European data on stem cell mobilization with plerixafor in non-Hodgkin's lymphoma, Hodgkin's lymphoma and multiple myeloma patients. A subgroup analysis of the European Consortium of stem cell mobilization

The effectiveness of the novel hematopoietic stem cell mobilizing agent plerixafor was evaluated in nationwide compassionate use programs in 13 European countries. A total of 580 poor mobilizers with non-Hodgkin's lymphoma (NHL), Hodgkin's lymphoma (HL) and multiple myeloma (MM) were enrolled. All patients received plerixafor plus granulocyte CSF with or without chemotherapy. Overall, the collection yield was significantly higher in MM patients (>2.0 × 10(6) CD34+ cells/kg: 81.6%; >5.0 × 10(6) CD34+ cells/kg: 32.0%) than in NHL patients (>2.0 × 10(6) CD34+ cells/kg: 64.8%; >5.0 × 10(6) CD34+ cells/kg: 12.6%; P<0.0001) and also significantly higher in HL patients (>2.0 × 10(6) CD34+ cells/kg: 81.5%; >5.0 × 10(6) CD34+ cells/kg: 22.2%) than in NHL patients (P=0.013). In a subgroup analysis, there were no significant differences in mobilization success comparing patients with diffuse large B-cell lymphoma, follicular lymphoma and mantle cell lymphoma. Our data emphasize the role of plerixafor in poor mobilizers, but further strategies to improve the apheresis yield especially in patients with NHL are required.     

BLyS and BLyS receptor expression in non-Hodgkin's lymphoma

OBJECTIVE: B Lymphocyte Stimulator (BLyS) protein and its receptor are new members of the tumor necrosis factor family, with specific effects exclusively on B cells. We have studied the tumor cell expression of the BLyS-Receptor (BLyS-R) and the serum BLyS protein levels in patients with different types of non-Hodgkin's lymphomas (NHL). METHODS: BLyS-R expression was assessed by flow cytometry on B cells from 43 NHL patients and 10 normal donors. BLyS protein serum levels were analyzed by ELISA. RESULTS: All B cells, tumor and normal, expressed BLyS-R. The mean fluorescence intensity (MFI +/- SD) of BLyS-R on normal B cells was 25.2 +/- 2.3 arbitrary units, while follicular NHL and chronic lymphocytic leukemia (CLL) exhibited significantly lower expression of the BLyS-R (17.7 +/- 3.1; 15.5 +/- 3.9, respectively, p < 0.0001 for both); other lymphoma subtypes expressed levels comparable to normal B cells (diffuse large cell, 24.8 +/- 4.3; mantle cell, 20 +/- 4.7; marginal zone, 20.7 +/- 3.7). BLyS protein serum levels were analyzed in 15 normal donors and 17 patients with follicular NHL. Levels of BLyS protein were, on average, threefold higher in patients with follicular lymphoma compared to normal donors (mean +/- SD; 13.4 +/- 5.6 ng/mL vs 4.6 +/- 0.7 ng/mL; p < 0.0001). BLyS protein alone was unable to stimulate proliferation in cultures of follicular lymphoma B cells or normal B cells. CONCLUSION: The specificity of the expression of BLyS-R by B-cell lymphomas opens new opportunities for the treatment of these cancers by targeting this ligand-receptor pair.     

The prevalence of autoantibodies and autoimmune hepatitis in patients with nonalcoholic Fatty liver disease

OBJECTIVES: Autoantibodies may exist in serum of patients with nonalcoholic fatty liver disease (NAFLD) although their prevalence and clinical significance is uncertain. We aimed at examining the prevalence of autoantibodies and autoimmune hepatitis among patients with NAFLD. METHODS: Prevalence of antinuclear antibodies (ANA), anti-smooth muscle antibodies (anti-SMA), and autoimmune hepatitis (AIH) based on the International AIH Group were determined in 225 patients with liver biopsy-proven NAFLD. RESULTS: Fifty-one patients [23% (95% CI 17.3-28.2%)] had autoantibodies in serum which is significantly higher than the prevalence in the general population. ANA were present in 46 patients (20%), SMA in 6 (3%), and both antibodies in one patient. Positive autoantibodies were associated with higher fibrosis stage (p= 0.03), higher inflammatory grade (p= 0.02), and higher levels of gammaglobulin (p= 0.01). Prior to liver biopsy, 45 of the 51 (88%) patients with positive autoantibodies fulfilled diagnostic criteria for 'probable' or 'definite' AIH. After liver biopsy, however, only four patients fulfilled diagnostic criteria. CONCLUSIONS: Routinely measured autoantibodies are present in one quarter of patients with NAFLD and are associated with more severe histological damage. Liver biopsy is required to rule out AIH in most NAFLD patients with positive autoantibodies.     

Complement activation in vitro by antiplatelet antibodies in chronic immune thrombocytopenic purpura

Two markers for cells in the growth fraction, the T9 antigen (i.e. the transferrin receptor) and the T10 antigen were investigated in frozen tissue sections of 105 non-Hodgkin lymphomas (NHL). The results were correlated with the histological subtype and the pattern of tumour infiltration by reactive cells. Special attention was directed to the density of natural killer (NK)-like cells using the anti-HNK1 (Leu7) antibody since the transferrin receptor (tfr) or other growth-associated membrane structures may serve as target for NK cells. Our study confirms a relationship between number of tumour cells with the T9 marker and tissue infiltration by HNK1+ cells in NHL of low (chronic lymphocytic leukaemia, hairy-cell leukaemia, immunocytic lymphoma, centroblastic-centrocytic lymphoma) and intermediate (centrocytic and centroblastic lymphoma) but not in NHL of high malignant grade (immunoblastic and lymphoblastic lymphoma). Comparable results were obtained with the T10 antigen although the correlation was less close. The percentage of cells in the growth fraction, defined by the expression of the T9 and T10 marker, corresponded with prognostically unfavourable subgroups with the remarkable exception of follicular NHL of centroblastic-centrocytic type. This lymphoma showed high numbers of cells with the T9 and the T10 marker in a microenvironment resembling normal germinal centres in many aspects.     

狼疮肾炎患者血清抗系膜细胞抗体及其靶抗原的研究

目的　通过观察狼疮肾炎 (LN)患者血清中抗系膜细胞抗体探讨其临床意义。方法　收集 96例肾活检证实的LN患者血清 ,以体外培养的人系膜细胞为抗原 ,用ELISA检测抗系膜细胞抗体 ;以人系膜细胞可溶性成分为抗原 ,在非还原条件下进行免疫印迹检测靶抗原 ;并分析各种不同自身抗系膜细胞抗体与临床表现的关系。结果　ELISA显示 ,LN患者抗系膜细胞抗体阳性率为37 5 % ,其吸光度 (A)值 (0 4 5 )与健康人 (0 17)比较差异有显著性 (P <0 0 0 1) ;免疫印迹显示 ,94例(94 / 96 ,97 9% )LN患者血清存在抗系膜细胞抗体 ,共 12种不同蛋白被识别。其中 ,女性患者抗 6 30 0 0抗体的阳性率 (5 9 8% )高于男性患者 (2 1 4 % ,P <0 0 1) ,有血尿的患者抗 74 0 0 0、抗 4 6 0 0 0、抗36 0 0 0抗体的阳性率 (36 8%、34 2 %、31 6 % )高于无血尿者 (5 0 %、10 0 %、5 0 % ,P <0 0 5 ) ,抗核抗体阳性的患者抗 6 30 0 0抗体的阳性率 (6 7 6 % )显著高于抗核抗体阴性者 (16 7% ,P <0 0 0 1) ,抗ds DNA抗体阳性的患者抗 180 0 0抗体的阳性率 (6 1 5 % )高于抗ds DNA抗体阴性者 (34 4 % ,P <0 0 5 )。结论　LN患者血清中含有直接针对系膜细胞的异质性自身抗体 ,提示原位免疫复合物形成在LN的发病中可能起重要的致病作用     

The role of allogeneic transplantation in non-Hodgkin's lymphoma

The evolution of combination chemotherapy regimens, combined with improvements in supportive care, has incrementally improved survival outcomes for patients with non-Hodgkin's lymphomas (NHL). Although 40-60% of younger patients with diffuse large cell lymphoma can now expect to be cured, significant numbers will either fail to achieve a remission or relapse after attaining a remission. In addition, certain histological subtypes are associated with particularly poor prognoses with combination chemotherapy alone (e.g. mantle cell lymphoma, B-cell prolymphocytic leukaemia). Relatively few of these patients can achieve long-term responses. Other NHL subtypes, whilst associated with more favourable prognoses in terms of overall survival, are rarely, if ever, cured (e.g. most low grade NHL including follicular lymphoma, chronic lymphocytic leukaemia and small lymphocytic lymphoma). For these reasons dose escalation and allogeneic transplantation have been investigated as potential ways of improving outcome, although this has mainly been in the setting of advanced disease. Any possible benefits have frequently been out-weighed by procedural morbidity and mortality. The parallel development of transplantation approaches that limit procedural toxicity along with advances in supportive care require that the role of allogeneic haematopoietic stem cell transplantation in the management of lymphoma be re-evaluated.     

Prevalence of Common Non-Hodgkin Lymphomas and Subtypes of Hodgkin Lymphoma by Nodal Site of Involvement: A Systematic Retrospective Review of 938 Cases

Non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) represent a heterogeneous group of malignant lymphoid tumors, which have distinct histological and/or biological characteristics with preferential nodal involvement. However, none of the previous studies have assessed the prevalence of common NHL and HL subtypes at each nodal site of involvement.The aim of our study was to determine the prevalence of HL and NHL subtypes depending on their nodal sites of involvement.We conducted a single-center retrospective study of 938 lymphoma cases diagnosed in the Pathology Department of Toulouse Purpan Hospital in France between 2001 and 2008, taking into account the site that corresponded to the diagnostic biopsy.The most frequent sites were cervical lymph nodes (36.8% of all cases), inguinal lymph nodes (16.4%), axillary lymph nodes (11.9%), and supraclavicular lymph nodes (11%). We found an unexpected association between intraparotid nodes and nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and between inguinal nodes and follicular lymphoma. The risk of having classical Hodgkin lymphoma (CHL) was 15 times greater in patients with mediastinal lymphoma compared to those with other sites of involvement. Regarding HL, nodal and extranodal mediastinal sites and supraclavicular nodes were more likely to be involved by nodular sclerosis Hodgkin lymphoma (NSCHL). In addition, intra-abdominal lymph nodes were more frequently involved by lymphocyte depleted Hodgkin lymphoma compared to inguinal nodes where NLPHL predominated.Our study shows that some lymph node sites have a disproportionate prevalence of specific subtypes of lymphoma. Identifying these sites may aid to diagnose and better elucidate the pathogenesis of these tumors.     

High prevalence of splenic marginal zone lymphoma among patients with acquired C1 inhibitor deficiency

Marginal zone lymphoma represents about 10% of all non‐Hodgkin lymphomas (NHLs). 33% of patients with acquired angioedema (AAE) due to acquired C1‐inhibitor (C1‐INH) deficiency (C1‐INH‐AAE) have or will develop NHLs. C1‐INH‐AAE is a rare condition. We report the follow‐up of 72 C1‐INH‐AAE patients, followed for a median of 15 years (range 1–24). Median age was 71 (range 64–79) years; median age at onset of angioedema symptoms was 57·5 (range 50–66) years and it was 63 [range 45–80) years at diagnosis]. Twenty patients were diagnosed with low‐grade non‐follicular B‐cell lymphomas (75% were splenic MZL), one with follicular and three with high‐grade lymphomas (two diffuse large B‐cell lymphomas and one mantle cell lymphoma). Fifteen NHLs were diagnosed at onset of AAE or thereafter (3 months to 7 years), eight had already been diagnosed at onset of angioedema. Two of 24 patients remain on watchful wait. Thirthen of 24 received chemotherapy, two received rituximab. Three underwent splenectomy. All 18 patients receiving therapy for NHL experienced post‐treatment reduction in AAE symptoms. Our study suggests that clonal B‐cell proliferation is the pathology underlying AAE leading to production of C1‐INH‐neutralizing autoantibodies and to NHLs. The post‐germinal centre origin of NHL suggests that immune stimulation may contribute to lymphomagenesis.     

Chimeric antigen receptor modified T cell therapy in B cell non-Hodgkin lymphomas

Chimeric antigen receptor modified T (CAR-T) cell therapy against the CD19 antigen has revolutionized the therapeutic landscape for patients with relapsed, refractory B cell non-Hodgkin lymphoma (NHL). Currently, there are two FDA approved products (axicabtagene ciloleucel and tisagenlecleucel) for B cell NHL, with several other constructs under clinical investigation. This review will focus on the clinical outcomes, toxicity profile, and differences among candidate CD19 CAR-T cell products for major subtypes of B cell NHL including diffuse large B cell lymphoma, follicular lymphoma, and mantle cell lymphoma. Lastly, we will describe novel CAR-T constructs currently under exploration in B cell NHL.     

Leukaemic non-Hodgkin's lymphomas with hyperdiploid cells and t(ll;14)(ql3;q32): a subtype of mantle cell lymphoma?

The present study describes five patients with leukaemic non-Hodgkin's lymphoma (NHL) detected on the basis of particular morphology and cytogenetic findings. With respect to histological, immunological and cytogenetic features these NHL are closely related to mantle cell Iymphoma/intermediate differentiated lymphocytic lymphoma. However, the presence of unusual large cells associated with the t(ll;14)(ql3;q32) translocation and numerical chromosome changes, in the near triploid or near tetraploid range, could delineate a particular subtype of mantle cell lymphoma.     

Hepatitis B and C virus infection in Romanian non-Hodgkin's lymphoma patients

We determined the hepatitis C virus (HCV) antibodies (anti-HCV) and the hepatitis B virus (HBV) surface antigen (HBsAg) in a cohort of 68 consecutive non-Hodgkin's lymphoma (NHL) patients diagnosed and treated in our institution between December 1997 and March 1999. 27 cases were diagnosed as low-grade, 33 as intermediate-grade, and eight as high-grade NHL. In 35 cases (51.4%) we found evidence of either HCV or HBV infection. Anti-HCV antibodies were found in 20 patients (29.5%) and HBsAg was found in 21 patients (30.8%). In six patients both anti-HCV and HBsAg were present. Anti-HCV were present in 12/27 low-grade NHL cases (44.4%) and in 8/41 intermediate/high-grade (aggressive) NHL cases (19.5%, P < 0.03). HBsAg was found in 10/27 low-grade NHL cases (37%) and in 11/41 aggressive NHL cases (26.8%). Evidence of liver disease, as reflected by elevated aminotransferases or typical alterations at liver biopsy, was present in eight patients. Cryoglobulins were present in six patients, all anti-HCV positive and with low-grade NHL. The prevalence of both HCV antibodies and HBsAg was significantly higher (P < 0.0001) in our NHL cases than in a sample of the general Romanian population, where the prevalence of anti-HCV was 4.9% and that of HBsAg was 6.3%. It is difficult to say whether either HCV or HBV had actually been involved in lymphomagenesis or if alpha-interferon treatment would be effective in this subset of patients.     

Autoimmune liver disease-related autoantibodies in patients with biliary atresia

AIM To investigate the prevalence and clinical significance of autoimmune liver disease(ALD)-related autoantibodies in patients with biliary atresia(BA).METHODS Sera of 124 BA patients and 140 age-matched non-BA controls were assayed for detection of the following autoantibodies: ALD profile and specific anti-nuclear antibodies(ANAs), by line-blot assay; ANA and antineutrophil cytoplasmic antibody(ANCA), by indirect immunofluorescence assay; specific ANCAs and antiM2-3 E, by enzyme linked immunosorbent assay. Associations of these autoantibodies with the clinical features of BA(i.e., cytomegalovirus infection, degree of liver fibrosis, and short-term prognosis of Kasai procedure) were evaluated by Spearman's correlation coefficient.RESULTS The overall positive rate of serum autoantibodies in preoperative BA patients was 56.5%. ALD profile assay showed that the positive reaction to primary biliary cholangitis-related autoantibodies in BA patients was higher than that to autoimmune hepatitis-related autoantibodies. Among these autoantibodies, anti-BPO was detected more frequently in the BA patients than in the controls(14.8% vs 2.2%, P 0.05). Accordingly, 32(25.8%) of the 124 BA patients also showed a high positive reaction for anti-M2-3 E. By comparison, the controls had a remarkably lower frequency of anti-M2-3 E(P 0.05), with 6/92(8.6%) of patients with other liver diseases and 2/48(4.2%) of healthy controls. The prevalence of ANA in BA patients was 11.3%, which was higher than that in disease controls(3.3%, P 0.05), but the reactivity to specific ANAs was only 8.2%. The prevalence of ANCAs(ANCA or specific ANCAs) in BA patients was also remarkably higher than that in the healthy controls(37.9% vs 6.3%, P 0.05), but showed no difference from that in patients with other cholestasis. ANCA positivity was closely associated with the occurrence of postoperative cholangitis(r = 0.61, P 0.05), whereas none of the autoantibodies showed a correlation to cytomegalovirus infection or the stages of liver fibrosis.CONCLUSION High prevalence of autoantibodies in the BA developmental process strongly reveals the autoimmunemediated pathogenesis. Serological ANCA positivity may be a useful predictive biomarker of postoperative cholangitis.     

Autologous bone marrow transplantation in follicular non-Hodgkin's lymphoma before and after histologic transformation

Patients with disseminated follicular non-Hodgkin's lymphoma (NHL) are only occasionally cured with standard chemotherapy regimens. Although most of these tumors are initially responsive to chemotherapy, in 40% to 70% of patients the lymphoma will eventually transform to an NHL of higher grade malignancy and a poorer prognosis. We treated 18 patients having an original diagnosis of follicular NHL with high-dose therapy and autologous bone marrow transplantation. The lymphomas of 10 of the patients had already undergone histologic transformation and eight still had a follicular histologic pattern. The former group had been followed for a longer time from the diagnosis of NHL and had been more extensively treated with conventional chemotherapy regimens. All eight patients with follicular NHL at the time of transplantation are alive for 246+ to 1,804+ days and seven of the patients are in complete remission. In contrast, of the 10 patients in histologic transformation only 1 is alive and in CR. This reflects the inability of these patients to tolerate the high-dose chemotherapy and myelosuppression as well as resistance of their lymphoma to this therapy. This difference in survival between the two groups was highly significant (P = .002). We conclude that the outcome of patients with follicular NHL transplanted early before histologic transformation is better than for those who are transplanted later in the course of their illness. Because of the relapsing behavior of follicular NHL, a longer follow-up is necessary to prove any impact on the natural history of the disease.     

Hepatitis C virus infection and B-cell non-Hodgkin's lymphoma: a cross-sectional study in Lyon, France

OBJECTIVES: The role of hepatitis C virus (HCV) infection in the pathogenesis of non-Hodgkin's lymphoma (NHL) is controversial. A high prevalence of HCV infection in patients with NHL has been reported in Italy and Japan. By contrast, several studies in Northern Europe and Canada have not found any increased prevalence of HCV in B-cell NHL, suggesting a possible geographic variation. We sought to determine whether such an association could be found in patients treated in the Rhone-Alpes region in south-east France. Our main interest was to identify histological subtypes preferentially linked to HCV. METHODS: We determined the prevalence of anti-HCV antibodies in 212 consecutive patients with B-cell NHL diagnosed in our institution between January 1997 and December 1998. The comparison group comprised 974 patients tested for HCV before transfusion at the same hospital during the same period. RESULTS: Anti-HCV antibodies were found in six (2.8%) NHL patients. The distribution by histopathological category was as follows: three gastric mucosa-associated lymphoid tissue (MALT) lymphomas, one marginal lymphoma and two diffuse large-cell lymphomas. Anti-HCV antibodies were found in 20 (2%) of 974 comparison patients. Overall, there was a positive but non-significant trend towards an association between NHL and HCV infection (odds ratio 1.31; 95% confidence interval 0.51-3.36). However, the prevalence of HCV antibodies was significantly higher in MALT lymphoma patients than in the comparison group (odds ratio 9.87; 95% confidence interval 2.59-37.69). CONCLUSIONS: To our knowledge, this is the first French study to show an association between HCV and MALT lymphoma. These results, although derived from a small number of patients, suggest a possible role of HCV in gastric MALT lymphomagenesis.     

The relationship of hepatitis B virus infection and non-Hodgkin's lymphoma and its impact on clinical characteristics and prognosis

AIM OF THE STUDY: This study aims to evaluate the association between hepatitis B virus (HBV) and lymphoma and to characterize HBV-related lymphomas. The efficacy of prophylactic lamivudine on HBV reactivation was also evaluated. METHODS: We compared the prevalence rate of HBV infection in 556 patients with lymphoma seen over a 4-yr period with that in a group of 4698 Singapore residents aged 18-69 who participated in the National Health Survey. Next, we compared the clinic-pathologic characteristics of HBV-positive and HBV-negative lymphoma cases. RESULTS: The prevalence rate of HBV infection in our study was 10.3% (57/556), higher than the prevalence rate of 4.1% (192/4698) in the general population (P < or = 0.001). The higher prevalence was observed in both sexes and across different age groups. An association was observed for non-Hodgkin's lymphoma (NHL) but not Hodgkin's lymphoma. The characteristics of HBV-infected patients with lymphoma were similar to those who were HBV-uninfected in terms of age, ECOG, extra-nodal involvement, LDH level, stage, complete remission rate and overall survival. Use of prophylactic lamivudine significantly decreased the incidence of HBV reactivation (13% vs. 38%, P = 0.02) and disruption to chemotherapy (43% vs. 4%, P = 0.02), with a trend towards improved overall survival. CONCLUSIONS: Our findings suggest that an association exists between HBV infection and NHL. However, HBV infection does not appear to have a significant impact on the clinical characteristics and prognosis of NHL. Prophylactic lamivudine should be considered in all HBV-infected patients receiving antracycline and/or steroid containing chemotherapy.     

Non-Hodgkin's lymphomas in Greece according to the WHO classification of lymphoid neoplasms. A retrospective analysis of 810 cases

The purpose of this retrospective study, the largest unselected series in our country, was to illustrate the clinicopathological features of non-Hodgkin's lymphoma (NHL) classified according to the World Health Organization (WHO) classification of lymphoid neoplasms. A retrospective analysis was conducted and clinical features of histological subtypes were established in 810 patients (age > or = 15 years) with NHL who were treated at 8 major centers representative of Greece. There were 435 males and 375 females 95% of them aged >30 years. B symptoms were present in 34% of the patients, while 45.3% had stages I-II and 54.6% had stages III-IV. LDH was increased in 37% of the patients. B cell lymphomas formed 88% of the cases whereas T cell lymphomas formed 12% of the total. Indolent lymphomas accounted for 31.1%, aggressive ones for 66.7% and very aggressive ones for 2.4% of all NHLs. Among indolent lymphomas extranodal ones (MALT B cell lymphoma) were the most common subset while follicular lymphoma grade I and II and small lymphocytic ones presented with equal frequency. Among the aggressive lymphomas diffuse large cell lymphoma (DLCL) was the most common subtype; this entity along with large-cell immunoblastic lymphomas accounted for 45.2% of all B cell lymphomas. Among the T cell lymphomas, peripheral T cell lymphomas and anaplastic large cell lymphomas of the T/null-cell type were the most common subtypes. The most common extranodal presentation was the gastrointestinal tract (GI). Next in frequency were primary extranodal NHL of the head and neck region. MALT B cell lymphomas were found in almost half of the patients with GI tract NHL, whereas in all other extranodal places DLCL was the predominant histological subtype. The median survival for indolent and aggressive NHL was 123.5 and 55.5 months, respectively. This is the first report of a large series of malignant lymphomas in Greece using the WHO classification. It appears that there are no significant differences between NHL in Greece and other large series as far as clinical and extranodal presentation is concerned. The frequency of follicular lymphoma in the current study is comparable to that reported from Asian countries and mainland Europe, but lower than that of US and Northern European series. There were no important differences in the incidence of the remaining histological subtypes between Greece and other European countries.     

Stem cell transplantation for indolent lymphoma.

Stem cell transplantation (SCT) has become the treatment of choice for patients with relapsed aggressive non-Hodgkin's lymphoma (NHL). The role of SCT in the management of patients with low-grade NHL remains more controversial, although increasing numbers of patients with advanced-stage follicular lymphoma, mantle cell lymphoma, and chronic lymphocytic leukemia are now undergoing SCT. To date, most patients with NHL have been treated with autologous SCT, currently using peripheral blood stem cells (PBSC) mobilized by chemotherapy and recombinant growth factors. There is increasing concern regarding toxicity of autologous SCT, especially the higher than expected long-term risk of development of myelodysplastic syndrome. This, among other factors, has led to renewed interest in the role of allogeneic SCT for patients with NHL. A major advantage of allogeneic SCT is the potential to exploit a graft-versus-lymphoma effect, and many studies are underway exploring the possibility of manipulating donor cells to maximize T cell responsiveness against lymphoma.     

High serum hepatocyte growth factor level in patients with non-Hodgkin's lymphoma

Higher pretreatment serum hepatocyte growth factor (HGF) levels were observed in patients with multiple myeloma and Hodgkin's disease, but not in those with non-Hodgkin's lymphoma (NHL). We examined patients' serum levels at diagnosis using enzyme-linked immunosorbent assay and histological expression of HGF in pathological specimens of lymphoma, in relation to clinical features. The subjects were 77 NHL patients and 40 healthy controls. The serum levels of HGF in NHL patients at diagnosis were significantly higher than those in healthy controls (median 1019 vs. 689 pg/mL, P < 0.001). At diagnosis, patients with more than two sites of extranodal involvement (P = 0.001), higher scores of international prognostic index (P = 0.015), and advanced Ann Arbor stage (P = 0.023) had a higher level of serum HGF. Although the association of pretreatment serum HGF level and survival was not significant, a correlation of serial change of serum HGF levels with treatment response was found in limited cases. Furthermore, HGF expression of lymphoma tissues was shown in 18 of 24 (75%) different NHL subtypes, including most of the diffuse large B cell lymphoma (12 of 15, 80%). In conclusion, our study showed higher pretreatment serum HGF levels in NHL patients, which was related to clinical features; and the serial change of HGF seemed to parallel the treatment response. The pathogenic role of HGF in NHL patients was further highlighted by a modest expression of HGF in most of the diffuse large B cell lymphoma.     

Elevated monoclonal and polyclonal serum immunoglobulin free light chain as prognostic factors in B‐ and T‐cell non‐Hodgkin lymphoma

The serum immunoglobulin free light chain (FLC) assay quantitates free kappa (κ) and lambda (λ) light chains. FLC elevations in patients with diffuse large B‐cell lymphoma (DLBCL), Hodgkin lymphoma (HL), and chronic lymphocytic leukemia (CLL) are associated with an inferior survival. These increases in FLC can be monoclonal (as in myeloma) or polyclonal. The goal was to estimate the frequency of these elevations within distinct types of B‐cell and T‐cell non‐Hodgkin lymphoma (NHL) and whether the FLC measurements are associated with event‐free survival (EFS). We studied serum for FLC abnormalities using normal laboratory reference ranges to define an elevated κ or λ FLC. Elevations were further classified as polyclonal or monoclonal. Four hundred ninety‐two patients were studied: 453 B‐cell and 34 T‐cell NHL patients. Twenty‐nine % (142/453) of patients had an elevated FLC of which 10% were monoclonal elevations. Within B‐cell NHL, FLC abnormalities were most common in lymphoplasmacytic (79%), mantle cell (68%), and lymphomas of mucosa associated lymphoid tissue (31%); they were least common in follicular (15%). The hazard ratio (HR) for EFS in all patients was 1.41 (95% CI; 1.11–1.81); in all B‐cell NHL the HR was 1.44 (95% CI 1.11–1.96); in all T‐cell NHL the HR was 1.17 (95% CI 0.55–2.49). FLC abnormalities predicted an inferior OS (HR = 2.75, 95% CI: 1.93–3.90, P < 0.0001). The serum FLC assay is useful for prognosis in both B‐cell and T‐cell types of NHL. In B‐cell NHL further discrimination between a monoclonal and polyclonal elevation may be helpful and should be analyzed in prospective clinical trials. Am. J. Hematol. 89:1116–1120, 2014. © 2014 Wiley Periodicals, Inc.     

Clinical significance of autoantibodies to soluble liver antigen in autoimmune hepatitis.

BACKGROUND/AIMS: Classification of autoimmune hepatitis (AIH) into different subgroups according to autoantibody status has been proposed: type I (ANA/SMA), type II (LKM-1) and type III (anti-SLA). However, whether type III AIH forms a clinically distinct disease entity remains controversial. The aim of this study was to evaluate the subclassification of AIH into ANA/SMA and anti-SLA positive patients with regard to clinical, biochemical and histologic differences. METHODS: Ninety-seven consecutive patients with a well-documented long-term course of AIH with ANA/SMA and/or anti-SLA autoantibodies were studied. Clinical, biochemical and histological features of patients with ANA/SMA and/or anti-SLA autoantibodies were compared in a secondary analysis of data acquired prospectively. RESULTS: Anti-SLA autoantibodies were found in 21.6% of patients. Anti-SLA-positive patients tended to have lower transaminases (mean: 153 vs. 247 IU/l), gamma-globulins (25 vs. 31%) and bilirubin (1.8 vs. 3.3 mg/dl) in comparison to ANA/SMA positive patients, but there was a large overlap. HLA-type A1 B8 was more frequent in anti-SLA positive patients, while there was no difference in HLA DR3 and DR4 allotype. Response to immunosuppressive therapy was excellent, but relapse occurred frequently. Diagnosis of anti-SLA positive AIH was often delayed (mean: 68 months from first elevation of transaminases) since testing for anti-SLA autoantibodies is currently not generally available. CONCLUSIONS: ANA/SMA and anti-SLA positive patients share most clinical, biochemical, histologic and prognostic features. Distinction between type I and type III AIH is therefore clinically not helpful. However, testing for anti-SLA autoantibodies helps in the diagnosis of AIH in many patients who may otherwise be misdiagnosed.