Basiliximab for steroid-refractory acute graft-versus-host disease: A real-world analysis.

Steroid-refractory (SR) acute graft-versus-host disease (aGVHD) is one of the leading causes of early mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We investigated the efficacy, safety, prognostic factors, and optimal therapeutic protocol for SR-aGVHD patients treated with basiliximab in a real-world setting. Nine hundred and forty SR-aGVHD patients were recruited from 36 hospitals in China, and 3683 doses of basiliximab were administered. Basiliximab was used as monotherapy (n = 642) or in combination with other second-line treatments (n = 298). The cumulative incidence of overall response rate (ORR) at day 28 after basiliximab treatment was 79.4% (95% confidence interval [CI] 76.5%-82.3%). The probabilities of nonrelapse mortality and overall survival at 3 years after basiliximab treatment were 26.8% (95% CI 24.0%-29.6%) and 64.3% (95% CI 61.2%-67.4%), respectively. A 1:1 propensity score matching was performed to compare the efficacy and safety between the monotherapy and combined therapy groups. Combined therapy did not increase the ORR; conversely, it increased the infection rates compared with monotherapy. The multivariate analysis showed that combined therapy, grade III-IV aGVHD, and high-risk refined Minnesota aGVHD risk score before basiliximab treatment were independently associated with the therapeutic response. Hence, we created a prognostic scoring system that could predict the risk of having a decreased likelihood of response after basiliximab treatment. Machine learning was used to develop a protocol that maximized the efficacy of basiliximab while maintaining acceptable levels of infection risk. Thus, real-world data suggest that basiliximab is safe and effective for treating SR-aGVHD.

[Effectiveness of CLAT Protocol for Treating Patients with Refractory Acute Myeloid Leukemia].

OBJECTIVE: To explore the clinical efficacy and toxicity of CLAT protocol (cladribine, cytarabine and topotecan) for treating patients with refractory acute myeloid leukemia (R-AML). METHODS: A total of 18 patients with R-AML (median age 37 years, range 18 to 58 years; male n = 16, female n = 2) were treated with CLAT protocol, which consisted of cladribine 5 mg/m(2)/d, i.v. on days 1-5, cytarabine 1.5 g/m(2)/d, i.v. on days 1-5, topotecan 1.25 mg/m(2)/d, i.v. on days 1-5 and G-CSF 300 µg/d subcutaneous injection on day 6 until neutrophile granulocyte recovery. RESULTS: Out of 18 patients 2 died of severe infection before the assessment. Among 16 evaluated patients, 10 (55.6%) achieved complete remission (CR), and 2 (11.1%) achieved partial remission (PR), the overall response rate was 66.7%, the rest 4 patients did not respond (NR). The median overall survival time and DFS for the CR patients was 9.5 months (95%CI: 6.7-16.64) and 9.5 months (95%CI: 6.1-16.7) respectively. The 1 year OS and DFS rates were 45% and 46.9%, respectively. All patients developed grade 4 of granulocytopenia and thrombocytopenia, the median duration was 13 (range 2 to 21) days and 12 days (range 2 to 21), respectively, all patients developed infection, 2 patients died of severe infection. The most common non-hematological side effects included nausea, vomiting, diarrhoea, rash, aminotransferase or bilirubin elevation and were grade 1 to 2. CONCLUSION: The CLAT protocol seems to have promising for the treatment of refractory AML patients, and patients well tolerated. This CLAT protocol offers an alternative treatment for R-AML patients who received severe intensive treatment, especially with anthracycline-containing chemotherapy.

[C-kit mutation in acute myeloid leukemia patients with AML1-ETO fusion gene and its clinical significance].

This study was aimed to investigate the c-kit mutation in acute myeloid leukemia (AML) patients with AML1-ETO and analyze its relation with clinical and laboratorial features and prognosis. PCR and sequencing methods were used to detect the c-kit 17 exon mutations in 31 AML patients with AML1-ETO. The relation of the c-kit mutation with clinical features, results of laboratorial examination and prognosis of disease were analyzed. The results showed that the c-kit mutation was found in 14 out of 31 AML patients and the mutation frequency was 45.16%. Male patients had a higher incidence of c-kit mutation than that of female patients (P = 0.020). The proportion of patients with newly diagnosed white blood cell>10×10(9)/L and with extramedullary infiltration in mutated group were higher than those in unmutated group respectively. No significant difference was observed at the age (P = 0.437) and the rate of bone marrow blasts(P = 0.510) between the above mentioned two groups. The difference in complete remission rate (64.29% vs 80%, P = 0.344)and relapse rate (58.33% vs 21.43%, P = 0.054) between c-kit mutated and c-kit unmutated groups were not significant. While the c-kit mutated group had a significant higher death rate as compared with c-kit unmutated group (57.14% vs 20%, P = 0.039). It is concluded that the c-kit mutation is frequent in AML patients with AML1-ETO and the c-kit mutated patients have a poor prognosis. It is important to detect c-kit mutation in routine clinical practice for patient's risk stratification, evaluation of prognosis and selection of effective treatment.

[Clinical study of intravenous injecting itraconazole as empirical antifungal therapy for patients with hematological malignancies].

This study was purposed to investigate the efficacy and safety of intravenous injecting itraconazole (ITCZ) as empirical antifungal therapy in the patients with hematological malignancies. According to recommendation in IDSA guidebook, the patients suffered from fever during neutropenia and inefficacy of treatment using broad-spectrum antibiotics for 4 days should receive intravenous injection of ITCZ as empirical antifungal therapy. The results showed that the overall clinical response rate to ITCZ injection was 62.9% (22/35), and the success rate of achieving composite endpoints was 54.3% (19/35). Mild adverse reactions were observed in 6 patients (17.1%). The injection of ITCZ was stopped in 2 patents (5.7%) due to adverse reaction. Further analysis revealed that the response rate was higher in patients with fever prior to the start of ITCZ within five days than beyond five days (P = 0.031). The response rate was higher in patients with possible invasive fungus infection (IFI) than that in patients with probable and confirmed IFI (P = 0.002). The prophylactic antifungal treatment during neutropenia displayed no significant influence on efficacy of empirical antifungal therapy with itraconazole (P = 0.054). It is concluded that the good efficacy and safety of empirical ITCZ injection for hematological malignancies patients is efficient and safe.

[A retrospective study of kidney insufficiency in adult patients after myeloablative allogeneic hematopoietic stem cell transplantation].

The aim of this study was to investigate the renal function in 149 patients receiving myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) from June 2005 to June 2010 in our hospital, and analyze the risk factors resulting in kidney insufficiency and experience in diagnose and therapy. The creatinine clearance (CrCL) and serial creatinine level were evaluated before and after allo-HSCT within 100 days and 1 year. Non-radiation conditioning regimens were used for any patients. The acute kidney insufficiency (AKI) was defined as at least a 1.5-fold rise in serum creatinine level after allo-HSCT within the first 100 days. The chronic kidney insufficiency (CKI) was defined as the creatinine clearance < basal level within 3 months to 1 year after allo-HSCT. The results showed that the kidney insufficiency was found in 41 patients, in which the incidence of AKI was 32/149 (21.5%). CsA, amphotericin B (P = 0.025) and ES (P = 0.022) were defined as risk factors for AKI. The incidence of CKI was 18/138 (13%). cGVHD (P = 0.013) and TA-TMA (P = 0.012) were associated with the development of CKI. The 2-year survival was lower in patients with kidney dysfunction than that in patients without kidney dysfunction (39% vs 74.1%, P < 0.001). The main factors resulting in kidney insufficiency were defined as infection (52%), GVHD (20%), TA-TMA (12%) and tumor relapse (12%). It is concluded that kidney insufficiency is an important complication of allo-HSCT. Careful monitoring kidney function, minimizing the use of amphotericin B, prophylaxis and effective treatment of fungal infection, GVHD and TA-TMA may be effective preventive measures to decrease the incidence of kidney insufficiency.

[A preliminary study on clinical diagnostic value of plasma elafin in skin acute graft-versus-host disease].

OBJECTIVE: To analyze the specificity, sensitivity and receiver operating characteristic (ROC) curve of plasma elafin for diagnosis of skin acute graft-versus-host disease (aGVHD), and to explore its clinical diagnostic value. METHODS: Incidence of skin aGVHD from fifty-three patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) were observed prospectively in Guangdong General Hospital from Apr 2010 to Aug 2011. The plasma concentrations of elafin were detected by enzyme-linked immunosorbent assay (ELISA). Skin biopsies were taken from 28 patients with skin rash, and elafin expression in the skin was detected by immunohistochemistry. Positive expression was defined as significant staining of at 50% of the depth of the epidermis, excluding the granular cell layer and the acrosyringium. RESULTS: Among 28 patients with skin rash, twenty-five were considered as skin aGVHD by clinical diagnosis, seventeen were confirmed as skin aGVHD by pathological biopsy. 11 cases were elafin positive by immunohistochemical staining. Elafin protein was overexpressed in aGVHD skin tissue (P = 0.001). Plasma concentrations of elafin were significantly higher in patients with skin aGVHD (positive) group than in those without skin aGVHD (negative) group (P = 0.005), among which there being no statistically significant difference in plasma elafin level between patients with grade I skin aGVHD group and negative group(P = 0.971), but being statistically significant difference compared patients with grade II-IV skin aGVHD group with those with grade I skin aGVHD group (P = 0.02) and with negative group (P = 0.008). Using the pathological diagnosis as the gold standard, the estimated specificity and the sensitivity of clinical diagnosis criteria were 27.3% and 100%, respectively, and those of tissue elafin protein level were 100% and 64.7%, respectively. The area under the ROC curve was 0.909 (0.797 - 1.021) when plasma concentrations of elafin was used in diagnosis of skin aGVHD. The sensitivity was 82.4% and the specificity was 81.8 % when the critical value was set at 1456.043 µg/L. CONCLUSION: Plasma concentration of elafin is significantly higher at the onset of skin aGVHD. It can be used as biochemical marker of skin aGVHD and has higher value in diagnosis of skin aGVHD.

[Expression of CD133 in the bone marrow of patients with myelodysplastic syndrome and its clinical significance].

OBJECTIVE: To investigate the expression of CD133 in the bone marrow of patients with myelodysplastic syndrome (MDS) and explore its clinical significance. METHODS: The expression of CD133 and CD34/CD38 in the bone marrow was detected using flow cytometry in 31 cases of refractory anemia with excess blasts (RAEB), 10 cases of refractory cytopenia with multilineage dysplasia (RCMD) and 11 cases of aplastic anemia (AA). RESULTS: The percentage of CD133-expressing cells was 6.75% in patients with RAEB, significantly higher than that in patients with RCMD (1.41%) and AA (2.70%) (P<0.05); the percentage of CD133-positive cells were similar between the latter two patient groups (P>0.05). The percentage of CD34(+)/CD38- cells was similar in the 3 groups (P>0.05), all lower than 1%. CONCLUSIONS: Advanced MDS patients are characterized by an increase of CD133-expressing cells, suggesting the value of CD133 in the diagnosis of RAEB. CD34(+)/CD38- cells do not show a significant value in the diagnosis of MDS.

Clinicopathologic features and survival of patients with colorectal mucinous, signet-ring cell or non-mucinous adenocarcinoma: experience at an institution in southern China.

BACKGROUND: Previous studies have shown conflicting results on the relation between clinicopathologic features and prognosis of patients with colorectal mucinous, signet-ring cell, or non-mucinous adenocarcinoma; only few such studies have been performed in China. This retrospective study analyzed data from our department to investigate clinicopathologic characteristics, prognosis and possible correlations of three histologic types - colorectal mucinous, signet-ring cell, and non-mucinous adenocarcinoma, to clarify the bases for observed differences which may lead to development of targeted therapies. METHODS: Of 2079 patients diagnosed with colorectal cancer between 1994 and 2007, 144 had mucinous, 25 had signet-ring cell, and 1837 had non-mucinous adenocarcinoma. Their clinicopathologic parameters and survival were analyzed using established statistical methodologies. RESULTS: Mucinous and signet-ring cell adenocarcinomas were common in younger patients (P < 0.001). Location, size and disease stage differed significantly among the three types. Signet-ring cell tumors were more commonly found in the rectum than mucinous and non-mucinous adenocarcinoma (P < 0.001). Mucinous and signet-ring cell tumors presented in a later stage in life more often than non-mucinous adenocarcinoma, with lymph node involvement, serosal infiltration, peritoneal dissemination, and adjacent organ invasion (P < 0.01). The rate of radical resection, hepatic metastasis and local recurrence did not differ among types (P > 0.05). Compared with patients with non-mucinous adenocarcinoma, patients with mucinous and signet-ring cell tumors who underwent potentially curative resections or stage II/III disease had poorer long-term overall survival. Survival did not differ by type for patients with either stage I or IV disease (P > 0.05). CONCLUSIONS: Mucinous and signet-ring cell adenocarcinoma have unique carcinogenesis and similar biologic behavior. Our study confirms that both histologic types, especially signet-ring cell tumors, are independent, negative prognostic factors for patients with colorectal cancer. Type does not appear to have a significant effect on survival when disease is either stage I or IV at presentation.

[Serum proteomics in patients with RAEB myelodysplastic syndromes].

OBJECTIVE: To screen the molecular markers for refractory anemia with excess blasts in transformation (RAEB) in myelodysplastic syndromes (MDS) by serum proteome profiling. METHODS: The serum protein were isolated from patients with RAEB, acute myeloid leukemia or normal subjects by 2-dimensional electrophoresis (2-DE), and the electrophoresis gels were obtained to identify the differentially reacting protein spots. The replica gels of the differentially reacting proteins were analyzed to locate the matching protein spots, which were identified by peptide mass fingerprint based on matrix-assisted laser desorption/ionization time of-flight mass spectrometry (MALDI-TOF-MS) and database searching. RESULTS: Seven differentially expressed proteins in RAEB were found by 2-DE. Of the 7 proteins, 4 were identified by MALDI-TOF-MS to have significantly differential expression in RAEB, including dipeptidyl peptidase (DPP/CD26), polymerase (DNA directed) kappa, PRO2044 and an albumin-like protein. CONCLUSION: 2-DE-based serum proteome profiling helps identify serum proteomic biomarkers related to MDS. DDP/CD26 has increased expression in the serum in RAEB subtype MDS, suggesting its possible role in advanced MDS.

Regimen containing perarubicin for the treatment of newly diagnosed young patients with acute myeloid leukemia.

BACKGROUND AND OBJECTIVE: Chemotherapy regimen containing anthracyclines has been used as the standard treatment for acute myeloid leukemia (AML). This study was to compare the efficacy and toxicity of the chemotherapy regimen containing perarubicin (THP) with that containing mitoxantrone (MIT) for young patients with newly diagnosed AML. METHODS: A total of 129 patients with newly diagnosed AML, aged 16 to 60 years olds, were assigned for induction chemotherapy containing one to two courses with standard-dose cytarabine (Ara-C) and an anthracycline antibiotic, THP or MIT. When complete remission was achieved after induction therapy, the patients received two courses of consolidation therapy identical to the induction regimen. From then, the patients were alternately given four courses of consolidation therapy consisting of Ara-C/THP or Ara-C/MIT every three weeks. Maintenance treatment continued for three years when patients were in continuous complete remission (CCR). RESULTS: Twenty-six out of 42 patients (61.90%) receiving THP therapy, and 48 out of 73 patients (65.75%) treated by MIT achieved CR (P>0.05). Nine (34.61%) and 11 (22.92%) out of CR patients treated by THP and MIT, respectively, relapsed within one year (P=0.28). Moreover, the incidences of toxicities, such as infection, nausea/vomiting and cardiac events, were similar in these two groups (P>0.05) except for alopecie, which was 26.19% in the THP group compared to 42.47% in the MIT group (P<0.01). CONCLUSIONS: Regimen containing THP plus Ara-C can be used for young adults with newly diagnosed AML for remission induction, but it is not superior to the regimen with MIT. Consolidation chemotherapy with THP or MIT is feasible for young adults with AML after CR.

[Acute pancreatitis induced by cyclosporine a following allogeneic hematopoietic stem cell transplant].

Pancreatitis has not been reported in allogeneic stem cell transplant (allo-SCT) recipients with cyclosporine in China. This article presented a case of acute pancreatitis in a 49-year-old patient with AML-M2a who received allogeneic stem cell transplant from her HLA identical sister. The preparative regimen consisted of busulfan and cyclophosphamide. The cyclosporine A, short-term methotrexate and antilymphocyte globulin (ATG), were used to prevent the graft-versus-host disease (GVHD). Clinical and laboratory signs of acute pancreatitis were found in the patient on day 20 post-transplant. A diagnosis of acute pancreatitis was made although the pancreas was apparently normal at abdominal contrast-enhanced tomography and ultrasonography. She recovered with supportive care and reduction of cyclosporine dose. In conclusion, cyclosporine is the probable cause of pancreatitis in this patient.

[Relationship between cyclins and prognosis of acute leukemia].

BACKGROUND & OBJECTIVE: Cell proliferation and differentiation are directed by cell cycle mechanism. When tumor cells proliferate abnormally, cyclins, which are positive agents of cell cycle, may be expressed abnormally at the same time. Now many references proved that cyclins are highly expressed in solid tumors. This study was designed to investigate the relationship between expression of cyclins and prognosis of acute leukemia. METHODS: Sixty-eight cases of acute leukemia were enrolled. Reverse transcription polymerase chain reaction (RT-PCR) was performed on tumor samples to examine the expression of cyclin A, cyclin D, cyclin E. All samples were divided into three groups: acute leukemia in complete remission (12 cases), newly diagnosed acute leukemia (16 cases) and refractory leukemia (40 case). Samples of benign hemopoietic patients were used as normal control (15 cases). RESULTS: All the 15 cases in the control group were negative of cyclin mRNA. No difference of cyclin A mRNA expression was shown between control group and the three experiment groups (P >0.05). But expression of cyclin D and cyclin E mRNA was significantly different between them (P< 0.01). There was no difference of expression of cyclin D and cyclin E mRNA among CR patients with acute leukemia(P >0.05), while the expression of cyclin D mRNA is significantly higher than that of cyclin E in refractory leukemia group. Furthermore the expression of cyclin D mRNA in recurrent refractory leukemia patients is significantly higher than that newly diagnosed cases (P< 0.05). All cyclins mRNA positive cases were divided into single cyclin gene expressed group and multiple cyclins gene expressed group. The positive rates of them were counted. No difference was found between complete remission group and refractory leukemia group (P >0.05). CONCLUSION: Cyclin D may act as a prognostic marker for acute leukemia. The amount of cyclins expressed cannot be used as a prognostic factor for acute leukemia.