Unrelated Donor Group Research Articles

Analysis of efficacy and prognosis of allogeneic hematopoietic stem cell transplantation for the treatment of combined immunodeficiency

Objective: To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation for the treatment of combined immunodeficiency (CID) and explore prognostic risk factors. Methods: In this retrospective cohort study, clinical characteristics, laboratory tests and prognosis of 73 CID children who underwent allogeneic hematopoietic stem cell transplantation from February 2014 to April 2022 in the Children's Hospital of Fudan University were analyzed. Based on the subtypes of diseases, all patients were divided into severe combined immunodeficiency disease (SCID) group and other CID group. Based on the types of donors, all patients were divided into matched sibling donor group, matched unrelated donor group, unrelated cord blood group, and haploidentical donor group. Kaplan-Meier method and Log-Rank test were used to analyze the survival data. Cox regression was used to analyze prognostic factors. Results: Among the 73 patients, there were 61 (84%) males and 12 (16%) females. Fifty-five (75%) patients were SCID, and 18 (25%) patients were other CID. Donor source included 2 (3%) matched sibling donors (MSD), 3 (4%) matched unrelated donors (MUD), 64 (88%) unrelated cord blood (UCB), and 4 (5%) haploidentical donors. The age at transplant was 10.7 (5.9, 27.5) months, and the follow-up time was 36.2 (2.5, 62.9) months. The 3-year overall survival rate of 73 patients with CID was (67±6) %. No significant difference was found in the 3-year overall survival rates between patients with SCID (55 cases) and other CID (18 cases) ((64±7) % vs. (78±10) %, χ2=1.31, P=0.252). And no significant difference was found in the 3-year overall survival rates among patients who received MSD or MUD (5 cases), UCB (64 cases), and haploidentical donor (4 cases) transplant (100% vs. (66±6)% vs. (50±25) %, χ2=2.30, P=0.317). Cox regression analysis showed that the medical history of sepsis (HR=2.55, 95%CI 1.05-6.20, P=0.039) and hypoalbuminemia at transplant (HR=2.96, 95%CI 1.14-7.68, P=0.026) were independent risk factors for the prognosis of allogeneic hematopoietic stem cell transplantation in pediatric patients with CID. Conclusions: Allogeneic hematopoietic stem cell transplantation is an effective treatment for CID. The medical history of sepsis and hypoalbuminemia at transplant were risk factors for prognosis. Enhancing infection prevention and nutritional intervention before transplant can improve patient prognosis.

Co-transplantation of umbilical cord mesenchymal stem cells and peripheral blood stem cells in children and adolescents with refractory or relapsed severe aplastic anemia

To evaluate the co-transplantation efficacy of umbilical cord mesenchymal stem cells (UC-MSCs) and peripheral blood stem cells (PBSCs) as a novel approach for refractory or relapsed severe aplastic anemia (R/R SAA) in children and adolescents, thirty-two children and adolescents diagnosed with R/R SAA underwent a retrospective chart review. The patients were categorized into two groups based on the source of PBSCs: the matched sibling donor (MSD) group and the unrelated donor (UD) group. No adverse events related to UC-MSC infusion occurred in any of the patients. The median time for neutrophil engraftment was 13 days (range: 10–23 days), and for platelets, it was 15 days (range: 11–28 days). Acute GVHD of Grade I–II and moderate chronic GVHD were observed in 21.8 and 12.5% of cases, respectively. No statistically significant differences were found between the MSD and UD groups in terms of engraftment, GVHD, and complications, including infection and hemorrhagic cystitis. The median follow-up time was 38.6 months (range: 1.4–140.8 months). As of October 31, 2021, five patients had succumbed, while 27 (84.4%) survived. The 5-year OS rate showed no statistically significant difference between the MSD and UD groups (84.8 ± 10.0 vs. 82.4 ± 9.2%, p = 0.674). In conclusion, the application of UC-MSCs in the treatment of R/R SAA in PBSC transplantation is reliable and safe, they had no graft rejection, low incidence of severe GVHD which may have been contributed by the co-infusion of MSC.

Allogenic hematopoietic stem cell transplantation outcomes of patients aged ≥ 55 years with acute myeloid leukemia or myelodysplastic syndromes in China: a retrospective study

BackgroundElderly patients with acute myeloid leukemia or myelodysplastic syndromes (AML/MDS) have historically had poor prognoses. However, there has been a recent increase in the use of allogenic hematopoietic stem cell transplantation (allo-HSCT) are in this patient population. Nevertheless, the optimal choice of donor type for the patients remains an unmet need. Limited data exist on the use of allo-HSCT in elderly patients with AML/MDS from China. To better understand and optimize the selection of donor type for the elderly patients, particularly for those with refractory or relapsed disease, in comparison with the previous studies in the US and Europe.MethodsOur retrospective study enrolled 259 patients aged over 55 years who underwent their first allo-HSCT between April 2015 and August 2022. These patients were divided into three groups based on donor type: haploidentical related donor group (haploidentical related donor transplantation [HID], n = 184), matched sibling donor group (matched sibling donor transplantation [MSD], n = 39), and matched unrelated donor group (matched unrelated donor transplantation [MUD], n = 36). Statistics were performed with the chi-square test, the log-rank and Fine-Gray tests.ResultsThe median age of the cohort was 57 years (range: 55–75) and 26.25% of patients were over 60 years old. Younger patients had a higher incidence of acute graft-versus-host disease (HR = 1.942, P = 0.035), faster neutrophil recovery (HR = 1.387, P = 0.012), and better overall survival (HR = 0.567, P = 0.043) than patients aged ≥ 60 years across the entire cohort. Patients with refractory or relapsed (R/R) diseases had delayed neutrophil engraftment (P = 0.010, HR = 0.752) and platelet engraftment (P < 0.001, HR = 0.596), higher incidence of relapses (HR = 2.300, P = 0.013), and inferior relapse-free survival (RFS) (HR = 1.740, HR = 0.016) regardless of donor type. When it came to graft-versus-host-disease-free, relapse-free survival (GRFS), MUDs turned out to be superior to HIDs (HR = 0.472, P = 0.026) according to the multivariable analysis. In contrast, we found MSDs had an inferior GRFS to HIDs in parallel (HR = 1.621, P = 0.043).ConclusionThe choice of donor type did not significantly affect the outcomes of allo-HSCT. However, when considering the quality of post-transplant life, MUDs or HIDs from younger donors may be the optimal choice for elderly patients.

HLA-B leader genotypes in a clinical population.

The -21 dimorphism in the leader sequences of HLA-B exon 1 is associated with risk of graft-versus-host disease (GVHD), relapse and overall survival after unrelated donor hematopoietic cell transplantation (HCT), haploidentical HCT and cord blood transplantation. Consideration of the leader dimorphism in the prospective selection of allogeneic donors for HCT may help to lower risks for patients, but requires understanding of the frequencies of the leader in patients and candidate transplant donors. We defined the frequencies of the HLA-B leader, and its association to HLA-B Bw4/Bw6 and C1/C2 KIR epitopes. Sequence variants of rs1050458 of exon 1 position -21 for 11,126 haplotypes were analyzed from high resolution HLA typing of over 5500 study subjects. HLA typing was performed by TruSight/AlloSeq NGS and analyzed using TruSight/AlloSeq Assign software. HLA-B Bw4/Bw6 and C1/C2 KIR epitopes were defined based on established sequence alignments and nomenclature. Alleles at rs1050458 of HLA-B exon 1 were validated as dimorphic: rs1050458-C or -T variants encoding threonine (T) or methionine (M) at anchor position 2 (P2) of nonameric HLA-B leader peptides, respectfully. No additional variants were observed. Among study subjects, 70% of HLA-B haplotypes encoded T-leader and 30% encoded M-leader sequences. The genotype frequencies of TT, MT, and MM were consistent among patient, related, and unrelated donor groups. The associations of M/T leader, Bw4/Bw6, and C1/C2 enhanced understanding of the Class I features involved in the innate immune response. A population of patients and transplant donors confirms the rs1050458 leader dimorphism and its association with HLA-B Bw4/Bw6 and C1/C2 KIR features.

Haploidentical donor stem cell transplantation had a lower incidence of bronchiolitis obliterans syndrome compared with HLA-matched sibling donor transplantation in patients with hematologic malignancies: Benefit from ATG?

Haploidentical donor stem cell transplantation (HID-SCT) based on antithymocyte globulin (ATG) for graft-versus-host disease (GVHD) prophylaxis had achieved a similar incidence of chronic graft-versus-host disease (cGVHD) with human leukocyte antigen (HLA)-matched sibling donor stem cell transplantation (MSD-SCT). However, bronchiolitis obliterans syndrome (BOS), which serves as pulmonary cGVHD, was rarely compared between HID and MSD transplantation. One thousand four hundred five patients with hematologic malignancies who underwent allogeneic SCT were enrolled in this retrospective study. Based on donor type, we divided the patients into three groups: HID, MSD, and match unrelated donor (MUD) groups. The cumulative incidences and risk factors of BOS were analyzed. The 5-year cumulative incidence of BOS was 7.2% in the whole population. HID transplantation had a lower 5-year cumulative incidence of BOS than MSD transplantation (4.1% vs. 10.0%, p < 0.001) and a similar incidence with MUD transplantation (4.1% vs. 6.2%, p = 0.224). The 5-year cumulative incidence of BOS was lower in the ATG group than that in the non-ATG group in both the whole and MSD populations (4.6% vs. 11.2%, p < 0.001, and 4.1% vs. 11.2%, p = 0.042, respectively). The 5-year incidence of BOS in mixed grafts [peripheral blood stem cell (PBSC) plus bone marrow] group was also lower than that in the PBSC group (4.2% vs. 9.1, p = 0.001). Multivariate analysis showed that HID, ATG, and mixed grafts were protective factors for BOS [odds ratio (OR) 0.3, 95% CI 0.2-0.6, p < 0.001; OR 0.3, 95% CI 0.2-0.7, p = 0.001; OR 0.3, 95% CI 0.1-0.8, p = 0.013], and acute graft-versus-host disease (aGVHD) and cGVHD were independent risk factors for BOS (OR 2.1, 95% 1.1-4.3, p = 0.035; OR 10.1, 95% CI 4.0-25.0, p < 0.001). HID transplantation had a lower incidence of BOS than MSD transplantation, which might be associated with ATG and mixed grafts.

Comparison of Outcomes of Elderly Patients with Acute Myeloid Leukemia (AML) in CR1 Receiving Reduced Intensity Allogeneic Stem Cell Transplantation (RICT) from Matched Sibling (MSD) or Unrelated Donors (URD)

BACKGROUND. Comparative data on the results of RICT from MSD or URD in elderly patients (pts) are scarce. We describe outcomes of AML CR1 pts > 50 years (yrs) allografted from MSDs or URDs as part of a multinational, prospective, controlled study (NCT00342316), which aims to compare RICT vs chemotherapy. The study started in 2004 and completed enrollment (339 pts) in 2016. In this report, we compare the impact of MSD or URD and therefore we focus only on the time period when both MSD and URD transplants were performed within the study (2010-2016).PATIENTS AND PROCEDURES. Included were 136 pts (53 females, 83 males). Median age was 64 (50-70) and 62 (52-70) yrs in URD and MSD groups, respectively. Pts were high (54%) or intermediate (IR) (46%) risk, donors were URD (n=81), and MSD (n=55). Prespecified high risk criteria were: poor risk cytogenetics, secondary or therapy-related AML, blasts >15% after induction #1, or FLT3-ITD+/NPM1-. Eight URDs were <8/8 HLA matched. Reduced intensity conditioning was busulfan/fludarabine based in 92% of transplants (Tx). Anti thymocyte globulin (ATG) pre Tx was used in 93% of URD and 25% of MSD pts. Pts received PBSC (94%) or BM (6%). Distribution of high/intermediate risk pts were: URD 58%/42% and MSD 48%/52% (p=0.29.) STATISTICSOverall survival (OS) and leukemia free survival (LFS) after Tx were estimated by means of the Kaplan-Meier method, whereas cumulative incidence functions were used for non-relapse mortality (NRM) and relapse incidence. The Cox regression model was used to analyze incidence rates.RESULTS. Median time from CR to Tx in URD and MSD groups was 4.0 (range 1.1-8.7), and 3.1 (0.8-10) mo, respectively (p<0.001). URD pts received more chemo pre Tx: ≥3 courses in 85% vs 60% (MSD group) p=0.001. Graft rejection occurred in 1 pt.Median follow-up from Tx for living pts was 23 (4-78) and 25 (3-82) mo for URD and MSD pts, respectively. During follow-up, 36 pts relapsed, 24 URD (30%) and 12 MSD (22%) and 47 pts died, 23 URD (28%) and 24 MSD (44%). Causes of deaths in the URD and MSD groups were AML (n=18,11), GvHD (1,5), infections (2,5) and other (2,3).Estimated 2-year OS for all pts was 64% (95% CI 54-72%). For the subgroups of high and IR risk pts OS at 2 yrs was 49% (36-61%) and 82% (69-90%), respectively. For MSD and URD groups OS were 53% (38-67%) and 72% (60-81%); hazard ratio (HR) 1.66 (0.94-2.95; p=0.08). If adjusting for confounders [risk category (high vs . IR), country (Canada/other vs . Sweden), gender, age] the HR for OS was 1.57 (0.80-3.08; p=0.19). LFS was similar in URD and MSD groups: 53% (38-66%) vs 63% (50-73%); adjusted HR 1.21 (0.65-2.26; p=0.54). The 2-yrs cumulative incidence (CI) of relapse (NRM competing) was 23% (13-35%) in the MSD group and 32% (21-43%) in the URD group; adjusted HR 0.71 (0.32-1.60; p=0.41). The 2-yrs CI of NRM (relapse competing) was 24% (13-37%) in the MSD group and 5% (2-11%) in the URD group, adjusted HR 3.45 (1.03-11.6; p=0.045).Grade III-IV acute GvHD and chronic extensive GvHD were less common in the URD group, 5% vs 21% (p=0.009) and 10% vs 45% (p <0.001), respectively. At 12 mo after CR1, 18% of URD pts and 58% of RD pts were on corticosteroids (p<0.001).CONCLUSION. No significant differences in OS, LFS or relapse rate were found between MSD and URD transplants. However, RICTs from URDs were associated with less acute and chronic GvHD, and less NRM. These findings may be explained by lower donor age, more chemo, longer time from CR to Tx in MUDs and probable contribution of ATG. Our data suggest that URD RICT may be used safely in older patients with AML with satisfactory OS. DisclosuresKiss:Otsuka: Membership on an entity's Board of Directors or advisory committees, Other: meeting attendance support, Research Funding; Alexion: Membership on an entity's Board of Directors or advisory committees, Research Funding. Delage:BMS: Research Funding; Pfizer: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; AbbVie: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding. Ritchie:Amgen Inc.: Honoraria. Sabloff:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Brune:Novartis: Other: reimbursement for lecture.

Allogeneic Hematopoietic Stem-Cell Transplantation for GATA2 Deficiency Using a Busulfan-Based Regimen

Background: GATA2 deficiency is an increasingly recognized bone marrow failure syndrome responsible for: MonoMAC, monocytopenia with atypical mycobacterial infection (MAC); DCML, dendritic cell, monocyte and lymphoid cell deficiency; Emberger syndrome with lymphedema and monosomy 7; and familial myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML). GATA2 deficiency can be reversed by hematopoietic stem cell transplantation (HSCT). However, the intensity of conditioning required to ensure engraftment and reverse the myelodysplastic syndrome (MDS) characteristic of the disease remains controversial.Methods: We carried out a prospective study of allogeneic HSCT in 22 patients (mean age 26 years; range 17 to 45 years) with GATA2 deficiency, or the MonoMac syndrome, using a myeloablative, busulfan-based conditioning regimen. All 22 patients had MDS and two had AML. Eleven patients had clonal cytogenetic changes in the bone marrow. There were two matched related donor (MRD) recipients, 13 matched unrelated donor (URD) recipients, and 7 haploidentical related donor recipients. MRD and URD recipients received conditioning with 4 days of busulfan (days -6 to -3) to target an AUC between 3600 and 4800 min*microm/L and 4 days of fludarabine 40 mg/m2/day (days -6 to -3). Haploidentical related donor recipients received low-dose cyclophosphamide for two days (days -6 and -5), fludarabine 30 mg/m2/day for 5 days (days -6 to -2), 2-3 days of busulfan depending upon cytogenetics, along with 200 cGY total body irradiation (TBI) on day -1. MRD and URD recipients received tacrolimus and short course methotrexate for post-transplant graft-versus-host disease (GVHD) prophylaxis, whereas haploidentical recipients received high-dose post-transplant cyclophosphamide (PT/CY) followed by tacrolimus and mycophenolate mofetil for GVHD prophylaxis.Results: Nineteen of the 22 patients are alive with resolution of the clinical phenotype and correction of the bone marrow MDS with eradication of the cytogenetic changes at a median follow-up of 23 months (range, 6 to 48 months) giving an overall disease-free survival of 86 percent. The three deaths all occurred in the URD group. Of the three deaths, one resulted from refractory acute myelogenous leukemia (AML), and two from complications related to treatment for GVHD. There was a 26 percent incidence of grade III-IV acute GVHD (aGVHD) in the MRD and URD groups, and no grade III-IV aGVHD in the haploidentical related donor cohort. Similarly, there was a 46 percent incidence of chronic GVHD (cGVHD) in the MRD and URD cohort, whereas two of the 7 (28 percent) of the haploidentical related donor recipients had cGVHD.Conclusions: Despite overall disease-free survival of 86 percent with eradication of the clonal cytogenetic abnormalities in the bone marrow, GVHD remains a limitation in the MRD and URD cohorts treated with standard post-transplant tacrolimus/methotrexate prophylaxis for GVHD. We are currently de-escalating the busulfan dosing based on the AUC in all cohorts and incorporating PT/CY in the MRD and URD cohorts to decrease toxicity and reduce the incidence of aGVHD and cGVHD. Together with our previous studies using a nonmyeloablative regimen, it appears that when GATA2 deficiency patients are transplanted when they have a hypocellular bone marrow with MDS and without cytogenetic changes, a nonmyeloablative regimen results in reliable engraftment in GATA2 deficiency since the GATA2 deficient marrow has a proliferative disadvantage. However, with clonal progression and unfavorable cytogenetic changes and/or a hypercellular marrow, where the malignant clone has a proliferative advantage, a higher dose regimen results in more reliable engraftment and eradication of the clone. Studies to identify the precise level of conditioning for the stages of the disease are ongoing. DisclosuresNo relevant conflicts of interest to declare.

Outcomes of Intermediate Risk Acute Myeloid Leukemia in First Remission Undergoing Autologous Stem Cell Transplantation Compared to Allogeneic Stem Cell Transplantation and Chemotherapy Consolidation: A Retrospective, Propensity-Score Adjusted Analysis

Introduction: Post-remission therapy (PRT) for acute myeloid leukemia (AML) remains an area of debate. Autologous stem cell transplantation (AutoSCT) is listed as a possible PRT in patients with intermediate risk AML in the 2017 European Leukemia Network Recommendations. Our center has frequently performed AutoSCT for patients with AML and we aimed to retrospectively compare this strategy with allogeneic SCT (AlloSCT) and consolidation chemotherapy (CMT).Methods: We compared overall survival (OS) and leukemia free survival (LFS) using propensity score (PS) adjusted analysis of patients receiving PRT with: AutoSCT, matched sibling (Sib) AlloSCT, unrelated/mismatch (UD/MM) AlloSCT and CMT. We included patients diagnosed between 1984-2003 (period of AutoSCT at our centre) in first complete remission (CR1) following induction CMT. The 2010 Medical Research Council cytogenetic classification [Grimwade D. Blood 2010;116(3):354-65] was used to define intermediate risk patients. PS-adjusted analysis was performed with marginal mean weighting through stratification (MMWS) method [Hong G. Psych Methods 2012;17(1):44-60.], accounting for sex, de-novo vs. secondary, year of diagnosis, age, chromosome, performance status and high risk features based on prior institutional guidelines (monocytic subtypes, white blood cell > 50x109/L and > 1 cycle to CR1). In brief, log(PS) were calculated from multinomial regression. We excluded cases with log(PS) outside common support area (20% standard deviation from minimum and maximum of each group). Log(PS) were then stratified into 6 strata. MMWS weight was the product of inverse proportion of treatment in each stratum multiplied by proportion of treatment in the whole population. Data was censored at failure or at 10 years. Unadjusted survival analysis was performed using Kaplan Meier method and multivariate logistic regression, and adjustment was also performed by MMWS weight.Results: We identified 259 patients (62 Sib-AlloSCT, 18 UD/MM-AlloSCT, 30 AutoSCT and 149 CMT). Baseline pre-PRT characteristics were used for PS calculation before and after weight adjustment (Table). All SCTs were performed with myeloablative conditioning regimens, most being busulfan-cyclophosphamide based. Median follow-up time for patients who survived beyond 1 year was 6.5 years. Unadjusted OS and LFS were as shown in Figure panel A and B. We excluded 38 patients (2 Sib-AlloSCT, 3 AutoSCT and 33 CMT) based on the PS calculation. The pre-PRT characteristics were well balanced after PS adjustment. Adjusted OS at 2 and 5 years were: Sib-AlloSCT 75.3% and 65.5%; UD/MM-AlloSCT 38.2% and 38.2%; AutoSCT 60.7% and 46.0%; CMT 48.0% and 30.4% (Figure panel C). Adjusted LFS were: Sib-AlloSCT 71.4% and 65.5%; UD/MM-AlloSCT 38.2% and 38.2%; AutoSCT 50.8% and 46.0%; CMT 21.9% and 17.4%, respectively (Figure panel D). Adjusted cumulative incidence of relapse and non-relapse mortality (considered as competing risks) at 5 years were: Sib-AlloSCT 17.2% and 20.9%; UD/MM-AlloSCT 32.6% and 33.3%; AutoSCT 48.4% and 10.8%; CMT 80.5% and 10.9%. Adjusted multivariate HR, 95% confidence interval (CI) and p-value for OS, considering CMT as reference, were: Sib-AlloSCT [0.34, 0.19-0.61, <0.001], UD/MM-AlloSCT [1.03, 0.40-2.66, 0.953] and AutoSCT [0.71, 0.33-1.51, 0.374], respectively. Adjusted multivariate HR, 95%CI and p-value for LFS were Sib-AlloSCT [0.22, 0.13-0.37, <0.001], UD/MM-AlloSCT [0.62, 0.27-1.43, 0.262] and AutoSCT [0.45, 0.21-0.96, 0.038], respectively.Conclusion: Our results show that intermediate risk AML patients who underwent Sib-AlloSCT in CR1 had the best outcomes. AutoSCT significantly improved LFS, in comparison to CMT. However, this benefit did not result in a significant improvement in OS, possibly due to subsequent SCT in the CMT group after relapse. Limitations of our findings include a lack of molecular data and the older time period of our cohort. In a more contemporary cohort, we anticipate that advancements in donor selection and supportive care might improve outcomes with AlloSCT, particularly for the unrelated donor group. Despite this, our results support AutoSCT as a valid option for intermediate risk AML patients who lack an HLA-matched sibling. Further studies integrating molecular genetics and minimal residual disease are needed to guide the selection of patients for AutoSCT who are likely to gain the greatest benefit. [Display omitted] DisclosuresHogge:Novartis, Roche, and Sanofi: Consultancy. Sutherland:Janssen: Honoraria. Gerrie:Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Lundbeck: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; Roche: Research Funding.

Psychological characteristics and associations between living kidney transplantation recipients and biologically related or unrelated donors

BackgroundAlthough recipients and donors in living kidney transplantation experience psychological distress—including depression and anxiety—during the pre-operative period, very few studies have evaluated the related psychological reactions. This study aimed to determine the characteristics and correlations of the mood states and personality of recipients and donors (genetically related and unrelated) of living kidney transplantations.MethodsA total of 66 pairs of living donors and recipients were enrolled from April 2008 to June 2019 in this study, of whom 53 eligible pairs of living donors and recipients were included in the retrospective analysis of their psychological assessments in the pre-transplantation states. While participants’ personality patterns were assessed using the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), mood states were evaluated via both the State-Trait Anxiety Inventory (STAI) and The Center for Epidemiologic Studies Depression Scale (CES-D). Statistical analysis was performed using paired t-tests and Spearman’s correlation analyses.ResultsThe recipient group showed significantly higher scores for Hypochondriasis (t = − 4.49, p = .0001), Depression (t = − 3.36, p = .0015), and Hysteria (t = − 3.30, p = .0018) of MMPI-2 and CES-D (t = − 3.93, p = .0003) than the donor group. The biologically unrelated recipient group reported higher scores of Hypochondriasis (t = − 3.37, p = .003) and Depression (t = − 2.86, p = 0.0098) than the unrelated donor group. Higher scores for Hypochondriasis (t = − 3.00, p = 0.0054) and CES-D (t = − 3.53, p = .0014) were found in the related recipient group. A positive association was found for Hypomania (r = .40, p = .003) of MMPI-2, STAI-S (r = .36, p = .009), and CES-D (r = .36, p = .008) between the recipient and donor groups.ConclusionsRecipients suffered from a higher level of depression and somatic concerns than donors before living kidney transplantation. Psychological problems like depression and anxiety can occur in both living kidney transplantation donors and recipients. This study suggests that clinicians must pay attention to mood states not only in recipients but also in donors because of emotional contagion.

Comparison of HLA-matched sibling and unrelated donor transplantation in adult patients with acquired severe aplastic anemia.

The recent improvements in the outcomes of severe aplastic anemia (SAA) patients who received allogeneic stem cell transplantation (SCT) from unrelated donors (URD) suggest the possibility of its alternative first-line treatment. To address this issue, results of adult SAA patients receiving allogeneic SCT were compared between the following three donor-type groups: 8/8-matched sibling (MSD; n = 153), 8/8 well-matched unrelated (WM-URD; n = 72), and 6-7/8 partially matched unrelated (PM-URD; n = 33). Proportion of patients who experienced immunosuppressive treatment failures was significantly higher in the URD groups than in the MSD group (P< 0.01). The incidences of graft failure and transplant-related mortality, and graft-vs.-host disease-free, failure-free survival rates of the MSD, WM-URD, and PM-URD groups were 14.6, 0, and 0% (P< 0.01); 6.1, 10.3, and 21.7% (P= 0.03); and 76.7, 55.5, and 51.5% (P< 0.01), respectively. The overall survival (OS) rate of the MSD group (93.9%) was higher than that of the PM-URD (78.3%; P < 0.01) group, but not to that of the WM-URD (86.2%; P= 0.18) group. Our study showed comparable OS between the MSD group and WM-URD group, which suggest that the URD-SCT can be used as a first-line treatment for adult SAA patients with WM-URD.

Hematopoietic Stem Cell Transplant Outcomes in Patients with Acute Myeloid Leukemia from a Tertiary Care Center in South Inida

<h3>Background</h3> Allogenic hematopoietic stem cell transplantation (allo-HSCT) is one of the best therapies for acute myeloid leukemia (AML) and a proven post-remission therapy for intermediate and high-risk AML. The best HSCT source seems to be a matched sibling donor (MSD), but in the absence of one, a readily available haplo-identical donor provides an equally high cure rate. This is of relevance in a developing country like India as the cost of an unrelated donor is usually unaffordable. We present our experience from a single centre. <h3>Methods</h3> We analysed retrospective data of 122 AML patients who have undergone HSCT between Jan-2012 to Jun-2019 at our centre. Fludarabine + Busulfan or Fludarabine + Melphalan based conditioning regimen were used in MSD transplant and John Hopkins's protocol was followed in haploidentical HSCT. Cyclosporine + methotrexate was used as GVHD prophylaxis in MSD and unrelated donor group and cyclophosphamide + tacrolimus + mycophenolate was used for haploidentical post-transplant. Day 100 Survival, overall survival, incidence of GVHD and CMV reactivation was computed. <h3>Results</h3> Out of 122 patients, 69 (56.6%) were males, the mean age was 29.05±20.13 (range, 1 -74) years. Peripheral blood stem cell (99%) was the predominant graft source with majority of matched sibling donor (MSD; 54.1%) compared to Haplo-identical donors (30%). Figure 1 shows the demographic and clinical details of the study patients. The incidence of acute GVHD (40.9% vs 32.6%; p=0.372) and chronic GVHD (16.7% vs 15.2%; p=0.837) are similar in MSD and Haplo transplantation. There were 25 (38%) deaths in MSD and 23 (50%) deaths haplo-identical transplantation (p=0.245). The day-100 survival and overall survival function is significantly better in MSD transplantation (p<0.05; Figure 2). Disease status at latest follow up showed that 81% were in remission and 19% had relapsed. <h3>Conclusion</h3> Our study showed comparable outcomes in MSD and Haplo-identical transplant with respect to incidence of GVHD and mortality. However, the survival function is better with MSD transplantation. Haplo-identical transplant is a feasible option in case of non-availability of MSD, due to ease of donor availability and strong motivation from the family donor to donate the stem cells.

Do Recipients of Genetically Related Donors Have Better Outcomes After Living Donor Liver Transplantation?

There are few data on genetic relation of the donor and outcomes in living donor liver transplantation (LDLT) recipients. We compared outcomes of LDLT between recipients of genetically related and unrelated donors in a large single-center series. The study included 1372 adult, ABO-compatible, primary LDLT recipients, who received a graft from either a first-degree relative (parent, sibling, son, or daughter; n = 756) or unrelated donor (spouse or relative of the spouse; n= 616). The mean age of the recipients with a related donor was 50.2 ± 10.8 years compared with 47.3±9.3 years for recipients with unrelated donors (P= 0.000). Chronic rejection was significantly more common in the genetically unrelated donor group than in the genetically related donor group (28 [4.5%] versus 9 [1.1%]; P= 0.000) at a mean follow-up of 37 months (15-95 months). There were no significant differences in other outcomes between the 2 groups. The 12-month and 36-month survival between the unrelated and related groups was 87.6% versus 90%, and 86.3% versus 89.7% respectively (P = 0.115). The multivariate analysis revealed genetically unrelated donors (odds ratio [OR]: 3.88, 95% confidence interval [CI]: 1.80-8.34, P= 0.001) and history of acute cellular rejection (OR: 3.39, 95% CI: 1.68-6.81, P= 0.001) as predictors of chronic rejection. Although chronic rejection was found to be more common in genetically unrelated donors, the patient survival after LDLT was similar.

Comparison of outcomes of haploidentical donor hematopoietic stem cell transplantation supported by third-party cord blood with HLA-matched unrelated donor transplantation

Previous study indicated that co-infusion of cord blood cells may potentially improve the outcome of haploidentical donor (HID) transplantation. In this study, we analyzed the outcomes of patients who underwent HID transplantation supported by cord blood when compared with HLA-matched unrelated donor (URD) transplantation. Starting in 2015, 40 patients with hematopoietic malignancies underwent HID transplantation and 26 patients underwent URD transplantation. Hematopoietic recovery, the incidences of grade II–IV acute graft-versus-host disease (GVHD) and chronic GVHD was comparable in the two groups. At two year, the relapse risk in HID group was significantly lower than in URD group (RR 4.630; 95%CI, 1.081–19.839; p = .039). Moreover, HID group have prolonged PFS (RR 2.642; 95%CI, 1.046–6.672; p = .040). In conclusion, HID transplantation supported by cord blood results in better outcomes compared with URD transplantation and it might be a favorable alternative to a HLA-matched URD transplantation.

An Update of Australasian Trends in Allogeneic Stem Cell Transplantation for Myelofibrosis in the Molecular Era

An Update of Australasian Trends in Allogeneic Stem Cell Transplantation for Myelofibrosis in the Molecular Era

Prospective Evaluation of Alternative Donor from Unrelated Volunteer Donor and Cord Blood in Adult Acute Leukemia and Myelodysplastic Syndrome: No Difference between Unrelated Donor and Cord Blood

Prospective Evaluation of Alternative Donor from Unrelated Volunteer Donor and Cord Blood in Adult Acute Leukemia and Myelodysplastic Syndrome: No Difference between Unrelated Donor and Cord Blood

The importance of graft cell composition in outcome after allogeneic stem cell transplantation in patients with malignant disease.

Graft-versus-host disease (GVHD) and relapse remain majobstacles ftreatment success in allogeneic hematopoietic stem cell transplantation (HSCT). In the present study, we evaluated the immune cell profile of the graft to outcome after HSCT. Flow cytometry data of graft cell subsets [CD34+ , CD3+ , CD19+ , CD4+ , CD8+ , CD3-CD56+ CD16+ , CD4+ CD127low CD25high ] from G-CSF primed peripheral blood stem cell (PBSC) donors was collected retrospectively from 299 patients with hematological malignancies undergoing HSCT between 2006 and 2013. The association to overall survival, transplant-related mortality (TRM), GVHD and probability of relapse was analyzed. Patients outcome from HLA-identical sibling (Sib) (n=97) and unrelated donors (URD) (n=202) were analyzed separately as all URD patients received anti-thymocyte globulin (ATG). Five-year overall survival was similar in the two cohorts (68% (Sib) vs 65% (URD)). The relapse incidence was significantly lower in the Sib cohort (24% vs 35%, P=0.04). Multivariate analysis in the URD group revealed an association between a higher CD8+ dose and less relapse (HR, 0.94; 95%CI, 0.90-0.98; P=0.006) as well as an association between higher CD34+ dose and both higher TRM (HR, 1.09; 95%CI, 1.02-1.20; P=0.02) and relapse (HR, 1.09; 95%CI, 1.01-1.17; P=0.025). The Sib analysis showed an association between a higher graft CD19+ dose and more severe acute GVHD (HR, 1,09; 95%CI, 1.03-1.15; P=0.003) and TRM (HR, 1.09; 95%CI, 1.01-1.17; P=0.036). In addition, a higher CD4+ graft content was associated to an increased risk for chronic GVHD (HR, 1.02; 95%CI 1.00-1.04; P=0.06). These data indicate an importance of PBSC dongraft composition in patients with a hematological malignancy.

Comparable Outcomes after Hematopoietic Stem Cell Transplantation from Mother Donors and Matched Unrelated Donors in Patients with Hematopoietic Malignancies.

Haploidentical transplantations have achieved comparable survival as HLA fully matched unrelated donors (URDs). When choosing the best donor for HLA haploidentical transplantations, most institutions prioritize using young male donors over mother donors. In a retrospective study we compared outcomes in mother donor and URD transplantations. We found that both 2-year overall survival and 2-year leukemia-free survival were comparable between the mother donor group and URD group (74.8% versus 72.9%, P = .937, and 71.7% versus 67.0%, P = .580, respectively). Higher incidences of grades II to IV acute graft-versus-host disease (GVHD) and chronic GVHD were observed in the mother donor group than in the URD group (43.5% versus 14.0%, P = .001, and 62.2% versus 38.7%, P = .007, respectively). The 2-year cumulative incidences of relapse were significantly decreased in the mother donor group (7.6% versus 20.9%, P = .036). These findings suggest mother donor transplantations could achieve comparable survival with URD transplantations and exhibited decreased rates of relapse but increased rates of GVHD, indicating that mother donors would be a suitable choice for patients without an identical sibling donor.

Comparable Outcomes after Hematopoietic Stem Cell Transplantation from Mother Donors and Matched Unrelated Donors in Patients with Hematopoietic Malignancies

BACKGROUND Haploidentical donor (HID) transplantations have achieved comparable survival as HLA fully matched unrelated donor (URD) transplantations. However, previous studies usually consider the two donor sources as whole populations when making the comparison, although there are actually subgroups within each. Based on current knowledge regarding donor selection, offspring and sibling donors were prioritized over parental donors in unmanipulated haplo-transplant settings, and maternal donors were considered as “the worst donors” under the Beijing Protocol due to the increased probabilities of GVHD and inferior survival. To compare efficacies of “the worst” mother donors and URDs would help to acquire a further understanding on donor selection of HIDs versus URDs.PATIENTS AND METHODS 43 and 92 patients who underwent transplantations with URDs or mother donors from June 2012 to June 2015 were enrolled. Their transplantation outcomes, including hematopoietic recovery, acute and chronic GVHD, relapse, transplant related mortality (TRM), overall survival (OS) and leukemia-free survival (LFS) were compared. Univariate and multivariate analysis were performed to explore risk factors for transplantation outcomes.RESULTS Both 2-year OS and 2-year LFS were comparable between the mother donor group and the URD group (74.8% versus 72.9%, p=0.937 and 71.7% versus 67.0%, p=0.580). Higher incidences of grade 2 to 4 acute GVHD and chronic GVHD were observed in the mother donor group than that in the URD group (43.5% versus 14.0%, p=0.001 and 58.8% versus 37.1%, p=0.013), although incidences of grade 3 to 4 aGVHD were similar between groups (mother donor group: 12%, URD group: 7%, p=0.374). Multivariate analysis indicated increased rates of acute GVHD were associated with mother donor transplantations (HR ratio: 2.049, p=0.017) and chronic GVHD was related to lower dose of CD34 cells infused (HR ration: 1.834, p=0.035) and female to male donations (HR ration: 1.733, p=0.047). The 2-year cumulative incidences of relapse were significantly decreased in the mother-donor group (7.6% versus 20.9%, p=0.036). Incidences of relapse were associated with donor types (URD vs mother donor: HR ratio 2.524, p=0.035) and disease status before transplantation (CR1 vs other: HR ratio 0.201, p=0.001) in multivariate analysis. These two groups were comparable in hematopoietic recovery and TRM (mother donor group: 21.1%, URD group: 11.6%, p=0.173).CONCLUSIONS Our findings suggest that mother donor transplantations could achieve comparable survival to unrelated donor transplantations, and exhibited decreased rates of relapse but increased rates of GVHD under the Beijing Protocol. This study not only shed light on donor selection by using one modality (the Beijing Protocol) to answer the universal question of HIDs versus URDs, but was also of practical significance due to possible shortage of unrelated donors, sibling donors and other suitable HIDs, especially in contemporary China with the one family one kid policy. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Immune Reconstitution and Infection Patterns after Early Alemtuzumab and Reduced Intensity Transplantation for Nonmalignant Disorders in Pediatric Patients

Hematopoietic stem cell transplantation (HSCT) is a therapeutic option for many nonmalignant disorders (NMD) and is curative or prevents disease progression. Reduced-intensity conditioning (RIC) in HSCT for NMD may reduce regimen-related acute toxicities and late complications. Myeloablation is often replaced by immune suppression in RIC regimens to support donor engraftment. The pace of immune reconstitution after immune suppression by RIC regimens is influenced by agents used, donor source, and graft-versus-host disease prophylaxis/treatment. In a multicenter trial (NCT 00920972) of HSCT for NMD, a RIC regimen consisting of alemtuzumab, fludarabine, and melphalan was substituted for myeloablation. Alemtuzumab was administered early (days -21 to -19) to mitigate major lymphodepletion of the incoming graft and the risk of graft rejection. Immune reconstitution and infectious complications were prospectively monitored for 1-year post-HSCT. Seventy-one patients met inclusion criteria for this report and received marrow or peripheral blood stem cell transplants. Immune reconstitution and infections are reported for related donor (RD) and unrelated donor (URD) transplants at 3 time-points (100days, 6 months, and 1 year post-HSCT). Natural killer cell recovery was rapid, and numbers normalized in both cohorts by day +100. Mean CD3, CD4, and CD8 T-lymphocyte numbers normalized by 6 months after RD HSCT and by 1 year in the URD group. CD4 and CD8 T-lymphocyte counts were significantly higher in patients who received RD HSCT at 6 months and at 1 year, respectively, post-HSCT compared with patients who received URD HSCT. The pace of CD19 B-cell recovery was markedly different between RD and URD cohorts. Mean B-cell numbers were normal by day 100 after RD HSCT but took 1 year post-HSCT to normalize in the URD cohort. Despite these differences in immune reconstitution, the timing and nature of infections did not differ between the groups, presumably because of comparable T-lymphocyte recovery. Immune reconstitution occurred at a faster pace than in prior reports using RIC with T-cell depletion. The incidence of infections was similar for both cohorts and occurred most frequently in the first 100days post-HSCT. Viral and fungal infections occurred at a lower incidence in this cohort, with "early" alemtuzumab compared with regimens administering serotherapy in the peritransplantation period. Patients were susceptible to bacterial infections primarily in the first 100days irrespective of donor source and had no increase in mortality from the same. The overall mortality rate from infections was 1.4% at 1 year. Close monitoring and prophylaxis against bacterial infections in the first 100days post-HSCT is necessary but is followed by robust immune reconstitution, especially in the T-cell compartment.

Allocation to Matched Related or Unrelated Donor Results in Similar Clinical Outcomes without Increased Risk of Failure to Proceed to Transplant among Patients with Acute Myeloid Leukemia: A Retrospective Analysis from the Time of Transplant Approval

Clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo-SCT) from unrelated donors (URDs) approach those of matched related donor (MRD) transplants in patients with acute myeloid leukemia (AML). Yet, available data fail to account for differences in pretransplantation outcomes between these donor selection strategies. In this regard, URD allo-HSCT is associated with longer waiting times to transplantation, potentially resulting in higher probabilities of failure to reach transplant. We retrospectively analyzed 108 AML patients accepted for first allo-HSCT from the time of approval to proceed to transplant. Fifty-eight (54%) patients were initially allocated to MRD, while URD search was initiated in 50 (46%) patients. Time to transplant was longer in patients allocated to a URD when compared with patients assigned to an MRD (median 142 days versus 100 days; p < .001). Forty-three of 58 (74%) patients in the MRD group and 35 of 50 (70%) patients in the URD group underwent transplantation (odds ratio [OR], 1.22; p = .63). Advanced disease status at the time of allo-HSCT approval was the only predictor of failure to reach transplantation in the multivariate analysis (OR, 4.78; p = .001). Disease progression was the most common cause of failure to reach allo-HSCT (66.7%) in both the MRD and URD groups. With a median follow-up from transplantation of 14.5 (interquartile range, 5 to 29) months, the 2-year estimate of overall survival (OS) from allo-HSCT was 46% in the MRD group and 57% in the URD group (p = .54). There were no differences in OS according to donor type allocation in the multivariate analysis (hazard ratio, 1.01; p = .83). When including patients from the time of transplant approval, 2-year OS was 39% in the MRD group versus 42% in the URD group. Our study suggests that allocation of AML patients to URDs may result in comparable clinical outcomes to MRD assignment without a significant increase in the risk of failure to reach transplant.