Unrelated Donor Hematopoietic Stem Cell Research Articles

Factors associated with registrant availability for unrelated adult donor hematopoietic stem cell donation: Analysis of the stem cell registry at Canadian Blood Services.

Greater use of unrelated donors to support hematopoietic cell transplantation can be hampered by unavailability of registrants when identified as potential candidates for donation. Multivariate analysis was performed to identify donor factors associated with availability for verification of human leukocyte antigen typing (VT) needed before donor activation. All VT requests for registrants on the Canadian Blood Services Stem Cell Registry between 1 January and 31 December 2018 were reviewed (n = 1358). Potential donors identified by transplant centers were categorized as available at the time of VT but ineligible for medical or other reasons (n = 130 and excluded from further analysis), available (n = 622) or unavailable (n = 566) due to scheduling, loss of interest, and/or inability to contact. With multivariate analysis, registrants who previously donated blood, those recruited online or from blood donation clinics, and a shorter interval between registration and VT request were significantly correlated with increased donor availability. Donor sex and geographic location, however, displayed no correlation. Online registration and recruitment at whole blood donation centers should be enhanced to increase the availability of registrants at VT. More insight is needed to maintain registrant availability following community in-person recruitment events, especially if the interval between registration and activation is prolonged. Recruitment of male registrants who are well informed should not negatively impact availability.

New global reporting system for serious (product) events and adverse reactions in hematopoietic stem cell donation and transplantation.

Annually more than 21,000 volunteer unrelated hematopoietic stem cell donations are performed worldwide for patients with life-threatening diseases such as acute leukaemia. Donor safety issues and donor protection is one of the top priorities for the international cooperation of unrelated hematopoietic stem cell donor registries represented by the World Marrow Donor Association (WMDA). With this new global reporting system for serious events and adverse reactions (S(P)EARs), the WMDA aims to become the global leading online platform for hematopoietic stem cell donor organisations to report their S(P)EARs from both unrelated and family donors. Software developer Cogapp developed the platform using a Knack environment based on requirements of experienced reporters and reviewers. On July 1st WMDA launched a robust online reporting system for S(P)EARs in order to provide accurate information about potential risks to donors. The collected data about S(P)EARs occurring in donors will be analysed and used to provide statistics on the type of reports being submitted and to put in place best practices to mitigate such effects and occurrences. Via the annual S(P)EAR reports the results will be disseminated worldwide.

Seasonal variation of human physiology does not influence the harvest of peripheral blood CD34+ cells from unrelated hematopoietic stem cell donors

There are many reports on factors predicting the outcome of PBSC (peripheral blood stem cell) mobilization, such as the donor’s gender, age, weight, white blood cell count, platelets pre apheresis, LDH and iron status. Although there are reports of seasonal variation in the physiology of the human immune system and hematopoiesis there are no data that such differences play a role in the response to G-CSF in healthy hematopoietic stem cell donors. The response to G-CSF could also impact the collection results during different seasons. To assess the possible impact of seasonal variation we performed a retrospective, single-center analysis of mobilization and harvest of PBSC in 330 healthy unrelated donors. We found no significant differences in the number of CD34+ cells in peripheral blood after G-CSF mobilization and in collection results when all donors were analyzed. In the subgroup of male donors the number of CD34+ stem cells after G-CSF mobilization was higher than average in summer and autumn (p = 0.036), however, it did not translate into clinically relevant differences in stem cell harvest.We conclude that although there is possible seasonal variation in the response to G-CSF in male donors there is no impact on PBSC harvest in healthy unrelated donors.

Health-Related Quality-of-Life Comparison of Adult Related and Unrelated HSC Donors: An RDSafe Study.

Multiple investigations have documented the health-related quality-of-life (HRQoL) and donation-related experiences of unrelated donors (URDs), but similar investigations of the related donor (RD) experience have been less common. The central goal of this study was to longitudinally examine and compare HRQoL of RD and URD hematopoietic stem cell (HSC) donors from predonation through 1 year postdonation. This prospective investigation included adult HSC donors ages 18 to 60 years who donated bone marrow or peripheral blood stem cells at one of 48 geographically diverse US transplant/donor centers and completed HRQoL interviews at predonation and 4 weeks and 1 year postdonation. At predonation, related donors were less ambivalent about donation (t=-3.30; P=.001), more satisfied with their decision to donate (t=2.65; P=.009), and more likely to define themselves as donors (t=2.94; P=.004) than were URDs. However, related donors were more concerned about the use of needles (odds ratio [OR]=2.19; P=.012), about who would pay for the procedure (OR=2.80; P=.011), and the possibility that they would feel responsible if the transplant failed (t=2.31; P=.022). Shortly postdonation, related donors were more likely to report donation-related pain (t=2.50; P=.013) and lightheadedness (OR=3.63; P=.028). At 1 year postdonation, related donors were less likely to be fully recovered from donation (OR=0.10; P=.010) and more likely to report a longer recovery period following donation (t=2.57; P=.011), although this latter finding was primarily due to the percentage of related versus unrelated donors not fully recovered at 1 year postdonation (10% versus 1%). Taken together, these findings suggest that current related donor management practices may be sufficient in preparing related donors for the psychological aspects of donation but that there may be more to do in terms of calibrating the description of donation-related experiences and recovery time to the related donor group (i.e., descriptions of donation experiences based on unrelated donation may not provide best estimates of experience for this group).

An assessment of the effectiveness of the search for unrelated hematopoietic stem cell donors for russian patients in the registry of Kirov Research Institute of Hematology and Blood Transfusion, Federal Medical and Biological Agency of Russia

We assessed the effectiveness of the registry of Kirov Research Institute of Hematology and Blood Transfusion, Federal Medical and Biological Agency of Russia, with a total of 35,117 hematopoietic stem cell donors recruited in 22 regions of the Russian Federation (as of 01 January 2019). It was established that a relatively small registry would be sufficient to find at least one fully matched donor for 43% of Russian patients. The sufficient representativeness of this hematopoietic stem cell donor registry is confirmed by the high concordance of established HLA haplotype profiles between the population of donors and the cohort of patients for whom a search of a matching donor was performed. This study was approved by the Independent Ethics Committee and Scientific Council of Kirov Research Institute of Hematology and Blood Transfusion, FMBA of Russia.

Ulusal Gönüllü Kök Hücre Verici Bankası (TÜRKÖK) Kurulması Akraba Dışı Hematopoietik Kök Hücre Nakli Etkinliğimizi Nasıl Etkiledi? Geriye Dönük Tek Merkez Değerlendirmesi

Ulusal Gönüllü Kök Hücre Verici Bankası (TÜRKÖK) Kurulması Akraba Dışı Hematopoietik Kök Hücre Nakli Etkinliğimizi Nasıl Etkiledi? Geriye Dönük Tek Merkez Değerlendirmesi

Outcomes of myeloablative, T cell deplete unrelated donor hematopoietic stem cell transplantation at a single center.

e19525 Background: Myeloablative conditioning (MAC) and unrelated donor (UD) hematopoietic cell transplantation (HCT) are associated with increased non-relapse mortality (NRM) compared with matched related donor (MRD) HCT [18%, 21%, and 32% for MRD, Matched UD (MUD), and mismatched MUD (MMUD), respectively, p < 0.001] (Saber et al, 2012). Our center uses alemtuzumab as means of T cell depletion to mitigate NRM risk in UD HCT. Here, we report outcomes utilizing this strategy. Methods: We retrospectively analyzed adult patients (pts) who received alemtuzumab-based T cell deplete MAC UD HCT from August 2012 to December 2017. Outcomes were estimated via Kaplan Meier and cumulative incidence methods. Results: Sixty-eight pts underwent T cell deplete MAC UD HCT for AML/MDS (n = 32), ALL (n = 18), lymphoma (n = 5), and other diseases (n = 13). Thirty-nine (57.4%) underwent a MUD HCT, while 29 (42.4%) underwent a MMUD (≤ 9/10 match) HCT. Median follow up was 35.5 months (m) (range 1.5 – 71.1). Median age was 46 years (range 21 - 68), 58.8% were male. Nineteen AML pts (67.9% of all AML) were considered high risk defined as secondary AML (n = 3), CR2 or more (n = 9), primary induction failure (n = 6) or having gross residual disease at time of HCT (n = 1). At 24 m, overall survival (OS) for the entire cohort was 65.3% (95%CI (CI) 53.5%- 77.2%), GVHD relapse-free survival (GRFS) was 54.8% (CI 42.8%- 66.9%), NRM was 10.4% (CI 4.5%- 19.2%), and relapse incidence (RI) was 27.3% (CI 17.1%- 38.5%). None of the 68 pts had graft failure or rejection. In the AML/MDS cohort, at 24 m OS was 52.3% (CI 33.9%- 70.7%), GRFS was 41.4% (CI 23.9%- 59%), NRM was 9.7% (CI 2.4%- 23.2%), and RI was 39.1% (CI 21.8%- 56.2%). Non-AML/MDS pts at 24 m had OS, GRFS, NRM and RI of 76.8% (CI 62.6%- 90.9%), 66.7% (CI 51.3%- 82.08%), 11.1% (CI 3.4%- 23.9%), and 16.7% (CI 6.6%- 30.6%), respectively. The table summarizes our outcomes. Conclusions: We show that alemtuzumab-based MAC conditioning for UD HCT has the benefit of being well tolerated with low NRM and high GRFS, while having comparable RI and OS compared to published outcomes of T cell replete MAC UD HCT (Saber et al, 2012). However, the retrospective nature without a comparator is a major limitation which necessitates a future prospective study to validate these findings. [Table: see text]

The role of HLA matching in unrelated donor hematopoietic stem cell transplantation for sickle cell disease in Europe.

We report the results of an analysis of unrelated allogeneic hematopoietic stem cell transplantations (HSCT) in 71 patients with sickle cell disease (SCD) transplanted in EBMT centers between 2005 and 2017. Median age was 9.3 years; graft type was bone marrow in 79% and peripheral blood in 21%. Recipient-donor HLA match at high resolution typing was 10/10 in 31, 9/10 in 20, and 8/10 in 4 patients; the other patients had intermediate resolution typing. The most frequent conditioning regimens were fludarabine-thiotepa-treosulfan (64%) or busulfan-cyclophosphamide (12%). Cumulative incidence of neutrophil engraftment was 92%; platelet engraftment was 90%. Eleven patients (15%) experienced graft failure. Grade II-IV acute graft-vs.-host disease (GvHD) was 23%; 3-year chronic GvHD was 23%. Three-year overall survival (OS) was 88 ± 4%. GRFS was 62 ± 6%. HLA matching was the most significant risk factor for OS: 3-year OS was 96 ± 4% in 10/10 group vs. 75 ± 10% in 9-8/10 (p = 0.042); GRFS was 69 ± 9% vs. 50 ± 12% (p = 0.114), respectively. In conclusion, unrelated donor HSCT is a valid option for SCD patients who lack an HLA-identical sibling donor, preferably in the context of clinical trials. Using a 10/10 HLA-matched unrelated donor yields better survival indicating that HLA matching is an important donor selection factor in this nonmalignant disease.

Young and Restless: Expansion of Donor-Origin Mutant HSCs after Transplantation

In a study of young adults chosen as unrelated hematopoietic stem cell donors for patients with hematological malignancies, leukemia-associated mutations were detectable in cells from 44% of donors. Donor-origin mutant clones engrafted in recipients and expanded during the first 100days after transplant, but donor-derived leukemia was not observed.

Prospective Identification of Unrelated Donors with Low Inhibitory Donor KIR3DL1 – Recipient HLA-B Interaction Decreases Relapse and Improves Survival after Allogeneic Hematopoietic Cell Transplantation for Myeloid Neoplasia

Retrospective studies indicate that the use of unrelated hematopoietic stem cell donors with Killer Ig-like Receptor (KIR) genotypes resulting in low inhibitory interactions with recipient HLA are associated with lower relapse and higher survival in patients with myeloid neoplasia undergoing allogeneic hematopoietic cell transplantation (allo HCT). To validate these findings in a prospective fashion and to determine if advantageous KIR donors can readily be identified for patients with myeloid neoplasia, we prospectively KIR genotyped and provided KIR/HLA-based ranking for unrelated donors (URD) evaluated for patients with a diagnosis of acute myeloid leukemia or myelodysplastic syndrome undergoing workup at our center for allo HCT. Donors were prioritized first to minimize inhibitory KIR3DL1 - HLA-Bw4 interactions, followed by prioritization of donors with non-tolerized activating KIR2DS1, and finally prioritizing donors homozygous for the centromeric B haplotype. We evaluated 2,079 donors for 527 patients (median 4 donors per patient), among whom 263 ultimately underwent allo HCT. In a multivariate analysis adjusting for age, HCT-CI, and conditioning intensity, we found that the use of a KIR3DL1-low-inhibition donor was associated with an improved hazard for survival (HR = 0.58 (95% confidence interval (CI): 0.35 – 0.96), P = 0.035) and event-free survival (HR = 0.61 (95% CI: 0.39 – 0.93), P = 0.023) due to a decreased hazard for relapse (HR = 0.52, 95% CI: 0.30 – 0.90, P = 0.021) without increased non-relapse mortality when compared to KIR3DL1-non-interacting or -high-inhibition donors. Donor KIR2DS1/HLA-C1 status and centromeric haplotype B content were not predictive of relapse or survival in this cohort. Among 339 HLA-Bw4+ patients evaluated for transplant, 242 (71.4%) had an available KIR3DL1-low-inhibition donor and 205 (60.5%) had a mixture of KIR3DL1-low-inhibition with either -high-inhibition or -non-interacting donors facilitating a choice using donor KIR3DL1 genotyping. Evaluating greater numbers of donors associated with an increased probability of identifying an advantageous donor based on inhibitory KIR3DL1 interactions (P

A Phase II Clinical Trial of Post-Transplant Cyclophosphamide for Graft Versus Host Disease Prevention Following Myeloablative Peripheral Blood Stem Cell Matched Unrelated Donor Hematopoietic Stem Cell Transplantation

<h3>Background</h3> The optimal regimen for graft versus host disease (GVHD) prophylaxis in matched unrelated donor (MUD) allogeneic hematopoietic stem cell transplantation (HSCT) is not well defined. Post-transplant cyclophosphamide (PT-Cy) mitigates GVHD after T-cell replete HLA haploidentical (Haplo) bone marrow transplant. We investigated the benefit of PT-Cy in preventing GVHD following myeloablative peripheral blood stem cell (PBSC) MUD HSCT. <h3>Methods</h3> We conducted a phase II clinical trial of PT-Cy for GVHD prophylaxis following MUD HSCT. GVHD prophylaxis consisted of 1 dose of PT-Cy 50mg/kg on day +3, mycophenolate mofetil starting day +5 to +35 and tacrolimus starting on day +5 with taper starting at day +100. The primary endpoint of the study was to determine the incidence of grade II-IV acute GVHD. Secondary endpoints included overall survival (OS), disease free survival (DFS), non-relapse mortlity (NRM) and time to engraftment. <h3>Results</h3> There were 39 patients enrolled in the study. The mean age of the study population was 47.36 years (SD 13.41). There were 23 females (59%) and majority of the patients were white (85%). Thirty six donors were 8/8 HLA MUD and 3 were 7/8 matched unrelated. The stem cells were collected from peripheral blood in all cases. Indications for HSCT included AML/MDS (62%), ALL (15%), myelofibrosis (10%), NHL/HL (10%) and CML (3%). The most commonly used conditioning regimen was Busulfan and Fludarabine (74%). All 6 patients with ALL received TBI (12 Gy) based conditioning. There was 1 death within the first 30 days before engraftment. The remaining 38 patients (97%) successfully engrafted. The median time to ANC engraftment was 12 days (range 9-14 days). The incidence of day 100 acute GVHD maximum grade was 36% for grade I/II and 5% for grade III/IV. The incidence of limited and extensive chronic GVHD was 10% and 36% respectively. There were 8 (21%) confirmed relapses within the first year after HSCT. Twenty four patients were alive at the 1-year mark after transplant and 17 of these were in complete remission. The 1-year and 2-year OS rates were 61.5% and 51.2% respectively. The median OS for the entire cohort was 21.2 months with a median follow up of 50 months (Figure 1). The day 100, 1-year and overall NRM rates were 10%, 28% and 33% respectively with infectious complications being the most common cause of death. <h3>Conclusion</h3> The use of one dose of PT-Cy in combination with MMF and tacrolimus is effective in preventing acute severe GVHD in myeloablative PBSC MUD HSCT recipients. We observe modest control over chronic GVHD with this regimen which may be explained by giving one dose of PT-Cy only. We report favorable survival outcomes along with acceptable levels of NRM for the entire cohort. The use of PT-Cy in combination with other immunosuppressant agents for GVHD prevention appears to be a promising strategy in MUD and may play a vital role in mismatched unrelated donor transplants as well.

Immunogenetic characteristics of unrelated hematopoietic stem cell donors recruited in the Sverdlovsk, Saratov, Yaroslavl and Vladimir regions

Aim of the study was to investigate the distribution features of HLA alleles and multilocus haplotypes in potential donors of hematopoietic stem cells recruting in the Sverdlovsk, Saratov, Yaroslavl and Vladimir regions. Material and methods. Sequence Based Typing technology was used to identify human leukocyte antigen (HLA)-A, -B, -C, -DRB1 alleles from 2683 Russian unrelated bone marrow volunteers living in the Sverdlovsk (n = 1018), Saratov (n = 825), Yaroslavl (n = 604) and Vladimir (n = 236) regions. HLA allele and haplotype frequencies were estimated via maximum-likelihood analysis from genotypic data through an expectation-maximization (EM) algorithm for unknown gametic phase. Results and discussion. In all studied populations, 16 HLA-A, 13 HLA-C, 13 HLA-DRB1 alleles were selected. In the locus HLA-B, 28 alleles were detected in the populations of the Sverdlovsk and Yaroslavl regions, 27alleles – in the Saratov region, 25 alleles – in the Vladimir. Seventeen alleles, HLA-A*02, HLA-A*03, HLA-A*01, HLA-A*24, HLA-B*07, HLA-B*35, HLA-С*07, HLA-С*06, HLA-С*04, HLA-С*03, HLA-С*12, HLA-DRB1*15, HLA-DRB1*07, HLA-DRB1*01, HLA-DRB1*13, HLA-DRB1*04, HLA-DRB1*11 exhibit frequencies over 10 %. The highest frequency extended haplotype in the all studied populations HLA-A*01-B*08-C*07-DRB1*03, was observed frequencies of 4,4 % – in the Sverdlovsk region, 3,2 % – in the Saratov region, 4,9 % – in the Yaroslavl region and 4,2 % – in the Vladimir region. Routine HLA typing allowed us to define four new HLA alleles in the populations of the Sverdlovsk and Saratov region.

Cost-Effective TA Cloning Applied to Sanger Sequencing and HLA Allele Typing

Polymerase chain reaction (PCR)-based technology for clinical HLA typing involves DNA Sanger sequencing of the PCR amplified products of polymorphic loci of HLA, such as HLA-A, -B, -C, -DPB1,-DQB1, and -DRB1, in support of unrelated donor hematopoietic stem cell transplantation. The TA cloning of all the amplicons, followed by Sanger sequencing, provides a primary screening tool of potential organ donors, or to identify individuals who might have potential adverse drug responses. The Class I exon 2 and 3 genes of HLA was amplified as a single fragment and cloned into a TA cloning vector pTZ57R/T, while the Class II exon 2 and 3 amplified fragments were added together in a ligation mix with the vector pTZ57R/T. Positive clones were subjected to Sanger sequencing, and HLA alleles determined using the IMGT database. Results indicate that all the exons of the HLA genes by could be cloned by the strategies described. Furthermore, we were also successful in achieving the amplification of all the desired amplicons as a multiplex PCR, thereby reducing the cost of the modified method further by almost 60 %. We present a cost-effective TA cloning strategy for achieving accurate allele typing of HLA at 2- digit resolution. Taken together, an efficient cloning methodology with a significant lower cost for accurate HLA typing presented here is encouraging. The data suggests that it may be employed for routine cloning of variable targets in molecular biology applications.

Association of Donor-Recipient HLA Matching with Outcome of Unrelated Donor Hematopoietic Stem Cell Transplantation: A Study from the Cellular Therapy and Immunobiology Working Party (CTIWP) of the European Society for Blood and Marrow Transplantation (EBMT)

Association of Donor-Recipient HLA Matching with Outcome of Unrelated Donor Hematopoietic Stem Cell Transplantation: A Study from the Cellular Therapy and Immunobiology Working Party (CTIWP) of the European Society for Blood and Marrow Transplantation (EBMT)

Results of Unrelated Donor Hematopoietic Stem Cell Transplantation for Sickle Cell Disease in Europe on Behalf of Paediatric Diseases (PDWP) and Inborn Errors Working Parties (IEWP) of the EBMT

Introduction: Allogeneic hematopoietic stem cell transplantation (HSCT) is, to date, the only curative treatment for sickle cell disease (SCD). Because a human leukocyte antigen (HLA) matched sibling donor is not always available, alternative stem cell sources such as unrelated or haploidentical related donors have been explored. The likelihood of finding a 10/10 (HLA-A, B, C, DRB1 and DQB1) matched donor varies among ethnic groups, with the lowest probability among individuals of African descent. To date, few series of SCD patients transplanted with an unrelated donor (UD) have been reported, but the high rates of rejection and chronic graft versus host disease (cGvHD) have limited its widespread application. Patients and methods: We report the results of a retrospective, registry based, survey on 70 UD HSCT performed in patients (pts) with SCD from UD in 22 European Society for Blood and Marrow Transplantation (EBMT) centers between 2005 and 2017. Data were collected from the EBMT database and missing information was updated by the centers. Median follow up was 38 (range 2-154) months. Most pts were HbSS (n=54; 78%), had positive serology for CMV (80%), and a Karnofsky score &gt;80% (98%). Eighteen pts had a major ABO incompatibility. Recurrent vaso-occlusive crisis (n=58), cerebral vasculopathy (n=23) and acute chest syndrome (n=24) were the main indications for HSCT. Red blood cell (RBC) transfusions pre-HSCT were reported in 97% of pts of whom 53% received more than 20 transfusions; 14% of the transfused pts had RBC alloantibodies. Hydroxyurea pre-HSCT was used in 65% of pts. Median age at HSCT was 9.6 years (range 2-43) with 87% of pts being ≤ 16 years. Stem cell source was bone marrow (BM) in 55 pts (79%) and peripheral blood (PBSC) in 15 (21%). The median number of infused TNC /kg was 3.6 x 108 for BM and 7.1 x 108 for PBSC; the median number of infused CD34/kg was 4.4 x 106 for BM and 8.3 x 106 for PBSC. HLA matching at high resolution typing was 10/10 (HLA-A, B, C, DRB1 and DQB1) in 31, 9/10 in 17 and 8/10 in 4 of the patient-donor pairs; intermediate resolution typing was available for 10 (10/10 or 9/10) and the HLA information was missing for the remaining 8 patient-donor pairs. The most frequent conditioning regimens were fludarabine-thiotepa-treosulfan (64%) and busulfan- cyclophosphamide (12%). GvHD prophylaxis was cyclosporine plus methotrexate in 59%. Anti-thymocyte globulin was used in 90% and alemtuzumab in 9% of pts. Results: The cumulative incidence (CI) of neutrophil engraftment at 60 days was 93% (95% CI 76-100), with median time to engraftment of 18 days; platelet engraftment at 180 days was 90% (95% CI 83-98) with a median time of 20 days. Ten pts had graft failure (5 primary and 5 secondary) of whom 6 had a second transplant and were all alive at last FU (median 9.5 months after second HSCT). The CI of grade II-IV aGVHD at 100 days was 23% (95% CI 15-36), and 8 pts (11%) had grade III-IV. Acute GVHD was more frequent in patients who received PBSC (PBSC 42.9%, BM 18.2%, p=0.062). Three-year CI of cGVHD was 23% (95% CI 15-36), 7 pts (10%) had limited and 9 (13%) extensive cGvHD. Three-year overall survival (OS) was 90±4%; three-year event free survival (EFS) (considering death and graft failure as events) was 76±6%; HLA matching between donor and recipient was the most important factor for OS and EFS. Considering only pts-donor pairs with high resolution HLA typing available (n=52), 3-year OS was 96±4% in 10/10 group compared to 77±11% in 9/10 plus 8/10 group (p 0.065), 3-year EFS was 85±7% vs 62±12% (p 0.040), respectively. No significant differences between the groups were observed in CI of neutrophil engraftment, aGVHD and cGVHD. Conclusion: UD HSCT is a valid option for SCD patients who lack an HLA-identical sibling donor. Nevertheless, efforts are still needed to improve outcomes after UD HSCT. Our results indicate that using a 10/10 HLA matched UD improves both OS and EFS compared to donors with 1 or more mismatches; so, when such a matched unrelated donor is not found, using an haplo relative or an unrelated cord blood as donor source should be evaluated. A prospective trial is in preparation to evaluate the use of haploidentical donors for HSCT in SCD (EudraCT number: 2018-002652-33). Disclosures No relevant conflicts of interest to declare.

A Phase II Clinical Trial of Post-Transplant Cyclophosphamide for Graft Versus Host Disease Prevention Following Myeloablative Peripheral Blood Stem Cell Matched Unrelated Donor Hematopoietic Stem Cell Transplantation

Background: The use of post-transplant cyclophosphamide (PT-Cy) in combination with other immunosuppressive agents for graft versus host disease (GVHD) prophylaxis in matched unrelated donor (MUD) allogeneic hematopoietic stem cell transplantation (HSCT) is not well defined. PT-Cy mitigates GVHD after T-cell replete HLA haploidentical (Haplo) bone marrow transplant. Extrapolating from the success of PT-Cy in haplo transplants, we investigated the benefit of PT-Cy (at a lower dose than that used in haplo HSCT) in preventing GVHD following myeloablative peripheral blood stem cell (PBSC) MUD HSCT. Methods: We conducted a phase II clinical trial between September 2013 and June 2018 of PT-Cy for GVHD prophylaxis following myeloablative MUD HSCT. GVHD prophylaxis consisted of 1 dose of PT-Cy 50mg/kg on day +3, mycophenolate mofetil starting day +5 till day +35 and tacrolimus starting on day +5 with taper starting at day +100. The primary endpoint of the study was to determine the incidence of grade II-IV acute GVHD. Secondary endpoints included overall survival (OS), disease free survival (DFS), non-relapse mortlity (NRM) and time to engraftment. Approval for the study was obtained from the Institutional Review Board. Results: There were 39 patients enrolled in the study (Table 1). The mean age of the study population was 47.36 years (SD 13.41). There were 23 females (59%) and majority of the patients were white (85%). Thirty six donors were 8/8 HLA MUD and 3 were 7/8 matched unrelated. The stem cells were collected from peripheral blood in all cases. Indications for HSCT included AML/MDS (62%), ALL (15%), myelofibrosis (10%), NHL/HL (10%) and CML (3%). Based on disease risk index (DRI) assessment, 6 (15%) patients were DRI high, 32 (82%) were intermediate and 1 (3%) was low. The most commonly used myeloablative conditioning regimen was Busulfan and Fludarabine (74%). All 6 patients with ALL received TBI (12 Gy) based conditioning. Three patients with NHL received Fludarabine and Melphalan. There was 1 death within the first 30 days before engraftment. The remaining 38 patients (97%) successfully engrafted. The median time to ANC engraftment was 12 days (range 9-14 days). The incidence of day 100 acute GVHD maximum grade was 36% for grade I/II and 5% for grade III/IV (Table 2). The overall incidence of limited and extensive chronic GVHD was 10% and 36% respectively. There were 8 (21%) confirmed relapses within the first year after HSCT. Twenty four patients were alive at the 1-year mark after transplant and 17 of them were in complete remission. The 1-year and 2-year OS rates were 61.5% and 51.2% respectively. The median OS for the entire cohort was 21.2 months with a median follow up of 50 months (Figure 1). The day 100, 1-year and overall NRM rates were 10%, 28% and 33% respectively with infectious complications being the most common cause of death. Conclusion: We report a low incidence of acute severe GVHD with the combination of one dose of PT-Cy in combination with MMF and tacrolimus following myeloablative PBSC MUD HSCT. The single dose of PT-Cy may explain the modest control over chronic GVHD with this regimen. We also report favorable survival outcomes along with acceptable levels of NRM for the entire cohort. The use of PT-Cy in combination with other immunosuppressant agents for GVHD prevention appears to be a promising strategy in MUD HSCT and may play a vital role in mismatched unrelated donor transplants as well. Disclosures Costa: Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy; Fujimoto Pharmaceutical Corporation Japan: Other: Advisor; GSK: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Speakers Bureau; Abbvie: Consultancy. Saad:Actinium Pharma Inc: Consultancy; Amgen: Other: Research Support; Kadmon: Other: Research Support; OrcaBio: Other: Research Support.

Lower Hematopoietic Progenitor Cell Counts and Yields at Subsequent Donations Is Influenced By a Shorter Inter-Donation Interval between the First and Subsequent Mobilizations

Introduction: Approximately 7% of unrelated hematopoietic stem cell (HSC) donors are asked to donate a subsequent time to the same or different recipient. In a recent large CIBMTR study of second time donors, Stroncek et al. incidentally found that second peripheral blood stem cell (PBSC) collections had lower total CD34+ cells, CD34+ cells per liter of whole blood processed, and CD34+ cells per kg donor weight. Based on smaller studies, the time between the two independent PBSC donations (inter-donation interval) as well as donor sex, race and baseline lymphocyte counts appear to influence CD34+ cell yields at subsequent donations. Our objective was to retrospectively evaluate factors contributory to CD34+ cell yields at subsequent PBSC donation amongst NMDP donors. Methods. The study population consisted of filgrastim (G-CSF) mobilized PBSC donors through the NMDP/CIBMTR between 2006 and 2017, with a subsequent donation of the same product. evaluated the impact of inter-donation interval, donor demographics (age, BMI, race, sex, G-CSF dose, year of procedure, need for central line) and changes in complete blood counts (CBC), on the CD34+ cell yields/liter (x106/L) of blood processed at second donation and pre-apheresis (Day 5) peripheral blood CD34+ cell counts/liter (x106/L) at second donation. Linear regression was used to model log cell yields as a function of donor and collection related variables, time between donations, and changes in baseline values from first to second donation. Stepwise model building, along with interactions among significant variables were assessed. The Pearson chi-square test or the Kruskal-Wallis test compared discrete variables or continuous variables, respectively. For multivariate analysis, a significance level of 0.01 was used due to the large number of variables considered. Results: Among 513 PBSC donors who subsequently donated a second PBSC product, clinically relevant decreases in values at the second donation were observed in pre-apheresis CD34+ cells (73.9 vs. 68.6; p=0.03), CD34+cells/L blood processed (32.2 vs. 30.1; p=0.06), and total final CD34+ cell count (x106) (608 vs. 556; p=0.02). Median time interval between first and second PBSC donations was 11.7 months (range: 0.3-128.1). Using the median pre-apheresis peripheral blood CD34+ cell counts from donation 1 as the cut-off for high versus low mobilizers, we found that individuals who were likely to be high or low mobilizers at first donation were also likely to be high or low mobilizers at second donation, respectively (Table 1). This was independent of the inter-donation interval. In multivariate analyses, those with an inter-donation interval of &gt;12 months, demonstrated higher CD34+cells/L blood processed compared to donors donating within a year (mean ratio 1.15, p&lt;0.0001). Change in donor BMI was also a predictor for PBSC yields. If donor BMI decreased at second donation, so did the CD34+cells/L blood processed (0.74, p &lt;0.0001). An average G-CSF dose above 960mcg was also associated with an increase in CD34+cells/L blood processed compared to donors who received less than 960mcg (1.04, p=0.005). (Table 2A). Pre-apheresis peripheral blood CD34+ cells on Day 5 of second donation were also affected by the inter-donation interval, with higher cell counts associated with a longer time interval (&gt;12 months) between donations (1.23, p&lt;0.0001). Further, independent of the inter-donation interval, GCSF doses greater than 960mcg per day associated with higher pre-apheresis CD34+ cells at second donation (1.26, p&lt;0.0001); as was a higher baseline WBC count (&gt;6.9) (1.3, p&lt;0.0001) (Table 2B). Conclusions: In this large retrospective study of second time unrelated PBSC donors, a longer inter-donation interval was confirmed to be associated with better PBSC mobilization and collection. Given hematopoietic stem cell cycling times of 9-12 months in humans, where possible, repeat donors may be chosen based on these intervals to optimize PBSC yields. Changes in BMI are also to be considered while recruiting repeat donors. Some of these parameters may be improved marginally by increasing G-CSF dose within permissible limits. In most instances, however, sub-optimal mobilizers at first donation appear to donate suboptimal numbers of HSC at their subsequent donation. Disclosures Pulsipher: CSL Behring: Membership on an entity's Board of Directors or advisory committees; Miltenyi: Research Funding; Bellicum: Consultancy; Amgen: Other: Lecture; Jazz: Other: Education for employees; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Medac: Honoraria. Shaw:Therakos: Other: Speaker Engagement.

P006 To test or not to test: The importance of HLA antibody testing and HLA-DP typing in unrelated donor hematopoietic stem cell transplantation (HSCT)

P006 To test or not to test: The importance of HLA antibody testing and HLA-DP typing in unrelated donor hematopoietic stem cell transplantation (HSCT)

Attrition at the final donor stage among unrelated haematopoietic stem cell donors: the British Bone Marrow Registry experience.

To investigate attrition at the finally selected donor stage among British Bone Marrow Registry (BBMR) donors, all recruited from blood donors. The success of searches for unrelated stem cell donors relies on the existence of large international donor registries and the availability of registered donors when matched with a patient. Withdrawal of donors may adversely affect patient outcomes. Data on 2942 planned donations were analysed to assess donor-related deferral rates and associated factors. Overall, 20·2% of requests were cancelled. Transplant centres activated more than half of the cancellations (52·6%). Donor reasons accounted for 46·7% of cancellations (9·4% of requests), of which 61·7% happened for medical and 38·3% for personal reasons. Medical ineligibility of the donor was associated with increasing age (odds ratio [OR]=1·36, P=0·011) and peripheral blood stem cell source (OR=2·22, P=0·006), and there was some evidence of association with low blood donation reliability (OR=1·52, P=0·054). The blood donor reliability score relates to blood donation, and the score worsens if donors consistently fail to attend a donation session when invited. Withdrawal on personal grounds showed associations with donor age (OR=1·72, P=0·017, 30-40 years vs other ages), peripheral blood stem cell source (OR=2·43, P=0·010) and low blood donor reliability (OR=1·94, P=0·007). To our knowledge, this is the first report on all-cause cancellation at the finally-selected donor stage for international stem cell donor provision, showing 9·4% donor-related cancellation rate. Scores associated with blood donation reliability may be useful to predict stem cell donor withdrawal.

HLA-B*40:62, an HLA-B*40 variant, detected in a Taiwanese potential unrelated hematopoietic stem cell donor.

One nucleotide substitution in codon 140 of HLA-B*40:01:01 results in a novel allele, HLA-B*40:62.