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M Bast

Publications and source records attributed to M Bast.

13 recordsLinked to original sources

Limited stage I and II follicular non-Hodgkin's lymphoma: the Nebraska Lymphoma Study Group experience.

The purpose of this study was to evaluate the outcome and prognostic factors of patients with limited stage follicular non-Hodgkin's lymphoma treated prospectively by the Nebraska Lymphoma Study Group (NLSG). Forty previously untreated patients, median age 64 years, with limited stage follicular lymphoma were prospectively treated according to the protocols of the NLSG between January 1980 and December 1990. The follicular large cell type represents 75% of the cases, and 14 of the biopsies also had a diffuse component (composite lymphoma). The initial treatment was radiation therapy (RT) to the involved field in 15 patients, anthracycline-containing combination chemotherapy (CT) in 20, and combined RT and CT in 5. Thirty-seven patients (92.5%) achieved a complete remission (CR). The median follow-up is 120 months (range, 20 to 214). Of the 37 patients achieving a CR, 7 patients are alive in first CR, one died due to sepsis, another because of a myeloproliferative disorder at 77 months following chemotherapy, 6 died because of unrelated causes in first CR. Twenty-two patients relapsed between 1 to 128 months following a CR. The estimated 10-year event-free survival is 21% (95% CI: 7 to 35). Two patients received no or palliative therapy after relapse and both died of progressive disease. Nineteen patients received salvage therapy and 15 achieved a second remission. The median survival after first relapse is 55 months. The estimated 10-year overall survival is 44% (95% CI: 28 to 60). Various factors including sex, histologic subtype, stage, and degree of follicularity do not influence the overall survival or event-free survival. CT with or without RT resulted in a better trend for 10-year event-free survival in stage IA patients compared to RT alone but estimated 10-year overall survival is no different. The overall survival is worse in the > or = 60 age group but this difference is not evident if data is adjusted for cause specific death. In conclusion, limited stage follicular lymphoma has an excellent initial response to radiation therapy or chemotherapy; however the recurrence rate is high and cure is limited.

Adult↗

A multicenter randomized double-blind placebo-controlled trial of adjunctive corticosteroids in the treatment of Pneumocystis carinii pneumonia complicating the acquired immune deficiency syndrome.

A multicenter placebo-controlled trial of early short-term high-dose methylprednisolone enrolled 78 patients with moderate to severe Pneumocystis carinii pneumonia (PCP) complicating HIV infection. The mean pressure of oxygen (PO2) at study entry was 55 mm Hg for the 71 patients who had blood gases monitored while breathing room air. Patients were randomized to receive methylprednisolone (40 mg) or placebo parenterally twice daily for 10 days, and the first dose of study medication was given within 24 h of the first dose of antimicrobial therapy for PCP. The primary end point included death, need for mechanical ventilation for > 6 days, or a partial PO2 < 70 mm Hg while breathing room air 10 days after initiation of treatment. There was no statistically significant difference in the primary end point between patients randomized to corticosteroid (CS) or placebo (PL) (p = 0.522; 95% CI = -0.30, 0.16). The incidence of superinfections during therapy or of other HIV-associated infections or malignancies in the 6 months following treatment for PCP was not significantly different between the two groups. More patients randomized to placebo had to discontinue treatment with trimethoprim-sulfamethoxazole because of hypersensitivity than those randomized to corticosteroids (p = 0.039). We conclude that addition of corticosteroids does not significantly affect the outcome of PCP in patients with HIV and a PO2 < 70 mm Hg on room air at presentation but lowers the incidence of hypersensitivity reactions to trimethoprim-sulfamethoxazole.

AIDS-Related Opportunistic Infections↗

Comparison of DNA content in non-Hodgkin's lymphoma as measured by flow cytometry and cytogenetics.

Specific cytogenetic changes such as t(14;18) and t(8;14) are associated with specific histologic subtypes of non-Hodgkin's lymphoma (NHL) and may predict disease outcome. Nonspecific cytogenetic changes include other structural rearrangements or numerical changes such as monosomies and trisomies, which may cause changes in total cellular DNA content. In many solid tumors, the presence of abnormal DNA content may be predictive of clinical behavior. NHL biopsies, however, contain normal (diploid) as well as abnormal cells, and DNA changes in the peridiploid range are detectable by cytogenetic analysis, but not consistently by flow cytometry. In the present study, we performed flow cytometric and cytogenetic analysis of DNA on biopsies from 129 patients with non-Hodgkin's lymphoma (NHL). Cytogenetic studies were successful on 88 (68%) of the samples. There was 55% concordance between flow cytometric and cytogenetic techniques in detecting aneuploid DNA content, with the majority of discrepancies occurring in the peridiploid range. We also detected six samples which were aneuploid by flow cytometry, but diploid by cytogenetics. We suggest that a reasonable approach to determine DNA content, as it relates to prediction of outcome in NHL, would be to combine data from both of these techniques and analyze the results in terms of ranges of DNA rather than by categorizing as diploid versus aneuploid.

Aneuploidy↗

Proliferative fraction and DNA content are lower in B-cell non-Hodgkin's lymphomas with the t(14;18).

The t(14;18), which juxtaposes the immunoglobulin enhancer region from chromosome 14 to the bcl-2 gene on chromosome 18, is a recurrent cytogenetic abnormality in the majority of follicular lymphomas (FL). This translocation results in overexpression of bcl-2, which increases cellular life span of the mutated cells by decreasing apoptosis. The t(14;18) also occurs in a subgroup of diffuse large cell lymphomas (DLCL), and current thought is that the majority of these represent transformation of FL. Low grade FL are characterized by low proliferation, and diploid/peridiploid DNA content. In this study, we compared proliferative activity (PF) and DNA content (DI) in FL containing the t(14;18) to DLCL with and without the t(14;18). The mean PF and DI were lower in the NHL containing t(14;18) irregardless of histologic subtype. We conclude that increased life span due to the presence of t(14;18) provides the conditions for accumulation of a different set of mutations as compared to those NHL developing from mutations in more rapidly proliferating precursors. This has implications for prognosis of patients with DLCL depending upon the presence or absence of t(14;18).

Cell Division↗

Peripheral T-cell lymphoma in childhood and adolescence. A clinicopathologic study of 22 patients.

BACKGROUND: Peripheral T-cell lymphoma (PTCL), although the most common T-cell lymphoma in adults, is relatively rare in childhood, and only small series have been reported. METHODS/RESULTS: Twenty-two cases of PTCL were studied that occurred in patients 18 months to 20 years of age. Nine were seen when the condition was diagnosed, and the other 13 were referred after they had relapses. The stage at diagnosis was I or II (45%), III (41%), and IV (14%). Patients with Stage IV disease were younger than those with Stage I or II disease (2.5 versus 14.8 years, P = 0.04). Twelve patients had extranodal disease when the diagnosis was made; the skin was the most common site. Ten tumors were classified as diffuse large cell type; five, as diffuse anaplastic large cell type; and seven, as diffuse mixed cell type. Twenty of the 21 tumors tested were CD30 (Ki-1 or Ber-H2) antigen positive. Of the nine patients seen when the diagnosis was made and treated by the authors, three had a relapse (median, 12 months), a 2-year relapse-free survival (RFS) rate of 61%. For the total group, the RFS was longer for patients older than 12 years of age compared with those who were younger (20 versus 12 months, P = 0.05). Overall, six patients remained in their first complete remission. Sixteen patients had a relapse, and 13 of these underwent bone marrow transplantation (BMT). Six of these remained in complete remission (median, 18 months after BMT). Overall, only 6 of 22 patients died (median survival, > 60 months). CONCLUSION: It was concluded that aggressive therapy, including BMT for relapses, can provide prolonged disease control in most children with PTCL.

Adolescent↗

Clinical features and prognosis of follicular large-cell lymphoma: a report from the Nebraska Lymphoma Study Group.

PURPOSE: Our purpose was to describe the treatment outcome of patients with follicular large-cell lymphoma (FLCL) and to identify prognostic factors that affect the treatment outcome. PATIENTS AND METHODS: Between 1980 and 1991, 107 newly diagnosed, previously untreated patients with FLCL were prospectively treated using treatment plans of the Nebraska Lymphoma Study Group (NLSG). Most stage I/II patients received two to three cycles of one of four closely related six-drug combination chemotherapy regimens (cyclophosphamide, doxorubicin or mitoxantrone, and procarbazine, plus bleomycin, vincristine, and prednisone or dexamethasone [CAP/BOP I-IV]) plus involved-field radiotherapy; 10 patients received involved-field irradiation only. Stage III/IV patients received six to eight cycles of CAP/BOP. RESULTS: Forty-four percent of patients had stage I/II disease. Stage I/II patients were older and more often female than stage III/IV patients. Cytogenetic studies were available on 35 patients: seven were normal; the most common abnormality was a translocation involving 14q32. Abnormalities of 1p or 1q were also common, often secondary to a 14q32 abnormality. The median follow-up of surviving patients is 2 years. The complete response rates observed were stage I/II, 88%; stage III/IV, 49%. Complete response rates were affected by both age and tumor bulk. Failure-free survival (FFS; time to first occurrence of progression, relapse after response, or death from any cause) at 3 years was estimated to be 61% for stage I/II patients and 34% for stage III/IV patients. Survival at 3 years was estimated to be 76% and 61%, respectively. FFS of stage III/IV patients was poorer for stage IV patients and those with composite lymphomas. Significantly poorer survival was only seen in patients older than 70 years of age. CONCLUSION: A proportion of stage I/II FLCL patients may obtain long-term disease control with combination chemotherapy plus radiotherapy. Results for patients with stage III/IV FLCL are similar to those seen for other follicular lymphomas.

Aged↗

Clinical significance of hematologic parameters in non-Hodgkin's lymphoma at diagnosis.

Three hundred seventeen patients with non-Hodgkin's lymphoma (NHL) (54 low grade, 180 intermediate grade, 76 high grade, and seven unclassified) treated with chemotherapy were evaluated for the presence of hematologic abnormalities at diagnostic staging. Anemia was present in 42%, leukopenia in 6%, thrombocytopenia in 13%, leukocytosis in 26%, and thrombocytosis in 14% at presentation. The presence of bone marrow involvement by lymphoma was more likely to be associated with leukopenia and thrombocytopenia than the absence of bone marrow involvement. Although anemia was slightly more common in patients with bone marrow lymphoma than in those without marrow lymphoma, the difference was not statistically significant. Hematologic parameters were similar for patients with B-cell or T-cell lymphoma. Evidence of bone marrow failure with multiple cytopenias was present in 26 patients (8%). Leukoerythroblastosis was present in 2%. Circulating lymphoma was present in 9.5%. Anemic patients had a shorter survival time than nonanemic patients, whether bone marrow was involved by lymphoma or not. Survival was not affected by the presence of leukopenia or mild leukocytosis, but, in patients without marrow lymphoma, leukocytosis with a leukocyte count greater than 20 x 10(9)/l was associated with short survival length. Thrombocytopenia was associated with short survival time only in patients with bone marrow involvement by lymphoma. Patients with multiple cytopenias or leukoerythroblastosis had short survival times, but the presence of circulating lymphoma did not alter survival when compared with other patients with bone marrow involvement by lymphoma. These data suggest that hematologic evaluation at the time of diagnostic staging of NHL provides useful prognostic information that may have therapeutic implications.

Anemia, Myelophthisic↗

Low proliferative activity is associated with a favorable prognosis in peripheral T-cell lymphoma.

Peripheral T-cell lymphoma (PTCL) consists of a diverse group of post-thymic tumors bearing a mature T-cell phenotype and, excluding mycosis fungoides, comprises approximately 10-20% of the non-Hodgkin's lymphomas in the United States. This category of non-Hodgkin's lymphomas exhibits considerable morphological, immunological, and clinical diversity and is generally considered to be a high-grade malignancy. In the present study, paraffin-embedded biopsy specimens of lymph nodes from 31 patients with PTCL who were treated with curative intent were evaluated by flow cytometry for DNA ploidy and proliferative activity (PA). DNA ploidy was not predictive of the clinical outcome. However, low PA, defined by less than or equal to 10% of cells in S + G2M phase of cell cycle, was associated with a favorable prognosis. Patients with tumors having low PA had a significantly higher complete remission rate (100%) as compared to those with high PA (55%; P less than 0.02), and the predicted actuarial 4-year survival of those with low PA was 85% versus only 50% for those with high PA (P less than 0.04). This is the first report of the effects of PA and DNA ploidy in patients with PTCL who were treated with curative intent. Additional studies of similar patients are needed to confirm these findings.

Bone Marrow↗

Bone marrow involvement by non-Hodgkin's lymphoma: the clinical significance of morphologic discordance between the lymph node and bone marrow. Nebraska Lymphoma Study Group.

Bone marrow specimens from 317 patients with non-Hodgkin's lymphoma (NHL) obtained at initial staging were evaluated for the presence of lymphoma or benign lymphoid aggregates. Thirty-two percent (102 patients) had lymphoma in their bone marrow, and 9% had benign lymphoid aggregates. Bone marrow lymphoma was present in 39% of low-grade, 36% of intermediate-grade, and 18% of high-grade lymphomas. The bone marrow was involved in 25% of patients with diffuse large-cell or immunoblastic NHL (ie, diffuse histiocytic lymphoma of Rappaport). Bone marrow involvement did not affect survival of patients with low-grade NHL, but survival was significantly shorter (P = .03) for patients with intermediate- and high-grade NHL with bone marrow involvement. Bone marrow involvement was equally common in B-cell and T-cell NHL (31% v 32%). However, patients with T-cell NHL and bone marrow involvement had shorter survival than B-cell NHL with marrow involvement (P = .02) or T-cell NHL without marrow involvement (P = .05). A high incidence of morphologic discordance between lymph node and bone marrow was observed (ie, 40%), always with a more aggressive subtype in the lymph node than in the bone marrow. Presence of large-cell lymphoma in the bone marrow predicted for short survival. Survival for patients with small-cell lymphoma in their bone marrow did not differ significantly from patients with negative bone marrows. We conclude that bone marrow involvement in large-cell NHL, especially in those of T-cell origin, portends a poor prognosis. However, the subgroup of patients with an aggressive histologic subtype of NHL in a lymph node biopsy and small-cell NHL in the bone marrow do not have a poorer outlook than those without bone marrow involvement.

Actuarial Analysis↗

Peripheral T-cell lymphoma.

Peripheral T-cell lymphoma is the most common type of T-cell lymphoma seen in adults in the United States. Clinical data were reviewed from 134 cases of peripheral T-cell lymphoma diagnosed in three centers. The median age of the patients was 57 years (range, 4-97 years), 59% were male, and 36 patients (27%) had a history of a preceding disorder of the immune system. The tumors were grouped histologically into large cell (43%), mixed large and small cell (40%), and small cell (17%). The stage at diagnosis was I (7%), II (21%), III (22%), and IV (50%). B symptoms were present in 57%. The most frequent sites of extranodal involvement were bone marrow (35%), skin (13%), and lung (11%). Eighty patients were treated with a multiagent chemotherapy regimen with proven curative potential in aggressive non-Hodgkin's lymphomas and the remainder of the patients received less intensive chemotherapy (36 patients), radiotherapy (nine patients), or no treatment (nine patients). Fifty percent of the intensively treated patients achieved complete remission and the actuarial 4-year survival was 45%. However, the 4-year, disease-free survival in patients with Stage IV disease was only 10%. Although peripheral T-cell lymphomas appeared similar in many ways to their B-cell counterparts, disease-free survival by stage was low and patients with Stage IV disease had an especially poor outlook.

Adolescent↗

Malignant lymphoma in Nebraska and Guangzhou, China: a comparative study.

Two hundred thirty-four consecutive cases of malignant lymphoma (192 non-Hodgkin's lymphomas and 42 Hodgkin's disease) from Guangzhou, China, and 589 cases (498 non-Hodgkin's lymphomas and 91 Hodgkin's disease) from the University of Nebraska Lymphoma Registry were examined in a retrospective histopathologic analysis and the results compared to those of the National Cancer Institute (NCI) Working Formulation Summary. Aggressive non-Hodgkin's lymphoma was excessive in Guangzhou (82.3 per cent; P less than 0.001) and Nebraska (80.3 per cent; P less than 0.001) when compared with the NCI data (54.2 per cent). The small noncleaved cell, lymphoblastic, and diffuse mixed-cell subtypes were more frequent in China (15.6 per cent each; P less than 0.001), whereas the small lymphocytic, follicular large cell, and immunoblastic subtypes predominated in Nebraska (8 per cent, 8.4 per cent, and 21.8 per cent, respectively; P less than 0.001). The overall median age of onset for non-Hodgkin's lymphoma was 42.0 years in Guangzhou and 63.5 years in Nebraska. Hodgkin's disease represented 18 per cent of the malignant lymphomas in Guangzhou and 15 per cent in Nebraska. The mixed-cellularity type was most common in Guangzhou (52 per cent; P less than 0.001) and the nodular-sclerosing type in Nebraska (56 per cent; P less than 0.010). The low median age and excess of certain aggressive subtypes of non-Hodgkin's disease in Guangzhou suggest a possible viral etiology, whereas the excess of certain subtypes of non-Hodgkin's lymphoma in Nebraska may be related to intense agricultural activity.

Adult↗