Alternative donors for allogeneic hematopoietic stem cell transplantation in poor-risk AML in CR1

Allogeneic hematopoietic stem cell transplantation (alloHSCT) remains the treatment of choice to consolidate remission in patients with poor-risk acute myeloid leukemia (AML). With increasing alternative donors available, the preferred donor or stem cell source is debated. We set out to study outcome in recipients of alloHSCT with poor-risk AML in first complete remission (CR1) by donor type. A total of 6545 adult patients with poor-risk AML in CR1 receiving an alloHSCT using matched related donor (MRD, n = 3511) or alternative donors, including 10/10 (n = 1959) or 9/10 matched unrelated donors (MUDs, n = 549), umbilical cord blood (UCB) grafts (n = 333), or haplo-identical (haplo) donors (n = 193) were compared. Overall survival (OS) at 2 years following MRD alloHSCT was an estimated 59 +/- 1%, which did not differ from 10/10 MUD (57 +/- 1%) and haplo alloHSCT (57 +/- 4%). OS, however, was significantly lower for 9/10 MUD alloHSCT (49 +/- 2%) and UCB grafts (44 +/- 3%), respectively (P < .001). Nonrelapse mortality (NRM) depended on donor type and was estimated at 26 +/- 3% and 29 +/- 3% after haplo alloHSCT and UCB grafts at 2 years vs 15 +/- 1% following MRD alloHSCT. Multivariable analysis confirmed the impact of donor type with OS following MRD, 10/10 MUD, and haplo alloHSCT not being statistically significantly different. NRM was significantly higher for alternative donors as compared with MRD alloHSCT. Collectively, these results suggest that alloHSCT with MRDs and 10/10 MUDs may still be preferred in patients with poor-risk AML in CR1. If an MRD or 10/10 MUD is not available, then the repertoire of alternative donors includes 9/10 MUD, UCB grafts, and haplo-identical donors. The latter type of donor is increasingly applied and now approximates results with matched donors.Peer reviewe

Hematopoietic stem cell therapy for autoimmune diseases - Clinical experience and mechanisms

With accumulating evidence and improved outcomes along with recognition that modern biological therapies are not universally effective, require chronic administration and have high acquisition costs, hematopoietic stem cell transplantation (HSCT) has become an emerging direction for cell therapy in autoimmune diseases (ADs). The goal of this therapy is to induce medication-free remissions by resetting the immune system into a naïve and self-tolerant state through eradication of the autoreactive immunologic memory and profound re-configuration of the immune system induced by the transplant procedure. Safety of HSCT has generally improved by implementing internal quality management and external accreditation. Inter-disciplinary guidelines for patient selection, transplant technique and supportive care along with greater center experience should optimize safe and appropriate delivery of HSCT in specific ADs. In this review, we discuss the current role and future perspectives of HSCT in AD, focusing on recent published clinical and scientific studies and recommendations in the field

The EBMT activity survey report 2017: a focus on allogeneic HCT for nonmalignant indications and on the use of non-HCT cell therapies.

Hematopoietic cell transplantation (HCT) is widely used for acquired and congenital disorders of the hematopoietic system. Number of transplants done in Europe and associated countries continues to rise with 45,418 HCT in 41,100 patients [(17,155 allogeneic (42%) and 23,945 autologous (58%)] reported by 683 centers in 50 countries in 2017. Main indications were myeloid malignancies 10,147 (25%; 96% allogeneic), lymphoid malignancies 26,488 (64%; 19% allogeneic), solid tumors 1,607 (3.9%; 2% allogeneic), and nonmalignant disorders 2,667 (7%; 81% allogeneic). Trends in donor choice seen before continue, with growing numbers of haploidentical HCT and decreasing use of cord blood. Of interest is that after many years of continued growth, the number of patients receiving an allogeneic HCT for marrow failure is decreasing slightly (p < 0.001). Such a change may be explained by the use of thrombopoietin analogs in aplastic anemia patients. Other nonmalignant indications, however continue to grow, most importantly HCT for hemoglobinopathies by 36%, equally for thalassemias and sickle cell disease. Non-HCT cell therapies have increased by 28% since 2015 and genetically modified T cells is type of cell therapy with the fastest growth. These annual reports reflect current activity and trends and are useful for health-care planning

The EBMT activity survey report 2017 : a focus on allogeneic HCT for nonmalignant indications and on the use of non-HCT cell therapies

Hematopoietic cell transplantation (HCT) is widely used for acquired and congenital disorders of the hematopoietic system. Number of transplants done in Europe and associated countries continues to rise with 45,418 HCT in 41,100 patients [(17,155 allogeneic (42%) and 23,945 autologous (58%)] reported by 683 centers in 50 countries in 2017. Main indications were myeloid malignancies 10,147 (25%; 96% allogeneic), lymphoid malignancies 26,488 (64%; 19% allogeneic), solid tumors 1,607 (3.9%; 2% allogeneic), and nonmalignant disorders 2,667 (7%; 81% allogeneic). Trends in donor choice seen before continue, with growing numbers of haploidentical HCT and decreasing use of cord blood. Of interest is that after many years of continued growth, the number of patients receiving an allogeneic HCT for marrow failure is decreasing slightly (p < 0.001). Such a change may be explained by the use of thrombopoietin analogs in aplastic anemia patients. Other nonmalignant indications, however continue to grow, most importantly HCT for hemoglobinopathies by 36%, equally for thalassemias and sickle cell disease. Non-HCT cell therapies have increased by 28% since 2015 and genetically modified T cells is type of cell therapy with the fastest growth. These annual reports reflect current activity and trends and are useful for health-care planning

Indications for haematopoietic cell transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2022

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

Indications for haematopoietic stem cell transplantation for haematological diseases, solid tumours and immune disorders : current practice in Europe, 2019

This is the seventh special EBMT report on the indications for haematopoietic stem cell transplantation for haematological diseases, solid tumours and immune disorders. Our aim is to provide general guidance on transplant indications according to prevailing clinical practice in EBMT countries and centres. In order to inform patient decisions, these recommendations must be considered together with the risk of the disease, the risk of the transplant procedure and the results of non-transplant strategies. In over two decades since the first report, the EBMT indications manuscripts have incorporated changes in transplant practice coming from scientific and technical developments in the field. In this same period, the establishment of JACIE accreditation has promoted high quality and led to improved outcomes of patient and donor care and laboratory performance in transplantation and cellular therapy. An updated report with operating definitions, revised indications and an additional set of data with overall survival at 1 year and non-relapse mortality at day 100 after transplant in the commonest standard-of-care indications is presented. Additional efforts are currently underway to enable EBMT member centres to benchmark their risk-adapted outcomes as part of the Registry upgrade Project 2020 against national and/or international outcome data

still a concern in patients with haematological malignancies and stem cell transplant recipients-authors' response

publishersversionpublishe

Hematopoietic stem cell transplantation for autoimmune diseases in the time of COVID-19: EBMT guidelines and recommendations

Coronavirus disease-19 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), represents one of the biggest challenges of 21st century, threatening public health around the globe. Increasing age and presence of co-morbidities are reported risk factors for severe disease and mortality, along with autoimmune diseases (ADs) and immunosuppressive treatments such as haematopoietic stem cell transplantation (HSCT), which are also associated with adverse outcomes. We review the impact of the pandemic on specific groups of patients with neurological, rheumatological, and gastroenterological indications, along with the challenges delivering HSCT in adult and pediatric populations. Moving forward, we developed consensus-based guidelines and recommendations for best practice and quality of patient care in order to support clinicians, scientists, and their multidisciplinary teams, as well as patients and their carers. These guidelines aim to support national and international organizations related to autoimmune diseases and local clinical teams delivering HSCT. Areas of unmet need and future research questions are also highlighted. The waves of the COVID-19 pandemic are predicted to be followed by an “endemic” phase and therefore an ongoing risk within a “new normality”. These recommendations reflect currently available evidence, coupled with expert opinion, and will be revised according to necessary modifications in practice

Long-term follow-up of IPEX syndrome patients after different therapeutic strategies : an international multicenter retrospective study

Background: Immunodysregulation polyendocrinopathy enteropathy x-linked(IPEX) syndrome is a monogenic autoimmune disease caused by FOXP3 mutations. Because it is a rare disease, the natural history and response to treatments, including allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppression (IS), have not been thoroughly examined. Objective: This analysis sought to evaluate disease onset, progression, and long-term outcome of the 2 main treatments in long-term IPEX survivors. Methods: Clinical histories of 96 patients with a genetically proven IPEX syndrome were collected from 38 institutions worldwide and retrospectively analyzed. To investigate possible factors suitable to predict the outcome, an organ involvement (OI) scoring system was developed. Results: We confirm neonatal onset with enteropathy, type 1 diabetes, and eczema. In addition, we found less common manifestations in delayed onset patients or during disease evolution. There is no correlation between the site of mutation and the disease course or outcome, and the same genotype can present with variable phenotypes. HSCT patients (n = 58) had a median follow-up of 2.7 years (range, 1 week-15 years). Patients receiving chronic IS (n 5 34) had a median follow-up of 4 years (range, 2 months-25 years). The overall survival after HSCT was 73.2% (95% CI, 59.4-83.0) and after IS was 65.1% (95% CI, 62.8-95.8). The pretreatment OI score was the only significant predictor of overall survival after transplant (P = .035) but not under IS. Conclusions: Patients receiving chronic IS were hampered by disease recurrence or complications, impacting long-term.disease-free survival. When performed in patients with a low OI score, HSCT resulted in disease resolution with better quality of life, independent of age, donor source, or conditioning regimen