Dose-enhanced immunochemotherapy followed by first-line autologous peripheral blood stem cell transplantation for young patients with high-risk aggressive B-cell lymphoma: an efficacy and prognostic factor analysis / 中华血液学杂志

Objective: This study aimed to determine the efficacy of dose-enhanced immunochemotherapy followed by autologous peripheral blood stem cell transplantation (ASCT) in young patients with newly diagnosed high-risk aggressive B-cell lymphoma. Methods: A retrospective study was conducted to examine the clinical and survival data of young patients with high-risk aggressive B-cell lymphoma who received dose-enhanced immunochemotherapy and ASCT as first-line treatment between January 2011 and December 2018 in Blood Diseases Hospital. Results: A total of 63 patients were included in the study. The median age range was 40 (14-63) years old. In terms of the induction therapy regimen, 52 cases received R-DA-EP (D) OCH, and the remaining 11 received R-HyperCVAD/R-MA. Sixteen (25.4% ) patients achieved partial response in the mid-term efficacy assessment, and ten of them were evaluated as complete response after transplantation. The median follow-up was 50 (8-112) months, and the 3-year progression-free survival (PFS) rate and overall survival (OS) rate were (83.9±4.7) % and (90.4±3.7) % , respectively. Univariate analysis demonstrated that age-adjusted international prognostic index ≥2 scores was a negative prognostic factor for OS (P=0.039) , and bone marrow involvement (BMI) was an adverse prognostic factor for OS (P<0.001) and PFS (P=0.001) . However, multivariate analysis confirmed that BMI was the only independent negative predictor of OS (P=0.016) and PFS (P=0.001) . Conclusions: The use of dose-enhanced immunochemotherapy in combination with ASCT as first-line therapy in the treatment of young, high-risk aggressive B-cell lymphoma results in good long-term outcomes, and BMI remains an adverse prognostic factor.

Clinical Analysis of Patients with MGUS, Primary Light Chain Amyloidosis, Multiple Myeloma or Multiple Myeloma with Concurrent Amyloidosis / 中国实验血液学杂志

OBJECTIVE@#To summarize and compare the clinical baseline characteristics of patients with monoclonal gammopathy of undetermined significance (MGUS), primary light chain amyloidosis (pAL), multiple myeloma (MM), or MM with concurrent amyloidosis, especially the differences in cytogenetic abnormalities.@*METHODS@#The clinical data of 15 cases of MGUS, 34 cases of pAL, 842 cases of MM and 23 cases of MM with concurrent amyloidosis were analyzed and compared retrospectively.@*RESULTS@#Cytogenetic statistics showed that the incidence of t (11; 14) in the four groups (MGUS vs pAL vs MM vs MM with concurrent amyloidosis) was 0%, 33.3%, 16.4%, and 15.8%, respectively (P=0.037); that of 13q deletion was 20.0%, 14.7%, 45.8% and 56.5%, respectively (P<0.001); gain of 1q21 was 50.0%, 12.5%, 47.4% and 40.9%, respectively (P=0.001). Proportion of pAL patients with 0, 1 and≥2 cytogenetic abnormalities (including 13q deletion, 17p deletion, 1q21 amplification and IgH translocation) accounted for 41.9%, 41.9% and 16.1%, respectively; while the proportion of the same category in MM was 17.6%, 27.3%, and 55.2% respectively; this ratio of MM with concurrent amyloidosis was more similar to MM. Subgroup analysis showed that genetic abnormalities (including 13q deletion, 17p deletion and 1q21 amplification) were comparable within t (11; 14) negative and positive groups. Compared with positive cases, t(11; 14) negative patients with MM or MGUS were more likely to have 13q deletions and multiple genetic abnormalities.@*CONCLUSION@#Clinical characteristics of pAL, especially cytogenetic abnormalities, are significantly different from MM with concurrent amyloidosis. It suggests that although the onset characteristics are similar, actually the two diseases belong to different disease subtypes which should be carefully predicted and identified.

The prognostic significance of POD24 in 106 cases with splenic marginal lymphoma with bone marrow invasion / 中华血液学杂志

Objective: To explore the effect of progression of disease within 24 months (POD24) on overall survival (OS) of splenic marginal lymphoma (SMZL) with bone marrow invasion, and to compare the clinical characteristics between POD24 SMZL with non-POD24 SMZL patients. Methods: The SMZL patients with bone marrow invasions were retrospectively analyzed between January 2002 and January 2017 treated in our institute, and the patients with sufficient follow-up time to judge POD24 were evaluated the clinical characteristics and prognosis, patients who died of non-progressive factors were excluded. Results: 106 patients were enrolled with a median age of 57 (25-79) years old. ①Clinical characteristics: All patients presented with bone marrow invasion and splenomegaly, 59.4% (63/106) with huge spleen, 14.8% (15/101) with hepatomegaly. Complex karyotype were found in 22.7% (18/79) patients; 13q deletion, 11q (ATM) deletion, 17p (TP53) deletion, and CEP12 abnormality patients presented with the percentage of 5.1% (4/78) , 1.3% (1/72) , 2.5% (2/80) , and 7.5% (4/53) , respectively.②Survival analysis: Univariate analysis showed that POD24, HGB less than 100 g/L and FISH detection of trisomy 12 were poor prognostic factors of OS. Multivariate analysis showed that only POD24 had independent prognostic significance[HR=20.116 (95%CI 2.226-181.820) , P=0.008]. ③Subgroup features: Patients with POD24 had significantly higher rates of mediastinal lymphadenopathy (63.6%vs 18.9%, P=0.005) and complex karyotype (50.0%vs 17.9%, P=0.024) than those without POD24. While the incidence of abdominal lymphadenopathy, anemia, thrombocytopenia, the lower albumin, and the increasing lactate dehydrogenase were higher in POD24 patients, but with no statistically difference. Conclusion: POD24 is an independent prognostic factor of the OS in SMZL. SMZL patients with mediastinal lymphadenopathy and complex karyotypes when diagnosed have a higher risk of POD24.

Clinical Analysis of B-CLPD with Cytopemia as the Predominant Characteristic / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics and therapeutic responte of patients with B-CLPD mainly manifested as cytopenia, so as to deeply understand this disease.@*METHODS@#The clinical data of 13 B-CLPD patients with hematocytopenia as main manifestation, and the absolute count of lymphocytes＜5×10/L, absence of hepatosplenic lymph-nodes and extramedullary invasion tin our department fron 2003 to 2018 were analyzed retrospectively. The clinical characteristics, therapeutic efficacy and adverse reactions of 3 patients were summarized.@*RESULTS@#The median age of patients was 59 (43-76) years old, the median of lymphocyte was 1.86 (0.69-4.8) ×10/L, the levels of LDH and β2-microglubulin were normal in most patients, the monolineage and multilencage hematopoietic failure of different degrees existed in most all patients. The lymphocyte ratio in patients was 18.5%-94.0%, CD20 was positive in all patients, and yet the CD5-positive and CD-negative existed in 7 and 6 cases respectively. There was no significant difference in ratio of lymphocyte invasion among different immunophemtype. The FISH detection showed that there were no high risk genetic types. 92.3% of patients received rituximab treatment, most of them received chemotherapy of rituximab combined with C0P/CHOP like regimen, only 2 patients received fludarabine for comparatively short course. The analysis indicated that 8 out of 13 patients showed a certain theropeutic efficacy, however the drug-related hematopoietic suppression occurred in both 2 patients treated with fludarabin.@*CONCLUSIONS@#The B-CLPD accompanied with hematocytopenia often displays bone marrow hypohematopoiesis of different degree and easily confuses with the congenital and acquired hemotopoietic faiture diseases. The rituximab treatment may be more appropreate for these patients, but for patients received chemotherapy containing fludarabin, the persistant hematopoietic failure must be especially watched out.

Prognostic factors in newly diagnosed multiple myeloma patients with 1q21 amplification/gain treated with bortezomib-based regimens followed by autologous hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To explore the prognostic factors in newly diagnosed multiple myeloma (NDMM) patients with 1q21 amplification/gain treated with bortezomib-based regimens followed by autologous hematopoietic stem cell transplantation (ASCT) . Methods: We retrospectively assayed 35 NDMM patients with 1q21 amplification/gain who received bortezomib-based chemotherapy followed by ASCT and maintenance therapy between January 2008 and August 2015. Results: ①The median age of 35 patients were 49(33-63)years old. Ratio of male to female was 22∶13. Monosomy1q21 amplification/gain was only seen in 3(8.6%) patients, the other 32 patients were with additional cytogenetic abnormalities including 13q14 deletion, t(11,14), t(4,14), t(14,16), 17p deletion and complex karyotype aberrations. ②The complete remission (CR) rate was 57.0% (20/35), the very good partial remission(VGPR) rate was 37.1%(13/35) and the partial remission (PR) rate was 5.7%(2/35) after ASCT. At a median follow-up of 24 (8-85) months, 3-year estimated progression free survival (PFS) and overall survival (OS) rate were (66.5±9.7)% and (69.6±9.9)%, respectively. ③As 13 patients with high-risk cytogenetic abnormalities, the median PFS and OS time was 26 and 28 months. The 3-year estimated PFS and OS was (28.0±15.9)% and (36.5±16.4)%, respectively. Another 22 patients without other high-risk cytogenetic abnormalities, the median PFS and OS time was 54 months and not reached. The 3-year estimated PFS and OS was (71.5±12.7)% and (92.3±7.4)% in this group, respectively. The presence of additional other high-risk cytogenetic abnormalities resulted in significantly shortened PFS (χ(2)=5.404, P=0.020) and OS (χ(2)=7.596, P=0.006) compared with no high-risk cytogenetic patients. Conclusion: NDMM patients with isolated1q21 amplification/gain were rarely and usually had additional other cytogenetic abnormalities. The outcomes in this group treated with bortezomib-based chemotherapy followed by ASCT and maintenance therapy were satisfied, additional other high-risk cytogenetic abnormalities made PFS and OS further shortened.

Clinical analysis of 24 patients of hairy cell leukemia treated by cladribine / 中华血液学杂志

Objective: To investigate the curative effect of hairy cell leukemia by clatabine. Methods: The clinical data of 24 patients with hairy cell leukemia treated by cladribine from November 2006 to October 2017 were analyzed retrospectively, then the curative effect and adverse drug reaction were analyzed. Results: ① A total of 24 patients including 22 male and 2 female, and the median age was 49.5 years (range 33 to 76) at diagnosis. There were 20 patients with of splenomegaly (4 patients with mild splenomegaly, 4 moderate splenomegaly, and 12 massive splenomegaly), 3 patients with enlargement of lymph nodes, and 1 patients who had undergone splenectomy. Five patients were pancytopenia, 15 were cytopenia in 2 lineages, and 4 patients were cytopenia only in one lineage. The median ratio of HCL cells detected by flow cytometry in bone marrow was 21.79% (0.69%-68.96%). BRAF mutation was detected in 15 patients by first generation or next generation sequencing technology. ② Among 24 patients, 20 were treated with cladribine alone (one course in 19 patients, 2 courses in 1 patient), and 4 patients were treated with cladribine combined with rituximab (one course in 3 patients, 2 courses in 1 patient). Excepting 5 patients whose follow-up time was not reaching 6 months, 19 patients were evaluated for efficacy in 6-12 months after treatment: 9 patients obtained CR, 9 obtained unconfirmed CR (Cru), the other 1 obtained PR, the CR/CRu rate was 94.7%, the overall response rate (ORR) was 100.0%. ③ All the 24 patients appeared 2-4 grade hematological adverse reactions after cladribine treatment, which were mainly grade 3/4 neutropenia (66.67%) and grade 3/4 thrombocytopenia (29.2%). All the adverse reactions were controlled or recovered spontaneously. ④ After the median follow-up time of 15 (3-133) months, no progression, recurrence or death occurred in the patients. Both median OS and PFS were not reached. Conclusion: This study suggests that treatment of HCL with cladribine has high response rate, controllable adverse reactions and the good prognosis.

Role of minimal residual disease detection by multiparameter flow cytometry in newly diagnosed multiple myeloma: an analysis of 106 patients / 中华血液学杂志

Objective: To assess the feasibility and prognostic value of the minimal residual disease (MRD) evaluated by multiparameter flow cytometry (MFC) in the newly diagnosed multiple myeloma (MM) patients of China. Methods: Clinical data of 106 consecutively newly diagnosed MM patients with MRD data were retrospectively analyzed in a single center in China from June 2013 to June 2015. Results: ① Of 106 patients, 48 (45.3%) achieved MRD negativity. The median time to MRD-negative was 3 months. More patients undergoing autologous stem cell transplantation (ASCT) achieved MRD negativity compared with non-ASCT patients (62.2% vs 36.2%, χ(2)=6.536, P=0.011). ② Of 48 patients in complete remission (CR), 7 (14.6%) was MRD positive, 5 of them showed disease progression (PD) during the follow-up, and 3 died. The median progression free survival (PFS) was 19 months, and the median overall survival (OS) was 28 months, both were significantly shorter than the CR patients with MRD-negative (P<0.05). ③At a median follow-up of 38 months, MRD-negative patients showed significantly superior outcomes compared with MRD positive ones, the PFS was not reach versus 17 months and the OS was not reach for both (P<0.001). Patients were grouped into 4 categories according to their MRD levels: 1% or higher, 0.1% to less than 1%, 0.01% to less than 0.1%, or negative. It showed that the outcomes (PFS and OS) tended to be improved along with the tumor depletion. ④ Multivariate prognostic analysis showed that MRD was a powerful independent prognostic factor for PFS[HR=0.133 (95% CI 0.062-0.288) , P<0.001] and OS[HR=0.156 (95% CI 0.050-0.484) , P=0.001]. According to MRD and cytogenetics, the patients were classified into 4 groups. High risk patients with MRD negative presented a significantly better outcome than high risk patients with MRD-positive, and a similar one to the standard risk patients with MRD-negative. Conclusions: MRD negativity by MFC was more popular in MM patients undergoing ASCT. MRD was an independent prognostic factor in MM. And the prognosis of MM patients can be stratified according to the level of MRD. MRD-negative patients with high risk cytogenetics presented a similar outcome to the standard risk ones. MRD by MFC should therefore be considered more widely applied in the clinic.

Real-time and retrospective analyze of cardiac remote monitoring based on differential threshold method / 中国医学装备

Objective:To observe the effects of real-time and retrospective analyze of cardiac remote monitoring based on differential threshold method.Methods: Xin An Bao XAB - M3AG ECG remote monitoring system which based on the differential threshold method of improvement being used to determine the parameters of electro cardio signal was installed in 8957 patients.Results: We had collected all 46967 ECG real-time data, including 9564 manual transmission, 25830 timing transmitting and 11573 automatically transmission. 5728 of automatically transmission was with arrhythmia (49.5%) and the others of automatically transmission was attribute to inference.Conclusion: The results showed that algorithm complexity based on the improved differential threshold method is low, the precision is high and it has a good real-time performance. It realized the real-time monitoring of ECG.

Prognostic value of serum IL-6 in patients with multiple myeloma / 中国实验血液学杂志

This study was aimed to evaluate the prognostic value of serum IL-6 (sIL-6) in patients with multiple myeloma (MM). The sIL-6 level in 288 patients with MM was retrospectively analyzed, and the clinical characteristics and prognosis in patients with different IL-6 level were compared. The newly diagnosed patients with MM were divided into two groups: the low sIL-6 group (sIL-6 < 100 pg/ml) and the high sIL-6 group (sIL-6 ≥ 100 pg/ml). The results showed that high sIL-6 level was more common in patients with ECOG score>3, myeloma bone disease (MBD) between grade 2 to 4, and high creatinine level. There was no significant differences in age, abnormal karyotype percentage, chromosome 13q14 abnormality percentage, CD138(+)/CD38(+) cells percentage and the level of calcium, phosphorus, albumin, C-reactive protein, β2-MG, lactate dehydrogenase, hemoglobin, platelet between the two groups at diagnosis, and also no significant difference in response to initial induction chemotherapy among the two groups. The overall survival was significantly different between the low and high IL-6 groups (P = 0.04, 35 m vs 29 m), but no difference in time to progress between the two groups (P = 1.93, 23 m vs 14 m). It is concluded that the sIL-6 level correlates with the clinical characteristics and prognosis. Radioimmunoassay is an appropriate measurement for human IL-6 in serum, and suitable for clinical application.

Analysis of the efficacy and prognosis on first-line autologous hematopoietic stem cell transplantation of patients with multiple myeloma / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the efficacy and prognosis of first-line autologous hematopoietic stem cell transplantation (ASCT) for newly diagnosed patients with multiple myeloma(MM).</p><p><b>METHODS</b>From January 2005 to December 31, 2012, 60 patients with MM were enrolled. All patients received thalidomide or/and bortezomib-based induction therapy, then received high-dose melphalan (200 mg/m²) and autologous stem cell support to get a ≥ partial response (PR), and followed by thalidomide-dexamethasone (TD) ±bortezomib as consolidation or maintenance treatment. With the follow up to December 31, 2012, the overall survival (OS), progression free survival (PFS) and the prognostic factors, including ISS stage, response and fluorescent in situ hybridization (FISH) data of cytogenetics were analyzed.</p><p><b>RESULTS</b>With a median follow up of 36.8 (12.0-102.5) months, the median OS and PFS estimate were not reached and 86.5 months, respectively. After transplantation, all (100%) patients received very good partial response (VGPR), and 34 (56.7%) patients achieved complete response (CR) after consolidation or maintenance treatment. The patients that achieved CR resulted in long term PFS (P=0.030), with no difference in OS (P=0.942). The univariate analysis showed that the abnormalities, including 13q14 deletion, 1q21 gain, IgH location and p53 deletion had the prognostic impacts. If the t(4;14) or p53 deletion was excluded, there would be no correlation between 13q14 deletion or 1q21 gain with PFS and OS. The patients with p53 deletion had a worst survival.</p><p><b>CONCLUSION</b>There has been significant improvement in the outcome for young MM patients by using ASCT and novel drugs. Cytogenetic abnormalities and response to therapy are the main factors affecting the survival of patients.</p>

Clinical feature and efficacy of patients with multiple myeloma and renal impairment treated with bortezomib based chemotherapy / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the efficacy and safety of bortezomib (btz) based chemotherapy in multiple myeloma (MM) patients with renal-function impairment (RI).</p><p><b>METHODS</b>Fifty-six MM patients with impaired renal function treated with bortazomib based regimens in our single center were retrospectively analyzed.</p><p><b>RESULTS</b>The median age was 59 (ranged 30-77) years. 39.3% were κ-restricted MM, while 57.1% were λ-restricted MM. Nine patients were IgD-MM, and 14 were light chain MM. Median creatinine clearance (CrCl) was 25.33 (7.23-59.55) ml/min. The number of patients with mild, moderate and severe RI was 6, 35 and 15, respectively. Overall response rate of MM was 82.4% (≥MR), including 32.4% complete response (CR), 17.6% very good partial response (VGPR) and 26.5% partial response (PR). The rate of renal response was 89.3%, including 62.5% CR, 14.3% PR and 12.5% minor response (MR). A median time of optimal response was 25.5 (ranged 5-240) days. There was no significant difference in the median overall survival and the time to progress in different RI groups. Adverse events observed were similar to those patients with normal renal function previously reported. Most adverse events were manageable, 55.6% patients developed peripheral neuropathy and 10 patients discontinued bortezomib.</p><p><b>CONCLUSION</b>The incidence of RI is higher in patients with IgD-MM and λ restricted MM. Bortezomib based treatment is a highly effective and safe option in MM patients with impaired renal function. In this analysis, renal function was improved in a substantial proportion of patients. Peripheral neuropathy is the major adverse events which limit its use in MM patients.</p>

Outcomes of younger than 60 years old adults with Ph/BCR-ABL positive acute lymphoblastic leukemia: a single center clinical trial of BDH ALL 2000/02 / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the treatment options for younger than 60 years old adults with Ph /BCR-ABL positive acute lymphoblastic leukemia (Ph⁺ ALL).</p><p><b>METHODS</b>From January 2001 to June 2012, 42 adult patients were enrolled in the study. All patients received standard VDCP±L ±imatinb (IM) as induction therapy followed by intensive consolidation of modified Hyper-CVAD/MA±IM. At complete remission 1 (CR1), patients with appropriate donor received allogeneic hematopoietic stem cell transplantation (allo-HSCT), the others sequentially received intensive consolidation ±IM and autologous HSCT (ASCT) at molecular CR (MCR), then MM±VP±IM as maintenance therapy. Overall survival (OS), disease free survival (DFS) and relapse rate (RR) were analyzed.</p><p><b>RESULTS</b>CR rate after 1 cycle of induction chemotherapy was 83.3%. 39(92.9%) patients achieved CR. The median DFS and OS were (22.0±3.5) and (37.0±5.3) months respectively, with cumulative RR of (43.7±9.7)% during a median follow-up of 26.5(8-75) months. All 7 patients in CT group relapsed. Two patients received IM pre- and post-ASCT maintained MCR for 35 and 12 months after ASCT. But the other 3 ASCT recipients without IM died of relapse within 1 year. The transplant-related mortality rate in allo-HSCT group was 12.5%. The estimated 3-year OS in allo-HSCT (n=16), ASCT (n=5) and CT (n=7) groups were (66.7±12.2)%, (25.0±21.7)% and (16.7±15.2)%, respectively (P=0.014); meanwhile, the estimated 3-year DFS in those groups were of (56.3±12.4)%, (26.7±22.6)% and 0, respectively (P=0.002).</p><p><b>CONCLUSION</b>IM combined with intensive chemotherapy significantly increased the CR rate with the improved quality of CR, which highlighted the feasibility of SCT. Allo-HSCT could decrease relapse to produce favorable OS and DFS in CR1 of young adults with Ph⁺ ALL. ASCT combined IM might be the treatment of choice for those achieved MCR but without donors.</p>

Effect of Low Molecular Weight Agarieus Blazei Murill Polysach-aride on Colon Carcinoma HT-29 Cell-endothelium migration and Adhesion / 医学研究杂志

Objective To investigate the effects of low molecular weight polysaccharide lsolated from agaricus blazei murill (LMPAB) on adhesion and migration of tumor cell and HUVECs. Methods HT-29 cell and HUVECs proliferation was analyzed by MTT.Adhesion and transmigration monolayer HUVECs ability of HT-29 was examined by spectrophotometry and transwell chambers.Results LMPAB showed no cytotoxic effect on HT-29 cells and HUVECs. LMPAB could significantly decrease HT-29 adhesion and transmigration through HUVECs.Conclusion LMPAB exerts the anti-tumor metastasis activity via inhibition of tumor cell adhesion and migration HUVECs.

Therapeutic effects of flunarizine combined with aspirin on patients with migrainous cerebral infaction / 中国临床药理学与治疗学

AIM: To explore the therapeutic effects of flunarizine combined with aspirin in the treatment of migrainous cerebral infaction. METHODS: 38 cases of patients diagnosed as migrainous cerebral infaction were respectively given flunarizine 10 mg combined with aspirin 100 mg every night for a month. The observed indices included the dysfunction scores of nervous system, the total classes of living ability, and the accumulating rate of platelet and viscosity of plasma before and after the treatment. RESULTS: Before the treatment the dysfunction scores of nervous system and the living ability of the patients were 13.51 ? 4.78 and 3.45 ? 1.13 , and after the treatment the values were 4.34 ? 1.85 and 1.79 ? 0.72 respectively (P

Simultaneous Determination of 1-Chloroanthracene and9-Bromoanthracene by Using Matrix Isopotential SynchronousFluorescence Spectrometry Combined with Derivative Technique / 分析化学

Matrix isopotential synchronous fluorescence spectrometric (MISF) method combined with derivative technique has been proposed to determine two spectrally-badly-overlapped anthracene derivatives, 1-chloroanthracene and 9-bromoanthracene,simultaneously. An optimal scanning route of MISF spectra was chosen. By using the novel method, 1-chloroanthracene and 9-bromoanthracene have been determined directly and simultaneously without tedious pre-separation in its mixture.The recoveries of 1-chloroanthracene and 9-bromoanthracene for the analysis are 83.5％～94% and 90.0%～94.0% respectively and their limits of detection are 0.69μg/L and 10μg/L respectively.