For over two decades, the EBMT has updated recommendations on indications for haematopoietic cell transplantation (HCT) practice based on clinical and scientific developments in the field. This is the eighth special EBMT report on the indications for HCT for haematological diseases, solid tumours and immune disorders. Our aim is to provide general guidance on HCT indications according to prevailing clinical practice in EBMT countries and centres. In order to inform patient decisions, these recommendations must be considered in conjunction with the risk of the disease, risk of HCT procedure and non-transplant strategies, including evolving cellular therapies. HCT techniques are constantly evolving and we make no specific recommendations, but encourage harmonisation of practice, where possible, to ensure experience across indications can be meaningfully aggregated via registry outputs. We also recommend working according to JACIE accreditation standards to maintain quality in clinical and laboratory components of practice, including benchmarking of survival outcomes. Since the last edition, the COVID-19 pandemic has affected clinical decision making and activity across indications. Although the full impact of the pandemic is yet to be determined, we recommend that decision making across indications is delivered with ongoing reference to EBMT and national COVID-19 guidance, in accordance with current local conditions.

PURPOSE: To review recent advances in peripheral-blood progenitor-cell (PBPC) transplantation in order to define the optimal cell dose required for autologous and allogeneic transplantation. MATERIALS AND METHODS: A search of MEDLINE was conducted to identify relevant publications. Their bibliographies were also used to identify further articles and abstracts for critical review. RESULTS: The CD34⁺ cell content of a graft is regarded as an accurate predictor of engraftment success. Postchemotherapy autologous PBPC transplantation with ≥ 5 × 10⁶ CD34⁺ cells/kg body weight leads to more rapid engraftment than does transplantation of lower cell doses. Further increases in transplant cell dose further accelerate platelet but not neutrophil engraftment. Evidence that long-term hematopoietic recovery may be more accurately predicted by the subpopulation of primitive progenitors transplanted suggests that the content of CD34⁺CD33⁻ and long-term culture-initiating cells in cell collection samples may be important for predicting successful engraftment, particularly in patients with poor mobilization. Allogeneic transplantation has been limited by concerns regarding graft-versus-host disease and the use of hematopoietic growth factors in donors. The risk of graft rejection and engraftment failure after HLA-mismatched allogeneic transplantation may be overcome by intensive chemoradiotherapy and the infusion of large numbers of T cell–depleted hematopoietic stem cells. CONCLUSION: An optimal cell dose of ≥ 8 × 10⁶ CD34⁺ cells/kg seems to be recommended for autologous PBPC transplantation. This dose facilitates the administration of scheduled chemotherapy on time and reduces the demand for other supportive therapies. A combination of growth factors may enable patients with poor mobilization to achieve a collection sufficient to allow transplantation. The optimum PBPC dose for allogeneic transplantation remains to be defined.

Purpose: Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV) –related malignancy expressing EBV antigens that are possible targets of cell therapy, including latent membrane protein 2 (LMP2). We conducted a clinical trial of EBV-targeted cell therapy with autologous virus-specific cytotoxic T lymphocytes (CTLs) for NPC refractory to conventional treatments. Patients and Methods: Ten patients with EBV-related stage IV NPC in progression after conventional radiotherapy and chemotherapy received intravenously autologous EBV-specific CTLs reactivated and expanded ex vivo from peripheral blood lymphocytes through stimulation with EBV-transformed autologous B-lymphoblastoid cell lines (LCL). Toxicity, specific cellular immune responses, and clinical tumor responses were evaluated. Results: EBV-specific CTLs could be generated in all patients and were predominantly CD3⁺/CD8⁺ T lymphocytes displaying specific killing of autologous EBV-LCL, autologous NPC cells as well as autologous targets bearing the EBV antigen LMP2. Patients received two to 23 infusions of EBV-specific CTLs that were well tolerated with the exception of grade 1 to 2 inflammatory reactions at the tumor site in two cases. Control of disease progression was obtained in six of 10 patients (two with partial response and four with stable disease). Analysis of interferon-γ–producing cells demonstrated an increased frequency of EBV-specific immunity, with appearance of LMP2-specific responses in four patients, of whom three had clinical benefit. Conclusion: Cell therapy with EBV-targeted autologous CTLs is safe, induces LMP-2-specific immunologic responses, and is associated with objective responses and control of disease progression in patients with stage IV NPC resistant to conventional treatments.

Early palliative care (EPC) in oncology has been shown to have a positive impact on clinical outcome, quality-of-care outcomes, and costs. However, the optimal way for activating EPC has yet to be defined. This prospective, multicentre, randomised study was conducted on 207 outpatients with metastatic or locally advanced inoperable pancreatic cancer. Patients were randomised to receive 'standard cancer care plus on-demand EPC' (n = 100) or 'standard cancer care plus systematic EPC' (n = 107). Primary outcome was change in quality of life (QoL) evaluated through the Functional Assessment of Cancer Therapy - Hepatobiliary questionnaire between baseline (T0) and after 12 weeks (T1), in particular the integration of physical, functional, and Hepatic Cancer Subscale (HCS) combined in the Trial Outcome Index (TOI). Patient mood, survival, relatives' satisfaction with care, and indicators of aggressiveness of care were also evaluated. The mean changes in TOI score and HCS score between T0 and T1 were -4.47 and -0.63, with a difference between groups of 3.83 (95% confidence interval [CI] 0.10-7.57) (p = 0.041), and -2.23 and 0.28 (difference between groups of 2.51, 95% CI 0.40-4.61, p = 0.013), in favour of interventional group. QoL scores at T1 of TOI scale and HCS were 84.4 versus 78.1 (p = 0.022) and 52.0 versus 48.2 (p = 0.008), respectively, for interventional and standard arm. Until February 2016, 143 (76.9%) of the 186 evaluable patients had died. There was no difference in overall survival between treatment arms. Systematic EPC in advanced pancreatic cancer patients significantly improved QoL with respect to on-demand EPC.

This review summarizes the cellular therapy approaches stemming from hematopoietic stem cell transplantation, their challenges, and opportunities.