Biomedical subjects

T E Witzig

Publications and source records attributed to T E Witzig.

141 records · Page 8Linked to original sources

PubMed1989

Detection of hypodiploidy using multi-parameter flow cytometric analysis: a prognostic indicator in multiple myeloma.

We analyzed 49 patients with multiple myeloma (MM) using propidium iodide (PI) staining and flow cytometry to assess DNA content of MM cells in bone marrow. In 12 patients the presence or absence of DNA content aneuploidy could not be determined by analysis of single-parameter DNA histograms alone. Using forward light scatter measurement, resolution of ploidy was readily obtained in all but three cases. Assuming the DNA content of the low light scatter population to be diploid, we were able to classify 7 cases as hypodiploid and 39 as hyperdiploid or diploid. Hyperdiploid or diploid patients survived a median of 24 months and hypodiploid patients only 2.5 months. We conclude that multiparameter analysis of DNA content and light scatter provides easier analysis for the presence or absence of aneuploidy. Patients with DNA content hypodiploidy have a short survival.

Bone Marrow↗

PubMed1989

Rapid S-phase determination of non-Hodgkin's lymphomas with the use of an immunofluorescence bromodeoxyuridine labeling index procedure.

Cell kinetic measurements are currently being investigated to determine if they are useful in the clinical management of patients with non-Hodgkin's lymphomas (NHLs). Although the tritiated thymidine labeling index (TLI) is the standard method of S-phase measurement, it is difficult to perform. The authors describe a slide-based immunofluorescence labeling index (LI) method that uses 5-bromo-2-deoxyuridine (BrdUrd) as the pulsing medium and a monoclonal antibody (BU-1) to BrdUrd. The BrdUrd LI was performed on 217 NHLs and compared with routine histologic results. The authors found a median BrdUrd LI of 0.9% for low-grade NHLs; 7.5% for intermediate-grade; 10.4% for high-grade; and 2.2% for T-cell NHLs. This method provides a rapid, reliable S-phase measurement that can be easily performed in the clinical laboratory. It should replace the TLI and allow wider application of S-phase measurements in the NHL.

Antibodies, Monoclonal↗

PubMed1989

Isolation of a heparin-like anticoagulant from the plasma of a patient with metastatic bladder carcinoma.

A 73-year-old woman with metastatic transitional cell carcinoma of the bladder developed vaginal bleeding a few days after undergoing radical cystectomy. She had no other signs of mucocutaneous bleeding. Coagulation studies revealed a markedly prolonged thrombin time (greater than 600 seconds), a slightly prolonged reptilase time (20 seconds), and mildly elevated fibrinogen (4.39 g/L), and fibrin D-dimer (200 to 500 ng/mL) levels. Treatment of the patient's plasma in vitro with protamine or barium sulfate normalized the thrombin time. The anticoagulant activity corresponded to 0.15 heparin U/mL when measured by a thrombin time assay using normal plasma as substrate and standardized with porcine heparin. The anticoagulant was quantitatively bound to and subsequently eluted with 1 mol/L NaCl from quaternary aminoethyl (QAE) Sephadex, and then isolated by affinity chromatography on immobilized antithrombin III. The isolated anticoagulant was shown to be sensitive to heparinase digestion. Therefore, the inhibitor has functional and chemical properties similar to those of high-affinity heparin. Thus far, this is the only anticoagulant of this type isolated from the plasma of a patient bearing a tumor other than plasma cell myeloma.

Aged↗

PubMed1988

Oncogene expression in T-cell lymphoproliferative disorders.

We have investigated the expression of oncogenes and other related genes in eleven patients with T-cell lymphoproliferative disorders and ten patients with other hematologic malignancies. The phenotypes of the T-cell disorders were determined using monoclonal antibodies specific for helper or suppressor subsets. RNA preparations were isolated from peripheral blood mononuclear cells and/or lymph node sections, 5'-end labeled with gamma-32P-ATP, and hybridized under stringent conditions to an excess of nitrocellulose-bound specific cloned DNA; autoradiographs were analysed by microdensitometry. Results revealed increased expression of K-ras, v-fps, transferrin receptor, alpha-tubulin and alpha-interferon in at least five of six helper T-cell lymphoproliferative disorders, while five of five suppressor T-cell disorders demonstrated levels of hybridization to these clones no higher than background. However, studies of T-suppressor disorders demonstrated enhanced levels of beta-interferon-specific RNA in five of five patients, an increase apparent in three of six T-helper chronic lymphoproliferative disorders. These results demonstrate different patterns of gene expression evident in T-helper and T-suppressor abnormalities.

Adult↗

PubMed1988

Peripheral blood B cell labeling indices are a measure of disease activity in patients with monoclonal gammopathies.

Labeling indices (LI) provide a rapid measure of the bone marrow (BM) plasma cell proliferation rate and are useful in the diagnosis and prognosis of monoclonal gammopathies. Because circulating B cells may be a part of the neoplastic clone, we examined peripheral blood B cells that were producing the same cytoplasmic light chain isotype as the patient's monoclonal; protein (M-protein) and determined the peripheral blood LI (PBLI) by a two-color immunofluorescence bromodeoxyuridine method. The 105 patients studied were divided into three disease activity groups by standard clinical criteria. Median PBLI was 0.2% for the 29 patients with inactive monoclonal gammopathies (monoclonal gammopathy of undetermined significance [MGUS] and smoldering multiple myeloma [SMM]), 0.8% for the 35 patients with new, untreated multiple myeloma (MM), and 1.7% for the 41 patients with relapsed MM. These differences between groups were statistically significant (P less than .001, Wilcoxon). Four patients had high PBLI but clinically inactive gammopathy at the time of study, and all developed active MM within 6 months that required treatment. In 92 patients a BMLI was performed simultaneously with the PBLI (rank correlation coefficient, 0.69). In patients with new, untreated MM, use of both tests identified 72% of patients (23 of 32) with high LI, rather than 56% (18 of 32) by BMLI alone or 63% (20 of 32) by PBLI alone. These results suggest that PB B cells bearing the same cytoplasmic light chain isotype as the monoclonal protein are part of the malignant clone and can be kinetically active. The LI of these cells can provide a measure of disease activity and may help to differentiate active from inactive disease.

B-Lymphocytes↗

PubMed1987

Immunofluorescence labeling indices in myeloma and related monoclonal gammopathies.

We measured plasma cell labeling indices (LI) in 52 patients with monoclonal gammopathies. Cytoplasmic reactivity with polyspecific or kappa- and lambda-specific light chain anti-Ig reagents identified monoclonal plasma cells, plasmablasts, and lymphocytoid plasma cells. Among newly diagnosed untreated patients, a high immunofluorescence LI distinguished those with multiple myeloma (MM) from those with stable monoclonal gammopathies (P less than 0.002). Among treated patients with MM, those in the plateau phase of the disease had low LI, whereas patients in the relapse phase or early in treatment had high LI. The immunofluorescence LI correctly classified three more patients with newly diagnosed MM than did the tritiated thymidine LI technique. LI specific for the neoplastic plasma cells resulted in excellent discrimination of patients with active disease. Because results are easily and rapidly obtained, this technique is useful clinically.

Amyloidosis↗

PubMed1986

Diagnosis of B-cell non-Hodgkin's lymphoma of the central nervous system by immunocytochemical analysis of cerebrospinal fluid lymphocytes.

Diagnosis of central nervous system (CNS) non-Hodgkin's lymphomas may be difficult despite the use of sophisticated scans and routine cytologic methods. The use of an immunoalkaline phosphatase technique to examine cerebrospinal fluid (CSF) containing many mononuclear cells is described. Monoclonal proliferations of B-lymphocytes were demonstrated in six patients with neurologic abnormalities, whose clinical findings and subsequent clinical courses were those of lymphoma. The diagnosis of CNS lymphoma could not be made, despite multiple diagnostic procedures, until the immunocytochemical studies were performed. In three other patients, a lymphoproliferative disorder was suspected; however, examination of CSF showed many T-lymphocytes but no monoclonal B-lymphocytes, consistent with a reactive lymphocytosis. The subsequent clinical courses of these patients have shown no evidence of CNS lymphoma. Immunocytochemical studies of CSF lymphocytes are useful in differentiating benign from malignant proliferations.

Adult↗

PubMed1986

T-cell chronic lymphocytic leukemia with a helper/inducer membrane phenotype: a distinct clinicopathologic subtype with a poor prognosis.

T-cell chronic lymphocytic leukemia (T-CLL) accounts for about 2% of the various types of CLL and can be subtyped into helper/inducer (h/i) and cytotoxic/suppressor (c/s) cell membrane phenotypes. Seven patients with CLL were shown to have T-CLL with a h/i cell membrane phenotype; four with monoclonal antibody reagents and three by demonstration of the E-rosette receptor and focal acid alpha naphthyl acetate esterase activity. The clinical courses, treatment responses, and laboratory findings of these seven patients were reviewed to determine the prognosis and unique clinicopathologic features of this subtype. Two patients presented with skin rashes, and five were diagnosed during evaluation for other medical problems. Initially, four patients had splenomegaly and two had lymphadenopathy, but none of the patients had hepatomegaly. Morphologic examination revealed uniform, small lymphocytes in three patients, and the lymphocytes had nuclear indentations in four patients. Sera from the three patients tested were negative for antibody to the human T-cell leukemia/lymphoma virus I. Peripheral blood mononuclear cells from one patient showed normal interleukin-2 production and lacked antibody-dependent cell-mediated cellular cytotoxicity and natural killer activity. Cytogenetic analysis was done on one patient, revealing an abnormal clone with several chromosomal abnormalities, including an X;14 translocation with a break point at 14q11. All patients required chemotherapy, and all died a median of 21 months from the time of diagnosis. The findings in these patients, in addition to those in 31 patients described in the literature, indicate that h/i T-CLL is associated with a poor prognosis and has distinct clinical and pathologic features that separate it from c/s T-CLL, adult T-cell leukemia/lymphoma, the cutaneous T-cell lymphomas, and B-CLL.

Adult↗

PubMed1985

Platelet transfusion therapy in acute leukemia: lack of effect of splenomegaly on transfusion requirements and risk of hemorrhage.

Platelet transfusions are an important supportive measure during treatment for acute nonlymphocytic leukemia (ANLL). The presence of splenomegaly may produce decreased posttransfusion platelet increments leading some to recommend an increased dose of platelets per transfusion in this situation. Forty-nine newly diagnosed patients with ANLL were evaluated during 1980 and 1981, and 24% had palpable splenomegaly. Although treated with usual doses of platelets per transfusion, there was no detectable statistical increase in transfusion requirement or incidence of hemorrhage in patients with splenomegaly. Experimental evidence indicates that the splenic platelet pool enlarges with splenomegaly, but the life span of circulating platelets is not significantly changed. Furthermore, the splenic platelet pool is in dynamic equilibrium with the circulating platelet pool thus allowing these platelets to participate in hemostasis. Although posttransfusion increment in platelet count may be less, it appears that platelet transfusion therapy need not be altered solely because of splenomegaly.

Acute Disease↗

PubMed1985

Immunofluorescent plasma cell labeling indices (LI) using a monoclonal antibody (BU-1).

Tritiated thymidine labeling indices (LI), although useful in diagnosis and prognosis of multiple myeloma, have not found wide-spread application because autoradiographic analysis is difficult and time consuming. Using a monoclonal antibody (BU-1) reactive with 5-bromo-2-deoxyuridine (BrdUrd), we have developed an immunofluorescent procedure that allows DNA S-phase measurements to be determined in 4 hr. Plasma cells are easily identified by reactivity with a fluorescein isothiocyanate-conjugated antihuman immunoglobulin, and cells in DNA S phase are detected via BU-1 and a rhodamine-conjugated antimouse immunoglobulin. Results using this method on 12 patients with multiple myeloma compare favorably (correlation coefficient 0.84), with those obtained by tritiated thymidine. This immunofluorescent slide method will facilitate application of labeling indices as a clinical test to measure disease activity in patients with multiple myeloma and other hematologic neoplasms.

Antibodies, Monoclonal↗

PubMedDate not supplied

Lymphoproliferative disorders of the head and neck.

Lymphoproliferative disorders are the frequent cause of indeterminate processes in the head and neck region for which otolaryngologists are often consulted by colleagues seeking a diagnosis. Because a wide spectrum of diseases may be represented, tissue diagnosis is often required. Recent advances in tissue immunotyping and DNA probes permit more precise identification and classification of these disorders. Lymphoproliferative disorders may be subdivided into five categories: Hodgkin's disease, non-Hodgkin's lymphoma, histiocytosis X, benign reactive lymphoproliferative disorders, and plasma cell neoplasms. Representative cases are presented, along with a brief discussion of each category.

Adult↗

PubMedDate not supplied

Biodistribution and dosimetry results from a phase III prospectively randomized controlled trial of Zevalin radioimmunotherapy for low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma.

UNLABELLED: Radiation dosimetry studies were performed in patients with non-Hodgkin's lymphoma (NHL) treated with 90Y Zevalin (90yttrium ibritumomab tiuxetan, IDEC-Y2B8) on a Phase III open-label prospectively randomized multicenter trial. The trial was designed to evaluate the efficacy and safety of 90Y Zevalin radioimmunotherapy compared to rituximab (Rituxan, MabThera) immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed NHL. An important secondary objective was to determine if radiation dosimetry prior to 90Y Zevalin administration is required for safe treatment in this patient population. METHODS: Patients randomized into the Zevalin arm were given a tracer dose of 5 mCi (185 MBq) (111)In Zevalin (111indium ibritumomab tiuxetan) on Day 0, evaluated with dosimetry, and then administered a therapeutic dose of 0.4 mCi/kg (15 MBq/kg) 90Y Zevalin on Day 7. Both Zevalin doses were preceded by an infusion of 250 mg/m(2) rituximab to clear peripheral B-cells and improve Zevalin biodistribution. Following administration of (111)In Zevalin, serial anterior and posterior whole-body scans were acquired and blood samples were obtained. Residence times for 90Y were estimated for major organs, and the MIRDOSE3 computer software program was used to calculate organ-specific and total body radiation absorbed dose. Patients randomized into the rituximab arm received a standard course of rituximab immunotherapy (375 mg/m(2) weekly x 4). RESULTS: In a prospectively defined 90 patient interim analysis, the overall response rate was 80% for Zevalin vs. 44% for rituximab. For all patients with Zevalin dosimetry data (N=72), radiation absorbed doses were estimated to be below the protocol-defined upper limits of 300 cGy to red marrow and 2000 cGy to normal organs. The median estimated radiation absorbed doses were 71 cGy to red marrow (range: 18-221 cGy), 216 cGy to lungs (94-457 cGy), 532 cGy to liver (range: 234-1856 cGy), 848 cGy to spleen (range: 76-1902 cGy), 15 cGy to kidneys (0.27-76 cGy) and 1484 cGy to tumor (range: 61-24274 cGy). Toxicity was primarily hematologic, transient, and reversible. The severity of hematologic nadir did not correlate with estimates of effective half-life (half-life) or residence time of 90Y in blood, or radiation absorbed dose to the red marrow or total body. CONCLUSION: 90Y Zevalin administered to NHL patients at non-myeloablative maximum tolerated doses delivers acceptable radiation absorbed doses to uninvolved organs. Lack of correlation between dosimetric or pharmacokinetic parameters and the severity of hematologic nadir suggest that hematologic toxicity is more dependent on bone marrow reserve in this heavily pre-treated population. Based on these findings, it is safe to administer 90Y Zevalin in this defined patient population without pre-treatment (111)In-based radiation dosimetry.

Antibodies, Monoclonal↗

PubMedDate not supplied

Thalidomide as an anti-cancer agent.

Thalidomide is a glutamic acid derivative initially introduced as a sedative hypnotic nearly forty years ago. It was withdrawn following numerous reports linking it to a characteristic pattern of congenital abnormalities in babies born to mothers who used the drug for morning sickness. It has gradually been re-introduced into clinical practice over the past two decades, albeit under strict regulation, since it was found to be useful in the management of erythema nodosum leprosum and HIV wasting syndrome. Recognition of its anti-angiogenic effect led to its evaluation in the treatment of various malignancies, where angiogenesis has been shown to play an important role. Numerous clinical trials done over the past four years have confirmed the significant anti-myeloma activity of this drug. It has also shown promise in preliminary trials in the treatment of a variety of different malignant diseases. The mechanisms of its antineoplastic effects continue to be the focus of ongoing research. It has become clear that even though its anti angiogenic effects play a significant role in the anti-tumor activity, there are other properties of this drug which are responsible as well. It also possesses anti-TNF alpha activity, which has led to its evaluation in several inflammatory states. In this concise review, we briefly describe the historical background and pharmacological aspects of this drug. We have concisely reviewed the current knowledge regarding mechanisms of its anti-neoplastic activity and the results of various clinical trials in oncology.

Antineoplastic Agents↗

PubMedDate not supplied

Efficacy of splenectomy for patients with mantle cell non-Hodgkin's lymphoma.

The purpose of this study was to define the role of splenectomy in patients (pts) with mantle cell lymphoma (MCL) with regard to improving cytopenias and symptoms of splenomegaly. 26 pts with MCL underwent splenectomy between January 1987 and October 1999 and were followed prospectively for hematologic response and operative morbidity and mortality. A positive response was defined at 1 month of follow-up as: a hemoglobin of > or = 1.0 g/dl in a pt with a preoperative value < 11.0 g/dl; or a platelet count of > or = 100 x 10(9)/L in a pt with a preoperative value < 100 x 10(9)/L. A positive hematologic response was achieved in 69.2% of pts with preoperative anemia, 90% with thrombocytopenia, and 50% with both anemia and thrombocytopenia. The peri- and post-operative morbidity were 3.8 and 19.2%, respectively, the operative mortality was 0%. The median duration of hospitalization was six days. Four (15.4%) pts have not required chemotherapy after splenectomy. Three of these four were previously untreated and they have maintained stable disease for eight years after splenectomy without chemotherapy. Eight additional pts did not require chemotherapy for > 13 months after splenectomy. These results suggest that splenectomy may provide durable remission in selected pts with refractory cytopenias or symptoms related to splenomegaly in pts with MCL. There is a subset of pts that have prolonged disease stabilization without the requirement for immediate chemotherapy after splenectomy.

Adult↗

PubMedDate not supplied

Rituximab toxicity in patients with peripheral blood malignant B-cell lymphocytosis.

Infusion related adverse events (AE) with day 1 rituximab in patients with B-cell non-Hodgkin's lymphoma (NHL) are common. The purpose of this study was to evaluate the AE occurring in patients with malignant B-cell lymphocytosis who received rituximab. Patients with a > or = 3 x 10(9)/L absolute lymphocyte count (ALC) receiving rituximab from 1998 to 1999 or participating in a phase I study of rituximab and interleukin-12 were reviewed. The AE occurring on the day of rituximab, the treatment provided (including hospitalization), and the subsequent ALC responses were recorded. Twenty-seven patients were identified; 14 had NHL, one Waldenstrom's macroglobulinemia, and 12 patients had chronic lymphocytic leukemia. The baseline median ALC was 9.58 x 10(9)/L (mean, 49.31; range, 3.56-380.95). All patients received rituximab as an outpatient. There were only two AE > or = grade 3. One patient was hospitalized for 1 day for i.v. fluids to treat an increase in creatinine that occurred with tumor lysis. A second patient developed a pulmonary syndrome five days after day 1 rituximab and required mechanical ventilation, but had no long-term lung toxicity. This study demonstrates that patients with high numbers of circulating blood B-lymphocytes can usually safely receive rituximab as outpatients. Patients who experience a rapid drop in ALC should be monitored closely for tumor lysis and the pulmonary syndrome.

Adult↗