Splenic rupture in a patient with plasma cell myeloma following G-CSF/GM-CSF administration for stem cell transplantation and review of the literature.

Recipients of granulocyte-colony stimulating factor/granulocyte macrophage-colony stimulating factor are not only individuals with underlying disorders, but also healthy donors undergoing peripheral blood progenitor cell (PBPC) mobilization. In addition to the known adverse effects associated with G-CSF, complications such as splenic rupture have also been reported. A review of the English literature, with addition of a patient with plasma cell myeloma, reveals that splenic rupture occurs not only in patients with underlying disease, but also in healthy PBPC donors. Although the cause of splenic rupture does not appear to be associated with any specific condition, physicians should be alerted to the possibility of this potentially fatal complication in individuals receiving G-CSF therapy.

Phase I/II trial of total lymphoid irradiation and high-dose chemotherapy with autologous stem-cell transplantation for relapsed and refractory Hodgkin's lymphoma.

BACKGROUND: The standard approach to treatment of relapsed/refractory Hodgkin's lymphoma (HL) is high-dose chemotherapy conditioning followed by autologous hematopoietic stem-cell transplantation (aHSCT). We report the results of a prospective phase I/II clinical trial of accelerated hyperfractionated total lymphoid irradiation (TLI) immediately followed by high-dose chemotherapy for relapsed/refractory HL. PATIENTS AND METHODS: Forty-eight patients underwent aHSCT with either sequential TLI/chemotherapy (n = 32) or chemotherapy-alone conditioning (n = 16), based on prior radiation exposure. The first 22 patients enrolled on trial received escalating doses of etoposide (1600-2100 mg/m(2)) with high-dose carboplatin and cyclophosphamide. RESULTS: No dose-limiting toxicity was seen and TLI/chemotherapy was well tolerated. The 5-year event-free survival (EFS) estimate for all patients was 44% with overall survival (OS) of 48%. Five-year EFS and OS for the TLI/chemotherapy group was 63% and 61%, respectively, compared with 6% and 27%, respectively, for the chemotherapy-alone group (P < 0.0001 and P = 0.04, respectively). Patients with primary induction failure HL who received TLI/chemotherapy had 5-year EFS and OS rate of 83%. The 100-day treatment-related mortality was 4.2% and two secondary cancers were seen. Significant factors predicting survival by multivariate analysis included TLI/chemotherapy conditioning and B symptoms at relapse. CONCLUSIONS: Sequential TLI/chemotherapy conditioning for relapsed/refractory HL is safe and associated with excellent long-term survival rates.

Histologic criteria for the diagnosis of mycosis fungoides: proposal for a grading system to standardize pathology reporting.

BACKGROUND: The histological diagnosis of early lesions of mycosis fungoides (MF) is often difficult for dermatopathologists and prior studies have shown a low agreement rate among pathologists. An important reason for such difficulty may be the lack of specific histological criteria. METHODS: We tested a new method to interpret and report biopsies suspicious for MF. The method is based on a grading system reflecting the pathologist's degree of diagnostic certainty. A panel of four pathologists independently assessed a set of 50 biopsies suspicious for MF first without (Phase I) and subsequently with specific histological criteria (Phase II). A third Phase was carried out after a training session, using a new set of cases with corresponding immunophenotyping and gene rearrangement analysis. Weighted and unweighted kappa statistics were used to assess inter- and intra-pathologist variation. RESULTS: The consensus rate among pathologists improved from 48% in Phase I to 76% in Phase III. Overall precision weighted kappas increased from 0.630 in Phase I to 0.854 in Phase III, indicating excellent inter-pathologist agreement by Phase III. There was a significant association between the presence of an abnormal phenotype and/or T-cell clonality and a higher diagnostic score. CONCLUSIONS: The use of uniform criteria and training sessions can substantially improve the consensus rate among pathologists in the diagnosis of MF.

Serum sCD23 level in patients with AIDS-related non-Hodgkin's lymphoma is associated with absence of Epstein-Barr virus in tumor tissue.

The cytokine soluble CD23 (sCD23) acts as a B cell growth factor and is associated with Epstein-Barr virus (EBV) infection. To elucidate the role sCD23 might play in the pathogenesis of AIDS-related non-Hodgkin's lymphoma (AIDS NHL), 101 AIDS NHL patients from the Multicenter AIDS Cohort Study were studied. Serum sCD23 within 18 months prior to lymphoma diagnosis was measured for all patients and EBV in tumor tissue was ascertained for 49 patients. Tumor morphology and primary site were verified from pathology reports and tumor specimens. Bivariate tests and multivariate regression were employed to determine whether serum sCD23 correlated with tumor EBV, morphology, and primary site. Higher levels of serum sCD23 were associated with the absence of tumor EBV and with small noncleaved cell morphology. Thus, the serum sCD23 level does not appear to be mediated by EBV in these patients, but could be related to a pathogenetic mechanism of small noncleaved cell lymphoma.

Serum soluble CD23 level correlates with subsequent development of AIDS-related non-Hodgkin's lymphoma.

The cytokine soluble CD23 (sCD23) has been shown to act as a B cell growth factor and to be elevated in serum prior to development of AIDS-related non-Hodgkin's lymphoma (AIDS NHL). To further characterize the elevation of serum sCD23 in AIDS NHL patients and investigate its potential as a diagnostic test, a matched case-control study of AIDS NHL (n = 101) was nested within the Multicenter AIDS Cohort Study. Serum sCD23 was measured in cases' and controls' serum specimens at three different time periods (0-6, 6-12, and 12-18 months) and CD4+ thresholds (0-99, 100-199, and 200-299 cells/microl) prior to the case's NHL diagnosis. Changes in serum sCD23 over time were examined in AIDS NHL cases relative to controls, and t tests were performed to determine whether cases' serum sCD23 exceeded that of controls at each time period and CD4+ threshold. Overall, cases' median serum sCD23 levels were approximately double those of controls. Serum sCD23 concentration was positively correlated with lymphocyte counts for both cases and controls. The difference in cases' and controls' serum sCD23 levels became greater as AIDS NHL diagnosis date approached: in the 18 months preceding the case's NHL diagnosis, serum sCD23 was stable in cases but dropped in controls. Although this difference was statistically significant (P < 0.05), it was not clinically significant. It is unlikely that serum sCD23 would make a useful test for AIDS NHL because the magnitude of the difference between cases and controls was small and there was no change in serum sCD23 in cases that would indicate disease.

Cutaneous CD8 T cell infiltrates in advanced HIV infection.

BACKGROUND: Aggressive non-Hodgkin's lymphomas are common among patients infected with HIV. Although such lymphomas are mostly of the B-cell type, various cases of cutaneous T-cell lymphoma (CTCL) have also been reported. Recent reports suggest that some HIV-related lymphoproliferative conditions may not be clonal processes, but polyclonal lymphoid proliferations. OBJECTIVE: We reviewed our experience with HIV patients seen at the dermatology clinics for possible CTCL. METHODS: A retrospective study was performed to evaluate clinical, laboratory, and histologic findings of HIV-infected patients with atypical T-cell cutaneous infiltrates. RESULTS: We observed 9 patients with advanced HIV infection and a cutaneous eruption characterized by a dense infiltrate of lymphocytes resembling mycosis fungoides histopathologically, but composed of CD8(+) cells. Although clonality was not identified in any of the 6 cases tested, 3 patients had similar CD8(+) infiltrates involving lymph nodes or bone marrow. Of the 9 patients, 8 died of AIDS wasting syndrome or infections in less than 1 year. CONCLUSION: Cutaneous and systemic infiltrates with polyclonal CD8 T lymphocytes can be seen in patients with advanced HIV infection and profound CD4 lymphopenia. The clinical presentation may resemble CTCL and is associated with a poor outcome.

CD10 antigen expression correlates with the t(14;18)(q32;q21) major breakpoint region in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a common morphologic term for a biologically diverse group of lymphomas. The chromosome translocation, t(14;18)(q32;q21), and its associated bcl-2 gene rearrangement are generally associated with follicular lymphomas. Some investigators, however, proposed that the presence of the t(14;18) in DLBCL suggests a possible follicle center cell origin and might correlate with a higher relapse rate after therapy. The CD10 antigen is expressed in a majority of follicular lymphomas but is also seen occasionally in DLBCLs. In this study, we examined 26 DLBCLs for CD10 expression by flow cytometric analysis and tested them for the t(14;18)(q32;q21) major breakpoint region by a polymerase chain reaction-based method. bcl-2 protein expression was analyzed by an immunoperoxidase method. Of the 26 DLBCLs, 9 (35%) were CD10 positive. bcl-2 protein was expressed in 7 (78%) of 9 CD10-positive cases and in 9 (53%) of 17 CD10-negative cases (P = .4). The t(14; 18) translocation was present in 6 (67%) of 9 CD10-positive cases but in only 2 (17%) of 12 CD10-negative cases (P = .03). Five cases did not yield amplifiable DNA for analysis. In summary, no difference in bcl-2 protein expression was seen in CD10-positive versus CD10-negative DLBCLs, but CD10-positive DLBCLs were significantly more likely than CD10-negative DLBCLs to harbor the t(14;18) translocation. This suggests that CD10 might be a marker of follicle center cell origin in DLBCL.

CD5- small B-cell leukemias are rarely classifiable as chronic lymphocytic leukemia.

Expression of the CD5 antigen by neoplastic cells often is considered a diagnostic criterion for B-cell chronic lymphocytic leukemia (B-CLL). However, published series frequently include a number of CD5- cases. We studied the spectrum of CD5- B-cell lymphoproliferative disorders presenting with leukemia involvement and reassessed the prevalence of CD5- B-CLL. We immunophenotyped 192 cases of clonal, small lymphocytic, B-cell disorders involving peripheral blood or bone marrow. Of these, 41 CD5- cases were further analyzed, correlating the immunophenotypic findings with pathologic material and clinical data. Only 3 CD5- cases were classified as CD5- B-CLL. These 3 cases had features unusual for B-CLL, including bright surface immunoglobulin expression, bright CD20 expression, and absence of CD23 expression (2 cases) or Richter syndrome (1 case). The remainder of the CD5- cases consisted of hairy cell leukemia, hairy cell variant, prolymphocytic leukemia, follicular center cell lymphoma, lymphoplasmacytic lymphoma, splenic marginal zone lymphoma (SMZL), small lymphocytic lymphoma with marrow fibrosis, and lymphoma, not further classified. Eight cases remained unclassified, but some displayed features of SMZL. CD5- lymphoproliferative disorders of peripheral blood or bone marrow are unlikely to be CLL and often are classified more appropriately as non-Hodgkin lymphoma in the leukemia phase.

Epstein-Barr virus-infected marmoset cells transfected with c-myc do not form lymphomas in mice with severe combined immunodeficiency.

Epstein-Barr virus (EBV) has been associated with several malignant processes in man, most notably Burkitt lymphoma in previously healthy individuals and lesions resembling large cell non-Hodgkin lymphomas in organ transplant recipients. Mice with the severe combined immunodeficiency phenotype (SCID mice) are exquisitely susceptible to the development of EBV-associated lymphoproliferative lesions following the intraperitoneal (ip) inoculation of EBV-infected human lymphocytes. Recently, we reported that EBV-infected marmoset lymphocytes do not form lymphomas in SCID mice following ip injection, while human lymphocytes infected with the same EBV strains do. On the assumption that the EBV-infected marmoset cells were lacking a factor necessary for tumor formation, we transfected a plasmid containing c-myc into EBV-infected marmoset cells (B95-8, FF41, and W91 cells). Despite expression of the c-myc protein as determined by immunoblot and flow cytometry when probed with a monoclonal antibody, no increase over baseline lesion development was seen in SCID mice inoculated with 5 x 10(6) c-myc-expressing marmoset lymphoblastoid cells. Thus, cells that express c-myc and harbor EBV are not sufficient to form lymphomas in certain immunocompromised hosts.

BCL-2 expression correlates with lower proliferative activity in the intermediate- and high-grade non-Hodgkin's lymphomas: an Eastern Cooperative Oncology Group and Southwest Oncology Group cooperative laboratory study.

An inverse relationship between BCL-2 expression and cell cycle transition has been suggested by recent studies in murine models. To investigate the clinical relevance of these laboratory studies, a group of 116 paraffin-embedded non-Hodgkin's lymphoma (NHL) biopsy specimens (Working Formulation Groups D-H, and J) from a cooperative group study of cellular DNA content were analyzed for the 14;18 translocation using polymerase chain reaction (PCR)-based methods and, if sufficient tissue remained, for BCL-2 and BAX expression by immunohistochemistry. The results of these studies were then compared with the results of the previously performed flow cytometric analysis of ploidy and proliferative activity (S-phase-fraction). BCL-2 expression was inversely associated with proliferative activity (P = .001; n = 41), but there was no association between staining for Bax and %S-phase. Ploidy was not associated with either BCL-2 or BAX expression. The t(14;18) was detected in 21 of the 54 cases in which PCR-amplifiable DNA was recovered; 20 of these occurred at the major breakpoint region and 1 at the minor breakpoint region. High levels of BCL-2 or BAX expression occurred independently of t(14;18). There was no association between t(14;18) and either ploidy or proliferative activity. The inverse relationship between BCL-2 expression and proliferative activity in the intermediate- and high-grade NHLs is consistent with recent studies suggesting that Bcl-2 both retards entry into the cell cycle and inhibits apoptosis.

Long term follow-up and late complications of 2-chlorodeoxyadenosine in previously treated, advanced, indolent non-Hodgkin's lymphoma.

BACKGROUND: The aim of this study was to determine the long term outcome and toxicities after the administration of 2-chlorodeoxyadenosine (2-CdA) to patients with previously treated, advanced, indolent non-Hodgkin's lymphoma (NHL). METHODS: Twenty-two patients (median age, 55 years) with relapsed or refractory low grade NHL (median disease duration, 2.8 years) were treated with 2-CdA by continuous infusion at 0.1 mg/kg/day over 5 or 7 days every 28 days, for a maximum of 6 cycles. RESULTS: The overall response rate was 45%. Two patients (9%) achieved a complete response (CR), 8 patients (36%) achieved a partial response, and 12 patients (55%) had no response. The two patients achieving CR have remained in CR for 46 and 38 months, respectively. Freedom from treatment failure at 24 months was 32%. Overall survival at 24 months was 59%. Three patients developed second malignancies: acute myelogenous leukemia (AML), myelodysplastic syndrome, and a cutaneous lymphoproliferative disorder. Fourteen patients have died after a median follow-up of 28 months (range, 3.9-49.2 months) due to progressive NHL (11 patients), infection (2 patients), and AML (1 patient). CONCLUSIONS: 2-CdA is an active agent for patients with previously treated, advanced, indolent NHL and may result in lasting remissions. Late complications following treatment may include delayed bacterial, fungal, or viral infection. Determination of whether the second malignancies that occurred in three patients reported herein were related to treatment with 2-CdA will require further study.

Prognostic implications of ploidy and proliferative activity in the diffuse, aggressive non-Hodgkin's lymphomas.

The International Index is a powerful predictor of outcome in the aggressive non-Hodgkin's lymphomas that is based solely on clinical features. Proliferative activity (% S-phase) measured by flow cytometry has been reported to have prognostic significance in many series and may represent a biologic correlate of clinical behavior that further defines prognosis. Flow cytometric analysis of cellular DNA content and proliferative activity (% S-phase) was performed on fixed paraffin-embedded biopsy specimens from 242 previously untreated patients with diffuse, aggressive non-Hodgkin's lymphomas entered on phase III intergroup clinical trials. The International Index was calculated for each patient based on stage, lactate dehydrogenase, performance status, number of extranodal sites, and age, as previously reported. The International Index consistently predicted response to therapy (P = .027) and survival (P = .007) in this series. DNA aneuploidy was shown in 57% of cases, but was not predictive of clinical outcome. The median % S-phase was 9.9 (median coefficient of variation, 3.6%), which was highly correlated with mitotic index (P = .0001). Although a trend associating low proliferative activity with good early survival and very high S-phase with a shortened survival was shown, International Index risk was the only significant predictor of survival in the multivariate analysis. Although proliferative activity quantitated by flow cytometric analysis of nuclei extracted from paraffin-embedded specimens is probably predictive of survival, it is a less powerful prognostic indicator than clinical parameters represented by the International Index and provides no additional prognostic information.

Castleman disease presenting as a pelvic mass.

BACKGROUND: To our knowledge, giant lymph node hyperplasia (Castleman disease) may present as a pelvic mass on magnetic resonance imaging (MRI). CASE: A postmenopausal woman with rapidly enlarging leiomyoma uteri was found to have a suspicious left adnexal mass mimicking an ovarian neoplasm on preoperative MRI. At laparotomy, the suspected uterus and normal ovaries were extirpated. In addition, a firm, 4 x 8-cm solid mass within the sigmoid colon mesentery was found and resected. The final histologic diagnosis was Castleman disease. CONCLUSION: Entities such as Castleman disease should be considered when assessing a pelvic mass. Characterization of the origin of pelvic masses can often be difficult, despite sophisticated diagnostic imaging studies such as MRI.

Epstein-Barr virus clonality in lymphomas occurring in patients with rheumatoid arthritis.

OBJECTIVE: A causative role for Epstein-Barr virus (EBV) in the development of lymphoma in patients with rheumatoid arthritis (RA) has been proposed. We investigated the molecular features of EBV-positive diffuse large cell lymphomas in 2 patients with RA. METHODS: Southern blot analysis for immunoglobulin gene rearrangements, terminal repeat analysis for clonality of the EBV genome, and double-labeling of the lymphoma cells by in situ hybridization and immunoperoxidase staining were performed. RESULTS: In both cases, double-labeling studies localized the EBV genome to the malignant B cells. Both neoplasms contained clonal immunoglobulin gene rearrangements and clonal EBV genomes. CONCLUSION: Our data indicate that EBV infection was an early step in the development of these neoplasms. The findings further extend knowledge on the similarity of this subset of lymphomas to posttransplantation lymphomas and emphasize the role of immunosuppression in their genesis.

Leukemogenic potential of adjuvant chemotherapy for early-stage breast cancer: the Eastern Cooperative Oncology Group experience.

PURPOSE: Since large numbers of patients with early-stage breast cancer now receive adjuvant chemotherapy containing cyclophosphamide, a known leukemogenic agent, it is important to determine the risk of secondary acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Therefore, we identified all cases of AML or MDS developing in patients treated on six clinical adjuvant chemotherapy trials conducted by the Eastern Cooperative Oncology Group (ECOG). PATIENTS AND METHODS: The patients population included 2,638 patients with previously untreated primary operable breast cancer entered onto six clinical trials conducted by the ECOG between 1978 and 1987. There are 19,200 persons-years of follow-up study and a mean follow-up duration of 7.3 years. Clinical data were obtained from flow sheets submitted to the ECOG Data Management Office. RESULTS: Of 2,638 patients at risk with 19,200 person-years of follow-up study, three patients developed MDS (two with a characteristic cytogenetic abnormality). Two patients developed acute leukemia; however, one had adult T-cell leukemia associated with human T-lymphotrophic virus type 1 (HTLV-1) and a second patient developed AML after receiving additional cyclophosphamide for metastatic breast cancer. The estimated incidence rate for MDS is three per 19,200 or 16 per 100,000 person-years of follow-up study with a 95 percent confidence interval of three to 46 per 100,000 person-years. If all five patients (three MDS and two acute leukemia) are included, the estimated incidence rate is five per 19,200 or 26 per 100,000 person-years of follow-up study with a 95 percent confidence interval of eight to 61 per 100,000 person-years. CONCLUSION: These data suggest that the risk of secondary AML or MDS among patients with early breast cancer who receive standard-dose cyclophosphamide-containing adjuvant chemotherapy is not much higher than in the general population. However, physicians must remain alert to the possible long-term consequences of alkylating agent and anthracycline-based chemotherapy.

Cladribine in the treatment of relapsed or refractory chronic lymphocytic leukemia.

PURPOSE: Cladribine (2-CdA), a purine analog resistant to adenosine deaminase, has significant activity in a variety of lymphoproliferative diseases. This study was designed to determine the efficacy of 2-CdA in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: Twenty-six patients aged 40 to 88 years (median, 64) who either had relapsed after an initial response or were refractory to conventional chemotherapy with at least an alkylating agent were treated with 2-CdA 0.1 mg/kg/d by continuous intravenous infusion for either 5 or 7 days every 28 days for a maximum of six cycles. RESULTS: No complete remissions (CRs) occurred. Eight of 26 patients (31%) achieved a partial remission (PR). The actuarial median time to progression (TTF) in responding patients is 16 months (range, 6 to 22). The actuarial median survival duration of the responding patients is 12 months (range, 8 to 28). Eight of 26 patients (31%) sustained early toxicity. Seven of these eight patients died before the first reevaluation of infection (n = 3), pericardial tamponade (n = 1), Stevens-Johnson syndrome (n = 1), and stroke (n = 2). No nausea, emesis, alopecia, or renal, hepatic, or cardiac toxicity was observed. CONCLUSION: 2-CdA has activity in patients with relapsed or refractory CLL. However, patients who have received multiple prior regimens that included fludarabine are less likely to respond, and there can be significant morbidity. Treatment of patients with less prior therapy earlier in the natural history of the disease may lead to improved and more durable responses.

Hodgkin's disease associated with chronic lymphocytic leukemia. Eight additional cases, including two of the nodular lymphocyte predominant type.

Several reports of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and of coexisting or subsequent Hodgkin's disease (HD) have raised the question how these two disorders are related. The authors have identified eight new cases of B-cell low-grade lymphoproliferative disorders (LGLPD) and HD. Six of these cases were similar to those previously reported on by others in that the HD were mixed cellularity, nodular sclerosing, and lymphocyte depleted subtypes. The morphology in these cases was typical of HD, as was the immunohistochemical profile. However, the two remaining cases were notable in that the HD was of the nodular lymphocyte predominant type (NLPHD). To our knowledge, this association has not been well documented previously. In the two cases in this study, CLL and NLPHD were found simultaneously when each patient presented with lymphadenopathy and a lymphocytosis that was comprised of small monoclonal B lymphocytes coexpressing CD5. Lymph node biopsies in each case revealed typical NLPHD, with large, indistinct nodules containing scattered lymphocytic-histiocytic (L&H) cells. Focal, but distinct areas of CLL/SLL were also present. Immunostaining of the lymph node biopsy specimens showed the L&H cells to be CD20- and CD45 positive, and to lack CD15 or evidence of light chain restriction. In one of these patients, a NLPHD-associated large cell lymphoma developed 8 months later. The large cells were CD20- and CD45 positive, with lambda light chain restriction. In contrast, the original CLL cells in this patient expressed kappa light chains. This report indicates that LGLPD can be associated with all subtypes of HD, including the NLP type. The discordant light chain restriction between the CLL and the NLPHD-associated large cell lymphoma in one of these cases indicates that the CLL and HD were probably not derived from the same clone.

Correlation of clinical responses with immunologic and morphologic characteristics in patients with cutaneous T-cell lymphoma treated with interferon alfa-2a.

BACKGROUND: Immunophenotyping may aid in distinguishing more aggressive forms of cutaneous T-cell lymphoma (CTCL), thereby improving classification and treatment. OBJECTIVE: Our purpose was to investigate the relations between clinical, histologic, and immunophenotypic profiles in determining variables with respect to outcome. METHODS: Thirty-seven cases of histologically proven CTCL were analyzed in relation to clinical responses to treatment with interferon alfa alone or in combination with PUVA. Clinical stage, immunophenotyping, and histologic features were noted. RESULTS: All patients with no response to therapy had deletion of T-cell CD7 antigen. In contrast, only 21% of patients with a complete response had CD7 deletion. Deletion of the CD5 antigen occurred in 50% of patients with no response and in no patients with complete response. Large cell histologic features were found in 16% of patients with a complete response, 42% with a partial response, and 83% with no response. The presence or absence of other T-cell antigens and the clinical stage of disease did not correlate with outcome. CONCLUSION: Immunophenotypic analysis may be of greatest value in identifying a subset of high-risk CTCL patients, including those previously classified as low risk on the basis of clinical stage.

Systemic T-cell lymphoma presenting with isolated neurological dysfunction and intraparenchymal brain lesions. Case report.

Secondary non-Hodgkin's lymphoma of the central nervous system is typically a late manifestation of systemic T-cell lymphoma, with a 2-month median survival time after the development of neurological disease. Of the reported patients with this late complication, only 1% manifest spread of the disease to the brain parenchyma. The authors report a patient with an unusual initial neurological presentation of systemic T-cell lymphoproliferative disorder and associated space-occupying lesions of the brain parenchyma. The diagnosis was supported by extensive molecular, immunological, and histopathological analysis. Neurological symptoms appeared early in the course of systemic disease and were characterized by spontaneous exacerbations and remissions. The patient has survived for more than 5 years since the onset of his neurological symptoms. Histopathological characterization including immunoperoxidase staining for T-cell markers, DNA content, and cell-cycle analysis of brain tissue obtained at stereotactic biopsy were compared to those of atypical lymphoid cells of peripheral blood, bone marrow, and liver. The neurological manifestations and possible etiologies of T-cell lymphoma are discussed.

Granulocytic sarcoma is associated with the 8;21 translocation in acute myeloid leukemia.

PURPOSE: Since the only three cases of granulocytic sarcoma among patients with acute myeloid leukemia (AML) seen at our institution during the last 12 years were each associated with the 8;21 translocation [t(8;21)], we sought to determine if this association is specific and more frequent than previously recognized. PATIENTS AND METHODS: We report three patients with AML and t(8;21) who developed granulocytic sarcomas, and review the world literature. RESULTS: Between 1980 and 1992, 53 cases of AML French-American-British (FAB) M2 were identified at our institution. Eight (15%) patients had t(8;21). Three of these eight patients (38%) developed granulocytic sarcoma. All three of our patients received conventional intensive antileukemic chemotherapy yet had short relapse-free survival durations. Several series of patients with t(8;21) report that granulocytic sarcomas occur in approximately 18% of this population, which is four times the expected incidence in AML. Thirty-seven cases have been previously reported. Although karyotype analyses were not reported in many cases of granulocytic sarcoma in the literature, the vast majority of abnormal karyotypes in patients with AML involved t(8;21). Recent work with a cell line derived from a patient with t(8;21) indicates that such cells are unusually adherent to culture bottles and are aggregable CONCLUSION: Our data suggest that this association is more common than generally recognized and may be specific. Patients with t(8;21) should be observed closely for signs and symptoms of granulocytic sarcoma. These patients may have a less favorable prognosis than other patients with t(8;21). Cooperative oncology groups should retrospectively identify patients with AML and t(8;21) who had a poor outcome to determine if they had a disproportionate incidence of granulocytic sarcoma. If so, aggressive therapy such as bone marrow transplantation may be warranted early in the therapeutic strategy.