Yanlong Zheng

Reduced-intensity allogeneic transplantation combined with imatinib mesylate for chronic myeloid leukemia in first chronic phase

Reduced-intensity allogeneic transplantation combined with imatinib mesylate for chronic myeloid leukemia in first chronic phase

Superiority of preemptive donor lymphocyte infusion based on minimal residual disease in acute leukemia patients after allogeneic hematopoietic stem cell transplantation.

Donor lymphocyte infusion (DLI) was used as salvage therapy in leukemia relapse after allogeneic hematopoietic stem cell transplantation (allo‐HSCT), but existing results on DLI administration to acute leukemia patients were disappointing. Although increasing minimal residual disease (MRD) after HSCT had been proven to be highly indicative of posttransplant relapse, preemptive DLI (pDLI) based on MRD has not been well evaluated.

Combining therapeutic antibodies using basiliximab and etanercept for severe steroid-refractory acute graft-versus-host disease: A multi-center prospective study

ABSTRACT Acute graft versus host disease (aGVHD) remains a major problem after allogeneic hematopoietic stem cell transplantation. Standard frontline therapy for aGVHD involves corticosteroids. However, fewer than half of patients have a lasting complete response. The long-term mortality rate of steroid-refractory aGVHD (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 a novel approach to treat severe (grades III–IV) SR-aGVHD with the combination of basiliximab and etanercept. Sixty-five patients with severe SR-aGVHD from six centers were included. The median number of basiliximab infusions was 4 (range 2–11) and of etanercept was 9 (range 2–12). At day 28 after starting the combination treatment, overall response (complete and partial response: CR+PR) to second-line treatment was 90.8% with 75.4% being CR. The incidences of CR per organ were 100%, 73.8%, and 79.7% for skin, liver, and gut involvement, respectively. Patients >30-y old (p = 0.043, RR = 3.169), development of grades III–IV liver aGVHD (p = 0.007, RR = 5.034) and cytomegalovirus (CMV) reactivation (p = 0.035, RR = 4.02) were independent predictors for incomplete response. Combined treatment with basiliximab and etanercept resulted in improved CR to visceral aGVHD and significantly superior 2-y overall survival (54.7% vs. 14.8%, p <0.001) compared with classical salvage treatments. Our data suggest that the combination of basiliximab and etanercept may constitute a promising new treatment option for SR-aGVHD.

An effective diagnostic index for lymphoma-associated hemophagocytic syndrome

Background Lymphoma-associated hemophagocytic syndrome (LAHS) is a highly fatal immune disorder. Poor prognosis is partly attributed to under diagnosis or delayed diagnosis. Aim Early identification of LAHS patients based on the laboratory findings could improve the outcomes. Design Retrospective observational cross-sectional study. Methods From January 2011 to June 2016, 282 adult patients with hemophagocytosis in bone marrow were enrolled, and 114 hemophagocytic lymphohistiocytosis (HLH) patients with definite underlying cause were finally included for analysis. The HLH patients were further divided into LAHS (76 out of 114) and non-malignancy-associated HLH (38 out of 114) groups. Results Compared to non-malignancy-associated HLH, LAHS patients had significantly elevated lactate dehydrogenase (LDH) levels, increased thickness of spleen, higher proportion of patients with lymphadenopathy and significantly decreased peripheral blood cell count. In multivariate logistic regression model analysis, thickness of spleen ≥5cm (OR = 17.9, 95%CI 1.35-236.6; P = 0.028), IL-6 level ≥55.1pg/mL (OR = 12.01, 95%CI 1.03-138.9; P = 0.047) and IL-10 level ≥425.9pg/mL (OR = 51.18, 95%CI 2.53-1035.1; P = 0.010) were independent predictors of LAHS diagnosis. Based on the regression parameters, we established a diagnostic index with weighted risk scores of 1 assigned to thickness of spleen and IL-6 level respectively, and a score of 3 assigned to IL-10 level. A diagnostic index ≥ 2 points had the best AUC value (0.889) with 84.2% of sensitivity and 93.7% of specificity for predicting LAHS. Conclusions LAHS can be considered when HLH patients have a diagnostic index ≥2 points, so actively looking for evidence of lymphoma and effective chemotherapy may be necessary.

Clinical features and outcomes in secondary adult hemophagocytic lymphohistiocytosis

Background Hemophagocytic lymphohistiocytosis (HLH) is a rare clinical syndrome characterized by an infrequent but immune-mediated life-threatening disease, with confusing clinical manifestations, rapidly deteriorating health, high morbidity and mortality and challenging diagnosis. Aim The purpose of this study was to improve the recognition and understanding of HLH. Design Retrospective observational cross-sectional study. Methods Data were collected for all cases of adult patients diagnosed with HLH in a large cohort managed at a single medical center from January 2011 to December 2015. Results The median age was 52 years (range 18-90 years) and 123 (60.0%) were male. Over 95% patients manifested fever, hyperferritinemia and elevated lactate dehydrogenase. Underlying triggers of HLH were as follows: 119 (58.0%) malignancies, 83 (40.5%) infections, 14 (6.8%) unknown triggers and 14 (6.8%) autoimmune disorders. The median overall survival was 55 days. And elderly patients (age ≥60 years) had a markedly worse survival compared with young patients (age <60 years) (median overall survival 24 days vs. 159 days, respectively; P <0.001). In a multivariable analysis, platelet <40 × 109/l (HR = 2.534; 95% CI 1.152-5.573; P = 0.021), PT prolonged >3 s (HR = 1.909; 95% CI 1.127-3.234; P = 0.016) and malignancy (HR = 1.614; 95% CI 1.008-2.582; P = 0.046) were correlated with poor survival. Conclusion HLH adult patients had very complex clinical manifestations as well as underlying diseases. Patients with PLT <40 ×109/l, PT prolonged >3 s and malignancy had inferior survival. It is of great importance to improve our understanding of this syndrome.

Clinical and histological features of primary testicular diffuse large B-cell lymphoma: a single center experience in China

Primary testicular lymphoma (PTL) is a rare and aggressive form of extranodal lymphoma. Approximately 80–98% of PTLs are diffuse large B-cell lymphoma (PT-DLBCL). The prognosis of DLBCL patients has improved with the addition of rituximab to systemic chemotherapy, but outcomes of PT-DLBCL remain poor. This may be explained by the high rate of relapse in the central nervous system (CNS) and contralateral testis. We analyzed 1,132 newly diagnosed DLBCL patients (37 with PT-DLBCL) who were treated at our hospital between January 2009 and December 2014. Twenty-five patients finished follow-up. We analyzed clinical characteristics, response to chemotherapy, overall survival, and relapse in the CNS and contralateral testis. All patients underwent orchiectomy. The median age was 60 (range: 43–82) years. Eleven patients had stage III/IV disease. Five patients experienced CNS relapse, and three experienced relapse in the contralateral testis. Median overall survival (OS) was not reached at the time of reporting. The 3-year OS rate was 57%. None of the nine patients who received radiotherapy to the contralateral testis experienced relapse in that location. Intrathecal prophylaxis did not reduce the risk of CNS relapse. All five patients who experienced CNS relapse had the germinal center B-cell-like subtype of DLBCL.

Blood biomarkers in adults with lymph node enlargement contribute to diagnostic significance of malignancy

Lymph node enlargement is a common presentation and has a possibility of malignancy like lymphoma that requires early diagnosis. This study aims to analyze the clinical characteristics of these patients and finds out useful predictors of malignant diseases. We retrospectively investigated 81 patients with lymph node enlargement between July 2, 2014 and May 17, 2016. The characteristics and laboratory findings were evaluated combining with the final diagnosis. The diagnoses were malignancy in 51 patients and benign lymphadenopathy in 30 patients. Increased beta2-microglobulin (B2M) (P = 0.012) was found to be associated with malignant diseases, and level of 3699.5 μg/L was used as a cut-off value to differentiate the malignancies from benign diseases, offering 63.4% sensitivity and 87.0% specificity. Immunoglobulin G (IgG) (P = 0.038) levels were significantly lower in malignant group, whose receiver operating characteristic curve showed that level of 1121.5 mg/dl had sensitivity and specificity as 58.5% and 82.6%. Moreover, through analysis of cytokines, we found interleukin-10 (IL-10) levels were elevated in malignant group compared with benign group. Serum B2M and IgG levels were concluded to be useful parameters for predicting malignancies. Besides, increased IL-10 levels indicated a higher risk of malignancy in some way.

Novel homobarringtonie‑containing therapy for the treatment of patients with primary acute myeloid leukemia that are resistant to conventional therapy

The current study investigated the efficacy and safety of a novel treatment regime consisting of homobarringtonie, cytosine arabinoside and etoposide (HCE) for the treatment of primary acute myeloid leukemia (AML). In the present study, 141 patients diagnosed with AML were divided into the HCE (n=47) and the conventional AML therapy, consisting of idamycin combined with cytarabine (IA; n=94), treatment groups. The measured patient outcome parameters were the emission and response rates, as well as medication-induced adverse events, with a median follow-up time of 28 months. There was no significant difference in the 3-year relapse-free survival rate between the HCE and IA treatment groups. The occurrence and severity of hematological or non-hematological toxicity did not differ between the two groups. However, of the 26 patients that demonstrated a poor response to the IA treatment, 19 cases were administered the HCE treatment and 14 of these patients achieved complete remission (CR). Of the 10 patients that demonstrated a poor response to the HCE treatment, 8 patients were administered the IA treatment and 7 of these achieved CR. Therefore, HCE may be an effective treatment regimen for patients with primary AML. As there was no cross-resistance between the HCE and IA regimens, HCE may be an alternative option for patients that respond poorly to IA induction therapy.

Risk factors and clinical characteristics of non-promyelocytic acute myeloid leukemia of intracerebral hemorrhage: A single center study in China

BACKGROUND Although high mortality in patients with acute leukemia (AL) is associated with intracranial hemorrhage (ICH), the clinical features and pathogenesis of AL patients with cerebral hemorrhage are not well known. METHODS We diagnosed 90 patients with ICH from a total of 1467 patients with non-promyelocytic AL who had been hospitalized in the First Affiliated Hospital of Medical School of Zhejiang University from January 2010 to October 2015. Moreover, the risk factors of ICH death were evaluated. RESULT Median age at ICH was 51years old, in which men accounted for 52.2%. They also accounted for 85.6% of acute myeloid leukemia. The relative incidence of ICH was the highest in M2 and M5 (60.1%). ICH presented with higher peripheral blood white blood cell count (WBC) (P<0.001), lower peripheral platelet counts (P<0.001), lower albumin (P<0.001), lower fibrous protein (P<0.001) and prolongation of prothrombin time (P<0.001) compared to those observed in the patients of NICH group; multivariate analysis, independent risk factors for death in patients with ICH include: WBC≥30.00×109/l and prothrombin time≥12.91 s. CONCLUSIONS Leukocytosis and coagulation dysfunctions might be the main pathogenesis of acute leukemia complicated with cerebral hemorrhage.

HAG (Homoharringtonine, Cytarabine, G-CSF) Regimen for the Treatment of Acute Myeloid Leukemia and Myelodysplastic Syndrome: A Meta-Analysis with 2,314 Participants.

Background In China, the combination of homoharringtonine, cytarabine, and G-CSF (HAG) has been extensively applied for treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Methods We performed a meta-analysis of 2,314 patients (AML, n = 1754; MDS, n = 560) to determine the overall safety and efficacy of this regimen. Results The complete response (CR) rate of AML patients (53%) was significantly higher than that of MDS/transformed-AML patients (45%; P = 0.007). The CR rate of patients with newly diagnosed AML (62%) was significantly higher than in patients with relapsed/refractory AML (50%; P = 0.001). There were no significant difference in CR rates between elderly AML patients (54%) and all AML patients (P = 0.721). When compared with non-HAG regimens for AML/MDS induction therapy, the CR rate of patients treated with HAG was significantly higher than in treated with intensive chemotherapy (P = 0.000). No significant differences in CR rates were observed between patients treated with HAG and those treated with CAG (cytarabine, aclarubicin, G-CSF) regimens (P = 0.073). HAG regimen was well tolerated, with early death (ED) in 2%, grade IV myelosurrpression in 52% and infection in 50%. Reports of ED and rates of myelosuppression were reduced as compared with intensive chemotherapy (P = 0.000 and P = 0.000, respectively). Conclusion The HAG regimen is an effective and safe regimen for the treatment of AML and MDS, and appears to be more effective and better tolerated than intensive chemotherapy. Future randomized controlled trials and further meta-analyses are strongly needed to confirm its efficacy and safety, especially in comparison with intensive chemotherapy.