Worldwide Network For Blood And Marrow Transplantation Research Articles

Radiation hazards of the Ukraine nuclear power plants: how can international blood and marrow stem cell transplant societies help?

Any conflict in countries that process nuclear power plants raises concerns of the potential radiation injuries to the people in that region and beyond such as the current conflict in Ukraine. International healthcare organizations and societies should prepare for the potential scenarios of nuclear incidents. The Worldwide Network for Blood and Marrow Transplantation (WBMT) and its members, have recent experience preparing for this type of events such as the Fukushima incident in 2011. In this article, we discuss the risks of radiation exposure, current guidelines, and scientific evidence on hematopoietic support, including the role of hematopoietic stem cell transplant (HCT) for those exposed to nuclear radiation, and the role that the WBMT and other global BMT societies can play in triaging and managing people suffering from radiation injuries.

Worldwide Network for Blood and Marrow Transplantation (WBMT) Global Study on Baseline Characteristics and Clinical Outcomes in NEWLY Diagnosed Multiple Myeloma Patients Undergoing Upfront Autologous STEM Cell Transplantation, a Study Off 61,725 Patients from 629 Centers

Background: Patients with newly diagnosed multiple myeloma (NDMM) undergoing upfront autologous stem cell transplantation (ASCT) have different characteristics worldwide, likely due to variances in transplant activity, patient factors and health economic factors including access to new myeloma therapies. The first aim of this retrospective study was to analyze the global baseline patient characteristics and outcomes of upfront ASCT in NDMM. Methods: Data on patient characteristics and transplant outcomes for patients with NDMM who received an upfront ASCT between 2013 and 2017 were provided to the Worldwide Network for Blood and Marrow Transplantation (WBMT) by the European Society for Blood and Marrow Transplantation (EBMT), the Center for International Blood and Marrow Transplantation (CIBMTR), the Asian Pacific Blood and Marrow Transplant Group (APBMT), the Australia and New Zealand Transplant and Cellular Therapies Registry (ANZTCT), the Eastern Mediterranean Blood and Marrow Transplant Group (EMBMT), the Latin American Bone Marrow Transplant Group (LABMT), and the Ottawa Canadian Registry. There primary endpoints were overall (OS) and non-relapse mortality (NRM) and the secondary were progression-free survival (PFS) and relapse incidence (RI). The Kaplan-Meier estimator and log-rank test were used for OS and PFS, and the crude cumulative incidence estimator and Gray's test were used for competing events (RI and NRM). Age at ASCT, sex, year of ASCT, disease stage, Karnofsky score, MM classification, preparative regimen, time between diagnosis and ASCT, ISS stage at diagnosis, cytogenetic risk, and HCT-CI score were studied for prognostic value. Multivariable (cause specific) models included a random effect for each country and were censored at 3 years for OS and PFS and at 1 year for RI and NRM. Results: 61,725 patients from 629 centers (median patients/center = 67) were included: 61% from EBMT, 26% CIBMTR, 6% APBMT (5% Japan, 1% Taiwan, 0.3% Malaysia), 5% AZTCT, 1% EMBMT, 0.5% LABMT and 0.3% Ottawa, Canada. The patient baseline characteristics are shown in Table 1. Males comprised 58% and the median age at diagnosis was 60 years. The predominant phenotypes were IgG (54%), light chain (24%) and IgA (19%). The ISS stage at diagnosis was I (38%), II (35%) or III (27%) and cytogenetic risk was standard in 70% and high in 30%. The median time from diagnosis to ASCT was 7.1 months. The year of ASCT was equally distributed between 2013 and 2017 (the annual percentage varied between 18% and 22%). The median age at ASCT was 60.8 years with 5.1% of patients older than 70 years. The HCT-CI risk at transplant was low in 52%, intermediate in 25% and high in 23%. The Karnofsky score at ASCT was 100 in 40% and ≤90 in 60%.Disease status was CR in 19%, VGPR in 38%, PR in 36%, MR/SD in 5% and refractory in 2%. The most frequent preparative regimen was melphalan 200 mg/m2 (82 %) and 140 mg/m2 comprised 14%. Tandem ASCT was reported in 6.7%. Of the 11% of patients with data on post-ASCT maintenance treatment, 51% received lenalidomide. The median follow-up was 41.1 months (95% CI: 40.5 to 41.6, IQR:19.2-60.4). Outcomes: non-relapse mortality (NRM) at 12 months was 1% (95% CI 1-2%); OS at 4 and 8 years was 76% (75-76%) and 45% (42-48%) respectively; PFS at 2 and 4 years was 65% (95% CI: 64-65%) and 40% (40-41%) respectively; RI at 6 and 12 months was 7% (7-7%) and 16% (15-16%) respectively. In the multivariate analysis (Table 2), later calendar year of ASCT, a better disease response at time of ASCT, higher Karnofsky score, and an IgG phenotype were all associated with an improved OS. A lower ISS stage, a lower HCT-CI score and standard risk cytogenetics were also associated with better OS (Table 2). Overall NRM was low. Younger age, higher Karnofsky score, higher melphalan dose, better disease response at ASCT, lower ISS stage at diagnosis and lower HCT-CI score were associated with a lower NRM. Conclusions: This study represents the largest study to date characterizing the outcomes of ASCT performed worldwide. The most frequent preparative regimen was melphalan 200 mg/m2. Unmeasured confounding (pre-existing toxicities/frailties) may partially explain the higher NRM in those with low dose melphalan. Globally, NRM was low at 1% at 12 months, while RI was 16%. Median OS was 7 years, median PFS was 3 years and differed across various risk factors. ASCT remains an effective and safe procedure for patients with NDMM world-wide. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Improvements in AML Treatment Outcomes By Twinning at the Instituto De Prevision Social Hospital in Paraguay

Background: The Central Hospital of the Instituto de Prevision Social (IPS) is the primary care point for 30% of the Paraguayan population. Patients with AML were treated on a general ward and had to change citizenship to receive allogeneic stem cell transplant (HSCT) abroad. Following the poor overall survival (OS) of the patients, a twinning program was started in 2015 with the help of the Worldwide network for Blood and Marrow Transplantation (WBMT). Physicians were trained at a JACIE/FACT accredited center for 6 months and the Hospital, staff, and nurses with an experience of 115 mostly autologous HSCT were inspected. The program started in 2016 by daily supervisory telemedicine visits including monitoring of vital signs, blood counts, chemistry and radiological analysis. In 2019, the need to improve treatment of AML prompted the Hospital to include newly diagnosed patients in the twining program. Now after 6 years, the outcome of AML patients was evaluated and compared to the results before the cooperation in 2012-2015. Changes: One of the biggest challenges was the availability of essential drugs. Busulfan and several other preparative regimens and immunosuppressive drugs for HSCT were either not available or accessible only as oral formulation. Supportive therapy was a challenge considering lack of modern antifungal and antiviral therapy. To start the program, essential medications according to the WBMT recommendations were either donated from outside the country, included in the Insurance medications or ordered through the Ministry of Health. The allogeneic HSCT program was started using standard operating procedures (SOP) for central venous line care, neutropenia care, febrile neutropenia, transfusion threshold, visitors, patients per room, multidrug resistant bacteria active search and isolation of colonized patients, bacterial, viral, and fungal prophylaxis, and treatment. It was soon realized that only very few patients with AML survived induction therapy and reached CR. Therefore, the HSCT program started to include patients with AML from diagnosis in 2019. Newly diagnosed AML patients were therefore treated either on the conventional ward with 2-6 beds per room and common bathrooms or in the HSCT unit according to the availability of beds. SOP from HSCT patients were used for induction and consolidation treatments wherever possible. As quality control, OS was evaluated in the AML patients diagnosed in 2019-2021 according to treatment location and compared to the historical controls of 2012-2015 and to the HSCT patients. Results: Between 2019 and 2021, 23 patients received intensive chemotherapy induction, 8 patients in the HSCT Unit (Group A1) and 15 in the Regular Ward (Group A2). The controls included 31 historical patients with AML treated between 2012 - 2015 (Group B) and 50 patients after autologous or allogeneic HSCT between 2016-2021 (Group C). Patient`s characteristics are shown in Table 1. In comparison to the historical controls, diagnostics improved, and the treatment was given according to international protocols. Causes of death due to infection were reduced substantially to 12.5% in group A1 in comparison to 40% and 51% in group A2 and B, respectively. No bleeding fatalities were observed in Group A1 possibly because of strict transfusions according to SOP. In the HSCT control Group C only 4% died of infection and none of bleeding. Figure 1 shows overall survival for all four groups. There were significant differences in median OS of the Group A1 (18 months), Group A2 (0,8 months), Group B (3,2 months) and Group C (not reached; p<0.0001). OS at 12 months amounted to 81% for Group A1, 15% for Group A2, 11% for Group B and 79% for Group C. Conclusions: Improved survival following standardized treatment according to SOP can be achieved with strict adherence to protocols. Lower infection rate following isolation and standardized infection prevention and handling. Infection rate similar to the highest intensity of conditioning (autologous HSCT) and immunodeficiency (allogeneic HSCT). Even with the addition of new antifungal drugs and antivirals available at the regular ward between 2019-2021patients had low overall survival mostly due to bacterial infections following missing isolation, active surveillance, and prophylaxis. With this measures mortality following induction can be reduced effectively and is comparable to regular HSCT patients from developed countries. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

International Differences in Baseline Characteristics and Practice Patterns in Patients with NEWLY Diagnosed Multiple Myeloma Undergoing Upfront Autologous STEM Cell Transplantation

Background: Worldwide, patients with newly diagnosed multiple myeloma (NDMM) undergoing upfront autologous stem cell transplantation (ASCT) have different characteristics and survival outcomes, likely due to variances in transplant activity, patient and health economic factors including access to new myeloma therapies. The goal of this retrospective study was to analyze differences in regional outcomes. Methods: Data on patient characteristics and transplant outcomes for patients with NDMM who received an upfront ASCT between 2013 and 2017 were provided to the Worldwide Network for Blood and Marrow Transplantation (WBMT) by the European Society for Blood and Marrow Transplantation (EBMT), the Center for International Blood and Marrow Transplantation (CIBMTR), the Asian Pacific Blood and Marrow Transplant Group (APBMT), the Australia and New Zealand Transplant and Cellular Therapies Registry (ANZTCT), the Eastern Mediterranean Blood and Marrow Transplant Group (EMBMT), the Latin American Bone Marrow Transplant Group (LABMT), and the Ottawa Canadian Registry. There primary endpoints were overall (OS) and non-relapse mortality (NRM) and the secondary were progression free survival (PFS) and relapse incidence (RI). The Kaplan-Meier estimator and log-rank test were used for OS and PFS, and the crude cumulative incidence estimator and Gray's test were used for competing events (RI and NRM). Results: 61725 patients from 629 were included: 37549 (61%) from EBMT, 16217 (26%) CIBMTR), 3815 (6%) APBMT (3122 Japan, 524 Taiwan and 169 Malaysia), 3,164 (5%) ANZTCT, 543 (0.9%) EMBMT, 339 (0.5%) LABMT and 188 (0.3%) Ottawa). The annual number of ASCTs steadily increased between 2013 (n=11317) and 2017 (n=13498) with the biggest relative increase seen in LABMT (from 36 to 109). Males comprised 58% and the median age at diagnosis was 59.9 years (IQR: 53.6-64.9). Race data was available in 45%: 73% White, 16% Asian and 11% African American. The predominant phenotypes were IgG (54%), light chain (24%) (lowest (4%) in Malaysia and highest (38%) in EMBMT), and IgA (19%) (lowest (13%) in EMBMT and highest (24%) in Ottawa). The ISS stage at diagnosis (54% available) was I in 38%, II 35% and III 27% (III lowest (24%) in ANZTCT and highest (45%) in LABMT). Cytogenetic risk (44% available) was standard in 70% and high in 30% (high risk was lowest (5%) in EMBMT, and highest (62%) in Ottawa). The median time from diagnosis to ASCT was 7 months (IQR:5.5-9.9) (shortest (6.4) in CIBMTR and Ottawa, and longest (13) in LABMT). The median age at ASCT was 60.8 years (IQR: 54.6-65.8) (lowest (53.6) in EMBMT, and highest (62) in Ottawa). Only 5% of patients were older than 70 years (lowest (3.5%) in EBMT, and highest (9.8%) in CIBMTR). HCT-CI at ASCT (28% missing) was reported as low risk (0) in 52%, intermediate (1-2) 25% and high risk (≥3) 23% (high risk was lowest (5.5%) in LABMT and highest (42%) in CIBMTR). The Karnofsky score at ASCT (2.2 % missing) was 100 in 40% and ≤90 in 60% (≤90 was lowest (44%) in LABMT and highest (92%) in Ottawa). Disease status (9.7% missing) was CR in 19%, VGPR 38%, PR 36%, MR/SD 5% and refractory 2%. A ≥VGPR status at ASCT was 60% in EBMT, 55% CIBMTR, 39% ANZTCT, 51% Japan, 64% EMBMT, 71% Taiwan, 76% LABMT, 51% Ottawa and 54% Malaysia. The most frequent preparative regimen was melphalan 200 mg/m2 (82 %) (lowest (60%) in Malaysia and highest (90%) in Ottawa), 140 mg/m2 accounted for 14% and others for 4%. Tandem ASCT was reported in 6.7% (10% in EBMT, 1.3% in CIBMTR and 0.6% LABMT and Taiwan). The source of stem cells was peripheral blood in 99.8%. Of the 11% reported with post-ASCT maintenance treatment, 51% received lenalidomide. The median follow-up was 41.1 months (95% CI: 40.5-41.6, IQR:19.2-60.4). Regionally, at 3 years, the OS was : 81%, 84%, 82%, 83%, 77%, 75%, 84%, 82%, 69% (p<0.001), the PFS was 46%, 55%, 48%, 63%, 44%, 53%, 56%, 53%, 43% (p<0.001) (Figure) and the RI was:16%, 15%, 16%, 17%, 24%, 16%, 16%, 13%, 24% (p<0.001) for EBMT, CIBMTR, ANZTCT, Japan, EMBMT, Taiwan, LABMT, Ottawa and Malaysia, respectively. NRM at 1 year was between 1-2% in each registry (Figure). Conclusions: This large worldwide study of patients with NDMM treated with upfront ASCT revealed marked regional differences in transplant activity and patient characteristics. NRM was low worldwide but with differences in relapse incidence and survival potentially reflect variable health economic factors, including different access to new myeloma drugs. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Narrowing the Gap for Hematopoietic Cell Transplantation in the East-Mediterranean/African Region: Comparison with Global HSCT Indications and Trends. A Report on Behalf of the East Mediterranean (EMBMT), African Blood and Marrow Transplantation Group (AFBMT) and Worldwide Network for Blood and Marrow Transplantation (WBMT)

Introduction: Hematopoietic Cell Transplantation (HCT) activity in the EMRO/African (EMRO/AFR) region was compared to the global activity in relation to frequency, indication, trends, donor type and geographical distribution.Methods: Surveys were obtained from international and national registries or by direct reporting by individual centers from 2006-2013. In 2013, activities were summarized from a total of 1570 teams in 78 countries over 6 WHO continental regions. Of these 1570 teams, only 29 teams were active in 12 countries of the EMRO/AFR region.Results: A total of 464,100 HCT have been reported worldwide since 2006, 54% of which were autologous and 46% allogeneic. The most frequent indications were lymphoproliferative disorders (53.1%), leukemias (35.5%), non-malignant diseases (6.2%), solid tumors (4.9%) and other non-specified rare diseases (0.3%). The annual HSCT activity increased by 52.6% from 46,543 in 2006 to 71,036 in 2013, primarily among allogeneic HSCT (+65%), particularly for non-malignant disorders (+86%), acute leukemias/MDS/MPN (+80%) and lymphoproliferative disorders (+42%). Of the allogeneic HSCT, 106,662 (49.8%) were performed from a family donor. Frequencies of autologous HSCT rose from 26,230 to 37,464 between 2006 and 2013 (+42.8%) primarily for Plasma Cell Disorders (PCD; +75.8%), non-malignant diseases (+50.3%) and lymphomas (+33.7%). Only 2.331 of the 71.036 HCT in 2013 were performed in the EMRO/AFR region. This represents a 90% increase from 2006, characterized by a high frequency of allogeneic compared to autologous HCT and by the almost exclusive use of family donors. Alternative HSCT in the EMRO/AFR region tended to use haploidentical donors rather than cord blood. This contrasts with the global activities, where the frequency of haploidentical HCT did not start to increase until 2012. There was an increase of 200% in HCT for hemoglobinopathies (Thalassemia and Sickle cell anemia; from 72/year in 2006 to 216/year in 2013), but this remains lower than in all other world regions. A total of 1033 HCT for hemoglobinopathies were performed globally in 2013 representing an increase of 164% from 2006 (n=392). This is an extremely low number considering the high prevalence and incidence of Thalassemia (40.000 born annually and 80 million carriers; Modell, WHO Bulletin 2008) and of sickle cell anemia patients in the EMRO/AFR region (e.g. 91,011 in Nigeria and 39,743 in Congo).Conclusion: The global data on HCT demonstrate the benefits of intensive global collaboration and data sharing, but illustrate important unmet needs, especially the continued underuse of HCT in the region despite evident progress. This information establishes a basis for competent authorities to provide adequate infrastructure and to improve the current situation in which access often remains limited. DisclosuresGreinix:Sanofi: Consultancy, Speakers Bureau; Bristol Myers Squibb: Consultancy, Speakers Bureau; Mallinckrodt: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau. Szer:Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Other: Travel Support, Research Funding.

Worldwide Network for Blood and Marrow Transplantation (WBMT) Recommendations Regarding Essential Medications Required To Establish An Early Stage Hematopoietic Cell Transplantation Program

Establishing a hematopoietic cell transplantation (HCT) program is complex. Planning is essential while establishing such a program to overcome the expected challenges. Authorities involved in HCT program establishment will need to coordinate the efforts between the different departments required to start up the program. One essential department is pharmacy and the medications required. To help facilitate this, the Worldwide Network for Blood and Marrow Transplantation organized a structured survey to address the essential medications required to start up an HCT program. A group of senior physicians and pharmacists prepared a list of the medications used at the different phases of transplantation. These drugs were then rated by a questionnaire using a scale of necessity based on the stage of development of the transplant program. The questionnaire was sent to 30 physicians, in different parts of the world, who have between 5 and 40 years of experience in autologous and/or allogeneic transplantation. This group of experts scored each medication on a 7-point scale, ranging from an absolute requirement (score of 1) to not required (score of 7). The results are presented here to help guide the prioritization of required medications.

Hematopoietic stem cell donor with IgA nephropathy: Challenges and management algorithm

Donor safety is of prime importance in allogeneic hematopoietic cell transplantation. The Worldwide Network for Blood and Marrow Transplantation (WBMT) standing committee on donor issues has issued a consensus statement regarding suitability criteria for related adult donors. This committee recommends that donors with a history of immune-mediated glomerulonephritis and abnormal urine tests should preferably undergo bone marrow harvest, to avoid the theoretical risk of granulocyte colony-stimulating factor (G-CSF) induced immune flare-up. We discuss here a unique situation where a related donor with a history of IgA nephropathy (IgAN) insisted on a peripheral blood stem cell harvest. We propose a management plan for this situation, which posed challenges about donor suitability.

How do we plan hematopoietic cell transplant and cellular therapy with the looming COVID-19 threat?

How do we plan hematopoietic cell transplant and cellular therapy with the looming COVID-19 threat?

One and Half Million Hematopoietic Stem Cell Transplants (HSCT). Dissemination, Trends and Potential to Improve Activity By Telemedicine from the Worldwide Network for Blood and Marrow Transplantation (WBMT)

HSCT is the only curative option for many malignant and non-malignant diseases. The WBMT was founded as an umbrella organization of societies involved in cellular therapies with the mission of promoting excellence in HSCT. As a non-governmental organization in official relation with the World Health Organization (WHO), the WBMT assisted in the founding of regional societies (Latin America Blood and Marrow Transplantation Group and African Blood and Marrow Transplantation Group), performs global activity surveys, conducts workshops and provides expert support for programs in evolving countries. In this retrospective evaluation we analyzed worldwide activity trends in HSCT up to the year 2016 and evaluated possibilities of improving availability of HSCT by the use of telemedicine. Methods: HSCT activity was collected annually from member societies, national registries and individual centers including donor type (allogeneic/autologous), stem cell source (bone marrow/peripheral blood stem cells/cord blood) and indications for transplant. Transplant rates (TR) were calculated as HSCT/10 million inhabitants without adjustment for patients transplanted in a country other than that of primary residence. Country team density (TD) was defined as teams/10 million inhabitants. Workshops were organized in a number of locations where there was little or no HSCT activity or where improvement in one or more aspect of local or regional HSCT activity was requested, including Vietnam, Brazil, China, South Africa and Morocco. Other countries were paired with established centers using WBMT affiliated partners. In two countries, a pilot program was established involving a 6 month physician training in a JACIE/FACT accredited center followed by daily telemedicine-guided supervision of clinical activities. Results: From 1957-2016 a total of 1,298,897 HSCT (57.1% autologous) procedures were collected. By the end of 2016, HSCT activity was reported from 87 of the 195 WHO member states. A total of 89,070 HSCT from 1662 centers was reported in 2016. Assuming a frequency of 84,000/year, 1.5 million HSCT will be reached in 2019, only 7 years after the 1 million report in 2012 (Figure 1). The global activity/year increased continuously from 10,000/year in 1991 to 82,718 first HSCT/year in 2016 with a global increase of &gt;7% (7.0% in autologous and 7.8% in allogeneic HSCT). As in previous years, slightly more autologous (53.5%) than allogeneic and more related (53,6%) than unrelated HSCT were reported. The further increase in related HSCT was caused mainly by an increase of non-identical family donors (39.5% of related HSCT). Increase in activities according to regions is given in Figure 2. TR and TD varied according to region and are highest in Nord America with 511.2 TR, followed by Europe with 390.9 TR, Latin America with 63.9 TR, APBMT with 46.2 TR and Africa/EMRO with 32.8 TR. In contrast, TD was highest in Europe (7.5 TD) followed by Nord America (6.0 TD), APBMT (1.9 TD), Latin America (1.9 TD) and Africa/EMRO (0.4 TD). Commonest indications were lymphoproliferative diseases for autologous and leukemia for allogeneic HSCT and continue to rise (Figure 3 autologous and Figure 4 allogeneic HSCT). Graft source were predominantly peripheral blood in autologous (99.7%) and 65% in unrelated HSCT, while umbilical cord blood as a stem cell source (13.8% of all unrelated) declined. More than 150 HSCT were performed in one country and one center without activities using daily telemedicine-guided supervision. In conclusion, the global distribution and activities are increasing continuously by more than 7,0% per year with numbers currently running at app. 90,000/year. Of note is the increase of haploidentical HSCT activity, while the use of umbilical cord blood HSCT continues to decrease. TR data show significant gaps between regions. Supervisory telemedicine is a powerful tool to overcome lack of experience and establish JACIE/FACT compatible new programs with collateral benefits for conventional hematology, blood banking, microbiology and virology. Abbreviations: EUR, Europe; AMR/PHA, America; SEAR/WPR, South-East Asia/Western Pacific; AFR/EMRO, African/Eastern Mediterranean. Disclosures Niederwieser: Daichii: Speakers Bureau; Cellectis: Consultancy. Atsuta:Kyowa Kirin Co., Ltd: Honoraria; Chugai Pharmaceutical Co., Ltd.: Honoraria; Mochida Pharmaceutical Co. Ltd: Honoraria; Janssen Paharmaceutical K.K.: Honoraria. Worel:Sanofi Genzyme, Malinckrodt Therakos: Research Funding; Jazz, Sanofi, Celgene, Novartis, Malinckrodt Therakos: Honoraria; Sanofi Genzyme, Malinckrodt Therakos: Speakers Bureau. Galeano:Szabo SA: Other: (Equity interest). Novitzky:Astellas, Roche: Consultancy. Szer:Prevail Therapeutics: Honoraria, Other: Travel, Research Funding; Novartis: Honoraria, Other: Travel, Research Funding; MSD: Honoraria, Other: Travel, Research Funding; Celgene: Honoraria, Other: Travel, Research Funding; Amgen: Honoraria, Other: Travel, Research Funding; Alexion: Honoraria, Other: Travel, Research Funding; Sanofi: Honoraria, Other: Travel, Research Funding; Takeda: Honoraria, Other: Travel, Research Funding; Pfizer: Honoraria, Other: Travel, Research Funding. Kröger:Celgene: Honoraria, Research Funding; DKMS: Research Funding; JAZZ: Honoraria; Medac: Honoraria; Neovii: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Riemser: Research Funding; Sanofi-Aventis: Research Funding. Weisdorf:Incyte: Research Funding; Pharmacyclics: Consultancy; Fate Therapeutics: Consultancy. Pasquini:Amgen: Consultancy; BMS: Research Funding; Medigene: Consultancy; Pfizer: Other: Advisory Board; Novartis: Research Funding; Kit Pharma: Research Funding.

Worldwide Network for Blood and Marrow Transplantation (WBMT) perspective: the role of biosimilars in hematopoietic cell transplant: current opportunities and challenges in low- and lower-middle income countries.

Health care costs attributed to biologics have increased exponentially in the recent years, thus biosimilars offer a possible solution to limit costs while maintaining safety and efficacy. Reducing expenditure is vital to health care especially in developing countries where affordability and access to health care is a major challenge. We discuss the opportunities and the challenges of biosimilars in the field of hematopoietic cell transplantation (HCT) in low- and lower-middle income countries. Developing countries can potentially invest in the forecasted costs reduction by utilizing biosimilars. This can be used to decrease the costs of procedures such as HCT, which is a rapidly growing field in many developing regions. The introduction of biosimilars in the developing regions faces many challenges which include, but are not limited to: legal and regulatory issues, lack of research infrastructure, and the presence of educational barriers. Thus, collaborative efforts are needed to ensure an effective and safe introduction of biosimilars into low- and lower-middle income countries.

Worldwide Network for Blood and Marrow Transplantation (WBMT) recommendations for establishing a hematopoietic stem cell transplantation program in countries with limited resources (Part II): Clinical, technical and socio-economic considerations

The development of hematopoietic stem cell transplantation (HSCT) programs can face significant challenges in most developing countries because such endeavors must compete with other government health care priorities, including the delivery of basic services. While this is may be a limiting factor, these countries should prioritize development of the needed expertise to offer state of the art treatments including transplantation, by providing financial, technological, legal, ethical and other needed support. This would prove beneficial in providing successful programs customized to the needs of their population, and potentially provide long-term cost-savings by circumventing the need for their citizens to seek care abroad. Costs of establishing HSCT program and the costs of the HSCT procedure itself can be substantial barriers in developing countries. Additionally, socioeconomic factors intrinsic to specific countries can influence access to HSCT, patient eligibility for HSCT and timely utilization of HSCT center capabilities. This report describes recommendations from the Worldwide Network for Blood and Marrow Transplantation (WBMT) for establishing HSCT programs with a specific focus on developing countries, and identifies challenges and opportunities for providing this specialized procedure in the resource constrained setting.

Worldwide Network for Blood and Marrow Transplantation (WBMT) recommendations for establishing a hematopoietic cell transplantation program (Part I): Minimum requirements and beyond

Hematopoietic cell transplantation (HCT) is a highly complex procedure that requires a dedicated multidisciplinary team to optimize its safety. In addition, institutions may have different needs regarding indications based on regional disease prevalence or may have an interest in developing specialized services. Yet, structured recommendations are not commonly available. Here, the Transplant Center and Recipient Issues Standing Committee for the Worldwide Network for Blood and Marrow Transplantation (WBMT) organized a structured review of all pertinent elements to establish a transplant program. First, we solicited components from committee members and grouped them in domains (infrastructure, staff, cell processing laboratory, blood banking, laboratory, radiology, pharmacy, HLA testing, ancillary services and quality). Subsequently, reviewers scored all elements on a 7-point scale, from an absolute requirement (score of 1) to not required (score of 7). An independent group of five experienced transplant physicians reviewed the rankings. Minimum requirements to establish any HCT program were identified among elements with mean score of ≤2.0, and specific elements for allogeneic and autologous HCT were identified. Mean scores >2.0–4.0 were classified as preferred recommendation, and mean scores of >4.0 to ≤7.0 were considered ideal recommendations for advanced and complex types of transplantation. This structured set of recommendations guides the prioritization of minimum requirements to establish a transplant program and to set the path for expansion and further development.

Special report: Summary of the first meeting of African Blood and Marrow Transplantation (AfBMT) group, Casablanca, Morocco, April 19–21, 2018 held under the auspices of the Worldwide Network for Blood and Marrow Transplantation (WBMT)

The first meeting of the African Blood and Marrow Transplantation (AfBMT) was held in Casablanca from April 19, 2018 to April 21, 2018, with the aim of fostering hematopoietic stem cell transplantation (HSCT) activity in Africa. Out of the 54 African countries, HSCT is available only in six (Algeria, Egypt, Morocco, Nigeria, South Africa, and Tunisia). During this meeting, African teams and international experts from the Worldwide Network for Blood and Marrow Transplantation (WBMT) gathered to share their experience and discussed ways to help fill the gap. Nurses and patients held their meeting in parallel. International support and collaboration can help by providing expertise adapted to local resources and regional population needs. Local engagement including government and private participants are necessary to initiate and develop local HSCT capability.

Worldwide Network for Blood and Marrow Transplantation Recommendations for Establishing a Hematopoietic Cell Transplantation Program, Part I: Minimum Requirements and Beyond.

Hematopoietic cell transplantation (HCT) is a highly complex procedure that requires a dedicated multidisciplinary team to optimize safety. In addition, institutions may have different needs regarding indications based on regional disease prevalence or may have an interest in developing specialized services. Structured recommendations are not commonly available, however. The Transplant Center and Recipient Issues Standing Committee of the Worldwide Network for Blood and Marrow Transplantation (WBMT) organized a structured review of all pertinent elements for establishing a transplantation program. First, we solicited components from committee members and grouped them into domains (infrastructure, staff, cell processing laboratory, blood banking, laboratory, radiology, pharmacy, HLA testing, ancillary services, and quality). Subsequently, reviewers scored each element on a 7-point scale, ranging from an absolute requirement (score of 1) to not required (score of 7). An independent group of 5 experienced transplantation physicians reviewed the rankings. The minimum requirements for establishing any HCT program were identified among elements with mean score of ≤2.0, and specific elements for allogeneic and autologous HCT were identified. Mean scores of >2.0 to 4.0 were classified as preferred recommendation, and mean scores of >4.0 to ≤ 7.0 were considered ideal recommendations for advanced and complex types of transplantation. This structured set of recommendations guides the prioritization of minimum requirements to establish a transplantation program and set the stage for expansion and further development.

Hematopoietic Stem Cell Transplant Activity in Latin America: Predominant Increase in Autologous and Modest Increase in Allogeneic HCT with High Use of Unrelated Cord Blood Grafts

More than a million HCT have been performed worldwide to date, but transplant rates and indications vary widely across regions. The Latin American Bone Marrow Transplantation Group (LABMT) was created under the auspices of the Worldwide Network for Blood and Marrow Transplantation (WBMT) in 2011 to assist in diffusing the practice, to integrate centers from multiple countries and to improve access to transplantation in the region. To evaluate the actual HCT activity, trends and contemporary practices in Latin America (LA), the LABMT surveyed centers for the annual activity from 2009 to 2012. Methods: The WBMT Global Activity Survey was used as a template and sent to all Hematology and HCT Societies in the region. This survey includes information of annual HCT numbers by center, indications, stem cell source and donor type. Results: A total of 11,116 HCT were performed between 2009 and 2012 with an increase in annual numbers from 2,517 in 2009 to 3,072 in 2012 (22%). The majority of the HCT were autologous (62%) with a 32% increase in activity over the period analyzed. In contrast, the increase in allogeneic HCT (6%) was relatively small. The majority of allogeneic HCT used related donors (n=3210), mostly HLA-identical peripheral blood (n=1812), bone marrow (n=1128) and non-identical related peripheral blood (n=156). Unrelated donor HCT (n=982) were performed mostly using cord blood (n=427), followed by bone marrow (n=332) and peripheral blood (n=223). In 2012, 91 teams from 12 countries reported 3,072 patients. Transplant rates (TR; HCT/10 million population) were 21 for allogeneic (ranging from 6 in Venezuela to 85 in Uruguay) and 60 for autologous HCT (ranging from 8 in Mexico to 215 in Uruguay). Unrelated donor TR was 5, ranging from 0 (Costa Rica, Panama, Peru, Paraguay and Venezuela) to 18 (Chile). Transplant center team density (team/10 million inhabitants) was 1.8 in 2012, with the highest in Uruguay (15), followed by Panama (8), Costa Rica (4), and Argentina (4). In comparison to other regions, transplant center density in LA was identical to the Asian Pacific region and lower than in Europe (7) or US/Canada (6). TR in LA compared to Asia/Pacific were higher for autologous (39 vs. 14) and lower for allogeneic (21 vs. 24, respectively, Table 1). Most transplant indications for autologous HCT (65% of all HCT) were plasma cell disorders (48%) and lymphomas (41%). Most allogeneic transplants (35% of all HCT) were performed for acute leukemias (58%, equally myeloid and lymphoid leukemias) and 18% for non-malignant disorders. Conclusion: While transplant indications are comparable to HCT performed in Europe and North America, transplant rates, transplant center and transplant team densities in LA are markedly lower. More autologous than allogeneic HCT are performed and autologous HCT increased considerably between 2009 and 2012. Unrelated donor TR is lower than in other regions. Initiatives are currently being taken to increase transplant activity, especially using alternative donor transplants within the region.Table 1Transplant Rates and Team Density WorldwideTransplant rates (HCT/10 million population)Team densityRegionPOPTOTALAUTOALLOFAMILYSIBLINGUNRELATEDLA511.760.039.220.916.014.34.91.8SEAR/WPR3078.038.614.224.412.58.211.91.8EUROPE846.4379.3222.5156.868.257.088.67.6USA/Canada348.0482.5264.9217.591.275.8126.36.2EMR/AFR690.929.812.717.215.715.01.40.4HCT, hematopoietic cell transplantation; POP, population; AUTO, autologous; ALLO, allogeneic; SEAR/WPR, South East Asia/Western Pacific Region; LA, Latin America; EMR/AFR; Eastern Mediterranean/African Region DisclosuresNo relevant conflicts of interest to declare.

Global Hematopoietic Stem Cell Transplantation (HSCT) At One Million: An Achievement Of Pioneers and Foreseeable Challenges For The Next Decade. A Report From The Worldwide Network For Blood and Marrow Transplantation (WBMT)

Since the first report by Nobel laureate, the late E. Donnall Thomas (NEJM, 1957, 257), HSCT has developed from an experimental to an established curative treatment for many congenital or acquired disorders of the hematopoietic system. The key steps of this success story are linked to progress in tissue typing, donor selection, supportive care and immunosuppression and fostered by intensive collaboration of physicians around the world through outcome and donor registries.The WBMT, a federation and official Non-governmental Organization of the World Health Organization, has collected HSCT activity data from its member societies and from national registries not part of an international HSCT society. Data collection did include the first transplants by ED Thomas and the first global report by M. Bortin (Transplantation 1970, 571). European data were derived from the Med A form of the European Group for Blood and Marrow Transplantation-EBMT for the years 1965-1989 and from the annual activity survey since 1990. Non-European data back to 1969 were provided by the Center for International Blood and Marrow Transplant Research-CIBMTR, with additional recent data provided by the Asia-Pacific Blood and Marrow Transplantation Group (APBMT, since 1974), the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR, since 1980), the Eastern Mediterranean Blood and Marrow Transplantation Group (EMBMT, since 1984), the Canadian Blood and Marrow Transplantation Group (CGBMT, since 2002), the Latin American Blood and Marrow Transplantation Group (LABMT, since 2009) and the African Blood and Marrow Transplant Group (AFBMT, since 2010). Double reporting was minimized by crosschecking registries and unrelated donations. Missing data from a few regions in 2012 were extrapolated from previous years assuming a 5% increase.As of December 2012, the 1450 transplant centers from 72 countries over 5 continents had reported 1.000.000 HSCT (58% autologous, 42% allogeneic). The dramatic recent increase in rate of utilization of HSCT is illustrated by the fact that there were 10.000 HSCTs worldwide by 1985, 50.000 by 1990, 100.000 by 1994, 500.000 by 2004 and 1.000.000 by December 2012. The absolute and relative contribution differed significantly with Europe providing 53%, the Americas 31%, Australasia 14% and Eastern-Mediterranean and Africa 2% to the total HSCT number (allogeneic HSCT: 45%, 32%, 20% and 3%; autologous HSCT: 58%, 31%, 10% and 1%). The increase in activity has been almost linear over the past 55 years with two exceptions, a decrease in autologous HSCT for breast cancer from 1999 especially in the Americas and a decrease in allogeneic HSCT for CML after 2000 seen everywhere except in the Eastern-Mediterranean/African region. The rise in HSCT numbers during the last decade was mainly due to an increase in allogeneic HSCT from unrelated donors; the relative increase being highest in Australasia. Recent growth was primarily due to increases in activity in existing transplant centers, rather than in the number of transplant centers. The main indications for autologous HSCT today are lymphoproliferative disorders 87% (myeloma 46% and lymphoma 41%), solid tumors 8.6% and AML 2.75%; for allogeneic HSCT leukemias 73% (AML 34.6%; ALL 16.8%; CML 4%; myelodysplastic and myeloproliferative disorders 13.3%; CLL 2.9% and other leukemias 1%), lymphoproliferative disorders 14.3% and bone marrow failure syndromes 5.5%. In 2010, cord blood was used as stem cell source in 19% of unrelated HSCT.These data were compiled through collaboration of the global HSCT community. Global collaboration has also been essential for the diffusion of HSCT as a therapy and especially for unrelated HSCT. More than 22 million unrelated donors are available today from a global network (World Marrow Donor Association, WMDA) of donor registries and cord blood banks and about 30% of unrelated HSCT involve a donor and recipient in different countries. The success of HSCT serves as a model for organ repair by the use of healthy stem cells and as a model for global cooperation in meeting the needs of an international patient population. These data also illustrate the challenges for the global medical community in providing state of the art care in regions with constrained resources and the need to find ways to make the therapy more available in order to provide better outcomes for patients with life-threatening but potentially curable diseases. Disclosures:Gluckman:Cord use: Honoraria; gamida: Honoraria.

Allogeneic hematopoietic stem cell donation—standardized assessment of donor outcome data: A consensus statement from the Worldwide Network for Blood and Marrow Transplantation (WBMT)

The number of allogeneic hematopoietic SCTs performed globally each year continues to increase, paralleled by an increased demand for donors of therapeutic cells. Donor characteristics and collection procedures have undergone major changes during recent decades, and further changes are foreseen. Information on short- and long-term donor outcomes is of crucial importance to ensure maximal donor safety and availability. Current data, predominantly from unrelated donors, give reliable information on the frequent early events associated with donation-most of them of mild-to-moderate intensity. Information on the type and relative risk of serious adverse reactions is more limited. Moreover, only few data exist on long-term donor outcome. On the basis of this need, recommendations for a minimum data set for prospective donor follow-up were developed in a workshop with the participation of an international group of investigators actively involved in allogeneic stem cell donation under the auspices of and approved by the Worldwide Network for Blood and Marrow Transplantation. Establishment of a standardized global follow-up for both, related and unrelated, donors will enable monitoring of the short- and long-term safety profiles of hematopoietic cell donation and form a solid basis for future donor selection and counseling.

Standards, regulations and accreditation for registries involved in the worldwide exchange of hematopoietic stem cell donors and products

The World Marrow Donor Association (WMDA) is working closely with other international organizations working in cellular therapy such as the Worldwide Network for Blood and Marrow Transplantation (WBMT) to develop and maintain global recommendations and requirements for a standardized practice. WMDA launched its registry accreditation program in September 2003. Since then, 17 of the 71 hematopoietic stem cell donor registries worldwide have been accredited. These accredited registries list over 80% of the hematopoietic stem cell donors and umbilical cord blood units listed in the database of BM Donors Worldwide. The goal of the WMDA Standards and Accreditation process is to protect donors while serving the needs of patients who are urgently seeking histocompatible donors in worldwide searches. These activities address the increasing governmental regulations regarding the quality and safety of stem cells collected internationally for national patients.