Family Donor Research Articles

Strategies to recover blood donors during the COVID-19 pandemic: a tertiary level hospital experience.

The SARS-CoV-2 pandemic has challenged blood banks. In Mexico, donors decreased 22% between April and May 2020 compared to the same months in 2019. This study analyzed the effect of the strategies to recover donors (altruistic and family) in a tertiary pediatric care center during the pandemic. The Blood Bank of the Hospital Infantil de México Federico Gómez implemented strategies to obtain blood components to ensure self-sufficiency. The effect of these strategies on donor recovery was analyzed. There were 7,315 eligible donors in 2019 and 5,070 in 2020. Blood component requirements decreased from 10,037 units in 2019 to 8,619 in 2020. The strategies aimed at attracting altruistic donors managed to increase the percentage of this type of donor when comparing the months in which these strategies were applied with the same months in 2019. In addition, it was observed that the greater the number of methods used simultaneously, the higher the percentage of altruistic donors (rho = 0.846, p = 0.002). In contrast, strategies aimed at attracting family donors did not increase the number of this type of donor. Actions to recruit altruistic donors increased the number of this type of donor to meet the hospital's needs.

Hematopoietic Stem Cell Transplantation and Results in Pediatric Patients with Thalassemia Major: Single-Center Study.

Objective:This study aimed to reveal whether patients with thalassemia major, who were followed up in our clinic, were given information about hematopoietic stem cell transplantation (HSCT) preparations, results, and complications.Materials and Methods:A total of 190 patients diagnosed with thalassemia major between 1991 and 2019 at the Pediatric Hematology-Oncology Clinics of Istanbul Kanuni Sultan Suleyman Education and Research Hospital were retrospectively analyzed.Results:Median age of the patients and follow-up time were 9 years (range 1-5) and 42.9 months (range 1-285), respectively. The IVSI-110 was the most frequently (30.4%) encountered mutation; there was no information about HSCT in 28 patients’ files, 36 patients had no human leucocyte antigen-matched donors, and 38 patients had undergone HSCT. Pretransplant median ferritin levels in thalassemia major patients who had undergone HSCT and who had not undergone HSCT were 1751 ng/mL (350–4000) and 1300 ng/mL (396-4000) (P = .149), respectively. The median age of HSCT was 6.5 years, and 24 patients were transplanted from human leucocyte antigen-matched sibling donors, 8 from human leucocyte antigen-matched family donors, and 5 patients from human leucocyte antigen-matched unrelated donors with the myeloablative conditioning regimen. Acute and chronic complication rate was higher in patients transplanted from human leucocyte antigen-matched family donors compared to human leucocyte antigen-matched sibling donors (50% vs 28% and 60% vs 8.3%), respectively; complication odd ratio was 6.7 (%95 CI 1.4-32).Conclusion:Human leukocyte antigen typing, donor search, and timely information about HSCT were noted to be performed in two-thirds of the thalassemia major patients, and around half of the patients underwent HSCT. Both acute and chronic complications were significantly higher in patients transplanted from matched unrelated donors.

Review of Treatment for Adenosine Deaminase Deficiency (ADA) Severe Combined Immunodeficiency (SCID)

Adenosine deaminase deficiency (ADA) is a purine salvage pathway deficiency that results in buildup of toxic metabolites causing death in rapidly dividing cells, especially lymphocytes. The most complete form of ADA leads to severe combined immune deficiency (SCID). Treatment with enzyme replacement therapy (ERT) was developed in the 1970s and became the treatment for ADA SCID by the 1980s. It remains an option for some infants with SCID, and a stopgap measure for others awaiting curative therapy. For some infants with ADA SCID who have matching family donors hematopoietic stem cell transplant (HSCT) is an option for cure. Gene therapy for ADA SCID, approved in some countries and in trials in others, is becoming possible for more infants with this disorder. This review covers the history of ADA SCID, the treatment options to date and particularly the history of the development of gene therapy for ADA SCID and the current state of the risks and benefits of the gene therapy option.

O-09: DURABLE ENGRAFTMENT AFTER PHARMACOLOGICAL PRE-TRANSPLANT IMMUNOSUPPRESSION FOLLOWED BY REDUCED-TOXICITY MYELOABLATIVE HAPLOIDENTICAL STEM CELL TRANSPLANTATION IN HIGHLY HLA-IMMUNIZED ADULTS WITH SICKLE CELL DISEASE

Purpose: Sickle cell disease (SCD) is the most common genetic disorder worldwide and despite advances in best supportive care, remains a disease with high morbidity and mortality. Allogeneic stem cell transplantation (AlloHSCT) is a curative treatment modality. Reports in adults are limited because of the high risk of transplant related toxicity, graft rejection and the lack of suitable donors. The development of reduced-toxicity myeloablative conditioning (RT-MAC) regimen and the use of partially matched family donors with post-transplantation cyclophosphamide (PT-Cy) have widened the access to AlloHSCT. Antibodies against donor-specific HLA (DSA) which are frequently detected in multi-transfused SCD patients increase the risk of engraftment failure in HLA mismatched AlloHSCT. Materials and methods: We report the results of five patients with severe SCD (22, 46, 27, 30 and 30 years old) and DSA who underwent an unmanipulated haploidentical bone marrow transplantation (HaploBMT) after a RT-MAC regimen. The conditioning regimen consisted in rabbit antithymoglobuline (ATG), fludarabine (flu) and busulfan. GVHD prophylaxis was performed with PT-Cy, cyclosporine A and mycophenolate mofetil. To reduce the risk of engraftment failure, a sequential two courses pharmacological pre-transplant immunosuppression (PTIS) phase was added prior to the conditioning regimen. This initially was based on flu in combination with dexamethasone and was later modified to include cyclophosphamide (cy) and ATG in patients with CNS involvement. The desensitization protocol of DSA consisted in rituximab, velcade and plasmapheresis followed by high dose intravenous immunoglobulins. (Figure 1) Importantly, the patients were highly immunized with severe hemolytic crises and high DSA titers (range, MFI 2000 – 10003); two patients had also a history of cerebrovascular complications whereas the 46 years old woman with sickle cell specific multi-organ damage. All donors were first degree family members (sibling, parent, child). Results: All patients successfully engrafted with neutrophil reconstitution on days 26, 31, 16, 24 and 21 days (median 23 days), respectively. The procedure was well tolerated with only mild toxicity. None of the patients developed acute GVHD. One patient developed moderate chronic skin GVHD at day +489 after HaploBMT with rapid response to conventional immunosuppressive therapy. After a follow-up of 2323, 1770, 994, 962 and 263 days (median 994 days) respectively, chimerism analysis and detection of hemoglobin S confirmed sustained donor engraftment. All patients were free of any pain symptoms with excellent quality of life. Conclusion: Our report shows that HaploHSCT after a busulfan-based RT-MAC regimen is feasible and safe and allows stable long-term engraftment and excellent disease control. Graft failure may be overcome by adding a PTIS phase prior to the conditioning regimen. Further studies are necessary to confirm these promising results and allow a widened access of this platform technology to patients with high-risk sickle cell disease.Desensitization procedure E. BERNIT declares a conflict of interest: Consultancy, Expert: NOVARTIS PHARMA

PB1767: OUTCOME OF RELAPSED CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA IN THE SOUTH OF TUNISIA SINGLE CENTER EXPERIENCE

Background: Relapsed acute lymphoblastic leukemia (ALL) has remained challenging to treat in children, with survival rates lagging well behind those observed at initial diagnosis. Although there have been some improvements in outcomes over the past few decades, only ∼50% of children with first relapse of ALL survive long term, and outcomes are much worse with second or later relapses. Aims: In this study we describe clinical characteristics and therapeutics results of first relapse of childhood ALL. Methods: Our study included children under 16 years on first relapse of ALL treated according to the EORTC 58951 protocol between January 2000 and December 2020 in the Hematology department of Hedi Chaker Hospital of Sfax. The marrow relapse was defined as the reapparition in the peripheral smears and/or the increase of blasts (>20%) in bone marrow (BM) after a period of complete remission (CR). A combined relapse included another extra medullary location, neurological (N) or gonadal (G). Relapse treatment was based on the COOPRALL 1997 protocol and since 2008, COPRALL 2007 protocol or the VHR group of the 58951 EORTC protocol. Results: Among the 262 Childs in CR, 81 was relapsed (31%) after a medium follow-up of 127 months. There are 27 females and 54 males. Median age was 7 years and 6 months. Relapse’s frequencies in the groups low risk, average risk 1, average risk 2 and high risk were respectively 4, 39, 18 et 39% of cases. Median of relapse timing was 12 months (2 to 83). Cumulative incidence of relapse at 1, 2 et 3 years after complete remission (CR) were respectively 51, 67 et 84%. Three relapses were occurred after 5 years of CR. Timing of relapse was not correlated with treatment group (p=0.8). The relapse was only medullary in 72% of cases, only neurological in 5% of cases and combined in 19% of cases (M+N= 6%, M+G= 9% et M+N+G= 4%). Second course was delivered to 57% of these patients. Protocol followed was the COOPRALL 1997 in 12 cases (26%), COOPRALL2007 in 28 cases (61%) and EORTC VHR in 6 cases (13%). The second CR (CR2) was get in 55% (44 patients) of treated patients, among them only 6 were allograft (24%). Toxic death before CR had occurred in 19% of treated cases. Among relapsed patients without curative treatment, only one was vivant (neurological relapse). Survivors after first relapse were less than 20%. Summary/Conclusion: In our cohort, relapse’s rate was more than rates reported in other literature series (31% vs 10 to 15%). Relapse’s prognostic factors validated by the literature were the ALL’s phenotype, cytogenetic abnormalities (phi +), timing of relapse, combined relapses (medullary is more serious) and intensity of treatment. Those factors were not been find in our cohort because of the little number of cases. CR2 rates was less than literature (55 vs 80%); the revision of followed relapse’s protocol is to be discussed. As well, the survival of our patients after ALL relapse was less then reported rates (less than 20% vs 35% at three years). This is due to the abstention of treatment in patient in precocious relapse haven’t a sibling familial HLA donor.

PB1812: CORE BINDING FACTOR ACUTE MYELOID LEUKEMIA IN PEDIATRIC POPULATION: THE RESULTS OF A MONOCENTRIC EXPERIENCE

Background: The core binding factor acute myeloid leukemia (CBF-AML) is characterized by t(8;21) and inv(16)(p13q22)/t(16;16)(p13;q22) cytogenetic abnormalities. It is associated with a good prognosis. Aims: In this study, we aimed to assess the treatment outcome of the pediatric CBF- AML in comparison with non CBF-AML treated in our center. Methods: We retrospectively reviewed data of patients under the age of 20 diagnosed with de novo AML in our center during january 2005 and december 2020. The treatment protocol includes: a course of induction (Cytarabine 200mg/m2/day associated with Daunorubicine (DNR) 60 mg/m2/day or Novantrone 12mg/m2/day). If a complete remission (CR) is achieved the chemotherapy is followed by: a cure of ADE (Cytarabin, DNR, Etoposide) associated with 2 cures of high dose of Cytarabine (12g/m2) before 2011 and a cure of ADE associated with 3 cures of high dose of cytarabine (18g/m2) after January 2011. Allogeneic stem cell transplantation (ASCT) from matched sibling donors was limited to patients who are in CR1, having an HLA-identical family donor before January 2011 and for patients who are in CR2 after January 2011. Endpoints were complete remission (CR), overall survival(OS), event free survival (EFS) and relapse rate. Survival statistical analysis performed with Kaplan Meyer method. Results: A total of 52 patients were included, of whom 16 (30%) presented CBF genes. The median age was 10years. The median white blood cells count at diagnostic was 28G/L. Distribution according to the FAB classification was as followed: 1(6%)M1, 8(50%) M2, 6(38%) M4 and 1(6%) M6.the most frequent subgroup was M2 (vs M1 in non CMF-AML, p=0.001). Cytogenetic analysis showed the Inv 16 (p13;q22) in 3 cases (18%) and t(8;21) (q22;q22) were observed in 11 cases (68%). Two patients had both CBFB–MYH11and AML-ETO rearrangement. Six cases (38%) had additional cytogenetic abnormalities. The correlation between cases with and without additional cytogenetic abnormalities did not conclude to any significent difference in terms of CR rate, OS and EFS. We observed a comparatively higher CR rate (87% vs 51% p=0.018) and also a better OS rate (83% vs 35%, p=0.02) at 5 years between CBF-AML and non CBF-AML. In contrast, there was no statisticly significent difference in terms of the EFS (67%vs 62%, p=0.4) and the relapse rate (31% vs 43%, p=0.3) between the 2 groups. Relapse occurred in 5 cases (31%) at a median of 13 months. A second remission was obtained in 2/5 patients. ASCT was performed in only 4 cases (3 after RC1 and 1 after relapse). Summary/Conclusion: The frequency of core binding AML in our study is higher than what has been reported in the literature (30 vs 15%) with predominance of The cytogenetic t(8,21) (68%). The additional cytogenetic abnormalities has no prognostic value. Long term survival in our series compared favorably with results reported by cooperative groups. It can be concluded that ASCT in CR1 for pediatric CBF-AML is no longer indicated.

PB1758: TWENTY-ONE YEARS’ EXPERIENCE OF THE EORTC 58951 PROTOCOL FOR THE TREATMENT OF CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA IN THE SOUTH OF TUNISIA

Background: Childhood acute lymphoblastic leukemia (ALL) is a hematologic malignancy with high rate of cure. Aims: We report the experience of the clinical hematology department of Sfax-Tunisia for the treatment of childhood ALL with the EORTC 58951 protocol. Methods: From January 2000 to December 2020, we retrospectively studied the outcome of childhood ALL aged less 16 years, treated with the EORTC 58951 pediatric protocol. For those patients we studied the leukemia characteristics (sex ratio, white blood cell counts WBC, blast’s phenotype, cytogenetic abnormalities) and response to treatment: response to prophase, remission rate, risk group stratification, treatment related mortality (TRM) (induction and post induction death) and survival (overall survival OS and event free survival. Results: From January 2000 to December 2020, 284 children were treated with the EORTC 58951 protocol. Medium age was 7 years (range: 1 to 15 years). Sex ratio M/F was 1.53. WBC counts more than 100 G/L were observed respectively in 41, 44 and 15% of cases. The blast’s phenotype was B in 70%. Cytogenetic abnormalities were noted in 37% of cases. A good response to prophase was noted in 80% and complete remission in 92% of cases. The EORTC risk group stratification was Low Risk (LR) in 5%, Average Risk1 (AR1) in 39%, Average Risk2 (AR2) in 25% and Very High Risk (VHR) in 31%. TRM was 10%: induction rate death was 6% and post-induction rate death was 4%. Twenty-eight patients from VHR group with sibling familial donor underwent allograft. The relapse rate was 29% of all patients in remission; 4% for LR group, 39% for AR1 group, 18% for AR2 group and 39% for VHR group. At a follow up of 126 months, OS and EFS at 10 years were respectively 61% and 56%. Summary/Conclusion: At diagnosis, childhood ALL in our study had poor characteristics particularly higher rate of T phenotype of blasts, higher rate of leukocytosis more than 100 G/L, higher rate of VHR therapeutic group and higher rate of cortico-resistant regarding occidental series. Despite the acceptable results concerning remission rate but survival rates remain lower than those observed in the literature, this is explained mainly by the high rate of relapse (29% vs ≃15%). It can be improved our results by detecting high risk patient with MRD study especially for AR1 risk group and doing allograft for VHR patients.

Successful outcomes of second hematopoietic stem cell transplantation for graft failure in pediatric patients with severe aplastic anemia

Severe aplastic anemia (SAA) is a life-threatening hematological disorder. The major therapies include matched sibling donor (MSD)- hematopoietic stem cell transplantation (HSCT), matched unrelated donor (MUD)-HSCT and immunosuppressive therapy (IST). However, there are many problems that can occur after HSCT, and graft failure (GF) is one of the most serious complications. To find an effective treatment, we analyzed 10 cases of second HSCT to treat SAA pediatric patients who suffered from GF and concluded that second haploidentical family donors HSCT is an effective treatment. Moreover, adding a small dose of busulfan or 2 ~ 3 Gy total body irradiation (TBI) in nonmyeloablative regimens (NMAs) can promote the engraftment. Although the study also showed that PBSCs, as a source of stem cells, can promote the implantation of neutrophil cells, due to small sample size, more research is still needed.

Outcomes following treatment for ADA-deficient severe combined immunodeficiency: a report from the PIDTC

AbstractAdenosine deaminase (ADA) deficiency causes ∼13% of cases of severe combined immune deficiency (SCID). Treatments include enzyme replacement therapy (ERT), hematopoietic cell transplant (HCT), and gene therapy (GT). We evaluated 131 patients with ADA-SCID diagnosed between 1982 and 2017 who were enrolled in the Primary Immune Deficiency Treatment Consortium SCID studies. Baseline clinical, immunologic, genetic characteristics, and treatment outcomes were analyzed. First definitive cellular therapy (FDCT) included 56 receiving HCT without preceding ERT (HCT); 31 HCT preceded by ERT (ERT-HCT); and 33 GT preceded by ERT (ERT-GT). Five-year event-free survival (EFS, alive, no need for further ERT or cellular therapy) was 49.5% (HCT), 73% (ERT-HCT), and 75.3% (ERT-GT; P < .01). Overall survival (OS) at 5 years after FDCT was 72.5% (HCT), 79.6% (ERT-HCT), and 100% (ERT-GT; P = .01). Five-year OS was superior for patients undergoing HCT at <3.5 months of age (91.6% vs 68% if ≥3.5 months, P = .02). Active infection at the time of HCT (regardless of ERT) decreased 5-year EFS (33.1% vs 68.2%, P < .01) and OS (64.7% vs 82.3%, P = .02). Five-year EFS (90.5%) and OS (100%) were best for matched sibling and matched family donors (MSD/MFD). For patients treated after the year 2000 and without active infection at the time of FDCT, no difference in 5-year EFS or OS was found between HCT using a variety of transplant approaches and ERT-GT. This suggests alternative donor HCT may be considered when MSD/MFD HCT and GT are not available, particularly when newborn screening identifies patients with ADA-SCID soon after birth and before the onset of infections. This trial was registered at www.clinicaltrials.gov as #NCT01186913 and #NCT01346150.

Peri‐anaesthetic management of three dogs undergoing renal transplantation surgery

AbstractThis report describes the perioperative anaesthetic management of three dogs undergoing renal transplant surgery at the University of Pennsylvania using a familial donor kidney. All three cases were pre‐medicated with morphine for preoperative sedation and analgesia. Two cases were induced with a combination of fentanyl, midazolam and propofol. One case was induced with etomidate and midazolam. Anaesthesia was maintained with isoflurane in oxygen and an opioid constant‐rate infusion in all three cases, with one case also receiving a ketamine constant‐rate infusion throughout the anaesthetic procedure. Intraoperative complications that were corrected included hypotension (N = 2), hypokalaemia (N = 2), hyperkalaemia (N = 2), metabolic and respiratory acidosis (N = 2), low colloid‐oncotic pressure (N = 2), tachycardia (N = 1), bradycardia (N = 1) and anaemia secondary to intraoperative haemorrhage (N = 1). All dogs survived to be discharged from the hospital. The total survival times were 623, 350 and 46 days, which are longer than the previously reported median survival time of 24 days from discharge.

The first experience of cord blood stem cells application in kidney transplantation: A descriptive study

Abstract. Kidney transplantation is recognized as the optimal method of end-stage kidney disease treatment, but chronic renal allograft rejection remains an unresolved issue and leads to transplanted organ function loss. Recent studies show positive effects of stem cell injections in a variety of diseases, including kidney transplantation.&#x0D; The present study aimed to analyze the first experience of umbilical cord blood stem cells application in living-related kidney transplantation in Shalimov’s National Institute of Surgery and Transplantation, give a preliminary assessment of their effectiveness and safety, evaluate the clinical course and especially the dynamics of laboratory parameters in the recipient’s postoperative period.&#x0D; Methods. The study group included 6 male, adult recipients of kidney transplants, who performed the first kidney allotransplantation from a living family donor in the Shalimov’s National Institute of Surgery and Transplantology in 2020 – 2021. Before surgery, all patients received intravenous administration of a fraction of nuclear cells from human umbilical cord blood at a dose of 2-3 x 106/kg body weight in combination with standard three-component immunosuppressive therapy. Immune system studies were performed before kidney transplantation, on the first and third days of the postoperative period, at the end of the first and second week, as well as on the first, third, sixth, and twelfth months, following kidney transplantation. Renal graft function was assessed by serum creatinine and glomerular filtration rate. Monitoring of clinical and laboratory parameters of blood and urine, the concentration of calcineurin inhibitors (C0) was carried out regularly three times a week for the first month, twice a month for 2-3 months, and once a month until the end of the year.&#x0D; Puncture biopsy of the transplanted kidney was performed three months after surgery to diagnose the pathology of the graft, namely the manifestations of acute and chronic rejection, the nature and degree of which were determined according to the Banff classification.&#x0D; The state of the immune system of the recipients was characterized by indicators of cellular and humoral immunity.&#x0D; Statistical processing of research results was performed using the statistical package StatSoft (2010) STATISTICA 9.1 for Windows StatSoft Inc, Tusla.&#x0D; Results. All patients received cord blood stem cells without complications. On the first day after surgery, an average diuresis was 9415 ± 928.1 ml. Normalization of graft function was observed on the second or third day (GFR more than 90 ml/ min/1.73 m2). There were no rejections of grafts and signs of opportunistic infections in the patients during 1 year follow-up period. Morphological studies did not reveal signs of significant pathological changes in transplanted kidneys in patients who received stem cells as induction therapy.&#x0D; The study of the state of the immune system of recipients in the dynamics, given the insufficient number of patients, requires further research.&#x0D; Conclusions. The administration of cord blood stem cells to recipients prior to kidney transplantation is safe and promotes rapid recovery of renal allograft function. There were no signs of morphological proven chronic graft rejection, which allows us to predict its long-term functioning in the future. To assess the response of the recipient's immune system to the application of cord blood stem cells requires the accumulation of additional data.

Autoimmune Cytopenias Post Hematopoietic Stem Cell Transplantation in Pediatric Patients With Osteopetrosis and Other Nonmalignant Diseases.

Autoimmune cytopenia (AIC) is a rare complication post hematopoietic stem cell transplantation (HSCT), with a higher incidence in nonmalignant diseases. The etiology of post-HSCT AIC is poorly understood, and in many cases, the cytopenia is prolonged and refractory to treatment. Diagnosis of post-HSCT AIC may be challenging, and there is no consensus for a standard of care. In this retrospective study, we summarize our experience over the past five years with post-HSCT AIC in pediatric patients with osteopetrosis and other nonmalignant diseases. All pediatric patients who underwent HSCT for nonmalignant diseases at Hadassah Medical Center over the past five years were screened for post-HSCT AIC, and data were collected from the patient’s medical records. From January 2017 through December 2021, 140 pediatric patients underwent HSCT for osteopetrosis (n=40), and a variety of other nonmalignant diseases. Thirteen patients (9.3%) presented with post-HSCT AIC. Of these, 7 had osteopetrosis (17.5%), and 6 had other underlying nonmalignant diseases. Factors associated with developing AIC included unrelated or non-sibling family donors (n=10), mixed chimerism (n=6), and chronic GvHD (n=5). Treatment modalities included steroids, IVIG, rituximab, bortezomib, daratumumab, eltrombopag, plasmapheresis, and repeated HSCT. Response to treatment was variable; Seven patients (54%) recovered completely, and three patients (23%) recovered partially, still suffering from mild-moderate thrombocytopenia. Three patients died (23%), two following progressive lung disease and one from sepsis and multi-organ failure after a 3rd HSCT. In our experience, post-HSCT AICs in pediatric patients with nonmalignant diseases may pose a challenging post-transplant complication with a variable presentation and a wide spectrum of severity. A relatively high prevalence is seen in patients with osteopetrosis, possibly due to difficult engraftment and high rates of mixed chimerism. There is a dire need for novel treatment modalities for better management of the more severe and refractory cases.

Liver transplantation in patients with liver failure: Twenty years of experience from China.

Liver transplantation (LT) is the only effective method of treating end-stage liver disease, such as various types of liver failure. China has the largest number of patients with hepatitis B virus-related disease, which is also the main cause of liver failure. From the first LT performed in 1977, and especially over the past two decades, LT has experienced rapid development as a result of continuous research and innovation in China. China performs the second-highest number of LTs every year worldwide, and the quality of LT continues to improve. Starting January 1, 2015, all donor's livers have been from deceased donors and familial donors. Thus, China entered into a new era of LT. However, LT is still a challenging procedure in China. In this review, we introduced the brief history of LT in China, the epidemiology, aetiology and clinical outcomes of LT for liver failure in China and summarized the experience of LT from Chinese LT surgeons and scholars. The future perspectives of LT were also discussed, and it is expected that China's LT research could be further integrated elsewhere in the world.

Myeloproliferative neoplasms – a global view

Myeloproliferative neoplasms – a global view

The results of ten years’ experience in allogeneic hematopoietic stem cell transplantation at the Russian Children’s Clinical Hospital

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a common treatment for a large number of pediatric diseases. Treatment planning is based on a careful selection of patients and donors, taking into account factors contributing to a successful outcome. The aim of our study was to analyze the results of 10 years’ experience in allo-HSCT gained at the Department of Bone Marrow Transplantation of the Russian Children's Clinical Hospital of the N.I. Pirogov Russian National Research Medical University. We retrospectively analyzed 506 patients who had undergone their first allo-HSCTs between January 2010 and December 2020. The study was approved by the Independent Ethics Committee and the Scientific Council of the N.I. Pirogov Russian National Research Medical University of Ministry of Healthcare of the Russian Federation. We included 243 patients who had received allo-HSCT before December 2015 and 263 patients who had received allo-HSCT after January 2016. The gender distribution was 60.1% male (n = 304) and 39.9% female (n = 202). The median age was 7.13 years. Allo-HSCT recipients were divided into two groups: 236 children with non-malignant disease, 270 children with malignant disease. In the malignant group, 89 patients were in first complete remission (CR1), 92 were in second complete remission (CR2), and 20 were in third complete remission (CR3) and beyond; 63 patients had active disease (AD); 6 patients received no prior treatment. Two hundred and twenty patients underwent allo-HSCT from a fully matched family donor (MFD), 172 from a matched unrelated donor (MUD), 33 from a mismatched unrelated donor (MMUD) and 81 from a haploidentical (mismatched) family donor (MMFD). Two hundred and eighty-eight patients received bone marrow as a stem cell source, 208 received peripheral blood stem cells; 10 transplants were performed using umbilical cord blood stem cells. The 5-year overall survival (OS) in the entire cohort was 71.34 %. The 5-year OS in the patients who had undergone allo-HSCT between 2016 and 2020 was higher (p = 0.0014). After 2015, the rates of primary graft failure, the incidence of grade III–IV acute “graft-versus-host” disease (GVHD), and recurrence rates were significantly lower. No difference in the incidence of grade III–IV acute GVHD (p = 0.494) and OS rates (p = 0.138) was seen between different sources of hematopoietic stem cells in the patients who received an HLA-compatible transplant (MFD, MUD). Chronic GVHD was significantly dependent on the severity of acute GVHD and donor type. The 3-year OS rate for the patients in CR1, CR2, ≥ CR3, and AD was 84.4 %, 60.5 %, 56.8 %, and 46 % (p = 0.0034), respectively. The relapse rate of the patients in any remission was lower than of those in active disease (p = 0.015). The transplantation-related mortality in the first 100 days after allo-HSCT was 6.92% (n = 35). The patients who had undergone allo-HSCT after 2015 had lower rates of primary graft failure, a decreased incidence of severe GVHD, improved OS and relapse-free survival rates. The frequency of grade III–IV acute GVHD strongly correlated with HLA compatibility. Chronic GVHD was less frequent in MFD recipients. The risk of chronic GVHD increased with the severity of acute GVHD. The HLA mismatch between a donor and a recipient was associated with a decrease in OS. With each subsequent remission, the OS rate decreased. The risk of recurrence was higher in the patients transplanted in active disease. The results of this study can be used in clinical practice to plan therapy, choose an optimal donor, and develop strategies for the prevention and treatment of complications.

Hematopoietic Stem-Cell Transplant Registry in Poland: 2020 Summaries

In the pandemic year 2020, 634 allogeneic hematopoietic stem-cell (HSC) transplants were performed in Poland, including fully matched and haploidentical family donors (n=248) as well as unrelated donors transplantation (n=386). In 48 recipients (7.6%) for allogeneic transplantation, hematopoietic bone marrow cells were transplanted, and in 586 recipients (92.4%), peripheral blood hematopoietic cells. The effect of the pandemic was noticeable but not disastrous-the number of HSC transplants from unrelated donors was lower by 9% compared to 2019 and the use of haploidentical donors slightly increased compared to 2019. Out of all 386 unrelated HSC transplants, the material for 143 transplants (37%) came from international donors, whereas for 243 transplants (63%) material collected from domestic donors was used. Along with the increase in the number of potential bone marrow donors in the national resources, the share of transplants from Polish donors in the total number of transplants increased noticeably from 2006 to 2020. The total number of allogeneic transplants performed in 18 Polish transplant centers between 2006 and 2020 is 7426. Total transplant rates (cumulative number of all allogeneic HSC transplants performed from 2006 to 2020 per 1 million inhabitants) differs between regions and for regions with nonzero number of transplants varies from 520 in Mazowieckie Voivodship to 14 in Lodzkie Voivodship.

Temporal trends in hematopoietic stem cell transplantation in Argentina between 2009 and 2018: A collaborative study by GATMO-TC and INCUCAI

Hematopoietic stem cell transplantation is the only curative treatment for many disorders and international data shows a growing trend. We aimed to evaluate the temporal trends in HSCT transplant rates in Argentina. A time-series analysis was performed for the period 2009 to 2018 using the national database from the National Central Coordinating Institute for Ablations and Implants. Crude and standardized transplant rates were calculated. A permutation joinpoint regression model analysis was used to identify significant changes over time. Altogether, 8,474 transplants were reported to INCUCAI by 28 centers (autologous 67.5%); the main indication was multiple myeloma (30%). The WHO age-sex standardized HSCT rates for the entire country were 153.3 HSCT/10 million inhabitants (95% CI 141.7-165.8) in 2009 and 260.1 HSCT/10 million inhabitants (95% CI 245.5-275.5) in 2018. There was a large gap in HSCT rates among the states and regions. The transplant rate was higher for autologous transplants throughout the years. Within the allogeneic group, the related donor transplant rate was higher than the unrelated donor transplant rate. The joinpoint regression analysis of HSCT rates for the whole country over time showed an observed annual percentage change of 6.3% (95% CI 5.4-7.3; p<0.01). No changes were observed for unrelated donors during the study period. Age-sex standardized HSCT rates in Argentina are increasing, mainly due to autologous and family donor allogeneic transplants. A wide variation across the country was found, demonstrating differences in the access to transplantation among Argentine regions.

TCRαβ-Depleted Haploidentical Grafts Are a Safe Alternative to HLA-Matched Unrelated Donor Stem Cell Transplants for Infants with Severe Combined Immunodeficiency

Hematopoietic stem cell transplantation and gene therapy are the only curative therapies for severe combined immunodeficiency (SCID). In patients lacking a matched donor, TCRαβ/CD19-depleted haploidentical family donor transplant (TCRαβ-HaploSCT) is a promising strategy. Conditioned transplant in SCID correlates to better myeloid chimerism and reduced immunoglobulin dependency. We studied transplant outcome in SCID infants according to donor type, specifically TCRαβ-HaploSCT, and conditioning, through retrospective cohort analysis of 52 consecutive infants with SCID transplanted between 2013 and 2020. Median age at transplant was 5.1 months (range, 0.8–16.6). Donors were TCRαβ-HaploSCT (n = 16, 31.4%), matched family donor (MFD, n = 15, 29.4%), matched unrelated donor (MUD, n = 9, 17.6%), and matched unrelated cord blood (CB, n = 11, 21.6%). Forty-one (80%) received fludarabine/treosulfan-based conditioning, 3 (6%) had alemtuzumab only, and 7 (14%) received unconditioned infusions. For conditioned transplants (n = 41), 3-year overall survival was 91% (95% confidence interval, 52–99%) for TCRαβ-HaploSCT, 80% (41–98%) for MFD, 87% (36–98%) for MUD, and 89% (43–98%) for CB (p = 0.89). Cumulative incidence of grade II–IV acute graft-versus-host disease was 11% (2–79%) after TCRαβ-HaploSCT, 0 after MFD, 29% (7–100%) after MUD, and 11% (2–79%) after CB (p = 0.10). 9/10 patients who received alemtuzumab-only or unconditioned transplants survived. Myeloid chimerism was higher following conditioning (median 47%, range 0–100%) versus unconditioned transplant (median 3%, 0–9%) (p < 0.001), as was the proportion of immunoglobulin-free long-term survivors (n = 29/36, 81% vs n = 4/9, 54%) (p < 0.001). TCRαβ-HaploSCT has comparable outcome to MUD and is a promising alternative donor strategy for infants with SCID lacking MFD. This study confirms that conditioned transplant offers better myeloid chimerism and immunoglobulin freedom in long-term survivors.

Young Indians’ Willingness to Make a Living Organ Donation

The large unmet need in India for organs to transplant calls for an increase in living organ donations. This study examined the positions of Indian university students on making a living organ donation. A convenience sample of 339 students from Karnatak University rated willingness to be a living donor in 48 scenarios consisting of all combinations of 5 factors: recipient's identity (close family member vs stranger), level of surgical risk for the donor, possible long-term health consequences for the donor, probability of transplant success, and likelihood of finding other donors (the subject is one of the rare compatible donors or one donor among others). Cluster analyses showed the existence of 4 qualitatively distinct positions called nondonors (9%); family donors (21%), for whom willingness was very high when recipients were family members and very low when they were strangers; universal donors (30%), for whom willingness was also quite high when a stranger was involved; and conditional donors (23%), who took a risk-benefit perspective. These finding suggest that the fundamental reason for the current shortage of organs in India is neither psychological nor cultural but more likely organizational.

320 - Safety and Efficacy of High Dose Granulocyte Colony Stimulating Factor Mobilization in Familial Haploidentical Adult Donors with Sickle Cell Trait Followed By CD34+ Cell Enrichment and Mononuclear Cell Add-Back Prior to Haploidentical Allogeneic Transplantation in High-Risk Sickle Cell Disease Recipients

320 - Safety and Efficacy of High Dose Granulocyte Colony Stimulating Factor Mobilization in Familial Haploidentical Adult Donors with Sickle Cell Trait Followed By CD34+ Cell Enrichment and Mononuclear Cell Add-Back Prior to Haploidentical Allogeneic Transplantation in High-Risk Sickle Cell Disease Recipients