers in the prevention, diagnosis, and management of short- and long-term complications. Methods: To capture the current CAR-T cell management among German centers to determine the medical need and specific areas for future clinical research, the DAG-HSZT (Deutsche Arbeitsgemeinschaft für Hämatopoetische Stammzelltransplantation und Zelluläre Therapie; German Working Group for Hematopoietic Stem Cell Transplantation and Cellular Therapy) performed a survey among 26 German CAR-T cell centers. Results: We received answers from 17 centers (65%). The survey documents the relevance of evidence in the CAR-T cell field with a homogeneity of practice in areas with existing clinical evidence. In contrast, in areas with no – or low quality – clinical evidence, we identified significant variety in management in between the centers: management of cytokine release syndrome, immune effector cell-related neurotoxicity syndrome, IgG substitution, autologous stem cell backups, anti-infective prophylaxis, and vaccinations. Conclusion: The results indicate the urgent need for better harmonization of supportive care in CAR-T cell therapies including clinical research to improve clinical outcome. [ABSTRACT FROM AUTHOR]

Introduction: Secondary haemophagocytic lymphohistiocytosis (sHLH) or Macrophage Activation Syndrome (MAS) is a life-threatening hyperinflammatory syndrome that can occur in patients with severe infections, malignancy or autoimmune diseases. It is also a rare complication of haematopoetic stem cell transplantation (HSCT), with a high mortality. It may be associated with graft vs. host disease in the allogeneic HSCT setting. It is also reported following CAR-T cell therapy, but differentiation from cytokine release syndrome (CRS) is challenging. Here, we summarise the literature and present results of a survey of current awareness and practice in EBMT-affiliated centres of sHLH/MAS following HSCT and CAR-T cell therapy. Methods: An online questionnaire was sent to the principal investigators of all EBMT member transplant centres treating adult patients (18 years and over) inviting them to provide information regarding: number of cases of sHLH/MAS seen in their centre over 3 years (2016–2018 inclusive); screening strategies and use of existing diagnostic/classification criteria and treatment protocols. Results: 114/472 centres from 24 different countries responded (24%). We report estimated rates of sHLH/MAS of 1.09% (95% CI = 0.89–1.30) following allogeneic HSCT, 0.15% (95% CI = 0.09–5.89) following autologous HSCT and 3.48% (95% CI = 0.95–6.01) following CAR-T cell therapy. A majority of centres (70%) did not use a standard screening protocol. Serum ferritin was the most commonly used screening marker at 78% of centres, followed by soluble IL-2 receptor (24%), triglycerides (15%), and fibrinogen (11%). There was significant variation in definition of "clinically significant" serum ferritin levels ranging from 500 to 10,000 μg/mL. The most commonly used criteria to support diagnosis were HLH-2004 (43%) and the H score (15%). Eighty percent of responders reported using no standard management protocol, but reported using combinations of corticosteroids, chemotherapeutic agents, cytokine blockade, and monoclonal antibodies. Conclusions: There is a remarkable lack of consistency between EBMT centres in the approach to screening, diagnosis and management. Further research in this field is needed to raise awareness of and inform harmonised, evidence-based approaches to the recognition and treatment of sHLH/MAS following HSCT/CAR-T cell therapy. [ABSTRACT FROM AUTHOR]

Hematopoietic stem cell transplantation (HSCT) remains the only curative treatment in patients with higher risk myelodysplastic syndrome (MDS), but the choice of the optimal alternative stem cell source is still a subject of debate in patients lacking an HLA-matched sibling donor. Here, we report on a large series of patients with MDS (N = 631) transplanted either with mobilized peripheral stem cells (PBs) from unrelated donors (n = 502) or with umbilical cord blood transplant (UCB, n = 129) as alternative grafts after reduced-intensity conditioning. Neutrophil engraftment was higher after PB (98% versus 78%, P < .0001). Acute graft-versus-host disease (GVHD) was similar after PB (31%) and UCB (29%), and chronic GVHD incidence was higher after PB (41% versus 23%). Two-year nonrelapse mortality was lower after PB (31% versus 42% P = .03). There was a better overall survival (OS) and disease-free survival (DFS) after PB (49% ± 2% versus 30% ± 4%, P < .0001 and 44% ± 2% versus 28% ± 4%, P < .0001). Multivariate analysis confirmed the advantage of PB for treatment-related mortality, OS, and DFS, whereas relative risk of chronic GVHD was similar. A multivariate analysis comparing PB from a 10/10 HLA-matched donor, PB from a 9/10 HLA-matched donor, and UCB showed an advantage on treatment-related mortality, DFS, and OS only in 10/10 PB. We conclude that in MDS patients lacking an HLA-matched sibling donor, PB from a 10/10 HLA-matched unrelated donor is the preferred source of hematopoietic stem cells. HLA-mismatched unrelated donor or cord blood seem to give similar inferior results except for neutrophil engraftment, which is delayed after UCB. [ABSTRACT FROM AUTHOR]