Mini-dose methotrexate combined with methylprednisolone for the initial treatment of acute GVHD: a multicentre, randomized trial.

BACKGROUND: There is an urgent unmet need for effective initial treatment for acute graft-versus-host disease (aGVHD) adding to the standard first-line therapy with corticosteroids after allogeneic haematopoietic stem cell transplantation (allo-HSCT). METHODS: We performed a multicentre, open-label, randomized, phase 3 study. Eligible patients (aged 15 years or older, had received allo-HSCT for a haematological malignancy, developed aGVHD, and received no previous therapies for aGVHD) were randomly assigned (1:1) to receive either 5 mg/m2 MTX on Days 1, 3, or 8 and then combined with corticosteroids or corticosteroids alone weekly. RESULTS: The primary endpoint was the overall response rate (ORR) on Day 10. A total of 157 patients were randomly assigned to receive either MTX plus corticosteroids (n = 78; MTX group) or corticosteroids alone (n = 79; control group). The Day 10 ORR was 97% for the MTX group and 81% for the control group (p = .005). Among patients with mild aGVHD, the Day 10 ORR was 100% for the MTX group and 86% for the control group (p = .001). The 1-year estimated failure-free survival was 69% for the MTX group and 41% for the control group (p = .002). There were no differences in treatment-related adverse events between the two groups. CONCLUSIONS: In conclusion, mini-dose MTX combined with corticosteroids can significantly improve the ORR in patients with aGVHD and is well tolerated, although it did not achieve the prespecified 20% improvement with the addition of MTX. TRIAL REGISTRATION: The trial was registered with clinicaltrials.gov (NCT04960644).

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.

Salvage haploidentical transplantation for graft failure after first haploidentical allogeneic stem cell transplantation: an updated experience.

Graft failure is a fatal complication following allogeneic stem cell transplantation where a second transplantation is usually required for salvage. However, there are no recommended regimens for second transplantations for graft failure, especially in the haploidentical transplant setting. We recently reported encouraging outcomes using a novel method (haploidentical transplantation from a different donor after conditioning with fludarabine and cyclophosphamide). Herein, we report updated outcomes in 30 patients using this method. The median time of the second transplantation was 96.5 (33-215) days after the first transplantation. Except for one patient who died at +19d and before engraftment, neutrophil engraftments were achieved in all patients at 11 (8-24) days, while platelet engraftments were achieved in 22 (75.8%) patients at 17.5 (9-140) days. The 1-year OS and DFS were 60% and 53.3%, and CIR and TRM was 6.7% and 33.3%, respectively. Compared with the historical group, neutrophil engraftment (100% versus 58.5%, p < 0.001) and platelet engraftment (75.8% versus 32.3%, p < 0.001) were better in the novel regimen group, and OS was also improved (60.0% versus 26.4%, p = 0.011). In conclusion, salvage haploidentical transplantation from a different donor using the novel regimen represents a promising option to rescue patients with graft failure after the first haploidentical transplantation.

Decreasing the steroid rapidly may help to improve the clinical outcomes of patients with intestinal steroid-refractory acute graft-versus-host disease receiving basiliximab treatment.

Intestinal steroid refractory acute graft-versus-host disease (SR-aGVHD) is the major cause of mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT). This retrospective cohort study aimed to identify the relationship between different steroid decreasing velocity and therapeutic response in patients with intestinal SR-aGVHD receiving basiliximab treatment, and also aimed to propose a reasonable steroid decreasing regimen for these patients. The median time for steroid dose decreasing to the 50% of initial dose and decreasing to the low-dose steroid for patients achieving ORR was 5 days and 12 days, respectively, which was both shorter than patients without achieving ORR. The ORR, NRM and survival in rapid and medium steroid decreasing group were all better than slow group. The cumulative incidence of ORR at any time was 90.4%, 78.1% and 62.3%, respectively, in rapid, medium, and slow group. The cumulative incidence of NRM at 1 year after basiliximab treatment was 18.7% (95% CI 11.3%-26.1%), 22.8% (95% CI 14.2%-31.4%) and 32.8% (95% CI 24.1%-41.5%), respectively, in rapid, medium, and slow group. The probability of OS at 1 year after basiliximab treatment was 76.9% (95% CI 68.9%-84.9%), 72.7% (95% CI 63.7%-81.7%), and 62.3% (95% CI 53.5%-71.1%), respectively, in rapid, medium, and slow group. Hence, it was helpful to decrease steroid to the 50% of initial dose ≤ 5 days and to the low-dose steroid ≤ 12 days after basiliximab treatment for intestinal SR-aGVHD patients, which may also be the reasonable steroid decrease protocol for these patients.

Pregnancy and neonatal outcomes in 25 pregnant women diagnosed with new-onset acute myeloid leukemia during pregnancy.

PURPOSE: The aim was to analyze the pregnancy and neonatal outcomes of pregnant women with new- onset acute myeloid leukemia (AML) diagnosed during pregnancy. METHODS: In this retrospective study 25 pregnant women who were diagnosed with new-onset AML during pregnancy from January 2010 to January 2021 were enrolled. RESULTS: A total of 4, 13 and 8 pregnant women with new-onset AML were diagnosed during the first, second, and third trimesters, respectively. Twelve of the 25 pregnant women underwent therapeutic abortion and 13 gave birth (9 preterm and 4 full-term newborns). The gestational age at initial clinical manifestations (13.4 ± 3.7 vs. 27.7 ± 5.6 weeks, P < 0.01) and diagnosis (16.9 ± 4.4 vs. 29.7 ± 5.5 weeks, P < 0.01) was lower in the pregnant women who underwent therapeutic abortion than in those who gave birth. Eighty-four percent (21/25) of the pregnant women with new-onset AML during pregnancy survived and were in remission and all the newborns were born alive. Three of the 13 newborns were exposed to chemotherapy, but no congenital malformations were observed. Eight newborns were admitted to the neonatal intensive care unit (NICU), and all recovered. The complete blood counts and biochemical examinations of the 8 newborns were normal. CONCLUSIONS: New-onset AML during an earlier stage of pregnancy may increase the risk of poor pregnancy outcomes. The neonatal outcomes of pregnant women with new-onset AML during pregnancy are good with proper treatment.

Clinical characteristics and outcomes of allogeneic hematopoietic stem cell transplantation recipients with coronavirus disease 2019 caused by the Omicron variant: a prospective, observational cohort study.

We aimed to describe the clinical characteristics, particularly the occurrence and risk factors of severe/critical illness, in allogeneic hematopoietic stem cell (allo-HSCT) recipients infected with coronavirus disease 2019 (COVID-19) caused by Omicron variant in an observational prospective study (n = 311). The median time from allo-HSCT to COVID-19 diagnosis was 8.5 months (range 0.8-106.1) months. Four patients (1.3%) were reported to be asymptomatic during Omicron variant infection, and 135 (43.4%) patients showed lower respiratory tract disease. Thirty-four (10.9%) patients were categorized into serious infection (severe illness n = 25; critical illness n = 9) and the median duration from COVID-19 diagnosis to serious infections was 6 days (range, 0-29) days. Thirteen (4.2%) and 6 (1.9%) patients required intensive care unit care and invasive mechanical ventilation, respectively. Receiving more than 1 type of immunosuppressive therapies at COVID-19 diagnosis was associated with severity and persistence of infection. Six patients (1.9%) died after diagnosis of COVID-19 infection. The 4-week probability of overall survival after COVID-19 diagnosis was 98.7%, which was 100% and 88.2% for non-serious and serious infection group (P < 0.001), respectively. Thus, we observed a relatively low serious infection and mortality rate in allo-HSCT recipients infected with COVID-19 caused by Omicron variant.

Mesenchymal stromal cells plus basiliximab improve the response of steroid-refractory acute graft-versus-host disease as a second-line therapy: a multicentre, randomized, controlled trial.

BACKGROUND: For patients with steroid-refractory acute graft-versus-host disease (SR-aGVHD), effective second-line regimens are urgently needed. Mesenchymal stromal cells (MSCs) have been used as salvage regimens for SR-aGVHD in the past. However, clinical trials and an overall understanding of the molecular mechanisms of MSCs combined with basiliximab for SR-aGVHD are limited, especially in haploidentical haemopoietic stem cell transplantation (HID HSCT). METHODS: The primary endpoint of this multicentre, randomized, controlled trial was the 4-week complete response (CR) rate of SR-aGVHD. A total of 130 patients with SR-aGVHD were assigned in a 1:1 randomization schedule to the MSC group (receiving basiliximab plus MSCs) or control group (receiving basiliximab alone) (NCT04738981). RESULTS: Most enrolled patients (96.2%) received HID HSCT. The 4-week CR rate of SR-aGVHD in the MSC group was obviously better than that in the control group (83.1% vs. 55.4%, P = 0.001). However, for the overall response rates at week 4, the two groups were comparable. More patients in the control group used ≥ 6 doses of basiliximab (4.6% vs. 20%, P = 0.008). We collected blood samples from 19 consecutive patients and evaluated MSC-derived immunosuppressive cytokines, including HO1, GAL1, GAL9, TNFIA6, PGE2, PDL1, TGF-ß and HGF. Compared to the levels before MSC infusion, the HO1 (P = 0.0072) and TGF-ß (P = 0.0243) levels increased significantly 1 day after MSC infusion. At 7 days after MSC infusion, the levels of HO1, GAL1, TNFIA6 and TGF-ß tended to increase; however, the differences were not statistically significant. Although the 52-week cumulative incidence of cGVHD in the MSC group was comparable to that in the control group, fewer patients in the MSC group developed cGVHD involving ≥3 organs (14.3% vs. 43.6%, P = 0.006). MSCs were well tolerated, no infusion-related adverse events (AEs) occurred and other AEs were also comparable between the two groups. However, patients with malignant haematological diseases in the MSC group had a higher 52-week disease-free survival rate than those in the control group (84.8% vs. 65.9%, P = 0.031). CONCLUSIONS: For SR-aGVHD after allo-HSCT, especially HID HSCT, the combination of MSCs and basiliximab as the second-line therapy led to significantly better 4-week CR rates than basiliximab alone. The addition of MSCs not only did not increase toxicity but also provided a survival benefit.

A prognostic score system in adult T-cell acute lymphoblastic leukemia after hematopoietic stem cell transplantation.

Adult T-cell acute lymphoblastic leukemia (T-ALL) is highly aggressive with poor prognoses, while hematopoietic stem cell transplantation (HSCT) is a curable option. However, no transplant-specific prognostic model for adult T-ALL is available. We identified 301 adult T-ALL patients who received HSCT at our hospital between 2010 and 2022. These patients were randomly assigned at a 7:3 ratio to a derivation group of 210 patients and a validation group of 91 patients. Next, we developed a prognostic risk score system for adult T-ALL with HSCT, which we named COMM, including 4 predictors (central nervous system involvement, Non-CR1 (CR2+ or NR) at HSCT, minimal residual disease (MRD) ≥ 0.01% after first induction therapy, and MRD ≥ 0.01% before HSCT). Patients were categorized into three risk groups, low-risk (0), intermediate-risk (1-4), and high-risk (5-12), and their 3-year overall survival (OS) were 87.5% (95%CI, 78-93%), 65.7% (95%CI, 53-76%) and 20% (95%CI, 10-20%; P < 0.001), respectively. The area under the subject operating characteristic curve for 2-, 3- or 5-year OS in the derivation cohort and in the validation cohort were all greater than 0.75. Based on internal validation, COMM score system proved to be a reliable prognostic model that could discriminate and calibrate well. We expect that the first prognostic model in adults T-ALL after HSCT can provide a reference of prognostic consultation for patients and families, and also contribute to future research to develop risk adapted interventions for high-risk populations.

Up-front autologous stem cell transplant in peripheral T-cell lymphoma patients achieving complete response after first-line treatment: A multicentre real-world analysis.

We conducted a retrospective, multicentre study to compare consolidation therapy with or without first-line autologous stem cell transplant (ASCT) for peripheral T-cell lymphoma (PTCL) patients in a real-world setting. We enrolled 347 PTCL patients who achieved complete response after first-line treatment. Of these, 257 received consolidation chemotherapy (non-ASCT group) and 90 received ASCT (ASCT group). Clinical outcomes were comparable between ASCT and non-ASCT groups. After propensity score matching, the 2-year cumulative incidence of treatment-related mortality and relapse remained similar between groups (1.9% vs. 2.0%, p = 0.985; 24.7% vs. 47.1%, p = 0.021). However, significant differences emerged in progression-free survival and overall survival probabilities. Within the T-cell lymphoma subgroup, ASCT patients exhibited favourable outcomes compared to non-ASCT patients: 2-year progression-free survival (73.4% vs. 50.8%, p = 0.024) and overall survival (92.1% vs. 73.5%, p = 0.021). Notably, no significant differences were observed for patients with NK/T-cell lymphoma. These real-world data suggest that up-front ASCT is a safe and effective consolidation option for PTCL patients in remission, particularly those with T-cell lymphoma.

Efficacy and safety of letermovir prophylaxis for cytomegalovirus infection after hematopoietic stem cell transplantation.

Letermovir is a specific inhibitor of cytomegalovirus (CMV) terminase complex. Several studies have reported that letermovir can effectively prevent CMV activation after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to identify the efficacy and safety of letermovir prophylaxis for CMV infection after allo-HSCT with a systemic review and meta-analysis. A literature search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. PubMed and Embase databases were searched. A total of 28 studies were included. The incidence of CMV activation at 14 weeks after HSCT was 0.10 (95% confidence interval [CI], 0.06-0.18), which was 0.10 (95% CI, 0.04-0.21) and 0% in adult and children (2 studies were included and both of them were 0%). In addition, the incidence of CMV activation at 14 weeks after allo-HSCT was 0.11 (95% CI, 0.06-0.21) and 0.07 (only 1 study included), respectively, in retrospective and prospective studies. The incidence of CMV activation at 100 and 200 days after HSCT was 0.23 (95% CI, 0.16-0.33) and 0.49 (95% CI, 0.32-0.67), respectively. The incidence of CMV disease at 14 weeks and at 6 months after HSCT was 0.01 (95% CI, 0.01-0.02) and 0.03 (95% CI, 0.01-0.09), respectively. Thus, our systemic review and meta-analysis suggested that letermovir prophylaxis was safe and effective for CMV activation after allo-HSCT.

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.

Clinical risk factors and prognostic model for patients with bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation.

Bronchiolitis obliterans syndrome (BOS) is a common and potentially devastating noninfectious pulmonary complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Currently, predictive tools for BOS are not available. We aimed to identify the clinical risk factors and establish a prognostic model for BOS in patients who undergo allo-HSCT. We retrospectively identified a cohort comprising 195 BOS patients from 6100 consecutive patients who were allografted between 2008 and 2022. The entire cohort was divided into a derivation cohort and a validation cohort based on the time of transplantation. Via multivariable Cox regression methods, declining forced expiratory volume at 1 s (FEV1) to <40%, pneumonia, cGVHD except lung, and respiratory failure were found to be independent risk factors for the 3-year mortality of BOS. A risk score called FACT was constructed based on the regression coefficients. The FACT model had an AUC of 0.863 (95% CI: 0.797-0.928) in internal validation and 0.749 (95% CI: 0.621-0.876) in external validation. The calibration curves showed good agreement between the FACT-predicted probabilities and actual observations. The FACT risk score will help to identify patients at high risk and facilitate future research on developing novel, effective interventions to personalize treatment.

The impact of donor-specific anti-HLA antibody levels on primary poor graft function and graft rejection in rituximab desensitized haploidentical stem cell transplantation.

This study investigates the influence of donor-specific anti-HLA antibodies (DSA) levels on primary poor graft function (PGF) and graft rejection (GR) after haploidentical stem cell transplantation (haplo-SCT) with rituximab desensitization. A total of 155 DSA-positive haplo-SCT candidates with mean fluorescence intensity (MFI) between 2000 and 10,000 were enrolled in this prospective clinical trial. Receiver operating characteristic (ROC) curves determined the optimal DSA MFI cutoff for identifying high-risk patients. Patients were categorized into two groups: DSA low-level group (2000 ≤ DSA MFI < 5000, Group A) and high-level group (5000 ≤ DSA MFI ≤ 10,000, Group B). The incidence of primary PGF was 6.5% (2.6%-10.3%), while GR incidence was 0.6% (0.0%-1.9%). Group A had significantly lower primary PGF rates than Group B (2.3% [0.0%-5.7%] vs. 12.9% [4.8%-21.0%], p = 0.017). Only one patient in Group B experienced GR. High DSA levels (5000 ≤ MFI ≤ 10,000) were identified as the sole independent risk factor for primary PGF and GR after haplo-SCT with rituximab desensitization (HR = 7.282, 95% CI 1.517-34.953, p = 0.013). The 4-year cumulative incidence of relapse, non-relapse mortality, disease-free survival, and overall survival were 14.7% (11.6%-17.8%), 16.3% (13.1%-19.4%), 69.0% (65.9%-76.2%), and 70.6% (66.4%-74.8%), respectively. DSA levels have an impact on efficiency of rituximab desensitization, and a DSA MFI threshold is provided for predicting primary PGF and GR.

Prognostic Factors and Outcomes in Patients With Septic Shock After Allogeneic Hematopoietic Stem Cell Transplantation.

Septic shock remains a potentially life-threatening complication among allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. There is a paucity of information on the clinical characteristics, outcome and prognostic factors of septic shock patients after allo-HSCT. We aimed to describe the clinical characteristics of septic shock after allo-HSCT and its associated health outcomes and to evaluate the role of patient demographics, transplantation-related laboratory and clinical variables associated with the short-term mortality of septic shock after allo-HSCT. We retrospectively studied 242 septic shock patients from 6105 consecutive patients allografted between 2007 and 2021. We assessed 29 risk factors as candidate predictors and used multivariable logistic regression to establish clinical model. The primary outcome was 28-day mortality. The median age of the subjects was 34 (IQR 24 to 45) years. A total of 148 patients (61.2%) had positive blood cultures. Gram-negative bacilli accounted for 61.5% of the positive isolates, gram-positive cocci accounted for 12.2%, and fungi accounted for 6.1%. Coinfections were found in 30 (20.3%) patients. Escherichia coli was the dominant isolated pathogen (31.1%), followed by Pseudomonas spp. (12.8%) and Klebsiella pneumoniae (10.1%). With a median follow-up of 34 (IQR: 2 to 528) days, a total of 142 (58.7%) patients died, of whom 118 (48.8%) died within the first 28 days after septic shock diagnosis, 131 (54.1%) died within 90 days, and 141 (58.3%) died within 1 year. A large majority of deaths (83.1% [118/142]) occurred within 28 days of septic shock diagnosis. Finally, 6 independent predictive variables of 28-day mortality were identified by multivariable logistic regression: time of septic shock, albumin, bilirubin, PaO2/FiO2, lactate, and sepsis-induced coagulopathy. Patients with late onset shock had higher 28-day mortality rates (64.6% versus 25.5%, P < .001) and more ICU admission (32.6% versus 7.1%, P < .001) than those with early onset shock. We highlight the poor survival outcomes in patients who develop septic shock, emphasizing the need for increasing awareness regarding septic shock after allo-HSCT. The information from the current study may help to assist clinicians in identifying high-risk patients.

Targeting TFH cells is a novel approach for donor-specific antibody desensitization of allograft candidates: an in vitro and in vivo study.

The presence of donor-specific antibodies (DSAs) are associated with graft failure either following HLA-mismatched allogeneic stem cell transplantation or after organ transplantation. Although targeting B cells and plasma cells have been used for desensitization, there have been reports of failure. T follicular helper (Tfh) cells assist B cells in differentiating into antibody-secreting plasma cells. We used haploidentical allograft as a platform to investigate the possibility of targeting Tfh cells to desensitize DSA. The quantities of cTfh cell subsets in allograft candidates were abnormal, and these cells, including the cTfh2 and cTfhem cell subsets, were positively related to the production of anti-HLA antibodies. Ex vivo experiments showed that the cTfh cells of anti-HLA antibody positive allograft candidates could induce B cells to differentiate into DSA-producing plasmablasts. The immune synapse could be involved in the assistance of cTfh cells to B cells in antibody production. In vitro experiments and in vivo clinical pilot studies indicated that targeting cTfh cells with sirolimus can inhibit their auxiliary function in assisting B cells. Ex vivo and in vivo studies demonstrated the effect of sirolimus and rituximab on DSA desensitization compared with either sirolimus or rituximab alone (60%, 43.75%, and 30%, respectively). Our findings provide new insight into the role of Tfh cells in the pathogenesis of DSA production in HLA-mismatched transplant candidates. Our data also indicate that targeting Tfh cells is a novel strategy for DSA desensitization and combination of sirolimus and rituximab might be a potential therapy.

Thrombopoietin level predicts the response to avatrombopag treatment for persistent thrombocytopenia after haploidentical haematopoietic stem cell transplantation.

Persistent thrombocytopenia (PT) has an unsatisfactory response to therapy after haploidentical haematopoietic stem cell transplantation (haplo-HSCT). We retrospectively evaluated the safety and efficacy of avatrombopag treatment in 69 patients with PT following haplo-HSCT and assessed whether baseline thrombopoietin (TPO) levels could predict treatment response. Overall response (OR) and complete response (CR) were defined as increased platelet levels to over 20 × 109/L or 50 × 109/L independent of platelet transfusion during or within 7 days of the end of avatrombopag treatment, respectively. The incidences of OR and CR were 72.5% and 58.0%, with a median of 11 and 29 days to OR and CR, respectively. ROC analysis suggested that the optimally discriminant baseline TPO level threshold for both OR and CR to avatrombopag was ≤ 1714 pg/mL. In multivariate analysis, a lower baseline TPO level (P = 0.005) was a significant independent factor of response to avatrombopag. For patients resistant to other TPO receptor agonists (TPO-RAs), 9/16 (56.3%) exhibited a response after switching to avatrombopag. Avatrombopag was well tolerated, and responders achieved improved overall survival (79.0% vs. 91.1%, P = 0.001). In conclusion, avatrombopag is a potential safe and effective treatment for PT after haplo-HSCT, and lower baseline TPO levels predicted a better response.

A predictive model of herpes zoster after allogeneic hematopoietic stem cell transplantation: VZV reactivation following antiviral prophylaxis discontinuation.

Herpes zoster (HZ) refers to the rash appearing on dermatomes due to varicella zoster virus (VZV) reactivation. The incidence of HZ is significantly higher in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients than in non-HSCT recipients. Although acyclovir prophylaxis is routinely administered to every allo-HSCT recipient for 1 year after transplantation, some individuals eventually develop late-onset HZ after completing prophylaxis. Little information is known about the clinical features of HZ after prophylactic antiviral treatment discontinuation, and an effective predictive model of late-onset HZ needs to be established. A total of 3366 patients who had received allo-HSCT from 2012 to 2017 were included in our study, among whom 201 developed HZ after 1 year (late-onset HZ). We designed a nested case-control study to identify potential predictors of late-onset HZ. Finally, we established a predictive model using binary logistic regression analysis. Age (p < .001), use of immunosuppressants at +1 year (p < .001), CD4-CD8 ratio at +1 year (p < .001), certain mental disorders (depression, anxiety, insomnia and adjustment disorder) (p < .001), engraftment time of neutrophils (p < .001), and CD8+ cell count at +30 days (p < .001) were independent predictors of late-onset HZ. A risk grading system was established based on regression coefficients. Discrimination and calibration analysis indicated that the model had good performance. We also identified several predictive factors of the incidence of HZ-related complications. This is the first scoring system for predicting the incidence of late-onset HZ after allo-HSCT. This model can be applied to identify individuals at high risk of late-onset HZ in the early period after receiving allo-HSCT.