Low-dose decitabine for previously untreated acute myeloid leukemia ineligible for intensive chemotherapy aged 65 years or older: a prospective study based on comprehensive geriatric assessment.

Background: The outcome of patients with acute myeloid leukemia (AML) aged ⩾65 years is poor. Effective treatment options are limited for patients with AML who cannot tolerate intensive chemotherapy. Objectives: We aimed to evaluate the efficacy of low-dose decitabine in previously untreated patients with AML aged ⩾65 years who were ineligible for intensive chemotherapy based on a comprehensive geriatric assessment. Design: We performed a prospective, multicenter, open-label, and non-randomized study. Methods: Patients were enrolled at four centers in Beijing between 1 January 2017 and 31 December 2020. They were treated with decitabine at a dose of 6 mg/m2 for 10 days. The treatment was repeated every 28 days for one cycle for a total of six cycles. The primary endpoint of our study was overall survival (OS) at the end of the first year after enrolment. The secondary endpoints included overall response rate, leukemia-free survival, relapse rate, treatment-related mortality (TRM), quality of life, safety, and transfusion dependence. Patients were continuously monitored for toxicity. Results: Overall, 47 patients (30 males and 17 females) participated in this study. The median age of the enrolled patients was 78 (range, 65-90) years. The median follow-up time was 22.2 (range, 4.6-38.8) months. Fifteen (31.9%) patients achieved complete remission (CR), 11 (23.4%) patients achieved partial remission, 3 (6.4%) patients achieved hematological improvement only, and 18 (38.3%) patients did not achieve remission. The median time to obtain CR was 2 months. The median CR was 8.5 months. Of the patients, 36 (76.6%) patients completed six cycles of treatment with low-dose decitabine, and the 1-year OS was 36.1%. According to instrumental activities of daily living scales, age, comorbidities, and albumin (IACA) scores, the median survival was 11.2 months in the unfit group and 6 months in the frail group. The 1-year OS rates in the unfit and frail groups were 49.2% and 23.4%, respectively. Grade ⩾3 non-hematological toxicity was observed in 70.2% (33/47) of the patients. TRM occurred in three patients. No early deaths occurred after treatment. Conclusion: In newly diagnosed older patients with AML whose IACA assessment was unfit or frail for standard chemotherapy, treatment with low-dose decitabine demonstrated clinical activity and good security in our study.

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.

Diagnostic performance of Neutrophil CD64 index, procalcitonin, and C-reactive protein for early sepsis in hematological patients.

BACKGROUND: Patients with hematological diseases are immunosuppressed due to various factors, including the disease itself and treatments, such as chemotherapy and immunotherapy, and are susceptible to infection. Infections in these patients often progress rapidly to sepsis, which is life-threatening. AIM: To evaluate the diagnostic efficacy of the neutrophil CD64 (nCD64) index, compared to procalcitonin (PCT) and high-sensitivity C-reactive protein (hs-CRP), for the identification of early sepsis in patients with hematological diseases. METHODS: This was a prospective analysis of patients with hematological diseases treated at the Fuxing Hospital affiliated with Capital Medical University, between March 2014 and December 2018. The nCD64 index was quantified by flow cytometry and the Leuko64 assay software. The factors which may affect the nCD64 index levels were compared between patients with different infection statuses (local infection, sepsis, and no infection), and the control group and the nCD64 index levels were compared among the groups. The diagnostic efficacy of the nCD64 index, PCT, and hs-CRP for early sepsis was evaluated among patients with hematological diseases. RESULTS: A total of 207 patients with hematological diseases (non-infected group, n = 50; locally infected group, n = 67; sepsis group, n = 90) and 26 healthy volunteers were analyzed. According to the absolute neutrophil count (ANC), patients with hematological diseases without infection were divided into the normal ANC, ANC reduced, and ANC deficiency groups. There was no statistically significant difference in the nCD64 index between these three groups (P = 0.586). However, there was a difference in the nCD64 index among the non-infected (0.74 ± 0.26), locally infected (1.47 ± 1.10), and sepsis (2.62 ± 1.60) groups (P < 0.001). The area under the diagnosis curve of the nCD64 index, evaluated as the difference between the sepsis and locally infected group, 0.777, which was higher than for PCT (0.735) and hs-CRP (0.670). The positive and negative likelihood ratios were also better for the nCD64 index than either PCT and hs-CRP. CONCLUSION: Our results indicate the usefulness of the nCD64 index as an inflammatory marker of early sepsis in hematological 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.

Development and validation of a prediction model (AHC) for early identification of refractory thrombotic thrombocytopenic purpura using nationally representative data.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare and life-threatening haematological emergency. Although therapeutic plasma exchange together with corticosteroids achieve successful outcomes, a considerable number of patients remain refractory to this treatment and require early initiation of intensive therapy. However, a method for the early identification of refractory iTTP is not available. To develop and validate a model for predicting the probability of refractory iTTP, a cohort of 265 consecutive iTTP patients from 17 large medical centres was retrospectively identified. The derivation cohort included 94 patients from 11 medical centres. For the validation cohort, we included 40 patients from the other six medical centres using geographical validation. An easy-to-use risk score system was generated, and its performance was assessed using internal and external validation cohorts. In the multivariable logistic analysis of the derivation cohort, three candidate predictors were entered into the final prediction model: age, haemoglobin and creatinine. The prediction model had an area under the curve of 0.886 (95% CI: 0.679-0.974) in the internal validation cohort and 0.862 (95% CI: 0.625-0.999) in the external validation cohort. The calibration plots showed a high agreement between the predicted and observed outcomes. In conclusion, we developed and validated a highly accurate prediction model for the early identification of refractory iTTP. It has the potential to guide tailored therapy and is a step towards more personalized medicine.

[Improvement of Method for Detecting Peripheral Blood Neutrophil CD64 Index in Patients with Hematologic Malignancies].

OBJECTIVE: To improve the method for detecting the neutrophil CD64 (nCD64) index and to enhance the detection rate and accuracy of nCD64 index in patients with hematologic malignancies. METHODS: The nCD64 index in peripheral blood of patients with hematologic malignancies combined with suspicious bacterial infection (255 cases-time) was detected by using array method. When the detection of nCD64 index in samples was interfered with abnormal cells in detection process of enrolled patients, the antibodies CD45, CD15 and CD10 were added into samples on the basis of routine detection by using the primary detection kit, in order to more accurately distinguish the neutrphils and obtain the nCD64 index. The nCD64 index as well as the efficiency of nCD64 index, PCT and CRP for diagnosis of sepsis before and after the improvement of deteation method were compared. RESULTS: The samples of 60 cases were interfered with abnormal cells in detection process, out of which the samples of 18 cases failed in detection, but these samples of 18 cases all got the effective results of detection after the detection method was improved. The detection showed that the nCD64 index before and after the improvement as well as the PCT and CRP levels in sepsis group were higher than those in non-sepsis group(P＜0.05). After improvement of method, the efficiency of nCD64 index for diagnosis of sepsis was suprior to the PCT and CRP, the nCD64 index obtained after the improvement of method possessed the diagnosis efficiency same as the efficiency obtained before improvement of method, moreover the detection results were more reliable. CONCLUSION: For the samples of patients with hematologic malignancies interfered with abnormal cells in the process of detecting the nCD64 index, the corresponding antibodies are added into detected samples according to the kinds of hemotologic diseases of patients, in order to more accurately gate the neutrophils in paripheral blood of patients, there by the detection rate and accuracy for detecting the nCD64 index are enhanced by accurately distinguishing the neutrophils.

[Clinical Analysis of 24 Acute myeloid Leukemia Patients Aged -over 80 Years].

OBJECTIVE: To investigate the clinical features of acute myeloid leukemia patients aged over 80 years. METHODS: The clinical data from 24 cases of acute myeloid leukemia (non-M3) aged over 80 years were analyzed retrospectively. Clinical characteristics, therapeutic efficacy and overall survival rate of the patients received low dose chemotherapy and/or decitabine were compared with that received only supportive care. RESULTS: According to FAB classification, the 10 patients were M2 subtypes (41.7%), the 7 patients were M4 subtypes (29.2%), the 4 patiens were M5 (16.7%), the 3 patients were unclassifed (16.5%). 22 patients (91.0%) were complicated with underling diseases. Among 13 patients received low dose chemotherapy or decitabine, 8 cases (61.5%) achived partial remission or higher remission. The median survival time of patients who reseived chemotherapy was 30 weeks, and signicantly longer than that of patients received supportive care (median survival time was 9 weeks (P<0.05)). The univariated analysis showed that WBC≥50×109/L, ECOG≥2 and received supportive care were unfavonrable prognostic factors for overall survival. CONCLUSION: More than half of patients aged over 80 years who received individudized treatment can achieve partial remission or higher remission, and can have more longer survival time..

Formal [5+2] cycloaddition of vinylethylene carbonates to oxazol-5-(4H)-ones for the synthesis of 3,4-dihydrooxepin-2(7H)-ones.

Under the catalysis of Pd2(dba)3 (2.5 mol%), PPh3 (10.0 mol%) and TMSCl (1.0 eq.), the formal [5+2] cycloaddition of vinylethylene carbonates to oxazol-5-(4H)-ones proceeded readily in THF at 60 °C to r.t., thus furnishing 3,4-dihydrooxepin-2(7H)-ones in 67-99% chemical yields. The chemical structure of one compound was confirmed by X-ray diffraction analysis, and the others were suggested by inference.

Diastereoselective and Enantioselective Synthesis of Barbiturate-Fused Spirotetrahydroquinolines via Chiral Palladium(0)/Ligand Complex Catalyzed [4 + 2] Cycloaddition of Vinyl Benzoxazinanones with Barbiturate-Based Olefins.

Under the catalysis of chiral palladium(0)/ligand complex, the [4 + 2] cycloaddition between vinyl benzoxazinanones and barbiturate-based olefins proceeded readily and provided barbiturate-fused spirotetrahydroquinolines in up to 96% chemical yield with up to >99:1 dr and 97% ee. The absolute configuration of barbiturate-fused spirotetrahydroquinolines was clearly identified by X-ray single crystal structure analysis. The reaction mechanism was proposed to shed light on the enantioselective formation of barbiturate-fused spirotetrahydroquinolines.

[Reseach Progress of Ki-67 in Acute Myeloid Leukemia-Review].

Ki-67 antigen expression is closely associated with the cell cycle. Its expression is in almost the entire mitosis in cell cycle. Detection of Ki-67 antigen can reflect the cell proliferation activity in hematological malignancies. Detection of Ki-67 has been widely applied in staging, therapy effect monitoring and prognosis judgment in lymphoma. There has been a lot of studies investigating the expression of Ki-67 in acute lymphocytic leukemia (ALL) and chronic lymphocytic leukemia (CLL), and investigating the relevance between Ki-67 expression and therapy effect and prognosis. However, there are a few studies about Ki-67 in acute myeloid leukemia (AML), and the results of studies are no consistant. In this review, the architecture, intracellular localization, expression regulation, physiological functions of Ki-67 and the application of Ki-67 in AML are summarized so as to understanding whether Ki-67 can play roles in diagnosis and prognostic evaluation of AML.

[Neutrophil CD64 Expression as A Biomarker in the Early Diagnosis of Sepsis in Malignant Hematologic Disease--Review].

Malignant hematologic disease with sepsis has been characterized by high mortality and difficulty in diagnosis at early stage. A good biomarker may help to improve the accuracy of diagnosis and to reduce the mortality rate. In the early diagnosis of sepsis, neutrophil CD64 expression is a better candidate for biomarker rather than C-reactive proteins. Moreover, neutrophil CD64 expression is also helpful for assessing the severity of infection and prognosis of disease. Unfortunately, there are few studies of neutrophil CD64 expression on the early diagnosis of malignant hematologic diseases. This review focuses on the advantages, limitations, feasibilities and progresses of neutrophil CD64 expression in the early diagnosis of infection in malignant hematologic diseases in this paper.

[Expression and clinical significance of PDCD5 in patients with acute myeloid leukemia].

OBJECTIVE: This study was aimed to investigate the roles of PDCD5 (programmed cell death 5) in pathogenesis of acute myeloid leukemia (AML) and the relevance of PDCD5 with the clinical characteristics and prognosis of patients by testing the PDCD5 expression in adult AML patients. METHODS: The mRNA and intracellular protein levels of PDCD5 from 36 newly diagnosed AML patients were analyzed by real-time fluorescence quantitative polymerase chain reaction (RQ-PCR) and flow cytometry (FCM), respectively. The correlation of mRNA levels and intracellular protein levels of PDCD5 with the clinical characteristics and survival time of patients were analyzed. RESULTS: The intracellular protein expression levels of PDCD5 in AML patients were significantly higher than those in normal controls (P < 0.05). The PDCD5 mRNA levels were not significantly different between patients and controls (P > 0.05). The mRNA and protein levels of PDCD5 did not significantly correlate with sex, age, WBC count, FAB subtype, extramedullary infiltration, WT1 gene, NPM1 gene mutation and the patients response to induction therapy. The patients with positive FLT3/ITD mutation displayed higher protein levels of PDCD5 as compared with negative FLT3/ITD mutation patients (P < 0.05). CONCLUSION: The intracellular protein of PDCD5 significantly increased in AML patients. However, the increased PDCD5 does not exert the pro-apoptotic effects on AML cells. The patients with positive FLT3/ITD mutation show higher protein levels of PDCD5.

[Expression and clinical significance of B-cell lymphoma 2 (BCL-2) in hyperleukocytic acute myeloid leukemia].

This study was aimed to investigate the role of B-cell lymphoma 2 (BCL-2) in pathogenesis of hyperleukocytic acute myeloid leukemia (AML). The levels of intracellular BCL-2 in 48 AML patients were detected by flow cytometry (FCM). Serum levels of BCL-2 in 40 AML patients were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that the serum levels of BCL-2 in hyperleukocytic AML and non-hyperleukocytic AML patients were significantly higher than that in normal controls (P < 0.05), but intracellular BCL-2 levels were not significantly different, as compared with normal controls (P > 0.05). There were no difference of intracellular and serum BCL-2 levels between hyperleukocytic and non-hyperleukocytic AML patients (P > 0.05). The serum and intracellular levels of BCL-2 between hyperleukocytic AML, non-hyperleukocytic AML patients and normal controls were not statistically correlated. It is concluded that leukemic cells in AML patients produce and secrete too much BCL-2, which may be involved in the pathogenesis of leukemia disease. However, the anti-apoptosis effect of BCL-2 has no significant impact on the pathogenesis of hyperleukocytic AML.

MRD-directed risk stratification treatment may improve outcomes of t(8;21) AML in the first complete remission: results from the AML05 multicenter trial.

We aimed to improve the outcome of t(8;21) acute myeloid leukemia (AML) in the first complete remission (CR1) by applying risk-directed therapy based on minimal residual disease (MRD) determined by RUNX1/RUNX1T1 transcript levels. Risk-directed therapy included recommending allogeneic hematopoietic stem cell transplantation (allo-HSCT) for high-risk patients and chemotherapy/autologous-HSCT (auto-HSCT) for low-risk patients. Among 116 eligible patients, MRD status after the second consolidation rather than induction or first consolidation could discriminate high-risk relapse patients (P = .001). Allo-HSCT could reduce relapse and improve survival compared with chemotherapy for high-risk patients (cumulative incidence of relapse [CIR]: 22.1% vs 78.9%, P < .0001; disease-free survival [DFS]: 61.7% vs 19.6%, P = .001), whereas chemotherapy/auto-HSCT achieved a low relapse rate (5.3%) and high DFS (94.7%) for low-risk patients. Multivariate analysis revealed that MRD status and treatment choice were independent prognostic factors for relapse, DFS, and OS. We concluded that MRD status after the second consolidation may be the best timing for treatment choice. MRD-directed risk stratification treatment may improve the outcome of t(8;21) AML in CR1. This trial was registered at http://www.chictr.org as #ChiCTR-OCH-12002406.

[Human herpesvirus 7 infection in patients after allogeneic hematopoietic stem cell transplantation].

OBJECTIVE: To study the prevalence of human herpesvirus 7 (HHV-7) infection in recipients following allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Peripheral blood samples were collected before and weekly after allo-HSCT from 72 consecutive recipients and 53 donors. Nested polymerase chain reaction (nPCR) was used to monitor HHV-7 DNAemia. RESULTS: HHV-7 DNAemia was detected at least once in 86.1% (62/72) of the 72 patients on the median day 15.6 (7 approximately 56 days) after allo-HSCT. Continuing HHV-7 DNAemia (HHV-7 DNAemia maintained at least 4 weeks) was evidenced in 40.3% (29/72) of the patients after allo-HSCT. The prevalence of continuing HHV-7 DNAemia in the patients receiving HLA mismatched or HLA matched unrelated allo-HSCT who underwent conditioning with anti-thymocyte globulin (ATG) was 48.9% (23/47), significantly higher than that in the patients receiving HLA matched related allo-HSCT with conditioning without ATG [24% (6/25), P = 0.040]. Enhanced incidence the prevalence of HHV-7 DNAemia in the patients receiving corticosteroid after allo-HSCT was 44.6% (39/65), significantly higher than that in the patients who did not receive corticosteroid [0% (0/7), P = 0.037]. No relationship was observed between HHV-7 infection and transplant-related complications including acute graft versus host disease, hemorrhagic cystitis, cytomegalovirus and HHV-6 infection. CONCLUSION: Common in allo-HSCT recipients, HHV-7 DNAemia is closely associated with conditioning with ATG and application of corticosteroid after allo-HSCT.

[Correlation between human herpesvirus 6 activation and acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation].

OBJECTIVE: To study the potential relationship between HHV-6 activation and acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation (HSCT). METHODS: Peripheral blood samples were collected before and weekly after HSCT from 72 consecutive recipients. HHV-6 DNAemia was monitored by nested polymerase chain reaction (PCR). The genotypes of HHV-6 were identified by Hind III restriction assay. RESULTS: Of the 72 patients, HHV-6 DNAemia were detected in 45 (62.5%) on a median of day 14 (range, 7 - 63 days) after HSCT. Grade I - IV aGHVD occurred in 40 (55.6%) on a median of day 26 (range, 9 -73 days). The median onset time of HHV-6 DNAemia was significantly earlier than that of aGHVD (P = 0.018). Compared with that in HHV-6 DNAemia negative [HHV-6(-)] patients, the cumulative incidence of grade I - IV aGHVD was higher (68.9% vs. 33.3% , P = 0.003) in HHV-6 (+) patients. Cumulative incidence of grade II - IV aGVHD in HHV-6 (+) cohort was also higher than that in HHV-6 (-) cohort (35.6% vs 14.8% , P = 0.027). Cumulative incidence of grade I - IV aGVHD was higher in patients with both HHV-6 and CMV positive (CMV+/HHV-6+) than in those with either CMV (CMV+/HHV-6-) or HHV-6 positive (CMV+/HHV-6+) and neither of them positive (CMV-/HHV-6-) [78.9% (30/38), 55. 6% (5/9) , 14. 3% (1/7) and 22. 2% (4/18), respectively, P = 0. 0001]. Cumulative incidence of grade II - IV aGVHD in CMV+/HHV-6+ group was also higher than that in CMV+/HHV-6-, CMV-/HHV-6+ and CMV-/HHV-6- groups [42.1% (16/38), 22.2% (2/9), 0% (0/7) and 11.1% (2/18), P = 0. 008]. CONCLUSIONS: Patients with HHV-6 activation or HHV-6/CMV co-infection maybe involved in the occurrence of aGVHD after HSCT.

The impact of human herpesvirus 6B reactivation on early complications following allogeneic hematopoietic stem cell transplantation.

Although human herpesvirus 6 (HHV-6) has been considered an important opportunistic and potentially fatal pathogen for allogeneic hematopoietic stem cell transplantation (HSCT), the clinical significance of HHV-6 reactivation remains controversial. In this study, we monitored HHV-6 DNAemia in 72 consecutive allogeneic HSCT recipients by real-time quantitative polymerase chain reaction. A total of 680 peripheral blood specimens were collected from the recipients before HSCT or at weekly intervals after HSCT. As the predominant variant, HHV-6B was detectable at least once in 47.2% (34/72) of HSCT recipients on the median day 21 (range, 7-84 days); HHV-6A reactivation occurred in only 1 recipient (1.4%). Detectable HHV-6B reactivation was associated with increased probability of skin rash by day 30 after HSCT (hazard ratio [HR], 3.68; 95% confidence interval [CI], 1.24-10.92; P = .019), cytomegalovirus (CMV) antigenemia (HR, 2.35; 95%CI, 1.32-4.19; P = .004), and hemorrhagic cystitis (HC) (HR, 2.59; 95%CI, 0.96-6.98; P = .061) by day 100 after HSCT. Neutrophil and platelet engraftment, mortality for 100 days after HSCT were not affected by HHV-6B reactivation. In conclusion, HHV-6 reactivation is a common event, and this study demonstrates a correlation between HHV-6B infection and CMV reactivation, early rash, and possibly increased incidence of HC after transplantation.

Surveillance of active human herpesvirus 6 infection in chinese patients after hematopoietic stem cell transplantation with 3 different methods.

Human herpesvirus 6 (HHV-6) reactivation was studied in 72 consecutive allogeneic hematopoietic stem cell transplant (HSCT) recipients and 53 "healthy" donors. The feasibilities of real-time quantitative polymerase chain reaction (RQ-PCR), nested-PCR, and antigenemia assays in the assessment of HHV-6 reactivation were also evaluated. HHV-6 DNA was detected in 62.5% and 48.6% of post-HSCT patients with the nested-PCR assay and RQ-PCR analysis, respectively, and HHV-6B was identified as the predominant variant. The incidence of HHV-6 infection peaked from the second to the seventh week, whereas the HHV-6B DNA loads peaked from the second to the third week. Compared with RQ-PCR analysis, the sensitivity and specificity of the nested-PCR assay were 100% and 88%, respectively, with positive and negative predictive values of 60% and 99%, respectively. For the HHV-6 antigenemia assay, the sensitivity and specificity were 89% and 97%, respectively, and the positive and negative predictive values were both 94%. Conditioning with antithymocyte globulin in HLA-mismatched or unrelated HSCT increased the possibility of HHV-6B reactivation after HSCT (hazard ratio, 5.92; 95% confidence interval, 1.99-17.59; P = .001). In conclusion, HHV-6B reactivation is commonly encountered after HSCT. Of the 3 methods we adopted for HHV-6 detection, both RQ-PCR analysis and the antigenemia assay could be seen as essential tests for predicting HHV-6 reactivation.

[Prevalence of human herpesvirus-6 in allogeneic hematopoietic stem cell transplant recipients in correlation with cytomegalovirus infection].

In order to study the prevalence of human herpesvirus 6 (HHV-6) in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients in China and to analyze the relationship between HHV-6 and cytomegalovirus (CMV) infection in post-HSCT patients, nested polymerase chain reaction (PCR) was used to monitor HHV-6 DNAemia in 72 consecutive allo-HSCT recipients. 680 EDTA anticoagulated peripheral blood specimens were gathered before HSCT or weekly until 12 weeks after allo-HSCT. The variants of HHV-6 were identified by Hind III restriction analysis. CMV-pp65 antigenemia was detected by immunofluorescence stain. The results showed that HHV-6 DNAemia was detected at least once in 62.5% (45/72) of the patients on the median day 14 (range, 7 - 63 days) after allo-HSCT, and HHV-6B was the predominant variant. CMV antigenemia was detected at least once in 65.3% (47/72) of the patients on the median day 43 (range, 14 - 105 days) after allo-HSCT. Co-infection of HHV-6 and CMV (HHV-6+/CMV+) occurred in 52.8% (38/72) recipients. The onset of HHV-6 DNAemia was earlier than that of CMV antigenemia (P < 0.0001). Patients with HHV-6 DNAemia positive were more likely to have concurrent CMV antigenemia than HHV-6 DNAemia negative patients (84.4% vs 33.3%, P = 0.0001) after allo-HSCT. Among the herpesvirus related disease, the relatively high incidence of hemorrhage cystitis (HC) occurred in 23.6% (17/72) of post-HSCT patients. 88.2% (15/17) of HC developed in HHV-6 positive patients, and 82.3% (14/17) occurred in CMV+/HHV-6+ patients. It is concluded that infection of HHV-6, co-infection of HHV-6 and CMV, commonly occurred in post-HSCT patients in China, HHV-6 infection closely related to CMV antigenemia.