Search PubMed⌕ Search

Biomedical subjects

T Han

Publications and source records attributed to T Han.

At least 91 records · Page 5Linked to original sources

Shared idiotype expression by chronic lymphocytic leukemia and B-cell lymphoma.

Antiidiotype (Id) antibodies identify unique determinants within the surface immunoglobulin (Ig) that are present on B-cell tumors. Anti-Ids have been used for diagnosis and therapy of B-cell lymphoma and leukemia. A panel of 29 anti-Id monoclonal antibodies (MoAbs) that recognize shared idiotypes (SIds) on B-cell lymphomas was tested for reactivity with both B-cell leukemias and lymphomas. Ten of 40 (25%) cases of chronic lymphocytic leukemia (CLL) reacted with at least one of the 29 anti-SId MoAbs. Three cases reacted with more than one anti-SId MoAb, but there was no repetitive pattern of a single anti-SId MoAb reacting with a large proportion of CLL cases. In contrast, for B-cell lymphoma, in which 11 of 31 (36%) cases reacted, one anti-SId (B4-1) reacted with five of the positive cases; all were diffuse histology. Restricted anti-SId reactivity may lead to important insights into the etiology of certain B-cell lymphomas. In addition, these anti-SIds may obviate the need to develop "tailor-made" antibodies for individual patients.

Antibodies, Monoclonal↗

Antibody-dependent, cell-mediated cytotoxicity by an anti-class II murine monoclonal antibody: effects of recombinant interleukin 2 on human effector cell lysis of human B-cell tumors.

Lym-1 is an IgG2a murine monoclonal antibody that reacts with variant Class II molecules expressed on B-cell malignancies. Lym-1 was shown to mediate antibody-dependent cellular cytotoxicity (ADCC) of human effector cells against a variety of malignant B-cell lines. Tumor cell lysis was Lym-1 specific because (a) the reaction was dose dependent with significant ADCC detectable at Lym-1 concentrations as low as 1 microgram/ml; (b) tumor targets not expressing the Lym-1 antigen were unaffected; (c) an isotype-matched irrelevant monoclonal antibody and an IgG1 anti-Class II monoclonal antibody failed to mediate ADCC; and (d) addition of Protein A (which binds avidly to Lym-1) blocked ADCC by 90 to 100%. Peripheral blood mononuclear cells obtained from normal donors as well as from cancer patients were able to interact with Lym-1 to elicit ADCC. Recombinant interleukin 2 (rIL-2) enhanced non-antibody-mediated tumor lysis and Lym-1 ADCC with an optimal concentration of 100 units/ml. Pulse treatment of normal peripheral blood mononuclear cells with rIL-2 was able to augment Lym-1 ADCC but was less effective than having the rIL-2 present through the assay. Peripheral blood mononuclear cells obtained from patients being treated with high doses of rIL-2 administered by continuous i.v. infusion demonstrated Lym-1 ADCC levels which were higher than normal individuals and which were further augmented by in vitro incubation with rIL-2.

Animals↗

Management of chronic lymphocytic leukemia.

Significant progress has been made in the past two decades in the understanding of immunobiology of CLL and the development of clinical staging systems and identification of other prognostic factors in CLL. A significant advance in the management of CLL has also been made. Now we know when to initiate therapy. We recommend that patients with stage 0 and patients with stages I and II associated with good prognostic features such as absence of disease-related symptoms, long lymphocyte doubling time, nondiffuse bone marrow infiltration, and low tumor load not be treated; they should be followed at 2- to 6-month intervals. We recommend initiation of therapy for patients with stages I and II, associated with poor prognostic features such as presence of disease-related symptoms, short lymphocyte doubling time, diffuse bone marrow infiltration, and high tumor load and for patients with stages III and IV. However, we still do not know what constitutes the optimal therapy for the disease. In one large randomized study, the response rate as well as survival superiority of CHOP (with low-dose Adriamycin) over COP in previously untreated patients with stage C disease was observed. In another large randomized study, only a response rate advantage of CHOP (with standard dose Adriamycin) over chlorambucil and prednisone (in previously untreated patients with stages B and C) was seen. No randomized studies have compared CHOP versus chlorambucil and prednisone in patients with stages III and IV or stage C. At present, our recommendation for the treatment of patients with advanced disease is chlorambucil and prednisone therapy. New drugs under clinical trials for CLL include (1) deoxycoformycin, (2) 2-chlorodeoxyadenosine, and (3) fludarabine monophosphate. Both deoxycoformycin and 2-chlorodeoxyadenosine have been shown to have some activity in previously treated CLL patients with advanced disease. The effectiveness of these agents, however, has not been tested yet in untreated patients with advanced disease. Fludarabine monophosphate, on the other hand, has been shown to be very effective in both previously treated and untreated patients with advanced disease. Allogeneic bone marrow transplantation recently has been found to be of benefit in some patients (37 to 46 years) in a preliminary study; this therapeutic procedure should be tested further in a larger population of younger patients (less than 50 years) with advanced CLL. New agents such as lymphokines (interferons and IL-2) and monoclonal antibodies have been investigated for their efficacy and found to be minimally effective in previously treated patients with advanced disease.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗

Prognostic factors and clinical staging in chronic lymphocytic leukemia.

There has been significant progress in the past 10 years in our ability to prospectively predict prognosis in CLL. The clinical staging systems have helped us identify three broad groups of patients with respect to their overall outlook for survival: low risk (stage 0), intermediate risk (stages I and II), and high risk (stages III and IV). It seems reasonable to distinguish those low- and intermediate-risk patients who are likely to have a benign or indolent clinical course if their blood lymphocyte doubling time is longer than 12 months and their bone marrow biopsy pattern of lymphocytic infiltration is nondiffuse. With these guidelines, it will be possible to initiate meaningful and reliable therapeutic trials in CLL in the immediate future.

Biomarkers, Tumor↗

Splenectomy in advanced chronic lymphocytic leukemia.

Between February 1972 and February 1989, splenectomies were performed in 30 patients with chronic lymphocytic leukemia (CLL) and three with prolymphocytic leukemia (PLL) at our institution. Indications for splenectomy included anemia and/or thrombocytopenia (hypersplenism) in 31 patients and symptomatic splenomegaly in two patients. Median time from the diagnosis of CLL to splenectomy was 25 months. Twenty (87%) of the 23 patients splenectomized for thrombocytopenia with or without anemia had platelet increments of greater than or equal to 50 x 10(9)/liter. Hemoglobin increments of greater than or equal to 3 gm/dl were noted in 12 (71%) of 17 patients splenectomized for anemia with or without thrombocytopenia. The median duration of platelet response was 18 months for 19 evaluable patients, and the median duration of hemoglobin response was 62 months for 10 evaluable patients. Median survival time from splenectomy was 36 months. Median survival from diagnosis was 103 months for 10 patients with stage III or IV disease at diagnosis and 79 months for 10 patients with stage II. A prospective study of the effect of splenectomy in a larger number of patients with advanced CLL should be considered.

Adult↗

Initial clinical trial of the macrophage activator muramyl tripeptide-phosphatidylethanolamine encapsulated in liposomes in patients with advanced cancer.

A phase I clinical trial of the macrophage activator, muramyl tripeptide-phosphatidylethanolamine has been carried out in 37 patients (47 courses) at doses of 0.01-6.0 mg/m2 intravenously twice weekly for 4 weeks. Activation of peripheral blood monocytes and drug toxicity were used as the parameters to monitor the trial. Toxicity was acute systemic responses of fever, chills, and hypertension without a clear dose response. No major organ-related toxicity was seen. A dose of 4.0 mg/m2 biweekly produced activation of blood monocytes; a dose of 6.0 mg/m2 produced inhibition. There was one complete response of 3 months duration in a patient with renal cell carcinoma with pulmonary metastases. The optimum dose for phase II studies is in the range of 1-4 mg/m2 twice weekly for 4 weeks, a dose that is well tolerated.

Acetylmuramyl-Alanyl-Isoglutamine↗

Wide-field radiation therapy plus simultaneous chemotherapy for refractory Hodgkin's disease.

Nine male patients with disseminated Hodgkin's disease who had relapsed and/or were refractory to two or more non-"cross-resistant" programs of combination chemotherapy (range, two to five previous programs; median, three) were admitted into a study of treatment with wide-field low-dose radiation therapy (2,000 cGy), to all lymph node bearing areas, the liver, the spleen, and in selected cases the lungs (1,000 cGy). Simultaneous with each course of radiation therapy, chemotherapy with BCNU and procarbazine given at 50% doses of a known program of chemotherapy (BOPP) with vincristine and prednisone was given. Treatment was completed in five patients. Three of these achieved a complete remission; the other two had a partial response. Of the other four, two died during treatment with interstitial pneumonitis (probably radiation induced), and two failed to respond. Remission durations were 18+, 38, and 44+ months. Pulmonary toxicity was severe; however, hematologic and other toxicities were acceptable. The incorporation of wide-field low-dose radiation should be considered in programs of rescue for patients with Hodgkin's disease who relapse or are refractory to standard combination chemotherapy.

Adolescent↗

Acute nonlymphocytic leukemia in a patient with a constitutional inv(4).

We describe a case of acute nonlymphocytic leukemia (ANLL) in a patient with a constitutional chromosome anomaly, inv(4)(p16q26). The patient had extensive occupational exposure to toxic chemicals. Reports of constitutional or acquired chromosome inversions in human malignancies are quite uncommon. The constitutional changes associated with hematologic malignancies include trisomy 21, balanced translocations, deletions, and sex chromosome anomalies. The breakpoints on chromosome 4 in our case are 4p16, to which the murine leukemia viral (v-raf) oncogene, pseudogene 1, has been mapped, and 4q26, which is the locus of the IL-2 gene. Activation of these genes could have played a role in the pathogenesis of the patient's leukemia.

Aged↗