Cord Blood Hematopoietic Stem Cell Transplantation Research Articles

High infection rates and risk‐adapted prevention strategies in contemporary pediatric allogeneic hematopoietic stem cell transplantation

AbstractWith recent changes in hematopoietic stem cell transplantation (HSCT) practices, such as the increasing use of alternative donors and ex vivo T‐cell depletion, how various risk factors interplay and affect the timeline of infections have not been well elucidated. We retrospectively reviewed the first 100 consecutive HSCT from April 2019 to October 2021 in the only pediatric HSCT center in Hong Kong. We found that the vast majority of the allogeneic transplant recipients (69/74, 93.2%) had infections after HSCT, amongst which bacterial, viral, and fungal infection rates were 35.1%, 90.5%, and 9.5%, respectively. In contrast, only 30.8% (8/26) of autologous transplant recipients had infections (rate of bacterial, viral, and fungal infection were 19.2%, 15.4%, and 3.8%, respectively). Human herpesvirus 6 (HHV‐6) and BK virus (BKV) typically occurred early after HSCT, adenovirus (ADV) and varicella zoster virus (VZV) thereafter, and cytomegalovirus (CMV) and Epstein–Barr virus (EBV) throughout the entire 2.5‐year observation period. Ex vivo T‐cell depletion was a general risk factor for viral infection with HHV‐6 (hazard ratio [HR] = 3.03), BKV (HR = 3.36), CMV (HR = 4.45), and EBV (HR = 7.15); all p < 0.02. Cancer in second‐complete remission compared with first‐complete remission was a risk factor for bacterial infection (OR = 6.0, 95% CI = 1.12–32.2, and p = 0.037). Patients with gut graft‐versus‐host disease were at risk for fungal infections (OR = 12.3, 95% CI = 1.33–114.4, and p = 0.027). The infection‐related mortality rate was 10.0%, which occurred only in allogeneic HSCT patients with hematological malignancies receiving cord blood (n = 4) or haploidentical HSCT (n = 6). Collectively, our findings in pediatric patients after contemporary HSCT support both time‐dependent and risk‐adapted measures against infective complications to improve transplant outcome.

Therapeutic efficacy of hematopoietic stem cell transplantation for Wiskott-Aldrich syndrome in 60 children

Objective: To evaluate the therapeutic efficacy of hematopoietic stem cell transplantation (HSCT) for Wiskott-Aldrich syndrome (WAS), and to analyze the factors related to the outcomes. Methods: The clinical data of 60 children with WAS received HSCT in Shanghai Children's Medical Center from January 2006 to December 2020 were retrospectively analyzed. All cases were treated with a myeloablative conditioning regimen with busulfan and cyclophosphamide, and a graft-versus-host disease (GVHD) prevention regimen based on cyclosporine and methotrexate. Implantation, GVHD, transplant-related complications, immune reconstitution and survival rate were observed. Survival analysis was performed by Kaplan-Meier method, and Log-Rank method was used for univariate comparison. Results: The 60 male patients had main clinical features as infection and bleeding. The age at diagnosis was 0.4 (0.3, 0.8) years, and the age at transplantation was 1.1 (0.6, 2.1) years. There were 20 cases of human leukocyte antigen matched transplantation and 40 mismatched transplantation; 35 patients received peripheral blood HSCT, and 25 cord blood HSCT. All cases were fully implanted. The incidence of acute GVHD (aGVHD) was 48% (29/60) and only 2 (7%) developed aGVHD of grade Ⅲ; the incidence of chronic GVHD (cGVHD) was 23% (13/56), and all cases were limited. The incidence of CMV and EBV infection was 35% (21/60) and 33% (20/60) respectively; and 7 patients developed CMV retinitis. The incidence of sinus obstruction syndrome was 8% (5/60), of whom 2 patients died. There were 7 cases (12%) of autoimmune hemocytopenia after transplantation. Natural killer cells were the earliest to recover after transplantation, and B cells and CD4+T cells returned to normal at about 180 days post HSCT. The 5-year overall survival rate (OS) of this group was 93% (95%CI 86%-99%), and the event free survial rate (EFS) was 87% (95%CI 78%-95%). EFS of non-CMV reactivation group is higher than that of CMV reactivation group (95% (37/39) vs.71% (15/21), χ2=5.22, P=0.022). Conclusions: The therapeutic efficacy of HSCT for WAS is satisfying, and the early application of HSCT in typical cases can achieve better outcome. CMV infection is the main factor affecting disease-free survival rate, which can be improved by strengthening the management of complications.

Epidemiology, Risk Factors and Outcome of Bacterial, Fungal, and Viral Infections in Pediatric Allogeneic and Autologous Hematopoietic Stem Cell Transplantation Recipients

Objectives Infection remains a major cause of morbidity and mortality after hematopoietic stem cell transplant (HSCT). With recent changes in transplant practices, such as the increasing use of alternative donors and T-cell depletion, how various risk factors interplay and affect the timeline of infections have not been well elucidated in children. While the epidemiology and risk factors for viral infections post-HSCT were well described for cytomegalovirus (CMV) and Epstein-Barr virus (EBV), the corresponding information on human herpes virus 6 (HHV-6), adenovirus (ADV) and BK virus (BKV) infection in children is limited. This study aims to review comprehensively the epidemiology, risk factors and outcome of bacterial, viral and fungal infections after contemporary HSCT to inform future infection prophylaxis strategies. Method We retrospectively reviewed the first 100 consecutive HSCT for malignant and non-malignant diseases from April 2019 to October 2021 in the only pediatric HSCT center in Hong Kong. The incidences were recorded and risk factors were analyzed for bacterial, viral and fungal infections and infection-related mortality. Results The vast majority of the allogeneic transplant recipients (69/74, 93.2%) had infections after HSCT, amongst which bacterial, viral and fungal infection rate was 35.1%, 90.5% and 9.5% respectively. In contrast, only 30.8% (8/26) of autologous transplant recipients had infections, and their respective rate of bacterial, viral and fungal infection was 19.2%, 15.4% and 3.8%. HHV-6 and BKV typically occurred early after HSCT, ADV and varicella zoster virus (VZV) thereafter, and CMV and EBV throughout the entire 2.5-year observation period. The cumulative incidences of HHV-6 and BKV were significantly higher in patients receiving umbilical cord blood (UCB) or haploidentical stem cell transplant (p = 0.0001; p <0.0001, respectively) when compared with matched sibling (MSD) or matched unrelated donor (MUD) transplant (Figure 1 and 2). Ex vivo T-cell depletion was a general risk factor for viral infection with HHV-6 (HR = 3.03), BKV (HR = 3.36), CMV (HR = 4.45) and EBV (HR = 7.15); all p < 0.02. Cancer in second- compared with first-complete remission was a risk factor for bacterial infection in multivariate analyses (OR = 6.0, 95% CI = 1.12-32.2, p = 0.037). Patients with gut graft-versus-host disease were at risk for fungal infections (OR = 12.3, 95% CI = 1.33-114.4, p = 0.027). The infection-related mortality (IRM) rate was 10%, which occurred only in allogeneic HSCT patients with hematological malignancies receiving cord blood (n = 4) or haploidentical HSCT (n = 6). History of bacterial infection after HSCT was associated with an increased risk of IRM (HR = 4.13, 95% CI = 1.05-16.3, p = 0.042). Conclusion Not all HSCT recipients are of equal risk to infections and IRM. Our findings in pediatric patients after contemporary HSCT support both time-dependent and risk-adapted measures against infective complications to improve transplant outcome. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A Prospective Trial Comparing Haploidentical Donor Transplantation With Cord Blood Versus HLA-Matched Sibling Donor Transplantation for Hematologic Malignancy Patients

Although haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT) has achieved similar survival to HLA-identical sibling donor (ISD) transplantation, the delayed hematopoietic engraftment as well as higher incidence of graft-versus-host-disease (GVHD), results in prolonged hospitalization, higher costs, and increased morbidity. In this study, a prospective, non-randomized clinical study was designed to evaluate the outcomes of patients who underwent HID HSCT supported by cord blood or ISD HSCT. Between May 2017 and November 2020, 113 patients were enrolled to undergo HID HSCT supported by cord blood (n=88) or ISD HSCT (n=25). The cumulative incidence of neutrophil and platelet engraftment at 30days was comparable in these two groups. Importantly, there was no significant difference in the cumulative incidence of grade II-IV aGVHD at 100days (20.5% [95% confidence interval [CI]: 12.2%–28.8%] versus 12.0% [95% CI: 0.2%–23.8%], P = 0.32) and cGVHD at 1 year (19.5% [95% CI: 11.2%–27.8%] versus 16.6% [[95% CI: 1.3%–31.9%] P = 0.70) between the two groups. Among the HID and ISD groups, the 2-year disease free survival was 76.8 and 80.0% (P = 0.83), the 2-year overall survival was 82.4 and 88.0% (P = 0.66), the 2-year GVHD-free, relapse-free survival was 68.9 and 75.3% (P = 0.62), respectively. Our results indicate that HID transplantation supported by cord blood may offer a good alternative to ISD HSCT for patients with hematopoietic malignancies. Trial registration: Effect of co-infusion third party umbilical cord blood stem cells on haploidentical hematopoietic stem cell transplantation https://www.chictr.org.cn Reg. No. ChiCTR-OIN-17011426.

Validating a Machine Learning Grading System for Acute Gvhd. a Study on Behalf of the EBMT Transplant Complications Working Party

Validating a Machine Learning Grading System for Acute Gvhd. a Study on Behalf of the EBMT Transplant Complications Working Party

Outcomes with Mismatched Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis

BackgroundAllogeneic hematopoietic stem cell transplantation (HCT) is the optimal and potentially curative therapy in various high-risk hematologic malignancies. Although a human leukocyte antigen (HLA)-matched sibling or unrelated donor is a clinically preferred stem cell source, the use of haploidentical family donors and umbilical cord blood HCT now offers the option of HCT in patients lacking a matched donor. However, many patients lack an appropriate donor, in particular the ethnic minorities. Mismatched unrelated donors (MMUD) have historically been utilized as alternative donor source for these patients due to ease of donor availability but is associated with increased risk of graft versus host disease (GVHD) and non-relapse mortality (NRM). In this systematic review and meta-analysis, we aimed to assess the outcomes with MMUD HCT.Methods:Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a comprehensive literature search was performed on three databases (PubMed, Cochrane Library, and ClinicalTrials.gov) from date of inception through February 2021 using the MeSH and entry terms for “hematopoietic stem cell transplantation”, OR “hematologic neoplasms”, AND unrelated donors“ AND ”treatment outcome“. A total of 2477 records were identified and primary and secondary screening was done. After excluding review, duplicate, and non-relevant articles, we included 13 studies (11 retrospective, 2 prospective) reporting outcomes following MMUD HCT. The Joanna Briggs Institute (JBI) critical appraisal checklist for studies reporting prevalence data and randomized control trial was used for quality assessment, and all studies were reported as good. Proportions along with a 95% confidence interval (CI) were extracted to compute pooled analysis using the ‘meta’ package by Schwarzer et al. in the R programming language (version 4.16-2). The variance between the studies was calculated using Der Simonian-Laird Estimator.Results:We identified 2588 patients from 13 included studies who had MMUD HCT. (Table 1) Median age was 51.7 (18-76) years and 52% (n=1347) were males. Source of primary graft was bone marrow (BM) in 19% (n=478/2508) and peripheral blood (PB) in 81% (n=2030/2508) HCT recipients. Median time to transplant was 10.45 (1.5-139.6) months and median follow up was 41.5 (0.4-136.5) months. Reduced intensity conditioning (RIC) conditioning was used for 73% (n=1884) of the patients while 27.2% (n= 704) patients received myeloablative conditioning (MAC). We estimated a pooled overall survival (OS) of 59% (95% CI 0.52-0.66, I 2 = 92%, n=2563) at one year and 44% (0.36-0.53, I 2=92%, n=1972) at three years. The pooled incidence of acute GVHD (grade II-IV), acute GVHD (grade III-IV), and chronic GVHD were 39% (95% CI 0.33-0.44, I 2=84%, n=2282), 19% (95% CI 0.15-0.23, I 2=65%, n=1417), and 38% (95% CI 0.32-0.47, I 2=93%, n=2477) respectively. Progression free survival (PFS) was 39.5% (95% CI 0.31-0.48, I 2=94% n=2505). The pooled incidence of relapse rate (RR) and NRM were 31% (95% CI 0.25-0.38, I 2=90%, n=2482) and 27% (95% CI 0.21-0.34, I 2 =90% n=2448) respectively.Conclusion:Mismatched unrelated donor HCT has shown favorable outcomes with acceptable toxicity profile. MMUD HCT represents a promising option for patients lacking an HLA-matched donor and has expanded access to HCT in patients with ethnic minorities who often lack a matched donor. [Display omitted] DisclosuresAbhyankar: Incyte/Therakos: Consultancy, Research Funding, Speakers Bureau. McGuirk: Juno Therapeutics: Consultancy, Honoraria, Research Funding; Fresenius Biotech: Research Funding; Novartis: Research Funding; Gamida Cell: Research Funding; Magenta Therapeutics: Consultancy, Honoraria, Research Funding; Pluristem Therapeutics: Research Funding; Allovir: Consultancy, Honoraria, Research Funding; EcoR1 Capital: Consultancy; Kite/ Gilead: Consultancy, Honoraria, Other: travel accommodations, expense, Kite a Gilead company, Research Funding, Speakers Bureau; Astelllas Pharma: Research Funding; Bellicum Pharmaceuticals: Research Funding; Novartis: Research Funding.

Similar Probabilities of Failure to Reach Transplantation and Transplant Outcomes after HLA-Identical Sibling or Unrelated Donor Transplant in Patients with Acute Myeloid Leukemia: A Single Institution Evaluation of a Donor Selection Algorithm

IntroductionThe increasing use of alternative donors has expanded allogeneic hematopoietic stem cell transplantation (HSCT) eligibility in patients with acute myeloid leukemia (AML) without HLA-identical siblings (matched-SIB). However, optimal donor selection remains controversial and current practice is largely based on transplantation centres' experience. Unrelated donor (URD) HSCT is associated with longer waiting times to transplantation than umbilical cord blood or haploidentical HSCT, but the impact of HSCT delays on transplantation rates and survival outcomes is unclear in this setting. In this study we evaluated the performance of a donor selection algorithm consisting in the allocation of patients with AML without matched-SIB to fully matched (8/8) or mismatched (7/8) URD.MethodsRetrospective analysis including adult patients with AML who received approval for first-time allogeneic HSCT with myeloablative conditioning at our institution between January 2011 and February 2017. Matched-SIB was the preferred donor choice for all patients. Fully matched (8/8) or mismatched (7/8) URD were selected through high-resolution HLA-A, HLA-B, HLA-C and DRB1 typing for those patients without an available matched-SIB. Non-parametric cumulative incidence and Kaplan-Meier estimates were obtained to assess transplantation and overall survival (OS) rates, respectively. Fine-Gray competing risks regression was used to identify predictors of failure to reach transplantation. Age, intention-to-treat (ITT) and disease status at the time of transplantation approval were included in the multivariate analysis.ResultsTable 1 summarizes the characteristics of the 113 eligible patients during the study period. Fifty-seven patients (50.4%) were allocated to a matched-SIB donor, whereas URD search was started in the remaining 56 patients (49.6%) without an available matched-SIB. Thirty patients (26.5%) failed to reach transplant after the approval to undergo transplantation. Figure 1 shows the cumulative incidence functions of transplantation from time of approval (Gray's p = 0.06). The estimated probabilities to reach transplantation were 74% and 71% for patients with or without a matched-SIB donor. Median time to HSCT from transplantation approval was shorter in patients with a matched-SIB donor (100 versus 136 days). Disease status at the time of transplantation approval was the only predictor of failure to reach transplantation in the multivariate analysis (sHR for any disease status versus CR1 = 1.69, p = 0.04). The 3-year OS from time of transplantation approval in the ITT population was 35% (28% versus 41% for patients with or without a matched-SIB donor, respectively; log rank p = 0.39), while the 3-year OS from time of transplantation was 46% (46% versus 54% for patients who underwent a matched-SIB HSCT or an URD HSCT, respectively; log rank p = 0.46).Conclusions8/8 or 7/8 URD selection in patients with AML without an available matched-SIB led to increased times to transplantation but did not have an impact on the probability of failure to reach transplantation and did not result in inferior survival outcomes in comparison with patients with a matched-SIB. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Anti-Thymocyte Globulin (ATG) for Prophylaxis of Severe Graft Vs. Host Disease after Hematopoietic Stem Cell Transplant: A Systematic Review and Meta-Analysis

Introduction: Hematopoietic stem cell transplantation (HSCT) is used for the treatment of multiple hematologic diseases. The donor cells kill the host malignant cells, but unfortunately, the immune response can cause graft vs. host disease (GvHD). Anti-thymocyte globulin (ATG) is an antibody derived from rabbits or horses. It targets antigens expressed on T-cells, B-cells, macrophages, natural killer cells, and dendritic cells, and used for the prevention of GvHD. We conducted a meta-analysis to assess the efficacy of ATG in preventing high-grade GvHD after hematopoietic stem cell transplant. Methods: A search was performed on PubMed, Cochrane, Embase, and Web of Science. We used the following mesh terms and Emtree terms, "antilymphocyte globulin" OR "antithymocyte globulin" AND "graft vs. host disease" from the inception of literature till 06/01/2020. We screened 5767 articles and included 10 randomized clinical trials (N=1,227) and 31 observational studies (N=14,895) in this meta-analysis. We extracted data for severe acute GvHD (grade III-IV or grade II-IV) and severe chronic GvHD (an extensive disease by Seattle criteria or moderate to severe disease according to NIH criteria). We excluded case reports, case series, preclinical trials, single-arm studies, review articles, meta-analysis, and controlled studies not providing any information about high-grade GvHD. We used the R programming language (version 4.0.2) to conduct a meta-analysis. Results: In 41 included studies (N=16,122), the median age was ≥40 years in 22 studies (N=12,099), ≤40 years in 16 studies (N=3536), and ≤18 years in 3 studies (N=487). 2986 patients had at least one HLA allele mismatch. Out of 41 studies, data for high-grade acute GvHD was available in 40 studies (N=16,047), and data for high-grade chronic GvHD was available in 33 studies (N=14,206), see Figure 1, 2. For high-grade acute GvHD, risk ratio (RR) was 0.68 (I2=24%, 95% CI=0.61-0.75) in favor of the use of ATG vs. no use of ATG in the prophylaxis of GvHD with HSCT. In 9 RCTs (N=1,152), RR was 0.59 (I2=38%, CI=0.42-0.82) in favor of ATG use. High-grade acute GvHD significantly improved in all subgroups, i-e., peripheral blood (PB) /bone marrow (BM) HSCT from related donors (RR=0.73; 95% CI=0.61-0.88), PB/BM transplant from unrelated donors (RR=0.62; CI=0.52-0.72) and umbilical cord blood (UC) HSCT (RR=0.61; CI=0.43-0.88). For high-grade chronic GvHD, RR was 0.47 (I2=49%, 95% CI=0.40-0.55) in favor of the use of ATG vs. no use of ATG in the prophylaxis of GvHD with HSCT. In 6 RCTs (N=714), RR was 0.40 (I2=58%, 95% CI=0.27-0.61) in favor of ATG use. High-grade chronic GvHD significantly improved with the use of ATG in both related donors (RR=0.44; 95% CI=0.34-0.58) and unrelated donors (RR=0.46; 95% CI=0.38-0.55) subgroups for BM / PB HSCT. However, there was no significant improvement in the risk of high-grade chronic GvHD with the use of ATG with cord blood HSCT (RR=0.98; 95% CI=0.73-1.31). Conclusion: ATG is effective in the prophylaxis of severe acute GvHD irrespective of donor relationship or type of HSCT. ATG is also effective in the prophylaxis of severe chronic GvHD with bone marrow or peripheral blood HSCT except for cord blood HSCT. Additional multicenter randomized double-blinded clinical trials are needed to confirm these results. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Reactivation of human herpesvirus 6 in pediatric allogeneic hematopoietic stem cell transplant recipients.

Reactivation of human herpesvirus 6 (HHV-6) occurs in 30%-50% of patients (pts) who receive allogeneic (allo) hematopoietic stem cell transplant (HCT). However, the recommendation for post-transplant HHV-6 monitoring and treatment in pediatric pts is not well established. HHV-6 incidence rates and the clinical outcomes were reported for 139 pediatric pts (≤18years) undergoing first allo-HCT at City of Hope from July 2011 to July 2017, for whom HHV-6 was monitored weekly throughout HCT hospitalization. For 57 pediatric pts, who underwent first HCT from January 2009 to July 2011, HHV-6 was tested as clinically indicated and only rates of HHV-6 viremia were collected. From July 2011 to July 2017, HHV-6 was detected in 88/139 pts (63%). The frequency of HHV-6 viremia was associated with malignant diagnoses, myeloablative conditioning, and cord blood HCT. Treatment with antiviral agents was offered to symptomatic pts with a higher viral load (VL), for whom the time to VL clearance was longer and the frequency of subsequent recurrences was higher. Pts with a lower VL cleared HHV-6 without treatment. HHV-6 viremia was associated with a higher frequency of grade II-IV acute graft-versus-host disease (GVHD) (P=.022), but did not affect overall survival (OS), disease-free survival (DFS), non-relapsed mortality (NRM), myeloid, or platelet (Plt) engraftment. HHV-6 weekly screening is not necessary for all HCT pts but may be considered for high-risk pts with malignant diagnoses undergoing cord blood HCT; otherwise, HHV-6 should be tested as clinically indicated. Only symptomatic pts (especially with a high VL>25000) could benefit from treatment. HHV-6 viremia at the time of initiation and administration of the conditioning regimen cleared promptly without the need to augment the transplant process.

ATIR101 administered after T-cell-depleted haploidentical HSCT reduces NRM and improves overall survival in acute leukemia

Overcoming graft-versus-host disease (GvHD) without increasing relapse and severe infections is a major challenge after allogeneic hematopoietic stem-cell transplantation (HSCT). ATIR101 is a haploidentical, naïve cell-enriched T-cell product, depleted of recipient-alloreactive T cells to minimize the risk of GvHD and provide graft-versus-infection and -leukemia activity. Safety and efficacy of ATIR101 administered after T-cell-depleted haploidentical HSCT (TCD-haplo + ATIR101) without posttransplant immunosuppressors were evaluated in a Phase 2, multicenter study of 23 patients with acute leukemia and compared with an observational cohort undergoing TCD-haplo alone (n = 35), matched unrelated donor (MUD; n = 64), mismatched unrelated donor (MMUD; n = 37), and umbilical cord blood (UCB; n = 22) HSCT. The primary endpoint, 6-month non-relapse mortality (NRM), was 13% with TCD-haplo + ATIR101. One year post HSCT, TCD-haplo + ATIR101 resulted in lower NRM versus TCD-haplo alone (P = 0.008). GvHD-free, relapse-free survival (GRFS) was higher with TCD-haplo + ATIR101 versus MMUD and UCB (both P < 0.03; 1-year rates: 56.5%, 27.0%, and 22.7%, respectively) and was not statistically different from MUD (1 year: 40.6%). ATIR101 grafts with high third-party reactivity were associated with fewer clinically relevant viral infections. Results suggest that haploidentical, selective donor-cell depletion may eliminate requirements for posttransplant immunosuppressors without increasing GvHD risk, with similar GRFS to MUD. Following these results, a randomized Phase 3 trial versus posttransplant cyclophosphamide had been initiated.

Retrospective Evaluation of the Use of Romiplostim after Hematopoietic Stem Cell Transplantation0

Background Prolonged thrombocytopenia following hematopoietic stem cell transplant (HSCT) is a common complication associated with risks of major bleeding and high platelet transfusion requirements. Although not approved in the setting of post-HSCT thrombocytopenia, few case series have investigated the use of thrombopoietin (TPO)-receptor agonist romiplostim for patients receiving HSCT. Herein, we reviewed its use in the setting of HSCT at our Institution. Methods From January 2006 to December 2017, 4642 patients received a first HSCT. Of these patients, 2152 (46%) received an autologous HSCT (auto-HSCT) while 2490 (54%) received an allogeneic HSCT (allo-HSCT). Among the patients in the allo-HSCT group, 752 (30%) received a matched related HSCT, 1125 (45%) a matched unrelated HSCT, 278 (11%) a mismatch unrelated HSCT and 335 (13%) a cord blood HSCT. A reduced intensity conditioning regimen was used in 629 (25%) patients receiving an allogeneic HSCT. An adequate clinical response was considered as a reduction of transfusion requirement and a platelet count PLT ≥ 50*103 /µL. This research was approved by the Institutional Review Board (IRB). Results Seven patients (adults n=5, children n=2) received romiplostim for thrombocytopenia. Patients' characteristics are reported in Table 1. All but one (who had CLL-related ITP) received the drug while in remission for the underlying hematologic disease. Romiplostim was used in 6 patients after an allo-HSCT and in 1 after an auto-HCT. Among the allo-HSCT recipients, all 6 reached neutrophil engraftment at a median time of 19 days (range 14-28 days). Romiplostim was administered for ITP (n=2) and poor graft function (PGF, n=4), at a median time of 7.5 months (range 2 - 34 months), with a median of 16 administrations (range 3-18) per patient. All patients received romiplostim weekly, with a median initial and maximum dose of 1 µg/kg (range 1-3 µg/kg) and 9.5 µg/kg (range 3-10 µg/kg), respectively. For the 2 ITP cases, romiplostim was given as third line of therapy, after a lack of response to both high dose steroids and intravenous immunoglobulin. One patient responded to the treatment, achieving a platelet count ≥ 50*103/µL after 2 months, while the other patient did not show any improvement and the drug was discontinued after 3 months. All the 4 PGF cases were thought to be secondary to medications, with one patient also having acute graft versus host disease (GvHD) as possible cause. Romiplostim was given as first line of treatment in all the cases; median platelet counts at the time of starting the treatment was 21*103/µL (range 13-42*103/µL). One patient did not show any response after 4 months of treatment and was subsequently switched to another TPO receptor agonist. Three patients showed a clinical benefit: one patient achieved a stable platelet count ≥50*103/µL after one month, another patient had a partial response achieving transfusion-independence after 3.5 months, but with PLT counts remaining below 50*103/µL; the third patient had a transient increase in platelet counts with decreased transfusion requirement, but the response was lost after two weeks. Overall romiplostim was well tolerated, with no major side effects related to its administration. In two cases mild increase in reticulin stain (grading 0-1) was observed. The auto-HSCT patient receiving romiplostim had Hodgkin's Lymphoma and was diagnosed with recurrent ITP 7.5 years after HSCT, while in complete remission for the underlying disease; he received romiplostim as part of the ITP treatment, and responded to a combination of romiplostim and mycophenolate mofetil without reporting adverse events. Conclusion In our analysis, the use of romiplostim was limited to very few cases of HSCT. The retrospective nature of this study along with a very small and heterogeneous cohort does not allow us to draw any efficacy conclusions. However, our data suggest that romiplostim could be considered a safe option to treat prolonged thrombocytopenia after HSCT. Prospective, randomized clinical trials using TPO-receptor agonists for thrombocytopenia in HSCT are needed to determine efficacy and potential side effects. Disclosures Lawrence: Amgen Inc.: Employment, Equity Ownership. Gernsheimer:Dova pharmaceuticals: Consultancy; Novartis: Honoraria; Amgen: Consultancy, Honoraria; Rigel: Consultancy; Shionogi: Consultancy; Cellphire: Consultancy; Fuji film: Consultancy; Bioverativ: Consultancy. Milano:Amgen: Research Funding; ExCellThera: Research Funding. OffLabel Disclosure: We investigated the use of Romiplostim for thrombocytopenia after hematopoietic cell transplant.

Outcomes of allogeneic haematopoietic stem cell transplantation from HLA-matched and alternative donors: a European Society for Blood and Marrow Transplantation registry retrospective analysis

The introduction of donors other than HLA-matched siblings has been a pivotal change in stem cell transplantation. We aimed to assess the evolution of outcomes within donor groups over time and explore whether donor-recipient HLA disparity might be advantageous in patients with aggressive disease. In this retrospective, multicentre study, we assessed the outcomes for adult patients (≥18 years) with haematological malignancies who underwent their first allogeneic hematopoietic stem cell transplantation (HSCT) between Jan 3, 2001, and Dec 31, 2015, and were reported to the European Society for Blood and Marrow Transplantation. The donor types studied were matched sibling, matched unrelated, mismatched unrelated, haploidentical, and cord blood donors. Unrelated non-cord-blood donors and recipients were typed at the allelic level for HLA-A, HLA-B, HLA-C, and HLA-DRB1. We evaluated trends in overall survival, non-relapse mortality, relapse incidence, progression-free survival, acute and chronic graft-versus-host disease (GVHD), and GVHD-free and relapse-free survival following transplantation from various donor types (matched sibling, matched unrelated, mismatched unrelated, haploidentical, and umbilical cord blood), and compared transplantation outcomes across three epochs (epoch 1: 2001-05; epoch 2: 2006-10; and epoch 3: 2011-15). We used Kaplan-Meier estimators for survival probabilities and cumulative incidence functions accounting for competing risks for probabilities of GHVD, relapse, and non-relapse mortality, using multiple imputations by chained equations to deal with missing data. In epoch 3, we directly compared outcomes by donor group, stratified by a novel three-level disease-risk scheme. We included 106 188 patients in our analysis. The median follow-up was 4·1 years (IQR 1·7-7·7). Overall survival at 3 years increased with all donor groups between epochs 2 and 3 (matched sibling: 54·0% [95% CI 53·1-54·8] to 54·6% [53·6-55·6]; matched unrelated: 49·1% [48·0-50·2] to 51·6% [50·7-52·6]; mismatched unrelated: 37·4% [35·7-39·2] to 41·3% [39·5-43·1]; haploidentical: 34·5% [31·4-37·9] to 44·2% [42·1-46·3]; and cord blood 36·3% [33·9-39] to 43·7% [40·8-46·8]). Improvement in overall survival seems to be driven by a reduction in non-relapse mortality, except in cord blood HSCT recipients, who had a lower relapse incidence. Comparing donor groups across disease-risk strata using the novel disease-risk scheme, overall survival among recipients of matched sibling transplantations remained better than other donor groups except in high-risk disease, where overall survival with matched unrelated transplantations was not different. Overall survival following allogeneic stem cell transplantation is improving with substantial progress among recipients of haploidentical and cord blood HSCT. Nonetheless, the traditional donor hierarchy of matched sibling donors followed by matched unrelated donors and then other donors holds. Our findings warrant further investigation and could inform decision making and the development of donor-selection algorithms. The Varda and Boaz Dotan Research Center in Haemato-Oncology, Tel Aviv University, and the Shalvi Foundation for Research.

Repair of the Blood Brain Barrier with Neutrophil Recovery Following HSCT for Cerebral Adrenoleukodystrophy

Introduction Cerebral leukodystrophy is an X-linked peroxisomal disease characterized by mutations in the ABCD1 gene, resulting in the lack of very long chain fatty acid (VLCFA) transport into peroxisomes. Resultant VLCFA build up in the blood and tissues leads to adrenal gland insufficiency in 95% of boys and an inflammatory cerebral demyelinating process in 40% of patients, which is progressive and most often fatal (cALD). A key clinical feature of cALD is disruption of the blood brain barrier (BBB) illustrated by gadolinium (gad) contrast enhancement on brain MRI at diagnosis and as an indicator of active cerebral disease. Only hematopoietic stem cell transplant (HSCT) has been shown to halt cerebral disease progression. After HSCT, gad enhancement resolves in 90% of cases by 100 days post HSCT in our experience. Objective A seminal question in the field is how recovery of donor-derived hematopoiesis relates to BBB repair and gad resolution. Methods We evaluated the pre-HSCT characteristics and 1-year post-HSCT outcomes in 66 boys undergoing marrow or umbilical cord blood HSCT for cALD. Results The median total nucleated cell (TNC) dose was 0.8 × 108 cells/kg and CD34+ cell dose was 1.27 × 106 cells/kg. Pre-HSCT characteristics included: cALD on MRI quantified using the Loes scoring system, neurologic disability using the neurologic function scale (NFS), plasma and cerebral spinal fluid (CSF) chitotriosidase level, and intensity of gadolinium on pre-HSCT MRI (gad score). We found 77% boys had gad resolution by day +28 (early) post-HSCT and 90% had gad resolution by day +100 (later) post-HSCT. Patients with gad resolution by day +60 post-HSCT had lower Loes scores at 1-year (p = 0.008), lower absolute NFS (p = 0.004), and less progression of neurologic symptoms (post-HSCT NFS – pre-HSCT NFS, p = 0.02). Importantly, we found neutrophil recovery occurred at a mean of 16 days in the patients with day +60 gad resolution compared to 20 days in those without gad resolution (p = 0.008). Other factors associated with early gad resolution were: lower Loes score (p = 0.003), lower NFS (p = 0.003), lower plasma chitotriosidase (p = 0.02), lower CSF chitotriosidase (p = 0.02), and lower gad score (p = 0.02). On multivariate analysis, only the day of neutrophil recovery post-HSCT remained significant with p = 0.04). There was no significant difference in cell dose between the groups. In patients with graft failure, day +60 gad resolution occurred in only 8% (n = 18, p = 0.01). Conclusion This is the first study to link neutrophil recovery following HSCT and early repair of the BBB (gadolinium resolution). This is an important observation, as gad resolution is thought to be an indicator of cerebral disease arrest and activity of neuroinflammation. This observation may also serve as a useful biomarker as new therapies for cALD are being developed, including gene therapy and CD34 expansion.

In Vitro Expansion of Anti-viral T Cells from Cord Blood by Accelerated Co-cultured Dendritic Cells

Hematopoietic stem cell transplantation (HSCT) using unrelated cord blood (CB) donors is a suitable approach when an HLA-matched donor is not available. However, one important drawback is the risk of life-threatening viral infections prior to immune reconstitution, particularly from adenoviruses (AdVs). Although adoptive therapy with ex vivo expanded virus-reactive donor T cells has proven effective to treat these infections in HSCT recipients, the manufacturing process is complex and requires large numbers of cells, which is incompatible with CB donor units. Here, we have adapted our previous accelerated co-cultured dendritic cell (acDC) method, which allows to efficiently and rapidly expand peripheral blood T cells reactive to a given antigen, for use on limited CB material. Selected cytokine cocktails induced DC differentiation and maturation from unfractionated CB mononuclear cell cultures and simultaneously stimulated and expanded, within 10 days, functional CD8+ T cells specific for the model antigen MelanA or AdV immunodominant peptides. In addition, the use of G-Rex cultures yielded numbers of AdV-reactive CD8+ T cells compatible with adoptive cell therapy applications. Our acDC strategy, which uses reagents compatible with good manufacturing practices, may be promptly translated into the clinic for treating intercurrent infections in CB HSCT recipients.

Early Transplantation-Related Mortality within 50 Days after Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Acute Leukemia and Myelodysplastic Syndrome

Background : Transplantation-related mortality (TRM) is a major obstacle to allogeneic hematopoietic stem cell transplantation (HSCT). Patient age, donor type, disease state, and regimen intensity are known to be associated factors of TRM. Within 50 days after transplantation, there is a high incidence of infection prior to engraftment and a high incidence of organ toxicity associated with the conditioning regimen. Patients without special complications will also be discharged within 50 days of transplantation. However, there is no study of early TRM within 50 days. Based on big data from National Health Insurance Service, we conducted a study to identify the incidence and risk factors associated with early TRM within 50 days in allogeneic HSCT.Methods : Patients were enrolled from 2003 to 2015 with the diagnostic codes of acute leukemia or myelodysplastic syndrome (MDS) and the infusion codes of allogeneic HSCT in South Korea. Based on the medical charge and drug codes, we compared the clinical characteristics of early TRM and non-TRM group.Results : The total number of patients was 5,487, the median age was 38 years and the male was 55.2%. Acute myeloid leukemia was 3,490 (63.6%), acute lymphoblastic leukemia was 1,905 (34.7%), and MDS was 92 (1.7%). The 5,268 (96%) patients were received myeloablative conditioning regimen and 219 (4%) patients received reduced intensity of conditioning. The number of transplants increased from 710 in 2003-2006, 1,321 in 2007-2009, 1,590 in 2010-2012, and 1,866 in 2013-2015. The 155 patients (2.8%) died within 50 days. The median age of non-TRM and early TRM group was 38 and 41 years, respectively (p=0.010). The proportion of women was higher in the early TRM group than non-TRM group (54.2% versus 44.6%, p=0.017). There was no difference in early TRM according to year, diagnosis, and regimen intensity. The duration from diagnosis to transplantation was significantly longer in the early TRM group (6.1 versus 5.1 months, p<0.001). The 335 patients (6.1%) had previously received at least one HSCT and early mortality was higher in these patients (9.3%, p<0.001). Also, the interval from the previous transplantation was significantly shorter in early TRM (11.1 versus 15.3 months, p=0.013). Early TRM was higher in patients who received more than 13 platelet transfusions (p=0.033) and 8 more red blood cell transfusions (p=0.003). The 803 patients (14.6%) had iron chelation prior to transplantation and their early TRM rate was as low as 0.2% (p<0.001). There was no increase in TRM in patients with more than 3 underlying diseases. Early TRM rates in peripheral blood, bone marrow, and cord blood HSCT were 3.0%, 1.7%, and 6.0%, respectively (p=0.001), cord blood transplant was significantly higher.Conclusions : In this study, the incidence of early TRM within 50 days was 2.8%. Early TRM was associated with age, gender, previous transplantation, duration of diagnosis-transplantation, previous transfusion, iron chelation, and stem cell source. DisclosuresNo relevant conflicts of interest to declare.

Repair of the Blood Brain Barrier and Neutrophil Recovery Following HSCT in Cerebral Adrenoleukodystrophy

▪Cerebral leukodystrophy is an X-linked peroxisomal disease characterized by mutations in the ABCD1 gene, resulting in the lack of very long chain fatty acid (VLCFA) transport into peroxisomes. Resultant VLCFA build up in the blood and tissues leads to adrenal gland insufficiency in 95% of boys and a progressive inflammatory cerebral demyelinating process in 40% of patients, which is progressive and most often fatal (cALD). Only hematopoietic stem cell transplant (HSCT) has been shown to halt cerebral disease progression. A key clinical feature of cALD is disruption of the blood brain barrier (BBB) illustrated by gadolinium (gad) contrast enhancement on brain MRI at diagnosis and as an indicator of “active” cerebral disease. Following successful donor neutrophil recovery after HSCT, gad enhancement resolves in the majority of cases by 100 days post HSCT in our experience. A seminal question in the field is how recovery of donor-derived hematopoiesis relates to BBB repair and gad resolution. We evaluated the pre-HSCT characteristics and 1- year post-HSCT outcomes in 78 boys undergoing marrow or umbilical cord blood HSCT for cALD. The median total nucleated cell (TNC) dose was 0.8 x 108cells/kg and CD34+ cell dose was 1.27 x 106cells/kg. Pre-HSCT characteristics included: cALD on MRI quantitated using the Loes scoring system, neurologic disability using the neurologic function scale (NFS), plasma and cerebral spinal fluid (CSF) chitotriosidase level, and intensity of gadolinium on pre-HSCT MRI (gad score). We found 39 boys (59%) had gad resolution by day +28 (early) post-HSCT and 79% had gad resolution by day +100 (later) post-HSCT. Patients with gad resolution by day +28 post-HSCT had lower Loes scores at 1-year (p = 0.008), lower absolute NFS (p = 0.004), and less progression of neurologic symptoms (post-HSCT NFS - pre-HSCT NFS, p = 0.02). Graft failure had occurred in 13% of patients with early gad resolution and in 40% in those without early gad resolution (Fishers exact test p = 0.01). Interestingly, in patients without graft failure we found neutrophil recovery occurred at a mean of 16 days in the early patients compared to 20 days in those without gad resolution (p = 0.02).Factors associated with early gad resolution were: lower Loes score (p = 0.003), lower NFS (p = 0.003), lower plasma chitotriosidase (p = 0.02), lower CSF chitotriosidase (p = 0.02), day of neutrophil recovery post-HSCT (p = 0.008), and lower gad score (p = 0.02). On multivariate analysis, only the day of neutrophil recovery post-HSCT remained significant with p = 0.04). There was no significant difference in cell dose between the groups. This is the first study to link neutrophil recovery following HSCT and early repair of the BBB (gadolinium resolution). This is an important observation, as gad resolution is thought to be an indicator of cerebral disease arrest and activity of neuroinflammation. This observation may also serve as a useful biomarker as new therapies for cALD are being developed, including gene therapy and CD34 expansion. DisclosuresLund:Magenta Therapeutics: Research Funding. Miller:Sangamo Therapeutics: Employment. Orchard:Magenta Therapeutics: Research Funding.

Cord Haploidentical Non-In Vitro T Cell Depletion Allogeneic Hematopoietic Stem Cell Transplantation Reduces Relapse of Refractory Acute Leukemia

Whether a graft-versus-graft (GVG) response in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) is associated with an enhanced graft-versus-leukemia (GVL) effect remains highly controversial. Furthermore, it is unknown if the GVG response overwhelms the impact of refractory acute leukemia. We aimed to compare the characteristics and therapeutic outcomes between patients undergoing a modified haploidentical cord blood (cord-haplo) HSCT protocol (n = 97) and those undergoing haploidentical HSCT (n = 42) for refractory acute leukemia. A reliable and stable predominant haploidentical donor chimerism was established. The 2-year relapse rate was more favorable in patients undergoing cord-haplo HSCT than in those undergoing haploidentical HSCT (25.9% versus 53.2%; P = .007), as was progression-free survival (PFS; 35.5% versus 17.9%; P = .049). Meanwhile, nonrelapse mortality at 2 years was not significantly different (38.0% versus 24.6%; P = .367). We also found that a higher number of mutual haploidentical donor-mismatched antigens, a concept similar to HLA mismatching, was associated with better disease control. Multivariate analysis identified cord-haplo HSCT as an independent significant predictor of reduced relapse (hazard ratio [HR], .44; P = .028) and improved PFS (HR, .58; P = .033), as was chronic graft-versus-host disease (GVHD) (relapse: HR, .42; P = .013; PFS: HR, .63: P = .052). However, the incidences of neutrophil and platelet engraftment, GVHD, and virus reactivation were comparable in the 2 groups. This study demonstrates that cord-haplo HSCT significantly enhances the GVL effect and improves PFS, providing a reliable and efficient therapeutic platform for patients with refractory acute leukemia.

A Naive NK Cell Repertoire in the Circulation of Haploidentical Stem Cell Donors Pre Mobilization Predicts Rejection of Cord Myeloid Cells in Patients Undergoing Combined Haploidentical and Unrelated Cord Blood HSCT

Background: For patients (pts) with severe aplastic anemia (SAA) lacking an HLA identical donor, outcomes of hematopoietic stem cell transplantation (HSCT) using unrelated cord blood (UCB) units or haplo-identical donors (HDs) have historically been associated with high graft failure rates and poor survival. In an ongoing clinical trial at the NHLBI, we have observed excellent engraftment (100%) and survival (91%) in SAA pts (n=27) receiving a transplant that co-infuses a single UCB unit with CD34-selectedCD3-depletedcells from a haplo-identical relative. Although cord myeloid engraftment(defined as cord ANC >500/μL) occurred at<day 100 in the majority of pts, a significant fraction of pts had delayed (>day 100) or no cord myeloid engraftment. In this analysis, we investigated factors that may have impeded cord myeloid engraftment following UCB/HD transplantation.Methods: Flow-based NK cell phenotyping using a BD Fortessa II instrument was performed on blood obtained pre-transplant from HDs used for the first 18 SAA pts undergoing UCB/HD transplantation. Lineage specific chimerism was measured by PCR of microsatellites (PowerPlex 16 HS Systemkit/Promega) using DNA from flow sorted cells (BD FACSAria) collected multiple time points post-transplant.KIR-ligand incompatibility in the HD vs UCB directionwas defined using high-resolution HLA typing.Results: 13/18 (72%) pts had cord myeloid engraftment before day 100 while 5/18 (28%) had delayed or no cord myeloid engraftment. Remarkably, delayed or no cord myeloid engraftment occurred exclusively in pts transplanted with KIR-ligand incompatibility in the HD vs UCB direction (n=9) (Figure 1A). In contrast, all 9 pts transplanted with KIR-ligand compatibility in the HD vs UCB direction achieved cord myeloid engraftment by ²day 48 (median day 35) post-transplant. Chimerism analysis performed on blood obtained 30+ days post-transplant revealed NK cell chimerism was ³ 90% cord in origin in all 9 pts transplanted with KIR-ligand compatible grafts. In contrast, amongst the 9 pts receiving a KIR-ligand incompatible transplant, NK cell chimerism was predominantly HD in origin with only a minor fraction of cord NK cells detected 30-200 days post-transplant (Figure 1B). Predominant HD NK cell chimerism in pts receiving a KIR-ligand incompatible transplant was associated with lower degrees of cord myeloid chimerism compared to KIR-ligand compatible recipients. Further analysis of the KIR-ligand incompatible cohort revealed distinct heterogeneity in the time to cord myeloid engraftment (Figure 1A). Although delayed or no cord myeloid engraftment was observed in 5/9 recipients of KIR-ligand incompatible transplants, 4/9 pts in this cohort had cord engraftment at a similar time as pts transplanted with KIR-ligand compatible grafts (median 35 vs. 35 days). This variability in time to cord myeloid engraftment was not associated with stem cell dose, degree of HD NK cell chimerism, type of KIR-ligand incompatibility or KIR haplotype. However, we observed a strong correlation between the proportion of naive NK cells in circulation of HDs before stem cell mobilization with delayed or no myeloid cord engraftment (Figure 1C). With the exception of one patient who had failed HD engraftment, only transplants of CD34+ cells from HDs with a predominantly naive NK cell repertoire, expressing high frequencies of the NKG2A receptor concomitant with low frequencies of NKG2C, Lir-1 and CD57 resulted in delayed or no cord myeloid engraftment (p<0.05).Conclusions: Our study provides the first evidence that NK cells from engrafting CD34+ cells from selected HDs can significantly delay or completely inhibit cord myeloid engraftment following UCB/HD transplantation. Suppression of cord hematopoiesis appears to be restricted to NK cells originating from HDs withHD vs UCB KIR-ligand incompatibility who have a large naive NK cell repertoire in their circulation prior to stem cell mobilization. The myelosuppressive effects of these NK cells are consistent with recentlypublished data showing a naive NK cell repertoire in stem cell donors predicts a reduced risk of AML relapse post-allogeneic HSCT.Further studies defining the mechanisms through which naive NK cells suppress cord hematopoiesis followingUCB/HDtransplantation could shed insights into methods to optimize NK cell mediated graft-vs-leukemia followingallogeneicHSCT of myeloid leukemias. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

P102 Prevalence of anti HLA antibodies in adult hematopoietic stem cell transplant recipients

Aim Recent studies have indicated that the presence of HLA donor specific antibodies (DSA) in patients undergoing mismatched hematopoietic stem cell transplantation (HSCT) represent a considerable risk factor for graft failure. Therefore, the role of pre-existing anti-HLA antibodies in HSCT has drawn increasing attention due to increased number of patients who receive partially HLA mismatched, HLA haploidentical and cord blood HSCT. The aim of this study is to determine the frequency of the presence of anti-HLA antibodies in our adult HSCT program. Method The presence of anti-HLA antibodies before transplantation was determined prospectively in 200 HSCT adult recipients at King Faisal Specialist Hospital and Research Center, using mixed screen beads in a solid phase assay Results Anti-HLA antibodies were detected in 127/200 of the patients (63%). Among those sensitized, 34/127 (27%) were sensitized to HLA class I only and 13/127 (10%) sensitized to HLA class II only and 80/127 (63%) sensitized to both HLA class I and HLA class II. Conclusion Our result has shown a higher level of HLA sensitization (64%) compared to several published studies that reported up to 40% HLA sensitization. Since our patient pool shows a higher prevalence of HLA sensitization, this further emphasizes the need to accurately identify the presence or absence of DSA; which if present poses a significant risk of delayed or complete graft failure.

Severe Combined Immunodeficiencies Resulting from Impaired Purine Metabolism: Single Center Experience

Objective: Deficiency of the purine salvage enzymes adenosine deaminase (ADA) or purine nucleoside phosphorylase (PNP) leads to severe combined immune deficiency (SCID). Since these enzymes are found in all cells, other tissues and organs are also affected, though more variably. Materials and Methods: Here we describe the clinical course and treatment of one PNP deficient and 4 ADA deficient patients who were diagnosed in infancy. All had very low T-cell count and immunoglobulins, consistent with T-B-NK- SCID. Results: Hematopoietic stem cell transplantation (HSCT) was performed in two patients with ADA deficiency. The ADA deficient patient who was treated with haploidentical HSCT (haplo-HSCT) died due to complications of HSCT. One of the ADA deficient patients died before HSCT and another ADA deficient patient is currently being treated with enzyme replacement treatment (ERT). The PNP deficient patient was treated with unrelated cord blood HSCT. Conclusion: With this study, it was highlighted once again that the deficiency of purine salvage enzymes is important subgroup of SCIDs in Turkey.