Biomedical subjects

T M Habermann

Publications and source records attributed to T M Habermann.

At least 55 records · Page 3Linked to original sources

PubMed1996

Phase I trial of dose escalation with growth factor support in patients with previously untreated diffuse aggressive lymphomas: determination of the maximum-tolerated dose of ProMACE-CytaBOM.

PURPOSE: The aim of this study was to determine the maximum-tolerated dose (MTD) of cyclophosphamide, doxorubicin, etoposide, prednisone, bleomycin, cytarabine, methotrexate, and leucovorin (ProMACE-CytaBOM) when the myelotoxic drugs cyclophosphamide, doxorubicin, etoposide, and cytarabine are escalated. PATIENTS AND METHODS: Thirty-eight eligible patients with diffuse aggressive non-Hodgkin's lymphoma were treated on a phase I trial of dose escalation using the ProMACE-CytaBOM regimen and granulocyte-macrophage colony-stimulating factor (GM-CSF; Schering, Kenilworth, NJ). Patients were treated with recombinant (r)GM-CSF 10 microg/kg/d subcutaneously from day 9 to 19. Twenty-seven patients had stage IV disease, four had stage III, and seven had bulky stage II. Half of the patients had bone marrow involvement. The median age was 45 years. RESULTS: We found that the MTD was 200% for the escalated drugs in this regimen (although we never escalated above the MTD or defined by dose-limiting toxicity) and that the normalized dose-intensity (NDI; defined as the ratio of the received dose-intensity to the 100% dose-intensity of ProcMACE-CytaBOM) decreased with each cycle and was lower for the day-8 drug (cytarabine) than for the day-1 drugs. The complete response (CR) rate was 66%, and 92% of patients who achieved CR are alive without disease with a median follow-up time for survival of 3.6 years. CONCLUSION: The MTD of cyclophosphamide, doxorubicin, etoposide, and cytarabine in the ProMACE-CytaBOM regimen given with growth factor support is 200%, and this dose should be tested in larger phase II trials.

Adult↗

PubMed1995

S-phase fraction by the labeling index as a predictive factor for progression and survival in low grade non-Hodgkin's lymphoma.

BACKGROUND: The purpose of this study was to learn if the bromodeoxyuridine labeling index (LI), a measure of the S-phase fraction, is an independent prognostic factor for overall survival (OS) for patients with newly diagnosed low grade non-Hodgkin's lymphoma (NHL). In addition, the ability of the LI to predict time to progression (TTP) in a group of patients observed without therapy after initial diagnosis was determined. METHODS: Patients eligible for this study had biopsy proven low grade NHL, adequate tissue to perform the LI, and were previously untreated. The bromodeoxyuridine LI was performed on fresh biopsy samples using a slide-based immunofluorescence procedure. RESULTS: One-hundred twelve patients were followed prospectively for OS, and 50 of these patients who initially were observed without therapy were eligible for an analysis of TTP. The LI (< or = 1% vs. > 1%) and presence of "B" symptoms were significant univariate prognostic factors for survival (P values of 0.004 and < 0.001, respectively). In a multivariate analysis, the LI and symptoms retained independent prognostic significance, whereas disease stage, histologic subtype, and age did not. In the group who were observed after diagnosis, the LI was not an independent predictor of TTP. CONCLUSIONS: The LI at initial diagnosis is an independent prognostic factor for OS of patients with low grade NHL, but it does not help choose patients for observation without therapy. Measurements of the LI should be considered as part of the on-study evaluation of patients entering cooperative group trials evaluating new therapies for this group of lymphomas.

Adult↗

PubMed1995

Occult systemic non-Hodgkin's lymphoma (NHL) in patients initially diagnosed as primary central nervous system lymphoma (PCNSL): how much staging is enough?

OBJECTIVE: To demonstrate the extent of staging necessary to exclude occult systemic stage IV NHL before making a diagnosis of stage I AE PCNSL. BACKGROUND: The diagnosis of PCNSL requires the demonstration of malignant lymphocytes within the CNS (usually by biopsy) and finding no evidence of systemic NHL. Different staging approaches have been recommended, ranging from extensive systemic evaluation (including bone marrow examination) to a more focused approach (abdominal and pelvic CT) to no systemic evaluation. We have employed a staging regimen that included: ophthalmologic evaluation (including slit lamp examination); CT of chest, abdomen, and pelvis; bilateral iliac crest aspirate and biopsy; flow cytometry of circulating lymphocytes; and, in men, testicular ultrasound. DESIGN/METHODS: We carried out a retrospective review of 128 patients entered into the Mayo Lymphoma Project data bank (1975-1994). RESULTS: Between the years 1975 and 1994, five patients (3.9%) were identified who fulfilled criteria for the diagnosis of PCNSL (typical clinical history, pathognomonic neuro-imaging, and histologic proof of NHL in brain tissue) but who had occult systemic NHL on staging (bone marrow 1, abdominal lymph nodes 3), or at autopsy (colon 1). Case histories are presented. CONCLUSIONS: Patients with apparent PCNSL may have systemic NHL. Complete staging is essential to the initial management of patients presenting as PCNSL to exclude systemic stage IV disease.

Aged↗

PubMed1995

Pretransplantation assessment of the risk of lymphoproliferative disorder.

Posttransplantation lymphoproliferative disorder (PTLD) is an uncommon but often fatal complication of solid organ transplantation that occurs in approximately 3% of patients. To determine the relative importance and relationship of potential risk factors for PTLD before transplantation (i.e., Epstein-Barr virus [EBV] serostatus of the recipient and the cytomegalovirus [CMV] sero-status of the recipient and the potential donor) and the principal risk factor after transplantation (immunosuppression with antilymphocyte antibody), we analyzed the findings for the first 381 consecutive adult nonrenal transplant recipients seen at Mayo Clinic. In the absence of the other risk factors, the incidence rate of PTLD for EBV-seronegative recipients was 24 times higher (95% confidence interval [CI]: 6.2, 89) than that for EBV-seropositive recipients. The additional risk factors of therapy with OKT3 for rejection and CMV seromismatch (i.e., a negative recipient and a positive donor) each further amplified this risk four- to sixfold. Together, all three risk factors acted synergistically to increase the incidence rate of fatal and/or CNS PTLD by a factor of 654 (CI: 368, 1,162) compared with the low incidence rate (.458 cases per 100 person years) when none of these risk factors were present. Pretransplantation determination of recipient EBV and CMV serostatus can identify a subgroup of patients whose risk for severe PTLD may preclude transplantation.

Adult↗

PubMed1995

Management of stage IE primary gastric lymphoma.

From 1975 to 1991, stage IE gastric lymphoma was diagnosed or treated in 40 patients at our institution. Thirty-five evaluable patients were the subject of this analysis (median age, 63 years). All histologic specimens were reviewed and classified according to the working formulation. Immunohistochemical stains were performed in 33 of 35 cases. The following histologic subtypes were identified: 26 patients had diffuse large cell, 2 had diffuse mixed cell, and 7 had mucosa-associated lymphocytic lymphoma (small lymphocytic lymphoma with features of MALT lymphoma). Of the 35 patients, 30 (86%) underwent laparotomy, with subtotal or total gastrectomy performed in 29. After gastrectomy, 17 patients had radiation therapy, 3 had chemotherapy, 2 had radiation plus chemotherapy, and 7 had no further treatment. Five patients were diagnosed with endoscopic biopsy and had radiation therapy, chemotherapy, or both without further surgical treatment. The median follow-up period was 69.2 months. The commonest presenting symptom was pain. The 5-year disease-free survival was 90% for the entire group and 88% for the 28 patients with working formulation intermediate histology. For patients with MALT lymphoma, the 5-year disease-free survival was 100%. The prognosis for patients with stage IE working formulation intermediate-histology gastric lymphoma is good and for those with stage IE MALT lymphoma, excellent.

Adult↗

PubMed1994

Treatment of stage IE primary lymphoma of bone.

PURPOSE: A retrospective analysis was performed to assess the efficacy of various treatments of Stage IE primary non-Hodgkins lymphoma of bone. METHODS AND MATERIALS: Sixty-three patients with Stage IE primary non-Hodgkins lymphoma of bone (single osseous focus) were seen at our institution between the years 1970 and 1989. Information was obtained regarding each patients' presentation and clinical course. The histology was reviewed in all patients. Modern immunohistochemical stains were performed on each case with available paraffin-embedded tissue. RESULTS: The histologic classification of the tumors was as follows: 43 diffuse large cell, 13 diffuse mixed cell, 3 small noncleaved, and 4 unclassified. The most common presenting symptom was pain (97%) and the following bony sites were involved: 36 long bone, 9 flat bone, 13 spine, and 5 pelvis. Of the 63 cases, 50 were treated with radiation alone, 10 with chemotherapy and radiation, 2 with chemotherapy alone, and 1 with surgery alone. Univariate analysis revealed a suggestion of an improved 5-year disease-free survival for patients treated with chemotherapy and radiation vs. radiation alone (90% vs. 57% respectively, p = .08). Multivariate analysis (controlling for extent of initial evaluation, extent of pathological evaluation and other potential prognostic factors) showed that neither treatment resulted in superior outcome with respect to disease-free survival, disease specific survival, or overall survival, however, doses of radiation greater than 4000 cGy resulted in improved overall survival compared to lower doses (p = 0.01). CONCLUSION: This study supports the use of primary RT (> 4000 cGy) for Stage IE PLB, however, the addition of chemotherapy to the radiotherapeutic management may decrease the initial relapse rate of some patients. Future studies should address this question.

Adolescent↗

PubMed1994

Neurological complications of peripheral and cutaneous T-cell lymphomas.

To determine the frequency and pattern of neurological complications of T-cell lymphoma (TCL), we retrospectively reviewed the medical records of 316 patients with TCL diagnosed between January 1984 and May 1991. Disease entities not included in this study were lymphoblastic lymphoma, primary central nervous system lymphoma, CD30-positive anaplastic large cell lymphoma, and lymphomas secondary to human immunodeficiency virus or human T-cell lymphotropic virus type I. Cases were classified as having direct complications (parenchymal, leptomeningeal, epidural, or peripheral) or indirect complications (paraneoplastic, disease related, or treatment related). Preexisting neurological conditions were excluded. The overall rate of neurological complications was 7.9%. The frequency of neurological complications in peripheral TCL and cutaneous TCL was 17% and 3%, respectively, with at least half of the neurological complications in both conditions due to direct involvement of the nervous system. Direct neurological complications of TCL were primarily due to leptomeningeal and parenchymal involvement. There were no cases of epidural spinal cord disease.

Adolescent↗

PubMed1994

Polymorphic reticulosis: a reappraisal.

We studied 18 patients (15 men and three women) evaluated for a destructive sinonasal lesion that had been diagnosed as "polymorphic reticulosis." The histologic features of each lesion were those of angiocentric immunoproliferative lesions," characterized by atypical lymphoid infiltrates with polymorphous, angiocentric, and necrotic features; 13 were grade 2 and five were grade 3. The neoplastic cells in each patient had a T-cell phenotype. Epstein-Barr virus RNA was detected in the neoplastic cells of 17 of the 18 T-cell lesions. Initial treatment consisted of local radiation therapy in each patient, chemotherapy in two patients, and prednisone in another patient. Two patients were lost to follow-up and the other 16 had a median follow-up of 14 years, 2 months (range, 4 months to 32 years, 5 months). Four patients are alive and disease free, four patients died not of disease or complication of therapy, and eight patients died of disease. The Kaplan-Meier estimate of survival was 63% at 5 years and 50% at 15 years. Histologic progression of angiocentric immunoproliferative lesions from grade 2 to grade 3 was observed in two patients, and a correlation between angiocentric immunoproliferative grade and survival could not be detected. These data suggest that polymorphic reticulosis is an Epstein-Barr virus-related angiocentric T-cell lymphoma.

Adult↗

PubMed1994

Incidence of leukemia in Olmsted County, Minnesota, 1975 through 1989.

OBJECTIVE: To determine the incidence of leukemia in Olmsted County, Minnesota, for a recent 15-year period and to compare the data with reported rates for the previous 40 years. DESIGN: We conducted a population study of leukemia diagnosed between 1975 and 1989 in residents of Olmsted County by review of medical records identified through diagnostic indexes, death certificates, autopsy files, and histologic preparations. MATERIAL AND METHODS: Diagnoses of leukemia were categorized into various subtypes, and age- and sex-specific incidence rates were calculated for leukemia as a whole and for each subtype. In addition, incidence rates were age- and sex-adjusted to the 1970 US white population for comparison with earlier published rates. Age and annual trends as well as sex differences were assessed with the generalized linear interactive model approach. RESULTS: During 1975 through 1989, the mean annual incidence rate for leukemia was 12.3 per 100,000 population in Olmsted County. When adjusted for age and sex, the rate per 100,000 was 13.6, in comparison with a similarly adjusted rate of 11.8 for the previous decade (1965 through 1974). The rates for chronic myelogenous leukemia and acute lymphocytic leukemia remained stable throughout the entire study period; however, rates for acute myelogenous leukemia and chronic lymphocytic leukemia increased, most prominently in patients 50 years of age or older. This increased rate occurred in both males and females, but the incidence rates for both subtypes began increasing earlier for males than for females. CONCLUSION: Although we cannot rule out an actual increase in incidence rates for these types of leukemia in the elderly population, we believe that the increase in persons older than 50 years of age reflects social change in improved health care and its better utilization by elderly persons, as well as the ability to diagnose leukemia earlier than in the past.

Adolescent↗

PubMed1994

Incidence of chronic lymphocytic leukemia in Olmsted County, Minnesota, 1935 through 1989, with emphasis on changes in initial stage at diagnosis.

OBJECTIVE: To determine whether the stage at the time of diagnosis of chronic lymphocytic leukemia (CLL) had changed during a 55-year period. DESIGN: We conducted a study of the cohort of residents of Olmsted County, Minnesota, who had been diagnosed as having CLL during the period from 1935 through 1989. MATERIAL AND METHODS: By analysis of medical records, patients with CLL were characterized by Rai stage, absolute lymphocyte count, age at diagnosis, need for therapy, and reported cause of death in nonsurvivors. Trends for these variables were analyzed by decade throughout the study period. RESULTS: The overall annual incidence rate of CLL per 100,000 population in Olmsted County increased from 2.6 in the 1935 through 1944 period to 5.4 in the 1975 through 1984 period; however, the increasing rate was found only for those 50 years of age or older and was especially dramatic for those 75 years old or older. Analysis of Rai stage over time demonstrated an increase in the proportion of cases diagnosed as Rai stage 0. In addition, the median absolute lymphocyte count decreased, the median time to initiation of therapy increased, and the median age of patients with Rai stage 0 CLL at the time of diagnosis increased over time. Overall, 54% of patients had received therapy for CLL by the time of last follow-up. Among the nonsurvivors, CLL was documented as the underlying or a contributing cause of death in 69%. CONCLUSION: The overall increase in CLL was thought to be due to enhanced methods of early diagnosis and improved health care for the elderly population. Thus, artifact may best explain the observed trend, although we cannot exclude the possibility of an actual increase in incidence rates over time.

Adult↗

PubMed1994

Primary cutaneous large cell lymphomas. Morphologic, immunophenotypic, and clinical features of 20 cases.

The morphologic, immunophenotypic, and clinical characteristics of 20 cases of primary cutaneous large cell lymphoma were analyzed. Immunoperoxidase stains in paraffin sections indicated B-cell phenotype in 14 cases and T-cell phenotype in six cases. By the Kiel classification, the B-cell lymphomas were classified into the following categories: follicular centroblastic (three patients), centroblastic/centrocytic with a predominance of large centrocytes (two patients), centroblastic (seven patients), and immunoblastic (two patients). The T-cell lymphomas (six cases) were all categorized as pleomorphic medium and large cell type. Three of these had an angiocentric growth pattern. The lymphocyte activation marker CD30 was expressed in three of the 20 cases. Among these 20 patients, the clinical course was remarkably variable. The only clinical or pathologic feature with prognostic significance was multicentricity of the skin lesions. All five patients with multifocal or disseminated skin lesions died within 13 months of their initial presentation; the median survival was 7 months. Most of the patients with localized skin lesions had an indolent clinical course with a median survival of 107 months. These results suggest that multicentricity of the skin lesions and necrosis are closely linked and are important prognostic features in cutaneous large cell lymphoma.

Adult↗

PubMed1994

Lymphoma involving the esophagus.

Fewer than 1% of all lymphomas involve the esophagus; however, lymphoma of the esophagus represents an important cause of dysphagia. This study reviewed all cases of biopsy-proven lymphoma involving the esophagus presenting at our institution between 1945 and 1992. Twenty-seven cases were identified. Three were primary esophageal lymphomas. Eleven percent of the cases presented Hodgkin's disease. Eighty-nine percent were non-Hodgkin's lymphoma. Eighty-nine percent of the patients experienced dysphagia. Eleven lymphomas (41%) were located at the gastroesophageal junction, while the other 17 were in the esophagus proper. Seven of these cases occurred at relapse. Three had mediastinal adenopathy with secondary esophageal involvement. Morbidity included tracheoesophageal fistula in 22%, and surgical repair was performed in half of these cases. Vocal cord paralysis occurred in 22%, with minimal sequelae. Esophageal stricture was present in 30%, usually necessitating dilation. The presentation, diagnosis, and management of this problem are multidisciplinary.

Adult↗

PubMed1994

Long-term follow-up of a CHOP-based regimen with maintenance therapy and central nervous system prophylaxis in lymphoblastic non-Hodgkin's lymphoma.

The Eastern Cooperative Oncology Group (ECOG) conducted a phase II trial in adult patients with lymphoblastic non-Hodgkin's lymphoma. Thirty-nine patients with no central nervous system (CNS) involvement were treated with an induction cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)/L-asparaginase regimen and CNS prophylaxis that included intrathecally administered methotrexate given 6 times and 24 Gy midplane cranial radiation in 12 fractions. Thirty-one patients (79%) achieved a complete remission (CR). Of the 31 patients with CRs, 12 relapsed (39%). CNS relapse occurred in three patients. All patients who entered a CR were treated with maintenance CHOP, cytosine arabinoside (AraC), and methotrexate and subsequently with Ara-C and methotrexate. Life-threatening leukopenia or thrombocytopenia was experienced in 69% of patients in the induction phase and in 70% in the maintenance phase. Nineteen of 39 patients (49%) remain in CR with a followup to 9 years. Bone marrow involvement was associated with a significantly worse survival (P = 0.03).

Adolescent↗

PubMed1992

Peripheral T-cell lymphoma involving the placenta.

BACKGROUND: Placental involvement by maternal malignant lymphoma is a rare complication of pregnancy. METHODS: The case of a 29-year-old woman found to have placental involvement by peripheral T-cell lymphoma (PTCL) diagnosed by morphologic study, immunoperoxidase stains, and molecular genetic studies is reported. RESULTS: The lymphoma was pathologic Stage IVB and although there were no adverse consequences for the child, but the neoplasm progressed rapidly during the postpartum period. CONCLUSIONS: The clinical course suggested that the immunologic changes of the pregnancy exerted a lymphoma-suppressive effect on the lymphoma. The authors know of no other report of a patient with placental involvement by PTCL.

Adult↗

PubMed1992

Mayo Clinic experience with allogeneic and syngeneic bone marrow transplantation, 1982 through 1990.

Between April 1982 and July 1990, 101 patients underwent allogeneic or syngeneic bone marrow transplantation at the Mayo Clinic. This patient population consisted of 30 with acute nonlymphocytic leukemia, 25 with acute lymphoblastic leukemia, 29 with chronic granulocytic leukemia, and 17 with other diseases (aplastic anemia in 7, myelodysplastic syndrome in 5, and lymphoma in 5). The results achieved in our patients who underwent transplantation in first complete remission of both acute nonlymphocytic leukemia and acute lymphoblastic leukemia compare favorably with previously reported results. Only 1 of 15 patients (7%) with acute nonlymphocytic leukemia and 2 of 8 patients (25%) with acute lymphoblastic leukemia who underwent transplantation in first complete remission had a relapse. Thus, we recommend early bone marrow transplantation during initial complete remission for patients with either of these disorders who have adverse prognostic factors. In contrast, of 12 patients with either acute nonlymphocytic leukemia or acute lymphoblastic leukemia who underwent transplantation during relapse, 11 died within 6 months. Therefore, such patients should be offered new experimental treatments. Our patients with chronic granulocytic leukemia fared better when they underwent transplantation early during the course of their disease rather than during the accelerated or blast phase. Prospective studies are needed to determine the best approach in these patients.

Academic Medical Centers↗

PubMed1992

Sequential administration of recombinant interferon alpha and deoxycoformycin in the treatment of hairy cell leukaemia.

Both recombinant interferon alpha and deoxycoformycin (dCF) are effective in the treatment of hairy cell leukaemia. In an attempt to reduce the complications from dCF therapy, a pilot study of the Eastern Cooperative Oncology Group (ECOG) first treated patients with interferon to improve peripheral blood cell counts before dCF treatment began. Thirty-four patients were treated for 3 months with recombinant interferon alpha-2a (rIFN alpha-2a), 3 x 10(6) IU subcutaneously three times a week for 3 months, and then by dCF, 4 mg/m2 intravenously every 2 weeks for a maximum of 12 months. The overall response rate was 94% (32/34); 76% of patients (26/34) had complete response (CR) (90% confidence interval, 62-88%) and 18% (6/34) partial response. One patient was found to have a Mycobacterium avium infection while receiving rIFN alpha-2a. Without specific antimycobacterial therapy and with continued administration of rIFN alpha-2a and dCF, the infection resolved and he achieved CR. Three patients had culture-negative febrile episodes during the dCF phase of treatment. Non-disseminated herpes zoster developed in four patients, but three of the episodes occurred only after treatment was discontinued. Sequential administration of rIFN alpha-2a and dCF resulted in fewer infections (P = 0.027) than in ECOG's previous study of dCF used alone. Two patients died, one of combined hairy cell leukaemia and non-Hodgkin's lymphoma of intermediate histologic type 17 months after entry into the study and the other of cardiac arrest 20 months after entry. Thirty-two patients were alive with a median follow-up of 21 months (range 13-31 months). This combination produces durable CRs with a low incidence of infection.

Adult↗

PubMed1991

Granulomatous angiitis of the spinal cord associated with Hodgkin's disease.

A 28-year-old man had a 5-month history of focal and generalized neurologic symptoms culminating in a thoracic myelopathy. Evaluation revealed granulomatous angiitis of the spinal cord in association with occult nodular sclerosing Hodgkin's disease. In previous reports, manifestations indicative of intracranial involvement have dominated the clinical presentation of granulomatous angiitis associated with Hodgkin's disease. Successful therapy for Hodgkin's disease may result in marked improvement of associated granulomatous angiitis, whereas the lack or failure of therapy results in a uniformly fatal outcome. Definitive antemortem diagnosis of granulomatous angiitis requires a biopsy of involved tissue. The cause of granulomatous angiitis, as well as the nature of its association with Hodgkin's disease, remains unexplained.

Adult↗

PubMed1991

Models of S-phase determination in lymphomas from flow cytometric DNA content histograms: comparison with the bromodeoxyuridine labeling index.

The estimated S-phase fraction (%S) of non-Hodgkin's lymphomas has been demonstrated to be of prognostic value. The %S can be determined by labeling index (LI) techniques or by various mathematical models applied to DNA content histograms. We performed DNA content analysis and a slide-based bromodeoxyuridine immunofluorescence LI on split samples from 117 biopsy specimens suspicious for lymphoma. The LI was compared with the %S determined by two computer models (rectangular and polynomial) with and without debris subtraction, and a manual gates computer model. In the 93 DNA diploid cases, the rectangular models had the highest correlation with the LI (R = 0.88). In the 24 aneuploid cases, the manual gates model was the most useful because of a high correlation with the LI (R = 0.70) and its ability to be used in most cases (23/24). The polynomial models had limited usefulness because they generally gave a higher %S than the LI and could be fitted in less than half of the DNA aneuploid histograms. These results suggest that in situations where the LI is not possible, an accurate %S estimate can usually be obtained with either a rectangular or manual gates model.

Bromodeoxyuridine↗