Allogeneic haematopoietic stem cell transplantation for adult T-lymphoblastic lymphoma: A real-world multicentre analysis in China.

In this multicentre, real-world study, we aimed to identify the clinical outcomes and safety of allogeneic haematopoietic stem cell transplantation (allo-HSCT) in T-lymphoblastic lymphoma (T-LBL). A total of 130 Ann Arbor stage III or IV T-LBL patients (>16 years) treated with allo-HSCT across five transplant centres were enrolled. The 2-year cumulative incidence of disease progression, the probabilities of progression-free survival (PFS), overall survival (OS) and non-relapse mortality (NRM) after allo-HSCT were 21.0%, 69.8%, 79.5% and 9.2% respectively. Patients with central nervous system (CNS) involvement had a higher cumulative incidence of disease progression compared with those without CNS involvement (57.1% vs. 18.9%, HR 3.78, p = 0.014). Patients receiving allo-HSCT in non-remission (NR) had a poorer PFS compared with those receiving allo-HSCT in complete remission (CR) or partial remission (49.2% vs. 72.7%, HR 2.21, p = 0.041). Particularly for patients with bone marrow involvement and achieving CR before allo-HSCT, measurable residual disease (MRD) positivity before allo-HSCT was associated with a poorer PFS compared with MRD negativity (62.7% vs. 86.8%, HR 1.94, p = 0.036). On multivariate analysis, CNS involvement at diagnosis and receiving allo-HSCT in NR were associated with disease progression. Thus, our real-world data suggested that allo-HSCT appeared to be an effective therapy for adult T-LBL patients with Ann Arbor stage III or IV disease.

Peripheral blood stem cell transplantation from haploidentical related donor could achieve satisfactory clinical outcomes for intermediate- or high-risk adult acute myeloid leukemia patients.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most important curative method for intermediate- and high-risk adult acute myeloid leukemia (AML) patients. We aimed to identify the clinical outcomes of haploidentical related donor (HID) peripheral blood stem cell transplantation (PBSCT) who receiving peripheral blood (G-PB) harvest, and the patients receiving bone marrow (BM) plus G-PB harvest (BM + PB) as grafts were enrolled as control. The engraftments of neutrophil and platelet in G-PB group were both faster than those in BM + PB group. The cumulative incidences of grade II-IV acute graft-versus-host disease (aGVHD), and moderate to severe chronic GVHD (cGVHD) were all comparable between G-PB and BM + PB groups. The cumulative incidence of relapse and non-relapse mortality at 3 years after HID HSCT was 12.6% versus 13.7% (p = 0.899) and 3.6% versus 7.3% (p = 0.295), respectively, in G-PB and BM + PB group. While the probabilities of GVHD-free/relapse-free survival, leukemia-free survival, and overall survival at 3 years after HID HSCT were 60.6% versus 53.4% (p = 0.333), 83.8% versus 79.0% (p = 0.603), and were 87.3% versus 82.9% (p = 0.670), respectively. We confirmed the safety and efficacy of HID PBSCT in intermediate- and high-risk AML patients in a large cohort.

A Scoring System for Predicting the Prognosis of Late-Onset Severe Pneumonia after Allogeneic Hematopoietic Stem Cell Transplantation.

Late-onset severe pneumonia (LOSP) is defined as severe pneumonia developing during the late phase of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Because of the high mortality in patients with LOSP, it is important to identify prognostic factors. In this study, we aimed to develop a risk score system with broad applicability that can help predict the risk of LOSP-associated mortality. We retrospectively analyzed 100 patients with LOSP after allo-HSCT between June 2009 and July 2017. The assessment variables included immune, nutritional, and metabolic parameters at the onset of LOSP. Of these 100 patients, 45 (45%) eventually died, and 55 (55%) were positive for organisms, most commonly viruses. In the multivariate analysis, higher monocyte count (≥0.20 × 109/L versus <0.20 × 109/L; P = .001), higher albumin level (≥30.5 g/L versus <30.5 g/L; P = .044), lower lactic dehydrogenase level (<250 U/L versus ≥250 U/L; P = .008) and lower blood urea nitrogen concentration (<7.2 mmol/L versus ≥7.2 mmol/L; P = .026) at the onset of LOSP were significantly associated with better 60-day survival. A risk score system based on the foregoing results showed that the probability of 60-day survival decreased with increasing risk factors, from 96.3% in the low-risk group to 49.1% in the intermediate-risk group and 12.5% in the high-risk group. Our results indicate that this scoring system using 4 variables can stratify patients with different probabilities of survival after LOSP, which suggests that patients' immune, nutritional, and metabolic status are crucial factors in determining outcome.

A risk score system for stratifying the risk of relapse in B cell acute lymphocytic leukemia patients after allogenic stem cell transplantation.

BACKGROUND: For patients with B cell acute lymphocytic leukemia (B-ALL) who underwent allogeneic stem cell transplantation (allo-SCT), many variables have been demonstrated to be associated with leukemia relapse. In this study, we attempted to establish a risk score system to predict transplant outcomes more precisely in patients with B-ALL after allo-SCT. METHODS: A total of 477 patients with B-ALL who underwent allo-SCT at Peking University People's Hospital from December 2010 to December 2015 were enrolled in this retrospective study. We aimed to evaluate the factors associated with transplant outcomes after allo-SCT, and establish a risk score to identify patients with different probabilities of relapse. The univariate and multivariate analyses were performed with the Cox proportional hazards model with time-dependent variables. RESULTS: All patients achieved neutrophil engraftment, and 95.4% of patients achieved platelet engraftment. The 5-year cumulative incidence of relapse (CIR), overall survival (OS), leukemia-free survival (LFS), and non-relapse mortality were 20.7%, 70.4%, 65.6%, and 13.9%, respectively. Multivariate analysis showed that patients with positive post-transplantation minimal residual disease (MRD), transplanted beyond the first complete remission (≥CR2), and without chronic graft-versus-host disease (cGVHD) had higher CIR (P  < 0.001, P = 0.004, and P  < 0.001, respectively) and worse LFS (P  < 0.001, P = 0.017, and P  < 0.001, respectively), and OS (P  < 0.001, P = 0.009, and P  < 0.001, respectively) than patients without MRD after transplantation, transplanted in CR1, and with cGVHD. A risk score for predicting relapse was formulated with the three above variables. The 5-year relapse rates were 6.3%, 16.6%, 55.9%, and 81.8% for patients with scores of 0, 1, 2, and 3 (P  < 0.001), respectively, while the 5-year LFS and OS values decreased with increasing risk score. CONCLUSION: This new risk score system might stratify patients with different risks of relapse, which could guide treatment.

Th2 polarization in target organs is involved in the alleviation of pathological damage mediated by transplanting granulocyte colony-stimulating factor-primed donor T cells.

Acute graft-versus-host disease (aGVHD) is caused by allo-activated donor T cells infiltrating target organs. As a regulator of immune function, granulocyte colony-stimulating factor (G-CSF) has been demonstrated to relieve the aGVHD reaction. However, the role of G-CSF-primed donor T cells in specific target organs is still unknown. In this study, we employed a classical MHC-mismatched transplantation mouse model (C57BL/6 into BALB/c) and found that recipient mice transplanted with G-CSF-primed T cells exhibited prolonged survival compared with that of the PBS-treated group. This protective function against GVHD mediated by G-CSF-primed donor T cells was further confirmed by decreased clinical and pathological scores in this aGVHD mouse model, especially in the lung and gut. Moreover, we found that T cells polarized towards Th2 cells and regulatory T cells were increased in specific target organs. In addition, G-CSF treatment inhibited inducible co-stimulator (ICOS) expression and increased the expression of tolerance-related genes in recipient mice. Our study provides new insight into the immune regulatory effects of G-CSF on T cell-mediated aGVHD, especially for its precise regulation in GVHD target organs.

Prevalence and risk factors of having antibodies to class I and II human leukocyte antigens in older haploidentical allograft candidates.

The effect of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) has been recognized as a factor in graft failure (GF) in patients who underwent umbilical cord blood transplantation (UBT), matched unrelated donor transplantation (MUDT), or haploidentical stem cell transplantation (haplo-SCT). Presently, we know little about the prevalence of and risk factors for having anti-HLA antibodies among older transplant candidates. Therefore, we analyzed 273 older patients with hematologic disease who were waiting for haplo-SCT. Among all patients, 73 (26.7%) patients had a positive panel-reactive antibody (PRA) result for class I, 38 (13.9%) for class II, and 32 (11.7%) for both. Multivariate analysis showed that females were at a higher risk for having a PRA result for class II (P = 0.001) and for having antibodies against HLA-C and HLA-DQ. Prior pregnancy was a risk factor for having a PRA result for class I (P < 0.001) and for having antibodies against HLA-A, HLA-B and HLA-DQ. Platelet transfusions were risk factors for the following: having a positive PRA result for class I (P = 0.014) and class II (P < 0.001); having antibodies against HLA-A, HLA-B, HLA-C, HLA-DP, HLA-DQ, and HLA-DR; and having higher mean fluorescence intensity (MFI) of PRA for class I (P = 0.042). In addition, previous total transfusions were at high risk for having higher numbers of antibodies to specific HLA loci (P = 0.005), and disease course (7.5 months or more) (P = 0.020) were related to higher MFI of PRAs for class I. Our findings indicated that female sex, prior pregnancy, platelet transfusions and disease courses are independent risk factors for older patients with hematologic disease for having anti-HLA antibodies, which could guide anti-HLA antibody monitoring and be helpful for donor selection.

Relationship of Cell Compositions in Allografts with Outcomes after Haploidentical Transplantation for Acquired Severe Aplastic Anemia: Effects of CD34+ and CD14+ Cell Doses.

BACKGROUND: The dose of certain cell types in allografts affects engraftment kinetics and clinical outcomes after allogeneic stem cell transplantation (SCT). Hence, the present study investigated the association of cell compositions in allografts with outcomes after unmanipulated haploidentical SCT (haplo-SCT) for patients with acquired severe aplastic anemia (SAA). METHODS: A total of 131 patients with SAA who underwent haplo-SCT were retrospectively enrolled. Cell subsets in allografts were determined using flow cytometry. To analyze the association of cellular compositions and outcomes, Mann-Whitney U nonparametric tests were conducted for patient age, sex, weight, human leukocyte antigen mismatched loci, ABO-matched status, patient ABO blood type, donor-recipient sex match, donor-recipient relationship, and each graft component. Multivariate analysis was performed using logistic regression to determine independent influence factors involving dichotomous variables selected from the univariate analysis. RESULTS: A total of 126 patients (97.7%) achieved neutrophil engraftment, and 121 patients (95.7%) achieved platelet engraftment. At 100 days after transplantation, the cumulative incidence of II-IV acute graft-versus-host disease (GVHD) was 32.6%. After a median follow-up of 842 (range: 124-4110) days for surviving patients, the cumulative incidence of total chronic GVHD at 3 years after transplantation was 33.7%. The probability of overall survival at 3 years was 83.0%. Multivariate analysis showed that higher total doses of CD14+ (P = 0.018) and CD34+ cells (P < 0.001) were associated with a successful platelet engraftment. A successful platelet was associated with superior survival (P < 0.001). No correlation of other cell components with outcomes was observed. CONCLUSIONS: These results provide evidence and explain that higher doses of CD34+ and CD14+ cells in haploidentical allografts positively affect platelet engraftment, contributing to superior survival for patients with SAA.

Prevalence and risk factors of antibodies to human leukocyte antigens in haploidentical stem cell transplantation candidates: A multi-center study.

We investigated the prevalence of and risk factors for antibodies to HLA in 1663 haploidentical transplant candidates. Among these cases, 349 (21.0%) showed positive panel-reactive antibody (PRA) either for class I or class II HLA. Multivariate analysis showed the following: i) risk factors associated with the prevalence of PRA either for class I or class II HLA were female gender (P = 0.018), prior transfusions (P < 0.001) or pregnancy (P < 0.001), and cases with MDS (P = 0.018); compared to other patients, subjects with ALL had a lower prevalence of class I antibodies (P = 0.017); and ii) risk factors associated with the prevalence of PRA both for class I and class II HLA were female gender (P = 0.014), prior transfusions (P = 0.003), previous pregnancy (P < 0.001), and diagnosis with MDS (P = 0.035). The percentages of antibodies against different antigens coded by the different HLA loci, including HLA-A, -B, -C, -DP, -DQ, and -DR, among all cases were 15.6%, 17.3%, 10.5%, 5.6%, 8.5%, and 9.7%, respectively. Risk factors associated with specific antibodies against HLA-A, -B, -C, -DP, -DQ, and -DR were female gender, prior transfusion, previous pregnancy, and underlying disease. Our findings suggest that gender, prior pregnancy, transfusion and underlying diseases are risk factors for HLA sensitization, which could guide HLA antibody monitor and donor selection.