Developing and validating a mortality prediction model for ICH in ITP: a nationwide representative multicenter study.

Intracranial hemorrhage (ICH) is a rare and life-threatening hemorrhagic event in patients with immune thrombocytopenia (ITP). However, its mortality and related risk factors remain unclear. Herein, we conducted a nationwide multicenter real-world study of ICH in adult ITP patients. According to data from 27 centers in China from 2005 to 2020, the mortality rate from ICH was 33.80% (48/142) in ITP adults. We identified risk factors by logistic univariate and multivariate logistic regression for 30-day mortality in a training cohort of 107 patients as follows: intraparenchymal hemorrhage (IPH), platelet count ≤10 × 109/L at ICH, a combination of serious infections, grade of preceding bleeding events, and Glasgow coma scale (GCS) level on admission. Accordingly, a prognostic model of 30-day mortality was developed based on the regression equation. Then, we evaluated the performance of the prognostic model through a bootstrap procedure for internal validation. Furthermore, an external validation with data from a test cohort with 35 patients from 11 other centers was conducted. The areas under the receiver operating characteristic (ROC) curves for the internal and external validation were 0.954 (95% confidence interval [CI], 0.910-0.998) and 0.942 (95% CI, 0.871-1.014), respectively. Both calibration plots illustrated a high degree of consistency in the estimated and observed risk. In addition, the decision curve analysis showed a considerable net benefit for patients. Thus, an application (47.94.162.105:8080/ich/) was established for users to predict 30-day mortality when ICH occurred in adult patients with ITP.

Replacement Therapy for Hemophilia Patients Undergoing Cardiac Surgery: Report of Three Cases.

Hemophilia is an X-linked recessive inherited bleeding disorder. Despite the improved treatment in recent years with the advent of replacement therapies, the progression of atherosclerosis is not slowed down after the reduction of clotting factors in hemophilia. As life expectancy increases, more hemophilia patients will suffer from age-related cardiovascular diseases. Since cardiac surgery needs heparinization and cardiopulmonary bypass (CPB), it is extremely challenging to balance hemostasis and coagulation in patients with hemophilia. Here we report three cases of hemophilia patients who underwent cardiac surgery successfully.

Benefit of high-dose idarubicin as induction therapy in acute myeloid leukemia: a prospective phase 2 study.

Idarubicin 12 mg/m2 has been recommended as a standard induction therapy for acute myeloid leukemia (AML). It is unknown whether a higher dose of idarubicin can improve the remission rate. This phase 2 prospective single-arm study enrolled 45 adults with newly diagnosed AML between September 2019 and May 2021 (NCT 04,069,208). Induction therapy included administration of idarubicin 14 mg/m2 for 3 days and cytarabine 100 mg/m2 every 12 h subcutaneously for 7 days. The primary endpoint was the composite complete response rate (complete response (CR) plus complete response with incomplete blood count recovery (CRi)). The median age was 45 years (range 14-60 years). Forty (88.9%) patients had CR or CRi, including 39 patients with CR and 1 patient with CRi after one course of induction therapy. The median times to recovery of absolute neutrophil and platelet counts were 21 days. Only 1 patient died of intracranial hemorrhage during induction therapy. After a median follow-up of 14 months (range 3.5-24 months), the estimated 18-month overall survival and disease-free survival (DFS) were 66.9% and 57.5%, respectively. In conclusion, idarubicin 14 mg/m2 plus cytarabine was a safe and efficient intensive regimen for younger and fit patients with newly diagnosed AML.

Effective treatment of progressive nodular histiocytosis by intermediate-dose cytarabine: a case report and literature review.

BACKGROUND: Progressive nodular histiocytosis (PNH) is a rare, clinically distinct non-Langerhans cell histiocytic neoplasm affecting the skin and mucous membranes with no signs of spontaneous regression of the lesions. Patients typically have hundreds of lesions of superficial xanthomatous papules to nodules and deep larger fibrous nodules, which can be life-threatening if laryngeal mucosa was involved. So far, few cases of PNH have been reported and no effective treatment has been shown to reverse the progressive clinical course. CASE PRESENTATION: Here we describe a case of PNH presenting as diffuse, progressively enlarging papules, nodules and even leonine appearance in a young woman. The diagnosis was confirmed by histological and immunohistochemical findings. Next-generation sequencing (NGS) showed identical missense mutation in XIAP Y404C and in-frame deletion in MAPK1 A2[6>5]. Since ERK inhibitor has not been on the market yet, the patient received chemotherapy instead. Traditional chemotherapy with intermediate-dose of cytarabine (500 mg/m2 cytarabine by 3-hour infusion every 12 hours for 3 days every 5 weeks) achieved favorable therapeutic effect as confirmed by clinical symptoms and PET/CT imaging. CONCLUSIONS: PNH is a rare, proliferative disorder with disfiguring lesions and deteriorative quality of life. Mutations in MAPK1, XIAP may play crucial roles in the pathogenesis of PNH. Intermediate-dose cytarabine can be considered as a promising treatment option for PNH patients.

Risk stratification and outcomes of intracranial hemorrhage in patients with immune thrombocytopenia under 60 years of age.

Intracranial hemorrhage (ICH) is a devastating complication of immune thrombocytopenia (ITP). However, information on ICH in ITP patients under the age of 60 years is limited, and no predictive tools are available in clinical practice. A total of 93 adult patients with ITP who developed ICH before 60 years of age were retrospectively identified from 2005 to 2019 by 27 centers in China. For each case, 2 controls matched by the time of ITP diagnosis and the duration of ITP were provided by the same center. Multivariate analysis identified head trauma (OR = 3.216, 95%CI 1.296-7.979, P =.012), a platelet count ≤ 15,000/µL at the time of ITP diagnosis (OR = 1.679, 95%CI 1.044-2.698, P =.032) and severe/life-threatening bleeding (severe bleeding vs. mild bleeding, OR = 1.910, 95%CI 1.088-3.353, P =.024; life-threatening bleeding vs. mild bleeding, OR = 2.620, 95%CI 1.360-5.051, P =.004) as independent risk factors for ICH. Intraparenchymal hemorrhage (OR = 5.191, 95%CI 1.717-15.692, P =.004) and a history of severe bleeding (OR = 4.322, 95%CI 1.532-12.198, P =.006) were associated with the 30-day outcome of ICH. These findings may facilitate ICH risk stratification and outcome prediction in patients with ITP.

Chinese guidelines for treatment of adult primary immune thrombocytopenia.

Primary immune thrombocytopenia (ITP) is a bleeding disorder commonly encountered in clinical practice. The International Working Group (IWG) on ITP has published several landmark papers on terminology, definitions, outcome criteria, bleeding assessment, diagnosis, and management of ITP. The Chinese consensus reports for diagnosis and management of adult ITP have been updated to the 4th edition. Based on current consensus positions and new emerging clinical evidence, the thrombosis and hemostasis group of the Chinese Society of Hematology issued Chinese guidelines for management of adult ITP, which aim to provide evidence-based recommendations for clinical decision making.

Evaluation of the implementation rate of primary antifungal prophylaxis and the prognosis of invasive fungal disease in acute leukemia patients in China.

BACKGROUND: Invasive fungal disease (IFD) is a major complication of acute leukemia, thus primary antifungal prophylaxis (PAP) is recommended by guidelines. Nevertheless, guidelines might not be commonly followed in developing countries due to economic factors. The primary objectives were to evaluate the implementation rate of PAP in acute leukemia patients in China and to compare the prognosis of IFD with and without PAP. The secondary objectives were to investigate the safety of PAP, clinical characteristics of IFDs and risk factors of breakthrough. METHODS: This was a retrospective observational single-center study, including non-M3 acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) patients receiving uniform induction or salvage chemotherapy between 2012 and 2016. RESULTS: There were 29.4% of patients without PAP among a total of 248 cases. The incidence of breakthrough proven/probable/possible IFDs was 24.7%, 6.5%, 5.5%, 5.4% and 5.3% in control (no prophylaxis), fluconazole, itraconazole, voriconazole and posaconazole group respectively (P = 0.007), while the percentage of patients requiring empirical or pre-emptive therapy was 54.8%, 45.7%, 23.3%, 18.9%, 10.5% respectively (P < 0.001). PAP could also significantly improve IFD-free survival (P < 0.001) and reduce 90-day overall mortality in patients on AML salvage regimen (P = 0.021). There were no statistical differences in PAP-related adverse events. Past history of IFD (OR 9.5, P = 0.006) was confirmed to be independent risk factors. CONCLUSIONS: There are a considerable number of acute leukemia patients without PAP in China, who have higher IFD incidence, increased empiric/pre-emptive antifungal drug use and worse IFD-free survival.

[CD200/CD200R Expression Levels and Its Significance after Allogeneic Hematopoietic Stem Cell Transplantation].

BACKGROUND: CD200 and its receptor CD200R are both type-1 membrane glycoproteins, which are members of the immunoglobulin superfamily (IgSF). Besides the inhibitory effect on macrophages, CD200/CD200R also play an important role in regulating the regulatory T cells, allergicreaction, autoimmune diseases, allograft, neurological diseases and other autoimmune-related diseases, etc. OBJECTIVE: To investigate the role of CD200 and its receptor in the graft versus host disease (GVHD). METHODS: Experimental samples were divided into aGVHD group, non-aGVHD group, cGVHD group and non-cGVHD group, the healthy persons were used as normal controls. Firstly, the expression levels of CD200 and CD200R on CD19+ cell, CD3+ cell and dendritic cell (CD19- CD14- CD1c+) surfaces in each group were detected by using flow cytometry, so as to determine whether there were expression differences among each groups. Then, the mRNA levels of each groups were tested by using real-time quantitative polymerase chain reaction for finding the differences of mRNA expression level among each group. Finally, the peripheral blood mononuclear cells of the patients and healthy controls were co-cultured with anti-CD200R1 antibody for 48 hours, and the interleukin-10 level in the co-culture system was tested by using enzyme linked immunosorbent assay for verifying the function of CD200/CD200R. RESULTS: The CD200 expression level on CD19+ cell surface in the aGVHD group and non-aGVHD group was both lower than that in healthy control group; that in the non-aGVHD group was higher than that in the aGVHD group. The CD200 expression level on CD19+ CD200+ cells in the non-cGVHD group were higher than that in the cGVHD group and healthy control group. There were no significant differences of CD200 and CD200R expression levels on CD3 cells and dendritic cells among all groups. The CD200 mRNA expression levels in the aGVHD group and cGVHD group were both lower than the healthy control group. The CD200 mRNA expression level was lower in the aGVHD group than in the non-aGVHD group, and was lower in the cGVHD group than in the non-cGVHD group. There was no significant difference of the CD200R mRNA expression level among all groups. After the peripheral blood mononuclear cells of the patients and healthy controls were co-cultured with anti-CD200R1 antibody for 48 hours, the interleukin-10 concentration decreased with the increasing of anti-CD200R1 antibody concentrations in the co-culture system. CONCLUSION: The CD200/CD200R may play a role in the pathogenesis of GVHD after allo-HSCT.

The clinical spectrum of IgM monoclonal gammopathy: A single center retrospective study of 377 patients.

OBJECTIVES: We retrospectively evaluated the clinical features, serum levels of IgM, and prevalence of IgM related diseases in patients with serum immunofixation electrophoresis (sIFE) confirmed IgM monoclonal gammopathy at our center. METHODS: We included patients with sIFE confirmed IgM monoclonal gammopathy between January 2008 and December 2014 in this retrospective study. We evaluated clinical data, sIFE, serum IgM levels, and diagnosis. RESULTS: In total, 7107 patients had sIFE confirmed monoclonal gammopathy, with 377 (5.3%) patients having the IgM type. The median age was 62 years (range, 19-105 years). The median level of serum IgM is 8.3g/L (range, 0.24-150g/L). The diagnosis included monoclonal gammopathy of undetermined significance (MGUS, 157 patients, 41.6%), Waldenstrom macroglobulinemia (WM, 105 patients, 27.9%), B cell non-Hodgkin's lymphoma (69 patients, 18.3%), primary cold agglutinin disease (pCAD, 16 patients, 4.2%), primary amyloidosis (14 patients, 3.7%), cryoglobulinaemia (six patients, 1.6%), IgM MGUS associated neuropathy (five patients, 1.3%), multiple myeloma (three patients, 0.8%), and POEMS syndrome (two patients, 0.5%). Levels of serum IgM>15.5g/L were 80.6% sensitive and 89.2% specific for the diagnosis of WM. Kappa type light chain indicated the diagnosis of WM, pCAD, IgM MGUS associated neuropathy and cryoglobulinaemia, while lambda type light chain indicated POEMS and amyloidosis. There were 41/157 (26.1%) MGUS patients diagnosed with complications due to IgM-unrelated autoimmune diseases. CONCLUSION: IgM monoclonal gammopathy contains a broad spectrum of diseases. Levels of serum IgM and the type of light chain can be used to help with differential diagnosis. The association between MGUS and some autoimmune diseases requires further investigation.

[Aeromonas Sobria Infection in Patients with Acute Leukemia:Clinical Features and Outcome].

OBJECTIVE: To investigate the clinical features and outcome of patients with acute leukemia and Aeromonas sobria infection. METHODS: The clinical data of two patients from Peking Union Medical College Hospital from 1994 to 2014 as well as patients reported in English literature (from PubMed and Medline databases) and Chinese literature (China Hospital Knowledge Database) during the same period were retrospectively analysed. Data were extracted and analyzed using Chi-square tests. RESULTS: Totally 15 patients worldwide were available for analysis with a male-to-female ratio of 12:3 and an acute myeloid leukemia to acute lymphoblastic leukemia ratio of 10:5. The median age was 49.5 years (range:27-80 years). Most patients were neutropenic at the time of onset of fever,and the most common manifestation was lower limb infection (66.7%). Despite empirical antibiotics treatment,the mortality was still as high as 80%. Chi-square tests revealed that among the dead patients,the rates of lower limb infection (P<0.01) and septic shock (P=0.02) were significantly higher. CONCLUSION: Aeromonas sobria infection is an uncommon but highly fatal condition that requires special attention in clinical settings.

[Prevalence and features of pathogenic bacteria in the department of hematology without bone marrow transplantation in Peking Union Medical College Hospital from 2010 to 2012].

OBJECTIVE: To investigate the incidence, pathogens, and clinical features of infection in consecutive cases from 2010 to 2012 in Peking Union Medical College Hospital. METHOD: The incidence, pathogen, treatment, and outcomes of patients with hematological diseases who had positive findings of bacterium in their samples from 2010 to 2012 were retrospectively analyzed. RESULTS: There were 449 positive samples (5.8%) from 4 890 patients during this period, among which 388 were proved to be with pathogenic bacteria. Samples separated from patients with community-aquired infections accounted for 8.4% of all positive samples. Most community-aquired infections were caused by Gram-negative bacteria (75%), although no multidrug-resistant bacteria was observed. Samples separated from patients with nosocomial infections accounted for 91.6% of all positive samples. Respiratory tract (49.4%) and peripheral blood (32.6%) were the most common samples with positive results. Skin soft tissues (10.4%), and urine (3.7%) were less common samples. Most of the pathogenic bacteria of the nosocomial infections were Gram-negative (66.9%). The most common Gram-negative bacteria included Escherichia coli (13.8%), Pseudomonas aeruginosa (12.1%), and Klebsiella pneumonia (12.1%), while Staphylococcus aureus (10.4%), Enterococcus faecium (7.0%), and Staphylococcus epidermidis (5.1%) were the most common Gram-positive bacteria. Gram-negative bacteria consisted of most of sputum samples and peripheral blood samples. Samples from the surface of skin wound and anal swab were composed largely by Gram-positive bacteria (63.8%). The detection rates of extended-spectrum beta-lactamase-producing Klebsiella pneumonia/Klebsiella oxytoca, Escherichia coli, and Proteus mirabilis were 24.0%, 87.9% and 38.4%, respectively. The resistance to Acinetobacter baumannii was serious. Multidrug-resistant, extensive drug resistant and pan drug resistant A. baumannii acountted for 74% of all A. Baumannii infections. Stenotrophomonas maltophilia showed low resistance to sulfamethoxazole/trimethoprim, levofloxacin and minocycline. Also, 22 methicillin-resistant Staphylococcus aureus and 9 methicillin-resistant Staphylococcus Epidermidis were detected, which were only sensitive to vancomycin, teicoplanin, and linezolid. All patients were treated in the haematology wards and most of them were under agranulocytosis or immunosuppression. Finally, 22 patients reached clinical recovery through anti-infective therapy, whereas 49 patients died. Among those deaths, 42 patients attributed to severe infections and infection-associated complications. Fourteen of all the deaths might be infected with drug-resistance bacteria. There were 61 samples proved to be bacteria colonization. Nonfermenters such as Acinetobacter baumannii and Stenotrophomonas maltophilia made up for a large amount of bacteria colonization. CONCLUSIONS: The pathogens of nosocomial infections in the hematology ward are mainly Gram-negative bacteria. The incidences and pathogens vary from different infection sites. Nosocomial infection still has a higher mortality rate. Once nonfermenters are detected positive, the pathogenic or colonial bacteria should be distinguished.

[The clinical analysis of 14 cases of systemic lupus erythematosus complicated by thrombotic thrombocytopenic purpura].

OBJECTIVE: To analyze the clinical features, diagnosis and treatment of thrombotic thrombocytopenic purpura (TTP) in patients with systemic lupus erythematosus (SLE). METHODS: Clinical manifestations, laboratory findings, diagnosis,treatment and prognosis of 14 SLE patients with TTP were retrospectively analyzed. RESULT: Of the 14 patients diagnosed with SLE and TTP, 4 were men and 10 were women. The median age at diagnosis was 23 (17-69) years old. In five patients, the onset of SLE preceded TTP, and in nine patients SLE and TTP occurred simultaneously. All the 14 patients had thrombocytopenia and hemolytic anemia, 12 had fever, 11 had neurologic abnormalities, and 11 had renal dysfunction. Eight patients presented with the classic pentad of symptoms. Six patients were given steroids (alone or in combination with intravenous immunoglobulin and cyclophosphamide), and eight patients were treated with steroids in combination with plasmapheresis, with response rates of 2/6 and 6/8, respectively. Six patients died, with overall mortality rate of 6/14. No patients relapsed during the follow-up period. CONCLUSIONS: SLE and TTP share some similar clinical symptoms. As a result, repeated examinations of peripheral blood smears are very important for early diagnosis. The renal damage in patients of co-existing diseases is more serious than those with TTP alone or SLE alone. Early diagnosis and prompt treatment with plasma exchange and steroids may improve the prognosis in SLE patients with TTP.

[Efficacy of radiotherapy for adult patients with Langerhans cell histiocytosis].

OBJECTIVE: To analyze efficacy of radiotherapy for adult patients with Langerhans cell histiocytosis (LCH). METHODS: Clinical features and efficacy of radiotherapy for biopsy-proven adult patient with LCH from January 2000 to October 2012 in our hospital were retrospectively analyzed. RESULTS: Seventeen (11 male and 6 female) adult LCH patients with a mean age of 31 (18-56) years old were treated by irradiation, all patients presented as single-system disease. The mean duration from diagnosis to irradiation was 8.3 (0-108) months. Although 12 of 17 patients (70.6%) had short-term response to radiotherapy, all patients but one (94.1%) progressed during long-term follow-up, the mean progression-free survival (PFS) was 14 (0-131) months. Of the progressed patients, one relapsed in situ, the remaining 15 patients progressed outside the irradiated region. Thirteen patients (76.5%) eventually progressed to multisystem disease. CONCLUSION: Though radiotherapy for LCH in adults produced a high short-term response up to 70.6%, most of patients eventually progressed in situ or outside the irradiation region during long-term follow-up.

[Efficacy and safety of rituximab therapy for refractory/relapsing thrombotic thrombocytopenic purpura].

OBJECTIVE: To evaluate the efficacy and safety of rituximab in treating patients with refractory and/or relapsing thrombotic thrombocytopenic purpura (TTP). METHODS: Totally three patients received rituximab as salvage therapy in our hospital. Rituximab was administered at a weekly dose of 375 mg/m(2) for 2 or 4 consecutive weeks. After clinical remission, patients were followed up every 3 months. RESULTS: All three patients achieved complete remission. The median time to platelet count recovery was 7 days (4-12 days) after the first rituximab infusion. During the follow-up (median: 12 months; range: 9-18 months), no patients experienced relapse. No side effect was noted during treatment and follow-up period. CONCLUSION: Therapy with rituximab is effective and well tolerated for patients with refractory or relapsing TTP.