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S J Horning

Publications and source records attributed to S J Horning.

At least 19 recordsLinked to original sources
PubMed1992

Dynamic assessment of quality of life after autologous bone marrow transplantation.

To determine the quality of life in adult patients after autologous bone marrow transplantation (BMT), we administered a questionnaire to a cohort of patients seen at a single referral-based center. The sample included adults 18 years and older during the 1 year following an autologous BMT. Both disease-free patients and those who relapsed with 1-year of follow-up data available were included. Of 59 eligible patients, 58 (98%) responded to the questionnaire. Patients completed a telephone questionnaire administered by a nurse specialist in the field of BMT approximately every 90 days. At the time of initial contact on day +90, the mean quality of life was 7.8 (range, 1 to 10) on a scale of 1 to 10, with 10 being the best. By the end of the first year of follow-up, the mean quality of life was 8.9 (range, 3 to 10). Seventy-eight percent of the patients were employed. Twenty-one percent lost weight during the first year, with the majority reporting voluntary weight loss. Fourteen percent reported difficulties with sexual activity. Only 5% reported difficulty with sleeping or with frequent colds. One patient felt that her appearance was worse, and none of the patients reported a poor appetite. Eighty-eight percent of surviving adult patients reported an above-average to excellent quality of life 1 year following autologous BMT. This outcome is encouraging and suggests that this procedure is not associated with long-term morbidity in the surviving adult patient.

Adult↗
PubMed1992

Granulocyte-macrophage colony-stimulating factor (GM-CSF) as an adjunct to autologous hemopoietic stem cell transplantation for lymphoma.

OBJECTIVE: To determine the hemopoietic effects of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients having autologous hemopoietic stem cell transplantation for Hodgkin or non-Hodgkin lymphoma. DESIGN: Placebo or GM-CSF was administered after bone marrow or peripheral blood stem cell transplantation or both in a randomized, double-blind phase III trial by daily intravenous infusion (10 micrograms/kg body weight) until absolute neutrophil counts reached greater than or equal to 1000/mm3 on 3 consecutive days. SETTING: Bone marrow transplantation unit in a university hospital. PATIENTS: Sixty-nine consecutive patients with Hodgkin or non-Hodgkin lymphoma received GM-CSF (36 patients) or placebo (33 patients). MEASUREMENTS AND MAIN RESULTS: Patients who received GM-CSF achieved absolute neutrophil counts greater than or equal to 500/mm3 (median, 12 compared with 16 days, P = 0.02) and absolute neutrophil counts greater than or equal to 1000/mm3 (median, 15 compared with 24 days, P less than 0.001) more quickly than patients who received placebo. Multivariate analysis indicated that use of GM-CSF, peripheral blood stem cells, and unpurged bone marrow were the strongest predictors for early neutrophil recovery greater than 500/mm3. Bacterial infections were significantly reduced in the GM-CSF group (P = 0.04). Delayed engraftment (neutrophils less than 500/mm3 at day 30) occurred in 26% and 17% of the placebo and GM-CSF groups, respectively, and correlated with the absence of detectable myeloid progenitor cells (colony-forming units-granulocyte macrophage, CFU-GM) (P less than 0.001) in marrow aspirate specimens obtained on day 15. Time to platelet independence, duration of hospital stay, severe adverse reactions, relapse, and disease-free survival rates did not differ significantly between the two groups. CONCLUSIONS: Administration of GM-CSF after autologous hemopoietic stem cell transplantation in patients with lymphoma resulted in accelerated myeloid recovery, particularly in patients who received peripheral blood stem cells and nonpurged bone marrow, and was associated with a decreased incidence of bacterial infections.

Actuarial Analysis↗
PubMed1992

The Stanford experience with combined procarbazine, Alkeran and vinblastine (PAVe) and radiotherapy for locally extensive and advanced stage Hodgkin's disease.

This report describes the efficacy and toxicity of PAVe (procarbazine, Alkeran, vinblastine) and irradiation (RT) in the management of 159 patients with locally extensive or advanced stage Hodgkin's disease (HD) at Stanford University. Patients received six courses of chemotherapy alternating with RT. The extent of RT and the schedule of treatment varied according to the stage of disease. About 2/3 of patients received PAVe/RT in the setting of prospective, randomized clinical trials. The rate of complete response was 93%. With a median follow-up of seven years (range 2-17), the 15 year actuarial freedom from progression (FFP) is 78% and overall survival is 75%. Ten-year FFP by stage is: 80% for locally extensive stage II, 90% for stage IIIA and 70% for stage IIIB. Excellent and equal results were attained with PAVe/RT vs. MOP(P) (mustard, Oncovin, procarbazine with or without prednisone)/RT in the randomized combined modality studies. Progression or recurrence was documented in 30 patients and was more common in irradiated sites. PAVe was well tolerated acutely. There were no treatment related fatalities. Twenty-three (14%) patients were admitted to the hospital for neutropenic fever. Five second malignancies have occurred after PAVe/RT only: one myelodysplastic syndrome, one acute myelogenous leukemia, one non-Hodgkin's lymphoma and two solid tumors including a case of non-small cell lung cancer and an in situ carcinoma of the cervix. Three patients died from myocardial infarction several years after the completion of treatment. These mature data show that PAVe/RT is effective and well-tolerated therapy for locally extensive stage II and IIIA/B HD.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Clinical significance of morphologic subdivision in diffuse large cell lymphoma.

Although diffuse large cell lymphomas can be morphologically divided into large cell (DLC) and immunoblastic (IBL) subtypes, the clinical significance of this subdivision remains controversial. The initial diagnostic materials from 85 patients with recorded diagnoses of diffuse large cell lymphoma who were treated at Stanford between 1975 and 1986 with cyclophosphamide, doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH), vincristine, and prednisone (CHOP); methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (M-BACOD); or methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) chemotherapy were retrospectively reviewed by a panel of hematopathologists and classified according to morphologic criteria of the Working Formulation. Based on the criterion of agreement of two of three observers, 60 patients were classified as having DLC, 19 as having IBL, and the lymphomas in 6 patients could not be additionally classified. No significant differences in complete response (CR) rate, freedom from disease progression (FFP), or overall survival were found between the DLC and IBL groups. There was also no significant difference in prognosis between DLC cases additionally subclassified as large cleaved cell (16 patients) and those with large non-cleaved cell (36 patients). Although IBL is considered to be a high-grade lymphoma, the authors concluded that it does not differ significantly in prognosis from DLC lymphoma and, therefore, does not justify a modified treatment selection based on IBL morphologic type alone. Definitive evaluation of the prognostic significance of morphologic subdivision may require a larger cohort of uniformly treated patients.

Actuarial Analysis↗
PubMed1991

Enhanced detection of the t(14;18) translocation in malignant lymphoma using pulsed-field gel electrophoresis.

The t(14;18) chromosomal translocation that results in the juxtaposition of the bcl-2 proto-oncogene with the heavy chain JH locus is a common cytogenetic abnormality in human lymphoma. In particular, it is seen in about 85% of follicular lymphoma (FL) and up to one-third of diffuse lymphomas (DL). The chromosome 18 breakpoints have been shown to cluster into two regions. The major breakpoint region (mbr) within the 3' untranslated region of the bcl-2 proto-oncogene accounts for approximately 60% of the cases and the minor cluster region (mcr) 30 kb 3' of bcl-2 accounts for approximately 25% of the breakpoints. Because of variability in the position of the breakpoint, detection of the t(14;18) by Southern blot analysis provides an important clonal marker for the tumor. However, conventional electrophoresis (CE) fails to detect the translocation in 15% to 25% of cases. We have applied pulsed-field gel electrophoresis (PFGE) to the detection of the t(14;18) in a series of lymphoma prospectively analyzed by CE, polymerase chain reaction (PCR), and cytogenetic analysis. PFGE readily detected t(14;18) rearrangements as indicated by comigration of bands detected with probes for the mbr region (chromosome 18) and the JH locus (chromosome 14). In a series of 40 patients with FL, this method proved to be the most comprehensive for detection of the translocation compared with standard methods; in fact, in one case only PFGE was able to detect the chromosomal rearrangement. Ten percent of the FL cases were negative by all methods tested. In a separate analysis of matched tissue specimens from cases of tumor progression of FL to diffuse lymphoma, PFGE detected a common t(14;18) rearrangement confirming a clonal origin in seven of seven cases, whereas CE detected a rearrangement in only three of seven cases. Overall, PFGE was able to detect a translocation in 8 of 12 cases that were negative by CE and four of eight negative by cytogenetic analysis. In conclusion, PFGE analysis is more comprehensive than CE, PCR, and cytogenetic analysis for the detection of the t(14;18) breakpoint in tissue biopsies of malignant lymphoma.

Chromosome Mapping↗
PubMed1991

The Stanford experience with high-dose etoposide cytoreductive regimens and autologous bone marrow transplantation in Hodgkin's disease and non-Hodgkin's lymphoma: preliminary data.

Seventy-seven Hodgkin's disease and non-Hodgkin's lymphoma (NHL) patients received high-dose etoposide in combination with cyclophosphamide and either fractionated total body irradiation (TBI) (n = 28) or carmustine (n = 49) prior to autologous bone marrow transplantation. Marrow from NHL patients was purged in vitro with a panel of monoclonal B- and T-cell antibodies and complement. Six toxic deaths (8%) occurred, all in patients who received carmustine. With a median follow-up of 1 year, 57 patients are alive and free from progressive disease. The 1-year actuarial survival and freedom from progression are 85 and 73% in fractionated TBI/etoposide/cyclophosphamide-treated patients and 79 and 72% in carmustine/etoposide/cyclophosphamide-treated patients. Forty-five of these patients participated in prospective trials for which eligibility criteria were (1) less than 25% curability with conventional therapy; (2) achievement of minimal disease state with conventional therapy; and (3) transplantation early in the course of disease. One-year actuarial survival for 18 patients with relapsed Hodgkin's disease is 80% and for 21 relapsed intermediate and high-grade NHL patients, 70%. One NHL Burkitt's patient was transplanted on a protocol for high-risk intermediate and high-grade NHL in first remission. Five patients with follicular mixed or small cleaved NHL were also transplanted in first remission.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Similar outcome of treatment of B-cell and T-cell diffuse large-cell lymphomas: the Stanford experience.

Although previous studies have suggested a relatively poor prognosis for some patients with peripheral T-cell lymphoma, the clinical significance of immunologic phenotype in diffuse large-cell lymphoma (DLCL) remains controversial. One hundred one patients with a uniform morphologic diagnosis of DLCL treated at Stanford between 1975 and 1986 with cyclophosphamide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), vincristine, and prednisone (CHOP), methotrexate, bleomycin, Adriamycin, cyclophosphamide, vincristine, and dexamethasone ([M]BACOD), or methotrexate, Adriamycin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) chemotherapy were studied with regard to immunologic phenotype. Immunologic analysis, performed on frozen or paraffin-embedded tissue, identified 77 cases of B-cell origin, 21 cases of T-cell origin, and three cases that lacked B-cell or T-cell markers. Analysis of complete remission (CR) rates (84% v 95%), 5-year actuarial freedom from disease progression (38% v 53%), and 5-year actuarial overall survival (52% v 79%) showed no statistically significant differences in prognosis between B- and T-cell patients, respectively. The 5-year actuarial survival of patients with stage IV T-cell DLCL (56%) also did not differ in a statistically significant way from stage IV B-cell patients (36%). We conclude that treatment selection for DLCL should not be based on immunologic phenotype alone.

Actuarial Analysis↗
PubMed1991

The Stanford Hodgkin's disease (HD) studies--an update.

Successive, prospective clinical trials for adults with HD have been conducted from 1962-1991. With approximately 75% of patients in continuous remission as a result of current therapy, attention may be focused on reducing treatment complications for the majority of patients and improving efficacy in selected, high risk populations. This overview will describe recently completed and ongoing clinical trials at Stanford University which address these therapeutic objectives.

Adult↗
PubMed1991

Molecular biologic studies in the clinical evaluation of non-Hodgkin's lymphoma.

Recent advances in DNA technology have revealed new information about the biology of the non-Hodgkin's lymphomas that is both provocative and exciting. Because these technologies are just beginning to be applied to the clinical evaluation of the non-Hodgkin's lymphomas, the results of clinical studies must be regarded as preliminary. At this time we can only speculate on how they might lead to improved clinical management or provide the basis for new therapies.

Gene Rearrangement↗
PubMed1990

CEPP(B): an effective and well-tolerated regimen in poor-risk, aggressive non-Hodgkin's lymphoma.

Eighty-three patients with intermediate- or high-grade non-Hodgkin's lymphoma were treated with CEPP(B) (cyclophosphamide, etoposide [VP-16], procarbazine, and prednisone with or without bleomycin) chemotherapy at Stanford University Medical Center (Stanford, CA) from January 1982 through June 1989. Sixty-nine received CEPP(B) as second-line or subsequent therapy after relapse from previous combination chemotherapy, and 14 patients received CEPP(B) as first-line therapy. Of 75 patients evaluable for response, 30 patients (40%) achieved a complete response (CR) and 24 patients (32%) achieved a partial response (PR), providing an overall response rate of 72%. Complete responses were recorded on 21 of 61 (34%) patients with recurrent disease and 9 of the 14 patients who received CEPP(B) as first line therapy (64%). Myelosuppression was the major side effect of treatment, resulting in eight neutropenic-febrile episodes from a total of 253 courses. A single fatal toxic event occurred on a patient who developed adult respiratory distress syndrome. Overall, CEPP(B) was well-tolerated and proved to be effective palliative therapy for patients with non-Hodgkin's lymphoma after relapse. As such, CEPP(B) may be considered for cytoreduction before ablative therapy and bone marrow transplantation. CEPP(B) may also be considered for initial therapy in selected patients who cannot tolerate doxorubicin-containing regimens.

Adult↗
PubMed1990

Detection of non-Hodgkin's lymphoma in the peripheral blood by analysis of antigen receptor gene rearrangements: results of a prospective study.

Analysis of immunoglobulin (Ig) and T-cell receptor gene rearrangements, using Southern blot hybridization, has been applied to peripheral blood lymphocytes (PBL) in 335 samples from patients with non-Hodgkin's lymphoma. The incidence of circulating lymphoma cells detected by gene rearrangement analyses is related to the histologic subtype, clinical stage of disease, and clinical status. Among 104 patients studied at diagnosis, the incidence of positive analyses was 34% in low-grade lymphoma and only 8% in intermediate-grade lymphoma. Clonal Ig gene rearrangements were detected nearly universally in the small lymphocytic histologic subtype. PBL studies were related to the initial stage of disease: positive studies were seen in 35% of patients with stage IV disease, 29% of patients with stage III disease, and 12% of patients with stages I-II disease. The incidence of PBL rearrangements at the time of disease recurrence in 32 patients requiring cytoreductive therapy was 48%, somewhat greater than at initial diagnosis. A group of patients with low-grade lymphoma, who had treatment deferred after diagnosis or recurrence, was also studied; the incidence of PBL rearrangements was 38% in this population. Among 157 patients clinically free of disease, DNA analyses of the PBL were positive in only 10%. Subsequent relapse of disease in 26 patients was antedated by PBL rearrangement in only one patient. Clonal rearrangements detected in 15 patients have been followed by recurrence of clinical disease in only one patient over a median of 24 months from the time of analysis. The lack of detectable rearrangements in the peripheral blood in the majority of patients may be due to methodology or the biology of the disease. These issues may be further addressed with alternative methods for assessment of minimal disease. However, rigorous testing of any new molecular tool requires an adequate patient population in which disease status is closely monitored over a sufficient period of time.

Blotting, Southern↗
PubMed1990

Prognostic significance of actual dose intensity in diffuse large-cell lymphoma: results of a tree-structured survival analysis.

While diffuse large-cell lymphoma (DLCL) is considered to be highly curable with current therapy, treatment failures are observed even with intensive combination chemotherapy regimens. In order to study the prognostic significance of actual dose intensity of chemotherapy in DLCL, we retrospectively analyzed 115 previously untreated patients treated as Stanford between 1975 and 1986 with cyclophosphamide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), vincristine, and prednisone (CHOP), methotrexate, bleomycin, Adriamycin, cyclophosphamide, vincristine, and dexamethasone ([M]BACOD), or methotrexate, Adriamycin, cyclosphosphamide, vincristine, prednisone, and bleomycin (MACOP-B). The actual relative dose intensity (RDI), the amount of drug actually administered to each patient during the first 12 weeks of therapy, was calculated as standardized to CHOP and analyzed in addition to clinical factors prognostic for survival by univariate analysis. Multivariate recursive partitioning (tree-structured) survival analysis identified the actual RDI of Adriamycin greater than 75% as the single most important predictor of survival. A model incorporating the actual RDI of Adriamycin and performance status, in combination with serum lactate dehydrogenase (LDH) and extranodal disease, defined three overall prognostic groups of patients with respective 3-year survival rates of 89%, 63%, and 18%. The three prognostic groups remained distinct, even when restricted to complete responders. This model was also predictive of survival when dose intensity was analyzed relative to the optimum dose defined for each of the three regimens and when applied to a subgroup of patients aged 50 years or younger. We conclude that actual RDI is an important prognostic factor for survival in DLCL and that analysis of RDI early in the course of treatment may allow modification of the treatment plan.

Aged↗
PubMed1990

Bone marrow transplantation for hematologic malignancies: the Stanford experience.

Allogeneic and autologous BMTs are highly effective and successful treatment modalities for selected patients. Use of BMT earlier in the course of disease yields better results when compared to patients with more advanced disease. Recent advances such as use of cloned growth factors, cytokines, etc..., will continue to contribute to lessen morbidity and mortality. Finally, as investigators understand, prevent, and treat expected side effects from BMTs, the patients' burden in terms of physical, psychological, and financial costs should lessen substantially.

Adult↗
PubMed1989

Hypercalcemia and vitamin D metabolism in Hodgkin's disease. Is there an underlying immunoregulatory relationship?

Hypercalcemia is not common in Hodgkin's disease, but in reported cases is often unassociated with bone involvement. A case is presented demonstrating a mechanism involving elevated levels of 1,25-dihydroxy vitamin D3 (calcitriol). Similar cases in the literature are reviewed. Data implicating calcitriol as a hematolymphoid regulatory hormone are discussed as they may relate to lymphomas, leukemias, and paraneoplastic lymphocyte and monocyte/macrophage activity.

Adolescent↗
PubMed1989

Treatment of B-cell lymphomas with anti-idiotype antibodies alone and in combination with alpha interferon.

Idiotypes are distinct clonal markers for B-cell lymphomas. Previously we reported the use of anti-idiotype antibodies in the therapy of patients with B-cell malignancies. Because synergy was demonstrated with the addition of alpha interferon to anti-idiotype antibodies in a murine lymphoma model, we performed a clinical trial combining these two agents. Here we provide an update of the original trial of anti-idiotype antibodies alone and report the outcome of the new combination trial. In 16 treatment courses of anti-idiotype antibodies alone there were seven partial responses and one complete response. In 12 courses of combination anti-idiotype antibody and alpha interferon there were two complete responses and seven partial responses. Substantial tumor regressions occurred with minimal toxicity in both trials even in patients refractory to conventional chemotherapy. Tumor specimens obtained at the time of disease progression often contained a preponderance of idiotype-negative lymphoma cells, suggesting that anti-idiotype antibody treatment exerted a strong antitumor effect against antigen-positive cells. Anti-idiotype antibodies have reproducible objective antitumor activity in B-cell lymphoma. The addition of alpha interferon may improve the initial rate of response to this treatment. Strategies that deal effectively with idiotype-negative lymphoma cells should improve the extent and duration of these responses.

Antibodies, Anti-Idiotypic↗
PubMed1989

Expression of LFA-1 in non-Hodgkin's lymphoma.

Lymphocyte function-associated antigen 1 (LFA-1) is a glycoprotein involved in virtually all aspects of the immune response requiring direct cell to cell contact. It has been suggested that lack of LFA-1 expression in lymphomas may represent a mechanism of escape from immunologic surveillance. We investigated the expression of LFA-1 in a series of more than 250 lymphoid neoplasms and reactive lymphoid proliferations using a frozen section immunoperoxidase technique. LFA-1 was expressed by all lymphoid populations in the reactive cases. In contrast, absence of LFA-1 alpha or beta chains was found in 44% of non-Hodgkin's lymphomas, including 50% of B-cell lymphomas. These findings suggest that loss of LFA-1 expression may be of great use in the differential diagnosis of benign versus malignant lymphoproliferations. Eighty percent of initial biopsy specimens of low-grade lymphoma exhibited LFA-1 expression, whereas only 8% of recurrent specimens retained expression of both LFA-1 subunits. However, we found no correlation between LFA-1 expression and clinical course in a series of 64 patients with diffuse large cell lymphomas.

Antigens, Differentiation↗