Continuous and differential improvement in worldwide access to hematopoietic cell transplantation: activity has doubled in a decade with a notable increase in unrelated and non-identical related donors.

Promoting access to and excellence in hematopoietic cell transplantation (HCT) by collecting and disseminating data on global HCT activities is one of the principal activities of the Worldwide Network for Blood and Marrow Transplantation, a non-Governmental organization in working relations with the World Health Organization. HCT activities are recorded annually by member societies, national registries and individual centers including indication, donor type (allogeneic/autologous), donor match and stem cell source (bone marrow/peripheral blood stem cells/cord blood). In 2018, 1,768 HCT teams in 89 countries (six WHO regions) reported 93,105 (48,680 autologous and 44,425 allogeneic) HCT. Major indications were plasma cell disorders and lymphoma for autologous, and acute leukemias and MDS/MPN for allogeneic HCT. HCT number increased from 48,709 in 2007. Notable increases were seen for autoimmune diseases in autologous and hemoglobinopathies in allogeneic HCT. The number of allogeneic HCT more than doubled with significant changes in donor match. While HCT from HLA identical siblings has seen only limited growth, HCT from non-identical related donors showed significant increase worldwide. Strongest correlation between economic growth indicator of gross national income/capita and HCT activity/ten million population was observed for autologous HCT (r=0.79). HCT from unrelated donors showed strong correlation (r=0.68), but only moderate correlation (r=0.51) was detected from related donors. The use of HCT doubled in about a decade worldwide at different speed and with significant changes regarding donor match as a sign of improved access to HCT worldwide. Although narrowing, significant gaps remain between developing and non-developing countries.

Allogeneic haematopoietic cell transplantation for chronic myeloid leukaemia in Switzerland in the face of rapid development of effective drugs.

AIM: Until the year 2000, allogeneic haematopoietic cell transplantation (HCT) was the standard treatment for young and fit chronic myeloid leukaemia (CML) patients. CML was the main indication for allogeneic HCT. The introduction of tyrosine kinase inhibitors changed the treatment of CML patients dramatically. Allogeneic HCT was rapidly replaced by tyrosine kinase inhibitors as first-line treatment for CML, and the indication shifted to the treatment of non-responders, patients intolerant to tyrosine kinase inhibitors and patients whose CML is transforming to the accelerated phase and blast crisis. This paper describes changes in the use of transplantation technology for CML patients in the face of rapid drug development. METHODS: All patients receiving a transplant for CML between 1997 and 2021 in Switzerland were included in the study. For the purpose of this analysis, time periods were analysed in quinquennia, 1997-2001 (Q1), 2002-2006 (Q2), 2007-2011 (Q3), 2012-2016 (Q4) and 2017-2021 (Q5), as the observation period spanned 25 years. RESULTS: Overall, 239 patients received a transplant. These included 96 in Q1, 56 in Q2, 25 in Q3, 34 in Q4 and 28 in Q5. Patient characteristics changed over time: recent patients were older and had a longer interval from diagnosis to transplantation because of tyrosine kinase inhibitor treatment. However, the proportions of patients receiving transplants during an early versus advanced disease stage differed little. Transplant technology changed, as well. Patients received intensive conditioning regimens less often due to higher age and more commonly had peripheral blood as opposed to bone marrow transplants. However, the type of stem cell donor selected did not differ. In a univariable analysis, there were no significant differences in survival, progression-free survival, non-relapse mortality, relapse incidence or incidences of acute and chronic graft-versus-host disease among the five quinquennia. In a multivariable analysis, older age, donors other than HLA-identical siblings and more advanced disease stage, but not the quinquennium, were associated with higher risk of death. CONCLUSION: Since the introduction of tyrosine kinase inhibitors haematopoietic cell transplantation has been used less frequently to treat CML. Patients in recent cohorts received transplants at an older age and later in the disease course; despite these higher risks, the outcome of allogeneic HCT has not worsened over time but has not improved, either. As the outcome is worse in advanced phases, it is important to conduct transplants before disease progression. Therefore, patients with advanced disease should be monitored closely and receive transplants in time.

Hematopoietic cell transplantation and cellular therapies in Europe 2022. CAR-T activity continues to grow; transplant activity has slowed: a report from the EBMT.

In 2022, 46,143 HCT (19,011 (41.2%) allogeneic and 27,132 (58.8%) autologous) in 41,854 patients were reported by 689 European centers. 4329 patients received advanced cellular therapies, 3205 of which were CAR-T. An additional 2854 patients received DLI. Changes compared to the previous year were an increase in CAR-T treatments (+27%) and decrease in allogeneic (-4.0%) and autologous HCT (-1.7%). Main indications for allogeneic HCT were myeloid malignancies (10,433; 58.4%), lymphoid malignancies (4,674; 26.2%) and non-malignant disorders (2572; 14.4%). Main indications for autologous HCT were lymphomas (7897; 32.9%), PCD (13,694; 57.1%) and solid tumors (1593; 6.6%). In allogeneic HCT, use of sibling donors decreased by -7.7%, haploidentical donors by -6.3% and unrelated donors by -0.9%. Overall cord blood HCT decreased by -16.0%. Use of allogeneic, and to a lesser degree autologous HCT, decreased for lymphoid malignancies likely reflecting availability of new treatment modalities, including small molecules, bispecific antibodies, and CAR-T cells. Pediatric HCT activity remains stable (+0.3%) with differences between allogeneic and autologous HCT. Use of CAR-T continues to increase and reached a cumulative total of 9039 patients treated with wide differences across European countries. After many years of continuous growth, increase in application of HCT seems to have slowed down.

Hematopoietic cell transplantation and cellular therapies in Switzerland. Evolution over 25 years. A report from the stem cell transplantation and cellular therapies working groups of the SBST 1997-2021.

The Swiss Blood Stem Cell Transplantation and Cellular Therapy Group (SBST) leads a mandatory national registry for all hematopoietic stem cell transplants (HCT) and cellular therapies. After 25 years, information was available for 11,226 patients receiving an HCT (4031 allogeneic and 7195 autologous), including 925 pediatric patients. We compared patient characteristics and outcome by quinquennia 1997-2001, 2002-2006, 2007-2011, 2012-2016, and 2017-2021. There were numerous changes over time. Allogeneic transplant recipients became older (median age 33.7 vs. 54.3) and had more frequently unrelated donors and reduced intensity conditioning in later quinquennia. Similarly, age increased for recipients of autologous HCT (median 48.3 vs. 59.9). We did not see a significant drop in transplant activity during the SARS-CoV-2 pandemic. Analysis of outcome showed overall survival (relative risk (RR) of death 0.664 (0.529-0.832) and progression free survival (RR 0.708 (0.577-0.870) being improved over time comparing the latest to the first quinquennium adjusting for risk factors. Non-relapse mortality decreased in recipients of allogeneic HCT (RR: 0.371 (0.270-0.509)) over time but relapse risks did not. Outcome of autologous HCT improved as well across quinquennia, this improvement was mainly due to decreased relapse risks (RR 0.681 (0.597-0.777)), possibly related to maintenance treatment or rescue treatment for relapse mainly in myeloma patients. Cellular therapies other than allogeneic or autologous HCT, particularly chimeric antigen receptor T-cells (CAR-T) treatment have started to increase after 2019, year of approval of the first commercial CAR-T product in Switzerland. Data on chimeric antigen receptor T-cell treatment are too early for comparative analyses. Detailed analyses of changes over time are presented. This study includes all HCTs, and cellular therapies, data useful for quality assurance programs, health care cost estimation and benchmarking. Between 50% and 60% of patients are long-term survivors after both types of HCT, indicating growing populations of surviving patients requiring long-term care.

Decrease of lethal infectious complications in the context of causes of death (COD) after hematopoietic cell transplantation: COD-2 and COD-1 study of the Infectious Diseases Working Party EBMT.

We previously analyzed trends in incidence and factors associated with lethal complications in ALL/AML/CML patients (causes of deaths; COD-1 study). The objective of this study was the analysis of incidence and specific causes of death after HCT, with focus on infectious deaths in two time periods, 1980-2001 (cohort-1) and 2002-2015 (cohort-2). All patients with HCT for lymphoma, plasma cell disorders, chronic leukemia (except CML), myelodysplastic/myeloproliferative disorders, registered in the EBMT-ProMISe-database were included (n = 232,618) (COD-2 study). Results were compared to those in the ALL/AML/CML COD-1 study. Mortality from bacterial, viral, fungal, and parasitic infections decreased in very early, early and intermediate phases. In the late phase, mortality from bacterial infections increased, while mortality from fungal, viral, or unknown infectious etiology did not change. This pattern was similar for allo- and auto-HCT in COD-1 and COD-2 studies, with a distinct and constant lower incidence of all types of infections at all phases, after auto-HCT. In conclusion, infections were the main cause of death before day +100, followed by relapse. Mortality from infectious deaths significantly decreased, except late phase. Post-transplant mortality has significantly decreased in all phases, from all causes after auto-HCT; it has decreased in all phases after allo-HCT except late phase.

Benchmarking of survival outcomes following Haematopoietic Stem Cell Transplantation (HSCT): an update of the ongoing project of the European Society for Blood and Marrow Transplantation (EBMT) and Joint Accreditation Committee of ISCT and EBMT (JACIE).

From 2016 EBMT and JACIE developed an international risk-adapted benchmarking program of haematopoietic stem cell transplant (HSCT) outcome to provide individual EBMT Centers with a means of quality-assuring the HSCT process and meeting FACT-JACIE accreditation requirements relating to 1-year survival outcomes. Informed by previous experience from Europe, North America and Australasia, the Clinical Outcomes Group (COG) established criteria for patient and Center selection, and a set of key clinical variables within a dedicated statistical model adapted to the capabilities of the EBMT Registry. The first phase of the project was launched in 2019 to test the acceptability of the benchmarking model through assessment of Centers' performance for 1-year data completeness and survival outcomes of autologous and allogeneic HSCT covering 2013-2016. A second phase was delivered in July 2021 covering 2015-2019 and including survival outcomes. Reports of individual Center performance were shared directly with local principal investigators and their responses were assimilated. The experience thus far has supported the feasibility, acceptability and reliability of the system as well as identifying its limitations. We provide a summary of experience and learning so far in this 'work in progress', as well as highlighting future challenges of delivering a modern, robust, data-complete, risk-adapted benchmarking program across new EBMT Registry systems.

Hematopoietic cell transplantation and cellular therapies in Europe 2021. The second year of the SARS-CoV-2 pandemic. A Report from the EBMT Activity Survey.

In 2021, 47,412 HCT (19,806 (42%) allogeneic and 27,606 (58%) autologous) in 43,109 patients were reported by 694 European centers. 3494 patients received advanced cellular therapies, 2524 of which were CAR-T treatments, an additional 3245 received DLI. Changes compared to the previous year were CAR-T treatment (+35%), allogeneic HCT +5.4%, autologous HCT +3.9%, more pronounced in non-malignant disorders. Main indications for allogeneic HCT were myeloid malignancies 10,745 (58%), lymphoid malignancies 5127 (28%) and non-malignant disorders 2501 (13%). Main indications for autologous HCT were lymphoid malignancies 22,129 (90%) and solid tumors 1635 (7%). In allogeneic HCT, use of haploidentical donors decreased by -0.9% while use of unrelated and sibling donors increased by +4.3% and +9%. Cord blood HCT decreased by -5.8%. Pediatric HCT increased overall by +5.6% (+6.9% allogeneic and +1.6% autologous). Increase in the use of CAR-T was mainly restricted to high-income countries. The drop in HCT activity reported in 2020 partially recovered in 2021, the second year of the SARS-CoV-2 pandemic. The transplant community confronted with the pandemic challenge, continued in providing patients access to treatment. This annual EBMT report reflects current activities useful for health care resource planning.

Allogeneic hematopoietic stem cell transplantation in non-Hodgkin lymphoma in Switzerland, 30 years of experience: Sooner is better.

Due to relatively high nonrelapse mortality (NRM), allogeneic hematopoietic stem cell transplantation (allo-HSCT) in non-Hodgkin's lymphoma (NHL) remains the ultimate line of treatment but the only curable approach in a setting of relapse/refractory disease. Here, we conducted a retrospective, multicenter, registry-based analysis on patients who underwent allo-HSCT for NHL in Switzerland, over 30-year (1985-2020) period. The study included 301 allo-HSCTs performed for NHL patients in three University Hospitals of Switzerland (Zurich, Basel and Geneva) 09/1985 to 05/2020. We assessed in univariate and multivariable analysis the impact on survivals (overall survival [OS], relapse free survival [RFS], relapse incidence [RI], and non-treatment related mortality [NRM]). The maximum follow-up was 25 years with median follow-up for alive patients of 61 months. The median age at allo-HSCT was 51 years. Three- and -year OS was - 59.5% and 55.4%; 3- and 5-year PFS was 50% and 44%; 3- and 5-year NRM was 21.7% and 23.6%. RI at 3 and 5 years was 27.4% and 34.9%. In conclusion, our analysis of the entire Swiss experience of allo-HSCT in patients with NHL shows promising 5- and possibly 10-year OS and relatively acceptable NRM rates for such population, the majority being not in complete remission (CR) at the time of transplantation.

Allogeneic hematopoietic stem cell transplantation in Hodgkin lymphoma in Switzerland, 20 years of experience: 2001-2020.

Despite the high cure rate with initial therapy, approximately 10% of Hodgkin lymphoma (HL) patients are refractory to initial treatment, and up to 30% of patients will relapse after achieving initial complete remission. Despite promising initial results of treatment by immune checkpoint inhibitors, most patients will eventually progress. We analyzed 62 adult patients with relapsed or refractory HL (rrHL) treated by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in one of three University Hospitals of Switzerland (Zurich, Basel, and Geneva) between May 2001 and January 2020. The primary endpoint was overall survival (OS). Secondary endpoints were relapse-free survival (RFS), non-relapse mortality (NRM), and relapse incidence, which were assessed in univariate analysis. The median follow-up was 61 months (interquartile range 59-139). The 2- and 5-year OS was 54% (standard error (SE) ±12) and 50.2% (SE ±13.3), respectively, and the 2- and 5-year RFS was 40.7% (SE ±16.3) and 34.4% (SE ±19.0), respectively. NRM was 23.1% (SE ±2.2) and 27.4% (SE ±2.5) at 2 and 5 years, respectively. The cumulative incidence of relapse was 36.1% (SE ±5.6) at 2 years and 38.2% (SE ±6.6) at 5 years. Our analysis of allo-HSCT outcomes in the context of rrHL shows encouraging OS and RFS rates, with the mortality rate reaching plateau at 50% at 2 years after allo-HSCT. This confirms that allo-HSCT still remains as a potentially curative option for half of patients with rrHL.

An Analysis of the Worldwide Utilization of Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) has an aggressive course and a historically dismal prognosis. For many patients, hematopoietic stem cell transplantation (HSCT) represents the best option for cure, but access, utilization, and health inequities on a global scale remain poorly elucidated. We wanted to describe patterns of global HSCT use in AML for a better understanding of global access, practices, and unmet needs internationally. Estimates of AML incident cases in 2016 were obtained from the Global Burden of Disease 2019 study. HSCT activities were collected from 2009 to 2016 by the Worldwide Network for Blood and Marrow Transplantation through its member organizations. The primary endpoint was global and regional use (number of HSCT) and utilization of HSCT (number of HSCT/number of incident cases) for AML. Secondary outcomes included trends from 2009 to 2016 in donor type, stem cell source, and remission status at time of HSCT. Global AML incidence has steadily increased, from 102,000 (95% uncertainty interval: 90,200-108,000) in 2009 to 118,000 (104,000-126,000) in 2016 (16.2%). Over the same period, a 54.9% increase from 9659 to 14,965 HSCT/yr was observed globally, driven by an increase in allogeneic (64.9%) with a reduction in autologous (-34.9%) HSCT. Although the highest numbers of HSCT continue to be performed in high-resource regions, the largest increases were seen in resource-constrained regions (94.6% in Africa/East Mediterranean Region [AFR/EMR]; 34.7% in America-Nord Region [AMR-N]). HSCT utilization was skewed toward high-resource regions (in 2016: AMR-N 18.4%, Europe [EUR] 17.9%, South-East Asia/Western Pacific Region [SEAR/WPR] 11.7%, America-South Region [AMR-S] 4.5%, and AFR/EMR 2.8%). For patients <70 years of age, this difference in utilization was widened; AMR-N had the highest allogeneic utilization rate, increasing from 2009 to 2016 (30.6% to 39.9%) with continued low utilization observed in AFR/EMR (1.7% to 2.9%) and AMR-S (3.5% to 5.4%). Across all regions, total HSCT for AML in first complete remission (CR1) increased (from 44.1% to 59.0%). Patterns of donor stem cell source from related versus unrelated donors varied widely by geographic region. SEAR/WPR had a 130.2% increase in related donors from 2009 to 2016, and >95% HSCT donors in AFR/EMR were related; in comparison, AMR-N and EUR have a predilection for unrelated HSCT. Globally, the allogeneic HSCT stem cell source was predominantly peripheral blood (69.7% of total HSCT in 2009 increased to 78.6% in 2016). Autologous HSCT decreased in all regions from 2009 to 2016 except in SEAR/WPR (18.9%). HSCT remains a central curative treatment modality in AML. Allogeneic HSCT for AML is rising globally, but there are marked variations in regional utilization and practices, including types of graft source. Resource-constrained regions have the largest growth in HSCT use, but utilization rates remain low, with a predilection for familial-related donor sources and are typically offered in CR1. Further studies are necessary to elucidate the reasons, including economic factors, to understand and address these health inequalities and improve discrepancies in use of HSCT as a potentially curative treatment globally.

Strategic priorities for hematopoietic stem cell transplantation in the EMRO region.

The World Health Organization-designated Eastern Mediterranean region (EMRO) consists of 22 countries in North Africa and Western Asia with a collective population of over 679 million. The area comprises some of the wealthiest countries per capita income and some of the poorest. The population structure is also unique and contrasts with western countries, with a much younger population. The region sits in the heart of the thalassemia belt. Many countries have a significant prevalence of sickle cell disease, and cancer is on the rise in the region. Therefore, the strategic priorities for the growth and development of hematopoietic stem cell transplantation (HSCT) differ from country to country based on resources, healthcare challenges, and prevalent infrastructure. Thirty-one reporting teams to the Eastern Mediterranean Blood and Marrow Transplantation Group have active HSCT programs in 12 countries; allogeneic transplants outnumber autologous transplants, and the proportion of allotransplants for non-malignant conditions is higher in the EMRO region than in Western Europe and North America. The vast majority (99%) of allotransplants are from matched related donors. Matched unrelated donors and other alternate donor transplants are underutilized. The chance of finding a matched related donor for allografts is higher, with a significant chance of finding matched donors among non-sibling related donors. Reasons for relatively lower rates of transplants compared with other countries are multifactorial. Capacity building, development of newer centers, innovative funding, and better utilization of information technology are required to make transplantation as an accessible modality to more patients. Cost-effectiveness and cost-containment, regulation, and ensuring quality will all be priorities in planning HSCT development in the region.

Increasing access to hematopoietic cell transplantation in Latin America: results of the 2018 LABMT activity survey and trends since 2012.

A total of 5642 hematopoietic cell transplants (HCT) in 5445 patients (2196-40% allogeneic and 3249-60% autologous) were reported by 127 teams in 14 Latin American countries that answered the 2018 LABMT/WBMT Global Transplant Activity survey. The transplant rate (defined as the number of first transplants per 10 million inhabitants per year) was 85 (51 autologous and 34 allogeneic) in 2018. The main indications for allogeneic HCT were acute leukemias (60%), while plasma cell disorders and lymphomas were the most common conditions warranting autologous HCT (50 and 36%, respectively). In the allogeneic HCT, HLA-identical siblings were the main type of donor (44%) followed by related mismatched/haploidentical donors (32%). Peripheral blood stem cells were used in 98% of the autologous and in 64% of the allogeneic transplants. From 2012 to 2018, there was a 64% increase of reported HCT (54% in autologous and 80% in allogeneic). In the allogeneic setting, the most pronounced increase in donor type was observed in haploidentical relatives (from 94 procedures in 2012 up to 710 in 2018), surpassing unrelated donors as of 2017. Significant trends detected in Latin America include rising numbers of the procedures reported, a faster increase in allogeneic HCT compared with autologous HCT and a significant increase in family mismatched/haploidentical donors. The LABMT/WBMT activity survey provides useful data to understand the HCT activity and trends in Latin America.

External Validation of the Revised Pretransplant Assessment of Mortality Score in Allogeneic Hematopoietic Cell Transplantation: A Cohort Study.

Pretransplant risk scores such as the revised Pretransplant Assessment of Mortality (rPAM) score help to predict outcome of patients receiving allogeneic hematopoietic cell transplantation (allo-HCT). Since the rPAM has not been validated externally in a heterogeneous patient population with different diseases, we aimed to validate the rPAM score in a real-world cohort of allo-HCT patients. A total of 429 patients were included receiving their first allo-HCT from 2008 to 2015. The predictive capacity of the rPAM score for 4-year overall survival (OS), nonrelapse mortality (NRM), and cumulative incidence of relapse (CIR) after allo-HCT was evaluated. Moreover, we evaluated the impact of the rPAM score for OS and used uni- and multivariable analyses to identify patient- and transplant-related predictors for OS. In rPAM score categories of <17, 17-23, 24-30, and >30, the OS probability at 4 years differed significantly with 61%, 36%, 26%, and 10%, respectively (P < 0.0001). In contrast to CIR, the NRM increased significantly in patients with higher rPAM scores (P < 0.001). Regarding the OS, the rPAM score had an area under the receiver operating characteristics curve of 0.676 (95% confidence interval [CI], 0.625-0.727) at 4 years. In the multivariable analysis, the rPAM score was associated with OS-independently of conditioning regimens (adjusted hazard ratio per 1-unit increase, 1.10; 95% CI, 1.06-1.10; P < 0.001). Additionally, forced expiratory volume in 1 second and the disease risk index were the components of the rPAM significantly associated with outcome. In our large real-world cohort with extended follow-up, the rPAM score was validated as an independent predictor of OS in patients with hematologic disorders undergoing allo-HCT.

Optimized cyclosporine starting dose may reduce risk of acute GvHD after allogeneic hematopoietic cell transplantation: a single-center cohort study.

Cyclosporine A (CsA) is commonly used for Graft versus Host Disease (GvHD) prophylaxis at a recommended starting dose of 3 mg/kg/d: Evidence for the effect of different CsA starting doses on GvHD risk is limited. We therefore estimated the association of 5 mg/kg/d (CsA5) and 3 mg/kg/d (CsA3) CsA starting doses with GvHD risk in two consecutive cohorts of allogeneic hematopoietic cell transplantation (allo-HCT) patients, exploring potential risk factors for incident acute GvHD, with a focus on CsA starting dose. We analyzed 519 patients within CsA5 (n = 153) and CsA3 (n = 366). The cumulative incidence function of acute GvHD grade ≥2 was higher in the CsA3 compared to the CsA5 group (41% vs. 33%, respectively; p = 0.043), without impacting chronic GvHD. In multivariable analysis, a CsA starting dose of 3 mg/kg/d, no ATG use, unrelated donor and high to very high disease risk index were significantly associated with acute GvHD grade ≥2. A higher CsA starting dose of 5 mg/kg/d was independently associated with lower acute GvHD risk, and higher CsA levels in the early period after allo-HCT were reached.

Impact of the SARS-CoV-2 pandemic on hematopoietic cell transplantation and cellular therapies in Europe 2020: a report from the EBMT activity survey.

In 2020, 45,364 HCT in 41,016 patients, 18,796 (41%) allogeneic and 26,568 (59%) autologous in 690 centers were reported. Changes observed were as follows: total number of HCT -6.5%, allogeneic HCT -5.1%, autologous HCT -7.5%, and were more pronounced in non-malignant disorders for allogeneic HCT and in autoimmune disease for autologous HCT. Main indications were myeloid malignancies 10,441 (25%), lymphoid malignancies 26,120 (64%) and non-malignant disorders 2532 (6%). A continued growth in CAR-T cellular therapies to 1874 (+65%) patients in 2020 was observed. In allogeneic HCT, the use of haploidentical donors increased while use of unrelated and sibling donors decreased. Cord blood HCT increased by 11.7% for the first time since 2012. There was a significant increase in the use of non-myeloablative but a drop in myeloablative conditioning and in use of marrow as stem cell source. We interpreted these changes as being due to the SARS-CoV-2 pandemic starting early in 2020 in Europe and provided additional data reflecting the varying impact of the pandemic across selected countries and larger cities. The transplant community confronted with the pandemic challenge, continued in providing patients access to treatment. This annual report of the EBMT reflects current activities useful for health care planning.

One and a half million hematopoietic stem cell transplants: continuous and differential improvement in worldwide access with the use of non-identical family donors.

The Worldwide Network of Blood and Marrow Transplantation (WBMT) pursues the mission of promoting hematopoietic cell transplantation (HCT) for instance by evaluating activities through member societies, national registries and individual centers. In 2016, 82,718 first HCT were reported by 1,662 HCT teams in 86 of the 195 World Health Organization member states representing a global increase of 6.2% in autologous HCT and 7.0% in allogeneic HCT and bringing the total to 1,298,897 procedures. Assuming a frequency of 84,000/year, 1.5 million HCT were performed by 2019 since 1957. Slightly more autologous (53.5%) than allogeneic and more related (53.6%) than unrelated HCT were reported. A remarkable increase was noted in haploidentical related HCT for leukemias and lymphoproliferative diseases, but even more in non-malignant diseases. Transplant rates (TR; HCT/10 million population) varied according to region reaching 560.8 in North America, 438.5 in Europe, 76.7 in Latin America, 53.6 in South East Asia/Western Pacific (SEA/WPR) and 27.8 in African/East Mediterranean (AFR/EMR). Interestingly, haploidentical TR amounted to 32% in SEA/WPR and 26% in Latin America, but only 14% in Europe and EMR and 4.9% in North America of all allogeneic HCT. HCT team density (teams/10 million population) was highest in Europe (7.7) followed by North America (6.0), SEA/WPR (1.9), Latin America (1.6) and AFR/EMR (0.4). HCT are increasing steadily worldwide with narrowing gaps between regions and greater increase in allogeneic compared to autologous activity. While related HCT is rising, largely due to increase in haploidentical HCT, unrelated HCT is plateauing and cord blood HCT is in decline.

Analysis of biological models to predict clinical outcomes based on HLA-DPB1 disparities in unrelated transplantation.

HLA compatibility is a key factor for survival after unrelated hematopoietic stem cell transplantation (HSCT). HLA-A, -B, -C, -DRB1, and -DQB1 are usually matched between donor and recipient. By contrast, HLA-DPB1 mismatches are frequent, although it is feasible to optimize donor selection and DPB1 matching with prospective typing. Because classical DPB1 allele mismatches are often unavoidable, however, several biological models have been developed to predict the optimal DPB1 mismatch combination for less graft-versus-host disease (GVHD) and better overall survival. In 909 recipient/donor pairs, we analyzed the role of 3 biological models: T-cell epitopes (TCEs) based on the immunogenicity of DPB1, cell surface expression of DPB1 molecules based on a single-nucleotide polymorphism located in the 3' untranslated region, and the Predicted Indirectly ReCognizable HLA Epitopes (PIRCHE) model based on the presentation of allogeneic peptides derived from mismatched HLA, compared with the classical allele mismatch. Matching for both DPB1 alleles remains the best option to prevent acute GVHD. In the situation of one DPB1 allele mismatch, the donor associated with the lowest acute GVHD risks is mismatched for an allele with a low expression profile in the recipient, followed by a permissive TCE3/4 mismatch and/or the absence of PIRCHE II potential against the recipient. In the context of 2 DPB1 mismatches, the same considerations apply for a permissive TCE3/4 mismatch and no PIRCHE II. By combining the biological models, the most favorable DPB1 constellation can be defined. This approach will help optimize donor selection and improve post-HSCT complications and patient prognosis.

Hematopoietic cell transplantation and cellular therapy survey of the EBMT: monitoring of activities and trends over 30 years.

Numbers of Hematopoietic cell transplantation (HCT) in Europe and collaborating countries continues to rise with 48,512 HCT in 43,581 patients, comprising of 19,798 (41%) allogeneic and 28,714 (59%) autologous, reported by 700 centers in 51 countries during 2019. Main indications were myeloid malignancies 10,764 (25%), lymphoid malignancies 27,895 (64%), and nonmalignant disorders 3173 (7%). A marked growth in CAR-T cellular therapies from 151 in 2017 to 1134 patients in 2019 is observed. This year's analyses focus on changes over 30 years. Since the first survey in 1990 where 143 centers reported 4234 HCT, the number has increased to 700 centers and 48,512 HCT. Transplants were reported in 20 countries in 1990, and 51, 30 years later. More than 800,000 HCT in 715,000 patients were reported overall. Next to the massive expansion of HCT technology, most notable developments include the success of unrelated donor and haploidentical HCT, an increase followed by decrease in the number of cord blood transplants, use of reduced intensity HCT in older patients, and the phenomenal rise in cellular therapy. This annual report of the European Society for Blood and Marrow Transplantation (EBMT) reflects current activity and highlights important trends vital for health care planning.

The Survey on Cellular and Tissue-Engineered Therapies in Europe in 2016 and 2017.

This report describes activity in Europe for the years 2016 and 2017 in the area of cellular and tissue-engineered therapies, excluding hematopoietic stem cell treatments for the reconstitution of hematopoiesis. It is the eighth of its kind and is supported by five established scientific organizations. In 2016 and 2017, a combined 234 teams from 29 countries responded to the cellular and engineered tissue therapy survey; 227 teams reported treating 8236 patients in these 2 years. Indications were categorized in hematology/oncology (40%; predominantly prevention or treatment of graft vs. host disease and hematopoietic graft enhancement), musculoskeletal/rheumatological disorders (29%), cardiovascular disorders (6%), neurological disorders (4%), gastrointestinal disorders (<1%), as well as miscellaneous disorders (20%), which were not assigned to the previous indications. The predominantly used cells were autologous (61%). The majority of autologous cells were used to treat musculoskeletal/rheumatological (44%) disorders, whereas allogeneic cells were mainly used for hematology/oncology (78%). The reported cell types were mesenchymal stem/stromal cells (MSCs) (56%), hematopoietic cells (21%), keratinocytes (7%), chondrocytes (6%) dermal fibroblasts (4%), dendritic cells (2%), and other cell types (4%). Cells were expanded in vitro in 62% of the treatments, sorted in 11% of the cases, and rarely transduced (2%). The processing of cells was outsourced to external facilities in 30% of the cases. Cells were delivered predominantly intravenously or intra-arterially [47%], as suspension [36%], or using a membrane/scaffold (16%). The data are compared with those from previous years to identify trends in a rapidly evolving field. In this edition, the report includes a critical discussion of data collected in the space of orthopedics and the use of MSCs.