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Thomas M Habermann

Publications and source records attributed to Thomas M Habermann.

At least 37 records · Page 2Linked to original sources
PubMed2005

Adult B-cell lymphomas with burkitt-like morphology are phenotypically and genotypically heterogeneous with aggressive clinical behavior.

Adult, de novo B-cell lymphomas meeting the WHO morphologic criteria for atypical Burkitt/Burkitt-like lymphoma cause diagnostic difficulty for pathologists because the genetic and clinical characteristics of this group of lymphomas have not been clearly defined. Thirty-one such lymphomas, designated as Burkitt-like lymphomas (BLL), were selected based on morphologic features and evaluated for immunophenotype, MYC and BCL2 status, and clinical features. Nine childhood Burkitt lymphomas (BL) and 87 adult, de novo diffuse large B-cell lymphomas (DLBL) were similarly evaluated for comparison. The BL group demonstrated uniform characteristics: all had Burkitt lymphoma morphology, an identical immunophenotype (positive for CD20, CD10, bcl-6, CD43, and p53; negative for CD138, CD23, bcl-2), high MIB-1 positivity, IGH/MYC translocation, no IGH/BCL2 translocation, and all patients were alive at the last follow-up. The BLL and DLBL groups were heterogeneous. Burkitt-like morphology alone correlated with decreased survival. IGH/MYC or IGL/MYC fusion was identified in 11 of 27 (41%) BLL and 4 of 76 (5%) DLBL and was associated with decreased survival in both groups. MIB-1 positivity did not correlate with morphology, MYC abnormalities, or survival. We propose that adult B-cell lymphomas with BLL morphology are a phenotypically and genetically heterogeneous group of aggressive lymphomas, biologically distinct from childhood BL. Until biologically accurate subgroups within this morphologically defined group are identified, it is appears that both recognition of BLL morphology and direct evaluation for the presence of MYC fusion to immunoglobulin genes are important for identification of adult patients with poorer prognosis than those with DLBL.

Adolescent↗
PubMed2004

Molecular profiling of diffuse large B-cell lymphoma identifies robust subtypes including one characterized by host inflammatory response.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with recognized variability in clinical outcome, genetic features, and cells of origin. To date, transcriptional profiling has been used to highlight similarities between DLBCL tumor cells and normal B-cell subtypes and associate genes and pathways with unfavorable outcome. To identify robust and highly reproducible DL-BCL subtypes with comprehensive transcriptional signatures, we used a large series of newly diagnosed DLBCLs, whole genome arrays, and multiple clustering methods. Tumors were also analyzed for known common genetic abnormalities in DLBCL. There were 3 discrete subsets of DLBCL-"oxidative phosphorylation," "B-cell receptor/proliferation," and "host response" (HR)-identified characterized using gene set enrichment analysis and confirmed in an independent series. HR tumors had increased expression of T/natural killer cell receptor and activation pathway components, complement cascade members, macrophage/dendritic cell markers, and inflammatory mediators. HR DLB-CLs also contained significantly higher numbers of morphologically distinct CD2+/CD3+ tumor-infiltrating lymphocytes and interdigitating S100+/gamma interferon-induced lysosomal transferase-positive (GILT+) CD1a-/CD123- dendritic cells. The HR cluster shared features of histologically defined T-cell/histiocyte-rich B-cell lymphoma, including fewer genetic abnormalities, younger age at presentation, and frequent splenic and bone marrow involvement. These studies identify tumor microenvironment and host inflammatory response as defining features in DLBCL and suggest rational treatment targets in specific DLBCL subsets.

Cluster Analysis↗
PubMed2004

Expression of BLyS and its receptors in B-cell non-Hodgkin lymphoma: correlation with disease activity and patient outcome.

BLyS, recently shown to be critical for survival of normal B cells, has been found to be elevated in a number of immune disease models. A role for BLyS in the survival of malignant B cells has also been revealed and we therefore sought to identify a role for BLyS and its receptors in non-Hodgkin lymphoma (NHL). We found that tumor cells from all NHL histologic subtypes expressed one or more of 3 known receptors (BCMA, TACI, and BAFF-R) for BLyS; however, the pattern of expression was variable. We provide evidence that BLyS is expressed in tumors from patients with NHL and that BLyS levels increase as tumors transform to a more aggressive phenotype. Additionally, we provide evidence that serum BLyS levels are elevated in a subgroup of patients with NHL. In patients with de novo large B-cell lymphoma, a high BLyS level correlated with a poorer median overall survival, the presence of constitutional symptoms, and elevated values of lactic dehydrogenase. When BLyS levels were correlated with response to therapy in all patients, responding patients had a significantly lower BLyS level than those with progressive disease. In summary, we found that BLyS and its receptors represent a potentially important therapeutic target in B-cell lymphoma.

Adult↗
PubMed2004

Chemotherapy with or without radiotherapy in limited-stage diffuse aggressive non-Hodgkin's lymphoma: Eastern Cooperative Oncology Group study 1484.

PURPOSE: To compare low-dose (30 Gy) radiotherapy (RT) with observation (OBS) in limited-stage aggressive lymphoma patients achieving complete remission (CR) after chemotherapy, and to measure conversion from partial response (PR) to CR with high-dose (40 Gy) RT. PATIENTS AND METHODS: From 1984 to 1992, stage I (with risk factors) and II adults with diffuse aggressive lymphoma in CR after eight cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) were randomly assigned to 30 Gy involved-field RT or OBS. PR patients received 40 Gy RT. RESULTS: Among 172 CR patients, the 6-year disease-free survival (DFS) was 73% for low-dose RT versus 56% for OBS (two-sided P = .05). Failure-free survival (two-sided P = .06), and time to progression (two-sided P = .06) also favored RT. Intent-to-treat analyses yielded similar results. No survival differences were observed. Three RT versus 15 OBS patients relapsed in initial disease sites. At 6 years, failure-free survival was 63% in PR patients; conversion to CR did not significantly influence clinical outcome. CONCLUSION: For patients in CR after CHOP, low-dose RT prolonged DFS and provided local control, but no survival benefit was observed. The majority of PR patients were event-free at 6 years despite residual radiographic abnormalities. Future efforts should be directed toward improved imaging and more effective systemic therapies.

Adult↗
PubMed2004

Clinical characteristics of familial vs. sporadic non-Hodgkin lymphoma in patients diagnosed at the Mayo Clinic (1986-2000).

There are few data on the clinical characteristics of familial vs. sporadic non-Hodgkin lymphoma (NHL). Using the NHL registry at the Mayo Clinic, we compared age of diagnosis, gender, tumor site and histologic subtype between patients with sporadic and familial NHL. In 2001, we identified all new cases of adult NHL diagnosed between 1986 and 2000 in the Mayo Clinic NHL database (n = 2289) and mailed out a family history questionnaire to all living patients with a current address (n = 1043). Each NHL patient was categorized according to their self-report of leukemia or lymphoma in first-degree (1 degree) relatives. We received complete FH information on 740 patients (71%). Age at diagnosis of NHL ranged from 18-88 years (mean = 59 years) and 53% of our cases were male. First-degree FH of lymphoma was reported by 43 patients (6%), 1 degree FH of leukemia by 27 patients (4%) and 1 degree FH of both in 4 (1%). There was a nonstatistically significant later age at diagnosis for cases with any family history of lymphoma or leukemia (mean age = 61.3 and 61.7 years, respectively) vs. no family history (59.0 years) (P = 0.58). The male to female ratio for those with a FH of leukemia (ratio = 2.9) was higher compared to those with FH lymphoma (0.95) or no FH (1.1) (P = 0.08). No differences were apparent between 1 degree FH and site of NHL (nodal vs. extranodal) (P = 0.53). Among recently diagnosed cases (since 1995), there was some suggestion of a greater proportion of aggressive tumors for those with any family history (69% and 55%) vs. none (50%) (P = 0.20). We found little evidence of large differences between familial and sporadic NHL with regard to age, gender, site or histologic subtype.

Adolescent↗
PubMed2004

Therapeutic options in patients with lymphoma and severe liver dysfunction.

OBJECTIVES: To determine the long-term outcome of patients presenting with synchronous lymphoma and severe liver dysfunction and to describe the outcome of patients treated with initial mechlorethamine-based therapy used as a bridge to more conventional chemotherapy. PATIENTS AND METHODS: We reviewed the clinical course of all patients diagnosed as having lymphoma who presented with severe liver dysfunction and received intravenous mechlorethamine between September 1988 and February 2003 at the Mayo Clinic in Rochester, Minn. RESULTS: Forty-one patients were identified, 33 (80%) of whom had newly diagnosed, previously untreated lymphoma. Thirty-seven (90%) had non-Hodgkin lymphoma, and 4 (10%) had Hodgkin disease. Thirty-four patients (83%) had stage IV disease, and 31 (84%) of 37 had an intermediate-high International Prognostic Index. The median total bilirubin level before therapy was 10.7 mg/dL (range, 2.5-30.2 mg/dL), and the median alkaline phosphatase level was 982 U/L (range, 233-3415 U/L). In addition to mechlorethamine, 34 patients (83%) received concomitant corticosteroids, and 12 (29%) received concomitant rituximab. Twenty-two patients (54%) had sufficient improvement in liver function to receive subsequent standard chemotherapy. Nine patients (22%) are alive and disease-free at a median of 31 months (range, 4 to > or = 87 months) after mechlorethamine treatment. Factors associated with improved overall survival included improvement in bilirubin levels (P < .001) and receiving subsequent standard chemotherapy (P = .001). CONCLUSION: Mechlorethamine, high-dose corticosteroids, and rituximab are useful therapeutic interventions for this unique group of patients with lymphoma and severe liver dysfunction. Substantial clinical improvement and long-term survival are possible.

Adrenal Cortex Hormones↗
PubMed2003

Association of aspirin and other non-steroidal anti-inflammatory drug use with incidence of non-Hodgkin lymphoma.

Non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, seem to have chemopreventive properties against several types of cancer, particularly colon cancer. Persons with rheumatoid arthritis, an autoimmune disease for which NSAIDs are used commonly, have been reported to be at lower risk of colon cancer but at elevated risk of non-Hodgkin lymphoma (NHL), raising the possibility that NSAIDs may be a risk factor for NHL. We evaluated the association of use of NSAIDs, arthritis history, and risk of NHL in a prospective cohort of 27,290 postmenopausal women from the state of Iowa. The frequency of use of aspirin and of other NSAIDs excluding aspirin (e.g., ibuprofen), as well as a physician diagnosis of rheumatoid arthritis (RA) or osteoarthritis (OA), were self-reported on a questionnaire mailed in 1992. The incidence of NHL was ascertained through annual linkages to the Iowa SEER Cancer Registry. Relative risks (RR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression. Through 7 years of follow-up, 131 cases of NHL were identified. Compared to women who did not use either aspirin or other non-aspirin NSAIDs, women using aspirin exclusively (RR = 1.71; 95% CI = 0.94-3.13), non-aspirin NSAIDs exclusively (RR = 2.39; 95% CI = 1.18-4.83), or both types of drugs (RR = 1.97; 95% CI = 1.06-3.68) were at increased risk of NHL. A diagnosis of RA (RR = 1.75; 95% CI = 1.09-2.79), but not OA (RR = 1.06; 95% CI = 0.67-1.68), was associated with risk of NHL, but the positive association of use of aspirin and other NSAIDs with NHL was independent of RA history. Multivariate adjustment for other NHL risk factors only attenuated slightly these associations, whereas exclusion of cases occurring during the first 2 years of follow-up strengthened the associations. These data suggest that use of NSAIDs, either aspirin or other non-aspirin NSAIDs, are associated positively with risk of NHL, and that this association is independent of RA history.

Age Distribution↗
PubMed2003

Strategies for improving attendance at medical grand rounds at an academic medical center.

OBJECTIVE: To evaluate, in this before-and-after study, the results of 5 strategies for improving attendance at medical grand rounds at a tertiary care academic medical center. METHODS: The strategies included (1) using electronic card readers to improve understanding of attendance patterns, (2) conducting yearly needs assessment surveys, (3) developing sessions of topical interest, (4) increasing formal participation by residents and faculty researchers, and (5) enhancing publicity. Attendance at medical grand rounds by Mayo Clinic faculty, fellows, residents, and others was measured by card readers between 1998 and 2001. RESULTS: After implementation of the 5 strategies, the mean +/- SD attendance (as measured by card readers) at medical grand rounds increased 39% from 99.0 +/- 24.6 persons in 1998 to 137.4 +/- 25.2 persons in 2001 (P < .001). CONCLUSION: An organized effort can improve attendance at medical grand rounds at an academic medical center.

Academic Medical Centers↗
PubMed2002

Anthropometric characteristics, physical activity, and risk of non-Hodgkin's lymphoma subtypes and B-cell chronic lymphocytic leukemia: a prospective study.

Anthropometric characteristics, physical activity, and risk of non-Hodgkin's lymphoma, its subtypes, and B-cell chronic lymphocytic leukemia (B-CLL) were evaluated in a prospective cohort study of 37,931 Iowa women who were aged 55-69 years at baseline in 1986. Through 1998, 261 cases of non-Hodgkin's lymphoma (137 diffuse, 58 follicular, and 32 small lymphocytic lymphomas) and 63 cases of B-CLL were identified by linkage to the Iowa Cancer Registry. Height, weight, body mass index, waist/hip ratio, and physical activity were not associated with risk of non-Hodgkin's lymphoma overall or with diffuse or follicular lymphoma in particular. After adjustment for other non-Hodgkin's lymphoma risk factors, there was an inverse association of baseline body mass index (relative risks (RRs) across quartiles: 1, 0.4, 0.4, 0.3; p trend = 0.03) with risk of small lymphocytic lymphoma. In contrast, for B-CLL there were suggestive positive associations with body mass index at age 50 years (RRs across quartiles: 1, 1.9, 1.5, 2.7; p trend = 0.03) and (more weakly) baseline body mass index (RRs across quartiles: 1, 1.1, 1.6, 1.3; p trend = 0.3). In summary, we found no evidence that height, weight, body mass, or physical activity plays an important role in non-Hodgkin's lymphoma overall or in diffuse or follicular lymphoma in particular. The opposite associations of body mass index with small lymphocytic lymphoma versus B-CLL may be a chance finding but, if confirmed, would suggest different etiologies for these malignancies.

Adult↗
PubMed2002

Subsequent chemotherapy regimens are well tolerated after radioimmunotherapy with yttrium-90 ibritumomab tiuxetan for non-Hodgkin's lymphoma.

PURPOSE: Yttrium-90 (90Y) ibritumomab tiuxetan (Zevalin; IDEC Pharmaceutical, San Diego, CA) is an effective therapy for patients with relapsed B-cell non-Hodgkin's lymphoma. The predominant toxicity of 90Y ibritumomab tiuxetan has been myelosuppression, and concern has been expressed about the tolerability of further treatment after this therapy. The goal of this analysis was to evaluate the therapy given to patients who relapsed after 90Y ibritumomab tiuxetan. PATIENTS AND METHODS: A retrospective analysis was performed on 58 patients treated at a single institution on five separate protocols that used 90Y ibritumomab tiuxetan 0.4 mCi/kg. All patients had experienced disease progression after 90Y ibritumomab tiuxetan treatment and received subsequent therapy. The toxicity seen in this cohort of patients with subsequent treatment regimens was analyzed and compared with that of control groups who did not receive 90Y ibritumomab tiuxetan. RESULTS: The median number of subsequent therapies was two (range, one to seven). Sixteen (28%) of the 58 patients received growth factor support with subsequent chemotherapy, and two patients were treated with reduced doses because of persistent pancytopenia. Eight patients subsequently had an autologous stem-cell transplantation with stem cells collected after 90Y ibritumomab tiuxetan therapy. Excluding patients hospitalized at the time of transplantation, 13 patients were hospitalized for neutropenic fever, thrombocytopenia, or both. When compared to patients who did not receive 90Y ibritumomab tiuxetan, there was no significant difference in toxicity. CONCLUSION: We conclude that chemotherapy or autologous stem-cell transplantation after prior therapy with 90Y ibritumomab tiuxetan is feasible and reasonably well tolerated. The toxicity with subsequent therapy seems similar to that in patients not treated with 90Y ibritumomab tiuxetan.

Adult↗
PubMed2002

Phase 1 study of interleukin-12 in combination with rituximab in patients with B-cell non-Hodgkin lymphoma.

Rituximab is a chimeric murine/human monoclonal antibody that binds to CD20 on B lymphocytes. Although binding of the Fab domain may induce apoptosis, the Fc domain recruits immune effector functions to mediate cell lysis. Interleukin-12 (IL-12) facilitates cytolytic T-cell responses, enhances the lytic activity of natural killer (NK) cells, and induces the secretion of interferon gamma (IFN-gamma) by both T and NK cells. Therefore, the hypothesis was considered that combining IL-12 with rituximab would augment the immune-mediated cell lysis induced by rituximab. A phase 1 study of IL-12 in combination with rituximab was conducted in 43 adults with B-cell lymphoma to determine the optimal immunologic dose of this combination. Rituximab was administered at a dose of 375 mg/m(2) by intravenous infusion weekly for 4 weeks, and IL-12 was given subcutaneously twice weekly. The starting dose of IL-12 was 30 ng/kg and this was escalated to 500 ng/kg. Constitutional symptoms and liver enzyme elevations at 500 ng/kg of IL-12 were dose limiting. A greater than 20-fold increase in the serum levels of IFN-gamma and a 2.5- to 5-fold increase in inducible protein 10 (IP-10) levels was seen at IL-12 doses of 100 ng/kg or greater. Objective responses occurred in 29 of the 43 patients (69%), with 8 of 11 complete responses seen at IL-12 doses of 300 ng/kg or greater. The optimal immunologic dose of IL-12 in combination with rituximab was determined to be 300 ng/kg subcutaneously twice weekly starting on day 2. These data suggest that IL-12 and rituximab is an active combination and further studies of this combination in B-cell non-Hodgkin lymphoma are warranted.

Adjuvants, Immunologic↗
PubMed2002

Menstrual and reproductive factors and risk of non-Hodgkin lymphoma: the Iowa women's health study (United States).

BACKGROUND: Endogenous sex hormones, particularly estrogens, modulate the immune system, and non-Hodgkin lymphoma (NHL) is a tumor that is related to immunologic status. METHODS: Self-reported menstrual and reproductive history and risk of NHL were evaluated in a cohort of 37,934 Iowa women who were aged 55-69 years when first enrolled in 1986. Through 1998, 261 cases of NHL were identified by linkage to the Iowa SEER Cancer Registry. RESULTS: After multivariate adjustment there was no association between NHL incidence and age at menarche, age at menopause, type of menopause, history of infertility, number of miscarriages, or history of induced abortion, while there were suggestive inverse associations with nulliparity (RR=0.65; 95% CI 0.36-1.16) and years of ovulation (RR = 0.76 for >37 compared to <28 ovulatory years: p-trend = 0.07). Among parous women there was no association with number of livebirths or age at first livebirth, but there was an inverse association with number of children who were breast-fed (RR=0.52 for breast-feeding >2 children versus none; 95% CI 0.33-0.82). CONCLUSIONS: Overall, menstrual and reproductive factors were not strongly related to NHL incidence. The inverse association with breast-feeding is novel but requires confirmation in other studies.

Abortion, Induced↗
PubMed2002

Involvement of the lacrimal drainage system by leukemia or lymphoma.

PURPOSE: To determine the clinical characteristics and outcomes of patients with leukemic or lymphomatous involvement of the lacrimal drainage system (LDS). METHODS: A computerized retrieval system was used to identify patients with histologically proven leukemic or lymphomatous involvement of the LDS. Medical records were reviewed. RESULTS: Biopsies of the lacrimal sac or nasolacrimal duct obtained during dacryocystorhinostomies (DCR) performed at the Mayo Clinic (Rochester, Minnesota) between January 19, 1989, and August 26, 1997, were positive for leukemia or lymphoma in 11 patients (15 LDS). Ten patients had previously diagnosed leukemia or lymphoma; the interval between the diagnosis of systemic disease and DCR averaged 5.8 years (range, 7 months to 13 years; median, 5 years). The median age at the time of LDS involvement was 72 years (range, 49 to 85 years). Seven patients (64%) were women, and all were white. The median postoperative follow-up after DCR was 38 months (range, 10 to 65 months). Eight patients had leukemic infiltration of the LDS, 2 patients had B-cell lymphoma, and 1 patient had cutaneous T-cell lymphoma. Four patients had bilateral LDS involvement, and the remainder had unilateral disease (right eye, 1 patient; left eye, 6 patients). The most common initial presentation, in 9 patients (82%), was epiphora. Lacrimal irrigation of 2 LDS was deferred because of acute dacryocystitis. Of the remaining 13 systems, 8 were completely obstructed. The blockage was low (in the lower sac or in the nasolacrimal duct) in 6 systems and high (in the upper sac or common internal punctum) in 2 systems. Four LDS were anatomically patent to irrigation but were functionally obstructed. Chemotherapy was the primary treatment in 7 patients, whereas 4 patients underwent radiation therapy. Nine patients responded well to treatment, with alleviation of signs and symptoms, and none of these patients had local recurrence during the follow-up interval. CONCLUSIONS: Leukemic or lymphomatous involvement of the LDS is an unusual cause of tearing in elderly patients, but it should be suspected in patients with known systemic disease. Treatment comprising multiple interventions improves the signs and symptoms of this complication of lymphoproliferative disorders in most patients.

Aged↗