Phase III trial of gemcitabine plus docetaxel versus capecitabine plus docetaxel with planned crossover to the alternate single agent in metastatic breast cancer.

BACKGROUND: Safety and efficacy of gemcitabine plus docetaxel (GD) and capecitabine plus docetaxel (CD) were compared in patients with metastatic breast cancer, where the alternate crossover monotherapy (GD→C or CD→G) was predetermined. PATIENTS AND METHODS: Patients were randomly assigned to 3-week cycles of either gemcitabine 1000 mg/m(2) on days 1 and 8 plus docetaxel 75 mg/m(2) on day 1 or capecitabine 1000 mg/m(2) twice daily on days 1-14 plus docetaxel 75 mg/m(2) day 1. Upon progression, patients received crossover monotherapy. Primary end point was time to progression (TtP). Secondary end points evaluated overall response rate (ORR), overall survival (OS), and adverse events (AEs). RESULTS: Despite over-accrual of 475 patients, the trial matured with only 324 of 385 planned TtP events due to patient discontinuations. Human epidermal growth factor receptor 2 status was not captured in this study. More CD patients (28%) discontinued due to AEs than GD patients (18.0%, P = 0.009). TtP [hazard ratio (HR) = 1.101, 95% confidence interval (CI) 0.885-1.370, P = 0.387] and OS (HR = 1.031, 95% CI 0.830-1.280, P = 0.785) were not significantly different comparing GD and CD. ORR was not statistically different (P = 0.239) comparing GD (72 of 207, 34.8%) and CD (78 of 191, 40.8%). TtP, OS, and ORR were not significantly different comparing crossover groups. GD caused greater fatigue, hepatotoxicity, neutropenia, and thrombocytopenia but not febrile neutropenia; CD caused more hand-foot syndrome, gastrointestinal toxicity, and mucositis. CONCLUSIONS: GD and CD produced similar efficacy and toxicity profiles consistent with prior clinical experience.

Photon tunneling microscopy of polymeric surfaces.

With photon tunneling microscopy it is possible to image polymeric and other dielectric surfaces by means of the unusual properties of photon tunneling or evanescent waves. Vertical resolution is 1 nanometer, limited by the detector, over a vertical range of half a wavelength. Lateral resolution is better than a quarter of a wavelength over a field of view up to 125 micrometers. Samples can be surveyed in real time in air, with no need for metallization, and without shadowing or the intrusive effects of electrons or scanning probes. The use of this technique to study single crystals of polyethylene and processes such as latex film formation and the evolution of polystyrene topography while dewetting above the glass transition temperature are described.

Stress triggering of the 1994 m = 6.7 northridge, california, earthquake by its predecessors.

A model of stress transfer implies that earthquakes in 1933 and 1952 increased the Coulomb stress toward failure at the site of the 1971 San Fernando earthquake. The 1971 earthquake in turn raised stress and produced aftershocks at the site of the 1987 Whittier Narrows and 1994 Northridge ruptures. The Northridge main shock raised stress in areas where its aftershocks and surface faulting occurred. Together, the earthquakes with moment magnitude M >/= 6 near Los Angeles since 1933 have stressed parts of the Oak Ridge, Sierra Madre, Santa Monica Mountains, Elysian Park, and Newport-lnglewood faults by more than 1 bar. Although too small to cause earthquakes, these stress changes can trigger events if the crust is already near failure or advance future earthquake occurrence if it is not.

Change in failure stress on the southern san andreas fault system caused by the 1992 magnitude = 7.4 landers earthquake.

The 28 June Landers earthquake brought the San Andreas fault significantly closer to failure near San Bernardino, a site that has not sustained a large shock since 1812. Stress also increased on the San Jacinto fault near San Bernardino and on the San Andreas fault southeast of Palm Springs. Unless creep or moderate earthquakes relieve these stress changes, the next great earthquake on the southern San Andreas fault is likely to be advanced by one to two decades. In contrast, stress on the San Andreas north of Los Angeles dropped, potentially delaying the next great earthquake there by 2 to 10 years.

Seismic potential revealed by surface folding: 1983 coalinga, california, earthquake.

The 2 May 1983 Coalinga, California, earthquake (magnitude 6.5) failed to rupture through surface deposits and, instead, elastically folded the top few kilometers of the crust. The subsurface rate of fault slip and the earthquake repeat time are estimated from seismic, geodetic, and geologic data. Three larger earthquakes (up to magnitude 7.5) during the past 20 years are also shown to have struck on reverse faults concealed beneath active folds.

Correlation of changes in gravity, elevation, and strain in southern california.

Measurements made once or twice a year from 1977 through 1982 show large correlated changes in gravity, elevation, and strain in several southern California networks. Precise gravity surveys indicate changes of as much as 25 microgals between surveys 6 months apart. Repeated surveys show that annual elevation changes as large as 100 millimeters occur along baselines 40 to 100 kilometers long. Laser-ranging surveys reveal coherent changes in areal strain of 1 to 2 parts per million occurred over much of southern California during 1978 and 1979. Although the precision of these measuring systems has been questioned, the rather good agreement among them suggests that the observed changes reflect true crustal deformation.

Multicenter clinical trial of mitoxantrone in non-Hodgkin's lymphoma and Hodgkin's disease.

In this phase II multicenter trial, the efficacy and safety of mitoxantrone (Novantrone; Lederle Laboratories, Wayne, NJ) were evaluated in the treatment of 206 patients with relapsed non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) previously treated with other agents. Sixty-nine percent of the patients had received prior therapy with doxorubicin. The patients received 14 mg/m2 of mitoxantrone every 3 weeks. Nineteen (12%) of the NHL patients and two (7%) of the HD patients had complete responses (CRs). The combined CR and partial response (PR) rates were 37% (60 of 163) for NHL patients and 36% (10 of 28) for HD patients; the median duration of response was 323 days for NHL patients and 209 days for HD patients. The median survival times were 337 days for patients with NHL and 469 days for patients with HD. The median survival time for patients with low-grade NHL was 589 days compared with 298 days for patients with intermediate-grade NHL and 167 days for patients with high-grade NHL. The median time to treatment failure was 73 days for NHL patients and 98 days for HD patients. The major toxicity was myelosuppression, which was moderate and reversible. Nausea, vomiting, and alopecia were mild. There were two cases of congestive heart failure (CHF) considered related to treatment; both patients had received prior treatment with doxorubicin. In this group of heavily pretreated patients, mitoxantrone was effective and well tolerated. Responses were seen with mitoxantrone in patients who had relapsed after prior therapy with doxorubicin and in patients who had failed to respond to prior therapy with doxorubicin. Mitoxantrone should be evaluated in less heavily pretreated patients and should be considered for incorporation into combination chemotherapeutic regimens for the treatment of malignant lymphoma.

Clinical features of 31 patients with Ki-1 anaplastic large-cell lymphoma.

Thirty-one patients were diagnosed by morphologic and immunophenotypic features as having primary Ki-1 anaplastic large-cell lymphoma (Ki-1 ALCL). the median age was 35 years (range, 4 months to 78 years); the male:female ratio was 18:13. B symptoms were observed in 13 patients. Peripheral adenopathy was present in 26 patients, while mediastinal adenopathy occurred in five. There was extranodal disease in 13 patients; the most common extranodal site was skin with seven affected. Seventeen patients had stage III/IV disease. Immunophenotypes were T cell in 24 patients and B cell in four patients; immunophenotype could not be determined in three patients. Cytogenetic abnormalities in chromosomes 2, 5, and 7 were detected in three patients. Although therapy was heterogeneous, the actuarial 2-year survival was 73%. Two-year disease-free survival was 39% for all patients; for stages I and II, it was 62% compared with 20% for stages III and IV (P = .001). Complete remission (CR) occurred in 21 of 23 patients receiving combination chemotherapy; however, nine relapses, including six of seven stage IV patients, occurred within 21 months of diagnosis. Preliminary observations suggest that Ki-1 ALCL may have a quiescent phase in the rare patient with only localized skin disease. However, the disease generally behaves as an intermediate- to high-grade lymphoma, and patients with Ki-1 ALCL should receive curative-intent combination chemotherapy.

T-cell-rich B-cell lymphomas: diagnosis and response to therapy of 44 patients.

PURPOSE: Clinicopathologic features of 44 patients with well-documented T-cell-rich B-cell lymphomas (TCRBCLs) were reviewed to determine if there were distinguishing clinical characteristics and to evaluate the responsiveness to therapy. PATIENTS AND METHODS: Forty-one patients had de novo TCRBCL, while three patients had a prior diagnosis of diffuse large B-cell lymphoma. Seventeen TCRBCLs were identified from a retrospective analysis of 176 lymphomas diagnosed before 1988 as peripheral T-cell lymphoma (PTCLs). The initial pathologic diagnosis was incorrect in 36 of 44 cases (82%), usually due to the absence of adequate immunophenotypic and/or genotypic studies at the initial study. RESULTS: The median age of patients was 53 years (range, 17 to 92), and the male-to-female ratio was 1.4:1. B symptoms were present in 22 of 41 patients (54%); splenomegaly was detected in 11 patients (25%). Clinical stage at diagnosis was as follows: I (n = 8), II (n = 6), III (n = 15), IV (n = 14), and unstaged (n = 1). Although therapy was heterogeneous, the disease-free survival (DFS) and overall survival (OS) rates at 3 years for patients with de novo TCRBCL were 29% and 46%, respectively. A complete response (CR) to combination chemotherapy for intermediate-grade lymphomas was observed in 16 of 26 patients (62%); 11 of these patients (42%) had a continuous CR, compared with one of 14 patients (7%) who received radiation therapy or therapy for low-grade lymphoma or Hodgkin's disease (HD) (P < .05). However, there was no difference in OS between patients who received chemotherapy for intermediate-grade lymphoma versus other therapies (49% v 48%) due to a high response rate to salvage therapies, including seven patients without disease after marrow transplantation. CONCLUSION: TCRBCLs are difficult to recognize without immunoperoxidase studies. Patients with TCRBCL have clinical features similar to patients with other large B-cell lymphomas, except they may have more splenomegaly and advanced-stage disease; they should receive combination chemotherapy directed at large-cell lymphomas.

Large-cell lymphomas: clinical and prognostic features.

We reviewed the clinical and pathologic features in 186 patients with large-cell lymphomas seen at Vanderbilt University Hospital between 1970 and 1986. Ninety-two cases (49%) were large noncleaved-cell lymphoma (LNCCL), 61 cases (33%) were large-cleaved-cell lymphoma (LCCL), 17 cases (9%) were peripheral T-cell lymphoma (PTCL), and 16 cases (9%) were immunoblastic sarcoma of B cells (IBS-B). These subsets of large-cell lymphoma did not differ with respect to median age, distribution by stage, or incidence of bone marrow involvement. Significant differences between groups were noted with regard to male:female ratio, incidence of symptoms, incidence of extranodal disease, and pattern of adenopathy. However, when LCCL was excluded from the analysis, none of these differences were significant. By univariate analysis, age, stage, marrow involvement, extranodal disease, B symptoms, elevated serum lactic dehydrogenase (LDH), and diffuse pattern were unfavorable prognostic features in large-cell lymphoma. However, when cases were stratified by cell of origin, nodular versus diffuse pattern was of no prognostic significance. Nodularity was favorable only because 71% of nodular and nodular-diffuse cases were LCCL, while the majority of diffuse cases were LNCCL. Although IBS-B is considered a "high-grade" lymphoma, we found no evidence for inferior survival in these patients compared with LNCCL or LCCL. In fact, survival was better in IBS-B than in LNCCL or LCCL, although this difference was not significant. However, survival was significantly inferior in PTCL (median, 11 months) compared with the other subsets of large-cell lymphoma (median, 46 months; P = .038, log-rank test). Since the association of PTCL and an inferior survival has most often been noted in the context of "second-generation" chemotherapy, we believe that this association may be therapy-dependent and may be minimized by the use of more aggressive chemotherapy regimens.

Non-Hodgkin's lymphoma of the gastrointestinal tract: an analysis of clinical and pathologic features affecting outcome.

Clinical and histopathologic data from 87 patients with primary non-Hodgkin's lymphoma of the gastrointestinal (GI) tract diagnosed between 1974 and 1984 were reviewed. B-cell lymphomas of intermediate- or high-grade histology constituted 78% of lesions. Stage of disease varied with histologic grade, with a preponderance of advanced disease (stages IIIE and IV) in patients with low-grade lymphoma (15 of 21) (71%), compared with higher grade lesions (38%, P = .01). Among patients with nonlocalized (stages IIE through IV) lymphoma of intermediate- or high-grade histology, surgical resection of the primary focus afforded a higher rate of complete remission (CR) (70% v 50%) and sustained CR (61% v 21%, P = .04) after cytotoxic therapy compared with the nonresected cohort. The median survival in the resected group was 51 months + compared with 13 months in the nonresected patients (P = .012). Differences in outcome were attributable to a high risk of treatment-related complications (perforation and/or hemorrhage) (43% v 0%, P = .001) and local relapse (29% v 4%, P = .05) in nonresected individuals. Life-threatening local complications were not observed in patients with low-grade lymphoma managed solely with medical therapy. Histologic findings from surgically staged patients identified presence of extravisceral disease and intermediate- or high-grade tumor histology as features predictive of transmural invasion, enabling potential identification of patients who might be optimally managed by resection of the primary GI focus before initiation of cytotoxic therapy.

Effective therapy for poor-prognosis non-Hodgkin's lymphoma with 8 weeks of high-dose-intensity combination chemotherapy.

PURPOSE: Despite substantial advances in the treatment of aggressive non-Hodgkin's lymphoma, therapeutic results with conventional regimens remain poor in some subsets of patients. In an attempt to improve the prognosis of such patients we used an 8-week, multidrug chemotherapy regimen of high dose-intensity. PATIENTS AND METHODS: Between April 1986 and April 1991, 70 patients with advanced intermediate- or high-grade non-Hodgkin's lymphoma were treated. The median age was 41 years (range, 18 to 69). Fifty-one patients (73%) had stage IV disease; 37 (53%) were Shipp's category 3; 17 (24%) had small noncleaved-cell lymphoma; 35 (50%) had Eastern Cooperative Oncology Group (ECOG) performance status > or = 2; 24 (34%) had two or more extranodal sites involved; and 17 (24%) had bone marrow involvement. The 8-week regimen included cyclophosphamide, etoposide, doxorubicin, vincristine, bleomycin, methotrexate with leucovorin rescue, and prednisone. RESULTS: Sixty-two of 70 patients completed the regimen as planned. Fifty-seven patients (81%) obtained a complete response (CR) and the actuarial 5-year failure-free survival rate is 52%. Thirty-seven patients remain alive and disease-free a median of 35 months (range, 7 to 68) after therapy. Adverse prognostic factors included age more than 50 years, bone marrow involvement, and serum lactic dehydrogenase (LDH) more than 500 IU/L (normal range, 125 to 250). Myelosuppression was responsible for most of the treatment-related toxicity. Severe leukopenia (< 1,000/microL) occurred in all patients and lasted a median of 9 days. Seven patients (10%) died of myelosuppression-related complications; five of these patients were older than 60 years. CONCLUSION: This brief but intensive therapy was effective in treating poor-prognosis patients with non-Hodgkin's lymphoma. With this therapy, patients with small noncleaved-cell lymphoma or Shipp's category 3 disease had treatment outcome similar to the group as a whole. This therapy was not well tolerated by patients older than 60 years, and should not be given to this subgroup. Verification of these results in a randomized trial setting is indicated.

Peripheral T-cell lymphoma: a clinicopathologic study of 42 cases.

Clinical and histopathologic material from 42 patients with peripheral T-cell lymphoma (PTCL) was reviewed. The median age was 63.5 years (range, 11-97 years). The male:female ratio was 2.8:1. Prior immune or lymphoproliferative diseases occurred in 36% of the patients. PTCL was advanced at presentation with B symptoms (67%), generalized adenopathy (69%), and stage III/IV disease (79%). Suspected lung or pleural involvement (21%), hepatomegaly (29%), and splenomegaly (43%) were common; marrow involvement was documented in 37% of the patients at presentation and in 51% of patients during the illness. Hypercalcemia and eosinophilia occurred in 19% and 29% of patients, respectively. Among patients receiving combination chemotherapy (BCOP, CHOP, BACOP, COMLA), eight (24%) of 33 achieved a complete remission and only four (12%) of 33 had a sustained complete remission. The median survival for PTCL was 11 months. Because of the poor response to standard therapy, clinical trials should identify cases of PTCL and evaluate newer regimens in this subset of aggressive lymphoma.

High-dose cytarabine and daunorubicin as consolidation therapy for acute myeloid leukemia in first remission: long-term follow-up and results.

In an effort to increase the proportion of patients with acute myeloid leukemia (AML) remaining in continued complete remission (CCR), we administered intensive postremission consolidation therapy with high-dose cytarabine (Ara-C) and daunorubicin. Eighty-seven patients, with a median age of 38 years (range, 7 to 71), received consolidation therapy after first complete remission was obtained with standard induction chemotherapy that included conventional doses of Ara-C. Consolidation therapy consisted of from one to three cycles of high-dose Ara-C (3 g/m2 intravenously [IV] over 1 hour every 12 hours for 12 doses) followed by daunorubicin (30 mg/m2/d IV bolus for 3 days). After completion of the high-dose Ara-C and daunorubicin, no further therapy was administered. Myelosuppression encountered with consolidation resulted in a median duration of neutropenia and thrombocytopenia of 3 weeks. Four patients (5%) died during consolidation due to infection and/or hemorrhage; 59% of patients experienced severe but nonfatal infectious or extramedullary organ toxicity. With a median follow-up of more than 3.5 years from diagnosis, the proportion of patients, by Kaplan-Meier product-limit estimate, remaining in CCR is 49% (95% confidence limits, 37% to 61%). In a Cox multivariate analysis, only age significantly (P less than .001) influenced the probability of remaining in CCR. The probability of remaining in CCR was 83%, 50%, and 23% for age groups of 25 or less, 26 to 45, and more than 45 years, respectively. These survival curves all have stable long-term plateaus, suggesting cure. In this study, the administration of brief, intensive nonmarrow ablative chemotherapy resulted in a large proportion of patients with AML remaining in CCR, results similar to those reported with allogeneic bone marrow transplantation. Relapse of acute leukemia was still the major reason for therapy failure, suggesting that more effective or additional postremission therapy will be required to further improve the likelihood of cure especially for older patients.

Cimetidine-induced neutropenia: a possible dose-related phenomenon.

Neutropenia associated with high-dose cimetidine therapy developed in a patient in whom earlier therapy, as well as rechallenge with low-dose cimetidine, did not result in neutropenia. As other factors cannot be implicated, a dose-related toxicity of cimetidine appears likely. Although the mechanism of cimetidine-induced neutropenia is unknown, it may involve the previously demonstrated ability of histamine H2 receptor antagonists to block the histamine-induced initiation of DNA synthesis in bone marrow stem cells.

Effects of high-dose cytarabine.

Plasma, urine, cerebrospinal fluid, and tear concentrations of cytarabine (ara-C) were measured in 15 patients receiving 3 gm/m2 IV ara-C given as a 1 hr infusion every 12 hr for 6 days. The two assay methods used for measuring ara-C concentrations (high-pressure liquid chromatography and radioimmunoassay) gave much the same results. Peak plasma ara-C concentrations (2.0 microM) after high-dose therapy were 50 times those achieved with more conventional (100 to 300 mg/m2) doses. High doses of ara-C were not sufficient to saturate cytidine deaminase; plasma ara-C half-lifes (t1/2) after high-dose therapy (distribution t1/2 = 6.2 min; elimination t1/2 = 154 min) were much the same as those after conventional ara-C doses. Kinetics of ara-C were not altered by repeated dosing over a 6-day period. Cerebrospinal fluid ara-C concentrations after high-doses (mean = 7.8 microM) were 10 times those after conventional intravenous dosing, bot were 0.5% to 1.0% those achieved by intrathecal ara-C doses. Tear concentrations of 22 and 38 micro M were measured in two patients who developed conjunctivitis after high-dose therapy so that the presence of ara-C in tears may be a cause of the conjunctivitis seen in some patients.

High-dose cytosine arabinoside and daunorubicin as consolidation therapy for acute nonlymphocytic leukemia in first remission: an update.

High-dose (HD) cytosine arabinoside (ara-C) is more effective treatment than conventional-dose ara-C regimens for patients with relapsed acute nonlymphocytic leukemia (ANLL). Previously, we have reported that HD-ara-C administered during the first remission of ANLL has resulted in long remission durations and a high proportion of patients with long-term disease-free survival. In this update, those patients have been observed further and additional patients have been treated, affirming the initial conclusions. Since August 1979, 55 adult patients with ANLL in first remission received one to three courses of HD-ara-C (3 g/m2 by one-hour infusion every 12 hours for 12 doses on days 1 to 6) alone or with daunorubicin (30 mg/m2 for two or three doses on days 7 to 9). Three patients died of sepsis or hemorrhage during consolidation and 19 patients have relapsed from 5 to 48 months after diagnosis. The remaining 33 patients remain in continued complete remission (CCR) from 5 to 75 months. Denoting all deaths in remission as relapse, the actuarial probability of CCR is 51% at 75 months with an apparent plateau in the survival curve. Of the first 22 patients is 27 months. Using univariate and multivariate analysis, age is the only statistically significant prognostic parameter with the actuarial CCR of ages less than 25, 25 to 44, and greater than 44 being 100%, 48%, and 23%, respectively. Due to its heightened antileukemic activity, HD-ara-C allows brief but effective consolidation of ANLL in first remission with long-term disease-free survival comparable with other approaches including bone-marrow transplantation.

Re-treatment of aplastic anemia with antithymocyte globulin or antilymphocyte serum.

Twenty-two patients with aplastic anemia were treated with antilymphocyte serum or antithymocyte globulin at Vanderbilt University and affiliated hospitals from 1980 to 1986. The median age was 42 (eight to 73 years); the male:female ratio was 8:14. Nineteen patients had severe aplastic anemia, and three had moderate disease. Twenty patients received antilymphocyte serum initially while two patients received antithymocyte globulin. Fifteen patients received fluoxymesterone 10 mg by mouth three times a day with antilymphocyte serum, and all received prednisone during the course of antilymphocyte serum or antithymocyte globulin. There were seven responses (31.8 percent) to the first course with four complete responses and three partial responses. Six of 15 patients who received fluoxymesterone showed a response, compared with zero of five treated without androgens (p less than 0.05). Eight patients with no initial response and a patient who experienced a relapse after a complete response were re-treated with either antithymocyte globulin (six) or antilymphocyte serum (three), with four of nine patients (44 percent) having a response (three complete responses, one partial response). Overall, 10 of 22 patients (45 percent) had a response (six complete responses, four partial responses). Median survival for those without a response is six months. Median survival for those with a response has not been reached, with follow-up ranging from 18 to 70 months. This study shows the benefit of a second cycle of antilymphocyte serum or antithymocyte globulin and a possible role for concomitant androgens in this treatment of aplastic anemia.

Lymphocyte-depleted Hodgkin's disease. Clinicopathologic review of 25 patients.

Clinicopathologic material from 25 patients with lymphocyte-depleted Hodgkin's disease was reviewed. The median age of the patients was 57 years. The patients had no prior diagnosis of Hodgkin's disease and were divided according to pathologic subtype of lymphocyte-depleted Hodgkin's disease: 11 diffuse fibrosis, 10 reticular, and four not otherwise specified. The clinical presentation included B symptoms of fever, weight loss, or night sweats (92 percent), subdiaphragmatic disease (88 percent), frequent marrow involvement (56 percent), and advanced-stage disease (100 percent). Four of 11 patients with diffuse fibrosis had peripheral adenopathy as compared with seven of 10 patients with the reticular subtype (p = 0.3); 10 of 11 patients with diffuse fibrosis had marrow involvement compared with two of nine patients with the reticular subtype (p = 0.006). Among patients who received chemotherapy, median survival was longer in the diffuse fibrosis subtype (nine patients, 39 months) than in the reticular subtype (10 patients, 10 months), p = 0.005. Of the 17 patients who received more than one cycle of combination chemotherapy with mechlorethiamine, vincristine, procarbazine, and prednisone, the median survival was 36 months with 11 (65 percent) complete remissions. In eight patients, disease remains in remission (12 to 127 months) with five patients surviving beyond five years. These results indicate that lymphocyte-depleted Hodgkin's disease has at least two clinicopathologic subtypes and is curable if adequate therapy can be given.

Lymphocyte-depletion Hodgkin's disease. Histopathologic diagnosis of marrow involvement.

Lymphocyte-depletion Hodgkin's disease (LDHD) is a rare and often misdiagnosed form of HD. Although marrow involvement is frequent in this disease, most pathologists are not familiar with the marrow lesion of LDHD, since the underlying disease is so unusual. In order to characterize the marrow lesion produced by LDHD, we reviewed biopsies or aspirates from the initial presentation of 22 patients meeting all the clinical and pathologic criteria for LDHD. These included 11 cases of the diffuse fibrosis subtype, eight cases of reticular subtype, and three cases not subclassified. Fifty-four percent of cases, primarily of the diffuse fibrosis subtype, had marrow involvement. Aspirations and biopsies were positive with essentially the same frequency. LDHD produces a characteristic consolidated lesion readily recognized on low-power examination and composed of amorphous, nonbirefringent eosinophilic background material, an inflammatory infiltrate, and Reed-Sternberg (RS) cells. Involvement may be focal and RS cells are generally scarce, requiring examination of multiple sections of well-fixed and stained material. Uninvolved marrow tends to be normocellular and frequently has increased numbers of eosinophils. The original diagnosis of LDHD often may be made from marrow examination alone. Early recognition of marrow involvement is important in facilitating prompt treatment and providing accurate staging without laparotomy.