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Biomedical subjects

D A Filippa

Publications and source records attributed to D A Filippa.

At least 55 records · Page 3Linked to original sources

Molecular analysis of breaks in BCL-1 proto-oncogene in B-cell lymphomas with abnormalities of 11q13.

The t(11;14)(q13;q32) is a recurring translocation that occurs infrequently but non-randomly in B-cell chronic lymphocytic leukemia, B-cell non-Hodgkin's lymphoma, and multiple myeloma. The putative oncogene BCL-1 located at the chromosomal band 11q13 has been cloned previously from a B-cell CLL with t(11;14). We studied the molecular structure of the BCL-1 gene in eight B-cell NHL tumors that exhibited a break at 11q13. The cytogenetic changes in these tumors were t(11;14) in three, t(1;11;14)(q32;q13;q32) in two and dup(11)(pter----q23::11q13----ter) in three. The BCL-1 gene was found to have rearranged in two tumors. By Southern blot analysis of single and double digested DNA from placenta and from the tumors, we mapped the breakpoint in BCL-1 to a 0.5 kb Pst-I-HindIII restriction fragment which was approximately 2kb away from the sites of previously mapped breakpoints. Sequential hybridization of Southern blots of these tumors with different immunoglobulin probes (for J region, Cu, Su) and BCL-1 probe identified co-migrating fragments with Su probe after BamHI restriction digestion. These results demonstrate that translocation breaks in the BCL-1 gene are not clustered in a short stretch of DNA at 11q13, and that the translocation related breaks in the immunoglobulin heavy chain can occur outside the joining region. The implications of these observations to the genesis of chromosomal translocations during B cell development are discussed.

B-Lymphocytes↗

Primary lymphoma of the liver.

Nine adult white men ranging in age from 27 to 76 (mean, 55 years) were treated for primary hepatic lymphoma between 1972 and 1986 at the Memorial Sloan-Kettering Cancer Center. Six patients presented with right upper quadrant or epigastric pain or discomfort, and three patients complained of fatigue and lethargy. Fever and night sweats were evident in two, and two patients had lost weight. One patient was asymptomatic; the liver mass was detected during the work-up for cancer of the prostate. Seven patients on whom computerized tomography was performed all had solitary masses in the liver although in three of them tumor had extended into both lobes as noticed at surgery. One had additional porta hepatic lymph node metastasis. Eight patients underwent an exploratory laparotomy; four had hepatic resection, and four had wedge biopsies of unresectable liver tumor. One patient had a percutaneous needle biopsy of the liver. Eight patients received combination chemotherapy. Six patients are alive, five of whom are in initial complete remission. All three patients who died had persistent or recurrent disease in the liver. The results of therapy and surgery to date in these and in other cases in the literature are encouraging.

Adult↗

Generalized lymphadenopathy with morphologic features of Castleman's disease in an HIV-positive man.

In recent years the literature has described a highly lethal "multicentric" variant of classic Castleman's disease (CD) with similar hyperplastic angio-follicular morphologic features. A 44-year-old man who was not known to be part of any established high-risk group for the acquired immune deficiency syndrome (AIDS) presented with clinical and laboratory features similar to "multicentric" CD. Serologic testing revealed antibody to the human immunodeficiency virus (HIV) by Western blot analysis. It is suggested that "multicentric" CD may be part of the clinicopathologic spectrum of HIV infection, and there should be a high index of suspicion for HIV in patients presenting with generalized lymphadenopathy and histopathologic features of CD.

Acquired Immunodeficiency Syndrome↗

Non-Hodgkin's lymphomas: characteristics of long-term survivors following conservative treatment.

A most important set of prognostic factors for survival among 467 patients with non-Hodgkin's lymphoma receiving conservative treatment was determined statistically by the Cox proportional hazards model. Non-Hodgkin's lymphoma was diagnosed in these patients between 1958 and 1969. Initial biopsy material was classified according to the Working Formulation, and the Rappaport, Kiel, and Lukes-Collins systems. The Cox analysis identified a group of 37 patients with a median survival of 150 months. These patients had the following characteristics: small lymphocyte, plasmacytoid lymphocyte, small cleaved, large cleaved or non-cleaved follicular center cell histologic subtype (Lukes-Collins); no bulky involvement of mesenteric nodes or critical organs--kidney, urinary tract, or pleura; stages I to III disease (78 percent stage I or IE); no B symptoms; age below 60 years; initial resection as a reflection of localized disease. Patients with advanced-stage non-Hodgkin's lymphoma receiving conservative treatment have a relatively short survival (median, less than five years) regardless of histologic subtype.

Adolescent↗

Malignant lymphoma of the breast. A study of 53 patients.

Fifty-three patients with non-Hodgkin's lymphoma of the breast were reviewed and classified using four current classifications of lymphoma. All patients were female with a mean age of 57 years. The majority of patients had histiocytic or large-cell lesions and presented as clinical Stage I. The tumors were described clinically as primary in the breast, and mammary parenchyma was found in 79% of the diagnostic biopsy specimens. The other specimens showed lymphoma in mammary adipose tissue. Survival was not influenced by the presence or absence of breast parenchyma in the biopsy. Statistically significant survival differences were found to be related to stage at presentation as well as to tumor grade, using Kiel and Working Formulation categories. Patients with Stage I disease and those with low-grade lesions had a more favorable prognosis. No discernible factors, including stage or histologic findings, appeared to affect the recurrence rate.

Adult↗

Chromosome abnormalities in AIDS-associated lymphadenopathy.

Cytogenetic studies were performed on direct and 24-hour culture preparations of eight lymph node biopsies from seven patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC)-associated lymphadenopathy in whom histological evidence of lymphoma was not detected. Three of these seven had chromosomal abnormalities, including chromosome instability in one and clonal chromosomal abnormalities in two; one of the latter was a t(8;14)(q24;q32). The remaining five showed normal karyotypes. Epstein-Barr virus (EBV) titers were elevated in all three patients that exhibited chromosome abnormalities, two of whom later developed malignant lymphoma. A control group of five patients with reactive lymphadenopathy not associated with AIDS failed to reveal chromosomal aberrations, but elevated EBV titers were present in two. These data are consistent with current views on the role of EBV and chromosome change in the development of lymphoma in immunodeficient states and suggest that karyotypically abnormal AIDS-related lymphadenopathy represents a prelymphomatous proliferation.

Acquired Immunodeficiency Syndrome↗

Intermediate- to high-grade histology of lymphomas carrying t(14;18) is associated with additional nonrandom chromosome changes.

We describe additional nonrandom chromosome abnormalities in 18 cases of intermediate- to high-grade non-Hodgkin's lymphoma (NHL) bearing t(14;18) that were ascertained in a prospective cytogenetic study of all lymphomas seen at Memorial Hospital during the period January 1, 1984, to December 31, 1986. These included seven cases that had histological evidence of transformation from a lower grade and 11 that lacked such evidence. The most common of the additional changes seen in both groups affected chromosomes 6 and 7 and comprised the loss of chromosome 6 or del(6q) and the presence of more than two copies of chromosome 7 or duplication of 7q. Changes affecting these two chromosomes were less frequent in low-grade lymphomas with t(14;18) as well as in lymphomas lacking the translocation. These data suggest that common cytogenetic mechanisms underlie expression of high-grade histologies by lymphomas carrying t(14;18). In addition, they may serve as indicators of transformation when encountered in low-grade lymphomas with t(14;18).

Adult↗

Cytogenetic and histologic correlations in malignant lymphoma.

Although a number of studies have indicated correlations between histologic subtypes of tumors and certain nonrandom chromosome changes, cytogenetic studies of lymphoma are in an early stage compared to those of leukemia. No comprehensive analysis of available data has so far been attempted in the literature either. Here we present an analysis of chromosome changes and their correlation with subtypes of lymphoma studied by conventional histology and cell surface markers, as observed in two sets of data: a group of 65 karyotypically abnormal tumors sequentially ascertained and studied by us during the period January 1, 1984 to April 30, 1985, and a larger data set derived by combining our data with those from two published series from the University of Minnesota that are comparable to our data. These combined data, which comprise the largest data set on the cytogenetics of lymphomas assembled so far, enabled a comprehensive analysis of correlation between chromosome change and tumor histology and the patterns of chromosome instability in these tumors. We found several significant associations, some previously described and others now recognized, between nonrandom chromosome gains, breaks, translocations, and deletions and histologic subtypes of tumors that characterize lymphomas. The data indicate that finding of chromosome breaks at certain sites (eg, 8q24, 14q32, 18q21) is of diagnostic value in dealing with cases of unusual lymphoma. Furthermore, nonrandom chromosome breakage exhibited three distinct patterns that reflected three levels of etiologically relevant genetic change.

Chromosome Aberrations↗

Recent results of multimodal therapy of gastric lymphoma.

The efficacy of multimodality treatment of gastric lymphoma was examined in a retrospective study of 46 patients treated at the Memorial Sloan-Kettering Cancer Center from 1971 to 1982. The principal treatment plan consisted of surgical resection of the gastric lymphoma (n = 36) where feasible, followed by radiation therapy of the whole abdomen (n = 23) with a boosting dose to the stomach-bed to 3700 cGy, and/or chemotherapy using mainly the CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) regimen as an adjuvant (n = 7), or CHOP plus other drugs for advanced disease. The median follow-up time of patients was 61 months (range, 30 months to 14 years). There was no operative mortality. No patient developed known relapse in the abdomen after resection and total abdominal irradiation, and none suffered relapses after adjuvant chemotherapy, for Stages I-E and II-E. At 5 years, the estimated survival rate after treatment was 95%, 78%, and 25%, respectively for Stages I-E (n = 20), II-E (n = 9) and IV (n = 17). The results for Stage I-E and II-E resectable tumors were significantly improved (P less than 0.05 and less than 0.1 respectively) over those of similar tumors treated in 1949 to 1970.

Adult↗

Evaluation of malignant lymphomas using three classifications and the working formulation. 482 cases with median follow-up of 11.9 years.

Three classifications and the Working Formulation for non-Hodgkin's lymphomas have been studied in 482 patients with a median follow-up of 11.9 years. Each classification was evaluated independently, and their similar and discrepant aspects were analyzed by comparing subgroups in the different schemes. Clinical staging was essential in the evaluation of some categories. There are several differences between the classifications that are not readily reconcilable. The Rappaport classification's principal groups are heterogeneous. Separation of follicular lymphomas into small and large cleaved cell types (Lukes-Collins) is significant. The addition of a follicular mixed cell type (Rappaport, Working Formulation) detracts from this significance. Centrocytic and lymphoplasmacytic tumors (Kiel) are well-defined categories and important in understanding some deficiencies in the other classifications. The small cleaved cell type, diffuse (Lukes-Collins, Working Formulation) is heterogeneous. Diffuse lymphomas of mixed cell types are poorly defined subgroups. Excluding lymphoblastic types, the presence of plasmacytic differentiation is important in identifying the high-grade lymphomas with the poorest prognosis. These results suggest that adjustments should be made in the classifications and in the Working Formulation.

Adolescent↗

Hairy cell leukemia. Durability of response to splenectomy in 26 patients and treatment of relapse with androgens in six patients.

Twenty-three of 26 patients with hairy cell leukemia evaluable for response to splenectomy had significant improvement in anemia, thrombocytopenia, and/or neutropenia. Eight of the 23 had a recurrence of cytopenia after a median response duration of 4 to 5 months (range, 1-22). The remaining 15 patients did not have a recurrence of cytopenia at 20 months median follow-up (range, 1-76). Six patients with postsplenectomy cytopenia were given androgenic steroids. Two of the six had an improvement in anemia and thrombocytopenia, and a third patient had an improvement in neutropenia. It was concluded that, although most patients with hairy cell leukemia have initial improvement in cytopenia with splenectomy, a significant number of them either fail to respond or have recurrent cytopenia after initial response to splenectomy. A trial of androgenic steroids is a reasonable therapeutic option in these patients. Alternative therapies are reviewed and recommendations made.

Adult↗

Primary pulmonary lymphomas. A clinicopathologic analysis of 36 cases.

The clinical and pathologic findings in 36 patients with primary pulmonary non-Hodgkin's lymphoma were retrospectively evaluated. Each lymphoma was classified according to the Rappaport, Lukes-Collins, Working Formulation, and Kiel criteria. Twenty-one (58%) of the 36 patients had lymphomas classified as lymphoplasmacytic/lymphoplasmacytoid type or LP immunocytoma (LPI) according to the Kiel classification. The remainder of the patients (42%) had lymphomas distributed among the follicular center cell (FCC) types and immunoblastic sarcoma in the Lukes-Collins classification. Survival of patients with LPI was significantly longer than that of patients with other types of lymphoma (88% versus 47% 5-year actuarial survival estimate), and the LPIs were more often confined to the lung without hilar or mediastinal lymph node involvement. Seven (33%) of the 21 LPI eventually recurred after a mean follow-up of 69 months, and 4 of these 7 developed serum paraproteins. Most of the patients with lymphomas other than LPI had persistent disease or an early recurrence. LPI, as described by Lennert, seems prone to arise in extranodal sites and to recur late. Measurement of serum immunoglobulins may be helpful in detecting recurrences of LPI.

Adolescent↗

Progression of nodular poorly differentiated lymphocytic lymphoma to Burkitt's-like lymphoma.

Histologic conversion of nodular lymphomas to more aggressive patterns has been well described and occurs in 15% to 40% of cases. Most conversions have involved changes from nodular to diffuse patterns and often from small to larger cell types. Conversions to undifferentiated lymphomas, but not specifically to the Burkitt's type, have infrequently been described. This report describes three cases of nodular poorly differentiated lymphocytic lymphoma that converted to a Burkitt's-like lymphoma. Conversion was associated with short survivals, increasing lactate dehydrogenase (LDH) levels, and changes in DNA stemline, RNA content, and S-phase values, as determined by flow cytometry. Karyotypes in two cases revealed a t(14;18). Surface immunoglobulin could be demonstrated on transformed Burkitt's-like cells from lymph node in one case, but in none of the cases on cells from bone marrow.

Adult↗

The non-Hodgkin's lymphomas. I. A retrospective clinical and pathologic analysis of 499 cases diagnosed between 1958 and 1969.

A retrospective clinical and histopathological review was made of 499 previously untreated cases of non-Hodgkin's lymphoma with adequate initial biopsy material diagnosed at Memorial Hospital between 1958 and 1969. Three hundred-eighty-four cases (77%) had diffuse, 104 (21%) nodular, nine (2%) nodular and diffuse, and two (less than 1%) unclassifiable histologic types. Overall median survival was 16 months, and 79% of the patients died with lymphoma. For all treatments, survival of responding patients was the same as that of nonresponders, a reflection of the palliative approach. Significant differences in survival were found between patients in the various Ann Arbor stages. Median survival was 42 months for the nodular group and 11.5 months for the diffuse (P less than 0.001). The ten-year survival was 12% for the diffuse and 22% for the nodular patients. The overall difference in survival was due to early deaths in the diffuse group. Long-term follow-up is necessary to appreciate the usual fatal course of patients with all types of non-Hodgkin's lymphomas treated conservatively.

Adolescent↗

Primary lymphomas of the gastrointestinal tract. Analysis of prognostic factors with emphasis on histological type.

We have analyzed the clinicopathological factors affecting survival in 60 primary gastrointestinal lymphomas seen at Memorial Hospital between 1949 and 1978. Patients with generalized lymphoma (Stages III and IV) at the time of diagnosis and those without follow-up information or adequate histological material were excluded from this study. Lymphomas were classified according to the Lukes-Collins, Kiel, and Rappaport schemes and the patients were staged retrospectively by a modified Ann Arbor system. The patients were treated by surgical resection, radiotherapy, or both. Survival was influenced by histological type (P = 0.0116), stage of the disease (P less than 0.0001), and size of the primary tumor (P = 0.0007). Low-grade lymphoplasmacytoid lymphomas, recognized in 26.6% of the cases, had a low rate of extra-abdominal recurrence; 74% of these patients were alive without evidence of recurrence after a median follow-up of 171 months, or died without evidence of lymphoma with a median survival of 147 months. Centrocytic (Kiel) or cleaved cell (Lukes-Collins) types were seen in 13% and 21%, and high grade (Kiel) or large noncleaved and immunoblastic (Lukes-Collins) in 33.3% and 30% of the cases, respectively. These groups had a high rate of extra-abdominal recurrences, and over 60% of the patients died of lymphoma, with a median survival of 8 for the centroblastic-centrocytic and 7 months for the high-grade tumors. Histological type and clinicopathological staging emerge as useful factors for the identification of patients with high risk of systemic recurrence, probably best treated with chemotherapy in addition to surgery and local radiotherapy.

Adult↗

Prognostic significance of receptors for the third component of complement an heavy chain phenotype in diffuse B-cell lymphomas.

As part of a larger study to determine the prognostic significance of cell marker phenotype in diffuse lymphomas, 51 patients with monoclonal B-cell lymphoma were further characterized by receptors for C3 (EAC rosettes) as well as heavy and light chain phenotypes. Patients with greater than 10% EAC rosette-forming cells were found to have a statistically significant longer survival than those with less than 10% EAC rosettes (p = 0.005). A similar trend in survival duration was found for patients whose cells expressed mu heavy chain on their surfaces when compared to those with gamma heavy chain on their cell surfaces (p = 0.05). No difference was observed for light chain phenotype. No correlation was observed between these prognostic groups and any of the three most frequently used histologic classifications (i.e., Rappaport, Lukes, Kiel).

Adult↗

Primary gastrointestinal lymphoma: a 30-year review.

The authors reviewed all cases of non-Hodgkin's lymphoma primarily involving the gastrointestinal tract treated at Memorial Hospital during the period from 1949-1978. Complete clinical records were available in 104 cases. Slides of original pathology specimens were available in 81 cases. Tumors were classified by Rappaport, Lukes-Collins and modified Kiel classifications. All patients were staged retrospectively, using modified Ann Arbor staging. The primary tumor was in the stomach in 76 patients, in the small bowel in 15 and in the large bowel in 13. The life-table survival for all patients at five years was 44% and for the 81 Stage I and II patients it was 53%. We found a trend toward improved survival for patients treated in the last decade (P = 0.05). Using Cox regression analysis, survival was found to be correlated with stage (P less than 0.0001) and involvement of adjacent structures (P = 0.007). For Stage I patients, resection and radiation therapy were equally effective alone in controlling local tumor even though factors responsible for the selection of either treatment could not be identified. For Stage II patients, resection combined with radiation therapy controlled local disease better than either treatment alone. For Stage II, patient survival was correlated with the pattern of nodal involvement (P less than 0.0001). Neither the choice of treatment (resection, radiation therapy, or resection with radiation therapy; P = 0.17) nor the involvement of resected margins (P = 0.22) affects survival. Among 81 Stage I and II patients, 68% had recurrences outside the primary field of treatment and 60% outside the abdomen. Systemic multiple modality therapy should be considered for patients at high risk for recurrence.

Adult↗