The diagnostic value of kappa/lambda ratios determined by flow cytometric analysis of biopsy specimens in B-cell lymphoma

Flow cytometry (FC) is widely utilized in the diagnosis of lymphoma and the light chain ratio (LCR) is especially useful in the diagnosis of B-cell malignancy. In this study we analysed, retrospectively, the predictive value of the LCR in the diagnosis of B-cell lymphoma in 105 consecutive patients with persistent lymph node enlargement or extranodal masses who underwent biopsy. We used a receiver-operating characteristic curve to establish a LCR threshold value of 2.0. The specificity, sensitivity, positive and negative predictive values were 92.3%, 73.1%, 90% and 77%, respectively. We concluded that determination of LCR is a useful adjunct to pathological diagnosis.     

Simplified sensitive method for the detection of B‐cell clonality in lymphoid malignancies

Molecular response and monitoring of minimal residual disease (MRD) is becoming an essential part of most protocols for treating leukemia and lymphoma patients. Detection of abnormal clones by PCR analysis of complementarity determining regions (CDRs) in immunoglobulin genes is currently standard practice for diagnosis, but is not widely used to monitor MRD because of the low sensitivity of assays that use consensus primers. Use of specific primers can improve the sensitivity of the assay, but is a cumbersome, expensive, and time‐consuming process. We developed a simple and cost‐effective approach to detect MRD in B‐cell malignancies that is usable in clinical laboratories. The new assay uses ligase chain reaction (LCR) to detect clonality. The sensitivity of the LCR assay is 1 per 500 000 cells, and it can detect all subclones that were present in the pretherapy diagnostic sample.     

B‐cell lymphoma,unclassifiable, with features intermediate between diffuse large B‐cell lymphoma and burkitt lymphoma: study of 39 cases

B‐cell lymphoma, unclassifiable (B‐UCL), with features intermediate between diffuse large B‐cell lymphoma and Burkitt lymphoma, is a poorly characterized entity. Therefore, we investigated cases of B‐UCL treated by the Nebraska Lymphoma Study Group (NLSG). We searched the NLSG registry for years 1985–2010 for cases of B‐UCL. Immunohistochemical stains and fluorescence in situ hybridization studies for MYC, BCL2 and BCL6 gene rearrangements were performed. Among the 39 cases studied, 54% were male and 46% were female, with a median age of 69 years. The majority of patients presented with advanced‐stage disease (62%) and had high (3–5) International Prognostic Index (IPI) scores (54%). The median overall survival (OS) was only 9 months and the 5‐year OS was 30%. Patients with low IPI scores (0–2) had a better survival than those with high scores (3–5). The cases were genetically heterogeneous and included 11 ‘double‐hit’ lymphomas with rearrangements of both MYC and BCL2 or BCL6. None of the immunohistochemical or genetic features was predictive of survival. This B‐cell lymphoma is a morphologically‐recognizable entity with a spectrum of genetic abnormalities. New and better treatments are needed for this aggressive lymphoma.     

Diagnosis of Burkitt lymphoma using an algorithmic approach – applicable in both resource‐poor and resource‐rich countries

Distinguishing Burkitt lymphoma (BL) from B cell lymphoma, unclassifiable with features intermediate between diffuse large B‐cell lymphoma (DLBCL) and BL (DLBCL/BL), and DLBCL is challenging. We propose an immunohistochemistry and fluorescent in situ hybridization (FISH) based scoring system that is employed in three phases – Phase 1 (morphology with CD10 and BCL2 immunostains), Phase 2 (CD38, CD44 and Ki‐67 immunostains) and Phase 3 (FISH on paraffin sections for MYC, BCL2, BCL6 and immunoglobulin family genes). The system was evaluated on 252 aggressive B‐cell lymphomas from Europe and from sub‐Saharan Africa. Using the algorithm, we determined a specific diagnosis of BL or not‐BL in 82%, 92% and 95% cases at Phases 1, 2 and 3, respectively. In 3·4% cases, the algorithm was not completely applicable due to technical reasons. Overall, this approach led to a specific diagnosis of BL in 122 cases and to a specific diagnosis of either DLBCL or DLBCL/BL in 94% of cases that were not diagnosed as BL. We also evaluated the scoring system on 27 cases of BL confirmed on gene expression/microRNA expression profiling. Phase 1 of our scoring system led to a diagnosis of BL in 100% of these cases.     

Role of endoscopic ultrasound‐guided fine‐needle aspiration with flow cytometry to diagnose lymphoma: A single center experience

Background and Aim: The use of endoscopic ultrasound‐guided fine‐needle aspiration (EUS?FNA) ± flow cytometry (FC) for the diagnosis of suspected lymphoma remains controversial. We report our experience and diagnostic yield for EUS ± FC for suspected lymphoma. Methods: Databases were queried for those who underwent EUS?FNA ± FC for suspected lymphoma. Hospital charts were reviewed to confirm the final cytological diagnosis, follow up and FC results if obtained. The final diagnosis was confirmed by the results of EUS?FNA ± FC, other biopsy and/or follow up. Results: In total, 54 patients underwent EUS?FNA of 72 lesions. The final diagnosis of lymphoma was made in 38 of the 54 (70%) patients, and 33 of the 54 (61%) patients relied on EUS?FNA. Cytopathology in 41 patients using EUS?FNA + FC showed lymphoma in 24 patients, atypical lymphoid cells in six and reactive lymph node in 11. In 9 of the 24 with lymphoma by EUS + FC, the diagnosis was confirmed by another diagnostic modality, like surgery, bone marrow biopsy and computed tomography‐guided biopsy. Of the six with atypical lymphoid cells, additional diagnostic methods confirmed lymphoma in three. The remaining 13 of the 54 patients underwent EUS?FNA without FC due to insufficient sample (n = 5) or operator choice (n = 8). Cytopathology in these 13 patients without FC showed lymphoma (9), atypical lymphoid cells (3) and reactive node (1). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of EUS?FNA for lymphoma in all 54 patients ranged from 80% to 87%, 92% to 93%, 97%, 60% to 75% and 83% to 89%, respectively. Conclusions: EUS?FNA is sensitive and specific for the diagnosis of suspected lymphoma. Confirmatory or further testing should be performed when EUS?FNA with or without FC is indeterminate and or non‐diagnostic.     

Establishment and characterization of a novel VEGF‐producing HHV‐8‐unrelated PEL‐like lymphoma cell line,OGU1

Primary effusion lymphoma (PEL) is a rare B‐cell lymphoma subtype that is characterized by lymphomatous effusion without the presence of masses, and it typically occurs in human immunodeficiency virus (HIV)‐infected individuals. Lymphoma cells are universally positive for human herpesvirus 8 (HHV‐8). Recently, a cavity‐based effusion lymphoma that is similar to PEL without HHV‐8 infection, called HHV‐8‐unrelated PEL‐like lymphoma, has been reported in non‐HIV‐infected individuals. However, the pathophysiology of this lymphoma is largely undefined. We established a novel B‐cell line OGU1 derived from a patient with HHV‐8‐unrelated PEL‐like lymphoma. Notably, OGU1 cells produced vascular endothelial growth factor (VEGF) and expressed VEGF receptor 1, whose inhibitors retarded cell growth. Because VEGF acts as a vascular permeability and growth factor, it could play a role, at least in part, in the pathogenesis of this unique lymphoma. Thus, the OGU1 cell line is useful for the investigation of HHV‐8‐unrelated PEL‐like lymphoma.     

Endosonography-guided fine needle aspiration cytology of intra-abdominal lymph nodes with unknown primary in a tuberculosis endemic region

Background and Aim: Intra‐abdominal lymphadenopathy poses a diagnostic and management challenge in highly endemic regions for tuberculosis. Opting for empirical anti‐tuberculosis treatment raises the risk of wrong or delayed treatment. Endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) is the procedure of choice for tissue acquisition from peri‐luminal lymph nodes. We studied the utility of EUS‐FNA in evaluating intra‐abdominal lymph nodes of unknown etiology, in the setting of high endemicity of tuberculosis. Methods: Consecutive patients with intra‐abdominal lymph nodes of unknown etiology underwent EUS‐FNA using a 22‐gauge needle. Final diagnosis was made on surgical histology or on 6‐months follow‐up. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic yield were calculated. Results: Sixty‐six patients were included. Final diagnoses were tuberculosis, 35 (53%); metastatic adenocarcinoma, 11 (16.7%); lymphoma, three (4.5%); carcinoid, one (1.5%) and reactive nodes, 16 (24.2%). EUS‐FNA provided a diagnosis in 61 patients (92.4%). Sensitivity, specificity, PPV and NPV for diagnosing tuberculosis via EUS‐FNA were 97.1%, 100%, 100% and 96.9%, respectively. In 10 (15.2%) patients receiving empirical anti‐tuberculosis treatment, the final diagnoses were metastatic adenocarcinoma (5), lymphoma (2), carcinoid (1) and reactive adenopathy (2). Conclusion: Despite being in a highly endemic area, almost half of the patients studied have a non‐tuberculosis etiology. EUS‐FNA is a safe and accurate procedure for establishing the diagnosis of unexplained intra‐abdominal lymphadenopathy.     

The aggressive peripheral T‐cell lymphomas: 2015

Background: T‐cell lymphomas make up approximately 10%–15% of lymphoid malignancies. The frequency of these lymphomas varies geographically, with the highest incidence in parts of Asia. Diagnosis: The diagnosis of aggressive peripheral T‐cell lymphoma (PTCL) is usually made using the World Health Organization classification. The ability of hematopathologists to reproducibly diagnosis aggressive PTCL is lower than that for aggressive B‐cell lymphomas, with a range of 72%–97% for the aggressive PTCLs. Risk Stratification: Patients with aggressive PTCL are staged using the Ann Arbor Classification. Although somewhat controversial, positron emission tomography scans seem to be useful as they are in aggressive B‐cell lymphomas. The most commonly used prognostic index is the International Prognostic Index. The specific subtype of aggressive PTCL is an important risk factor, with the best survival seen in anaplastic large‐cell lymphoma—particularly young patients with the anaplastic lymphoma kinase positive subtype. Risk‐Adapted Therapy: Anaplastic large‐cell lymphoma is the only subgroup to have a good response to a CHOP‐like regimen. Angioimmunoblastic T‐cell lymphoma has a prolonged disease‐free survival in only ～20% of patients, but younger patients who have an autotransplant in remission seem to do better. PTCL‐not otherwise specified is not one disease. Anthracycline‐containing regimens have disappointing results, and a new approach is needed. Natural killer/T‐cell lymphoma localized to the nose and nasal sinuses seems to be best treated with radiotherapy‐containing regimens. Enteropathy‐associated PTCL and hepatosplenic PTCL are rare disorders with a generally poor response to therapy, although selected patients with enteropathy‐associated PTCL seem to benefit from intensive therapy. Am. J. Hematol. 90:666–673, 2015. © 2015 Wiley Periodicals, Inc.     

The role of bone marrow biopsy and FDG‐PET/CT in identifying bone marrow infiltration in the initial diagnosis of high grade non‐Hodgkin B‐cell lymphoma and Hodgkin lymphoma. accuracy in a multicenter series of 372 patients

Bone marrow infiltration (BMI), categorized as an extra‐nodal site, affects stage and is associated with poor prognosis in newly diagnosed lymphoma patients. We have evaluated the accuracy of PET/CT and bone marrow biopsy (BMB) to assess BMI in 372 lymphoma patients [140 Hodgkin Lymphoma (HL) and 232 High Grade B‐cell non‐Hodgkin Lymphoma (HG B‐NHL), among them 155 Diffuse Large B‐Cell Lymphoma (DLCL)]. For HL cases, and taking into account PET/CT, sensitivity, negative predictive value (NPV) and accuracy were 96.7, 99.3, and 99.3% while those of BMB were 32.3, 83.8, and 85%, respectively. For HG B‐NHL and considering PET/CT, sensitivity, NPV, and accuracy were 52.7, 81.7, and 84.1%, while those of BMB were 77.6, 90.2, and 90.7%, respectively. In the HG B‐NHL group, 25 patients would have been under‐staged without BMB. These results lead us to recommend PET/CT and the avoidance of BMB to assess BMI in HL. In the case of HG B‐NHL, bone marrow status should be assessed firstly by means of PET/CT; only in either focal or diffuse PET/CT with low borderline SUV max values or in negative cases, should BMB be carried out afterwards. In the HG B‐NHL setting and at the present moment, both techniques are complementary. Am. J. Hematol. 90:686–690, 2015. © 2015 Wiley Periodicals, Inc.     

Possible prediction of underlying lymphoma by high sIL-2R/ferritin ratio in hemophagocytic syndrome

In some instances, because of the lack of mass formation and the absence of prominent lymph node enlargement, diagnosis of lymphoma-associated hemophagocytic syndrome (LAHS) is difficult, which results in the development of progressive disease with unfavorable prognosis. Therefore, in the diagnosis of secondary hemophagocytic syndrome (HPS), markers for underlying malignant lymphoma are required. We reviewed 110 Japanese patients, including 57 LAHS cases and 53 benign disease-associated HPS cases, and demonstrated that the values of the serum sIL-2R level and sIL-2R/ferritin ratio in LAHS patients were both statistically higher than those of patients with benign disease-associated HPS. Most LAHS patients showed high values of both indices. The positive predictive value of patients showing high values of both indices for LAHS was 95.6%. On the other hand, the predictive value of patients showing low values of both indices for benign disease-associated HPS was 92.1%. We propose serum sIL-2R/ferritin ratio as a novel useful marker for predicting underlying malignant lymphoma in HPS patients.     

Impact of prior rituximab on outcomes of autologous stem‐cell transplantation in patients with relapsed or refractory aggressive B‐cell lymphoma: a multicentre retrospective Spanish group of lymphoma/autologous bone marrow transplant study

The use of highly effective rituximab‐containing therapy for treating diffuse large B‐cell lymphoma (DLBCL) makes it more difficult to salvage relapsed or refractory patients. Autologous stem‐cell transplantation (ASCT) is the reference treatment for these patients, but the impact of previous exposure to rituximab on the subsequent results of ASCT remains unknown. We analysed 248 patients with relapsed or refractory DLBCL or grade 3B follicular lymphoma pre‐treated with rituximab as part of first‐line therapy (R+ group) who received ASCT, in comparison with a control group of 127 patients without previous exposure to rituximab (R? group). The complete remission (CR) rates were similar in both groups. Multivariate analysis identified age‐adjusted International Prognostic Index at diagnosis, extranodal involvement and disease status at transplant, and the number of previous chemotherapy lines as independent factors with a negative influence on CR rate. Compared with R? patients, those in the R+ group had a significantly better progression‐free survival (63% vs. 48% at 5 years) and overall survival (72% vs. 61% at 5 years). This observation was independent of other prognostic factors that affected these outcomes. In conclusion, ASCT is no less effective in patients with relapsed or refractory aggressive B‐cell lymphoma pre‐treated with first‐line rituximab‐containing therapy than in rituximab‐naive patients.     

The CD19+ B-cell counts at peripheral blood stem cell mobilization determine different levels of tumour contamination and autograft purgability in low-grade lymphoma

The tumour load of peripheral blood stem cell (PBSC) harvests and the outcome of ex vivo immunomagnetic B-cell purging was investigated in 19 patients with low-grade lymphoma. To quantify the tumour load, we combined fluorescence-activated cell sorting measurement of CD19+ B-cells and determination of the B-cell light chain ratio (LCR) with consensus complementarity-determining region III-polymerase chain reaction (CDRIII-PCR) and gene scan analysis. The number of tumour cells was calculated using B-cell extracts from the PBSCs. Two different patterns were distinguished. In eight patients (42%) with CD19+ B cells >1% in the apheresis product, a high tumour load was found, characterized by a monoclonal LCR, positive PCR in seven out of eight cases, >5 x 10(7) extracted lymphoma cells in six out of seven PCR-assessable cases, and the presence of residual lymphoma after purging in six of seven cases. In 11 patients (58%) with <1% CD19+ B-cells in the product, a low tumour load was indicated by a polyclonal LCR, positive PCR in only 4 out of 11 cases, >5 x 10(7) extracted lymphoma cells in zero out of four PCR-assessable cases, and the presence of residual lymphoma after purging in zero out of four of these cases. The level of residual lymphoma following purging largely depended on the level of tumour contamination. CD19+ B-cells >50/microl in the peripheral blood at mobilization predicted a high tumour load in the apheresis product.     

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.     

Diagnostic markers for CNS lymphoma in blood and cerebrospinal fluid: a systematic review

Diagnosing central nervous system (CNS) lymphoma remains a challenge. Most patients have to undergo brain biopsy to obtain tissue for diagnosis, with associated risks of serious complications. Diagnostic markers in blood or cerebrospinal fluid (CSF) could facilitate early diagnosis with low complication rates. We performed a systematic literature search for studies on markers in blood or cerebrospinal fluid for the diagnosis CNS lymphoma and assessed the methodological quality of studies with the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS‐2). We evaluated diagnostic value of the markers at a given threshold, as well as differences between mean or median levels in patients versus control groups. Twenty‐five studies were included, reporting diagnostic value for 18 markers in CSF (microRNAs ‐21, ‐19b, and ‐92a, RNU2‐1f, CXCL13, interleukins ‐6, ‐8, and ‐10, soluble interleukin‐2‐receptor, soluble CD19, soluble CD27, tumour necrosis factor‐alfa, beta‐2‐microglobulin, antithrombin III, soluble transmembrane activator and calcium modulator and cyclophilin ligand interactor, soluble B cell maturation antigen, neopterin and osteopontin) and three markers in blood (microRNA‐21 soluble CD27, and beta‐2‐microglobulin). All studies were at considerable risk of bias and there were concerns regarding the applicability of 15 studies. CXCL‐13, beta‐2‐microglobulin and neopterin have the highest potential in diagnosing CNS lymphoma, but further study is still needed before they can be used in clinical practice.     

Asian variant of intravascular large B cell lymphoma causes patients to frequently develop the syndrome of inappropriate antidiuretic hormone secretion

The Asian variant of intravascular large B cell lymphoma is a special type of intravascular lymphoma with hemophagocytic syndrome and hypercytokinemia including interleukin-6, which stimulates antidiuretic hormone synthesis in the hypothalamus. We present here that the syndrome of inappropriate antidiuretic hormone secretion frequently occurs in patients with the Asian variant of intravascular large B cell lymphoma. The syndrome of inappropriate antidiuretic hormone secretion was found in eight of 118 (6.8%) lymphoma patients at the first diagnosis. Although there were six (5.1%) among 118 lymphoma patients with the Asian variant of intravascular large B cell lymphoma, four of the six patients (66.7%) developed the syndrome of inappropriate antidiuretic hormone secretion. In four patients with the Asian variant of intravascular large B cell lymphoma with the syndrome of inappropriate antidiuretic hormone secretion, elevated serum interleukin-6 and low sodium levels were almost normalized after chemotherapy. The Asian variant of intravascular large B cell lymphoma patients frequently develop the syndrome of inappropriate antidiuretic hormone secretion, and interleukin-6 might play a role in the occurrence of this disease. We should pay attention to hyponatremia caused by the syndrome of inappropriate antidiuretic hormone secretion in patients with the Asian variant of intravascular large B cell lymphoma.     

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.     

Lymphoma diagnosis at an academic centre: rate of revision and impact on patient care

Few studies have examined the value of a mandatory second review of outside pathology material for haematological malignancies. Therefore, we compared diagnoses on biopsies referred to an academic medical centre to determine the rate and therapeutic impact of revised diagnoses resulting from a second review. We reviewed 1010 cases referred for lymphoma during 2009–2010. For each case, referral diagnosis and second review diagnosis were compared. Revised diagnoses were grouped into major and minor discrepancies and all major discrepancies were reviewed by a haematologist to determine the effect the diagnostic change would have on therapy. There was no change in diagnosis in 861 (85·2%) cases. In 149 (14·8%) cases, second review resulted in major diagnostic change, of which 131 (12·9%) would have resulted in a therapeutic change. The highest rates of revision were for follicular, high‐grade B‐cell, and T‐cell lymphomas. We found higher rates of major discrepancy in diagnoses from non‐academic centres (15·8%) compared to academic centres (8·5%; P = 0·022), and in excisional biopsies (17·9%) compared to smaller biopsies (9·6%; P = 0·0003). Mandatory review of outside pathology material prior to treatment of patients for lymphoma will identify a significant number of misclassified cases with a major change in therapy.     

The lymphocyte to monocyte ratio improves the IPI‐risk definition of diffuse large B‐cell lymphoma when rituximab is added to chemotherapy

The peripheral blood lymphocyte to monocyte ratio (LMR) at diagnosis can be clinically relevant in patients with diffuse large B‐cell lymphoma (DLBCL). We reviewed the outcome of 1,057 DLBCL patients followed from 1984 to 2012 at four centers. LMR was analyzed as a clinical biomarker by receiver‐operating characteristic (ROC) analysis and Harrell's C‐statistics. Patients were characterized by a median age of 61 years, International Prognostic Index (IPI) score of >2 in 39%, and were treated with a rituximab‐containing chemotherapy in 66%. LMR proved strongly predictive for survival in patients treated with rituximab‐based programs, but not in those receiving chemotherapy alone. Additionally, an LMR value of ≤2.6 (as determined by ROC analysis) was associated with a worst performance status, a higher lactate dehydrogenase (LDH) level, an advanced clinical stage, and a higher IPI score (P = 0.000). In patients treated with rituximab‐supplemented chemotherapy programs, an LMR value of <2.6 was found in most of the primary refractory patients (75%) which proved as the best cutoff to predict both response and survival (P = 0.018). Finally, multivariate analysis and Harrell's C‐statistics confirmed the IPI‐independent role of LMR on survival (P = 0.0000). In conclusion, LMR is a potent predictor of clinical response and survival in DLBCL treated with rituximab‐containing chemotherapy. Am. J. Hematol. 88:1062–1067, 2013. © 2013 Wiley Periodicals, Inc.     

Fine needle aspiration and core needle biopsy in the diagnosis of lymphadenopathy of unknown aetiology

The clarification of enlarged lymph nodes is a common issue in clinical routine. By now, open surgery with complete lymph node extirpation, followed by histopathology, is considered as standard. We investigated the value of fine needle aspiration (FNA) and core needle biopsy (CNB) when supporting the conventional morphology by immunotyping. In total, 101 lymph nodes (reactive, n = 19; lymphoma, n = 46; metastatic, n = 36) were examined. CNB specimens were sufficient for unequivocal diagnosis by histopathology in 95 %. The FNA cytology allowed a correct diagnosis in 49 %. When supported by immunocytology, the success rate improved to 72 %. By accepting "suspicious of" as correct diagnosis, the ratio increased to 91 %. Additional use of flow cytometry in 46 samples minimized the "suspicious of" diagnoses and increased the proportion of unequivocal diagnoses in FNA specimens to 87 %. Flow cytometry allowed a correct subtyping in 20 of 21 B cell lymphoma but recognised only one of five Hodgkin lymphoma. All eight reactive samples were correctly diagnosed by flow cytometry. In summary, CNB allows a reliable clarification of an unclear lymphadenopathy. FNA is a powerful first diagnostic approach, especially if cytology is supported by immunocytology. The most substantial contribution of flow cytometry in FNA is the discrimination between reactive lymphadenopathy and B cell lymphoma.     

High dose chemotherapy and autologous stem cell transplantation in nodular lymphocyte‐predominant Hodgkin lymphoma: A retrospective study by the European society for blood and marrow transplantation‐lymphoma working party

Whilst autologous stem cell transplantation (auto‐SCT) is considered standard of care for relapsed/refractory classical Hodgkin lymphoma, the role of auto‐SCT in nodular lymphocyte‐predominant Hodgkin lymphoma (NLPHL) is not well defined due to limited data. We report the first study on auto‐SCT for NLPHL with a larger cohort. Eligible for this retrospective registry study were patients reported to the EBMT between 2003 and 2013, aged 18 or older with relapsed/refractory NLPHL who underwent first auto‐SCT with disease chemosensitive to salvage therapy. NLPHL transformed to diffuse large B cell lymphoma were excluded. Sixty patients (83% male; median age 40 years) met the eligibility criteria. The median time between diagnosis and transplant was 21 months (IQR 13–58), and the median number of prior treatment lines was 2 (range 1–5), including rituximab in 63% of the patients. At auto‐SCT, 62% of the patients were in complete remission (CR) and 38% in partial remission. Seventy‐two percent of the patients received BEAM as high‐dose therapy. With a median follow‐up of 56 months (range 3–105), 5‐year progression‐free and overall survival (OS) were 66% and 87%, respectively. Univariate comparisons considering age, time from diagnosis to transplant, prior chemotherapy lines, and prior rituximab use failed to identify significant predictors for any survival endpoint except for being in CR at the time of auto‐SCT (vs PR, P = .049) for OS. Auto‐SCT in patients with relapsed/refractory NLPHL who are sensitive to salvage therapy gives excellent disease control and long‐term survival independent of the time interval between diagnosis and transplant.