Unrelated Donor Hematopoietic Stem Cell Research Articles

135 - Outcomes of Unrelated Donor Hematopoietic Stem Cell Transplantation for Pediatric Patients: The First Report From Iran

135 - Outcomes of Unrelated Donor Hematopoietic Stem Cell Transplantation for Pediatric Patients: The First Report From Iran

85 - Impact of ABO-Mismatching Following HLA- Mismatched Unrelated Donor Hematopoietic Stem Cell Transplantation for AML—a Report From the ALWP of the EBMT

85 - Impact of ABO-Mismatching Following HLA- Mismatched Unrelated Donor Hematopoietic Stem Cell Transplantation for AML—a Report From the ALWP of the EBMT

Does MHC Class I Chain-Related Gene A Matter?

In this issue of Biology of Blood and Marrow Transplantation, Askar et al. evaluate the association of MHC class I chain–related gene A (MICA) polymorphisms with the development of graft-versus host-disease (GVHD) after unrelated donor hematopoietic stem cell transplantation (HCT) [1]. Prior reports have provided conflicting results, leaving the effect of MICA donor-recipient mismatch in HCT unanswered.

Matched unrelated donor hematopoietic stem cell transplantation - our results

Introduction. Allogeneic stem-cell transplantation is only potentially curative therapy for variety of hematology malignancies, such as acute and chronic leukemia, myelodisplastic syndrome and aplastic anemia, but also promising treatment option for other disorders. If we know that only 25% of patients have an human leukocyte antigen identical sibling donor, it is obvious that matched unrelated donor hematopoietic stem cell transplantation is an alternative for the rest of the patients. Material and Methods. Since 2013, matched unrelated donor hematopoietic stem cell transplantation has been performed routinely in the Military Medical Academy. Results. We hereby present the outcome after 77 procedures in 75 patients. Considering primary diseases, 35 patients had acute myeloid leukemia, 25 patients had acute lymphoid leukemia, 5 patients had chronic myeloid leukemia, 9 patients had myelodisplastic syndrome and we performed the transplant on 1 patient with chronic lymphocyte leukemia, 1 patient with aplastic anemia and 1 patient with T lymphoblastic lymphoma. Conclusion. It is difficult to make clear conclusions based on this heterogeneous group of patients, but it seems that these results are encouraging. Future research will be performed to evaluate matched unrelated donor and identical sibling hematopoietic stem cell transplantation in the homogenous groups with respect to primary diseases.

Effectiveness of Search for an Unrelated Donor of Hematopoietic Stem Cells using Russian Date Base "Bone Marrow Donor Search": Experience of Raisa Gorbacheva Memorial Institute for Children Oncology, Hematology and Transplantation

Background & Aims. The key condition for allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the presence of HLA-compatible related or unrelated donor. If related donor is not found, further search is carried out in the Bone Marrow Donor Worldwide (BMDW) international data base, which is not effective enough (about 80-85 %), because of genotype specificity of Russian Federation residents. The recruitment procedure using BMDW takes a lot of time and is expensive. Therefore, there are good reasons to develop an alternative Russian data base, Bone Marrow Donor Search (BMDS), which includes data from Russian bone marrow donor registries and has a good potential. The aim is to evaluate the effectiveness of hematopoietic stem cell (HSC) donor search and transplant quality using the BMDS search system. Methods. 34 allo-HSCT recipients with malignancies and hematological diseases were enrolled in the study in RM Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation from November, 2012, to March, 2016. A HLA-compatible donor was found for each patient in the BMDS (www.bmds.info), which includes data from 13 Russian registries of HSC donors. Results. 34 allo-HSCTs were performed from unrelated donors recruited using Russian registries: 1 in 2012; 3 in 2013; 5 in 2014; 21 in 2015; and 4 in the 1<sup>st</sup> quarter of 2016. The greatest effectiveness of the BMDS search was in 2015 (14 %, n = 17). In 30 cases (88.2 %) a complete 10/10 compatibility for 5 HLA-gene loci was observed; in 4 cases (11.8 %) there was an incomplete compatibility (9/10). AB0 compatibility was only in 7 cases (20.6 %). In 15 cases (44.1 %) bone marrow was used for transplant harvesting; in 19 cases (55.9 %) peripheral blood stem cells were harvested by means of cytapheresis. The CD34+ count in the transplant was 1.2-12.0 х 10<sup>6</sup> CD34+ cell/kg (median: 5.0 * 10<sup>6</sup> CD34+ cell/kg). Engraftment was observed in 79.4 % of cases (п = 27), graft failure in 17.7 % of cases (n = 6), and early posttransplant mortality in 2.9 % of cases (n = 1). Conclusion. There was an increasing efficiency of search for a HLA-compatible unrelated HSC donor using a Russian BMDS search system for Russian residents with a graft quality similar to the one found in the international BMDW database.

Unrelated Hematopoietic Stem Cell Donor Recruitment of the Korean Red Cross: 20 Years Experience

Unrelated Hematopoietic Stem Cell Donor Recruitment of the Korean Red Cross: 20 Years Experience

Predictors of General Discomfort, Limitations in Activities of Daily Living, and Intention of a Second Donation in Unrelated Hematopoietic Stem Cell Donation

We performed a retrospective study to predict the risk factors related to general discomfort, limitations in activities of daily living (ADLs), and intention of a second donation in hematopoietic stem cell (HSC) donation. The subjects of this study were 1,868 consecutive unrelated volunteer donors who donated HSCs through the Korea Marrow Donor Program between November 2007 and April 2014. Bone marrow (BM) collections were performed without administration of granulocyte-colony stimulating factor (G-CSF) and peripheral blood stem cell (PBSC) collections were performed after mobilization with G-CSF administered subcutaneously for 4 or 5 consecutive days at a daily dose of around 10 mcg/kg of body weight. General discomfort and limitations in ADLs were assessed by numerical measurement (scores of 0 to 10), and donor’s intention of a second donation by yes or no reply. The post-donation questionnaires were completed within 48 hours after HSC collection, and at 1 week, 4 weeks, and 4 months thereafter. Pre-donation and post-donation predictors of general discomfort and limitations in ADLs were identified using univariate and multivariate linear regression considering donor demographic and clinical characteristics (age, sex, collection method, collection period) and the intention of a second donation on day 1. Pre-donation and post-donation predictors of the intention of a second donation were identified using univariate and multivariate logistic regression considering donor demographic and clinical characteristics (age, sex, collection method, collection period). Men represented 76.77% of donors. The median age at donation was 28 years (range, 19-51), and about 93.00% of donors were younger than 40 years of age. Among HSC collection, 61.88% were completed in a day. PBSC and BM collections accounted for 94.49% and 5.51% of HSC collections, respectively. Predictors of general discomfort included female sex (P< 0.0001), BM collection (P< 0.0001) or PBSC collection through a central line (P= 0.0349), 2-day collection (P= 0.0150), and negative or undetermined intention of a second donation on day 1 (P< 0.0001). Predictors of limitations in ADLs included age group of 30-39 years (P= 0.0046), female sex (P< 0.0001), BM collection (P< 0.0001) or PBSC collection through a central line (P< 0.0001), and negative or undetermined intention of a second donation on day 1 (P< 0.0001). The only predictor of positive intention of a second donation was male sex (P= 0.0007). Age, sex, collection method and period, and intention of a second donation should be considered risk factors when unrelated HSC donation is performed. As a collection method, PBSC collection through a peripheral line is recommended to alleviate physical stress and to improve ADLs. Female donors are more sensitive to HSC collection than male donors, and male sex of the donor is predictive of positive intention of a second donation. DisclosuresNo relevant conflicts of interest to declare.

Single HLA Mismatch Unrelated Donor Allogeneic Stem Cell Transplantation in Caucasian Recipients: Outcomes in HLA-A, -B, -C, -DRB1 and -DQB1 Mismatch Hematopoietic Stem Cell Transplantation: A Study on Behalf of the Francophone Society of Stem Cell Transplantation and Cellular Therapy (SFGM-TC) and the Francophone Society for Histocompatibility and Immunogenetics (SFHI)

▪INTRODUCTION: Matching all alleles of the HLA-A, -B, -C, and -DRB1 loci (8/8 match) is associated with the highest overall survival (OS) rates after unrelated donor (URD) hematopoietic stem cell transplantation (HSCT). In Europe, patients (pts) are also matched at the HLA-DQB1 loci (10/10 match), although there is no evidence of better OS. Data on Caucasian pts receiving a single HLA mismatch URD HSCT are still controversial. We therefore conducted a multicenter retrospective study to assess the impact of a single HLA mismatch (9/10 match) on outcomes after URD HSCT in a large cohort of French pts. METHODSWe collected data from 1092 pts who underwent HSCT between January 2000 and December 2012 at 32 French transplantation centers. Informed consent was obtained in accordance with the Declaration of Helsinki. High-resolution typing was performed for HLA-A, -B, -C, -DRB1, -DQB1 loci for all donor/recipient pairs. Clinical data were obtained through ProMISe (Project Manager Internet Server), an internet-based system shared by all French transplantation centers. Endpoints of interest were classical HSCT outcomes: engraftment, Graft versus host disease (GvHD), treatment related mortality (TRM) and relapse. GvHD free relapse free survival was also studied (defined as alive with no previous grade III-IV aGvHD, no moderate or severe chronic GvHD (cGvHD) and no relapse). Myeloablative conditioning was defined as a combination of agents expected to produce profound pancytopenia and myeloablation within 1-3 weeks after administration; pancytopenia is long lasting, usually irreversible and in most instances fatal, unless hematopoiesis is restored by hematopoietic stem cell infusion (Bacigalupo, et al.. Biology of Blood and Marrow Transplantation, 2009). Models were adjusted for disease risk, recipient age, CMV and sex matching, stem cell source, GVHD prophylaxis and conditioning regimen. For adjusted analysis DQB1 was used as the reference category. Disease risk was classified as standard or high risk using the American Society for Blood and Marrow Transplantation Request for Information 2006 risk scoring schema. RESULTSPopulation characteristics are shown in Table 1. Gender balance was the only difference between groups (p<0.013). Median follow-up was 84 months. Engraftment rates were not different between groups (overall, 91.8% (95% Confidence interval (CI) (90.1 to 93.4)). Overall Cumulative Incidence of aGVHD grade II-IV and grade III-IV were 39.9% (95% CI, (38.0 to 41.8)) and 22.2% (95% CI, (20.2 to 24.2)), respectively. Myeloablative Conditioning (MAC) using Total Body Irradiation (TBI)>4Gy [Hazard Ratio (HR) HR:1.95 (95% CI, 1.45 to 2.63)] and high disease risk [HR :1.34 (95% CI, 1.09 to 1.66)] were significantly associated with an increased cumulative incidence of grade II-IV aGVHD, whereas only MAC with TBI>4Gy was a risk factor for grade III-IV aGVHD [HR:1.91 (95% CI, 1.28 to 2.87)].Overall Cumulative Incidence of cGVHD was 38.1% (95% CI, 35.9 to 40.1) at 84 months. Overall relapse rate was 33.8% (95% CI, 30.5 to 37.1) with no differences according to HLA mismatch subtype. CI of TRM was 36.0% (95% IC, 32.9 to 39.1). Single HLA-A mismatch [HR:1.55 (95% CI , 1.11 to 2.17)], high disease risk [HR:1.40 (1.12 to 1.74)], a female donor for a male recipient [HR:1.41 (1.10 to 1.79)], and the use of a MAC regimen [HR:1.50 (1.08 to 2.08)] were significantly associated with a higher TRM after adjusted analysis. Overall GRFS was 14.5% (12.1 to 17.3). Single HLA-A mismatch [HR:1.25 (95% IC, 1.01 to 1.54)] and high disease risk [HR:1.45 (95% IC, 1.26 to 1.67)] were significantly associated with a lower GRFS (Figure1). CONCLUSIONIn this large cohort of Caucasian pts who received a single HLA mismatch URD HSCT, high disease risk was the major prognostic factor related to higher rates of both acute GvHD and treatment related mortality, and eventually a lower GRFS. HSCT outcomes were similar according to HLA single mismatches except for HLA-A mismatch, which was associated with a significant increase in TRM, and a worse GFRS. This study also highlights the high rates of both TRM and relapse after single mismatch URD HSCT (9/10) which justifies the use of reduced toxicity conditioning regimens, as well as the addition of targeted therapies pre- and post- HSCT in this setting. [Display omitted] [Display omitted] DisclosuresMichallet:Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Astellas Pharma: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Genzyme: Consultancy, Honoraria. Peffault De Latour:Amgen: Research Funding; Alexion: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding.

Association Between Multiple Mismatches at the HLA-DPB1 and DRB3/4/5 Genes and Adverse Outcomes in HLA-a, -B, -C, -DRB1 and -DQB1 Identical Hematopoietic Stem Cell Transplantation: A Study on Behalf of the Francophone Society of Stem Cell Transplantation and Cellular Therapy (SFGM-TC) and the Francophone Society for Histocompatibility and Immunogenetics (SFHI)

Background: Matching for all alleles of the HLA-A, -B, -C, and -DRB1 loci (8/8 match) is associated with the highest overall survival (OS) rates after unrelated donor (URD) hematopoietic stem cell transplantation (HSCT). In Europe, patients (pts) are also matched at the HLA-DQB1 loci (10/10 match) with no overall evidence of improved OS. HLA-DPB1 mismatching has been associated with a higher risk of acute graft-versus-host disease (aGvHD) and a decreased risk of relapse. A detrimental role of additional HLA-DQB1, HLA-DPB1 and HLA-DRB3/4/5 mismatches (MM) has been recently identified on OS but only in 7/8 HLA-A, -B, -C, and -DRB1 loci URDs HSCT. We investigated the impact of HLA-DPB1 and HLA-DRB3/4/5 MM on outcomes in a large cohort of 10/10 matched URD HSCTs.Patients and methods: 2,393 pts who received an initial HSCT from a 10/10 matched URD in 35 French centers were included between January 2000 and October 2012. Informed consent was obtained in accordance with the Declaration of Helsinki. High-resolution typing was performed for HLA-A, -B, -C, -DRB1, -DQB1, -DPB1 and -DRB3/4/5 loci for all donor/recipient pairs. Clinical data were obtained through ProMISe (Project Manager Internet Server), an internet-based system shared by all French transplantation centers. Impact of HLA-DRB3/4/5 and -DPB1 MM was quantitatively and qualitatively evaluated. For quantitative evaluation, patients were classified into 5 different groups according to their global matching level for the 7 considered loci (14/14, 13/14, 12/14, 11/14, 10/14). For qualitative evaluation, MM type and directionality (GvH and host versus graft (HvG) directions) were evaluated. HLA-DPB1 MM were classified as permissive or non-permissive (K Fleischhauer, Lancet Oncol. 2012). The primary composite endpoint for the analysis was GvHD-free and relapse-free survival (GRFS). We defined early GRFS as being alive at 3 months after HSCT with no previous grade III-IV aGvHD and no relapse and late GRFS as being alive >3 months with no previous grade III-IV aGvH, no relapse and no moderate or severe chronic GvHD (cGvHD). Late GRFS was evaluated at months 6, 12, 24 and 36 after HSCT. Acute GvHD, cGvHD, relapse and OS were also studied. Models were adjusted for HSCT period, disease risk, age, sex matching, stem cell source, and conditioning regimen.Results: Table 1showspopulation characteristics and distribution of cumulative MM. The median follow-up was 59 months. Compared to 14/14 pairs, quantitative evaluation showed a significantly lower early GRFS for pts who received a 10-11/14 (Hazard Ratio HR 2.0, 95% CI 1.4 to 2.9, p=0.0003) or a 12/14 URD HSCT (HR 1.4, 95% CI 1.1 to 1.8, p=0.01). This was related to a significantly increased risk of grade III-IV aGVHD associated with 10-11/14 (HR 2.3, 95% CI 1.5 to 3.7, p=0.0004) and 12/14 pairs (HR 1.7, 95% CI 1.2 to 2.4, p=0.003). 10-11/14 pairs were also associated with a higher risk of death at 3 months (HR 2, 95% CI 1.1 to 3.6, p=0.024). Qualitatively, in pts matched for HLA-DRB3/4/5 but MM for HLA-DPB1 (n=1846, 77.1%), 2 HLA-DPB1 MM and non-permissive HLA-DPB1 MM were associated with a lower early GRFS (HR 1.4, 95% CI 1.1 to 1.9, p=0.01 and HR 1.3, 95% CI 1.0 to 1.7, p=0.02 respectively) due to an increased risk of aGvHD (HR 1.7, 95% CI 1.2 to 2.5, p=0.002 and HR 1.50, 95% CI 1.08 to 2.08, p= 0.017 respectively). Outcomes were not influenced by either GvHD or HvG mismatch directions. Late GRFS analyses once adjusted were not significantly different according to MM numbers, type and directions. Only 19 pairs (0.8%) were DPB1 matched and DRB3/4/5 mismatched (high linkage disequilibrium between DRB3/4/5 and DRB1); HLA-DRB3/4/5 MM could thus not be qualitatively analyzed.Conclusion: MultipleHLA-DPB1 and HLA-DRB3/4/5 MM have an early impact after 10/10 matched URDs HSCT. The best outcomes are seen in 13 and 14/14 pairs. Early GRFS is significantly impacted by 10-11/14, 12/14, 2 DPB1 MM as well as non-permissive HLA-DPB1 MM URD HSCT which is related to an increased risk of grade III-IV aGvHD. There is a significantly increased risk of mortality for 10-11/14 pairs at 3 months. Prospective evaluation of matching for HLA-DPB1 and HLA-DRB3/4/5 is warranted to reduce early post-HSCT toxicity in donor-recipient 10/10 matched pairs. [Display omitted] DisclosuresMichallet:Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Astellas Pharma: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Genzyme: Consultancy, Honoraria. Peffault De Latour:Pfizer: Consultancy, Honoraria, Research Funding; Alexion: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Amgen: Research Funding.

A novel allele, HLA-DRB1*12:60N, detected in a Taiwanese unrelated hematopoietic stem cell donor.

One nucleotide deletion at residue 157 of HLA-DRB1*12:02:01 results in a new allele, HLA-DRB1*12:60N.

Predictors of general discomfort, limitations in activities of daily living and intention of a second donation in unrelated hematopoietic stem cell donation.

We performed a retrospective study of 1868 consecutive unrelated donors to predict the risk factors related to general discomfort, limitations in activities of daily living (ADLs) and intention of a second donation in hematopoietic stem cell (HSC) donation. General discomfort and limitations in ADLs were assessed by numerical measurement (scores of 0-10) and donor's intention of a second donation by yes or no reply. The post-donation questionnaires were completed within 48 h after HSC collection and at 1 week, 4 weeks, and 4 months thereafter. Predictors of general discomfort included female sex (P<0.0001), bone marrow (BM) collection (P<0.0001) or PBSC collection through a central line (CL; P=0.0349), 2-day collection (P=0.0150) and negative or undetermined intention of a second donation on day 1 (P<0.0001). Predictors of limitations in ADLs included age group of 30-39 years (P=0.0046), female sex (P<0.0001), BM collection (P<0.0001) or PBSC collection through a CL (P<0.0001) and negative or undetermined intention of a second donation on day 1 (P<0.0001). The only predictor of positive intention of a second donation was male sex (P=0.0007). Age, sex and collection method and period should be considered risk factors when unrelated HSC donation is performed.

Identification of DPB1 Permissive Unrelated Donors Is Highly Likely

HLA-DPB1 permissive matching based on T cell epitope (TCE) groups should be considered when selecting among equally matched HLA-A, -B, -C, -DRB1 unrelated hematopoietic stem cell donors to improve patient survival. Previous studies have defined 3 TCE groups based on functional assays of alloreactivity. Combinations of donor and recipient DPB1 alleles with low immunogenic potential identify permissive donors, who provide no increased risk of mortality compared with DPB1–matched donors. To determine the likelihood of identifying a DPB1 permissive–matched (includes both allele-matched and DPB1-permissive mismatched) unrelated donor for patients with high-resolution matches at 10/10 HLA-A, -B,- C, -DRB1, and -DQB1 in the Be The Match Registry, preliminary search requests from United States' transplant centers for 595 DPB1-typed patients were evaluated for existence of a DPB1 permissive–matched donor, identified either among already typed donors or by prospective DPB1 typing. The baseline DPB1 permissive match rate was 69% and improved to 80% after additional donor DPB1 typing (median, 4 donors per patient). When seeking a 10/10-matched, young (18- to 32-year-old) donor in the registry, the probability of finding a DPB1 permissive–matched donor started lower at 59% and improved to 70% after additional DPB1 testing. Our results show that most patients with a 10/10 match can find a DPB1 permissive–matched donor.

INFECTIOUS COMPLICATIONS AFTER UMBILICAL CORD-BLOOD TRANSPLANTATION FROM UNRELATED DONORS

Umbilical cord-blood (UCB) is a well-recognized alternative source of stem cells for unrelated donor hematopoietic stem cell transplantation (HSCT). As compared with other stem cell sources from adult donors, it has the advantages of immediate availability of cells, absence of risk to the donor and reduced risk of graft-versus-host disease despite donor-recipient HLA disparity. However, the use of UCB is limited by the delayed post-transplant hematologic recovery due, at least in part, to the reduced number of hematopoietic cells in the graft and the delayed or incomplete immune reconstitution. As a result, severe infectious complications continue to be a leading cause of morbidity and mortality following UCB transplantation (UCBT). We will address the complex differences in the immune properties of UCB and review the incidence, characteristics, risk factors, and severity of bacterial, fungal and viral infectious complications in patients undergoing UCBT.

Safety of Living Donation of Hematopoietic Stem Cells.

More than 12 000 volunteer unrelated hematopoietic stem cell donations are undertaken annually, and the World Marrow Donor Association established an expert committee to examine all reports of adverse events affecting donors globally, eventually making such reporting a necessary part of World Marrow Donor Association accreditation. The committee evaluates and responds to reported events in a nonpunitive confidential process designed to alert the community of rare events which might be missed by local follow-up. Each report is evaluated by the committee for imputability (causal link between the donation and the adverse event) and compared with that submitted by the reporting registry. In 2014, there were 50 reports received from 16 different registries in 15 countries. There were 16 reports of malignancies arising in donors including 3 hematologic malignancies. All but 2 of the 16 occurred more than a year after donation. There were 4 reports of autoimmune phenomena in donors all occurring more than a year postdonation. Of the 30 remaining events, 6 were allergic, 4 cardiac, 3 gastrointestinal, 2 infections, 2 pulmonary, and 13 miscellaneous. Causation was assessed differently to the reporting registry in 17 events with 6 thought to be less likely causally linked to the donation and 10 more likely with 1 requiring more information. Volunteer unrelated hematopoietic stem cell donation is a safe and effective altruistic contribution to the treatment of patients with life-threatening hematologic disorders. A decade of detailed examination of adverse donor events has contributed to the safety of these donations.

Efficacy and security of matched unrelated donor hematopoietic stem cell transplant with transfusion of multipotent mesenchymal cells in pediatric severe aplastic anemia

目的探讨HLA相合无关供者造血干细胞移植（MUD-HSCT）联合脐带间充质干细胞（MSC）输注治疗儿童重型再生障碍性贫血（SAA）的疗效及安全性。方法回顾性分析19例行MUDHSCT联合MSC治疗的儿童SAA患者临床资料，观察移植后造血重建及移植相关并发症。结果19例患儿移植后均获得迅速造血重建，粒细胞中位植入时间为12(9~21) d，血小板中位植入时间为14(8~24) d, 1例患儿于移植后4个月出现继发植入失败。9例患儿发生Ⅰ度急性移植物抗宿主病（aGVHD），1例发生Ⅲ度aGVHD并于移植后6个月发生广泛型慢性移植物抗宿主病。CMV阳性15例，出血性膀胱炎2例。10例患儿移植后出现不同程度、不同部位的感染。中位随访时间为27(8~70）个月，19例患儿截至随访终点均无病存活，其中1例患儿于移植后4个月发生淋巴细胞增殖性疾病，接受利妥昔单抗联合化疗治疗后发生继发性植入失败，后接受以父亲为供者的单倍体造血干细胞移植成功植入。结论MUD-HSCT联合MSC输注治疗儿童SAA是安全有效的。

Impact of HLA-Mismatch in Unrelated Donor Hematopoietic Stem Cell Transplantation: A Meta-Analysis.

The magnitude of risk associated with 9/10 mismatched unrelated donor (MMURD) hematopoietic stem cell transplantation and that of mismatches at the individual HLA loci remain unclear. We performed a meta-analysis to assess the difference in clinical outcomes between matched unrelated donor (MUD) and MMURD transplantation. A comprehensive search of Medline and Embase for manuscripts regarding transplantation outcomes in primarily adult patients with hematologic malignancies was performed. The pooled effect estimates were calculated using DerSimonian-Laird random effects models. A total of 13 studies were included, reporting on 13,446 transplants. 9/10 MMURD transplantation was associated with worse overall survival compared to 10/10 MUD transplantation (pooled HR: 1.27, 95% CI: 1.12-1.45; n = 7 studies). Mismatch at HLA-A, -B, or -C was associated with significantly worse overall survival compared to MUD transplantation, while there was no significant difference associated with -DQ or -DPB1 mismatch. Inferior survival associated with HLA-DRB1 mismatch could not be ruled out. Data on acute and chronic graft-versus-host disease were scarce but favored MUD transplantation. In summary, this meta-analysis of the available literature favored MUD over MMURD transplantation in hematologic malignancies and further quantifies the risks associated with specific HLA-allele mismatches. Am. J. Hematol. 91:551-555, 2016. © 2016 Wiley Periodicals, Inc.

A protocol for matched unrelated donor hematopoietic stem cell transplantations for severe combined immunodeficiency

Hematopoietic stem cell transplantation using HLA-mismatched related donors for the treatment of severe combined immunodeficiency has led to disappointing outcomes at our institution. This created an impetus to consider other donor sources when an HLA-matched related donor was not available. In 1988, a new protocol using HLA-matched unrelated donors was developed at our institution and continues to be used to date. This has contributed to improved outcomes and change in practice for patients with severe combined immunodeficiency. Statement of novelty: This report describes in detail the protocol for hematopoietic stem cell transplantations using HLA-matched unrelated donors for patients with severe combined immunodeficiency at our institution. This protocol is published for those centres wishing for guidance in setting up procedures for hematopoietic stem cell transplantation.

High Risk HLA Allele for Severe Acute Graft-Versus-Host-Disease and Mortality in Unrelated Donor Hematopoietic Stem Cell Transplantation

High Risk HLA Allele for Severe Acute Graft-Versus-Host-Disease and Mortality in Unrelated Donor Hematopoietic Stem Cell Transplantation

Risk factors and outcome of graft failure after HLA matched and mismatched unrelated donor hematopoietic stem cell transplantation: a study on behalf of SFGM-TC and SFHI

Graft failure remains a severe complication of hematopoietic stem cell transplantation (HSCT). Several risk factors have already been published. In this study, we re-evaluated them in a large cohort who had the benefit of the recent experience in HSCT (2006-2012). Data from 4684 unrelated donor HSCT from 2006 to 2012 were retrospectively collected from centers belonging to the French Society for Stem Cell Transplantation. Among the 2716 patients for whom HLA typing was available, 103 did not engraft leading to a low rate of no engraftment at 3.8%. In univariate analysis, only type of disease and status of disease at transplant for malignant diseases remained significant risk factors (P=0.04 and P<0.0001, respectively). In multivariate analysis, only status of disease was a significant risk factor (P<0.0001). Among the 61 patients who did not engraft and who were mismatched for 1 HLA class I and/or HLA-DP, 5 donor-specific antibodies (DSAs) were detected but only 1 was clearly involved in graft failure, for the others their role was more questionable. Second HSCT exhibited a protective although not statistically significant effect on OS (hazard ratio=0.57 [0.32-1.02]). In conclusion, only one parameter (disease status before graft) remains risk factor for graft failure in this recent cohort.

Evolving hematopoietic stem cell transplantation strategies in severe aplastic anemia.

Significant improvements in unrelated donor hematopoietic stem cell transplantation (HSCT) in recent years have solidified its therapeutic role in severe aplastic anemia (SAA) and led to the evolution of treatment algorithms, particularly for children. Advances in understanding the genetics of inherited bone marrow failure syndromes (IBMFS) have allowed more confidence in accurately diagnosing SAA and avoiding treatments that could be dangerous and ineffective in individuals with IBMFS, which can be diagnosed in 10-20% of children presenting with a picture of SAA. Additionally long-term survival after matched sibling donor and matched unrelated donor HSCT now exceed 90% in children. Late effects after HSCT for SAA are minimal with current strategies, and compare favorably to late effects after upfront immunosuppressive therapy, except for patients with chronic graft versus host disease. Careful assessment for signs or symptoms of IBMFS, along with genetic screening for these disorders, is of major importance. Matched sibling donor HSCT is already considered the standard of care for upfront therapy and some groups are evaluating matched unrelated donor HSCT as primary therapy. Ongoing studies will continue to challenge treatment algorithms and may lead to an even more expanded role for HSCT in SAA.