Cumulative Relapse Rate Research Articles

Patients with primary focal segmental glomerulosclerosis with detectable urinary CD80 are more similar to patients with minimal change disease in clinicopathological features

Background Focal segmental glomerulosclerosis (FSGS) is an important cause of refractory nephrotic syndrome (NS) in children and adults. Urinary CD80 is elevated in some patients with primary FSGS, however, its clinical value is not fully clarified. This study aims to evaluate the clinical and pathological significance of urinary CD80 in patients with primary FSGS. Methods Sixty-one adult patients with biopsy-proven primary FSGS, with standard treatment and long-term follow up, were enrolled retrospectively. Urinary CD80, on the day of kidney biopsy, was measured using commercial ELISA kits and adjusted by urinary creatinine excretion. Their associations with clinical and pathological parameters were investigated. Results Urinary CD80 was detectable in 30/61 (49.2%) patients, who presented with a higher level of proteinuria (10.7 vs. 5.8 g/24h; p = 0.01), a lower level of serum albumin (19.3 ± 3.9 vs. 24.2 ± 8.2 g/L; p = 0.005), a higher prevalence of hematuria (70.0 vs. 38.7%; p = 0.01), and showed a lower percentage of segmental glomerulosclerosis lesion [4.8 (3.7–14.0) vs. 9.1 (5.6–21.1) %; p = 0.06]. The cumulative relapse rate was remarkably high in these patients (log-rank, p = 0.001). Multivariate analysis identified that the elevated urinary CD80 was an independent risk factor for steroid-dependent NS (OR 8.81, 95% CI 1.41–54.89; p = 0.02) and relapse (HR, 2.87; 95% CI 1.29–6.38; p = 0.01). Conclusions The elevated urinary CD80 is associated with mild pathological change and steroid-dependent cases of primary FSGS adults, which indicates these patients are more similar to minimal change disease (MCD) in clinicopathological features.

Effect of Immunopeptidome Gap Caused By Recipient-Donor HLA Mismatch in Umbilical Cord Blood Transplantation and HLA-Haploidentical Hematopoietic Stem Cell Transplantation

Introduction The immune response by alloreactive T cells plays a crucial role in allogeneic hematopoietic stem cell transplantation (allo-HCT), causing not only graft-versus-leukemia but also harmful graft-versus-host disease (GVHD). Human leukocyte antigens (HLA), which are highly polymorphic and differ widely among individuals, are the key molecules that present antigens to T cells. This individual variation in antigen-presenting capacity, the immunopeptidome, is thought to be assessable as HLA evolutionary divergence (HED) between alleles. Several autoimmune diseases are explained by HED, and HED is reported to be associated with outcome in HLA-matched allo-HCT. Thus, HED can be a useful indicator of potential immune reactivity. HLA-mismatched allo-HCT, including umbilical cord blood transplantation and HLA-haploidentical allo-HCT (Haplo-HCT), has been increasing in recent years. The combination of HLA mismatch alleles varies from case to case, thus speculating that it causes individual differences in immune responses is easy. HLA mismatches have long been known to be associated with recurrence and GVHD, but a few risk assessment studies have focused on the immunopeptidome gap due to each HLA mismatch in individual cases. Aim This study aimed to examine the prognostic impact of the gap of immunopeptidome in mismatched HLA between recipient and donor in HLA-mismatched allo-HCT. Methods Allo-HCT was performed on 317 patients at our institution from 2006 to 2022. Of the 272 patients with evaluable allele data, 123 patients who underwent more than 3 alleles HLA-mismatched allo-HCT were retrospectively analyzed. Graft sources included cord blood (n=69, 56.1%) and haploidentical stem cells derived from peripheral blood (n=54, 43.9%). The median age at allo-HCT was 44 (range: 16-67) years and the median observation period was 545 [8-5551] days. Diagnoses include acute myeloid leukemia (n=61, 49.6%), acute lymphoblastic leukemia (n=24, 19.5%), malignant lymphoma (n=24, 19.5%), myelodysplastic syndrome (n=10, 8.1%), and others (n=4, 3.2%). The conditioning regimens was non-myeloablative (n=89, 72.4%). GVHD prophylaxis for 54 Haplo-HCT was anti-thymocyte globulin in 27 (50%) and post-transplant cyclophosphamide in 27 (50%) patients. The immunopeptidome gap of HLA mismatch (HED-mis) was evaluated between each mismatched allele. Grantham distance, which predicts amino acids from HLA allelic information and attempts to measure evolutionary distance based on the chemistry of the two amino acids, was used to calculate HED-mis. HLA allele data were drawn from clinical records. Tobias Lenz et al. produced the calculator program (https://hladiv.net/). HED-mis for each HLA class I: HLA-A (HED-mis A), HLA-B (HED-mis B), and HLA-C (HED-mis C) were calculated to evaluate acute and chronic GVHD (aGVHD and cGVHD), cumulative relapse rate (CIR), and overall survival (OS). Result The median [range] of HED-mis for 123 patients was 0.13 [0.00-13.70] for HED-mis A, 7.15 [0.00-11.25] for HED-mis B, and 4.19 [0.00-7.58] for HED-mis C. Patients were divided into 4 groups at each HED-miss value quartile: Q1, Q2, Q3, and Q4. Non-Q4 (Q1, Q2 and Q3 with the lower gaps) and Q4 with the highest gap of HED-mis A, B, and C were compared to confirm the effect of gap size. Univariate analysis revealed that non-Q4 of HED-mis B was associated with increased aGVHD 2-4 up to 100 days after all-HCT, compared to Q4 (non-Q4 49.8% vs. Q4 25.0%, p=0.017), but was unrelated to the incidence of severe aGVHD 3-4 ( p=0.58). Q4 of HED-mis A demonstrated no difference in aGVHD 2-4 compared to non-Q4 ( p=0.20) but was associated with increased severe aGVHD 3-4 (non-Q4 of 0.06% vs. Q4 of 20.7%, p=0.019, Table and Figure). Similarly, multivariate analysis adjusted for each HED-mis, graft, and conditioning revealed that Q4 of HED-mis A was a risk factor for severe aGVHD 3-4 (hazard ratio [HR]: 3.85, p=0.015), and non-Q4 of HED-mis B was a risk factor for developing aGVHD 2-4 (HR: 3.64, p=0.017). HED-mis C was unrelated to any grade aGVHD, but Q4 of HED-mis C may have a better 2-year CIR in univariate (20.3%, vs. in non-Q4, 46.2%, p=0.055) and multivariate analyses (HR: 0.34, p=0.051). No association was found with each HED gap and each quartile for cGVHD and OS. Conclusion Gaps in the immunopeptidome of HLA-mismatched alleles, especially in HLA-A, should be considered in severe aGVHD development during donor selection.

A Modified Busulfan/Cyclophosphamide Preconditioning Regimen Incorporating Selinexor for Allogeneic Hematopoietic Stem Cell Transplantation in Relapsed/Refractory Hematologic Malignancies

Objective: To investigate the safety and efficacy of a modified busulfan (Bu)/cyclophosphamide (Cy) conditioning regimen incorporating Selinexor for allogeneic hematopoietic stem cell transplantation in relapsed/refractory hematologic malignancies. Methods: We retrospectively evaluated the clinical outcomes of patients with hematologic malignancies who had received allo-HSCT with conditioning incorporating Selinexor at the Institute of Hematology and Blood Disease Hospital. Results: Between September 2022 and June 2023, 13 adult patients with high-risk hematologic malignancies were enrolled including 6 males and 7 females with a median age of 49 (13-58) years. There were 7 patients with acute myeloid leukemia (AML), 4 with myelodysplastic syndromes (MDS)/AML, 1 with multiple myeloma (MM) and 1 with extramedullary plasmacytoma. Six patients were in complete remission (CR), four in CR1, two in ≥CR2, five in non-remission (NR), and two patients were in a progressive disease status (PD) prior to conditioning. Three patients received matched-sibling donors transplant, while ten received related haploid hematopoietic stem cell transplantation. All patients had received myeloablative conditioning regimen incorporating Selinexor. Eleven patients received the conditioning: Bu (3.2mg/kg/d*2d); Melphalan (Mel, 60mg/m 2/d*2d), Fludarabine(Flu 30mg/m 2/d*3d) or CLA (5mg/m 2/d*3d), Cy (40mg/kg/d*2d), Selinexor 60mg/d*2d. The other 2 patients received the conditioning: Decitabine (DAC, 20mg/m 2/d*5d), Bu (3.2mg/kg/d*3d), Cy (40mg/kg/d *2d), Flu 30mg/m2/d*3d, Selinexor 60mg/d*2d. The median amount of infused mononuclear cell and CD34 + stem cell were 11.72×10 8/kg(range, 9.66 to 14) and 2.92×10 6/kg(range, 2.35 to 9.61), respectively. All the 13 patients achieved neutrophil engraftment with a median time of 12 (range, 9 to 18) days and 9 patients achieved platelet engraftment with a median time of 13 (range, 11 to 30) days. Four patients were still experiencing prolonged isolated thrombocytopenia. All patients achieved complete donor chimerism and minimal residual disease (MRD) negative at 30 days post-transplantation.The cumulative incidence of cytomegalovirus (CMV) reactivation was 15.4%, while Epstein-Barr virus (EBV) reactivation was not observed. Six patients (46.2%) experienced mucosal barrier injury, comprising three cases of oral mucosal ulcer, one case of digestive tract hemorrhage, and two cases of hemorrhagic cystitis. The cumulative incidence of II-IV and III-IV acute GVHD was 23.1% and 15.4%. The median follow-up for all the participants was 93 (40-316) days after transplantation. Only one patient was dead due to Thrombotic Microangiopathy (TMA) 78 days after transplant. One patient experienced molecular relapse 156 days after transplant, and another patient experienced hematology relapse 20 days after transplant. The two relapsed patients had received donor lymphocyte infusions after chemotherapy. The other 10 patients were still in CR with complete donor chimerism and MRD negative. The cumulative transplant-related mortality (TRM) and relapse rates are 7.7% (1 case) and 15.4% (2 cases), respectively. Conclusions: Incorporating Selinexor into the modified BU/CY conditioning regimen for allogeneic HSCT in patients with relapsed/refractory hematologic malignancies demonstrated a favorable safety profile. Ongoing prospective trials will provide valuable insights into the potential benefits of Selinexor in patients undergoing HSCT.

Cytoreductive Chemotherapy in Induction Therapy Plays a Key Role in the Prognosis of Patients with Low-Risk Acute Promyelocytic Leukemia

Introduction: Despite the success for low-risk acute promyelocytic leukemia (APL) in the all-trans retinoic acid (ATRA) plus arsenicals era, several important clinical issues continue to account for treatment failure including early death (ED) and disease relapse. The present study was conducted to explore the potential role of cytoreduction during induction therapy on prognosis. Methods: All consecutive low-risk APL patients who received ATRA plus arsenic for induction and consolidation therapy at the Peking University People's Hospital, Peking University Institute of Hematology, between February 2014 and September 2021, were analyzed. Kaplan-Meier was used to estimate relapse rates and OS. Exploration of factors associated with relapse was based on Cox proportional hazards regression model. Results: Here 282 patients were diagnosed with low-risk APL and received ATRA plus arsenic as an induction and consolidation therapy. During induction therapy, six patients died early. Nine patients were withdrawn after induction therapy. Of the 282 patients evaluable for OS, the 5-year OS was 97.9%. Of the 267 patients evaluable for relapse, 14 patients (5.2%) relapsed throughout follow-up, with the 5-year cumulative relapse incidence of 5.9%. The median time to relapse, including hematological, molecular and extramedullary relapse, was 18.5 (IQR 12.25-24.5, range 6.2-52.0) months after hematological CR. After induction therapy, all 276 evaluable patients (100%) achieved hematological CR. Cytoreduction therapy, including hydroxycarbamide, anthracyclines and cytarabine during induction therapy was administrated based on the 2018 Chinese APL guidelines. Given the unavailability and inconveniences of intravenous chemotherapy at some stage in the COVID-19 pandemic, our center explored the routine of oral etoposide as cytoreductive therapy from January 2020. Etoposide was administered to patients with a WBC count of 3.2-9.8×10 9/L at diagnosis. The cumulative mean dose of etoposide was 706.5 mg (range, 150-1700 mg) during the induction therapy. In terms of different cytoreduction therapies, 86 patients were administered with hydroxycarbamide (30.5%), 113 with anthracyclines or cytarabine (40.1%), 31 with etoposide (11.0%), and 52 with no cytoreductive therapy (18.4%) during induction therapy. We previously explored that promyelocytic leukemia retinoic acid receptor alpha (PML-RARA) transcript level of 6.5% or more after induction therapy was associated with a subsequent risk of relapse. Compared to patients with no cytoreduction therapy or only hydroxycarbamide during induction therapy, the incidence of PML-RARA transcript levels of ≥6.5% was significantly decreased at the end of induction therapy in those who received anthracyclines/cytarabine and etoposide (27.5% vs. 26.2% vs. 15.5% vs. 0%, P = 0.003, Table 1). Notably, 2-year cumulative relapse rates were significantly lower in the anthracyclines/cytarabine treatment group and the etoposide treatment group (3.962% vs. 8.861% vs. 1.887% vs. 0%, P = 0.040, Table 1). The hydroxycarbamide treatment group did not decrease the relapse rate compared to the no cytoreduction group (11.4% vs. 5.9%, P = 0.289). To estimate RFS, the hydroxycarbamide treatment group and the no cytoreduction treatment group were merged to create a single group (the H/N group, 5-year RFS, 90.391%). Compared with the H/N group, the anthracyclines/cytarabine treatment group and the etoposide treatment group showed improved 2-year RFS (93.064% vs. 98.113% vs. 100.0%, P = 0.046, Figure 1). Multivariate Cox regression analysis revealed that myeloblasts in bone marrow at diagnosis, Leukocytosis during induction therapy, PML-RARA of ≥6.5%, and anthracyclines/cytarabine cytoreductive treatment were associated with a subsequent risk of relapse. Conclusions: In summary, the present study indicated that cytoreductive chemotherapy had a dual effect of both cytoreduction and prevention of relapse in low-risk APL. Oral etoposide as cytoreduction therapy combined with oral ATRA plus RIF is expected to be a regimen with low relapse, good tolerance and great convenience. A prospective, randomized, controlled, interventional study on oral etoposide versus intravenous daunorubicin for cytoreductive chemotherapy in induction therapy in patients with low-risk APL is now going on (NCT05832320).

Therapeutic advancement in inflammatory bowel disease by incorporating plant-based diet.

Identification and recognition of the ubiquitous environmental factor are prerequisite for treatment and prevention of the disease. The biggest problem with current practice in inflammatory bowel disease (IBD) is the lack of a widely appreciated ubiquitous environmental factor for the disease. The incidence of IBD is associated with dietary transition from a traditional diet to the current (westernized) diet. Prospective cohort studies and case-control studies indicate that the current diet is a risk factor for IBD. The current diet tends to cause gut microbial dysbiosis resulting in a pro-inflammatory state. Therefore, we regard our current diet as this factor. Even nutritionally balanced meals are unable to suppress relapse, particularly in Crohn's disease (CD). Therefore, we developed a plant-based diet (PBD) (lacto-ovo-semi-vegetarian diet) to counter the current diet. By incorporating the PBD into practice, we achieved far better outcomes in both ulcerative colitis (UC) and CD in both the induction and quiescent phases compared to the current standard therapy. All patients were treated on an inpatient basis and provided with a PBD. CD is far more untenable than UC and is destined to follow a disabling course. Therefore, infliximab was indicated in all patients with CD, but only in severe cases with UC. This infliximab and PBD as first-line (IPF) therapy broke the barrier of primary nonresponders to biologics (around 30%): the remission rate was 96% (44/46) in CD and 76% (13/17) in severe UC. A PBD can induce remission without medication in approximately one-third of mild cases of UC. All patients were advised to adhere PBD after discharge. In CD, a relapse-free outcome was achieved in nearly a half of patients (52%) at 10-year follow-up without biologics or immunosuppressants. Cumulative relapse rates for 51 initial episode cases of UC (18 mild, 30 moderate, 3 severe) at 1 and 5 years were 14% and 27%, respectively. We believe our assertion that the current diet is the ubiquitous environmental factor underlying IBD is correct and a PBD is right diet for the disease.

Clinical characteristics and outcome of autoimmune pancreatitis based on serum immunoglobulin G4 level: A single-center, retrospective cohort study.

Autoimmune pancreatitis (AIP) has been linked with elevated immunoglobulin (Ig) G4 levels. The characteristics and outcomes of AIP based on serum markers have not been fully evaluated. To compare clinical features, treatment efficacy, and outcome of AIP based on serum IgG4 levels and analyze predictors of relapse. A total of 213 patients with AIP were consecutively reviewed in our hospital from 2006 to 2021. According to the serum IgG4 level, all patients were divided into two groups, the abnormal group (n = 148) with a high level of IgG4 [> 2 × upper limit of normal (ULN)] and the normal group (n = 65). The t-test or Mann-Whitney U test was used to compare continuous variables. Categorical parameters were compared by the χ2 test or Fisher's exact test. Kaplan-Meier curves and log-rank tests were established to assess the cumulative relapse rates. Univariate and multivariate analyses were used to investigate potential risk factors of AIP relapse. Compared with the normal group, the abnormal group had a higher average male age (60.3 ± 10.4 vs 56.5 ± 12.9 years, P = 0.047); higher level of serum total protein (72.5 ± 7.9 g/L vs 67.2 ± 7.5 g/L, P < 0.001), IgG4 (1420.5 ± 1110.9 mg/dL vs 252.7 ± 106.6 mg/dL, P < 0.001), and IgE (635.6 ± 958.1 IU/mL vs 231.7 ± 352.5 IU/mL, P = 0.002); and a lower level of serum complement C3 (100.6 ± 36.2 mg/dL vs 119.0 ± 45.7 mg/dL, P = 0.050). In addition, a lower number of cases with abnormal pancreatic duct and pancreatic atrophy (23.6% vs 37.9%, P = 0.045; 1.6% vs 8.6%, P = 0.020, respectively) and a higher rate of relapse (17.6% vs 6.2%, P = 0.030) were seen in the abnormal group. Multivariate analyses revealed that serum IgG4 [(> 2 × ULN), hazard ratio (HR): 3.583; 95% confidence interval (CI): 1.218-10.545; P = 0.020] and IgA (> 1 × ULN; HR: 5.908; 95%CI: 1.199-29.120; P = 0.029) and age > 55 years (HR: 2.383; 95%CI: 1.056-5.378; P = 0.036) were independent risk factors of relapse. AIP patients with high IgG4 levels have clinical features including a more active immune system and higher relapse rate. Several factors, such as IgG4 and IgA, are associated with relapse.

Relapse rate and predictors of relapse after cessation of glucocorticoid maintenance therapy in type 1 autoimmune pancreatitis: a multicenter retrospective study

BackgroundType 1 autoimmune pancreatitis responds well to glucocorticoid therapy with a high remission rate. Moreover, glucocorticoid maintenance therapy can help prevent relapse. However, the relapse rate following cessation of long-term glucocorticoid therapy is unknown. The aim of this study was to clarify the relapse rate and predictors of relapse following long-term glucocorticoid therapy cessation.MethodsWe analyzed 94 patients who achieved remission after undergoing glucocorticoid therapy, discontinued treatment after at least 6 months of maintenance therapy, and were subsequently followed up for at least 6 months. The patients were divided into three groups based on treatment duration (< 18, 18–36, and ≥ 36 months), and their relapse rates were compared. Univariate and multivariate analyses of clinical factors were conducted to identify relapse predictors.ResultsAfter discontinuing glucocorticoid therapy, relapse was observed in 43 (45.7%) patients, with cumulative relapse rates of 28.2% at 1 year, 42.1% at 3 years, 47.0% at 5 years, and a plateau of 77.6% at 9 years. Of the 43 patients who relapsed, 25 (58.1%) relapsed within 1 year after after cessation of glucocorticoid therapy. Relapse and cumulative relapse rates did not differ significantly according to treatment duration. In the multivariate analysis, an elevated serum IgG4 level at the time of glucocorticoid cessation was found to be an independent predictor of relapse (hazard ratio, 4.511; p < 0.001).ConclusionsA high relapse rate occurred after cessation of glucocorticoid maintenance therapy, regardless of the duration of maintenance therapy, especially within the first year after cessation. However, the normalization of long-term serum IgG4 levels may be a factor in considering cessation.

Evaluation of Dupilumab in Patients With Bullous Pemphigoid

Dupilumab is a theoretically novel therapy for bullous pemphigoid (BP). However, its effectiveness and safety have yet to be confirmed in a large-scale study. To assess the efficacy and safety of dupilumab in patients with BP and evaluate factors that potentially affect short-term and long-term outcomes. A retrospective cohort study was conducted from January 1, 2021, to July 31, 2022. The median (IQR) follow-up period was 24.6 (11.5-38.4) weeks. This multicenter study was performed in 6 dermatology departments of the National Autoimmune Bullous Diseases Cooperative Group of China. Adult patients with BP that received 300 mg of dupilumab every 2 weeks following an initial dose of 600 mg were included. Patients were eligible if they had a clinical presentation of BP combined with immunological or pathological evidence. Patients with drug-induced BP, with less than 4 weeks of follow-up, and who received dupilumab or any other biologics within 6 months were excluded. The primary outcome was the proportion of patients who achieved disease control within 4 weeks. Disease control was defined as the absence of new lesions and pruritus, combined with the healing of existing lesions. Complete remission rates, relapse rates, changes in Bullous Pemphigoid Disease Area Index (BPDAI) scores, itching numerical rating scale (NRS) scores, laboratory results within 64 weeks, and adverse events (AEs) were also assessed. Among 146 patients (median [IQR] age, 73 [64-85] years; 86 [58.9%] male patients) included in the study, 127 (87.0%) patients achieved disease control within 4 weeks, with a median (IQR) time of 14 (7-14) days. A total of 52 (35.6%) patients achieved complete remission, and 13 (8.9%) patients relapsed during the observation period. The complete remission rate and cumulative relapse rate at week 64 were 62.5% (5 of 8) and 30.9%, respectively. There was rapid and sustained improvement in clinical indicators and laboratory examination results after dupilumab treatment, including BPDAI scores, itching NRS scores, serum anti-BP180 and anti-BP230 antibodies, total IgE levels, and eosinophil count. Of these 146 patients, 107 (73.3%) did not report any AEs. The most common AEs were infections and eosinophilia. Serum anti-BP180 antibody levels of greater than 50 relative units (RU)/mL (OR, 3.63; 95% CI, 0.97-12.61; P = .045) were associated with 4-week disease control, and male patients were more likely to relapse (HR, 10.97; 95% CI, 1.42-84.92; P = .02). In this retrospective cohort study, dupilumab treatment was associated with improved clinical symptoms in patients with BP. The safety profile was favorable, although concurrent infection and eosinophilia might pose potential concerns. This study suggests that patients with anti-BP180 antibody levels of at least 50 RU/mL and female sex may respond better.

Effect and safety of 10-day decitabine-containing conditioning regimen for allogeneic hematopoietic stem cell transplantation in 31 patients with acute myeloid leukemia/myelodysplastic syndrome

Objective: To investigate the early effect and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a 10-day decitabine-containing conditioning regimen in the treatment of acute myeloid leukemia (AML) /myelodysplastic syndrome (MDS) . Methods: From April 2021 to May 2022, 31 AML/MDS patients who received allo-HSCT with a 10-day decitabine-containing conditioning regimen were analyzed. Results: AML (n=10), MDS-AML (n=6), CMML-AML (n=1), and MDS (n=14) were identified in 31 patients, 16 males, and 15 females, with a median age of 41 (20-55) yr. Neutrophils and platelets were successfully implanted in 31 patients (100%), with a median implantation duration of 12 (9-30) and 14 (9-42) days, respectively. During the preconditioning period, 16 patients (51.6%) developed oral mucositis, with 15 cases of Ⅰ/Ⅱ grade (48.4%) and one case of Ⅲ grade (3.2%). After transplantation, 13 patients (41.9%) developed CMV viremia, six patients (19.4%) developed hemorrhagic cystitis, and four patients (12.9%) developed a local infection. The median time of acute graft versus host disease (aGVHD) following transplantation was 33 (12-111) days. The cumulative incidence of aGVHD and Ⅲ/Ⅳ grade aGVHD was 41.9% (95% CI 26.9%-61.0%) and 22.9% (95% CI 13.5%-47.5%), respectively. There was no severe cGVHD, and mild and moderate chronic GVHD (cGVHD) incidence was 23.5% (95% CI 12.1%-43.6%). As of November 30, 2022, only one of the 31 patients had relapsed, with a 1-yr cumulative relapse rate (CIR) of 3.2% (95% CI 0.5%-20.7%). There was only one relapse patient death and no non-relapse deaths. The 1-yr overall survival (OS) and disease-free survival (DFS) rates were 92.9% (95% CI 80.3%-100%) and 96.8% (95% CI 90.8%-100%), respectively. Conclusions: A 10-day decitabine-containing conditioning regimen for allo-HSCT reduced relapse and was safe and feasible in treating AML/MDS.

HBV relapse rates in patients who discontinue tenofovir disoproxil fumarate with or without switching to tenofovir alafenamide.

The incidence and relapse pattern in patients stopping tenofovir alafenamide (TAF), a prodrug of tenofovir which is more concentrated in hepatocytes, is unknown. HBeAg-negative CHB patients stopping tenofovir disoproxil fumarate (TDF) (off-TDF) or who had switched to TAF more than 3 months before discontinuation (off-TAF) were recruited. The propensity score-matching method (PSM) was used, creating a ratio of 1:3 between the off-TAF versus the off-TDF groups to adjust for associated factors. After PSM, 180 off-TDF and 60 off-TAF patients were analyzed. The cumulative rates of virological and clinical relapse at 52 weeks were 75.1% and 58.5% respectively in the off-TDF group and 91.1% and 61.6% in the off-TAF group. Patients in the off-TAF group had significantly higher rates of virological relapse than those in the off-TDF group (p=0.021), but not clinical relapse (p=0.785). Multivariate cox regression analysis showed that off-TAF group was an independent factor for virological relapse, but not clinical relapse. Severity of clinical relapse and hepatic decompensation rate were comparable between off-TDF and off-TAF groups CONCLUSIONS: The off-TAF group had a higher virological relapse rate than the off-TDF group. The difference in clinical relapse pattern and severity was not clinically important between the two groups.

Serum IgG4 level during initial treatment as a predictor of relapse in IgG4-related disease.

We aimed to investigate the predictors of relapse in immunoglobulin G4-related disease (IgG4-RD), focusing on the serum IgG4 levels during initial treatment. We retrospectively recruited 57 patients with IgG4-RD who were treated with immunosuppressants and elevated serum IgG4 levels in a tertiary hospital between January 2011 and December 2020. They were followed up for ≥ 6 months after initiation of immunosuppressive therapy. Clinical and laboratory findings including serum IgG4 levels (reference value: 6-121 mg/dL) were compared between relapsed (n = 13) and non-relapsed (n = 44) groups. Multivariate Cox regression analysis was used to assess the predictors for relapse. We performed a Kaplan-Meier analysis with a log-rank test to evaluate the cumulative relapse rate for two years. Median serum IgG4 levels at baseline were 321 mg/dL in the relapsed group and 299 mg/dL in the non-relapsed group. Serum IgG4 levels were normalized after six months in five (38.5%) relapsed and 28 (63.6%) non-relapsed patients. In multivariate Cox regression analysis, the normalization of serum IgG4 levels at six months was associated with a lower risk of relapse, with a hazard ratio of 0.232 (p = 0.019). Central nervous system involvement was associated with the relapse, with a hazard ratio of 21.130 (p = 0.015). The cumulative relapse rate for two years was lower in the normal serum IgG4 group at six months than in the elevated serum IgG4 group at six months (p = 0.027). Our study suggests that normalization of serum IgG4 levels during immunosuppressive treatment for IgG4-RD independently predicts relapse-free outcomes. Thus, monitoring serum IgG4 levels might be used as a marker of prognosis.

Abstract P2-11-12: Pattern of distant relapse according to intrinsic molecular subtype in patients with HER2-positive breast cancer: a combined analysis of ShortHER, CherLOB, and two institutional cohorts

Abstract Background: All intrinsic molecular subtypes are represented among HER2-positive breast cancer, with implications on clinical outcome and treatment sensitivity. The impact of molecular subtypes on the pattern and site of relapse is largely unexplored. Methods: 677 patients with HER2-positive early breast cancer from the Shorther trial (n=437), the CherLOB trial (n=84) and two Institutional cohorts (Istituto Oncologico Veneto IRCCS Padova n=39 and Hospital Clinic Barcelona n=117) were included. Only patients with available PAM50 intrinsic molecular subtyping were considered. We analyzed the incidence of distant relapse (at any site and at specific sites) as the first event. Cumulative incidence was estimated according to competing risk analysis (Fine and Gray’s method). Competing risk regression was used to calculate the subdistribution Hazard Ratios (subHR) and their 95% Confidence Interval (CI). Results: The distribution of molecular subtypes was: 130 LumA (19%), 75 LumB (11%), 347 HER2-e (51%), 46 Basal (7%), 79 Normal (12%). Median follow up was 8.4 years (95%CI 8.2-8.6). The 10-yr cumulative incidence rates of distant relapse as first event were: LumA 7.9%, LumB 14.8%, HER2-e 14.7%, Basal 15.5%, Normal 10.4% (HER2-e vs LumA: SubHR 2.21, 95%CI 1.05-4.64, p=0.037). Table 1 shows the 5-yr and 10-yr cumulative incidence rates of distant metastases at specific sites (as first event) according to intrinsic subtype. HER2-e enriched and Basal tumors were more prone as compared to other subtypes to develop brain and lung metastasis as first event, respectively. Isolated brain metastases without extracranial disease occurred only in patients with HER2-e tumors. All brain metastases as first event occurred within 5 years from diagnosis. Bone-only disease as first event was less frequent in HER2-e and Basal subtype (subHR HER2-e vs LumA: 0.32, 95%CI 0.10-10.4. p=0.058). Next, we analyzed the frequency of site-specific first metastasis among patients who experienced a distant metastasis as first event (n=77). Lung metastases were more frequent in Basal tumors (LumA 25.0%, LumB 20.0%, HER2-e 24.4%, Basal 71.4%, Normal 0.0%, p=0.037) and bone metastases were more frequent in Luminal tumors (LumA 100.0%, LumB 60.0%, HER2-e 31.1%, Basal 42.9%, Normal 57.1%, p=0.006). Among 45 HER2-e patients with a first distant relapse, 25.6% were diagnosed with a brain metastasis and 15.6% had brain-only disease. Conclusions: Molecular subtypes influence the metastatic behaviour of clinically HER2-positive breast cancer. These results, if further validated, may have implication in planning personalized monitoring strategies. Table 1. 5-yr and 10-yr cumulative incidence rates of distant metastasis at specific sites (as first event) according to intrinsic subtype. Citation Format: Maria Vittoria Dieci, Giancarlo Bisagni, Stefania Bartolini, Antonio Frassoldati, Daniele Giulio Generali, Federico Piacentini, Gaia Griguolo, Enrico Tagliafico, Fara Brasó-Maristany, Nuria Chic, Francesca Porra, Roberto Vicini, Roberto D’Amico, Sara Balduzzi, Aleix Prat, PierFranco Conte, Valentina Guarneri. Pattern of distant relapse according to intrinsic molecular subtype in patients with HER2-positive breast cancer: a combined analysis of ShortHER, CherLOB, and two institutional cohorts. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-12.

Ventilator-Associated Pneumonia in COVID-19 Patients Admitted in Intensive Care Units: Relapse, Therapeutic Failure and Attributable Mortality—A Multicentric Observational Study from the OutcomeRea Network

Introduction: Ventilator-associated pneumonia (VAP) incidence is high among critically ill COVID-19 patients. Its attributable mortality remains underestimated, especially for unresolved episodes. Indeed, the impact of therapeutic failures and the determinants that potentially affect mortality are poorly evaluated. We assessed the prognosis of VAP in severe COVID-19 cases and the impact of relapse, superinfection, and treatment failure on 60-day mortality. Methods: We evaluated the incidence of VAP in a multicenter prospective cohort that included adult patients with severe COVID-19, who required mechanical ventilation for ≥48 h between March 2020 and June 2021. We investigated the risk factors for 30-day and 60-day mortality, and the factors associated with relapse, superinfection, and treatment failure. Results: Among 1424 patients admitted to eleven centers, 540 were invasively ventilated for 48 h or more, and 231 had VAP episodes, which were caused by Enterobacterales (49.8%), P. aeruginosa (24.8%), and S. aureus (22%). The VAP incidence rate was 45.6/1000 ventilator days, and the cumulative incidence at Day 30 was 60%. VAP increased the duration of mechanical ventilation without modifying the crude 60-day death rate (47.6% vs. 44.7% without VAP) and resulted in a 36% increase in death hazard. Late-onset pneumonia represented 179 episodes (78.2%) and was responsible for a 56% increase in death hazard. The cumulative incidence rates of relapse and superinfection were 45% and 39.5%, respectively, but did not impact death hazard. Superinfection was more frequently related to ECMO and first episode of VAP caused by non-fermenting bacteria. The risk factors for treatment failure were an absence of highly susceptible microorganisms and vasopressor need at VAP onset. Conclusions: The incidence of VAP, mainly late-onset episodes, is high in COVID-19 patients and associated with an increased risk of death, similar to that observed in other mechanically ventilated patients. The high rate of VAP due to difficult-to-treat microorganisms, pharmacokinetic alterations induced by renal replacement therapy, shock, and ECMO likely explains the high cumulative risk of relapse, superinfection, and treatment failure.

Central nervous system relapse in younger patients with diffuse large B-cell lymphoma: a LYSA and GLA/DSHNHL analysis

AbstractMost patients with diffuse large B-cell lymphoma (DLBCL) can be cured with immunochemotherapy such as R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Patients with progression or relapse in the central nervous system (CNS) face dismal outcomes. The impact of more aggressive regimens used in frontline therapy has not been systematically investigated in this context. To this end, we analyzed a large cohort of 2203 younger patients with DLBCL treated on 10 German (German Lymphoma Alliance [GLA]/The German High Grade Non-Hodgkin's Lymphoma Study Group [DSHNHL]) and French (The Lymphoma Study Association [LYSA]) prospective phase 2 and 3 trials after first-line therapy with R-CHOP, R-CHOEP (R-CHOP + etoposide), dose-escalated R-CHOEP followed by repetitive stem cell transplantation (R-MegaCHOEP), or R-ACVBP (rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycine, and prednisone) followed by consolidation including multiple drugs crossing the blood-brain barrier (BBB). Patients with DLBCL with an age-adjusted International Prognostic Index (aaIPI) of 0 to 1 showed very low cumulative incidence rates of CNS relapse regardless of first-line therapy and CNS prophylaxis (3-year cumulative incidences 0%-1%). Younger high-risk patients with aaIPI of 2 to 3 had 3-year cumulative incidence rates of 1.6% and 4% after R-ACVBP plus consolidation or R-(Mega)CHO(E)P, respectively (hazard ratio 2.4; 95% confidence interval: 0.8-7.4; P = .118). Thus, for younger high-risk patients, frontline regimens incorporating agents crossing the BBB may reduce often fatal CNS relapse.

Chidamide-based 3-drug combination regimen reverses molecular relapse post transplantation in AML1-ETO-positive acute myeloid leukemia.

Objective: We aimed to explore a new method to reverse early relapse in patients with AML1-ETO-positive acute myeloid cell transplantation. Methods: A chidamide-based 3-drug combination regimen was used in our center to treat patients with AML1-ETO-positive AML post transplantation but negative flow cytometry results. A retrospective analysis was performed of the survival rate and possible influencing factors of patients with relapse treated with this regimen in our center from January 2018 to January 2022. Results: The overall response rate was 95.8% (23/24), and the median number of treatment courses was 4 (range, 3-12 courses). The total molecular complete response (MCR) was 79.1% (19/24) after all treatments, and the molecular complete response was 37.5% (9/24) after one cycle of treatment but reached 58.3% (14/24) after four cycles; overall, the proportion of MCR increased gradually with the increase in treatment cycles. The projected 5-year overall survival rate was 73.9%. The projected 5-year leukemia-free survival rate was 64.8%, and the projected 1-year cumulative relapse rate was 35.5%. The incidence of grade II-IV graft-versus-host diseases (GVHD) was 29.2% (7/24), and that of grade III-IV GVHD was 20.8% (5/24), which could be effectively controlled by glucocorticoid therapy combined with calcineurin inhibitors The total incidence of chronic GVHD was 29.2% (7/24), and all cases were localized chronic GVHD. The total infection rate was 33.3% (8/24), mainly involving bacterial and fungal infections, and the incidence of life-threatening infections was 4.17% (1/24). The treatment-related mortality rate was 0%; and the total mortality rate was 20.8% (5/24). Nausea and vomiting, thrombocytopenia, and neutropenia were common adverse reactions, all of which were Common Terminology Criteria for Adverse Events grade 2-3 events and reversible after drug withdrawal. In terms of immunity, Th1 cell counts gradually increased, Th17 cell counts gradually decreased, and the Th1/Th17 ratio gradually increased after treatment. The CD8+ T lymphocyte count increased gradually, while the CD4+ T lymphocyte count did not change significantly. Conclusion: Our chidamide-based 3-drug combination regimen led to a high remission rate and tolerable adverse reactions in patients with AML1-ETO-positive post-transplant relapse, and most patients can achieve long-term survival with this regimen.

Clinical characteristics and long-term outcome of patients with gastrointestinal involvement in eosinophilic granulomatosis with polyangiitis.

This study aims to investigate clinical characteristics, potential risk factors, as well as long-term outcome in EGPA patients with GI involvement. A total of 94 EGPA patients were included in this cohort study. We retrospectively reviewed the clinical data, treatment, and outcome of 21 EGPA patients with GI involvement and compared them with other 73 EGPA patients without GI involvement. Multivariate logistic regression was used to find potential risk factors associated with GI involvement in EGPA patients. Compared with EGPA patients without GI involvement, EGPA patients with GI involvement had higher level of hs-CRP (65.1 (24.5-138.9) vs. 21.3 (5.7-39.1) mg/L, p=0.005), higher grades of Birmingham vasculitis activity score (BVAS) (20 (13-29.5) vs. 12 (16-19), p=0.022), higher Five Factor Score (FFS) (1 (1-2) vs. 0 (0-1), p<0.001), and were more likely to have weight loss (66.7% vs. 38.4%, p=0.021) at baseline. In EGPA patients with GI involvement, the most common gastrointestinal symptoms were abdominal pain (90.5%) and diarrhea (42.9%). Weight loss was identified as a potential risk factor for GI involvement in EGPA patients (OR = 4.304, 95% CI 1.339-13.841). During follow-up, EGPA patients with GI involvement showed lower 1-year cumulative survival rate (75.2% vs. 100.0%, P <0.0001) and 3-year cumulative survival rate (67.7% vs. 100.0%, P<0.0001), lower long-term remission rate (33.3% vs. 86.3%, P<0.001), but higher 1-year cumulative relapse rate (19.2% vs. 3.8%, P=0.03) and 3-year cumulative relapse rate (54.6% vs. 13.1%, P<0.001) compared with patients without GI involvement. EGPA patients with GI involvement had distinct features from those without GI involvement, including higher hs-CRP level, higher BVAS and FFS scores. EGPA patients with GI involvement showed lower cumulative survival rate, lower long-term remission rate and higher cumulative relapse rate compared with those without GI involvement.

The Addition of Hypomethylating Agents to Low-Intensity Induction Chemotherapy Does Not Improve Outcomes in Elderly Acute Myeloid Leukemia Patients: A Single-Center Retrospective Study

Background and Objectives: This study aimed to evaluate whether the addition of hypomethylating agents (HMA) to low-intensity chemotherapy can enhance the clinical efficacy of induction treatment for elderly acute myeloid leukemia (AML) patients who are unsuitable for standard induction therapy. Materials and Methods: This study retrospectively analyzed 117 patients over 60 years old who were initially diagnosed with AML and received low-intensity induction treatment in the Department of Hematology in Anhui provincial hospital from January 2015 to December 2020. Twenty-three patients were excluded, and the remaining 94 patients were divided into two groups according to the selection of induction regimens. Results: Forty-four patients received HMA combined with low-intensity chemotherapy, and the other 50 patients received only low-intensity induction chemotherapy. Forty-three patients (45.7%) obtained complete remission (CR) after the initial induction treatment. The CR rate in the HMA plus low-intensity chemotherapy group was 34.1% (15/44), and in the single low-intensity chemotherapy group was 56.0% (28/50) (p = 0.04). The 30 days cumulative early death rates were 9.1% (95% CI: 3.5-22.4%) in the HMA plus low-intensity chemotherapy group and 6.0% (95% CI: 2.0-17.5%) in the single low-intensity chemotherapy group, respectively (p = 0.59), and the one-year cumulative relapse rates were 21.1% (95% Cl: 9.8-41.9%) and 33.3% (95% Cl: 20.3-51.5%), respectively (p = 0.80). The one-year overall survival (OS) rates for patients in the HMA plus low-intensity chemotherapy group and the single low-intensity chemotherapy group were 37.3% (95% Cl: 23.1-51.5%) and 55.4% (95% Cl: 40.5-67.9%), respectively (p = 0.098), and the one-year event-free survival (EFS) rates were 8.5% (95% Cl: 2.2-20.6%) and 20.6% (95% Cl: 9.1-35.3%), respectively (p = 0.058). Conclusions: This study showed that the addition of HMA to low-intensity induction chemotherapy does not improve prognosis in elderly AML patients who are unsuitable for standard induction chemotherapy.

Epidemiology and predictors of relapse in giant cell arteritis: A systematic review and meta-analysis.

The aim of this study was to estimate the timing of relapse, the prevalence of multiple relapses and the predictors of relapse in patients with giant cell arteritis (GCA). PubMed, Embase and Cochrane databases were searched from inception till November, 30 2021. Outcome measures include cumulative relapse rate (CRR) of first relapse at year 1, 2, and 5 after treatment initiation, CRR of second and third relapse and predictors of relapse. Thirty studies (2595 patients) were included for timing of relapse, 16 studies (1947 patients) for prevalence of multiple relapses and 40 studies (4213 patients) for predictors of relapse. One-year, 2-year and 5-year CRRs were 32% [95% confidence interval (CI) 22-43%], 44% [95% CI 31-59%], and 47% [95% CI 27-67%], respectively. The duration of scheduled glucocorticoid therapy was negatively associated with the 1-year CRR (P=0.03). CRR of second and third relapse were 30% [95% CI 21-40] and 17% [95% CI 8-33%], respectively. Female sex (OR 1.43) and large vessel involvement (OR 2.04) were predictors of relapse. Relapse occurred in almost half of GCA patients mainly during the first two years after diagnosis. One in three patients had multiple relapses. The optimal glucocorticoid tapering schedule, which seeks a balance between the lowest relapse risk and the shortest glucocorticoid duration, needs to be determined in future studies. Longer scheduled glucocorticoid therapy or early introduction of glucocorticoid-sparing agents may be warranted in female patients and patients with large vessel involvement.

The impact of donor-to-recipient gender compatibility on outcomes of haploid hematopoietic stem cell transplantation in patients with hematological malignancies

Objective: To investigate how gender differences between the donor and the recipient affect the effectiveness of antithymocyte globulin (ATG) and pure peripheral blood stem cell (PBSC) hematopoietic stem cell transplantation (haplo-HSCT) in the treatment of malignant hematological diseases. Methods: From February 2015 to September 2020, 648 hematological malignancies patients underwent myeloablative condition regimen haplo-HSCT treatment at the Bone Marrow Transplant Center of the First Affiliated Hospital of Zhejiang University. The median age was 32 (14-62) years, with 363 males (56.0% ) and 285 females (44.0% ) present. 242 cases of acute lymphoblastic leukemia (ALL) (37.3% ) , 293 cases of acute myeloid leukemia (AML) (45.2% ) , 56 cases of myelodysplastic syndrome (MDS) (8.7% ) , 27 cases of non-Hodgkin's lymphoma (NHL) (4.2% ) , and 30 cases of other hematological malignancies (4.6% ) . Results: ① The 3-year overall survival (OS) , DFS, the incidence of Ⅱ-Ⅳ grade acute graft-versus-host disease (aGVHD) , the incidence of Ⅲ-Ⅳ grade aGVHD, the 3-year incidence of moderate & severe chronic GVHD (cGVHD) , severe cGVHD, the 3-year incidence of relapse, and NRM of the whole group were (73.10±1.90) % , (70.80±1.90) % , (33.96±1.87) % , (13.08±1.33) % , (35.10±2.14) % , (10.66±1.38) % , (19.43±1.67) % , and (9.80±1.24) % , respectively. ②There was no statistically significant difference between the donor-recipient gender match and donor-recipient gender mismatch groups in the 28-day cumulative neutrophil engraftment rate, 28-day cumulative platelet engraftment rate, the incidence of Ⅱ-Ⅳ grade aGVHD, the incidence of Ⅲ-Ⅳ grade aGVHD, 3-year OS, 3-year DFS, the cumulative incidence of relapse, NRM, and incidence of moderate & severe cGVHD, severe cGVHD. ③The 28-day cumulative neutrophil engraftment rate did not differ statistically between the male-female, female-female, male-male, and female-male groups (P=0.148) . The incidence of Ⅱ-Ⅳ grade aGVHD, the incidence of Ⅲ-Ⅳ grade aGVHD, 3-year OS, 3-year DFS, cumulative relapse rate, and NRM, and the incidence of cGVHD were not statistically different among the four groups (P>0.05) . The 28-day cumulative platelet engraftment rate of the female-male group was significantly lower than male-female group, and the female-female group [ (91.45±2.63) % vs. (94.77±1.75) % , P=0.004; (91.45±2.63) % vs. (95.54±2.05) % , P=0.005]. No significant difference existed in the 28-day cumulative platelet engraftment rate between the female-male group and the male-male group [ (91.45±2.63) % vs. (95.08±1.41) % , P=0.284]. ④Among patients ≤35 years old, the 3-year incidence of severe cGVHD patients receiving sister donors and sibling donors were (26.71±5.90) % and (10.33±4.43) % , respectively (P=0.054) . Patients accepting daughter donors and son donors had a 3-year incidence of moderate and severe cGVHD that was 40.07% vs. 27.41% , respectively, among those over 35 (40.07±6.65) % vs. (27.41±4.54) % (P=0.084) . ⑤Female donors to male recipients had a significantly lower 28-day cumulative platelet engraftment rate compared to the other groups [ (91.45±2.63) % vs. (95.08±0.95) % , P=0.037]. ⑥ Female donors to male recipients had a significantly lower 28-day cumulative platelet engraftment rate than the other groups in the ATG-Fresenius (ATG-F) 10 mg/kg group [ (89.29±4.29) % vs. (94.49±1.45) % , P=0.037]. But when compared to the other groups in the Rabbit Antihuman Thymocyte Immunoglobulin (rATG-T) 6 mg/kg group, the 28-day cumulative platelet implantation rate between female donors and male recipients was not significantly different [ (93.44±3.38) % vs. (95.62±1.26) % , P=0.404]. Conclusion: The main clinical outcomes of patients with malignant blood diseases following transplantation are unaffected by the gender combination of the donor and patient in the haplo-HSCT mode based on ATG and PBSC sources. Female donors to male recipients have a lower 28-day cumulative platelet engraftment rate and longer platelet engraftment times.

Second hematopoietic stem cell transplantation as salvage therapy for relapsed acute myeloid leukemia/myelodysplastic syndromes after a first transplantation.

Second allogeneic hematopoietic stem-cell transplantation (HSCT2) is a therapeutic option for patients with acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) relapsing after a first transplant (HSCT1). However, patients allocated to HSCT2 may be a selected group with better prognosis and the added efficacy of HSCT2 is not well established. We retrospectively analyzed 407 consecutive patients with relapsed AML/MDS after HSCT1. Sixty-two patients had HSCT2 (15%) and 345 did not. The 2-year cumulative incidence rates of non-relapse mortality and relapse after HSCT2 were 26% (95% confidence interval [95% CI]: 17-39%) and 50% (95% CI: 39-65%), respectively. The 5-year overall survival rates were 25% (95% CI: 14-36%) and 7% (95% CI: 4-10%) in the HSCT2 and no-HSCT2 groups, respectively. Multivariate analysis identified female gender (hazard ratio [HR]=0.31, P=0.001), short remission duration after HSCT1 (HR=2.31, P=0.05), acute graft-versus-host disease after HSCT1 (HR=2.27, P=0.035), HSCT2 from a haplo-identical donor (HR=13.4, P=0.001) or matched unrelated donor (HR=4.53, P=0.007) and relapse after HSCT1 in earlier years (HR=2.46, P=0.02) as factors predicting overall survival after HSCT2. Multivariate analysis of all patients including HSCT2 as a timedependent variable identified relapse within 6 months after HSCT1 (HR=2.32, P<0.001), acute graft-versus-host disease before relapse (HR=1.47, P=0.005), myeloablative conditioning in HSCT1 (HR=0.67, P=0.011), female gender (HR=0.71, P=0.007), relapse in earlier years (HR=1.33, P=0.031) and not having HSCT2 (HR=1.66, P=0.010) as predictive of overall survival after relapse. In conclusion, HSCT2 is associated with longer survival compared to non-transplant treatments and may be the preferred approach in a subset of patients with relapsed AML/MDS after HSCT1.