Large Cell Immunoblastic Lymphoma Research Articles

Primary Cardiac Tumors Operated on in Côte d’Ivoire: They Are Almost All Myxomas

Objective: Through this surgical series, we present the epidemiological and anatomical-clinical aspects and the surgical results concerning patients operated on for a primary cardiac tumor at the Abidjan Heart Institute. Materials and Method: This is a retrospective descriptive study covering the period of January 1982 to December 2022, based on the medical records of patients operated on for a primary cardiac tumor at the Abidjan Heart Institute. Results: Twenty-seven (27) patients underwent surgery for a primary cardiac tumor, including 14 women and 13 men with a mean age of 41.5 years (range 19 - 76 years). The main circumstances of discovery were exertional dyspnea, palpitation and syncope or pseudo-syncope. The main site was the septal wall of the left atrium. The diagnosis of myxoma was confirmed by pathological examination of the surgical specimen in 96.3% (n = 24) of the patients and it was a malignant large cell immunoblastic lymphoma of the myocardium in 3.7% (n = 1) of the patients. The mean largest diameter was 46.1 mm. The postoperative course was marked by an ischaemic stroke (n = 1); recurrence of a left atrial myxoma 5 years after the first tumor removal (n = 1). Two cases of death were noted, one due to the evolution of immunoblastic large cell lymphoma and the other due to an extracorporeal circulation accident. Conclusion: Almost all primary cardiac tumors operated on in Abidjan are myxomas. The circumstances of the discovery of these cardiac tumors are multiple and varied but dominated by exertional dyspnea, palpitation and syncope. Whatever their histological type, primary cardiac tumors are serious affections, in view of the haemodynamic and rhythmic disorders they cause.

Differential Expression of BCL-6, CD138/Syndecan-1, and Epstein-Barr Virus–Encoded Latent Membrane Protein-1 Identifies Distinct Histogenetic Subsets of Acquired Immunodeficiency Syndrome–Related Non-Hodgkin's Lymphomas

AbstractThis study was aimed at defining the histogenesis of the pathologic spectrum of acquired immunodeficiency syndrome–related non-Hodgkin's lymphomas (AIDS-NHL), including AIDS-related small noncleaved cell lymphoma (AIDS-SNCCL), AIDS-related large noncleaved cell lymphoma (AIDS-LNCCL), AIDS-related large cell immunoblastic lymphoma plasmacytoid (AIDS-IBLP), and AIDS-related primary effusion lymphoma (AIDS-PEL). Forty-six cases of AIDS-NHL were investigated for the expression pattern of BCL-6, a protein specifically expressed by germinal center (GC) B-cells, and CD138/syndecan-1 (syn-1), a marker of post-GC B-cell differentiation. Expression of BCL-6 and syn-1 segregated two major phenotypic patterns among AIDS-NHL: (1) the BCL-6+/syn-1− pattern associated with AIDS-SNCCL and AIDS-LNCCL; (2) the BCL-6−/syn-1+ pattern associated with AIDS-IBLP and AIDS-PEL. Among systemic AIDS-NHL infected by Epstein-Barr virus (EBV), expression of the EBV-encoded latent membrane protein-1 (LMP-1) preferentially associated with the BCL-6−/syn-1 + profile. Analysis of nonneoplastic lymph nodes showed that the two phenotypic patterns detected in AIDS-NHL correspond to physiologic stages of B-cell development, ie, GC B-cells (BCL-6+/syn-1−) and preterminally differentiated post-GC B-cells (BCL-6−/syn-1+). Thus, BCL-6+/syn-1− AIDS-NHL reflects a GC stage of differentiation, whereas AIDS-NHL which are BCL-6−/syn-1+, and LMP-1+when infected by EBV, derive from B cells that have entered post-GC plasmacell differentiation. These findings are relevant for the pathogenesis and differential diagnosis of AIDS-NHL.

Classificação de 86 casos de linfoma em bovinos de acordo com a Working Formulation (WF) of Non-Hodgkin's Lymphomas for Clinical Usage e a Revised European-American Classification of Lymphoid Neoplasms (REAL)

Resumo Por meio de um estudo retrospectivo, realizou-se avaliação fenotípica (histologia) e imunofenotípica (imuno-histoquímica [IHQ]) de 86 casos de linfoma bovino. Quanto ao padrão de distribuição, todos os linfomas foram incluídos como difusos. Em relação à dimensão dos linfócitos neoplásicos, 83,8% dos linfomas foram considerados como de grandes células e 11,6% como de pequenas células. Linfomas mistos, ou seja, constituídos por grandes e pequenas células, representaram apenas 4,6% dos casos. Quanto ao número de mitoses, 84,9% dos linfomas foram incluídos como de grau intermediário, 10,5% como de baixo grau e 4,6% como de alto grau. No que se refere à morfologia do núcleo, linfomas em que predominavam linfócitos não clivados (58,2%) ou linfócitos clivados (37,2%) foram mais frequentes do que aqueles em que havia uma mistura igualmente proporcional de linfócitos clivados e não clivados (4,6%). Com base nestes resultados, os 86 linfomas foram assim distribuídos utilizando-se a classificação proposta pela Working Formulation (WF) of Non-Hodgkin's Lymphomas for Clinical Usage: difuso de grandes células não clivadas (46,5%), difuso de grandes células clivadas (33,7%), difuso de pequenas e grandes células (4,6%), difuso de pequenas células - tipo plasmocitoide (7%), imunoblástico (3,5%), difuso de pequenas células - tipo intermediário (2,3%), difuso de pequenas células não clivadas (1,2%) e difuso de pequenas células não clivadas - tipo Burkitt (1,2%). Na imuno-histoquímica, 27 dos 86 (31,4%) linfomas foram positivos para o anticorpo monoclonal CD79αcy, utilizado para detecção de linfócitos B, e nenhum caso foi positivo para o anticorpo policlonal CD3, utilizado para detecção de linfócitos T. Com base nestes resultados, os 27 linfomas B foram assim distribuídos utilizando-se a Revised European-American Classification of Lymphoid Neoplasms (REAL): linfoma difuso de grandes células B (81,5%), linfomas imunoblásticos de grandes células (11,1%) e linfomas linfoplasmocíticos (7,4%). Os resultados aqui apresentados permitem concluir que à semelhança do que vem sendo descrito em outras partes do mundo, os linfomas bovinos são basicamente difusos e predominantemente de grau intermediário, de grandes células, com núcleos clivados ou não clivados. Esses linfomas são decorrentes da proliferação neoplásica de linfócitos B e correspondem, em sua quase totalidade (92,6%), ao que atualmente é incluído na REAL como linfoma difuso de grandes células B.

Downregulation of glutathione transferase π sensitizes lymphoma/leukaemia cells to platinum‐based chemotherapy

Downregulation of glutathione transferase π sensitizes lymphoma/leukaemia cells to platinum‐based chemotherapy

Cytologic and immunocytochemical features of EBV negative primary effusion lymphoma: Report on seven Japanese cases

Primary effusion lymphoma (PEL) is very rare type of non-Hodgkin's lymphoma (NHL) usually confined to the body cavities such as the pleural space, pericardium, and peritoneum. PEL is a human herpes virus-8 (HHV-8)-associated lymphoma and commonly observed in human immunodeficiency virus (HIV)-infected patients. However, HIV-infected patients are extremely fewer in Japan in comparison with those in Western countries; PEL is usually not associated with HIV infection in Japan. This report presents seven Japanese cases of PEL. In situ hybridization revealed that the PEL cells were negative for EBV in all cases. An immunocytological analysis showed that only one case was positive for HHV-8, and PEL cells were positive for CD20 in all cases. MUM1 was positive, but CD10 and CD138 were negative in six cases. One case each was positive for CD30 and BCL-6. The phenotypic patterns of HIV-related is BCL6-/MUM1+/CD138+, thus, the phenotypic findings observed by immunocytochemistry in this study were somehow different from those reported in Western countries. However, the cytomorphological features of PEL cells showed large cell size, abundant basophilic cytoplasm, coarse chromatin, and occasional binucleated or multinucleated cells, similar to a large cell immunoblastic and anaplastic large cell lymphoma, indicating that the cytomorphological characteristics of PE cells in Giemsa and Papanicolaou stain were consistent with those reported abroad. The prognosis for PEL in these cases was poor, but the survival time was variable ranging from 1 month to 54 months, and was different from that of Western cases. No p16/CDKN2A expression was observed, and one case showed PEL cells with a BLIMP1 mutation.

15 Year Follow-up of ABMT for NHL: Surprisingly Favorable Outcome for Younger Adults.

Despite the fact that autologous bone marrow/stem cell transplantation (ABMT) has been successfully used to treat patients with relapsed Non Hodgkin's Lymphoma (NHL) for over 25 years, few series report follow-up beyond 10 years. We have followed a cohort of 110 NHL patients who underwent ABMT from 9/1988 through 12/1993, all treated with a uniform preparative regimen of CBV (Cyclophosphamide, BCNU, Etoposide (VP-16)). At the present time, 38 (35%) are alive and 72 patients have expired. Among the 38 living patients, the median follow-up is 15 years. NHL histology for all transplanted patients was based on the Working Formulation, and 21% had low grade, 54% intermediate grade, 25% high grade (the majority of the high grade group had diffuse immunoblastic large cell lymphoma). Median age at transplant was 47 years; 85% were sensitive to salvage chemotherapy; 31% had elevated LDH at the time of diagnosis; age adjusted IPI at ABMT was 0 (7%), 1 (56%), 2 (29%), 3 (7%). Multivariable analysis analyzing prognostic factors for survival predictably revealed that sensitivity to chemotherapy, and LDH status at the time of transplant, had significant impact on survival. Additionally, age at transplant was also highly significant (p=0.002). This is shown graphically below: [Display omitted] The incidence of low grade histologies was similar for all three groups. The younger group had a lower incidence of relapse mortality, as shown below: [Display omitted] It is commonly believed that age is of limited importance with respect to survival after ABMT. However, this data suggests that age may play a very important prognostic role. The causes are not well defined, but the continued relapse and mortality risk may warrant surveillance indefinitely for patients undergoing ABMT for NHL.

Eltrombopag Decreases Proliferation of Human Leukemia and Lymphoma Cell Lines In Vitro.

Eltrombopag is a novel, oral platelet growth factor that interacts with the thrombopoietin receptor on bone marrow progenitors to stimulate megakaryocyte and platelet production. Clinical trials have demonstrated that eltrombopag increases platelet counts in healthy volunteers and in patients with idiopathic thrombocytopenic purpura (ITP) and hepatitis C. Because thrombopoietin (TPO) receptors are expressed on lymphoma and leukemia cell lines and recombinant human TPO (rhTPO) has been shown to stimulate their proliferation in vitro, experiments were conducted to evaluate the effects of eltrombopag on the proliferation of leukemia and lymphoma cells in vitro. Five leukemia and lymphoma cell lines (ie, CCRF-CEM, K562, MOLT-4, RPMI-8226 and SR) representing lymphoblastic T cell leukemia, chronic myelogenous leukemia, acute lymphoblastic T cell leukemia, plasmacytoma and immunoblastic large cell lymphoma, were exposed to eltrombopag (0.1–40 ug/mL), rhTPO (100 ng/mL) or both for 3 days. Proliferation was measured by 18-hour incubation with tritiated thymidine incorporation. As expected, rhTPO alone led to a small, statistically significant increase in the proliferation of CCRF-CEM and RPMI-8226 cells, while it had no effect on the other cell lines. However, the addition of eltrombopag to rhTPO negated the increased proliferation seen with rhTPO alone. Even more remarkable, treatment with eltrombopag alone inhibited the proliferation of all five leukemia and lymphoma cell lines with an IC50 range of 0.56 to 5.9 ug/mL and 100% inhibition (IC100) of thymidine incorporation at 10 ug/mL (Table). Previous studies have shown that eltrombopag induces proliferation and differentiation of bone marrow progenitor cells in vitro and increases platelet counts in vivo. While eltrombopag and rhTPO interact with the TPO receptor to stimulate the production of platelets, there are differences in the site of receptor interaction and their signaling pathways. The findings of the current study suggest that eltrombopag may inhibit the proliferation of leukemia and lymphoma cell lines unlike the effect that has been demonstrated with rhTPO. Interestingly, eltrombopag may also serve to mitigate rhTPO-mediated proliferation of malignant hematologic cell lines. These findings merit further evaluation of the effects of eltrombopag on leukemia, lymphoma, and solid tumor cell proliferation.Cell lineIC50 (ug/mL)IC100 (ug/mL)CCRF-CEM0.7410K5621.8010MOLT-40.564RPMI-82265.9010SR0.774

Primary effusion lymphoma

Primary effusion lymphoma (PEL) is a human herpes virus-8 (HHV-8)-associated and very rare type of lymphoma usually confined to the body cavities and commonly observed in human immunodeficiency virus (HIV)-infected patients. A comparison was made between the cytologic and immunocytochemical features of 4 cases of PEL encountered in the authors' department with those reported to date in the literature. A comprehensive comparison of the cytologic and immunocytochemical features of the 4 cases with those reported in the literature was conducted. Cytologically, the most consistent features of the 4 cases and those in the literature included large cell size, moderate to abundant cytoplasm, a single nucleus in most cells with occasional bi- or multinucleated giant cells, single to multiple prominent nucleoli, and coarse chromatin. Immunocytochemically, only 2 (50%) of the current cases were of the null-phenotype compared with 93% of cases in the literature; the other 2 cases had a T-cell phenotype. Activation markers were expressed in 50% and 78% of the current cases and the literature cases, respectively. Positivity for HHV-8 was proven in the 4 cases by immunocytochemistry. Cytomorphologically, PEL exhibits features bridging large cell immunoblastic and anaplastic large cell lymphoma. Although it is usually of null-phenotype, it may occasionally express B-cell or T-cell markers, rendering its distinction difficult from other lymphomatous effusions on a cytologic and immunocytochemical basis alone. Therefore, HHV-8 detection is an essential confirmatory ancillary test in suspected cases of PEL.

Cytomorphological and immunocytochemical study of non‐Hodgkin's lymphoma in pleural effusion and ascitic fluid

Non-Hodgkin's lymphoma (NHL) is often complicated by pleural effusion and ascites. The present study is an attempt to categorize the lymphomatous effusions according to the WHO classification, using archival material. May-Grünwald-Giemsa and Papanicolaou-stained smears of 31 lymphomatous effusion specimens were reviewed. Of these, detailed cytological assessment was done on 12 pleural effusions and ten ascitic fluid specimens from 22 patients using the WHO lymphoma classification system. Immunocytochemical studies were performed in 21 specimens. Based on cytomorphological features, the 22 lymphomatous effusion specimens were categorized into lymphoplasmacytoid lymphoma (1), follicle centre cell (FCC) grade-1 (centrocytic) lymphoma (3), FCC grade-2 (centrocytic-centroblastic) lymphoma (3), FCC grade-3 (centroblastic) lymphoma (4), large cell immunoblastic lymphoma (4), lymphoblastic lymphoma (2), anaplastic large cell lymphoma (3) and miscellaneous types (2). Immunocytochemically, the lymphoma cells were T-cell (positive for CD3) and B-cell type (CD20 positive) in five and six cases respectively. Cytological examination of pleural effusion and ascitic fluid samples, supported by immunocytochemical studies, may be useful for the classification of lymphomas under the WHO system.

Retrospective Study of 82 Cases of Canine Lymphoma in Austria based on the Working Formulation and Immunophenotyping

In human beings the prevalence of different non-Hodgkin's lymphoma (NHL) subtypes varies according to geographical region. The aim of this study was to classify canine lymphomas in Austria and to compare the results with those of similar studies in other countries. Eighty-two NHLs were classified according to their morphology (based on the Working Formulation) and their immunophenotype (determined with anti-T-cell and anti-B-cell antibodies). Forty-two (51.2%) were of B-cell subtype, 24 (29.3%) of T-cell subtype, and 16 (19.5%) remained unclassified, because of either negative labelling (9/16) or immunoreaction with both antibodies (7/16). Diffuse lymphomas predominated (99%) over follicular lymphomas, while intermediate grade lymphomas (61%) outnumbered high-grade lymphomas (23.2%) and low grade lymphomas (13.4%). The most common subtype was the diffuse large cell lymphoma (40.2%), followed by the large cell immunoblastic lymphoma (13.4%) and the diffuse small lymphocytic lymphoma (13.4%). Follicular large cell lymphoma and small noncleaved cell lymphoma were uncommon (1.2%). Generally, these findings accord with those of similar studies in Western Europe, making the existence of specific risk factors in Austria unlikely.

The Large-Cell Lymphomas.

Diffuse large-cell and immunoblastic lymphoma (DLCL), considered together, are the most common histologic subtypes of non-Hodgkin's lymphoma (NHL). There will be approximately 15,500 new cases of DLCL in 1995 and this represents a dramatic increase over the last 20 years. The cause of KLCL is unknown, but its association with acquired and inherited immunodeficiency syndromes implicates immune dysregulation as an etiologic factor. Combination chemotherapy is standard treatment for all stages of DLCL. The use of adjutant radiation therapy (RT)_ in stage I-II patients remains controversial, but continues to play an important treatment role. Adjutant RT may permit the use of fewer cycles of chemotherapy and may improve freedom from relapse and survival. The International NHL Prognostic Factors Project has derived a model that helps predict which patients with KLCL will have a poor outcome. This analysis reveals that there are certain early=-stage patients with a poor prognosis who may benefit form more aggressive treatment. This review attempts to provide guidelines for the workup, treatment, and long-term prognosis of patients with early stage DLCL.

Serous effusions in malignant lymphomas: A review

Serous effusions are a common complication of lymphomas. Although the frequency of pleural effusion is 20-30% in non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD), the involvement of peritoneal and pericardial cavities is uncommon. Among lymphoma subtypes, T-cell neoplasms, especially the lymphoblastic lymphomas, more frequently involve the serous fluids. The thoracic duct obstruction and impaired lymphatic drainage appear to be the primary mechanism for pathogenesis of pleural effusion in HD and direct pleural infiltration is the predominant cause in NHL. There is wide variation in rate of positive cytologic findings of NHL in pleural effusion (22.2-94.1%). Cytologic features of specific lymphoma subtypes such as lymphoblastic lymphoma, follicular center cell lymphoma, including Burkitt-type lymphoma, marginal zone lymphoma, MALT lymphoma, and anaplastic large-cell lymphoma, etc., have been described in the literature. The differential diagnostic problems of lymphomas in serous effusions include reactive lymphocytoses, early involvement by lymphomatous process, small round-cell tumors (SRCT), and presence of look-alike of Reed-Sternberg cells. To overcome these difficulties, various ancillary studies, including immunocytochemistry (ICC), morphometry, flow cytometry (FCM), and cytogenetics/molecular genetics (PCR, in-situ hybridization, and Southern blotting), have been performed on effusion specimens. ICC not only distinguishes lymphomas from reactive lymphocytoses and SRCTs, it significantly modifies the morphologic diagnosis to achieve a better classification of lymphomas. Combined morphology and immunophenotyping by FCM, has a sensitivity as well as specificity of 100%. Morphometry also distinguishes reactive lymphocytoses from malignant lymphoma with a high degree of sensitivity (>85%) and specificity (>95%). Limitations of individual ancillary techniques can be overcome by using multiple parameters. Although lymphomas rarely present as serous effusions without the involvement of other thoracic and extrathoracic sites, a small group of lymphomas called primary effusion lymphomas (PEL) exhibit exclusive or dominant involvement of serous cavities, without a detectable solid tumor mass. This body cavity based lymphoma (BCBL) is a distinct clinicopathologic entity and is found predominantly in AIDS patients with preexisting Kaposi sarcoma. In the absence of obstructive or infiltrative tumor mass, its pathogenesis has been attributed to stimulation by vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF), leading to vascular leakage. Cytomorphologically, PEL is usually a large-cell lymphoma, which appears to bridge features of large-cell immunoblastic and anaplastic large-cell lymphoma (ALCL). Most of these cases comprise a unique subgroup of B-cell lymphoma, with features of both high-grade anaplastic and B-immunoblastic lymphoma, but T-cell and/or natural killer cell immunophenotypes are described. Its association with various viral DNAs has been studied in detail by molecular techniques. Pleural effusion due to lymphomas, either primary or otherwise, is considered as one of the factors adversely influencing overall survival. The presence of pleural effusion at the time of presentation is not only associated with extremely poor outcome of lymphomas, it is also a predictor of disease relapse after chemotherapy and decreased survival. When the patients of lymphomatous pleural effusions with and without mediastinal mass present in respiratory distress, thoracocentesis is the initial diagnostic and therapeutic choice in these patients. In such situations, cytology along with ancillary studies not only gives a quick diagnosis of lymphoma, but also offers prognostically significant information such as classification of lymphomas, its grade and immunophenotype, and presence/absence of viral DNAs and tumor lysis syndrome.

Is Diversified Clinical Presentation of Kaposi Sarcoma–Associated Herpesvirus/Human Herpesvirus-8–Associated Lymphoma Related to the Host's Changed Conditions?

Kaposi Sarcoma–Associated Herpesvirus/Human Herpesvirus-8 Kaposi sarcoma–associated herpesvirus (KSHV), also known as human herpesvirus-8 (HHV8), was initially discovered in tissue biopsies of AIDS-related Kaposi sarcoma (KS), a tumor consistently infected by this virus.1 In addition to KS, KSHV/HHV8 has been shown to associate with distinct lymphoproliferative diseases, occurring most commonly in persons with (HIV) infection/AIDS.2 Kaposi sarcoma–associated herpesvirus/human herpesvirus-8–associated lymphoproliferative diseases traditionally included primary effusion lymphoma (PEL),3 multicentric Castleman’s disease (MCD),4 and MCDassociated plasmablastic lymphoma.5,6 Today, the classification of KSHV/HHV8– associated lymphomas is changing increasingly because of new cases that are being reported whose clinical presentation varies. Recently, KSHV/HHV8 has been detected by immunohistochemistry and/or polymerase chain reaction in lymphoma cases presenting as tissue masses in persons with MCD6-9 or AIDS-associated KS.9-13 These lymphomas were described histologically as diffuse large-cell lymphoma or immunoblastic lymphoma with a PEL-like morphology.

Hepatosplenic Large Cell Immunoblastic Lymphoma in a Bottlenose Dolphin ( Tursiops truncatus) with High Levels of Polychlorinated Biphenyl Congeners

This report describes a large cell immunoblastic lymphoma in a bottlenose dolphin found stranded alive in Gran Canaria, Spain. Diffuse infiltration of round neoplastic cells was observed in the splenic cords and sinuses and in hepatic sinusoids, resulting in moderate organ enlargement. The tumour cells (immunophenotype IgG+ and CD3-) showed scant, lightly eosinophilic or basophilic cytoplasm, distinct cell boundaries and hyperchromatic nuclei, each with one or more nucleoli. Mitoses were common. On the basis of histopathological, immunohistochemical and ultrastructural features, the tumour was classified as an immunoblastic lymphoma. Eleven polychlorinated biphenyl (PCB) congeners, 23 organochlorine pesticides and 16 polycyclic aromatic hydrocarbons (PAHs) were detected in the blubber and liver. High concentrations of PCBs 153, 180, 138 and 187 found in the liver may have been associated with the hepatosplenic lymphoma.

Experimental Infection of NOD/SCID Mice Reconstituted with Human CD34 + Cells with Epstein-Barr Virus

Epstein-Barr virus (EBV)-induced lymphoproliferative disease is an important complication in the context of immune deficiency. Impaired T-cell immunity allows the outgrowth of transformed cells with the subsequent production of predominantly B-cell lymphomas. Currently there is no in vivo model that can adequately recapitulate EBV infection and its association with B-cell lymphomas. NOD/SCID mice engrafted with human CD34(+) cells and reconstituted mainly with human B lymphocytes may serve as a useful xenograft model to study EBV infection and pathogenesis. We therefore infected reconstituted mice with EBV. High levels of viral DNA were detected in the peripheral blood of all infected mice. All infected mice lost weight and showed decreased activity levels. Infected mice presented large visible tumors in multiple organs, most prominently in the spleen. These tumors stained positive for human CD79a, CD20, CD30, and EBV-encoded RNAs and were light chain restricted. Their characterization is consistent with that of large cell immunoblastic lymphoma. In addition, tumor cells expressed EBNA1, LMP1, and LMP2a mRNAs, which is consistent with a type II latency program. EBV(+) lymphoblastoid cell lines expressing human CD45, CD19, CD21, CD23, CD5, and CD30 were readily established from the bone marrow and spleens of infected animals. Finally, we also demonstrate that infection with an enhanced green fluorescent protein (EGFP)-tagged virus can be monitored by the detection of infected EGFP(+) cells and EGFP(+) tumors. These data demonstrate that NOD/SCID mice that are reconstituted with human CD34(+) cells are susceptible to infection by EBV and accurately recapitulate important aspects of EBV pathogenesis.

Epstein–Barr virus-related plasmablastic lymphomas arising from long-standing sacrococcygeal cysts in immunosuppressed patients

Epstein–Barr virus-related plasmablastic lymphomas arising from long-standing sacrococcygeal cysts in immunosuppressed patients

Painless erythema of the hands associated with non-Hodgkin's lymphoma in a lung transplant recipient

Acral erythema limited to the fingers or the hands has been described in systemic disease. We report the case of a 17-year-old patient who had undergone lung transplantation for cystic fibrosis. Six weeks after transplantation, rapidly growing large-cell immunoblastic non-Hodgkin's lymphoma of the lungs and mediastinum was diagnosed. Sharply demarcated, painless, glovelike erythema was found on both hands. Therapy was reduction of immunosuppression and 12 cycles of extracorporeal photophoresis. After 4 months, lymphoma was in clinical and radiologic remission. Bilateral erythema of the hands also had disappeared. Acral erythema has been reported in association with chemotherapy, collagen vascular disease, infections as with HIV, hepatitis C virus, parvovirus B19, or cytomegalovirus. None of the described associations were detected in this case. (J Am Acad Dermatol 2002;46:S159-60.)

Radiation therapy after a partial response to CHOP chemotherapy for aggressive lymphomas

Purpose: To analyze the results with involved-field radiotherapy after aggressive lymphomas had decreased in size by 50–99% in response to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy. Methods and Materials: From 1988 through 1996, 294 previously untreated patients with Working Formulation intermediate-grade or large-cell immunoblastic lymphomas underwent CHOP-based chemotherapy on 2 consecutive protocols at the M. D. Anderson Cancer Center. Forty-four (15%) of these patients achieved, based on international working group guidelines, a partial (50–75%) response ( n = 25), or unconfirmed complete (76–99%) response ( n = 19) to a median of 6 cycles of chemotherapy. These patients were treated with salvage involved-field radiotherapy ( n = 32) or chemotherapy ( n = 12), e.g., MINE-ESHAP, without autologous stem-cell rescue (ASCR). Results: Median follow-up was 43 months. Partial responders experienced similar outcomes to unconfirmed complete responders. Local control (4-year rates: 86% vs. 53%, p = 0.009) and progression-free survival (4-year rates: 67% vs. 8%, p < 0.0001), but not overall survival (4-year rates: 70% vs. 50%, p = 0.067) were significantly better in those who received salvage radiotherapy, which was well tolerated. Conclusion: Progression-free and overall survival in aggressive lymphoma patients who underwent salvage radiotherapy were similar to results reported for high-dose chemotherapy with ASCR. The role of salvage radiotherapy in partial and unconfirmed complete responders to CHOP chemotherapy justifies examination in a large, cooperative group trial.

Dose-response analysis for radiotherapy delivered to patients with intermediate-grade and large-cell immunoblastic lymphomas that have completely responded to CHOP-based induction chemotherapy

Purpose: To test the hypothesis that prechemotherapy tumor size affects the dose of radiation that should be delivered to intermediate-grade and large-cell immunoblastic lymphomas that have completely responded to cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)-based induction chemotherapy. Methods and Materials: From September 1988 through December 1996, 294 patients with newly diagnosed, Stage I–IV, intermediate-grade or large-cell immunoblastic lymphomas were enrolled on 2 prospective protocols at the M. D. Anderson Cancer Center. Treatment consisted of CHOP-based chemotherapy with or without involved field radiotherapy. One hundred seventy-two patients, with 178 nodal sites and 87 nonbony, extranodal sites of disease achieved a complete response to 2–6 cycles of chemotherapy and underwent involved field radiotherapy. Total radiation doses ranged from 30.0 to 50.4 Gy (mean ± standard deviation: 39.7 ± 2.5 Gy) over 22–49 days using a daily fraction size of 1.3–2.3 Gy. Because various fraction sizes were delivered, the linear-quadratic model was used to convert total radiation doses to biologically equivalent doses given at 1.8 Gy per fraction (D1.8). An α/β ratio of 10 Gy was used for the lymphomas, resulting in D1.8 ranging from 29.1 to 50.8 Gy. Regression tree analysis was performed on nodal sites of disease to determine which of the following factors were predictive of local control: age, tumor size, D1.8, total radiation dose, and duration of radiotherapy. Based on the results of the regression tree analysis, Kaplan-Meier analysis was used to determine the probability of local control per site as a function of tumor size and D1.8. Regression tree analysis was also performed on patients with nonbony disease who received D1.8 = 29.1–39.1 Gy to determine if small lymphomas could be locally controlled with relatively low doses of radiation. The log-rank test was used to compare local control curves. Results: The median length of follow-up among survivors was 63 months. Regression tree analysis of nodal sites identified 3 distinct groups: (a) lymphomas ≤ 10 cm and D1.8 = 29.1–39.1 Gy; (b) lymphomas ≤ 10 cm and D1.8 = 39.2–50.8 Gy; and (c) lymphomas > 10 cm. For nonbony lymphomas that measured < 3.5 cm, low doses of radiation resulted in excellent local control (5-year rates: 96% vs. 97% for D1.8 = 29.1–39.1 Gy vs. D1.8 = 39.2–50.8 Gy; p = 0.610). For 3.5–10.0 cm lymphomas, higher doses of radiation resulted in better local control (5-year rates: 40% versus 98% for D1.8 = 29.1–39.1 Gy versus D1.8 = 39.2–50.8 Gy, p < 0.0001). A narrow dose range (D1.8 = 39.2–40.7 Gy) was delivered to the 8 lymphomas measuring > 10 cm that completely responded to 6 cycles of chemotherapy, resulting in a 5-year local control rate of only 70%. There was no difference in local control for nodal versus nonbony, extranodal sites of disease. Conclusion: D1.8 ranging from 29.1 to 39.1 Gy yielded excellent local control for nonbony lymphomas measuring < 3.5 cm that had completely responded to a median of 3 cycles of CHOP-based chemotherapy. D1.8 ranging from 39.2 to 50.8 Gy yielded excellent local control for nonbony lymphomas measuring 3.5–10.0 cm that completely responded to either 3 or 6 cycles of chemotherapy. For nonbony lymphomas measuring > 10 cm that completely responded to 6 cycles of chemotherapy, D1.8 ranging from 39.2 to 40.7 Gy yielded suboptimal local control, suggesting that higher doses of radiation are indicated.

155 oral International prognostic index-based outcomes in patients with intermediate grade and large-cell immunoblastic lymphomas

155 oral International prognostic index-based outcomes in patients with intermediate grade and large-cell immunoblastic lymphomas