Tolerance and pharmacodynamics phase Ⅰ clinical trial study of chimeric anti-CD20 monoclonal antibody IBI301 in Chinese patients with CD20-positive non-Hodgkin’s lymphoma / 中华血液学杂志

Objective@#To evaluate the tolerance and safety of a human-mouse chimeric anti-CD20 monoclonal antibody IBI301 in Chinese patients achieved objective response with CD20+ B-cell non-Hodgkin’s lymphoma (NHL).@*Methods@#Nine patients with CD20+ B-cell NHL received dose-escalating IBI301 infusions (250 mg/m2, n=3; 375 mg/m2, n=3; 500 mg/m2, n=3, respectively). The data of all patients were collected for safety analyses. The median exposures of 125 mg/m2, 375 mg/m2, 500 mg/m2 dose groups were 243, 690 and 980 mg, respectively. Safety and tolerability were evaluated by monitoring adverse events (AE). The ratios of CD19+, CD20+ B cells and the levels IgG and IgM were detected to evaluate the pharmacodynamics.@*Results@#Totally 52 events of AE were observed, including 18 events of AE in 125 mg/m2 group, 14 events of AE in 375 mg/m2 group and 20 events of AE in 500 mg/m2 group, respectively. There were 26 adverse reactions of 52 cases of AE, 22 reactions were judged to be probably related to IBI301, and 4 reactions were not probably related to IBI301, all disappeared or returned to baseline levels. Common AE in this study included decreased WBC, upper respiratory infection, decreased neutrophil count, dyspepsia, hyperuricemia, paresthesia, oral mucositis and dizziness. No patients quitted or trial discontinued. No severe AE (SAE) were reported. No dose-limiting toxicity (DLT) events were observed in the study. The ratio of CD20+ and CD19+ B cells decreased in all subjects. There was no significant changes of the levels of IgG and IgM.@*Conclusions@#The single dose of IBI301 injection was well tolerated, and the AE occurred in the patients recovered. No SAE were reported, No DLT events were observed in the study. The IBI301 caused an elimination of the peripheral CD20-expressing B cells in all patients.@*Clinical trial registration@#Chinadrugtrials, CTR20140762.

Clinical analysis of 25 patients with aggressive peripheral T-cell lymphoma in advanced stage treated with autologous stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the outcomes of autologous stem cell transplantation (ASCT) for patients with aggressive peripheral T-cell lymphoma (PTCLs) in advanced stage.</p><p><b>METHODS</b>The clinical data of 25 patients in complete remission (CR) with aggressive PTCLs received ASCT from May 1997 to June 2013 were retrospectively analyzed.</p><p><b>RESULTS</b>① Of the 25 cases, 16 were unspecified PTCL (PTCL-U), 4 with angioimmunoblastic T cell lymphoma (AITL), 3 with anaplastic large cell lymphoma (ALCL) and 2 with hepatosplenic T cell lymphoma (HSTL), with a median age of 30(12-54) years old. Ratio of male to female is 16∶9. The distribution of stages was 8 cases with stage Ⅲ and 17 patients with stage Ⅳ. Nine patients presented with bone marrow involvement. Before ASCT, 18 patients were in CR1 and 7 patients were in CR2. ②Two patients with HSTL in stage ⅣB and IPI score 4/5 in CR1 relapsed and died within 12 months after ASCT. At a median follow-up of 38 (range 14-110) months, the estimated 3-year probability of PFS and OS for the other 23 patients was (63.1 ± 10.5)% and (71.8 ± 9.9)%, respectively. The patients in first CR had a better survival than the patients in second CR. The 3-year probability of PFS were (74.9 ± 11.0)% vs (33.3 ± 19.2)% (P=0.092) and OS were (80.2 ± 10.4)% vs (50.0 ± 20.4)% (P=0.043), respectively. The 3-year probability of PFS and OS were (40.0 ± 17.4)% and (53.3 ± 17.3)% in bone marrow involvement patients and the corresponding figure were (77.9 ± 11.3)% and (84.4 ± 10.2)% in non- bone marrow involvement patients.</p><p><b>CONCLUSION</b>ASCT could improve the survival of aggressive PTCLs. Non CR1 status and bone marrow involvement had negative influence on OS in patients with aggressive PTCLs treated by ASCT. The prognosis was very poor in patients with HSTL and satisfactory regimens should be investigated.</p>

Clinical and biological characteristics of non-IgM lymphoplasmacytic lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To observe the clinical and biological characteristics of Non-IgM-secreting lymphoplasmacytic lymphoma (LPL) and draw the differences between non-IgM LPL and Waldenström macroglobulinemia (WM).</p><p><b>METHODS</b>Records of 13 patients with non-IgM LPL were retrospectively analyzed between January 2000 and December 2013. The cytogenetic aberrations were detected by fluorescence in situ hybridisation (FISH).</p><p><b>RESULTS</b>In the cohort, 7 males and 6 females with a median age of 63 years (range 43 to 74), two patients were IgA secreting, 6 with IgG secreting and 5 patients without monoclonal globulin. The major complaint at diagnosis included anemia associated symptom (53.8%), mucocutaneous hemorrhage and superficial lymphadenopathy (15.4%). Eight patients had B symptom at diagnosis. All of the 13 patients had bone marrow involvement and anemia, and 10 patients had 2 or 3 lineage cytopenia. In 5 patients with available immunophenotypic data, all expressed CD19, CD20, CD22 and CD25, but missed the expression of CD10, CD103 and CD38. Two cases had CD5 or sIgM positive alone. Another 2 patients were CD23 or CD11c positive and 3 patients were FMC7 positive. Cytogenetic aberrations had been detected by FISH in 7 patients, but only two (28.6%) patients had aberrations with del(6q).</p><p><b>CONCLUSION</b>The clinical and biological characteristics had no significantly difference between non-IgM LPL and WM.</p>

Clinical analysis of multiple myeloma patients with bone-related extramedullary disease: a longitudinal study on 834 consecutive patients in a single center of China / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyse the incidence, clinical features, prognosis of bone-related extramedullary disease （bEMD） and its relationship with strict EMD (sEMD) in MM patients.</p><p><b>METHODS</b>The records of 834 consecutive newly diagnosed patients with MM in our hospital between 1993 and 2013 were retrospectively reviewed.</p><p><b>RESULTS</b>①Among 834 patients at diagnosis, 32 cases (3.8%) showed bEMD, and 40 cases (4.8%) showed sEMD. Patients with bEMD at presentation showed significant lower level of lactate dehydrogenase (180.9 U/L vs 299.2 U/L, P=0.034) and higher overall response rate (ORR) (95.7% vs 66.7%, P=0.009) compared with sEMD patients. While the above two parameters were comparable between patients with bEMD and without EMD. ②As to the prognosis of patients without autologous hematopoietic stem cell transplantation (auto-HSCT), the overall survival (OS) of patients with sEMD, bEMD and without EMD was 14.0, 37.5, and 38.0 months, respectively. The time to progression (TTP) of the three groups was 11.5, 27.0, and 22.0 months, respectively. Compared to the patients with sEMD, the outcomes (both OS and TTP) of the other two groups was significantly better (P<0.05). Patients with bEMD at presentation was comparable to the patients without EMD, but the two groups were better than the patients with sEMD. ③The incidence of bEMD during follow-up was 0.5%. The OS of patients with sEMD, bEMD and without EMD during follow-up was 26.0, 17.0, and 40.0 months, respectively. The TTP of the three groups was 13.0, 11.0, and 25.0 months, respectively. The outcomes (both OS and TTP) of patients with bEMD at relapse/progression showed no significant difference as compared with the other two groups (P>0.05).</p><p><b>CONCLUSION</b>The clinical features of MM patients with bEMD are different from the patients with sEMD. Outcomes of this population is significantly better than the latter, and is comparable to the patients without EMD. It suggests that bEMD alone has no negative prognostic significance in MM patients.</p>

Distinct characteristics and new prognostic scoring system for Chinese patients with Waldenström macroglobulinemia / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Waldenström macroglobulinemia (WM) is an uncommon lymphoid malignancy. The characteristics and prognosis of WM have never been systematically studied in the East.</p><p><b>METHODS</b>We analyzed the clinical characteristics and the prognostic factors of 90 Chinese WM patients, and compared them with the Western reports.</p><p><b>RESULTS</b>The median age was 62 years old with a male-to-female ratio of 3.74. The most common symptoms at diagnosis were fatigue (77.8%) and bleeding (20%), while only 6 patients (6.7%) were asymptomatic. In the univariate analysis, age >62 years, thrombocytopenia, leucopenia, cytopenias ≥ 2, and high risk on the international prognostic scoring system for WM were the adverse risk factors, but only age >62 years and ≥ 2 cytopenias were the independent prognostic factors in the multivariate analysis. Using age <62 years and ≥ 2 cytopenias, three significantly different prognostic groups could been distinguished, with 5-year overall survival of 71.6%, 48.6%, and 17.0% (P < 0.001).</p><p><b>CONCLUSION</b>Distinct characteristics exist in WM in China compared to the West and we describe a new simple prognostic model for newly diagnosed WM patients.</p>

The immunophenotypic characteristics of 260 patients with CD5 + B cell lymphoproliferative disorders / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the immunophenotypic characteristics of CD5⁺ B cell lymphoproliferative disorders (B-LPD) of Chinese patients.</p><p><b>METHODS</b>Immunophenotyping of bone marrow and (or) of peripheral blood was performed in patients with B-LPD by four color multiparameter flow cytometry analysis using a panel of monoclonal antibodies, and the patients clinical data were retrospectively analyzed. The difference in immunophenotypes and the related clinical features were retrospectively analyzed. Fluorescence in situ hybridization (FISH) for t(11;14) detection was applied to diagnose or exclude mantle cell lymphoma.</p><p><b>RESULTS</b>(1)A total 260 CD5⁺ B-LPD patients were enrolled in this study, including 186 chronic lymphocytic leukemia (CLL), 40 mantle cell lymphoma (MCL), other B-LPD including 5 splenic marginal zone lymphoma (SMZL), 2 B-cell prolymphocytic leukemia (B-PLL), 3 hairy cell leukemia (HCL). The other 26 cases (10%)were not classified and defined as unclassified B-LPD (BLPD-U). MCL patients were all positive for t(11;14) detected by FISH, while all the BLPD-U patients were negative for t(11;14). (2) All patients expressed CD19, CD20 and CD5. According to the immunophenotypic score system, 186 CLL patients scored 4-5, 99.5% of patients with CD23⁺, 11.3% with sIgM⁺, 10.2% with FMC7⁺, 44.1% with CD22⁺ and 51.1% with CD11c⁺. MCL patients scored 2-3, with 50% expressing CD23 and sIgM, 81.6% expressing FMC7, 92.1% expressing CD22 and 5.3% expressing CD11c. In aspect of BLPD-U and other B-LPD, the expression of CD23, sIgM, FMC7, CD22 and CD11c were 73.1% and 50%, 34.6% and 50%, 88.5% and 100%, 92.3% and 90%, 69.2% and 70%, respectively. (3)In comparison of CLL with MCL, there was a significant difference in the expression of CD23, sIgM, FMC7, CD22 and CD11c between the two groups (P<0.01). Between MCL and BLPD-U, similar expression type of CD23, sIgM, FMC7 and CD22 was found except CD11c, which was highly expressed in BLPD-U (P<0.001). The difference of CD11c expression was also statistically significant between MCL and other B-LPD (P<0.01). In comparison of MCL with other B-LPD, there was a significant difference in the expression of CD11c (P<0.01). The expression of CD23 and sIgM in MCL are 7%-21% and 82%-100% respectively in Western population, while the expression of other immunophenotypic markers is similar with our study.</p><p><b>CONCLUSION</b>The significant high incidence of CD23 and low incidence of sIgM compared to the Western population was observed in Chinese patients, and CD11c coud serve as a useful marker to distinguish MCL from CLL and other CD5⁺ B-LPD.</p>

Detection of BRAF V600E mutation in hairy cell leukemia by high- resolution melting analysis / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the feasibility and diagnostic implication of BRAF V600E mutation identified by high-resolution melting (HRM) assay in patients with hairy cell leukemia (HCL).</p><p><b>METHODS</b>The V600E mutation of BRAF exon 15 in four HCL patients were detected by HRM assay and patients' clinical data were retrospectively analyzed.</p><p><b>RESULTS</b>All four HCL patients were positive for the BRAF V600E mutation, which were identical to the results of DNA sequencing.</p><p><b>CONCLUSION</b>The HRM assay for BRAF V600E mutation provides a useful tool to aid the laboratory diagnosis of HCL with easy operability, accuracy, and low cost.</p>

Retrospective clinical analysis of fludarabine and cyclophosphamide with or without rituximab for the treatment of patients with chronic lymphocytic leukemia / 中国肿瘤临床

Objective:This study aimed to compare the clinical efficacy and prognosis between rituximab plus fludarabine and cyclophosphamide (FCR) and fludarabine and cyclophosphamide (FC) regimens for patients with chronic lymphocytic leukemia (CLL). Methods:The clinical data of 58 patients with CLL treated with FCR or FC regimens from December 2002 to January 2012 were analyzed retrospectively. Therapy efficacy and prognosis were compared between the two groups. Results:Among the 58 pa-tients, 27 (44.4%) experienced complete remission (CR) in the FCR group and 31 patients (19.4%) experienced CR in the FC group (P=0.039). The overall response rate (ORR) of the FCR group was higher than that of the FC group (81.5%and 51.6%, respectively, P=0.017). Fourteen patients achieved MRD-negative rating after therapy. PFS and OS in MRD-negative patients were superior compared with the MRD-positive group (P=0.000, 0.003). The proportion of MRD-negative patients in the FCR group was higher than that in the FC group (37.0%and 12.9%, respectively, P=0.032). PFS in high-risk genetic patients was lower than that in low-risk genetic patients (P=0.011, 0.027). The OS time between the two groups did not exhibit any difference. Conclusion:FCR produced a high CR and ORR in patients with CLL. Many patients in the FCR group were responsive to the treatment. Thus, FCR could be a more effective regimen than FC for patients with CLL.

Successful treatment of B cell prolymphocytic leukemia by fludarabine, cyclophosphomide and rituximab therapy: own experience and literature review / 白血病·淋巴瘤

Objective To explore the clinical characteristics of B cell prolymphocytic leukemia (B-PLL).Methods The clinical manifestation,treatment and outcome of a 33-year-old man with B-PLL were reported.Results The young patient had thrombocytopenia and systemic B-symptoms,markedly raised lymphocyte'count,bulky splenomegaly and lymphadenopathy.He refused stem cell transplant,so RFC regimen (fludarabine,cyclophosphomide and rituximab) therapy were administered.After 4 cycles of RFC therapy,the patient achieved a complete immunophenotypical and hematological remission response.Conclusion RFC therapy might be a feasible and useful treatment option for B-PLL.

Cladribine for treatment on hairy cell leukemia: three cases report and literatures review / 白血病·淋巴瘤

Objective To observe clinical response of the cladribine in the treatment of hairy cell leukemia.Methods Three patients were treated with cladribine 10 mg ivgtt for 3 or 5 days.Results Among 3 patients,2 patients achieved complete remission and 1 patient achieved near complete remission.Conclusion Cladribine has high efficacy and a favorable toxicity when adminisered to patients with hairy cell leukemia.

Investigation of long-term follow-up results of 135 patients with chronic myeloid leukemia receiving imatinib / 白血病·淋巴瘤

Objective To evaluate the efficacy and safety of imatinib in chronic myeloid leukemia (CML) patients and analyse the factors affecting the survival. Methods 135 CML patients receiving imatinib were evaluated for hematologic, cytogenetic, and molecular responses and adverse events. Results The median follow-up was 20 (range 3-67) months. The rate of cumulative complete hematological response (CHR), major cytogenetic response (MCyR), complete cytogenetic response( CCyR ) and complete molecular response (CMoR) in chronic phase CML patients were 97.9 %, 78.3 %, 72.2 % and 35.1%, respectively.These rates were significantly higher in chronic phase than in accelerated phase and blastic phase (P ＜0.001).The rate of CCyR in low-risk patients was significantly higher than high-risk patients (P =0.048). The estimated overall survival (OS) rate at 1, 3 and 5 year for chronic phase patients were (97.8±1.5) %, (95.2±2.4) % and (91.9±3.2) %, respectively. The estimated progression-free (PFS) survival rate at 1, 3 and 5 year were (92.6±2.7) %, (85.5±3.7) % and (81.3±4.3) %, respectively. The OS rate for accelerated phase patients at 6, 12 and 24 month were (93.8±6.1) %, (72.5±11.8) % and (64.5±12.9) %, the PFS rate were (92.3±7.4) %,(64.5±14.7) %, (53.7±15.7) %, respectively. The OS rate for blastic phase patients at 6, 12 and 19 month were (86.4±7.3) %, (45.4±11.4) %, (19.4±9.8) %, the PFS rate were (70.1±12.6) %, (37.6±15.6) % and (18.8±15.4) %, respectively. The OS and PFS of patients in chronic phase who achieved CCyR or CMoR were better than patients only achieved CHR (P ≤0.001). Multivariate analysis for survival of chronic phase patients indicated that imatinib resistance was the unfavourable factor for PFS (P =0.000, RR =46.744) and OS(P =0.007, RR =20.270). The non-hematological toxicity of imatinib was slight and tolerable, severe hematological toxicity was the major reason for dose reduction or drug discontinuation. Conclusion The efficacy of imatinib in chronic phase CML patients is significantly superior to which in accelerated phase and blastic phase; Achieving CCyR even CMoR is the most important thing for longer survival, iinatinib resistance is the major problem in the treatment with imatinib.

Blastic plasmacytoid dendritic cell neoplasm: two cases report and review of literatures / 中华内科杂志

Objective To identify the clinical and pathological features of blastic plasmacytoid dendritic cell neoplasm (BPDC). Methods The characteristics of BPDC hematodermic neoplasm were discussed with a report of two new cases and review the literatures. Results Both patients presented with skin nodules and the tumors were CD+4 and CD+56. Lineage specific markers for B- and T-cell were negative and the tumors did not express myeloperoxidase. Systemic chemotherapy resulted in complete remission, but the disease relapsed quickly and were unresponsive to further chemotherapy. The patients died 26 months and 11 months respectively after diagnosis. Conclasion BPDC hematodermic neoplasm is a rare subtype of lymphoma with distinct clinicopathologic and immunophenotypic features. The disease often has a fulminant course with a poor prognosis. More recent studies suggest that there is a derivation from a plasmacytoid dendritic cell precursor.

Analysis on complications of 203 chronic lymphocytic leukaemia patients / 白血病·淋巴瘤

Objective To summarize the common complications of chronic lymphocytic leukemia (CLL). Methods 203 cases of CLL patients from the Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC, were retrospectively reviewed and followed up.The common complications of CLL were also summarized. Survival analysis was used to analyze the prognostic value of these common complications. Results 40 (19.7 %) patients sustained infectious complications,and the respiratory tract infections were the most common type (75.6 %). 15 (7.4 %) patients complicated with autoimmune diseases (AID), and the autoimmune hemolytic anemia(AIHA) were the most common type(31.3%). 8(3.94 %) patients suffered from secondary cancers, including lung cancer, etc.3(1.48 %) patients developed other high-grade lymphomas, 2 of them transformed to prolymphocytic leukemia (PLL), 1 of them transformed to diffuse large B cell lymphoma (DLBCL) which was called Richter syndrome. Complicating infections and secondary cancers or transformations were associated with poor prognosis.Complicating AIDs was not an adverse prognostic factor. Conclusion Infections, AIDs and secondary cancers or transformations are common complications of CLL patients.Lung is the most common infectious site, and AIHA is the most common AID type,none secondary cancer s incidence rate is specifically higher than the others. Infections and secondary cancers or transformations indicate poor prognosis.

Report of nine cases of aggressive natural killer-cell leukemia / 白血病·淋巴瘤

Objective To identify the clinical and pathological features of aggressive natural killercell leukemia (ANKL). Methods 9 cases of ANKL fulfilling the criteria defined by the World Health Organization classification were retrospectively analyzed with literature review, Results Systemic symptoms, hepatomegaly, splenomegaly, lymphadenopathy were frequently observed. Liver dysfunction, neutropenia, anemia and thrombocytopenia were often seen during the course of the disease. Most of the bone marrow shows focal or subtle infiltration by the neoplastic cells. The immunophenotype of cells was characteristic for CD+56, sCD-36, and variable expression of CD2, CD7, CD8 and CD11b. T-cell receptor (TCR) genes rearrangement were in germline configuration. Median survival time was 9 weeks. Conclusion ANKL is an entity of mature cytotoxic NK-cell neoplasms with distinct phenotype and disease presentations. The disease often has a fulminant course with a poor response to chemotherapy and a short survival time. Patients achieving CR showed significantly longer survival time, but the remission did not translate into cure of the disease.

The clinical characteristics,survival and prognosis of 27 mantle cell lymphoma patients / 中国实用内科杂志

Objective To analyze the clinical characteristics,therapeutic outcome and prognostic factors of mantle cell lymphoma(MCL)in China.Methods Clinical records of 27 MCL patients were retrospectively analyzed.The results of rituximab combined therapy and conventional therapy regimens were compared,and prognostic factors were analyzed.Results The median age of the 27 patients was 59,with marked male predominance(2.4∶1).There were 88.9% patients with bone marrow involvement at clinical stage Ⅲ～Ⅳ,59.3% with spleen involvement,44.4% with LDH elevated,33.3% with B symptoms and 11.1% with liver involvement.Among the 21 patient with conventional cytogenetic results,7 patients had additional chromosome aberration and 4 patients had more than 4 chromosomes aberration.15/20 patients were misdiagnosed in local hospitals,most of which were diagnosed as CLL/SLL.In 24 untreated patients,the CR/CRu,3 years' OS and PFS in rituximab combined therapy(RCT group)were all significantly higher than those in CT group(87.5% vs 31.3%,87.5% vs 24.1%,70.0% vs 26.9%,P