CAR T-Cells for the Treatment of Refractory or Relapsed Large B-Cell Lymphoma: A Single-Center Retrospective Canadian Study.

BACKGROUND: Chimeric antigen receptor (CAR) T-cells are an important new third-line treatment option for large B-cell lymphoma (LBCL). The objective response rates in pivotal early phase clinical trials with CAR T-cells were very promising. The objective of this study was to describe the efficacy results obtained with CAR T-cells infusions in our institution and to compare the toxicities of our cohort with those of pivotal trials and studies conducted in a real-life setting. PATIENTS AND METHODS: Efficacy and safety data were retrospectively collected from 25 patients with LBCL treated with CAR T-cells therapy at CHU de Québec-Université Laval. A literature search was then performed to identify other efficacy or safety data from a real-life setting. RESULTS: At 3 months post infusion, the objective response rate (ORR) in our population with tisagenlecleucel and axicabtagene-ciloleucel were 20% and 47%, respectively. Bulky disease was the only negative predictor of poor response at 3 months (0% vs. 53%, P = .03). Bulky disease was associated with a median PFS of 2 months compared to 5 months for non-bulky disease (P = .0009). Grade ≥ 3 hematological toxicities were greater in patients treated with axi-cel (60% vs. 20%, P = .048), without bone marrow involvement (55% vs. 0%, P =.046), without stage IV disease (72% vs. 21%, P =.02), with refractory disease (67% vs. 10%, P =.01) or having been affected by cytokine release syndrome (58% vs. 0%, P =.02). CONCLUSION: The poor response rate at 3 months after infusion in our cohort was influenced mainly by bulky disease. Further studies are needed to better characterize the loss of efficacy of CAR T-cells because the majority of patients will relapse over time.

Incidence and severity of early electrolyte abnormalities following autologous haematopoietic stem cell transplantation.

BACKGROUND: Haematopoietic stem cell transplantation (HSCT) has gained worldwide acceptance as a therapeutic option for many haematological and non-haematological conditions. Local experience supports that electrolyte abnormalities are quite common; however, the incidence and timing of these abnormalities are unknown. METHOD: We conducted a retrospective descriptive study of 48 consecutive adult patients in order to study the incidence and the timing of electrolyte abnormalities following autologous HSCT. Clinical and pharmacological data were collected by the review of patient charts. Potassium, magnesium, calcium, phosphorus and albumin levels were retrieved from the laboratory. RESULTS: HSCT was performed for multiple myeloma (28/48), lymphoma (8/48), Hodgkin disease (4/48), amyloidosis (4/48) and other neoplasia (4/48). At baseline, 21% of patients (10/48) had low electrolyte levels. Following autologous HSCT, hypokalaemia occurred in 81% (39/48), hypomagnesaemia in 67% (32/48), hypocalcaemia in 49% (17/35) and hypophosphataemia in 91% (39/43) of the patients. The nadir of the electrolyte levels occurred between day 8 and 10 after stem cell transplant while the engraftment occurred at day 11.6+/-0.6. The use of amphotericin B and furosemide was associated with more pronounced hypokalaemia and hypomagnesaemia. Hypocalcaemia was more pronounced in patients with multiple myeloma. High levels of electrolytes occurred in only 25% of the patients, none of which required specific treatment. CONCLUSION: We conclude that low electrolyte levels are extremely common after HSCT and the pathophysiology of these abnormalities are complex and multifactorial.

Adaptation of clinical guidelines: literature review and proposition for a framework and procedure.

PURPOSE: The development and updating of high-quality clinical practice guidelines require substantial resources. Many guideline programmes throughout the world are using similar strategies to achieve similar goals, resulting in many guidelines on the same topic. One method of using resources more efficiently and avoiding unnecessary duplication of effort would be to adapt existing guidelines. The aim was to review the literature on adaptation of guidelines and to propose a systematic approach for adaptation of guidelines. DATA SOURCES: We selected and reviewed reports describing the methods and results of adaptation of guidelines from those found by searching Medline, Internet, and reference lists of relevant papers. On the basis of this review and our experience in guideline development, we proposed a conceptual framework and procedure for adaptation of guidelines. RESULTS: Adaptation of guidelines is performed either as an alternative to de novo guideline development or to improve guideline implementation through local tailoring of an international or national guideline. However, no validated process for the adaptation of guidelines produced in one cultural and organizational setting for use in another (i.e. trans-contextual adaptation) was found in the literature. The proposed procedure is a stepwise approach to trans-contextual adaptation, including searching for existing guidelines, quality appraisal, detailed analysis of the coherence between the evidence and the recommendations, and adaptation of the recommendations to the target context of use, taking into account the organization of the health care system and cultural context. CONCLUSIONS: Trans-contextual adaptation of guidelines is increasingly being considered as an alternative to de novo guideline development. The proposed approach should be validated and evaluated to determine if it can reduce duplication of effort and inefficient use of resources, although guaranteeing a high-quality product, compared with de novo development.