allo-HSCT Patients Research Articles

Effect of Philadelphia Chromosome Karyotype and Allogeneic Hematopoietic Stem Cell Transplantation on Patients with Acute Lymphoblastic Leukemia

The data of 429 patients with all from January 2012 to December 2020 were retrospectively analyzed. According to the results of cytogenetic karyotype analysis, they were divided into Ph+ group (n=64), Ph- monomeric karyotype (MK) group (n=53) and Ph- NMK group (n=312). According to the treatment plan, they were divided into allo-HSCT group (n=236) and non-allo-HSCT group (n=193). The effects of karyotype and allo-HSCT on the short-term and long-term outcomes of all patients were analyzed. Among the 429 patients, 6 (1.40%) died during induction therapy, 60 (13.99%) had no response, 363 (84.62%) achieved complete remission (CR) and 287 (66.90%) achieved minimal residual disease negative (MRD-). There was no significant difference in short-term efficacy (CR%, CR1%, MRD-%) among Ph+ group, Ph- MK group and Ph- non-MK group (P>0.05). The median OS was 6.9 months (95% CI: 4.6-8.2 months) for 60 unresponsive patients and 39.8 months (95% CI: 28.6-45.9 months) for 363 CR patients. There was no significant difference in the long-term efficacy ［5-year cumulative recurrence rate (CIR%), disease-free survival rate (DFS%) and overall survival rate (OS%) among Ph- group, Ph- MK group and Ph- non-MK group (P>0.05). Among 429 patients, 55.01% (236/429) underwent allo-HSCT. The short-term efficacy (CR%, MRD-%) and long-term efficacy (CIR%, DFS%, OS%)］ of patients with allo-HSCT after more than 2 consolidation cycles were better than those of patients with non-allo-HSCT (P<0.05). For the three subgroups of Ph+ group, Ph- MK group and Ph- non-MK group, the short-term and long-term efficacy of allo-HSCT patients was better than that of non-allo-HSCT patients. Multivariate logistic regression analysis showed that liver/spleen/lymph node enlargement was a risk factor for CIR, DFS and OS, with adjusted or of 1.23 (95% CI: 1.08-2.78, P=0.032), 1.21 (95% CI: 1.03-2.34, P=0.038) and 1.25 (95% CI: 1.08-2.97, P=0.028), respectively. No transplantation was a risk fator for CIR, DFS, OS. The adjusted or were 2.34 (95% CI: 1.18-5.39, P<0.001), 2.15 (95% CI: 1.10-4.34, P<0.001) and 2.28 (95% CI: 1.09-4.11, P<0.001), respectively. Karyotype (Ph+/- and MK/non-MK) seems to have no effect on the short-term and long-term efficacy of all patients; allo-HSCT can affect the short-term and long-term efficacy of all patients and improve their prognosis; liver/spleen/lymph node enlargement and non-implementation of allo-HSCT treatment strategy are the risk factors for poor prognosis of all patients.

Strong SARS-CoV-2 T-Cell Responses after One or Two COVID-19 Vaccine Boosters in Allogeneic Hematopoietic Stem Cell Recipients.

A full exploration of immune responses is deserved after anti-SARS-CoV-2 vaccination and boosters, especially in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although several reports indicate successful humoral responses in such patients, the literature is scarce on cellular specific immunity. Here, both B- (antibodies) and T-cell responses were explored after one (V3 n = 40) or two (V4 n = 12) BNT162b2 mRNA vaccine boosters in 52 allo-HSCT recipients at a median of 755 days post-transplant (<1 year n = 9). Results were compared with those of 12 controls who had received only one booster (BNT162b2 n = 6; mRNA-1273 n = 6). All controls developed protective antibody levels (>250 BAU/mL) and anti-spike T-cell responses. Similarly, 81% of the patients developed protective antibody levels, without difference between V3 and V4 (82.5% vs. 75%, p = 0.63), and 85% displayed T-cell responses. The median frequency of anti-spike T cells did not differ either between controls or the whole cohort of patients, although it was significantly lower for V3 (but not V4) patients. COVID-19 infections were solely observed in individuals having received only one booster. These results indicate that four vaccine injections help to achieve a satisfactory level of both humoral and cellular immune protection in allo-HSCT patients.

Mucus-degrading Bacteroides link carbapenems to aggravated graft-versus-host disease

The intestinal microbiota is an important modulator of graft-versus-host disease (GVHD), which often complicates allogeneic hematopoietic stem cell transplantation (allo-HSCT). Broad-spectrum antibiotics such as carbapenems increase the risk for intestinal GVHD, but mechanisms are not well understood. In this study, we found that treatment with meropenem, a commonly used carbapenem, aggravates colonic GVHD in mice via the expansion of Bacteroides thetaiotaomicron (BT). BT has a broad ability to degrade dietary polysaccharides and host mucin glycans. BT in meropenem-treated allogeneic mice demonstrated upregulated expression of enzymes involved in the degradation of mucin glycans. These mice also had thinning of the colonic mucus layer and decreased levels of xylose in colonic luminal contents. Interestingly, oral xylose supplementation significantly prevented thinning of the colonic mucus layer in meropenem-treated mice. Specific nutritional supplementation strategies, including xylose supplementation, may combat antibiotic-mediated microbiome injury to reduce the risk for intestinal GVHD in allo-HSCT patients.

The impact of Rituximab administered before transplantation in patients undergoing allogeneic hematopoietic stem cell transplantation: A real-world study.

Rituximab is used to eliminate B cells as a chimeric monoclonal antibody directed against CD20, a B-cell antigen expressed on B cells. To explore the impact of rituximab administered before transplantation, we implemented a retrospective, monocentric study and utilized real-world data collected at our center between January 2018 and December 2020, and then followed until December 2021. Based on whether a dose of 375mg/m2 rituximab was used at least once within two weeks before transplantation, patients undergoing allo-HSCT were classified into two groups: rituximab (N=176) and non-rituximab (N=344) group. Amongst all the patients, the application of rituximab decreased EBV reactivation (P<0.01) and rituximab was an independent factor in the prevention of EBV reactivation by both univariate and multivariate analyses (HR 0.56, 95%CI 0.33-0.97, P=0.04). In AML patients, there were significant differences in the cumulative incidence of aGVHD between the two groups (P=0.04). Our data showed that rituximab was association with a decreased incidence of aGVHD in AML patients according to both univariate and multivariate analyses. There was no difference between the two groups in other sets of populations. Thus, our study indicated that rituximab administered before transplantation may help prevent EBV reactivation in all allo-HSCT patients, as well as prevent aGVHD in AML patients after allo-HSCT.

Feasibility of Cyclosporine Prophylaxis Withdrawal in Critically Ill Allogenic Hematopoietic Stem Cell Transplant Patients Admitted to the Intensive Care Unit With No GVHD

Twenty percent of allogenic hematopoietic stem cell transplantation (allo-HSCT) patients require intensive care unit (ICU) admission. Feasibility and long-term consequences of cyclosporine graft-versus-host disease (GVHD) prophylaxis withdrawal in the ICU are unknown. To assess the impact of cyclosporine prophylaxis withdrawal in critically ill allo-HSCT patients admitted to the ICU on GVHD incidence and to evaluate 6-month overall survival according to cyclosporine withdrawal and GVHD occurrence. From 2010 to 2020, 101 critically ill allo-HSCT patients admitted to the ICU in our institution were included. All received cyclosporine as GVHD prophylaxis. None of them had GVHD at ICU admission. Patients were admitted in the ICU after a median time of 11 days (5.5-18) after allo-HSCT. ICU, hospital mortality, and 6-month mortality were 43.6%, 56.4%, and 59.4%, respectively. Cyclosporine was withdrawn for 52 and continued for 49 patients in the ICU. A total of 38.6% (n=39) developed secondarily acute GVHD (aGVHD) after a median of 28 days (15-40) after cyclosporine was discontinued. In 74.4% (n=29) of cases, patients in the hematology ward developed aGVHD after ICU discharge. Cyclosporine dosages were similar in both groups. Factors independently associated with aGVHD occurrence in multivariate analysis were cyclosporine withdrawal in the ICU (subdistribution hazard ratios [sHR]=2.04, 95% confidence interval [CI]=1.02-4.1, P=.044), renal replacement therapy (RRT) (sHR=0.43, 95% CI=0.19-0.9, P=.03) and fungal prophylaxis (sHR=2.62, 95% CI=1.35-5.07, P=.004). Cyclosporine withdrawal in the ICU was associated with poorer 6-month overall survival (OS) (HR=1.96, 95% CI=1.16-3.33, P=.012), but after adjusting on severity (simplified acute physiology score, vasopressors, mechanical ventilation and RRT requirement), 6-month OS did not differ (HR=1.35, 95% CI=0.76-2.42, P=.30). GVHD occurrence after ICU stay was significantly associated with better 6-month OS in unadjusted (HR=0.53, 95% CI=0.31-0.90, P=.02) and severity-adjusted analysis (HR=0.54, 95% CI=0.31-0.93, P=.028). Cyclosporine prophylaxis withdrawal in critically ill allo-HSCT patients in the ICU appears to be feasible and did not impair long-term outcome.

The Prognostic Value of FOSB Gene in Acute Myeloid Leukemia

The genome, transcriptome, gene chip and clinical information from multiple public databases were statistical analyzed. The expression of FOSB gene in AML patients was significantly higher than that in normal people. The prognostic analysis of the 163 patients showed that the patients with high FOSB expression showed longer OS and EFS than those with FOSB low expression. The patients were further divided into chemotherapy group and allogeneic hematopoietic stem cell transplantation (allo-HSCT) group according to the treatment method, and then each group was divided into two subgroups (FOSBhigh, FOSBlow) according to the median expression level of FOSB. In the allo-HSCT group, the patients with FOSB high expression was longer event-free survival (EFS: P=0.017) and overall survival (OS: P=0029). At the same time, allo-HSCT in patients with high FOSB expression could improve the prognosis of the patients (Chemotherapy vs Allo-HSCT, OS: P<0.001, EFS: P=0.007). Multivariate analysis showed that the high expression of FOSB was an independent favorable prognostic factor for EFS and OS (EFS: HR=0.501， P=0.019; OS: HR=0.461， P=0.009) of the patients. The high expression of FOSB indicated a good prognosis for acute myeloid leukemia.

Ocular surface disease index questionnaire as a sensitive test for primary screening of chronic ocular graft-versus-host disease.

BackgroundAfter allogeneic hematopoietic stem cell transplantation (allo-HSCT), patients are followed up by transplant clinicians. Finding an effective primary screening method that transplant clinicians or patients can master is essential in the early referral of suspected chronic ocular graft-versus-host disease (coGVHD) to an ophthalmologist. This study investigated if the ocular surface disease index (OSDI) questionnaire could be used for coGVHD primary screening.MethodsThis case-controlled, cross-sectional study enrolled 161 allo-HSCT patients. All participants completed an OSDI questionnaire and underwent a silt-lamp examination. Bulbar conjunctival injection (BCI) was assessed using torchlight, while tear volume was measured via the Schirmer test (ST). The receiver operating characteristic curve was used to evaluate the sensitivity, specificity, and cutoff values of OSDI, ST, and BCI grading. Performance comparisons of the 3 tests applied in isolation, parallel, and series were made.ResultsThere were 84 patients with and 77 patients without coGVHD. Compared to those without coGVHD, patients with coGVHD had significantly higher median values of OSDI, corneal fluorescein staining, conjunctival injection, conjunctival fibrosis, and meibum quality, but lower ST scores (All P values <0.001). The cutoff values for OSDI, ST, and BCI grade in the diagnosis of coGVHD were 19.4 points, 7 mm, and grade 0, respectively. The sensitivity and specificity of the tests based on the cutoff values were, respectively, 89.3% and 89.6% for OSDI, 91.7% and 59.7% for ST, and 78.6% and 70.1% for BCI. The area under the curve (AUC) value of OSDI was significantly higher than that of ST (0.931 vs. 0.826; P=0.010) and BCI grade (0.931 vs. 0.781; P<0.001). The AUC values of the combinations were lower than that of OSDI alone.ConclusionsThe OSDI questionnaire can be used as a simple screening test for coGVHD as demonstrated by its high sensitivity and specificity in the transplant clinic and patients’ self-monitoring. An OSDI greater than 19.4 could be considered an ophthalmology referral criterion.

Extracorporeal photopheresis for the treatment of chronic graft versus host disease

ABSTRACT Objectives Chronic graft versus host disease (chronic GVHD) still remains the leading cause of late morbidity and mortality for allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. In this retrospective study, 53 consecutive allo-HSCT patients with chronic GVHD refractory to corticosteroids were treated with extracorporeal photopheresis (ECP). Methods This study was performed as a retrospective single-center study. Medical records of a total of 59 patients treated with ECP for chronic GVHD were reviewed. Results Best organ responses to ECP were observed in skin, mouth mucosa, eyes and liver. Overall response rate (ORR) to ECP was 81.2% (CR 17% and PR 64.2%). Overall survival (OS) was 84.9% and 36.7%, at 1 and 3 years, respectively. Female sex appears to have an advantage on ORR. Patients achieving ORR were able to maintain their responses with a prolonged continuation of treatments for +6 and +12 months indicating the benefits of longer ECP treatment. Discussion We found that patients with chronic GVHD who were treated with ECP for 12 months or longer had a higher response rate. Our findings in line with the data reported previously suggest that patients responding to ECP should continue longer therapy schedules to achieve a better and sustained response. In our cohort, long-term ECP therapy was safe and well-tolerated with no significant adverse effects. Best responses were observed in the patients with skin, eye, liver and oral involvement. The ECP procedure offers the advantage relative to the problems with typical immunosuppressive agents. The female sex appeared to have an advantage based on the cumulative probability of the OR after ECP for chronic GVHD.

Efficacy and safety of Venetoclax in the treatment of 25 patients with recurrent hematologic malignancies after an allogeneic hematopoietic stem cell transplantation

目的观察维奈克拉（VEN）治疗异基因造血干细胞移植（allo-HSCT）后复发恶性血液病患者的疗效及安全性。方法回顾性分析2021年2月至2021年11月在中国医学科学院血液病医院接受VEN治疗的25例allo-HSCT后复发患者的临床资料，其中微小残留病（MRD）阳性患者15例（抢先治疗组），形态学复发患者10例（挽救治疗组）。两组VEN剂量均为400 mg/d，联合唑类抗真菌药物时减量至100 mg/d。结果①抢先治疗组男7例，女8例，中位年龄32（18～52）岁；急性髓系白血病（AML）13例，急性淋巴细胞白血病（ALL）1例，原发性骨髓纤维化（PMF）1例；MRD阳性至应用VEN中位时间为2.5（0～12.5）个月。VEN中位疗程数为2（1～4）个。第1疗程治疗第7天VEN中位血药浓度为1 945（688～5 383）µg/L。VEN治疗1疗程后8例患者MRD转为阴性（获得主要反应），4例MRD较治疗前下降50％，3例无效，总体反应率（ORR）为80％（12/15）。9例治疗第7天VEN血药浓度<1 000 µg/L或>3 000 µg/L患者中3例（33.3％）MRD转阴，6例VEN血药浓度1 000～3 000 µg/L患者中5例（83.3％）MRD转阴。5例患者出现3/4级中性粒细胞减少，5例患者出现3/4级血小板减少，无新发严重感染致死病例。②挽救治疗组男7例，女3例，中位年龄44（28～59）岁；AML 6例，ALL 2例，不典型慢性髓性白血病（aCML）1例，骨髓增生异常综合征难治性血细胞减少伴有多系发育异常（MDS-RCMD）1例；复发至应用VEN中位时间为0（0～1）个月；VEN中位疗程数为1（1～2）个；第1疗程治疗第7天VEN中位血药浓度为2 419（1 200～6 155）µg/L。VEN治疗1疗程后3例获得完全缓解（CR）（主要反应），3例获得部分缓解（PR），4例无效，ORR为60％（6/10）。4例治疗第7天VEN血药浓度>3 000 µg/L患者中1例获得CR，6例VEN血药浓度1 000～3 000 µg/L患者中2例获得CR。10例患者均出现3/4级中性粒细胞减少及3/4级血小板减少。1例患者因严重肺感染死亡。③中位随访4.5（1～8.5）个月，抢先治疗组、挽救治疗组总生存（OS）率分别为（70.2±12.7）％、（50.0±15.8）％（χ2＝1.873，P＝0.171）。1疗程VEN治疗获得主要反应、未获得主要反应患者的OS率分别为（90.9±8.7）％、（36.2±14.7）％（χ2＝6.843，P＝0.009）。3例存在TP53突变的患者在VEN治疗后均获得主要反应。结论应用VEN对allo-HSCT后复发的恶性血液病患者进行抢先/挽救治疗有一定疗效且耐受性良好，监测VEN血药浓度有望提高疗效。VEN抢先/挽救治疗1个疗程未获得主要反应的患者预后较差，需尽早转换其他治疗方案。

Treosulfan-based conditioning vs. low-dose busulfan-based conditioning for allogeneic hematopoietic stem cell transplantation: a cost-utility analysis in Poland

Introduction: In Poland, busulfan conditioning is used for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Cost-utility analyses comparing alternative conditioning regimens in patients undergoing allo-HSCT have not been conducted so far. Material and methods: A United Kingdom-based partitioned survival model was adapted to the Polish setting to compare treosulfan to low-dose busulfan conditioning regimen from the public payer’s perspective in Poland. Patient characteristics, overall survival (OS), event-free survival (EFS), and the rate of adverse events were obtained from the randomized MC-FludT.14/L trial. Parametric survival models of up to 5 years (the cure threshold), with subsequent mortality defined using survival of the general population of Poland adjusted for cancer survivors, were used to extrapolate OS and EFS beyond the trial duration. Published utilities were adjusted for age using age-dependent general population utilities. The costs of treatment, adverse events, and inpatient/outpatient care were assessed via official remuneration schemes. Results: Treosulfan-based conditioning outperformed low-dose busulfan, i.e. it was more effective with incremental quality-adjusted life years (QALY) of 0.78 and less expensive by 1,139 PLN per patient over the lifetime horizon. Deterministic sensitivity analyses revealed treosulfan was highly cost-effective (i.e. incremental cost-utility ratio was lower than the gross domestic product per capita in Poland) compared to low-dose busulfan, if most uncertain parameters are changed or alternative scenarios are implemented. The probability of treosulfan being cost-effective with a threshold of 155,514 PLN was 99.6%. Conclusions: Compared to low-dose busulfan, treosulfan is a highly cost-effective conditioning regimen for allo-HSCT patients ineligible for standard conditioning regimens.

P1365: DONOR LYMPHOCYTE INFUSION IN ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION: RESULTS FROM A RETROSPECTIVE STUDY

Background: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a therapeutic option with curative intent in hematological malignancies. Despite improvements in alloHSCT, relapse of the underlying disease is still one of the main causes of mortality. Donor lymphocyte infusion (DLI) is an immunotherapy that can be used after alloHSCT in patients with high-risk disease (prophylaxis), mixed donor chimerism or minimal residual disease (preemptive) and relapse (therapeutic). Donor derived graft versus tumor effects induce a durable remission after DLI. Aims: To characterize the use of DLI as prophylaxis, preemptive or therapeutic strategy in alloHSCT and evaluate overall survival (OS). Methods: A retrospective unicenter study was conducted to evaluate the use of DLIs in a cohort of 50 patients (91 DLIs), treated in a Bone Marrow Transplantation Unit, between January 2005 and December 2021. The chi-square test (categorical variables) and t-test or Wilcoxon-Mann-Whitney test (continuous variables) were used. OS was estimated according to Kaplan-Meier and compared by the log-rank test. Statistical analysis was made using SPSS28®. Results: Our cohort showed male predominance (n= 29, 58%) and a median age of 40 years (4-65), with 4 pediatric patients. Patients were affected by acute myeloid leukemia (n=20), acute lymphoblastic leukemia (n=12), chronic myeloproliferative leukemia (n=6), Hodgkin lymphoma (n=2), myelodysplastic/myeloproliferative syndrome (n=4), non-Hodgkin lymphoma (n=3), chronic lymphocytic leukemia (n=1), mixed phenotype leukemia, (n=1), multiple myeloma (n=1). Conditioning regimen was myeloablative in 19 (38%) patients and reduced-intensity in 31 (62%). All 50 donors were HLA-matched, and 8 (16%) were HLA-matched unrelated (MUR). DLIs use was prophylactic in 2 (4%) patients, preemptive in 7 (14%) and therapeutic in 41 (82%) patients. The median number of DLI/patient was 1 (1-8) and the median dose of total CD3+ cells infused was 1,0x107/Kg (0,1-13,48). The median time between alloHSCT and the first DLI was 17 months (1-133). Complete Response (CR) was defined by completed donor chimerism or no MRD detected. CR was maintained in 1/2 (50%) patients undergoing prophylactic DLIs. Patients who received preemptive and therapeutic DLIs achieved CR in 2/7 (29%) and 9/41 (22%) cases, respectively. Overall, 11 patients (22%) developed GVHD after DLIs. Presence of GVHD was associated with higher number of DLIs (2,45 vs 1,64) and with CR (p=0,041) No significant differences were observed in age (p=0,154), number of CD3+ infused (p=0,414), DLIs strategy (p=0,433), time between alloHSCT to first DLI (p=0,668) and CR. Death occurred in 30 (60%) patients. OS survival was defined as time from date of first DLI to date of last follow-up (FU) or date of death. With a median FU of 141 months, the OS was superior in patients who achieved CR compared to relapsed patients (34 months), Log-rank p=0.109. OS was significantly superior in preemptive and prophylaxis DLIs compared with therapeutic DLIs (Log-rank p<0,01). Overall, 8/19 (42%) patients are currently alive in CR. Summary/Conclusion: DLI has been widely applied to the therapeutic intervention, with promising results in prevention and preemptive strategy. Although with the limits of a relatively small and heterogeneous cohort, we describe our experience in the use of DLI and demonstrate that it is an effective prophylactic and preemptive treatment option in alloHSCT patients. Prospective studies on homogeneous patient cohorts are needed improve the effectiveness of DLI.

S241: NON-RESTRICTIVE DIET DOES NOT INCREASE GASTROINTESTINAL INFECTIONS AND FEBRILE NEUTROPENIA IN PATIENTS WITH NEUTROPENIA AFTER STEM CELL TRANSPLANTATION: DATA FROM A MULTICENTRE, RANDOMIZED TRIAL

Background: Infections represent a major cause of morbidity and mortality during neutropenia, especially after hematopoietic stem cell transplantation (HSCT). Multiple preventive measures, including low microbial diet, have been adopted to reduce these complications. However, the effect of a protective diet (PD) in this setting has never been explored prospectively and evidence-based results lack. Conversely, there is evidence that PD could negatively affect the quality of life and that a prolonged fasting duration can increase the incidence of acute gastrointestinal graft-versus-host disease (aGVHD) in allo-HSCT recipients. Aims: To prospectively compare infection and aGVHD rates in patients receiving a non-restrictive diet (NRD) compared to PD after HSCT. Methods: Since July 2016 we conducted a multicentre randomized interventional study comparing the use of a PD (Arm A) vs NRD (Arm B) in hematological patients aged≥18 years hospitalized to receive autologous or allogenic HSCT. Stratification for allo-HSCT patients was planned. Patients received the assigned diet during the entire period of neutropenia. For PD, foods cooked >80°C and/or thick peel fruit were considered diet-specific. For the NRD, raw fruit and vegetables (adherent to hospital hygiene standards) were considered diet-specific. The primary objective was to demonstrate the lack of significant differences in incidence of infections grade >2 (according to CTCAE 4.0) and deaths during neutropenia between the two arms. Secondary endpoints included assessment of gastrointestinal infections and fever of undetermined origin (FUO), change in body weight, length of hospitalization, overall survival estimated at 30 days and cumulative incidence of aGVHD within 100 days after allo-HSCT. Results: Overall, 162 patients were analyzed at interim analysis, 80 patients in PD group and 82 in NRD group. The two arms were well balanced in terms of: sex, age, disease type, number of previous therapeutic lines, disease status at enrollment, antimicrobial prophylaxis, and reason for hospital admission. Moreover, 32 patients received an allo-HSCT, 17 in the PD and 15 in the NRD group respectively. Detailed patients’ characteristics are summarized in Table 1. We did not observe a significant difference in terms of infections in the two randomized arms; infections grade >2 or death were reported in 35 (43.7%) patients in arm A and in 34 (41.5%) patients in arm B [relative risk RR=1.05, confidence interval (CI)95%=0.76-1.4]. The number of patients developing gastrointestinal infections and FUO during hospitalization was 8 (10%) vs 8 (9.8%) [RR=1.01, CI95%=0.57-1.53] and 32 (40%) vs 28 (34.1%) [RR=1.13, CI95%=0.82-1.54] in arm A and arm B, respectively. No differences in weight variations from admission to discharge were observed comparing arm A and arm B (mean 4.15kg vs 3.66kg, p=0.3). Average hospitalization length in the two arms was respectively 20.6 vs 21.5 days (p=0.4). No deaths were reported at day+30. For 32 allo-HSCT recipients, aGVHD grade ≥2 incidence at day +100 was 5% vs 1.2% in arm A and arm B, respectively (RR 1.65, CI95%=0.77-2.19). Image:Summary/Conclusion: Results of this multicentre prospective trial show similar rate of infections and deaths between patients receiving a PD versus a NRD during neutropenia after HSCT. These data suggest that the use of NRD could be considered for transplanted patients without risks of more infective events.

GUT MICROBIOTA EFFECTS IN HEMATOPOIETIC STEM CELL TRANSPLANT PATIENTS

Objective: In our study, we analyzed gut microbiota in allo-HSCT patients and aimed to evaluate the relationship of gut microbiota with transplant complications, mainly GVHD. Materials and Methods: A total of 25 adult recipients and donors who underwent allo-HSCT at Istanbul Anadolu Medical Center were included in the study. Stool samples were collected twice, before chemotherapy regimen and after allo-HSCT. Samples were analyzed by High Melting (HRM) Analysis and Next Generation Sequencing (NGS) methods after nucleic acid isolation. Sequencing was done with Illumina MiSeq. Bacteria Silva database was used for taxonomic classification and QIIME 2 programs were used for analysis. Statistical analyses were carried out with the R statistical programming language. Results: Twenty-five allo-HKHN recipients were included in the study. The mean age was 46.24±14.86 years in recipients and 43.40±13.20 years in donors. Gender distribution was M/F: 15/10 in patients and M/F: 17/8 in donors. Recipient and donor sibling HLA match was 10/10. The rate of GVHD associated with Allo-HSCT was 16%, and the relapse rate was 16%. It was observed that the Firmicutes and Proteobacteria phyla changed significantly before and after transplantation. The number of Entereccocus species was found to be higher in patients who developed GVHD and died. The loss of diversity was found to be statistically significant in the pre-transplant and post-engraftment samples of the patients. Conclusion: Gut microbiota diversity may guide the monitoring of GVHD and also may be manipulated for the treatment of GVHD. It is thought that increasing the diversity of commensal bacteria can also positively affect the prognosis of the disease.

Cytomegalovirus infection and rehospitalization rates after allogeneic hematopoietic stem cell and solid organ transplantation: a retrospective cohort study using German claims data

PurposeThis study aimed to describe the cytomegalovirus (CMV) infection rate, rehospitalizations, and comorbidities following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and solid organ transplantation (SOT).MethodsPatients who received allo-HSCT or SOT in 01/07/2015–30/06/2018 were identified using anonymized German claims data. The transplantation-related hospital admission date was defined as the index date, and patients were followed for up to 12 months (or death, first event relevant). The frequency of CMV infections (confirmed outpatient/inpatient diagnoses, ICD-10-GM codes: B25.-/B27.1) and the rate, number, and duration of all-cause rehospitalizations in the follow-up period were evaluated.ResultsA total of 226 allo-HSCT and 250 SOT patients were identified (mean age 52.8 years, 38.9% female). During the 12 months after transplantation, 29.2% of allo-HSCT patients and 16.8% of SOT patients received a CMV diagnosis. The majority of these diagnoses were given during the initial hospitalization or within the following 3 months. Across transplantation types, CMV patients had more hospital readmission days per patient-year (allo-HSCT 93.3 vs. 49.4, p = 0.001; SOT 42.0 vs. 20.7, p = 0.005), with a longer mean duration of readmissions (allo-HSCT 22.4 vs. 15.4 days, p < 0.001; SOT 11.6 vs. 7.5 days, p = 0.003). Comorbidity burden in transplantation patients was substantial, with several diagnoses being significantly more common among patients with CMV vs. non-CMV. One-year mortality did not differ significantly between patients with/without CMV.ConclusionBurden of transplant recipients with CMV in terms of rehospitalizations and comorbidities is substantial, highlighting the need for improved CMV prevention and treatment.

Need for hemodialysis in patients undergoing hematopoietic stem cell transplantation: risk factors and survival in a retrospective cohort

IntroductionAllogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) patients are exposed to acute and chronic nephrotoxic events (drugs, hypotension, infections, and microangiopathy). The need for hemodialysis (HD) may be associated with high mortality rates. However, the risk factors and clinical impact of HD are poorly understood. AimTo analyze survival and risk factors associated with HD in allo-HSCT Patients and methods: single-center cohort study 185 (34 HD cases versus 151 controls) consecutive adult allo-HSCT patients from 2007-2019. We performed univariate statistical analysis, then logistic regression and competing risk regression were used to multivariate analysis. Survival was analyzed by Kaplan-Meier and Cox proportional-hazards models. ResultsThe one-year HD cumulative incidence was 17.6%. Univariate analysis revealed that HD was significantly associated with male gender, age (p 0.056), haploidentical donor, grade II-IV acute GVHD, polymyxin B, amikacin, cidofovir, microangiopathy, septic shock (norepinephrine use) and steroid exposure. The median days of glycopeptides exposure (teicoplanin/vancomycin) was 16 (HD) versus 10 (no HD) (p 0.088). In multivariate analysis, we found: norepinephrine (hazard ratio, HR:3.3; 95% confidence interval, 95%CI:1.2-8.9; p 0.024), cidofovir drug (HR:11.0; 95%CI:4.6- 26.0; p < 0.001), haploidentical HSCT (HR:1.94; 95%CI:0.81-4.65; p 0.14) and Age (HR:1.01; 95%CI: 0.99-1.03; p 0.18) . The HD group had higher mortality rate (HR:6.68; 95% CI: 4.1-10.9; p < 0.001). ConclusionHD was associated with decreased survival in allo-HSCT. Carefully use of nephrotoxic drugs and improving immune reconstitution could reduce severe infections (shock) and patients requiring cidofovir, which taken together may result in lower rates of HD, therefore improving survival.

Soluble T Cell Immunoglobulin and Mucin Domain-3 (sTIM-3) Predicts Graft-Versus-Host Disease (GVHD) in Iranian Allogeneic Hematopoietic Stem Cell Transplantation

Background: T cell immunoglobulin and mucin domain-3 (TIM-3) is an immune-checkpoint molecule that is upregulated following allogeneic immune responses and could play an important role in the development and pathogenesis of graft-versus-host disease (GVHD). The soluble form of TIM-3 (sTIM-3) is increased following the upregulation of membranous TIM-3. Objectives: The aim of this study was to evaluate the association between plasma level of sTIM-3 and acute GVHD (aGVHD) incidence in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Blood samples were collected from 42 allo-HSCT patients and 20 healthy individuals 2 weeks after allo-HSCT. The plasma level of sTIM-3 was measured using enzyme-linked immunosorbent assay (ELISA). The clinical and demographic data of patients were collected from the clinical documents. Data analysis was evaluated using student t-test and one-way ANOVA tests. P-values less than 0.05 were assumed statistically significant. Results: Among 18 (42.8%) patients with aGVHD symptoms, 10 (23.8%) had severe GVHD and 8 (19%) experienced mild GVHD. Plasma sTIM-3 levels at day +14 were significantly higher in patients who developed aGVHD compared to allo-HSCT patients without GVHD and also the healthy control individuals (P-value = 0.015 and &lt; 0.001). Among the aGVHD patients, the sTIM-3 levels in those with severe GVHD were approximately 2.5 times higher than those with mild GVHD (P-value &lt; 0.001). Conclusions: We have identified a high plasma level of sTIM-3 as a valuable biomarker in predicting the development of acute GVHD, especially severe aGVHD in allo-HSCT patients.

Neurological complications in adult allogeneic hematopoietic stem cell transplant patients: Incidence, characteristics and long-term follow-up in a multicenter series.

Neurological complications (NCs) represent a diagnostic and clinical challenge in allogeneic hematopoietic stem cell transplant (alloHSCT) patients. We retrospectively analyzed NC incidence, etiology, timing, characteristics, outcome, and long-term effects in 2384 adult patients transplanted in seven Italian institutions between January 2007 and December 2019. Ninety-three (3.9%) patients were affected by 96 NCs that were infectious (29.2%), immune/inflammatory (26%), drug-related (12.5%), cerebrovascular (5.2%), metabolic (3.1%), related to central nervous system disease relapse (11.5%) and malignancy (3.1%), or undefined (9.4%). Six patients (6.4%) had neurological manifestations of chronic graft-versus-host disease (GVHD). NCs occurred on average at day +128 (from -5 to +4063). Early (< day +120) and late NCs had similar frequencies (46.9% vs 53.1%, p = 0.39). Thirty-one patients (33.3%) were affected by acute or chronic GVHD at the NC onset. With a median follow-up of 25.4 (0.4-163) months, the overall mortality due to NCs was 22.6%. The median time between NC onset and death was 36 (1-269) days. Infectious NCs were the main cause (61.9%) of NC-related mortality. A persistent neurological impairment occurred in 20.4% patients, 57.9% of whom being affected by immune/inflammatory NCs. This study highlights the rare, yet severe impact of alloHSCT-associated NCs on patient survival and long-term functional ability.

Central nervous system infection with Seoul Orthohantavirus in a child after hematopoietic stem cell transplantation: a case report

BackgroundPatients with allogeneic hematopoietic stem cell transplantation (allo-HSCT) are prone to complicate viral infection. Central nervous system (CNS) involvement caused by the viruses is rare but with poor prognosis. Hantavirus, which usually cause hemorrhagic fever with renal syndrome (HFRS), and none case has been reported about these infection in allo-HSCT patients.Case presentationIn August 2021, a 13-year-old male child developed intermittent fever and refractory hypotension after allo-HSCT. Magnetic resonance imaging of the head revealed abnormal signal foci in the left midbrain cerebral peduncle and bilateral thalamus. His family reported traces of mouse activity in the patient’s home kitchen. HFRS was suspected, but with no significant kidney damage. The specific immunoglobulin (Ig) G and M of hantavirus were negative. The metagenomic next-generation sequencing (mNGS) detected Seoul Orthohantavirus (SEOV) sequences directly in cerebrospinal fluid and blood.ConclusionsAllo-HSCT patients are a high-risk group for infection. Usually the causative agent of infection is difficult to determine, and sometimes the site of infection is concealed. This report highlights the importance of suspecting hantavirus infection in allo-HSCT patients with CNS symptoms despite the absence of renal syndromes. The mNGS is a powerful tool for detecting pathogens. CNS infection with Seoul orthohantavirus in transplant patients is rare but possible as demonstrated in this case. To the best of our knowledge, this is the first reported case employing mNGS to diagnose SEOV caused CNS infection in an allo-HSCT patient.

Current Status and Perspectives of Allogeneic Hematopoietic Stem Cell Transplantation in Elderly Patients with Acute Myeloid Leukemia.

As in younger patients, allogeneic stem cell transplantation (alloHSCT) offers the best chance for durable remission in older patients (≥60 years) with acute myeloid leukemia (AML). However, defining the best treatment strategy (and in particular, whether or not to proceed to alloHSCT) for elderly patients with AML remains a difficult decision for the hematologist, since potential toxicity of conditioning regimens, risks of graft-versus-host disease, impaired immune reconstitution and the need for prolonged immunosuppression may be of major concern in these vulnerable patients with complex needs. Hopefully, significant progress has been made over the past decade in alloHSCT for elderly patients and current evidence suggests that chronological age per se (between 60 and 75) is not a reliable predictor of outcome after alloHSCT. Here, we review the current state of alloHSCT in elderly patients with AML and also discuss the different approaches currently being investigated to improve both accessibility to as well as success of alloHSCT in these patients.

Antibody response to COVID-19 vaccine in 130 recipients of hematopoietic stem cell transplantation.

We evaluated anti-spike protein antibody (anti-S) production in 130 hematopoietic stem cell transplant (HSCT) recipients who received the coronavirus disease-2019 vaccine. Sixty-five received allo-HSCT and 65 received auto-HSCT. Disease-specific treatments were being administered to 43.1% of allo-HSCT and 69.2% of auto-HSCT patients. Seropositivity was observed in 87.7% of allo-HSCT and 89.2% in auto-HSCT patients. Anti-S antibody production was significantly impaired in auto-HSCT patients compared with controls (178U/mL [0.4–4990.0] vs. 669 U/mL [40.3–4377.0], p < 0.001), but not in allo-HSCT patients (900 U/mL [0.4–12,893.0] vs. 860 U/mL [40.3–8988.0], P = 0.659). Clinically relevant anti-S antibody levels (> 264 U/mL) were achieved in 59.2% of patients (76.9% in allo-HSCT and 41.5% in auto-HSCT). The main factors influencing the protective level of the antibody response were the CD19 + cell count and serum immunoglobulin G levels, and these were significant in both allo-HSCT and auto-HSCT patients. Other factors included time since HSCT, complete remission status, use of immunosuppressive drugs, and levels of lymphocyte subsets including CD4, CD8 and CD56 positive cells, but these were only significant in allo-HSCT patients. Allo-HSCT patients had a relatively favorable antibody response, while auto-HSCT patients had poorer results.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12185-022-03325-9.