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PubMed1997

Incidence, predictive factors, and outcome of lymphoma transformation in follicular lymphoma patients.

PURPOSE: To assess the incidence of lymphoma transformation in the natural history of follicular lymphoma (FL) patients and the factors that are predictive of this event. PATIENTS AND METHODS: Two hundred twenty patients with FL treated in our institution between 1975 and 1990, with a median follow-up duration of 9 years, were included in this retrospective analysis. RESULTS: Transformation was proven by histology in 34 patients or by cytology in 13 patients and was considered as highly probable on clinical arguments in five patients for an overall incidence of 24%. The probability of transformation was 22% at 5 years and 31% at 10 years and tended to plateau after 6 years. Predictive factors for transformation were nonachievement of complete remission (CR) after initial therapy (P < 10(-4), low serum albumin level (< 35 g/L) (P = .001), and beta 2-microglobulin level greater than 3 mg/L (P = .02) at diagnosis. In a multiparametric analysis, only beta 2-microglobulin level retained prognostic significance for freedom-from-transformation (FFT) survival (P = .04). Transformation accounted for 44% of deaths and was associated with a poor outcome, with a median survival time of 7 months. CONCLUSION: Transformation is an early event in the course of the disease and is mainly observed in patients with known adverse prognostic factors or those who do not achieve CR after initial treatment. These findings may be useful to select follicular lymphoma patients for intensive therapeutic approaches.

Adult↗

PubMed2003

Summary statement on primary central nervous system lymphomas from the Eighth International Conference on Malignant Lymphoma, Lugano, Switzerland, June 12 to 15, 2002.

Under the sponsorship of the International Extranodal Lymphoma Study Group, a Multidisciplinary Workshop on primary CNS lymphoma (PCNSL) with over 50 participants from Europe, North America, Israel, and Australia was held as part of the Eighth International Conference on Malignant Lymphoma in Lugano, Switzerland (June 12 to 15, 2002). The main purposes of the Workshop were to exchange the latest scientific information, to analyze methodologic issues in the design of clinical trials, to reach a consensus on treatment recommendations and prognostic factors, to discuss clinical and molecular targets for future studies, and to establish an international collaborative group to conduct laboratory and clinical investigations in PCNSL. This article summarizes the contents of the Workshop, analyzes the current knowledge on the most relevant biologic and clinical issues in PCNSL, and focuses on fundamental challenges to be addressed in future studies.

Animals↗

PubMed2001

Value of CD23 determination by flow cytometry in differentiating mantle cell lymphoma from chronic lymphocytic leukemia/small lymphocytic lymphoma.

Mantle cell lymphoma (MCL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) share many morphologic and immunophenotypic features. In addition to histomorphologic examination, it is customary to use the absence of CD23 to differentiate MCL from CLL/SLL, based primarily on reported comparisons of immunohistochemical staining of tissue sections. These findings are widely extrapolated to flow cytometric analysis, although available data are contradictory and not sufficiently detailed. We compared expression of CD23 by flow cytometry in 22 cases of MCL and 25 cases of CLL/SLL. Lymphoma cells in 12 of 22 MCLs were negative for CD23, and 10 showed dim expression. In contrast, none of 25 CLL/SLLs were negative for CD23, 4 were dimly positive, and 21 were moderately or brightly positive. Thus, a significant proportion of MCL exhibited overlap of CD23 expression in the low-intensity range with CLL/SLL. Clinically, there was no correlation between the intensity of CD23 expression and clinical stage at diagnosis or survival. These findings emphasize that by flow cytometry, MCL can be differentiated reliably from CLL/SLL using CD23 if negative expression is observed. However, with dimly positive expression, interpretation should be cautious.

Adult↗

PubMed2000

Progression of an orbital T-cell rich B-cell lymphoma to a B-cell lymphoma in a dog.

An 11-year-old Shetland Sheepdog was presented for exophthalmos caused by a locally extensive, poorly defined mass located behind the right eye. The primary orbital mass was identified by light microscopy and immunohistochemistry as a T-cell rich B-cell lymphoma (TCRBCL) composed predominantly of BLA.36-positive large neoplastic lymphoid cells admixed with fewer CD3- and CD79a-positive small lymphocytes. The dog was treated for lymphoma, but 6 months after presentation it was euthanatized for suspected hepatic and gastrointestinal metastasis. Gross findings revealed an enlarged liver with multiple well-demarcated, randomly distributed 0.1-1.5-cm white nodules, five firm white submucosal jejunal nodules, and ileocecal, mediastinal, and hilar lymphadenopathy. Metastatic liver lesions consisted of sheets of monomorphic large neoplastic lymphoid cells that effaced and expanded portal and centrilobular zones. These cells were morphologically similar to the large neoplastic cells of the original orbital tumor and were CD3-negative and variably BLA.36-positive, consistent with B-cell lineage. Similar cells comprised the jejunal nodules and effaced the lymph nodes. The progression of TCRBCL to a diffuse B-cell lymphoma in this case is consistent with reported human cases and has not been previously reported in the dog.

Animals↗

PubMed2001

Health-related quality of life and its potential prognostic implications in patients with aggressive lymphoma: a Nordic Lymphoma Group Trial.

This study was conducted to explore treatment and disease-related effects on health-related quality of life (HRQoL) in patients with aggressive lymphoma, to identify predictors for impaired long-term HRQoL, and to analyze the prognostic value of pretreatment HRQoL. Ninety-five patients with aggressive lymphoma, constituting a subset of a randomized multicenter trial comparing CHOP and MACOP-B, entered a HRQoL study, using the EORTC QLQ-C30 questionnaire. Patient scores were compared to scores from an age- and gender-adjusted reference population sample, and evaluation of the prognostic value of pretreatment QoL scores in relation to clinical prognostic factors was performed. Before treatment, patients exhibited lower scores of global QoL, physical, role, and social functions, and more appetite loss, compared to the reference population. Role functioning improved compared to baseline, but remained depressed compared to the reference group more than 8 mo after end of treatment. By then, the patient group displayed no difference in other HRQoL variables compared to that of the reference population. No reliable predictor for impaired long-term HRQoL could be identified. In multivariate analysis, including the factors of the International Prognostic Index, pretreatment global QoL was an independent prognostic marker for overall survival. In conclusion, in this population with aggressive lymphoma and favorable prognostic features, HRQoL was not substantially affected during the first year after diagnosis. Pretreatment global QoL may constitute a significant prognostic factor, meriting further investigation in prospective studies.

Adolescent↗

PubMedDate not supplied

Transformation of "signet ring cell" lymphoma to typical nodular, poorly differentiated lymphocytic lymphoma: light microscopic, immunohistochemical and electron microscopic observations.

Malignant lymphoma with intracellular immunoglobulins giving a "signet ring" appearance to the lymphocytes is a recently described morphologic variant with specific ultrastructural and immunohistochemical characteristics. We report a case that had this distinctive morphology when initially biopsied but on subsequent biopsy 2 1/2 years later had the typical appearance of a poorly differentiated lymphocytic lymphoma without "signet ring" cells. The same monoclonal immunoglobulin class and light chain type was demonstrated in both biopsies using immunohistochemical techniques. Rare cells in the second biopsy showed the characteristic ultrastructural findings. These findings support the concept of a continuum of cell types in malignant lymphoma, with transformation toward a cell line lacking the peculiar characteristics resulting in this unique appearance.

Adult↗

PubMed2001

Phenotypic characterization of subsets of T cell lymphoma: towards a functional classification of T cell lymphoma.

T cell non-Hodgkin's lymphomas (T-NHL) have traditionally been classified according to a variety of criteria including histological and clinical features, sites of involvement and etiologic agents. Except in select T-NHL types (e.g. CD30-positive anaplastic large cell lymphoma (ALCL)), immunophenotypic criteria are not used for routine subclassification of T-NHL. In this article. we outline the current models for classification and diagnosis of T cell tumors. We also briefly review the current understanding of non-neoplastic T cell subsets with regards to expression of activation markers belonging to the tumor necrosis factor receptor (TNFR) gene family. We summarize the currently available information on expression of these subset markers in T cell tumors, focusing on TNFR family members CD30 and CD134/OX40. CD134/OX40 expression is characteristic of certain entities (angioimmunoblastic lymphoma, angiocentric T-NHL) and a subset of T-NHLs of unspecified type, whereas CD30 expression is characteristic of ALCL and a largely non-overlapping subset of T-NHLs of unspecified type. Immunophenotypic stratification of T-NHL, using TNFR family members and other T cell subset-specific gene products, may provide a functional model for T-NHL classification as is currently the case for B cell tumors.

Humans↗

PubMed1992

Constitutive production of the interleukins IL-5 and IL-6 by the lymphoma cell line OCI-Ly 17 derived from a patient with malignant lymphoma and hypereosinophilia.

Peripheral blood cells of a patient with diffuse large cell non-Hodgkin's lymphoma presenting with hypereosinophilia were used to establish an EBV negative lymphoma cell line termed OCI-Ly17. Cells of the line stained positive for CD2 and CD5 determinants and demonstrated rearrangement of the T-cell receptor beta chain. The immunoglobulin heavy chain gene was found to be in germ line configuration. Northern blot studies using probes for IL-1 alpha, IL-3, IL-4, IL-5, IL-6, and GM-CSF showed message for IL-5 and IL-6. Supernatants of the cell line were evaluated on normal non-adherent, E-rosette depleted bone marrow cells to determine the presence of growth promoting activities for clonogenic eosinophilic progenitors. Eosinophilic colonies were observed. Their frequency depended upon the amount of supernatant added to the cultures. The growth promoting activity in the supernatant was reduced in a dose dependent manner by preincubation with increasing concentrations of anti-IL-5 antibodies. The supernatants of the cell line were also tested on the IL-6 sensitive human myeloma line OCI-My4 and myeloma colonies grew in response. This stimulatory activity within the supernatant was neutralized by addition of increasing concentrations of anti-IL-6 antibodies. Although producing IL-5 and IL-6 constitutively, the lymphoma line did not increase proliferation in response to either interleukin, nor did it show a reduced proliferative rate when antibodies to IL-5 or IL-6 were added to the cultures.

Aged↗

PubMed1993

Pilot study and randomised trial of mitozantrone and ifosfamide for relapsed non-Hodgkin's lymphoma. Scotland and Newcastle Lymphoma group (SNLG) Working Party on Therapy.

This report compares a pilot study followed by a trial of the combination of mitozantrone and ifosfamide for relapsed lymphoma. In the pilot study (15 patients) toxicity and activity of the combination was tested on a variety of relapsed non-Hodgkin's lymphoma. In the trial (19 patients) the therapy was confined to patients with high and intermediate grade non-Hodgkin's lymphoma in which the combination was compared against single agent mitozantrone. The median survival of patients on the pilot and trial was very poor at around six months, but some individuals survived for several years from both groups. The main toxicities of treatment were, predictably, nausea and vomiting and bone marrow suppression on the combination, and bone marrow suppression alone on the single agent mitozantrone. There was no obvious disadvantage of the single agent treatment when compared with the combination, but this statement has to be interpreted with caution given the high death rate amongst all patients and the very small numbers who entered the randomised trial.

Adult↗

PubMed1993

Clinical implication and prognostic significance of small lymphoma cells in the peripheral blood and bone marrow of B-cell non-Hodgkin's lymphomas.

It seems possible that small lymphoma cells (SLC) may have a role even in aggressive B-cell non-Hodgkin's lymphoma (B-NHL) such as large-cell lymphoma. However, SLC are often difficult to distinguish morphologically from normal or reactive small lymphocytes. In this study, we used a flowcytometric technique (kappa-lambda imaging; KLI) for detection of SLC. Peripheral blood (PB) and bone marrow (BM) samples taken from 41 patients with surface immunoglobulin positive (sIg+) B-NHL were analysed. SLC were detected in about 90% (37/41) of the untreated patients when either PB or BM was analysed by KLI. The presence of SLC correlated well with disease activity. However, a few SLC were present even in the PB (16%) or BM (27%) of the 31 patients who achieved complete remission, indicating that minimal residual disease (MRD) was present. In some cases, the reappearance of SLC in the PB or BM preceded clinical relapse. Furthermore, the initial volume of SLC, particularly in the BM, tended to be related to the prognosis (P = .068). These results suggest that the detection of SLC by KLI may be helpful not only for the screening and clinical staging of sIg+ B-NHL, but also for monitoring disease activity and detecting MRD. Moreover, the volume of SLC in the BM may be a useful predictor of prognosis.

Bone Marrow↗

PubMed1995

A retrospective analysis of treatment outcome in 106 cases of localized gastric non-Hodgkin lymphomas. Danish Lymphoma Study Group, LYFO.

197 cases of gastric lymphoma were reported to a population-based Danish registry of non-Hodgkin's lymphomas. 106 of these cases were localized, representing stages IE and II1E, and were analyzed retrospectively, using Cox regression analysis. 67 had surgical resection, 51 chemotherapy, and 55 radiotherapy, or combinations thereof. No type of treatment showed any superiority as regards survival (p = 0.13). Overall 5-year survival was 67%. The pretherapeutic presence of fever or S-LDH-elevation had a far more significant influence on survival than histology or any of the treatments or treatment combinations. Surgical resection was associated with a significantly higher risk of late complications than radiotherapy, suggesting that radiotherapy may be preferable to surgery as the primary treatment in localized gastric lymphoma. It could not be determined from the available data whether the addition of chemotherapy to the primary treatment provides any survival benefit.

Aged↗

PubMed1999

Graft-versus-lymphoma effect after allogeneic peripheral blood stem cell transplantation for primary central nervous system lymphoma.

Allogeneic peripheral blood stem cell transplantation (allo PBSCT) is a recognized treatment modality for hematological malignancies resistant to conventional chemoradiotherapy. The post-transplant immune-mediated graft-versus-leukemia effect has major curative potential. In this case presentation, the allogeneic approach to resistant recurrent primary central nervous system (CNS) lymphoma using peripheral blood stem cells from an HLA identical sibling after immuno-suppressive non-myeloablative conditioning, was examined clinically. The patient in question had relapsing refractory primary CNS lymphoma and is the first to be treated with this modality. She developed early skin and liver-localized grade II graft-versus-host disease after allo PBSCT, which then responded to short-term treatment. Chimeric studies at the time showed 100% donor cells and repeated magnetic resonance imaging of the brain revealed gradual shrinkage of the tumor. Three months after transplant the cerebral mass was no longer evident and currently, 30 months after transplantation, the patient continues to be disease free. The absence of any signs of malignancy suggests the development of a durable graft-versus-lymphoma effect in this brain tumor and indicates that this effect may be achieved even after non-myeloablative conditioning.

Adult↗

PubMed2001

Non-Hodgkin's lymphoma presenting with spinal involvement: the Sheffield Lymphoma Group experience (1970-2000).

Spinal non-Hodgkin's lymphoma is rare. We retrospectively reviewed the clinical and histopathologic records of 39 consecutive patients referred to the Sheffield Lymphoma Group from 1970 to 2000 and analysed the prognostic differences between localised (stage IE and IIE) and secondary (stage III and IV) spinal non-Hodgkin's lymphoma (S-NHL) patients. Forty-five percent of all patients were over 60 years old. More patients were male (58%); presented with stage IE and IIE (63%), mostly of intermediate/high grade histology (74%); over a third had symptoms; nearly a third (11 patients) were paraplegic and 14 had sphincter dysfunction at diagnosis. The overall survival of all patients was 39% at 5 years (median 24.7 months), whilst that of localised S-NHL was 51% (median 89.7 months). Univariate analysis showed better survival for patients with good mobility status at presentation (p < 0.0l) and complete response to initial treatment (p < 0.00l). In primary S-NHL, histology (p < 0.05) significantly influenced overall survival. In conclusion, disease is frequently locally advanced at presentation with aggressive histologic grade: thorough staging should always be performed to exclude widespread disease. Good mobility status predicts for good survival outcome. Optimal treatment is still uncertain.

Actuarial Analysis↗

PubMed2006

Bone marrow involvement in systemic ALK+ anaplastic large cell lymphoma: morphological resemblance with Hodgkin's lymphoma.

A 21 years old male presented with enlarged cervical lymph nodes. Diagnosis of anaplastic large cell lymphoma was made on lymph node biopsy and confirmed by immunohistochemistry using a panel of monoclonal antibodies including ALK-1. Bone marrow aspiration revealed the presence of large lymphoma cells and trephine biopsy showed interstitial involvement. In addition, there was presence of binucleate cells, lymphocytes, plasma cells and eosinophils. All these features resulted in a strong resemblance of the morphology with Hodgkin's lymphoma.

Activin Receptors, Type II↗

PubMedDate not supplied

[Treatment of aggressive primary lymphomas of the digestive system by intensive chemotherapy. Experience of the Study Group on Lymphomas in Adults with the LNH-84 protocol].

Ninety-one patients with primary gastrointestinal lymphoma included in the LNH-84 multicentric regimen were analyzed to determine the efficacy and the toxicity of intensive combination chemotherapy and of surgical debulking. All these patients had aggressive histological subtypes: 56 patients had localize disease, stage IE or IIE, and 35 patients had stage IV disease; 40 patients had bulky disease. Specific sites included stomach (43 cases), small bowel (35), ileo-cecum (13), colon (10), and rectum (6). Although 71 patients (78%) had an attempted surgical resection, only 28 (31%) had complete tumor excision. Patients were treated with 3 or 4 cycles of ACVB chemotherapy followed by sequential consolidation. Nine patients died during chemotherapy. With a median follow-up of 3 years, 10 patients have relapsed and predicted 4-year survival of the entire group is 62%. In stage IE or IIE patients, survival and disease-free survival are similar in patients who underwent complete resection or incomplete or no surgical resection prior to the administration of chemotherapy. Prognostic factors predicting for survival were similar to the entire group of patients treated with the LNH-84 regimen. Aggressive gastrointestinal lymphoma patients treated with intensive chemotherapy have outcome and prognostic factors comparable to those of other similarly staged aggressive lymphoma patients. Surgical resection prior to the administration of combination chemotherapy did not influence survival or disease-free survival in patients with localized disease.

Adolescent↗

PubMed2003

[Autologous hematopoietic stem cell transplantation for the treatment of aggressive non-Hodgkin's lymphoma. The experience of Polish lymphoma research group].

We analysed the outcome of 200 patients, aged 38 (13-72) years, with aggressive non-Hodgkin's lymphoma (NHL) treated with high-dose chemotherapy followed by autologous haematopoietic stem cell transplantation (autoHSCT) in ten oncohaematological centres belonging to Polish Lymphoma Research Group (PLRG). The source of stem cells for transplantation was peripheral blood (autoPBSCT, n = 153), bone marrow (autoBMT, n = 40) or both blood and bone marrow (n = 7). The probability of overall survival (OS) and progression-free survival at 10 years was 51% (+/- 7%). The transplant-related mortality rate equalled 7%. In multivariate analysis, the only factor influencing independently the probability of OS was disease status at transplantation (p < 0.00001). The outcome of patients transplanted in first or subsequent complete remission or first partial remission (PR) was significantly better compared with subjects given autoHSCT in PR 2 or those with primary or secondary refractoriness. Regarding histological subtypes, the highest OS rate (87%) was observed for anaplastic large T cell lymphoma. The outcome after autoBMT was better compared with autoPBSCT (OS probability: 67% vs. 43%), although the difference did not reach statistical significance. We conclude that high-dose therapy followed by autoHSCT is an effective option for high-risk aggressive NHL. Remission status is a major factor determining long-term outcome. This should be taken into account when referring patients for autoHSCT.

Adolescent↗

PubMed1992

Bone marrows of non-Hodgkin's lymphoma patients with a bcl-2 translocation can be purged of polymerase chain reaction-detectable lymphoma cells using monoclonal antibodies and immunomagnetic bead depletion.

Using the extremely sensitive technique of polymerase chain reaction (PCR) to detect the bcl-2 translocation, only 50% of bone marrows could be purged of PCR-detectable lymphoma cells using a cocktail of three anti-B-cell monoclonal antibodies (MoAbs) and complement-mediated lysis. This observation is of clinical importance because those patients whose reinfused marrows harbored residual lymphoma cells showed a significantly increased incidence of relapse. To improve purging, we used PCR detection of the bcl-2 translocation to compare the efficiency of complement-mediated lysis with immunomagnetic bead depletion. Using either a three or a four MoAb cocktail followed by immunomagnetic bead depletion, all PCR-detectable cells were purged after three cycles of treatment. In these same patient samples, treatment with three MoAbs and complement purged only 11 of the 25 (44%) samples. The addition of a fourth MoAb followed by complement lysis purged the marrows of only an additional five patients. Immunomagnetic bead depletion was specific because there was no loss of committed myeloid progenitor cells. The above results suggest that immunomagnetic bead depletion of the harvested marrow will likely be superior to our previous method of purging and the lack of nonspecific toxicity to myeloid progenitor cells predicts that it will not impair engraftment. This methodology will now be used to determine whether the reinfusion of lymphoma free marrow affects the incidence of relapse after autologous bone marrow transplantation.

Antibodies, Monoclonal↗

PubMed1992

[Primary cerebral lymphoma in 10 patients with AIDS. Comparative clinico-radiologic study with cerebral toxoplasmosis, cerebral tuberculoma and primary cerebral lymphoma in non-immunodepressed patients].

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is the second cause of cerebral masses in patients with the acquired immunodeficiency syndrome (AIDS). The present study evaluated the possible presence of clinical or radiologic signs permitting differentiation of AIDS patients and PCNSL from those with cerebral masses of other etiologies. METHODS: Clinical history and cranial computerized tomography (CT) of patients with PCNSL and AIDS from the Hospital Clinic i Provincial in Barcelona were reviewed. Results were compared with those of patients with PCNSL without evidence of immunosuppression and with those with AIDS and cerebral toxoplasmosis or tuberculoma diagnosed during the same period. RESULTS: Of 685 patients with AIDS, 10 were identified with PCNSL. The clinical picture was not different to that observed in patients with AIDS and cerebral toxoplasmosis or tuberculomas. In contrast to PCNSL in non immunodepressed patients, the cerebral CT in patients with PCNSL and AIDS demonstrated hyperdense lesions in only 44% and contrast enhancement was not homogeneous in any case. These characteristics were similar to those observed in the CT of patients with cerebral toxoplasmosis or tuberculoma with the exception that only 8% of the lesions by toxoplasmosis were spontaneously hyperdense. CONCLUSIONS: The clinical-radiological data of primary central nervous system lymphoma in patients with the acquired immunodeficiency syndrome are similar to those observed in other etiologies. However, the presence of a sole spontaneously hyperdense region in cranial computerized tomography is more suggestive of primary central nervous system lymphoma than cerebral toxoplasmosis.

Acquired Immunodeficiency Syndrome↗