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Biomedical subjects

E S Jaffe

Publications and source records attributed to E S Jaffe.

At least 55 records · Page 3Linked to original sources
PubMed1999

Angiogenesis and hematopoiesis induced by Kaposi's sarcoma-associated herpesvirus-encoded interleukin-6.

Kaposi's sarcoma-associated herpesvirus (KSHV; also known as human herpesvirus 8 [HHV-8]) is a herpesvirus linked to the development of Kaposi's sarcoma (KS), primary effusion lymphoma, and a proportion of Castleman's disease. KSHV encodes viral interleukin-6 (vIL-6), which is structurally homologous to human and murine IL-6. The biological activities of vIL-6 are largely unknown. To gain insight into the biology of vIL-6, we expressed vIL-6 in murine fibroblasts NIH3T3 cells and inoculated stable vIL-6-producing clones into athymic mice. vIL-6 was detected selectively in the blood of mice injected with vIL-6-expressing clones. Compared with controls, vIL-6-positive mice displayed increased hematopoiesis in the myeloid, erythroid, and megakaryocytic lineages; plasmacytosis in spleen and lymph nodes; hepatosplenomegaly; and polyclonal hypergammaglobulinemia. vIL-6-expressing NIH3T3 cells gave rise to tumors more rapidly than did control cells, and vIL-6-positive tumors were more vascularized than controls. Vascular endothelial growth factor (VEGF) was detected at higher levels in the culture supernatant of vIL-6-expressing cells compared with controls, and immunohistochemical staining detected VEGF in spleen, lymph nodes, and tumor tissues from mice bearing vIL-6-producing tumors but not control tumors. Thus, vIL-6 is a multifunctional cytokine that promotes hematopoiesis, plasmacytosis, and angiogenesis. Through these functions, vIL-6 may play an important role in the pathogenesis of certain KSHV-associated disorders.

3T3 Cells↗
PubMed1999

Differential chemokine expression in tissues involved by Hodgkin's disease: direct correlation of eotaxin expression and tissue eosinophilia.

Hodgkin's disease (HD) is a lymphoid malignancy characterized by infrequent malignant cells surrounded by abundant inflammatory cells. In this study, we examined the potential contribution of chemokines to inflammatory cell recruitment in different subtypes of HD. Chemokines are small proteins that are active as chemoattractants and regulators of cell activation. We found that HD tissues generally express higher levels of interferon-gamma-inducible protein-10 (IP-10), Mig, RANTES, macrophage inflammatory protein-1alpha (MIP-1alpha), and eotaxin, but not macrophage-derived chemotactic factor (MDC), than tissues from lymphoid hyperplasia (LH). Within HD subtypes, expression of IP-10 and Mig was highest in the mixed cellularity (MC) subtype, whereas expression of eotaxin and MDC was highest in the nodular sclerosis (NS) subtype. A significant direct correlation was detected between evidence of Epstein-Barr virus (EBV) infection in the neoplastic cells and levels of expression of IP-10, RANTES, and MIP-1alpha. Levels of eotaxin expression correlated directly with the extent of tissue eosinophilia. By immunohistochemistry, IP-10, Mig, and eotaxin proteins localized in the malignant Reed-Sternberg (RS) cells and their variants, and to some surrounding inflammatory cells. Eotaxin was also detected in fibroblasts and smooth muscle cells of vessels. These results provide evidence of high level chemokine expression in HD tissues and suggest that chemokines may play an important role in the recruitment of inflammatory cell infiltrates into tissues involved by HD.

Adult↗
PubMed1999

Primary follicular lymphoma of the testis in childhood.

BACKGROUND: Follicular lymphoma in childhood is rare. The authors present four unusual primary follicular lymphomas of the testis in children. METHODS: Tumor tissue was evaluated using light microscopy, immunohistochemistry, flow cytometry, and polymerase chain reaction (PCR) for immunoglobulin heavy chain (IgH) and bcl-2 gene rearrangements. Southern blot and immunohistochemical analyses were used to detect bcl-6 gene rearrangements and protein expression, respectively. RESULTS: Four young boys ranging in age from 3 to 10 years were diagnosed with Stage IE follicular large cell lymphoma (Grade 3). A B-cell phenotype was documented in all four cases; monoclonality was confirmed in three cases by demonstration of light chain restriction or clonal IgH gene rearrangement. None of the lymphomas expressed Bcl-2 or p53 protein, and bcl-2 gene rearrangements were not found in the three lymphomas studied. In contrast, Bcl-6 protein was expressed by all three lymphomas studied, and a bcl-6 gene rearrangement was detected in the one case analyzed by Southern blot. All four boys were treated by orchiectomy and combination chemotherapy and are alive with no evidence of disease 18-44 months following their initial diagnoses. CONCLUSIONS: Follicular lymphomas may rarely occur as primary testicular tumors in prepubertal boys and, when localized, appear to be associated with a favorable prognosis. In contrast to follicular lymphoma in adults, pediatric follicular lymphomas of the testis are usually of large cell type (Grade 3) and lack bcl-2 or p53 abnormalities. The identification, in one case, of a bcl-6 gene rearrangement suggests an alternate molecular pathogenesis for pediatric follicular lymphoma.

Child↗
PubMed1999

A study of adult T-cell leukemia/lymphoma incidence in central Brooklyn.

Adult T-cell leukemia/lymphoma (ATL), a rare outcome of infection with human T-lymphotropic virus (HTLV-I), is endemic in central Brooklyn, which has a large Caribbean migrant population. Previous studies have suggested that HTLV-I prevalence in central Brooklyn may be similar to that recorded in the Caribbean islands. We established a pilot 1-year surveillance program to identify cases of ATL in 7 of 10 hospitals serving the residents of 18 zip codes of central Brooklyn with a combined population of 1,184,670. Of the 6,198 in-patient beds in the catchment area, approximately 83% were covered. Twelve incident cases of ATL were ascertained, all among persons of Afro-Caribbean descent, indicating an annual incidence in African-Americans in this community of approximately 3.2/100,000 person-years. Unexplained hypercalcemia was the most useful screening method, identifying 3 of 5 patients not referred for possible ATL by a local hematologist. The female:male ratio was 3:1. The age pattern was different from that reported in the Caribbean Basin and closer to the pattern seen in Japan. Our study supports evidence that HTLV-I infection and ATL are endemic in central Brooklyn and suggests that a more intensive surveillance program for this disease coupled with intervention efforts to reduce HTLV-I transmission are warranted.

Adult↗
PubMed1999

Expression of potentially oncogenic HHV-8 genes in an EBV-negative primary effusion lymphoma occurring in an HIV-seronegative patient.

Primary effusion lymphoma (PEL) is a novel lymphoproliferative disorder associated with human herpesvirus 8 (HHV-8) infection. Most PELs develop in HIV-seropositive individuals and are nearly always positive for Epstein-Barr virus (EBV), a finding which obscures the role of HHV-8 in lymphomagenesis. However, rare EBV-negative PEL cases occurring in HIV-seronegative patients have been reported, suggesting that HHV-8 may be pathogenetic by itself. To investigate whether HHV-8 may contribute to PEL development in the absence of EBV, the expression of seven potentially oncogenic HHV-8 open reading frames (ORFs) (ORF72/viral cyclin D, ORF16/viral bcl-2, ORF74/viral G-protein coupled receptor, ORFK2/viral IL-6, ORFK13/viral FLICE inhibitory protein, ORFK9/viral interferon regulatory factor, and ORFK1, equivalent to the gene encoding herpesvirus saimiri transforming protein) was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) in an EBV-negative PEL presenting in an HIV-negative patient. RNA transcripts were demonstrated for the seven HHV-8 genes, and this was confirmed by hybridization to specific oligonucleotide probes. The expression of potentially oncogenic HHV-8 genes in this HIV-, EBV-negative PEL case suggests that HHV-8 may induce malignant transformation of B-lymphocytes through different molecular pathways in the absence of EBV infection.

Gene Expression↗
PubMed1999

Interleukin-18, interferon-gamma, IP-10, and Mig expression in Epstein-Barr virus-induced infectious mononucleosis and posttransplant lymphoproliferative disease.

T cell immunodeficiency plays an important role in the pathogenesis of posttransplant lymphoproliferative disease (PTLD) by permitting the unbridled expansion of Epstein-Barr virus (EBV)-infected B lymphocytes. However, factors other than T cell function may contribute to PTLD pathogenesis because PTLD infrequently develops even in the context of severe T cell immunodeficiency, and athymic mice that are T-cell-immunodeficient can reject EBV-immortalized cells. Here we report that PTLD tissues express significantly lower levels of IL-18, interferon-gamma (IFN-gamma), Mig, and RANTES compared to lymphoid tissues diagnosed with acute EBV-induced infectious mononucleosis, as assessed by semiquantitative RT-PCR analysis. Other cytokines and chemokines are expressed at similar levels. Immunohistochemistry confirmed that PTLD tissues contain less IL-18 and Mig protein than tissues with infectious mononucleosis. IL-18, primarily a monocyte product, promotes the secretion of IFN-gamma, which stimulates Mig and RANTES expression. Both IL-18 and Mig display antitumor activity in mice involving inhibition of angiogenesis. These results document greater expression of IL-18, IFN-gamma, Mig, and RANTES in lymphoid tissues with acute EBV-induced infectious mononucleosis compared to tissues with PTLD and raise the possibility that these mediators participate in critical host responses to EBV infection.

Adolescent↗
PubMed1999

Composite low grade B-cell lymphomas with two immunophenotypically distinct cell populations are true biclonal lymphomas. A molecular analysis using laser capture microdissection.

Low grade B-cell lymphomas comprise several well defined, clinically and immunophenotypically distinct disease entities. Composite lymphomas showing phenotypic characteristics of more than one of these tumor subtypes in the same site are rare, and both common and separate clonal origins of the two tumor parts have been reported for cases studied by molecular methods. We describe the detailed immunohistochemical and molecular findings in three cases with features of composite low grade B-cell non-Hodgkin's lymphoma (B-NHL). All three neoplasms contained morphologically distinct but interwoven compartments of different cell types, which exhibited discordant expression of several markers, including CD5, CD10, CD43, and cyclin D1. According to their morphology and phenotypes, they were classified as mantle cell lymphoma and follicular lymphoma (Case 1), follicular lymphoma and small lymphocytic lymphoma (Case 2), and mantle cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma (Case 3). PCR analysis of DNA obtained from whole tissue sections failed to reveal evidence for biclonality in any of the cases. We therefore isolated cell populations with different antigen expression patterns by laser capture microdissection and analyzed them by polymerase chain reaction amplification and sequencing of clonal immunoglobulin heavy chain gene rearrangements and oncogene rearrangements. Sequence analysis revealed unrelated clonal rearrangements in each of the two tumor parts in all three cases, suggesting distinct clonal origins. In addition, Case 1 showed a bcl-2 rearrangement present only in the follicular lymphoma part. Our findings suggest that low grade B-NHL with two distinct morphological and immunophenotypic patterns in the same anatomical site are frequently biclonal. This is in keeping with current classification schemes, which recognize subtypes of low grade B-NHL as separate disease entities. Furthermore, our analysis demonstrates the power of laser capture microdissection in revealing molecular microheterogeneity in complex neoplasms.

Aged↗
PubMed1999

The World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues. Report of the Clinical Advisory Committee meeting, Airlie House, Virginia, November, 1997.

INTRODUCTION: Since 1995, the European Association of Pathologists (EAHP) and the Society for Hematopathology (SH) have been developing a new World Health Organization (WHO) Classification of hematologic malignancies. The classification includes lymphoid, myeloid, histiocytic, and mast cell neoplasms. DESIGN: The WHO project involves 10 committees of pathologists, who have developed lists and definitions of disease entities. A Clinical Advisory Committee (CAC)) of international hematologists and oncologists was formed to ensure that the classification will be useful to clinicians. A meeting was held in November, 1997, to discuss clinical issues related to the classification. RESULTS: The WHO has adopted the 'Revised European American Classification of Lymphoid Neoplasms' (R.E.A.L.), published in 1994 by the International Lymphoma Study Group (ILSG), as the classification of lymphoid neoplasms. This approach to classification is based on the principle that a classification is a list of 'real' disease entities, which are defined by a combination of morphology, immunophenotype, genetic features, and clinical features. The relative importance of each of these features varies among diseases, and there is no one 'gold standard'. The WHO Classification has applied the principles of the R.E.A.L. Classification to myeloid and histiocytic neoplasms. The classification of myeloid neoplasms recognizes distinct entities defined by a combination of morphology and cytogenetic abnormalities. The CAC meeting, which was organized around a series of clinical questions, was able to reach a consensus on most of the questions posed. The questions and the consensus are discussed in detail below. Among other things, the CAC concluded that clinical groupings of lymphoid neoplasms were neither necessary nor desirable. Patient treatment is determined by the specific type of lymphoma, with the addition of grade within the tumor type, if applicable, and clinical prognostic factors such as the international prognostic index (IPI). CONCLUSION: The experience of developing the WHO Classification has produced a new and exciting degree of cooperation and communication between oncologists and pathologists from around the world, which should facilitate progress in the understanding and treatment of hematologic malignancies.

Hematologic Neoplasms↗
PubMed1999

Complete molecular remissions induced by patient-specific vaccination plus granulocyte-monocyte colony-stimulating factor against lymphoma.

Lymphomas express a tumor-specific antigen which can be targeted by cancer vaccination. We evaluated the ability of a new idiotype protein vaccine formulation to eradicate residual t(14;18)+ lymphoma cells in 20 patients in a homogeneous, chemotherapy-induced first clinical complete remission. All 11 patients with detectable translocations in their primary tumors had cells from the malignant clone detectable in their blood by PCR both at diagnosis and after chemotherapy, despite being in complete remission. However, 8 of 11 patients converted to lacking cells in their blood from the malignant clone detectable by PCR after vaccination and sustained their molecular remissions. Tumor-specific cytotoxic CD8+ and CD4+ T cells were uniformly found (19 of 20 patients), whereas antibodies were detected, but apparently were not required for molecular remission. Vaccination was thus associated with clearance of residual tumor cells from blood and long-term disease-free survival. The demonstration of molecular remissions, analysis of cytotoxic T lymphocytes against autologous tumor targets, and addition of granulocyte-monocyte colony-stimulating factor to the vaccine formulation provide principles relevant to the design of future clinical trials of other cancer vaccines administered in a minimal residual disease setting.

Adult↗
PubMed1999

Allelic loss of 11q13 as detected by MEN1-FISH is not associated with mutation of the MEN1 gene in lymphoid neoplasms.

Deletions and rearrangements involving the long arm of chromosome 11 are not infrequent occurrences in the non-Hodgkin's lymphomas. Recently, a tumor suppressor gene, the multiple endocrine neoplasia type 1 gene (MEN1) was cloned and mapped to chromosome 11q13. To assess the potential involvement of this gene in lymphomagenesis, we examined 94 primary cases of lymphoma and 12 cell lines by a combination of fluorescent in situ hybridization and PCR-SSCP analysis. In our initial analysis of 41 primary B or T lymphomas, MEN1 FISH analysis revealed allelic deletions in 15 cases (three of four B cell chronic lymphocytic leukemias, six of 15 follicular lymphomas, three of nine diffuse large B cell lymphomas, two of five mantle cell lymphomas, one of four Burkitt's lymphoma). To discern whether the MEN1 gene was in fact the target of the deletions, we assessed 20 of these 41 cases and an additional 74 primary lymphomas and 12 cell lines for MEN1 gene mutations using PCR-SSCP analysis. Abnormal SSCP patterns were found in exon 2 in two of the primary lymphoma cases and in one of the cell lines, but not in any of the original cases that showed MEN1 deletions by FISH. Furthermore, sequencing analysis revealed that the abnormal SSCP patterns in exon 2 were the result of a previously described genetic polymorphism (S145S: AGC --> ACT), and in one sample, the result of this S145S polymorphism associated with a second nucleotide substitution at position 498 which left the encoded amino acid unchanged. Our study indicates that the 11q13 locus is a frequent target of deletion in lymphoid neoplasms, but that there are no associated mutations of the MEN1 gene. This suggests that the 11q deletions either target another gene in lymphomas, or that the MEN1 gene is inactivated through means other than mutation.

Amino Acid Substitution↗
PubMed1999

The revised European-American Classification of Lymphoid Neoplasms (REAL): a preferred approach for the classification of cutaneous lymphomas.

The Revised European-American Classification of Lymphoid Neoplasms (REAL) classification is based on the principle that each type of lymphoma is a distinct disease defined by morphology, immunophenotypic and genetic features, clinical presentation, and course. If either primary or secondary involvement of the skin is a constant factor, this aspect is considered integral to disease definition. Organ-specific classification schemes, such as that proposed by the European Organization for Research and Treatment of Cancer (EORTC) for cutaneous lymphomas, are not required, and indeed may impede the recognition of common features of diseases involving multiple anatomic sites. The use of multiple classification systems is a step backward, and may lead to confusion among hematologists/oncologists and dermatologists. Nevertheless, cutaneous lymphomas in many instances are distinct. Their natural history is often more indolent than nodal lymphomas, and for that reason they often require different therapeutic approaches. We agree with the efforts of the EORTC classification to emphasize the unique clinical aspects of many cutaneous lymphomas, as this recognition is essential for appropriate clinical management. As has been learned for nodal lymphomas, clinical features play an important role in prognosis and should be used in guiding therapy. For cutaneous lymphomas, the presence or absence of systemic spread is particularly important.

Hodgkin Disease↗
PubMed1999

Primary nodal marginal zone lymphomas of splenic and MALT type.

The existence of primary nodal marginal zone lymphomas (MZL) is controversial, as is their relationship to putative extranodal counterparts. Most nodal lymphomas with monocytoid B cell/marginal zone differentiation exhibit the morphologic and immunophenotypical characteristics of extranodal MALT-lymphomas. Splenic marginal zone lymphoma (SMZL) is also of putative marginal zone derivation, but it differs immunophenotypically from MALT lymphoma. To clarify the relationship between nodal and extranodal MZLs and to investigate the possible existence of a nodal variant of SMZL, 36 MZL initially considered to be primary nodal neoplasms were examined. Other low-grade lymphomas with marginal zone differentiation were excluded (small lymphocytic lymphoma/chronic lymphocytic leukemia [SLL/CLL], follicular lymphoma, and mantle cell lymphoma). Six nodal MZLs showed morphologic and phenotypic characteristics similar to those of SMZL, whereas 30 tumors were more similar to MALT-type lymphomas. The six tumors with SMZL features showed a polymorphic infiltrate surrounding residual germinal centers with absent or very attenuated mantle cuffs. These lymphomas were IgD positive (6/6) but cyclin D1 (0/5), CD5 (0/6), and CD23 (0/6) negative. Five of these patients came for treatment in stage I or II. No patient manifested splenomegaly, peripheral blood, and/or bone marrow infiltration either at diagnosis or during follow-up. Lymph nodes from 30 patients with MALT-type features showed a perisinusoidal and perivascular infiltration of monocytoid/centrocytoid cells and residual germinal centers with a relatively well-preserved mantle cuff. The neoplastic cells were negative for IgD (0/17), cyclin D1 (0/8), and CD5 (0/12). Seven of 16 (44%) patients with a detailed history and clinical follow-up had evidence of extranodal lymphoma. These observations suggest that most nodal B cell lymphomas with marginal zone differentiation are of the MALT type and that they are frequently associated with an extranodal component. In addition, a primary nodal counterpart of splenic MZL also exists, and may occur in the absence of splenomegaly.

Adult↗
PubMed1999

Lymphoproliferative disorder of fetal origin presenting as oligohydramnios.

Lymphoma involving the placenta or fetus remains a very rare event. All cases reported to date have shown the lymphoma cells to be of maternal origin in that the tumor cells have preferentially involved the intervillous spaces with sparing of the villi and fetal circulation. We report a novel case of a monoclonal primary placental Epstein-Barr virus (EBV)-associated B-cell lymphoma of fetal origin. The placenta of a 20-week stillborn fetus born to a 19-year-old gravida 1 para 0 woman, presenting with oligohydramnios, showed a large cell infiltrate confined within villi and sparing the intervillous spaces, indicative of preferential involvement of the fetal circulation. Necropsy did not show any other site of involvement by malignant lymphoma or other abnormalities. Immunophenotypic studies showed the tumor cells to be of B-cell phenotype with a relatively high proliferation rate. EBV EBER1 RNA was identified in more than 95% of tumor cells, and polymerase chain reaction studies showed EBV EBNA1 strain type A and wildtype EBV LMP1. Analysis of the immunoglobulin heavy chain by polymerase chain reaction showed a monoclonal B-cell population. In situ hybridization studies using a commercially available probe directed at repeated sequences on the human Y chromosome showed a single intense signal within trophoblastic epithelium and lymphoma cells, indicative of male origin. The mother remains in good health 11 months after delivery.

Diagnosis, Differential↗
PubMed1999

Peripheral T-cell lymphoma with Reed-Sternberg-like cells of B-cell phenotype and genotype associated with Epstein-Barr virus infection.

We report three cases of nodal peripheral T-cell lymphoma (PTCL) with Reed-Sternberg-like (RS-like) cells of B-cell pheno- and/or genotype. Histologic analysis in all cases revealed diffuse nodal effacement by atypical lymphoid cells of variable size. Two of the three cases had features of angioimmunoblastic T-cell lymphoma (AILT). Large mononuclear and binucleated cells with prominent eosinophilic nucleoli and abundant cytoplasm resembling classic RS cells and mononuclear variants were scattered throughout all biopsies. The lymphoma cells in the three cases were of T-cell lineage (CD3+, CD43+, and CD45RO+). The RS-like cells from all cases were CD30 and CD15 positive. In contrast to the neoplastic T cells, the RS-like cells lacked all T-cell markers and in two cases were positive for CD20. Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) and EBER 1 (2/2) were detected in the RS-like cells in all cases. The neoplastic T cells were negative for EBV. Polymerase chain reaction (PCR) analysis demonstrated clonal rearrangements of the T-cell receptor gamma chain gene in the three cases. PCR analysis of microdissected RS-like cells for immunoglobulin heavy chain gene rearrangements in cases 1 and 3 showed an oligoclonal pattern. The presence of RS-like cells in PTCL represents a diagnostic pitfall, because in one case this observation led to a misdiagnosis of Hodgkin's disease (HD). The oligoclonal expansion of EBV-infected cells may be related to underlying immunodeficiency associated with T-cell lymphomas and AILT in particular. This phenomenon may provide the basis for some cases of Hodgkin's disease after T-cell lymphomas and suggests that they are clonally unrelated neoplasms. The expression of LMP1 appears to be crucial for the immunophenotype and probably for the morphology of the RS and RS-like cells appearing in diverse lymphoid malignancies, including HD, chronic lymphocytic leukemia, and PTCL.

Aged↗
PubMed1999

Autoimmune lymphoproliferative syndrome: a syndrome associated with inherited genetic defects that impair lymphocytic apoptosis--CT and US features.

PURPOSE: To describe the imaging findings in patients with autoimmune lymphoproliferative syndrome (ALPS) and to relate the findings to the clinical and genetic features of this recently recognized syndrome. MATERIALS AND METHODS: Retrospective or prospective reviews of the computed tomographic (CT) and ultrasonographic (US) studies and the clinical features in 19 consecutive patients with ALPS were performed. RESULTS: Most patients presented in the 1st year of life with symptoms of adenopathy and hepatosplenomegaly. At the time of presentation to the institution, 12 patients had already undergone splenectomy, and 14 patients had developed autoimmune disorders. All patients had multifocal adenopathy, which was massive in some patients; 14 of 15 patients who underwent CT of the chest had an enlarged thymus, and all six patients who retained their spleens and who underwent imaging had splenomegaly. Ten of 18 patients who underwent liver imaging had hepatomegaly. The adenopathy at US was hyper- and/or isoechoic relative to the liver and thyroid and was enhanced at CT in some patients. All patients had defective lymphocytic apoptosis, or programmed cell death, which was due to specific Fas (APT1 [TNFRSF6]) mutations in 15 patients. CONCLUSION: Patients with ALPS demonstrate nonspecific but often dramatic imaging findings of lymphoproliferative disorders, such as adenopathy, splenomegaly, thymic enlargement, and hepatomegaly. The stability of the clinical findings over months to years and the pattern of lymph node echogenicity may suggest the diagnosis of ALPS.

Adolescent↗
PubMed1999

Increased incidence of Hodgkin's disease after allogeneic bone marrow transplantation.

PURPOSE: Immune dysregulation associated with allogeneic bone marrow transplantation (BMT) is linked to an increased risk of posttransplant lymphoproliferative disorders (PTLD); however, reports of Hodgkin's disease (HD) after transplantation are rare. PATIENTS AND METHODS: We evaluated the risk of HD among 18,531 persons receiving allogeneic BMT between 1964 and 1992 at 235 centers. The number of HD cases was compared with that expected in the general population. Risk factors were identified using Poisson regression and a nested case-control study. RESULTS: Risk of HD was increased in the postBMT population compared with the general population with an observed-to-expected incidence ratio (O/E) of 6.2 (observed cases, n = 8; 95% confidence interval [CI], 2.7 to 12). A significantly increased risk of HD remained after excluding two human immunodeficiency virus-positive patients (observed cases, n = 6; O/E = 4.7, 95% CI, 1.7 to 10.3). Mixed cellularity subtype predominated (five of eight cases, 63%). Five of six assessable cases contained Epstein-Barr virus (EBV) genome. Posttransplant HD differed from PTLD by later onset (> 2.5 years) and lack of association with established risk factors (such as T-cell depletion and HLA disparity). Patients with HD were more likely than matched controls to have had grade 2 to 4 acute graft-versus-host disease (GVHD), required therapy for chronic GVHD, or both (P =.002), although analysis included small numbers of patients. CONCLUSION: The increased incidence of HD among BMT recipients adds support to current theories which link overstimulation of cell-mediated immunity and exposure to EBV with various subtypes of HD. The long latency of HD after transplant and lack of association with risk factors for PTLD is noteworthy and should be explored further for possible insights into pathogenesis.

Adolescent↗