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Cytomegalovirus (CMV) infection and acute graft-versus-host disease (aGVHD) are two major complications that contribute to a poor prognosis after hematopoietic stem cell transplantation (HSCT). Superior early immune reconstitution (IR) is associated with improved survival after HSCT. However, when all three factors, CMV infection, aGVHD, and IR, are concomitantly considered, the effects of the triple events on HSCT are still unknown and should be studied further. Thus we enrolled 185 patients who were diagnosed as hematological malignancies and treated with HLA-matched sibling transplantation (MST) between January 2010 and December 2014, of whom 83 were positive for CMV infection and 82 had aGVHD. Results showed that patients with both aGVHD and CMV infection had significantly higher non-relapse mortality (NRM), lower overall survival (OS), and delayed CD8+ T-cell IR. Multivariate analyses showed that both aGVHD combined with CMV infection and delayed CD8+ T-cell IR were independent risk factors for prognosis post-MST. Recurrent CMV infections are associated with poor CD8+ T-cell reconstitution. However, superior IR could protect against the negative effects of aGVHD and CMV infection on the transplant outcomes. Co-occurrence of aGVHD and CMV infection significantly affect the outcomes of HLA-matched sibling hematopoietic stem cell transplantation. However, superior immune reconstitution (IR) could protect against the negative effects of aGVHD and CMV infection (double positive, DP) on the transplant outcomes. [ABSTRACT FROM AUTHOR]

To explore the incidence, risk factors, and outcomes of central nervous system (CNS) relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute lymphoblastic leukemia (ALL) and to compare the differences in CNS relapse between haploidentical donor HSCT (HID-HSCT) and HLA-identical sibling donor HSCT (ISD-HSCT). We performed a retrospective nested case-control study on patients with CNS relapse after allo-HSCT. The cumulative incidence of CNS relapse was 4.06% after allo-HSCT in ALL, with a significantly poor prognosis. The incidence was 3.91% and 5.36% in HID-HSCT and ISD-HSCT, respectively (p = .227). Among the patients with CNS relapse, the overall survival (OS) at 3 years was 56.2 ± 6.8% in the HID-HSCT subgroup and 76.9 ± 10.2% in the ISD-HSCT subgroup (p = .176). The 3-year cumulative incidence of systemic relapse was also comparable between the two subgroups (HID-HSCT, 40.6 ± 7.4%; ISD-HSCT, 13.3 ± 8.7%, respectively, p = .085). Younger age (p = .045), T-ALL (p = .035), hyperleukocytosis at diagnosis (p < .001), advanced disease stage at transplant (p < .001), pre-HSCT CNS involvement (p < .001), and absence of chronic graft vs host disease (cGVHD) (p < .001) were independent risk factors for CNS relapse after allo-HSCT. In conclusion, CNS relapse was a significant complication after allo-HSCT in ALL and was associated with poor prognosis. The incidences and outcomes were comparable between HID-HSCT and ISD-HSCT. [ABSTRACT FROM AUTHOR]

This retrospective multicenter cohort study aimed to compare the outcome of haploidentical hematopoietic stem cell transplantation (HID‐HSCT) with matched sibling donor (MSD) and unrelated donor (URD) transplantation in severe aplastic anemia (SAA) patients 40 years of age and older. With a median follow‐up time of 17.6 months, 85 consecutive patients were enrolled in the study, and the median patient age was 45 years (40, 58). The cumulative engraftment rates of neutrophil and platelet were 98.8 ± 0.0% and 92.9 ± 0.1%. The cumulative incidences of Grade 2‐4 acute graft‐versus‐host disease (aGvHD) and chronic graft‐versus‐host disease (cGvHD) at 3 years were 14.1 ± 0.1% and 17.3 ± 0.2%. The 3‐year estimated overall survival (OS) and failure‐free survival (FFS) were 91.2 ± 3.2% and 89.7 ± 3.5%. In multivariate analysis, the only factor associated with inferior survival was an ECOG score ≥2. HID‐HSCT was associated with a higher incidence of GvHD, but the difference of 3‐year estimated OS between HID group and the other two cohorts was not significant (86.7 ± 6.4% for HID vs 92.1% ± 4.4% for MSD and 100% for URD, P =.481). HID‐HSCT might be a feasible alternative option for selected SAA patients aged 40 years and older without a matched donor. [ABSTRACT FROM AUTHOR]

Abstract A key issue in the haploiedntical hematopoietic stem cell transplantation (haplo-HSCT) setting is the search for the best donor, because donor selection can significantly impact the clinical outcomes. We aimed to identify the role of collateral related donors (CRDs) in donor selection for haplo-HSCT through comparing the clinical outcomes between CRDs (n = 60) and maternal donors (MDs, n = 296), which were the last choice of donor selection in immediate related donors (IRDs). The cumulative incidence of graft-versus-host disease was comparable between CRDs and MDs. The 5-year cumulative incidence of relapse and non-relapse mortality was 22.0% (95% CI, 11.3%–32.7%) versus 17.4% (95% CI, 13.0%–21.8%) (P = 0.455) and 25.0% (95% CI, 13.9%–36.1%) versus 23.1% (95% CI, 18.2%–28.0%) (P = 0.721) for the CRDs and MDs, respectively. The 5-year probabilities of disease-free survival and overall survival was 53.2% (95% CI, 40.4%–66.0%) versus 59.5% (95% CI, 53.8%–65.2%) (P = 0.406) and 56.5% (95% CI, 43.8%–69.2%) versus 61.8% (95% CI, 56.1%–67.5%) (P = 0.458) for the CRDs and MDs, respectively. Female donor/male recipient (FDMR) CRDs were associated with the poorest clinical outcomes, and the clinical outcomes of non-FDMR CRDs were comparable to those of MDs. In summary, our results showed that CRDs did not showed superiority over MDs. Thus, IRDs should be the first choice of donor selection, and CRDs could only be the donors for those without IRDs. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To explore the possible risk factors for the occurrence and mortality of thrombotic microangiopathy (TMA) with concomitant acute graft‐vs‐host disease (aGVHD) and to investigate outcomes and treatments of this disorder after allo‐HSCT. Methods: Fifty cases diagnosed with TMA with concomitant aGVHD and 150 controls were identified from a cohort composed of 3992 patients who underwent allo‐HSCT from 2008 to 2016. Results: Grade III‐IV aGVHD (P = .000), acute kidney injury (AKI) (P = .033), and hypertension (P = .028) were significant independent risk factors associated with the occurrence of TMA with concomitant aGVHD. A haptoglobin level below normal (P = .013), a maximum volume of diarrhea >2500 mL/d (P = .015), and bloody diarrhea (P = .049) were significant markers for death in both univariate and multivariate analyses. Patients diagnosed with TMA with concomitant aGVHD had a lower overall survival (OS), a higher non‐relapse mortality (NRM), but a lower risk of relapse. Conclusions: Thrombotic microangiopathy with concomitant aGVHD is a significant complication after allo‐HSCT, with a worse outcome, including significantly lower OS and higher NRM. There are specific risk factors associated with occurrence and mortality of this complication. [ABSTRACT FROM AUTHOR]

Objective To retrospectively identify characteristics and risk factors of viral encephalitis ( VE) in patients who underwent a haplo-identical hematopoietic stem cell transplant ( HSCT). Methods A nested case-control study was designed. Cases with VE and controls were identified from a cohort composed of 1274 patients who underwent a haplo-identical HSCT from 2012 to 2015. Results VE was identified in 30 patients (2.4%). The median time from HSCT to diagnosis was 144.5 days. The viruses detected included RSV-B (43.3%), BKV (23.3%), more than one virus (10%), cytomegalovirus ( CMV) (6.7%), RSV-A (6.7%), HSV (3.3%), HHV-6 (3.3%), and CVB3 (3.3%). Alterations of consciousness and seizures were the most frequently presented symptoms. Neuroimaging detected abnormalities in 19 (76%) patients. The cerebral spinal fluid cell count, protein, and glucose concentration were elevated in eight (26.7%), 18(60%), and nine (30%) patients, respectively. The treatment efficacy and prognoses varied considerably based on the different causative viruses. Multivariate analyses revealed that acute graft-versus-host disease (grade III- IV), CMV viremia, and engraftment syndrome were significantly and independently associated with VE. The cumulative mortality rate was significantly higher in patients suffering from VE than in the controls. Conclusion Characteristics, such as onset time, response to treatment, and outcome, varied based on the different causative viruses. [ABSTRACT FROM AUTHOR]

We determined the incidence, clinical manifestations, and outcomes of engraftment syndrome ( ES) in haploidentical stem cell transplantation ( SCT) recipients. We compared the incidence of ES between the patient group that received haploidentical SCT ( n = 516) and the patient group that received HLA-identical sibling SCT ( n = 393). The transplantations were performed in the Peking University People's Hospital in the period between October 2001 and October 2012. The ES incidence data were collected retrospectively. Patients that presented non-infectious fever or skin rash within the 24-h window before or after the beginning of neutrophil recovery were diagnosed with ES in accordance with the Maiolino criteria. ES incidence in haploidentical SCT recipients (21.9%) was significantly higher than that in HLA-identical sibling SCT recipients (2.0%; P < 0.001). Major symptoms included fever (119/121, 98.3%), skin rash (98/121, 81.0%), and diarrhea (51/121, 42.1%), with the median time of +10 d (range: 6-20 d). The median C-reactive protein level of the ES group (99.0 mg/L; n = 13) was significantly higher than that of the non- ES group (13.9 mg/L; n = 38; P < 0.001). Similarly, the results showed that the median C3 plasma concentration of the ES group (1.30 g/L) was higher than that of the non- ES group (1.16 g/L, P = 0.003). ES was not associated with non-relapse mortality or overall survival. High incidence of ES was observed in haploidentical SCT recipients; however, ES did not predict poor clinical outcomes. [ABSTRACT FROM AUTHOR]

The clinical significance and prognostic impact of IRFR in pediatric recipients of haploidentical SCT are not clearly understood. Therefore, we attempted to determine how IRFR affects clinical outcomes in children. Clinical data from 100 consecutive pediatric patients (60 boys and 40 girls; median age, 12 yr [range, 2-18 yr] after haploidentical SCT between January 2010 and December 2012 were collected retrospectively. IRFR was described as unexplained fever (>38 °C) within 24 h after the infusion of haploidentical PBSCs. Thirty-eight (38.0%) cases met the criteria for IRFR. ES was found in 24 (63.2%) of the 38 children with IRFR, with the median time of developing ES of +9 (7-16) days, while only 15 (25.4%) of the 59 children without IRFR were found with ES (p < 0.001). Similarly, the cumulative incidence rates of grade II-IV aGVHD were 50.0% in the IRFR group and 29.3% (p = 0.012) in the non-febrile group. Multivariate analysis identified IRFR as the risk factor for ES and aGVHD. In the haploidentical setting, IRFR is associated with the development of ES and aGVHD. We attempted to determine how IRFR affects clinical outcomes in children after haploidentical SCT. Thirty-eight children comprised the IRFR group, and 59 were in the control (non-IRFR) group. High incidence of ES was observed in children with the occurrence of IRFR. Similarly, the incidence of stage I-IV and II-IV aGVHD was significantly higher in the febrile group. Multivariate analysis showed IRFR to be the risk factor for ES and aGVHD. [ABSTRACT FROM AUTHOR]

Membranous nephropathy (MN) is a rare complication that can occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT). MN patients may develop nephrotic syndrome or even kidney failure, which greatly affects their quality of life and prognosis. However, current knowledge regarding MN after allo-HSCT is limited. Thus, a multicenter nested case‒control study was conducted. Patients who had been diagnosed with MN after allo-HSCT were retrospectively identified at 8 HSCT centers. A total of 51 patients with MN after allo-HSCT were included. The median age of MN patients after allo-HSCT was 38 years, and the median duration from HSCT to MN was 18 months. The use of HLA-matched donors (P = 0.0102) and peripheral blood as the graft source (P = 0.0060) were identified as independent predisposing risk factors for the onset of MN after allo-HSCT. Compared to those in the control group, the incidence of extensive chronic graft-versus-host disease was greater in the MN patients (P = 0.0002). A total of 31 patients developed nephrotic syndrome. Patients receiving combination treatments of corticosteroids and immunosuppressants appeared to have better outcomes. In conclusion, MN is a rare but occasionally severe complication following HSCT and may require active treatment. [ABSTRACT FROM AUTHOR]

Background: Haploidentical transplantation has been proposed as an effective treatment for severe aplastic anemia (SAA). The majority of patients have more than one HLA-haploidentical donor. Herein, we compared the outcomes between different donor-recipient relationships for optimal haploidentical donor selection in acquired SAA. Methods: We conducted a multicenter study based on a registered database of 392 patients with SAA treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) between 2006 and 2018. In total, 223 patients received grafts from father donors, 47 from mother donors, 91 from siblings, 29 from children, and 2 from collateral donors. Results: Of the 381 patients who survived more than 28 days, 379 (99.5%) recipients were engrafted. The 2-year overall survival (OS) was 86.6 ± 2.5%, 87.1 ± 4.9%, 84.3 ± 3.9%, and 92.2 ± 5.1% for recipients of father, mother, sibling, and child grafts, respectively, (P = 0.706). The 2-year failure-free survival (FFS) was 82.8 ± 2.7%, 86.7 ± 5.1%, 80.8 ± 4.2%, and 92.5 ± 5.1% for recipients of father, mother, sibling, and child grafts, respectively, (P = 0.508). There was no difference in the incidence of either acute or chronic graft-versus-host disease (GVHD) among the different donor sources in multivariate analyses. There were also no differences in the OS or FFS among the different donor sources in the Cox regression analysis. However, OS was significantly better in the patients with a shorter history of aplastic anemia (< 12 months), better performance status (ECOG scores 0–1), or moderate graft mononuclear cell (MNC) counts (6–10 × 108/kg), and in female recipients with male donors. The FFS was also higher in patients with a shorter history of aplastic anemia (< 12 months) and better performance status (ECOG scores 0–1). Conclusions: Fathers, mothers, siblings, and children are all suitable haploidentical donors for patients with SAA. [ABSTRACT FROM AUTHOR]

• We report the incidence of acute pancreatitis (AP) after allo-HSCT. • We identify younger age, grades II to IV aGVHD, a history of DLI, and pre-existing gallstones as independent risk factors of post-transplant AP. • We describe the outcomes of patients with post-transplant AP. • We establish an exploratory risk score model to help risk stratification in such patients. Acute pancreatitis (AP) has been recognized as an uncommon yet potentially lethal complication after hematopoietic stem cell transplant (HSCT). This retrospective, nested, case-control study reviewed data from 5284 consecutive patients who underwent allogeneic (allo)-HSCT between 2009 and 2018 at a single center, identifying 40 patients (0.76%) with AP after allo-HSCT. The diagnosis and severity of AP were established and classified according to existing criteria. Younger age (P =.008), grades II to IV acute graft-versus-host disease (P =.010), a history of donor lymphocyte infusion (P =.033), and pre-existing gallstones (P =.003) were independent risk factors of AP after allo-HSCT. Post-transplant AP had a trend to negatively influence overall survival (OS) and nonrelapse mortality (NRM) (P =.063) for allo-HSCT recipients, but no significant difference was found. Patients with moderately severe and severe AP had significantly lower OS (P =.002) and higher NRM (P =.000) than other patients. Based on these findings, a risk score model was also established to predict the occurrence of AP. Our risk score model performed well in terms of discrimination when applied to derivation samples. Patients were classified into a low-risk group (0 to 1 point), a medium-risk group (2 to 3 points), and a high-risk group (4 points or more). Significant difference was observed in AP incidence among the 3 groups. The predictive tool explored by our study might contribute to target high-risk patients and guide personalized AP prevention in allo-HSCT recipients. [ABSTRACT FROM AUTHOR]

• The incidence of immune-mediated neuropathies (IMN) following haploidentical hematopoietic stem cell transplantation was reported. • Cytomegalovirus viremia and chronic graft-versus-host disease were identified as independent risk factors of post-transplant IMN. •T The outcomes of patients with post-transplant IMN were described. Immune-mediated neuropathies (IMNs) following hematopoietic stem cell transplantation have been described recently, which, excluding Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy, may present with atypical patterns. This retrospective, nested, case-control study reviewed data from 3858 patients who received haploidentical hematopoietic stem cell transplantation (haplo-HSCT) during the past 10 years at a single center, and 40 patients (1.04%) with IMN following haplo-HSCT were identified. Chronic graft-versus-host disease (cGVHD) (P =.043) and cytomegalovirus (CMV) viremia (P =.035) were recognized as independent risk factors for the development of IMN after haplo-HSCT. There were no significant differences in overall survival (P =.619), disease-free survival (P =.609), nonrelapse mortality (P =.87), or the incidence of relapse (P =.583) between patients with and without IMN after haplo-HSCT. However, patients with post-transplant IMN were at higher risk of developing cGVHD (P =.012) than patients who did not develop IMN. Twenty-four of the 40 patients with IMN (60%) attained neurologic improvement after treatments including vitamins B 1 and B 12 and/or immunomodulatory agents. However, 19 (47.5%) patients still had persistent motor/sensory deficits despite receiving timely treatment. More studies are needed to help develop standardized diagnostic and therapeutic strategies for patients with post-transplant IMN. [ABSTRACT FROM AUTHOR]

Poor graft function (PGF) is a severe complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The question of whether the bone marrow (BM) immune microenvironment is involved in the pathogenesis of PGF remains unresolved. In total, 10 patients with PGF, 30 matched patients with good graft function after allo-HSCT, and 15 healthy donors were enrolled in this nested case-control study. The Th1, Th2, Tc1, Tc2, and active phenotypes were analyzed by flow cytometry. IFN-γ and IL-4 levels in BM plasma were evaluated using cytometric beads assay. Relative to other subjects, patients with PGF had significantly higher proportions of stimulated CD4 + and CD8 + T cells that produced IFN-γ (Th1 and Tc1 cells) but notably decreased proportions of IL-4-producing T cells (Th2 and Tc2 cells), resulting in a shift of the IFN-γ/IL-4 ratio towards a type 1 response and an elevated percentage of activated CD8 + T cells. Changes in IFN-γ and IL-4 levels in BM plasma were consistent with the cellular results. Our results suggest that dysregulated T cell responses may contribute to the occurrence of PGF after HSCT. [ABSTRACT FROM AUTHOR]