Hematological Disease Patients Research Articles

Omicron SARS-CoV-2 infection management and outcomes in patients with hematologic disease and recipients of cell therapy.

Scarce real-life data exists for COVID-19 management in hematologic disease (HD) patients in the Omicron era. To assess the current clinical management and outcome of SARS-CoV-2 infection diagnosed, identify the risk factors for severe outcomes according to the HD characteristics and cell therapy procedures in a real-world setting. A retrospective observational registry led by the Spanish Transplant Group (GETH-TC) with 692 consecutive patients with HD from December 2021 to May 2023 was analyzed. Nearly one-third of patients (31%) remained untreated and presented low COVID-19-related mortality (0.9%). Nirmatrelvir/ritonavir was used mainly in mild COVID-19 cases in the outpatient setting (32%) with a low mortality (1%), while treatment with remdesivir was preferentially administered in moderate-to-severe SARS-CoV-2 infection cases during hospitalization (35%) with a mortality rate of 8.6%. The hospital admission rate was 23%, while 18% developed pneumonia. COVID-19-related mortality in admitted patients was 14%. Older age, autologous hematopoietic stem cell transplantation (SCT), chimeric antigen receptor T-cell therapy, corticosteroids and incomplete vaccination were factors independently associated with COVID-19 severity and significantly related with higher rates of hospital admission and pneumonia. Incomplete vaccination status, treatment with prior anti-CD20 monoclonal antibodies, and comorbid cardiomyopathy were identified as independent risk factors for COVID-19 mortality. The results support that, albeit to a lower extent, COVID-19 in the Omicron era remains a significant problem in HD patients. Complete vaccination (3 doses) should be prioritized in these immunocompromised patients. The identified risk factors may help to improve COVID-19 management to decrease the rate of severe disease, ICU admissions and mortality.

Prevalence, Risk Factors, and Prognostic Value of Anxiety and Depression in Acute Myeloid Leukemia

Introduction: Limited studies report anxiety and depression prevalence and their correlations with prognosis in acute myeloid leukemia (AML). Even worse, their risk factors for AML remained unclear. This study aimed to investigate the prevalence, risk factors, and prognostic value of anxiety and depression in AML patients. Methods: Totally, 132 de novo AML patients, 60 non-malignant hematological disease patients (as disease controls), and 60 healthy controls were enrolled. Anxiety and depression status were evaluated by the Hospital Anxiety and Depression Scale (HADS) in all participants. Results: HADS-anxiety score (8.2 ± 3.2 vs. 6.1 ± 2.9 vs. 4.7 ± 2.8), anxiety rate (48.5% vs. 25.0% vs. 10.0%), HADS-depression score (7.8 ± 3.0 vs. 5.8 ± 3.0 vs. 4.0 ± 2.8), and depression rate (43.2% vs. 23.3% vs. 8.3%) were highest in AML patients, followed by disease controls, and the lowest in healthy controls (all p < 0.001). Multivariate logistic regression analysis identified that factors independently associated with anxiety included male (p = 0.002, odds ratio [OR] = 0.240), smoking (p = 0.043, OR = 2.474), education duration (p = 0.024, OR = 0.889), and NCCN high-risk stratification (p = 0.008, OR = 2.347), while those independently associated with depression were age (p = 0.005, OR = 1.055), single/divorced/widowed status (p = 0.014, OR = 3.149), NCCN high-risk stratification (p = 0.002, OR = 3.077), and white blood cell (WBC) (p < 0.001, OR = 1.062). Additionally, depression was correlated with shorter accumulating event-free survival (p = 0.012) and overall survival (p = 0.041) in AML patients, whereas anxiety was not. Conclusions: Anxiety and depression are prevalent, among which depression is associated with poor survival profile, but anxiety is not; moreover, age, male, education, single/divorced/widowed status, smoking, NCCN high-risk stratification, and WBC were independent related factors of anxiety and depression in AML patients.

Epidemiological Characteristics and Drug-Resistance Genotype of CRE in Patients with Hematological Diseases in a Single Center of China

Patients with blood diseases have a significantly higher risk of infections and mortality rates compared with other type of patients. Referring to the 2019 CDC criteria for CRE, we examined the carbapenemase producing genotype and resistance characteristics of CRE strains (760 strains) in patients with hematological diseases. Among these, carbapenemase producing CRE (CP-CRE) accounts for 60.39% (459/760), non-carbapenemase producing CRE (non-CP-CRE) accounts for 39.61% (301/760). The data indicated that the most common bacteria in patients with hematologic disorders were Escherichia coli, Klebsiella pneumoniae and Enterbater cloacae, which primarily produced NDM-type metallo-β-lactamases. The rates of drug resistance in CP-CRE strains with MIC≥16 to Meropenem and Imipenem were 92.51% (420/454) and 86.12% (391/454), respectively. The drug resistance rates of non-CP-CRE strain with MIC≥16 to Meropenem and Imipenem were only 22.22% and 15.34%, respectively. Furthermore, we discovered that 36.88% (111/301) of non-CP-CRE strains were resistant to Ertapenem alone but still susceptible to Meropenem and Imipenem. The therapy of such CRE may differ significantly from that of other CRE strains, ETP-CRE may not be a typical CRE. In conclusion, Our data determined that the CRE colonized or infected in patients with hematological diseases was dominated by Escherichia coli and metallo-carbapease-producing types, among which the NDM genotypes was predominant. This is quite different from the domestic statistics, indicating that the CRE types infected by hematological disease patients are special and not consistent with other patients. We discovered that some patients with hematological diseases carried or were infected with ETP-CRE, which was sensitive to Meropenem and Imipenem. In terms of therapy, ETP-CRE strains may differ from other CRE in patients with hematological diseases，it may not be a typical CRE.

Prevention of pneumocystis pneumonia in patients with hematological diseases: Efficacy oflow-dose atovaquone.

At our institution, patients with hematological disease who require Pneumocystis jirovecii pneumonia (PJP) prophylaxis were administered atovaquone at a low dose (750 mg/day). However, there have been few reports on the efficacy of low-dose atovaquone administration, and the purpose of this study is, therefore, to investigate its effectiveness. We investigated the expression of PJP in patients with hematological disease who received atovaquone administration. Atovaquone was administered at a low dose of 750 mg once daily, and the follow-up time was the period of PJP prophylaxis that included atovaquone administration. 85 patients were included in the study. The median age of the study population was 72 years (range: 33-97). The duration of atovaquone treatment and follow-up time were 150 days (22-1,018) and 258 days (22-1,457), respectively. In hematologic diseases, multiple myeloma was high in 31 patients and malignant lymphoma in 28 patients. No patients exhibited PJP during the observation period. In hematological disease patients with relatively low risk of PJP, low-dose atovaquone may prevent the onset of PJP.

Comparison of humoral and cellular immune responses in hematologic diseases following completed vaccination protocol with BBIBP-CorV, or AZD1222, or BNT162b2 vaccines against SARS-CoV-2.

Vaccination has proven the potential to control the COVID-19 pandemic worldwide. Although recent evidence suggests a poor humoral response against SARS-CoV-2 in vaccinated hematological disease (HD) patients, data on vaccination in these patients is limited with the comparison of mRNA-based, vector-based or inactivated virus-based vaccines. Forty-nine HD patients and 46 healthy controls (HCs) were enrolled who received two-doses complete vaccination with BNT162b2, or AZD1222, or BBIBP-CorV, respectively. The antibodies reactive to the receptor binding domain of spike protein of SARS-CoV-2 were assayed by Siemens ADVIA Centaur assay. The reactive cellular immunity was assayed by flow cytometry. The PBMCs were reactivated with SARS-CoV-2 antigens and the production of activation-induced markers (TNF-α, IFN-γ, CD40L) was measured in CD4+ or CD8+ T-cells ex vivo. The anti-RBD IgG level was the highest upon BNT162b2 vaccination in HDs (1264 BAU/mL) vs. HCs (1325 BAU/mL) among the studied groups. The BBIBP-CorV vaccination in HDs (339.8 BAU/mL ***p < 0.001) and AZD1222 in HDs (669.9 BAU/mL *p < 0.05) resulted in weaker antibody response vs. BNT162b2 in HCs. The response rate of IgG production of HC vs. HD patients above the diagnostic cut-off value was 100% vs. 72% for the mRNA-based BNT162b2 vaccine; 93% vs. 56% for the vector-based AZD1222, or 69% vs. 33% for the inactivated vaccine BBIBP-CorV, respectively. Cases that underwent the anti-CD20 therapy resulted in significantly weaker (**p < 0.01) anti-RBD IgG level (302 BAU/mL) than without CD20 blocking in the HD group (928 BAU/mL). The response rates of CD4+ TNF-α+, CD4+ IFN-γ+, or CD4+ CD40L+ cases were lower in HDs vs. HCs in all vaccine groups. However, the BBIBP-CorV vaccine resulted the highest CD4+ TNF-α and CD4+ IFN-γ+ T-cell mediated immunity in the HD group. We have demonstrated a significant weaker overall response to vaccines in the immunologically impaired HD population vs. HCs regardless of vaccine type. Although, the humoral immune activity against SARS-CoV-2 can be highly evoked by mRNA-based BNT162b2 vaccination compared to vector-based AZD1222 vaccine, or inactivated virus vaccine BBIBP-CorV, whereas the CD4+ T-cell mediated cellular activity was highest in HDs vaccinated with BBIBP-CorV.

A clinical analysis of Candida tropicalis bloodstream infections associated with hematological diseases, and antifungal susceptibility: a retrospective survey.

To assess the clinical features and outcomes of hematological disease patients with Candida tropicalis bloodstream infections and determine the antifungal susceptibility of C. tropicalis. This is a retrospective, single-center, observational study conducted in the Department of Hematology at The First Affiliated Hospital of Guangxi Medical University from January 2013 to December 2021. A total of 26 hematological disease patients with C. tropicalis bloodstream infections were enrolled, and their clinical features, treatment plans, and prognoses were assessed. Univariate analysis was performed by Kaplan-Meier analysis and multivariate analysis was conducted using a Cox regression model. The antifungal susceptibility of C. tropicalis was determined from patient blood cultures. The patients had a mean age of 35 years (range: 10-65 years), 50% were male (13/26) and 88.5% had hematologic malignancies (23/26) while the remaining three patients included two cases of severe aplastic anemia and one case of β-thalassemia. All patients had neutropenia. Seven patients were initially given azole alone (26.9%), five of whom failed treatment and died (71.4%). Fifteen patients were treated with echinocandin (57.7%), three of whom failed treatment and died (20.0%), and eight patients were treated with amphotericin B (30.8%), two of whom failed treatment and died (25.0%). The total and attributable mortality rates were 42.3 and 34.6%, respectively. Univariate analysis showed that there are six risk factors for attributable deaths among hematological disease patients with C. tropicalis blood infections. These risk factors included septic shock, Pitt bacteremia scores ≥4, procalcitonin levels ≥10 ng/mL, positive plasma (1,3)- β-D glucan assay, serum albumin levels <30.0 g/L, time from fever to antifungal treatment initiation ≥5 days and time between neutropenia and antifungal treatment ≥10 days. Moreover, skin and mucosal infections and a treatment schedule that included amphotericin B and drug combinations are protective factors for attributable deaths. Multivariate analysis showed that septic shock (p = 0.006) was an independent risk factor for attributable death. All isolates were sensitive to flucytosine and amphotericin B. The intermediate or resistance of C. tropicalis to fluconazole, itraconazole and voriconazole were 41.7, 50, and 41.7%, respectively. Hematological disease patients with C. tropicalis bloodstream infections had a high mortality rate, and early antifungal therapy significantly reduced mortality. Candida tropicalis was highly resistant to azole drugs and sensitive to flucytosine and amphotericin B. According to our study, the preferred agent is amphotericin B and drug combinations should be considered for severe infections.

Pattern of Hematological Diseases treated at Birat Medical College and Teaching Hospital

Introduction: Hematological diseases are increasing day to day in the eastern region of Nepal. There are very few centers providing treatment to hematological diseases patients in the eastern region of Nepal.&#x0D; Objectives: The aim of this study is to stratify the types of hematological diseases treated at Birat Medical College and Teaching Hospital along with their demographic and clinic-pathological features.&#x0D; Methodology: This descriptive cross-sectional study was conducted from 21 December 2020 to 20 July 2021 in the Department of Hemato-Oncology. All the clinically as well as laboratorically proven hematological disease patients receiving treatment during the study period were taken as study population. Hematological diseases are blood related diseases like anemia, blood cancers (like leukemia , lymphoma , multiple myeloma) ,hemolytic diseases , coagulation disease ,thrombocytopenia, etc. Data were entered and analyzed in Microsoft Excel version 2010 and IBM SPSS Statistics version 22 respectively.&#x0D; Result: There were a total of 48 cases who received treatment during the study duration. The mean age of the cases was 50 (range 2-92) years with female gender almost equal to male gender. About 29% cases were involved in tobacco/ smoking . Majority of the cases involved were leukemia (33%), lymphoma (21%) ,hemolytic disease(11%) and Immune thrombocytopenic purpura(11%) cancer.We have good clinical remission (61%) of the cases, majority of which were non malignant cases. Total 77% of the cases were alive, 4% were referred while 19 % of the cases expired during the study period, majority of which were acute leukemias.&#x0D; Conclusion:There is a rise of hematological cancer in eastern Nepal and hence there is a need for a comprehensive hematological center in the eastern region of Nepal.

PB2268: IMPACT OF HEMATOLOGICAL DISORDERS ON MORTALITY AND SERIOUS OUTCOMES IN SARS-COV-2 INFECTION: A MULTICENTER COHORT STUDY

Background: Presence of hematologic diseases has been associated with worse outcomes in patients with SARS-CoV2 virus infection, including higher mortality rates than patients without these comorbidities. This cohort study included patients with and without prevalent hematologic diseases. Aims: To determine the impact of hematologic disorders on 30-day mortality and other severe outcomes in patients with SARS-COV-2 infection. Methods: A prospective cohort study was conducted in 6 COVID-19 reference centers in Mexico between March 1, 2020 and January 31, 2021. The main objective of our study was to determine the impact of hematologic disease status on 30-day mortality and on a composite outcome of severe complications(AKI, ARDS, and liver failure). Using data from patients treated in the largest center, those with COVID-19 and hematologic diseases were compared to non-hematologic COVID-19 controls. Pairing was performed according to COVID-19 treatment, age, sex, BMI, and CDC-defined variables of high mortality risk. As a secondary objective, a multi-center analysis was performed to determine risk factors for 30-day mortality in hematologic disease patients, determined by univariate and multivariate analysis. Results: For the main objective, 59 patients were recruited(matched 1:1). In the 30-day mortality analysis, we found no differences between the two groups: HR 1.08 (95% CI 0.52-2.24)p=0.833, OR 1.08 (95% CI 0.46-2.48)p=0.872. Regarding the composite outcome of severe complications, we found a HR 1.03, (95% CI 0.59-1.80)p=0.896. There was no difference in the 30-days survival between the two groups(p=0.832)(Figure 1). For our secondary objective, 158 patients were recruited: 46.6% women, median age 45 years, BMI 26.3 (IQR 23.2-29.7), 19.0% diabetes, 14.6% hypertension and 18% smokers, and 83.5% with hematologic malignancies. Supplementary oxygen was used in 81.6%, in hospital-treatment was necessary in 84.1%, and 41.4% required ICU admission. 30-day mortality was 42.4%. Complications during hospitalization included respiratory failure in 84.5%, of which only 48% received VMI; reasons for not receiving VMI included a non-intubation order issued by the patient or family members and lack of infrastructure. Regarding COVID-19 treatment, 30% received dexamethasone 6 mg/day and 30% received thromboprophylaxis. In the univariate analysis, the following were predictive factors of mortality: all types of malignancy HR 2.64 (95% CI 1.06-6.59)p=0.030, lymphoid malignancy HR 2.52 (95% CI 1.06-6.95)p=0.035, last treatment <3months HR 2.3 (95% CI 1.15-4.61)p=0.018, and palliative treatment HR 3.01 (95% CI I.35–7.72)p=0.007. Complete response was a protective factor HR 0.229 (95% CI 0.093–0.53)p=0.001. The use of dexamethasone was not a protective factor in this population HR 1.32 (95% CI 0.80-2.18)p=0.273. In the multivariate analysis, palliative status HR 4.8 (95% CI 1.07-22.18)p=0.040 and complete response HR 0.22 (95% CI 0.062-0.815)p=0.023 were risk and protective factors, respectively. Image:Summary/Conclusion: After careful pairing according to clinical characteristics, including CDC variables predictive of high mortality risk, we observed survival didn’t differ between groups, concluding hematologic disease did not impact 30-day mortality in COVID-19 patients. This is striking, since previous reports have described a higher mortality risk among patients with hematologic diseases, although the pairing process hadn’t been as thorough as ours. Also of note, use of dexamethasone was not associated with lower 30-day mortality in patients with hematologic diseases.

Clinical Features and Prognosis of Patients with Hematological Disease Complicated with Mucor Infection

To investigate the clinical features, treatment and prognosis of patients with hematological diseases complicated with mucor infection. The risk factors, clinical features, treatment regimen and prognosis of 18 hematological disease patients with mucor infection diagnosed by histopathology in our center from April 2014 to June 2020 were retrospectively analyzed. Thirteen males and five females, with an average age of 30 (13－54) years old, were diagnosed as mucor infection by histopathological examination at the site of infection, including 16 cases of mucor infection alone and 2 cases of mucor + aspergillus mixed infection. There were 12 cases with malignant hematological disease and 6 cases with severe aplastic anemia, all of whom with long-term agranulocytosis, and their clinical manifestations and imaging findings were not specific. The common sites of infection were sinuses and lungs, and some patients showed multiple systemic manifestations. The remission status of hematological diseases and recovery of immune function showed an impact on the prognosis. All the patients were treated with amphotericin B liposome combined with posaconazole, and 15 patients were treated with surgery combined with antifungal drugs, 9 of whom were effective and 6 were ineffective, while intravenous administration in 3 cases was ineffective. It is difficult to diagnose hematological disease complicated with mucor infection. After early diagnosis, prognosis can be improved by amelioration of primary state and combination of drugs and surgery.

Clinical features in maxillary sinus fungus ball in patients with malignant hematological disease.

Previous studies on fungus balls have primarily focused on immunocompetent patients, and only a few studies have described the clinical characteristics of fungus balls in malignant hematological disease (MHD) patients. Therefore, we compared the clinical features of maxillary sinus fungus ball (MSFB) between immunosuppressive patients with MHD and immunocompetent patients. Twenty patients with MHD and 40 randomly selected immunocompetent patients were enrolled and divided into MHD and non-MHD groups. All patients were diagnosed with MSFB and their clinical features were retrospectively analyzed. Patients in the MHD group had non-specific clinical symptoms and endoscopic manifestations of MSFB, similar to those in the non-MHD group. On computed tomography (CT), the MHD group showed higher Lund-Mackay scores, lesser single sinus opacifications, more multiple sinus opacifications on the affected side, and more bilateral opacifications compared to the non-MHD group. The MHD group had a lower frequency of central hyper-density and heterogeneous opacifications than the non-MHD group. There were no significant differences between the two groups in terms of the fungal-infected side, lateral sinus wall ratio, sclerosis of the lateral sinus wall, erosion of the inner sinus wall, and nasal septum deviation. The clinical symptoms and endoscopic manifestations of MSFB in patients with MHD were similar to those of immunocompetent patients. However, more atypical signs and wider mucosal inflammation were found on CT scans of MSFB patients with MHD. These results indicate that caution should be executed when excluding the possibility of fungus balls in immunosuppressive patients.

Hypofibrinogenemia is associated with a high degree of risk in infectious diseases: a post-hoc analysis of post-marketing surveillance of patients with disseminated intravascular coagulation treated with thrombomodulin alfa

BackgroundIn patients with infectious diseases, disseminated intravascular coagulation (DIC) is often diagnosed without the fibrinogen value. The relationship between hypofibrinogenemia and outcomes of DIC in infectious diseases has thus remained unclear.MethodsWe analyzed 3204 patients who received with thrombomodulin alfa (TM-α) for DIC and suspected DIC. Hypofibrinogenemia was defined by a fibrinogen level < 1.5 g/L.ResultsHypofibrinogenemia was observed in 10.3% of patients with infectious diseases. The frequencies of both bleeding and organ failure symptoms, and the scores for organ failure or the DIC diagnostic criteria were significantly higher in infectious disease patients with hypofibrinogenemia, suggesting that in patients with infectious diseases, hypofibrinogenemia is associated with more progressive and severe DIC. Although the 28-day survival rate and the DIC resolution rate were both significantly lower for infectious disease patients with DIC with hypofibrinogenemia than for those without hypofibrinogenemia, this difference was not observed in DIC patients with hematological diseases.ConclusionsHypofibrinogenemia among infectious disease patients with DIC may reflect increased consumption of fibrinogen due to accelerated coagulation reactions, while hypofibrinogenemia among hematological disease patients with DIC may be caused by fibrinogenolysis due to hyperfibrinolysis, and frequently results in bleeding and multiple-organ failure.

Long-Term Results of Total Hip Arthroplasty in Young Patients With Osteonecrosis After Allogeneic Bone Marrow Transplantation for Hematological Disease: A Multicenter, Propensity-Matched Cohort Study With a Mean 11-Year Follow-Up

BackgroundThe number of young patients with hematological disease requiring total hip arthroplasty (THA) is expected to increase. We aimed to investigate the long-term THA outcomes in patients with osteonecrosis of the femoral head (ONFH) following allogeneic bone marrow transplantation (BMT) for hematological disease. MethodsAll patients who underwent THA for osteonecrosis after BMT from 1997 to 2012 were identified at 2 institutions. Using propensity scores, 75 THAs in 45 patients were matched for age, gender, body mass index, American Society of Anesthesiologists score, and year of surgery with 75 THAs in 58 patients with idiopathic ONFH without a history of hematological disease (1:1 ratio). The mean age at surgery was 36.7 years and 52% were men. Clinical and radiographic evaluations were performed and clinical scores were obtained at last follow-up. Kaplan-Meier analyses were used to compare survivorship. ResultsAt a mean follow-up of 10.6 ± 3.5 years, clinical, radiographic, and survivorship outcomes, and the Harris hip scores were similar between both groups. The 13-year survivorship for all-cause revision was 93.4% for the BMT group and 95% for the control group (P = .928). No significant differences were observed between groups in the rates of reoperation (4% vs 5.3%, P = 1.000), 90-day readmission (all 5.3%), or overall mortality (4.4% vs 1.7%, P = .681). No hips had periprosthetic joint infection or septic loosening in either group. Osteolysis occurred in none of the BMT patients and in 2 hips (2.7%) of the control patients (P = .497). ConclusionThis large cohort multicenter survey at 11-year follow-up shows that contemporary cementless THA in young hematological disease patients after allogeneic BMT is not associated with a higher risk for surgical complications, revision, reoperation, readmission, and mortality compared to a matched cohort of idiopathic ONFH.

PB2361 INCIDENCE, RISK FACTORS AND OUTCOMES OF SINUSOIDAL OBSTRUCTION SYNDROME AFTER HAPLOIDENTICAL ALLOGENEIC STEM CELL TRANSPLANTATION

Background:Recent studies have reported that the outcomes after haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT) are comparable to those after matched related donor (MRD) HSCT in hematological disease patients. Hepatic sinusoidal obstruction syndrome (SOS) is a rare but lethal complication with a reported incidence of 8%∼14% and a mortality rate higher than 80% for the severe type of SOS after MRD HSCT. Although sufficient information is available on SOS after MRD HSCT, few studies have systematically investigated SOS after HID HSCT. Here, we conducted a retrospective multicenter study in China to assess the incidence, clinical characteristics, risk factors and transplant outcomes of SOS following HID HSCT.Aims:The aim of this study is to compare the incidence, clinical characteristics, risk factors and transplant outcomes of SOS after HID HSCT and MRD HSCT.Methods:We retrospectively evaluated 36 consecutive patients with a confirmed diagnosis of SOS after allogeneic HSCT (allo‐HSCT) (HID: 23 patients, MRD: 13 patients) at four large HSCT centers in China between January 2003 and July 2018. The diagnosis of SOS was based on clinical criteria that required the occurrence of two of the following events: hyperbilirubinemia (≥ 2 mg/dL), hepatomegaly or right upper quadrant pain of hepatic origin, or unexplained weight gain (&gt; 2% of baseline body weight) due to fluid accumulation. The SOS severity was defined as mild, moderate, severe or very severe. Kaplan‐Meier survival analysis was used to estimate the cumulative incidence of relapse, overall survival (OS) and transplant‐related mortality (TRM), and a log‐rank test was performed to assess the statistical significance. Cox regression analysis was used to identify potential risk factors affecting the occurrence of SOS.Results:SOS developed in 0.4% of the patients (HIDs: 0.4%, MRDs: 0.5%, p = 0.952) at a median time of 21.50 days (range, 1‐55) after allo‐HSCT. No significant difference was found between the two groups in gender, disease distribution, interval from diagnosis to HSCT, disease status at the time of HSCT, donor‐patient sex match, donor‐patient ABO match, stem cell source, follow‐up time, engraftment time and cumulative incidence of acute graft‐versus‐host disease (GVHD) or chronic GVHD. The HID and MRD groups were comparable in terms of the median time to diagnosis (HIDs: 24 days, MRDs: 20 days, p = 0.316) and the presentation and severity of SOS. For patients diagnosed with SOS, the 2‐year cumulative incidences of relapse were 22.7% and 22.4% in patients receiving HID and MRD transplantations, respectively (p = 0.584). OS at 2 years was 10.4% and 38.5% in the two groups, respectively (p = 0.113). The TRM at 100 days was 60.9% in the HID group and 38.5% in the MRD group (p = 0.178). According to the multivariate analysis, significant independent risk factors for the occurrence of SOS were delayed platelet engraftment (p = 0.007) and an advanced disease status at the time of HSCT (p = 0.009). The frequency of SOS did not differ significantly in terms of the donor type (p = 0.222).Summary/Conclusion:Haploidentical transplantation may achieve results similar to those of transplantation with matched related donors in terms of the SOS incidence and outcomes. The occurrence of SOS did not differ by donor type.

Ruxolitinib Combined with Etanercept for Patients with Corticosteroid-Refractory Acute Graft Versus Host Disease after Allogeneic Stem Cell Transplantation: A Multi-Center Prospective Study

Background and Aim: Acute graft versus host disease (aGVHD) remains a major problem after allogeneic hematopoietic stem cell transplantation (allo-SCT). Steroids currently represent the gold-standard treatment for aGVHD based on prospective randomized trials, while fewer than half of patients have a lasting complete response. The long-term mortality rate of steroid-refractory (SR) aGVHD remains around 70%. To date, no consensus has been reached regarding the optimal salvage treatment for SR-aGVHD. We performed the first prospective, multi-center clinical trial to assess the efficacy and safety of the combination of ruxolitinib and etanercept as a novel approach to treat grades II-IV SR-aGVHD .Methods: Thirty-one malignant hematologic disease patients with grades II-IV SR-aGVHD after allo-SCT from three centers in East China were enrolled from January 2017 to January 2018. All of them received ruxolitinib and etanercept as salvage-therapy for SR-aGVHD. Ruxolitinib was initiated at a dose of 5-10 mg BID for 2 months, and then tapered gradually for another one month. Etanercept was administrated at 25mg BIW for 2-8 weeks.Results: At day 30 after starting the combination treatment, overall response (complete and partial response: CR+PR) was 90.3% with 74.2% being CR. The incidences of CR per organ were 93.5%, 84.2% and 82.6% for skin, liver, and gut involvement, respectively. The median time from combination therapy to the optimal response was 12 days.The patients who received ruxolitinib within 14 days after aGVHD onset have a higher CR rate that those with delayed ruxolitinib therapy (94.7% vs. 50.0%, p=0.007). And the patients without gut infections have a higher CR rate than infected cohort (90.0% vs. 54.5%,p=0.037). Only time from aGVHD to ruxolitinib (RR=3.17, 95%CI 2.40~5.33, p=0.009) were independent predictors for incomplete response. III-IV Cytopenia and CMV-reactivation were observed during ruxolitinib treatment in 29.0% and 41.9% of patients. A significant decline in the level of IL-6, IFN-y and TNF-α was observed during 2-week treatment. The number of peripheral effector Tregs and Treg/Th17 ratio were significantly increased in responding patients.Compared with the historical cohort of basiliximab and etanercept for SR-aGVHD in our center (n=31), no significant difference was found on the baseline, such as age, gender, underlying disease, disease status, conditioning intensity, as well as SR-aGVHD characteristics. Although the ORR in patients treated with ruxolitinib and etanercept is identical with the historical cohort (90.3% vs. 90.3%), ruxolitinib group achieved rapider remissions in liver aGVHD and gut aGVHD than the historical cohort (median time to remission for liver aGVHD: 21days vs. 28 days, p=0.0049; median time to remission for gut aGVHD: 11 days vs. 17 days, p=0.0026).Among 31 patients in the study cohort, 9 cases (29.0%) were complicated with severe infection >= 2 grade, including military tuberculosis(n=1), CMV-interstitial pneumonia(n=1), carbapenem-resistant enterobacteriaceae (CRE) sepsis(n=2), invasive fungal infection (IFI,n=1), human herpesvirus-6 acute limbic encephalitis (n=1) and bacteria pneumonia (n=3). The 1-year overall survival (OS) and 1-year non-relapse mortality (NRM) were 73.9% and 22.9%, respectively, and the 1-year relapse rate was 8.3% after ruxolitinib.Conclusion: Combined treatment with ruxolitinib and etanercept resulted in a rapid CR to visceral aGVHD and meanwhile reserve graft anti-leukemia (GVL) effect as the relapse rate of primary disease is relatively lower. The various infection complications associated with ruxolitinib merit more attention. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Clinical and prognostic significance of ABO promotor methylation level in adult leukemia and myelodydysplastic syndrome

Objective: To investigate the clinical and prognostic significance of ABO promotor methylation level in adult patients with leukemia and myelodydysplastic syndrome(MDS). Methods: ABO promoter methylation level of 182 malignant hematological disease patients and 68 normal controls were detected by bisulfite sequencing PCR.Then clinical features and outcome were compared between hypermethylation group and hypomethylation group. Results: The median methylation rate of ABO promoter in newly diagnosed acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) were 46.98% and 11.01% respectively, which were both higher than that in controls (2.30%, P<0.05). The methylation rates in remission AML and ALL were 1.58% and 2.30% respectively, which were comparable with that in normal group (P>0.05). As to relapse AML and ALL, methylation rates were 41.26% and 17.50% respectively, also significantly higher than that in controls (P<0.05).In patients with chronic myeloid leukemia (CML) chronic phase, the median methylation rate was 1.00%, which was similar to normal group. But a CML patient who transformed to ALL hadextremely high methylation rate 92.56%. The median methylation rate in patients with MDS significantly elevated as 5.81% compared with that in controls (P<0.05). The median overall survival (OS) of ALL and AML (non-M3) patients with hypermethylation were 12.5 months and 15.3 months, which were significantly shorter than those with hypomethylation (24.0 months and 20.0 months)(P<0.05).The median disease-free survival (DFS) of ALL and AML (non-M3) patients with hypermethylation were 9.9 months and 12.0 months, which were significantly shorter than those with hypomethylation (22.3 months and 18.5 months), (P<0.05). Multivariable analysis suggested that ABO promoter methylation level was an independent predictive factor of OS and DFS in ALL and AML (non-M(3)) patients. Conclusion: ABO promoter hypermethylation is closely related to genesis, development and prognosis of leukemia and MDS. Hypermethylationis related to a clinical poor prognosis compare with hypomethylation.

Clinical prognostic factors for time to positivity in cancer patients with bloodstream infections.

Time to positivity (TTP) has been used in recent years as a simple and rapid method for the additional characterization of the degree of bacteremia. However, prognostic factors for TTP in cancer patients with bloodstream infections have rarely been studied. The aim of this study was to investigate the clinical factors for TTP involving various isolated organisms in cancer patients. We analyzed 386 episodes of bloodstream infections (BSIs) in patients with or without cancer during a 19month period. Information on age, gender, tumor type, ICU stay, organisms, multidrug resistance (MDR), TTP and outcome was collected. Multivariate logistic regression analysis was performed. The mean TTP of Enterobacteriaceae in patients with hepatocellular carcinoma, gastroenterological cancer, and lung cancer was shorter than in non-cancer patients (9.86±3.22, 10.05±3.47, 8.85±2.78 vs 13.11±5.37h). The mean TTP of nonfermentative bacilli in patients with lung cancer (12.37±5.96h) and hematologic diseases (8.72±4.21h) was also shorter than in non-cancer patients (20.74±2.46h), and the mean TTP of Staphylococcus isolates was significantly different between non-cancer patients (22.06±3.71h) and hematologic disease patients (11.93±5.44h). The presence of a benign tumor was a significant prognostic factor for a long TTP only in the Staphylococci group (OR 0.076, 95% CI 0.014-0.412), according to multivariate analysis. MDR (OR 2.178, 95% CI 1.196-4.239) was an independent significant predictor in the Enterobacteriaceae group, with a short TTP, and it was also a significant clinical factor for a long TTP in nonfermentative bacilli and the Staphylococci group (OR 5.037, 95% CI 1.065-23.82; OR 0.167, 95% CI 0.059-0.474). Time to positivity provides useful diagnostic and prognostic information for the differentiation of frequently isolated organisms. This information may help clinicians to use the correct antibiotics in a timely manner to treat cancer patients with BSIs based on clinical factor analysis.

A Case of Reactivation of Hepatitis B and Fulminant Hepatitis which developed 3 months following Chemotherapy Including Rituximab in a Patient with Lymphoma

&lt;title&gt;Abstract Since Wands et al. reported for the first time in 1975 the reactivation of the hepatitis B virus in hematologic disease patients who had been receiving chemotherapy, the efficacy of chemotherapy and immunosuppressants has improved. As a result, the frequency of the reactivation of hepatitis B is increasing. Reported herein is a case of a non-Hodgkin lymphoma patient in her 70s who was suspected to have had HBsAg negative/anti-HBs negative occult HBV infection. The patient experienced fulminant hepatitis caused by the reactivation of hepatitis B, and died three months after the R-CHOP regimen was completed. In the HBsAg negative plus HBV DNA-negative case, there were few instances of viral activation of HBV. In this case, antiviral therapy was needed when the patient was confirmed to have become HBV DNA positive through regular monitoring, but its necessity is often overlooked, unlike the preemptive antiviral treatment in the HBsAg positive cases.&lt;/p&gt;

Generation of iPS cells from normal and malignant hematopoietic cells

Induced pluripotent stem cells (iPSCs) can be generated from various types of cells with transduction of defined transcription factors. In addition to regenerative medicine, iPSCs have been used for the study of pathogenesis of inherited genetic diseases. Here, we presented the examples of the establishment of iPSCs from hematopoietic cells or fibroblasts from hematological disease patients. Hematopoietic cells would be a good donor source for establishing iPSCs owing to the high reprogramming efficiency. iPSCs can be generated not only from normal cells, but also from several types of tumor cells. However it is not so easy, because iPSCs from hematological malignancies have been established only from myeloproliferative neoplasms including chronic myelogenous leukemia (CML) and JAK2-V617F mutation-positive polycythemia vera (PV). iPSC technology has great potential to promote oncology research based on patient samples.

Efficacy of oral ribavirin in hematologic disease patients with paramyxovirus infection: analytic strategy using propensity scores.

Few antiviral agents are available for treating paramyxovirus infections, such as those involving respiratory syncytial virus (RSV), parainfluenza virus (PIV), and human metapneumovirus (hMPV). We evaluated the effect of oral ribavirin on clinical outcomes of paramyxovirus infections in patients with hematological diseases. All adult patients with paramyxovirus were retrospectively reviewed over a 2-year period. Patients who received oral ribavirin were compared to those who received supportive care without ribavirin therapy. A propensity-matched case-control study and a logistic regression model with inverse probability of treatment weighting (IPTW) were performed to reduce the effect of selection bias in assignment for oral ribavirin therapy. A total of 145 patients, including 64 (44%) with PIV, 60 (41%) with RSV, and 21 (15%) with hMPV, were analyzed. Of these 145 patients, 114 (78%) received oral ribavirin and the remaining 31 (21%) constituted the nonribavirin group. Thirty-day mortality and underlying respiratory death rates were 31% (35/114) and 12% (14/114), respectively, for the oral ribavirin group versus 19% (6/31) and 16% (5/31), respectively, for the nonribavirin group (P = 0.21 and P = 0.56). In the case-control study, the 30-day mortality rate in the ribavirin group was 24% (5/21) versus 19% (4/21) in the nonribavirin group (P = 0.71). In addition, the logistic regression model with IPTW revealed no significant difference in 30-day mortality (adjusted hazard ratio of 1.3; 95% confidence interval [95% CI] of 0.3 to 5.8) between the two groups. Steroid use (adjusted odds ratio, 5.67; P = 0.01) and upper respiratory tract infection (adjusted odds ratio, 0.07; P = 0.001) was independently associated with mortality. Our data suggest that oral ribavirin therapy may not improve clinical outcomes in hematologic disease patients infected with paramyxovirus.

Comparative Outcomes of Reduced-Intensity and Myeloablative Conditioning in Unrelated Cord Blood Transplantation for Adult Standard-Risk Hematological Diseases

Abstract 4498 Background:Unrelated cord blood transplantation (uCBT) using reduced-intensity conditioning (RIC) is increasingly used for older and medically unfit patients. Data on the efficiency of hematopoietic stem cell transplantation (HCT) after RIC in younger and standard-risk patients are limited relative to myeloablative conditioning (MAC). Objective and method:To compare the outocomes of RIC to MAC in uCBT for adult patients with standard-risk hematological diseases, we retrospectively reviewed medical records of 57 standard risk hematological disease patients who underwent first uCBT at Toranomon Hospital from Jan. 2005 to December.2011. The definition of standard risk disease is severe aplastic anemia (SAA), myelodysplastic syndrome (MDS) in RA, RARS, and RCMD, acute myeloid or lymphoid leukemia (AML, ALL) in complete remission (CR) 1 or 2, chronic myeloid leukemia (CML) in chronic phase, malignant lymphoma (ML) and adult T-cell leukemia (ATL) in CR. RIC and MAC are defined according to previously reported criteria. Result:The median age of the studied patients was 55 years (range; 26–70). Twenty nine of patients received RIC and 28 MAC. Eleven patients of SAA, 7 MDS, 17 AML, 12 ALL, 5 CML, 2 ML, and 3 ATL were included in this study. Median follow-up days of survivors was 299 (11–2522). Cumulative incidence of neutrophil engraftment was 89.2% and the median days of engraftment is 20 days (11–51). Cumulative incidence of grade 2 to 4 acute graft versus host disease (aGVHD) was 42.9%. The 5-year disease-free and overall survival (DFS and OS) rates were 49.1% and 42.6%, respectively. The 5-years OS was comparable between MAC and RIC (RIC= 52.1% versus MAC= 44.2%; P=0.90). The 5-years OS of the elderly patients >54 years (n=27, 47%) were significantly lower than that in the younger patients (n=30, 53%) (35.1% versus 63.7%; P=0.042). The 5-years transplant-related mortality (TRM) was comparable between MAC and RIC (RIC= 35.0% versus MAC= 28.6%; P=0.56). The relapse rate was also comparable in two groups (RIC=11.9% versus MAC=33.6%; P=0.2) Conclusion:This study showed that uCBT with RIC for standard risk disease patients with median age of 55 years old had the similar results as MAC regimens in the 5-years OS, DFS, TRM and relapse rate. Disclosures:No relevant conflicts of interest to declare.