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F Swan

Publications and source records attributed to F Swan.

48 records · Page 3Linked to original sources

Discordant bone marrow involvement in diffuse large-cell lymphoma: a distinct clinical-pathologic entity associated with a continuous risk of relapse.

From 1975 to 1988, 50 patients with lymph node biopsy-documented diffuse large-cell lymphoma (DLCL) presented with bone marrow involvement. Twenty-four patients (48%) had large-cell lymphoma (LCL) in the bone marrow and were compared with 19 (38%) patients who had small cleaved-cell lymphoma (SCCL) in the marrow. Additionally, seven patients (14%) had mixed small- and large-cell lymphoma (ML) in the marrow. Patients who had LCL marrow involvement were younger (P less than .02) and more frequently had elevated lactic dehydrogenase (LDH) levels (P less than .001), high tumor burden (P less than .01), and more sites of extranodal disease (P less than .05) than those with SCCL in the marrow. The complete response (CR) rate to multiagent chemotherapy was 16.7% in the LCL group and 89.4% in the SCCL group (P less than .001). One third of the patients with LCL in the marrow developed CNS involvement, compared with only one patient in the SCCL group (P = .06). Overall 5-year survival was 79% in patients with SCCL marrow involvement, compared with only 12% in patients with LCL in the marrow (P = .002). Despite a high CR rate, patients with marrow involved by SCCL were at a high continuous risk of relapse with only a 30% failure-free survival at 5 years. We conclude that bone marrow involvement with LCL predicts for extremely poor prognosis with low response rate and short survival. Patients with SCCL in the bone marrow have a high rate of CR and a high rate of 5-year survival; however, there is a high risk of late relapse, and only 15% are in a continuous remission at 8 years.

Adolescent↗

Small noncleaved cell lymphoma in adults: superior results for stages I-III disease.

Small noncleaved cell lymphoma (SNCCL), a rare lymphoma in adults, is associated with not only a rapid complete response (CR) to chemotherapy but also with the potential to rapidly relapse both systemically and in the CNS. We treated 44 assessable adults with two similar protocols, consisting of three sequential chemotherapy combinations and intrathecal prophylaxis with methotrexate and cytarabine. The overall CR rate was 80%; it was 100% in patients with Ann Arbor (AA) stages I-III disease and 57% in those with stage IV disease. The overall survival (OS) rate at 5 years was 52%. The overall 5-year freedom from tumor mortality (FTM) rate was 63%; it was 95% for patients with AA stages I-III disease, and 29% for those with stage IV disease. Stepwise multivariate analysis of factors associated with remission duration and survival indicated that advanced-disease stage and age of 40 years or over were predictors of poor prognosis. Twelve patients with positive human immunodeficiency virus (HIV) serology were also included in this series. They had an 83% CR rate and an 83% 5-year FTM, but only a 36% 5-year OS; most deaths were secondary to opportunistic infection. Histologic subtype (Burkitt's lymphoma [BL] or non-Burkitt's lymphoma [NBL]) did not correlate with patient age, site of tumor presentation, response to therapy, or survival. Both protocols achieved comparable results. The approach used in these protocols is highly effective for patients with early staged disease, regardless of their HIV status; however, better therapy is necessary for those with SNCCL presenting in an advanced stage.

Adult↗

Recent trends in the management of lymphomas at M.D. Anderson Cancer Center.

The overall therapeutic strategy for the management of lymphomas at the M.D. Anderson Cancer Center consists of devising new drug combinations that are tested first in patients with relapsed lymphoma and, if successful, are then incorporated into first-line management. This article describes the preliminary results of the alternating triple therapy (ATT) first-line regimen for patients with M.D. Anderson stages B, C, and D of intermediate-grade lymphomas. This regimen is based on three non-cross-resistant combinations, two of which were originally developed as salvage therapy. Statistically significant improvement in the overall survival and failure-free survival at 1 year has already been seen for the stage D patients (high tumor burden and high lactate dehydrogenase levels). A new therapeutic strategy in current use for patients with Ann Arbor stages III and IV low-grade lymphoma is also described. This regimen consists of CHOP-Bleo (cyclophosphamide, doxorubicin, vincristine, prednisone-bleomycin) alternating with ESHAP (etoposide, Solu-medrol [methylprednisolone, Upjohn Company], Ara-C [cytarabine], platinum) and NOPP (Novantrone [mitoxantrone, American Cyanamid Company], Oncovin [vincristine Eli Lilly and Company], procarbazine, prednisone). Maintenance interferon (IFN) is also used for 1 year. Finally, the current salvage regimen in use at the M.D. Anderson Cancer Center is described. This MINE-ESHAP regimen consists of an induction with mesna, ifosfamide, Novantrone (mitoxantrone), and etoposide, which is administered until maximum response and followed by consolidation with 3 to 6 courses of ESHAP. The preliminary results of this regimen are encouraging, but more follow-up is required before any conclusions can be drawn.

Adult↗

NOVP: a novel chemotherapeutic regimen with minimal toxicity for treatment of Hodgkin's disease.

Patients with early-staged Hodgkin's disease have had a higher relapse rate following radiotherapy alone if they have B symptoms, large mediastinal masses, hilar involvement, or stage III disease. From June 1988 to December 1989, 27 previously untreated patients with early-staged Hodgkin's disease with adverse features for disease-free survival received combined-modality therapy. Seventeen patients had stage I or II disease, 10 had stage III, 5 had B symptoms, 13 had large mediastinal masses, and 6 had peripheral masses measuring 10 cm or more in diameter. All patients initially received three cycles of a novel chemotherapeutic regimen combining Novantrone (mitoxantrone, American Cyanamid Company), vincristine, vinblastine, and prednisone (NOVP). Twenty-four patients with clinically staged I or II disease with adverse features or stage III disease did not undergo laparotomy; three patients had favorable stage I or II disease and at laparotomy had stage III disease. Radiotherapy-treatment fields depended on the extent of nodal involvement. Twenty-six patients completed all therapy as planned to complete remission (CR) and one of these has had progression; she is in second CR following additional radiotherapy. With a median follow-up of 12 months, all patients are alive. Tolerance to treatment was excellent with only grade 1 or 2 nausea, alopecia and myalgias, and brief myelosuppression. NOVP is an effective adjuvant chemotherapy regimen for inducing responses, with minimal toxicity, prior to definitive radiotherapy for patients with early-staged Hodgkin's disease.

Adult↗

Risk classification as the basis for clinical staging of diffuse large-cell lymphoma derived from 10-year survival data.

Two hundred and fifty previously untreated adult patients with diffuse large-cell lymphomas were treated with a chemotherapy combination of cyclophosphamide, adriamycin, vincristine, prednisone, and low-dose bleomycin (CHOP-Bleo) with or without radiotherapy between 1974 and 1984. The 10-year survival rates for patients with Ann Arbor stages II, III, or IV disease of 55%, 42%, and 40%, respectively, were not significantly different. However, the survival rate of 76% for patients with stage I disease was clearly better. Factors more indicative of prognosis than stage, as found by univariant analysis, were tumor burden, serum lactic dehydrogenase level (LDH), age, and constitutional symptoms. From these, a multivariant analysis selected tumor burden, LDH level, and age as major independent factors for predicting survival (P less than .001). A prognostic risk model constructed on the basis of tumor burden and LDH levels identified four distinct risk groups (A, B, C, D) with 10-year survival rates of 85%, 66%, and 43% for A, B, and C. No patient in group D survived 10 years. These risk groups also had a strong correlation with complete remission rates and with relapse rates. Thus this model proved more effective for identifying patient populations according to their expected responses, durations of remission, and survivals than the Ann Arbor staging system. Detailed information supporting the use of this system for predicting prognosis and for treatment selection for patients with diffuse large-cell lymphomas is provided.

Adolescent↗

Refractoriness to chemotherapy and poor survival related to abnormalities of chromosomes 17 and 7 in lymphoma.

PURPOSE: Lymphoma cells usually show cytogenetic abnormalities, but their relationship to prognosis has not been as extensively studied as in leukemia. A group of previously untreated cases of lymphoma with evaluable metaphases was examined for the association between cytogenetic abnormalities and clinical outcome. PATIENTS AND METHODS: The study consisted of 104 patients, from whom fresh tumor samples were obtained for cytogenetic tests. Because of the complexity of lymphoma karyotypes, the cases were divided into four patterns according to the type of abnormality of chromosome 17 or 7 present. Treatment of patients was given based on histologic grade and stage of disease. Response to treatment was evaluated according to previously described methods. RESULTS: Patients with true abnormalities of chromosome 17 or 7 (defined as those with either structural abnormalities of the short arm of these chromosomes or monosomy of these chromosomes with no associated unidentified markers) were observed to have an adverse prognosis. The overall response rate and tumor-related mortality were less favorable for patients with these cytogenetic abnormalities. By applying multivariate analysis, we found that this observation was independent of the effect of serum lactic dehydrogenase level, histologic grade, or tumor burden. CONCLUSION: True abnormalities of chromosome 17 or 7 in patients with lymphoma are associated with a poor response to chemotherapy, short time to treatment failure, and high tumor-related mortality rate. These findings raise the question of the potential involvement of some gene or oncogene, perhaps the p53 oncogene, which might impart a survival advantage to the malignant cells.

Adult↗

A new serologic staging system for large-cell lymphomas based on initial beta 2-microglobulin and lactate dehydrogenase levels.

We report results of our investigation of prognostic factors for patients with large-cell lymphoma who were entered on the same treatment protocol and who had known pretreatment serum beta 2-microglobulin (beta 2M) and lactate dehydrogenase (LDH) levels. beta 2M and LDH levels were the most significant and independent variables for predicting time to treatment failure (TTF) and survival. The serum level of beta 2M correlated with tumor burden. These two serum markers defined three significantly different prognostic groups. All 27 patients in the low-risk group remain alive and in remission; in contrast, 22 of the 27 patients (81%) in the high-risk group have failed treatment, and only seven (26%) remain alive. In comparison with the Ann Arbor staging system, serum levels of beta 2M and LDH may provide a more precise system for defining risk groups and thereby allow a more rational approach to the development and analysis of treatment strategies.

Adult↗

Analysis of peripheral blood granulocyte-macrophage colony growth by limiting dilution assay.

Analysis of myeloid progenitor cells in the peripheral blood (peripheral blood colony-forming unit granulocyte-macrophage; PBCFU-GM) is limited by their low frequency and by the presence of inhibitory cell populations. These factors limit the study of cytokines and cellular influences on PBCFU-GM in semisolid media assays and complicate the interpretation of data. We have developed a limiting dilution assay (LDA) in liquid culture for PBCFU-GM that allows evaluation of inhibitory or accessory effects of other cell populations and estimation of progenitor cell frequency. Using this system we have examined the inhibitory effect of autologous monocytes on in vitro colony growth. After monocyte depletion by counterflow centrifugal elutriation and adherence, colony growth with recombinant human granulocyte-macrophage colony-stimulating factor was linear over a wide range of cell densities, indicating a direct proliferative effect on circulating myeloid progenitor cells. Simultaneous PBCFU-GM assays in agar demonstrated monocyte inhibition but did not afford reliable interpretation of either progenitor frequency or linear growth kinetics in a statistically verifiable fashion. LDA in liquid culture may be a useful tool to study the effects of various cytokines and cell populations on PBCFU-GM in vitro and in vivo.

Colony-Forming Units Assay↗

Results of recent salvage chemotherapy regimens for lymphoma and Hodgkin's disease.

From 1981 to 1983, 208 patients with recurrent or refractory lymphoma were treated with methylglyoxal-bis-guanylhydrazone (methyl-GAG), ifosfamide, methotrexate, etoposide (MIME). The complete remission (CR) rate was 24% and CR plus partial remission (PR) was 60%. Response was higher for aggressive than for indolent cell types. Median duration of CRs was 16.5 months and median survival of all patients was 9 months. In view of the in vitro synergism between cisplatin and high-dose cytarabine, we recently designed the DHAP regimen, which consists of cisplatin, 100 mg/m2 IV over 24 hours; cytarabine, 2 g/m2 IV over two hours every 12 hours for two doses; and dexamethasone, 40 mg orally daily for 4 days. There were 28 of 90 (31%) CRs and 22 of 90 (24%) PRs. Median duration of CR is 15 months; median survival of all patients is 6 months. The major toxicities have been infection (31%) and moderate to severe renal dysfunction (20%). In contrast to MIME, response rates did not differ significantly between aggressive and indolent cell types. A high-dose regimen (CBV) consisting of cyclophosphamide, 6 g/m2; carmustine, 300 mg/m2; and etoposide, 250 mg/m2 daily for 3 days followed by autologous bone marrow transplant (ABMT) has been successfully used to treat 62 patients with Hodgkin's disease recurrent or refractory after mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine, dacarbazine (MOPP/ABVD)-like regimens. A CR rate (47%) has been observed; 83% of these CRs remain alive and free of disease with a median follow-up of 19 months. This regimen appears to have curative potential in 40% of all cases and in 60% of cases treated after the first or second relapse.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗

Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP).

Ninety patients with progressive recurrent lymphoma were treated with a combination of cisplatin 100 mg/m2 intravenously (IV) by continuous infusion over 24 hours, followed by cytosine arabinoside in two pulses each at a dose of 2 g/m2 given 12 hours apart. Dexamethasone, 40 mg orally or IV, was given on days 1 through 4. Vigorous hydration was reinforced by routine use of mannitol. Treatments were repeated at 3- to 4-week intervals for six to ten courses. Most patients had not achieved complete remission (CR) with prior therapies, which included Adriamycin (all patients) and methotrexate and VP-16 (58 patients). Median patient age was 55 years. Intermediate-grade lymphoma was the most frequent pathologic diagnosis. Seven patients died within two weeks of therapy; of the remaining 83 patients, 28 (34%) or 31% if all patients are considered, achieved CR, and 22 (26.5%) achieved partial remission (PR). Response was evident after the first two cycles of chemotherapy and appeared to be independent of the histopathologic type of lymphoma. To date, only eight of the complete responders have relapsed at a median follow-up of 11 months. The overall 2-year survival in 25%. Further analysis showed that patients with low tumor burden and normal lactic acid dehydrogenase (LDH) had a high CR response rate (67%) and a survival rate of 61% at 2 years. In contrast, patients with both high tumor burden and elevated serum LDH levels had a negligible CR rate, and only 5% are surviving at 1 year. Patients with either high tumor burden with normal LDH or low tumor burden with elevated LDH had an intermediate survival. Myelosuppression-related infection was the most frequent serious complication of this regimen (31%) and the cause of death of ten patients. Acute lysis syndrome was also observed in five patients with high tumor burden and was the cause of death in three of these patients. DHAP has proven to be an effective non-crossresistant regimen for patients with relapsing or refractory lymphoma, particularly for patients who have favorable prognostic characteristics.

Antineoplastic Combined Chemotherapy Protocols↗