Biomedical subjects

D J Ellison

Publications and source records attributed to D J Ellison.

15 recordsLinked to original sources

PubMed1994

Immunomorphologic analysis of bone marrow biopsies after treatment with 2-chlorodeoxyadenosine for hairy cell leukemia.

Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine (2-CdA) induces complete remissions in 85% of patients. Complete remission has been defined as the absence of hairy cells in the bone marrow after routine morphologic examination. To determine if hairy cells could be detected in complete remission bone marrows using immunohistochemical techniques with antibodies L26 (CD20) and DBA.44, 154 bone marrow biopsies performed between 3 months and 25 months after therapy were studied. Of the biopsies, 50% exhibited staining with L26 and/or DBA.44 in five or more cells with morphologic features of hairy cells. Minimal residual disease was usually less than 1% of the total cellular population. DBA.44-positive cells were demonstrated in 91% of the biopsies, although in 48% of these the morphologic features of the positive cells were not sufficiently distinctive for hairy cells. The proportion of biopsies with residual hairy cells was similar over the 25 months of follow up, indicating a relatively stable amount of residual disease. Immunomorphologic analysis is a more sensitive method for detecting residual hairy cells than morphology alone. Although further follow up is necessary to determine the clinical significance of the L26/DBA.44-positive staining in cells with and without distinctive morphologic features of hairy cells, we conclude that many patients in a stable clinical remission may have residual hairy cells.

Antibodies, Monoclonal↗

PubMed1994

Complete hematologic remissions in chronic-phase, Philadelphia-chromosome-positive, chronic myelogenous leukemia after 2-chlorodeoxyadenosine.

BACKGROUND: 2-Chlorodeoxyadenosine (Cladribine, Leustatin, Ortho Biotech, Raritan, NJ) (2-CdA) is a purine analog with activity in the treatment of lymphoid neoplasms. Interferon induces cytogenetic remissions in chronic myeloid leukemia (CML) and partial remissions in hairy cell leukemia, a disorder in which single courses of 2-CdA induce complete remissions. In vitro clonal growth of immature myeloid progenitors from normal marrow is markedly inhibited by 2-CdA. METHODS: 2-CdA was administered to 12 patients with Philadelphia-chromosome-positive CML, 11 chronic phase, and 1 accelerated phase, at 0.1 mg/kg/day by continuous intravenous infusion for 7 days every 28-35 days, until maximum peripheral hematologic response. RESULTS: Of 12 patients, 10 (83%) achieved complete hematologic responses and 2 (17%) partial hematologic responses after a median of two courses of 2-CdA. The median first hematologic response duration was 3 months. Of the seven patients who relapsed and were retreated with a median of two further courses of 2-CdA, five obtained responses (four complete and one partial) and two did not respond. The median second hematologic response duration was 4 months. No patient had significant Philadelphia-chromosome suppression. Reversible myelosuppression and severe cumulative T-cell immunosuppression associated with opportunistic infections in four patients were the principal toxicities. CONCLUSIONS: 2-CdA is active in CML, inducing complete hematologic responses, but the absence of cytogenetic responses and severe immunosuppression may limit its clinical use.

Adult↗

PubMed1994

Identification of monoclonal immunoglobulins and quantitative immunoglobulin abnormalities in hairy cell leukemia and chronic lymphocytic leukemia.

Serum and urine samples from 161 cases of hairy cell leukemia (HCL) and 50 cases of chronic lymphocytic leukemia (CLL) were analyzed for monoclonal immunoglobulin (MIg) by using a combination of high-resolution protein electrophoresis, immunoelectrophoresis, and immunofixation. Quantitative immunoglobulin analysis also was performed on all serum samples. Monoclonal immunoglobulin, usually of low intensity, was identified in serum or urine in 26 (16.1%) cases of HCL compared with 27 (54%) cases of CLL. Forty-eight (29.8%) cases of HCL had an increase in one or more immunoglobulins; increases in IgG were the most frequent. In CLL, 48 (96.0%) cases had a decrease in one or more immunoglobulins, with decreases in IgG, IgA, and IgM in 76%, 68%, and 56% of the cases, respectively. The correlation between serum or urine monoclonal immunoglobulin light chain and the surface membrane light chain was 88% in CLL compared with 47.4% in HCL. These findings confirm previous observations of frequent polyclonal hyper-gamma-globulinemia in HCL, hypo-gamma-globulinemia in CLL, and weak monoclonal immunoglobulins in both disorders. The contrasting immunoglobulin abnormalities in HCL and CLL indicate distinctive biologic differences in these chronic B-cell leukemias.

Adult↗

PubMed1994

The Scripps Clinic experience with 2-chlorodeoxyadenosine in the treatment of hairy cell leukemia.

Follow-up data is now available on 144 patients with hairy cell leukemia treated with 2-chlorodeoxyadenosine (2-CdA) at the Scripps Clinic. Of 144 patients followed for a median of 14.2 months, 123 (85%) obtained complete responses, 17 (12%) partial responses, 3 (2%) did not respond and 1 patients was unevaluable. So far, only 4 patients have relapsed at a median of 36 months. Fever was the major toxicity occurring in 43% of patients. Five patients resistant (3 patients) or intolerant (2 patients) to 2'-deoxycoformycin were also treated. Of these 5 patients, 4 obtained complete responses, including 2 patients resistant to 2'-deoxycoformycin, and 1 patient a partial response, suggesting a possible lack of cross-resistance between 2'-deoxycoformycin and 2-CdA in hairy-cell leukemia. More than 200 patients have been treated with 2-CdA worldwide with 82% obtaining complete remission and 12% partial remissions. Serial peripheral blood immunophenotypic analyses have documented the absence of circulating hairy cells. When bone marrow biopsies were examined using sensitive immunohistochemical staining techniques, residual hairy cells were detected in 25-50% of morphologic complete responders. Patients will need to be observed longitudinally to determine if this staining is predictive of relapse. A double-blind, placebo-controlled study of pentoxifylline, a modulator of tumor necrosis factor-alpha and other cytokines, was performed in 2-CdA-treated hairy cell leukemia patients to determine whether the incidence of neutropenic fever would be reduced. Although pentoxifylline resulted in less febrile, hospital and antibiotic therapy days than placebo, only the number of days in the hospitalized patients achieved statistical significance. 2-CdA is emerging as the treatment of choice for hairy cell leukemia given the high percentage of long-lasting, complete responses that follow a single course of therapy.

Cladribine↗

PubMed1993

Diagnostic application of two-color flow cytometry in 161 cases of hairy cell leukemia.

Recent immunophenotypic studies of hairy cell leukemia (HCL) have suggested specific patterns of immunoreactivity that may aid in diagnosis. We studied peripheral blood (PB) from 161 cases of HCL using two-color direct immunofluorescence flow cytometry and an extended panel of antibody combinations. Circulating hairy cells were identified by immunophenotypic features in 92% of the cases and could be detected even when representing < or = 1% of circulating lymphocytes. The 133 cases with > or = 2% detectable hairy cells were analyzed in detail. HCL showed a uniform and unique B-cell phenotype, with each of the following features identified in 99% to 100% of cases: (1) positive staining for B-ly7, coexpressed with CD19; (2) very intense, uniform expression of CD11c, with CD19; (3) moderately intense staining for CD25, with CD19; (4) very intense staining for CD22; (5) moderate to very intense staining for CD20; and (6) moderately intense monoclonal surface Ig. Phenotypic variability existed in expression of CD10 (26%) and CD5 (4%). Based on these features, HCL was easily distinguished from 50 cases of chronic lymphocytic leukemia (CLL). Although CLL exhibited frequent expression of CD11c (74%) and CD25 (68%), the intensity of staining was significantly less than HCL. Furthermore, CLL was uniformly positive for CD5 and showed weak staining for CD20, CD22, and surface Ig. B-ly7 proved to be the most specific marker, reacting with 100% of HCL cases, but absent in all cases of CLL. We conclude that two-color flow cytometry with specific antibody combinations is an efficacious method for characterization and sensitive detection of hairy cells in PB. Application of the phenotypic criteria described should help to increase accuracy in diagnosis of HCL.

Antigens, CD↗

PubMed1992

Identification of a novel cell population in nonhealing wounds in tumors.

We have explored wound healing in tumors as a possible model for tumor-host interaction. This work demonstrated tumor wound healing failure to be the result of intense inhibition of fibroblasts although the tumor cells did not appear to be the direct source of the inhibitors. The inflammatory infiltrate found in tumor wounds was then examined for possible sources of the observed fibroblast suppression. Although the tumor wound infiltrate contains cell populations similar to a normal wound infiltrate, it also contains a large, vacuolated, nonadherent, phagocytic mononuclear cell which has morphologic and cytochemical characteristics of a lipid-laden macrophage. However, the cell also proliferates under normal culture conditions and has an immunophenotype more characteristic of lymphocytes than those of macrophages with striking expression of the CD8 surface antigen. Conditioned media from this cell population markedly inhibit fibroblast proliferation suggesting it is the source of fibroblast inhibitors within the tumor wound. Mechanical dissociation of non-wounded tumors yielded evidence that the tumor wound cell is normally present in small numbers within the tumor.

Animals↗

PubMed1992

T-cell receptor variable region gene expression in cutaneous T-cell lymphomas.

The cutaneous T-cell lymphomas (CTCL) are a group of diseases characterized by malignant proliferations of CD4 positive T-cells having monoclonally rearranged T-cell receptor (TCR) genes. A recent study using monoclonal antibodies to two TCR beta-chain variable (V) region gene products showed preferential expression of the V beta 8 gene product in these tumors. The finding of predominant usage of a single V beta gene would imply that selection by antigen is important in the etiology of these tumors. We have studied eight cases of cutaneous T-cell lymphoma and one cell line derived from a patient with mycosis fungoides/Sezary syndrome, using an extended panel of antibodies to V region gene products. Contrary to the previous report, in our study expression of the V beta 8 gene product by tumor cells was not observed in any of the cases of CTCL or in the tumor cell line studied; preferential use of any of the variable region genes recognized by the antibodies in the panel was not observed.

Adult↗

PubMed1991

Correlation of model chromosome number of cultured non-small cell lung carcinomas with DNA index of solid tumor tissue.

The modal chromosome number of 13 non-small cell lung carcinomas placed into culture was compared to the DNA index of the tumor tissue as measured by flow cytometry in order to determine whether cytogenetic results from such cultures are representative of the original solid tumor. The modal chromosome number observed in culture, which ranged from 45-146, fell within the range of aneuploidy predicted from the DNA content of the original tissue in all 13 cases. In 7 cases, flow cytometry results showed that the aneuploid G1/G0 population of the tumor tissue (DNA index of 1.5 or higher) represented 11-76% of the cells present, while diploid cells (presumably normal tissue) made up the remainder of the population. In these 7 cases, modal chromosome numbers of 61-92 were found in tumor cells cultured from the tissue. In 3 cases, only a diploid or near-diploid population was found by flow cytometry, consistent with the near-diploid modal chromosome number of cultured cells observed (45-55). In 3 cases, the aneuploid G1/G0 population (DNA index of 1.5, 1.6, and 3.2) of the original tissue represented only a small fraction of the solid tumor (1-5% of cells). Modal chromosome number found in cells cultured from these 3 cases was 64-69, 62-68, and 136-146, which is in close agreement with the aneuploid peak observed in the tissue. Histological analysis of the tumor tissue in two of the latter cases showed large numbers of infiltrating lymphocytes and/or stromal tissue which could have dominated the measurement by flow cytometry. In the third case, tumor cells made up at least 75% of the specimen examined, implying that part of the population in the "diploid" peak contained tumor cells in this specimen. Only the aneuploid population was detected in culture of this tumor. Agreement between flow cytometry and cytogenetics was found in cases in which metaphase spreads were obtained within a few days of culture as well as after several months. These results indicate that highly aneuploid populations are found in many, but not all, non-small cell lung tumors. Although in some cases multiple populations may exist in the tumor which do not all proliferate in vitro, tumor cells which are found in culture of solid lung carcinomas are representative of the original tumor. Flow cytometry findings in the solid tumors confirmed the findings of aneuploidy observed by cytogenetic analysis.

Aneuploidy↗

PubMed1991

Intratumoral T lymphocytes from small cleaved follicular center cell lymphomas show unrestricted T-cell receptor alpha-chain variable region gene usage.

The relationship between the reactive T cells and neoplastic B cells of follicular center cell lymphomas is unclear. It is not known whether the T cells are recruited nonspecifically by the neoplastic B cells or are responding through the T-cell antigen receptor (TCR), to tumor-related antigen(s). This question was addressed by polymerase chain reaction analysis of TCR alpha chain variable (V) region gene expression in intratumoral T lymphocytes from three cases of small cleaved follicular center cell lymphoma. In all three cases studied, the tumor-associated T cells showed unrestricted expression of all 18 alpha-chain V region genes. These findings imply that the T cells admixed with the neoplastic B cells of small cleaved follicular center cell lymphomas are not recruited based on TCR recognition of a single or limited number of tumor-related antigens.

DNA↗

PubMed1990

Immunogenetic analysis of bone marrow aspirates in patients with non-Hodgkin lymphomas.

The immunogenetic analysis (IGA) on the staging bone marrow aspirates in 15 patients with non-Hodgkin lymphoma (NHL) is reported. We found the sensitivity of IGA and morphologic examination in detecting bone marrow involvement by malignant lymphoma to be 91% and 82%, respectively. In 11 cases there was agreement between the morphologic findings and IGA. In 8 of these 11 cases, IGA confirmed the morphologic involvement of the bone marrow by demonstrating clonal rearrangement of either the immunoglobulin heavy- and/or light-chain or the T-cell receptor beta chain (TCR) genes. In 3 of these 11 cases, morphology showed no involvement and IGA showed germline configurations for both the immunoglobulin heavy- and light-chain or the TCR genes. In 2 additional cases the techniques proved to be complementary, as involvement was detected by only 1 of the 2 procedures. In 1 of these 2 cases, IGA showed gene rearrangement while morphologic examination was negative for involvement by NHL, while in the other case, morphologic examination showed involvement by NHL, but IGA did not show gene rearrangement. IGA was also useful in determining the clonality of solitary lymphoid nodules in the 2 remaining cases when morphologic interpretation was equivocal. In the 12 cases with bone marrow involvement, the immunophenotype and immunogenotype agreed in 11 cases. In the one case in which there was a discordance between the immunophenotype and immunogenotype, the immunophenotype was incorrectly interpreted as B-cell lineage, while the immunogenotype demonstrated a T-cell lineage. IGA also demonstrated a clonal population in 1 case of T-chronic lymphocytic leukemia where other techniques could not demonstrate the clonality of the pathologic process. IGA analysis may detect bone marrow involvement in NHL which may not be detected by morphologic examination because of patchy distribution.

B-Lymphocytes↗

PubMed1990

Cutaneous malakoplakia simulating relapsing malignant lymphoma.

This report describes the case of a 42-year-old man with malignant lymphoma, diffuse large non-cleaved cell type, who developed cutaneous malakoplakia in the left groin. The patient had widespread lymph node involvement, including a left inguinal mass which was clinically thought to represent recurrent lymphoma. The inguinal mass failed to regress after chemotherapy and irradiation, although lymphoma in other sites responded to chemotherapy. A skin biopsy of the area showed an ulcer and an abscess involving the dermis and subcutaneous tissue. Microscopically, a diffuse infiltrate of foamy histiocytes was seen with numerous intracellular and extracellular, round and laminated bodies. Some of these bodies had a "targetoid" appearance, stained strongly with von-Kossa's calcium stain and showed the typical appearance of Michaelis-Gutmann bodies by electron microscopy. Cultured monocytes from the peripheral blood of the patient showed ultrastructural features similar to their tissue counterparts, suggesting a systemic involvement of the monocyte macrophage lineage. This case represents an unusual presentation of malakoplakia of the skin associated with relapsing malignant lymphoma in a patient on immunosuppressive drugs.

Adult↗

PubMed1989

Interfollicular small lymphocytic lymphoma: the diagnostic significance of pseudofollicles.

The pathologic, immunologic, and clinical features of 25 cases of interfollicular (IF) small lymphocytic lymphoma (SLL) characterized by pseudofollicles (PFs) in the IF region of the lymph nodes and by multiple reactive follicles (RFs) were examined. IFSLL is characterized morphologically by variable numbers and sizes of prolymphocytes (nuclei showing one centrally located prominent nucleolus) in the PFs and by small round lymphocytes in the IF region. The lymph nodes in our cases had multiple RFs (100%) and patent or partially patent sinuses (72%), with moderate expansion of the IF region (48%) and typically absent or minimal perinodal infiltration (48%). In 48% of the cases, the PFs surrounded the RFs, producing a pseudo-mantle zone pattern. Immunologic study showed the medium and large prolymphocytes to be mildly LN 1- and LN 2-positive, whereas the small prolymphocytes and lymphocytes were LN 1-negative and moderately LN 2-positive. Few cells in the IF region stained with UCHL-1 antibody. These data indicate the marked preponderance of the non-follicular center cell type of B cells in the IF areas. In all 11 cases tested, a monoclonal B cell population was found. The mean age of the patients was 62 years, with a male to female ratio of 1:1.7. B symptoms were present in 20% of the patients. Nineteen percent of the patients had clinical stage I or II disease, whereas 81% had stage IV disease. The median absolute lymphocyte count was 3,239 X 10(6), with a range of 767 to 13,770 X 10(6) cells/L. In six cases, the lymphocyte count was above 4,000 X 10(6), and in no case was it more than 15,000 X 10(6). It was difficult to distinguish these cases of IFSLL from lymphadenitis and other non-Hodgkin's lymphomas because it was difficult to recognize the subtle PF pattern in the presence of a partially preserved lymph node architecture. Because of the partially retained lymph node architecture and the expansion of the IF region by PFs, this lymphoma is thought to originate from the IF small B lymphocytes, which displayed an in situ growth pattern. Moreover, because of the predominant disease in the lymph nodes and the similarity of features in PFs and follicles, we conclude that IFSLL is a disease that is primary to the lymph nodes. IFSLL should be distinguished from mantle zone lymphoma and chronic lymphocytic leukemia.

Adult↗

PubMed1989

Differential diagnosis between T-cell lymphoma and Hodgkin's disease: the value of mitotic counts and pericapsular infiltration.

The distinction between peripheral T-cell lymphoma (PTCL) and Hodgkin's disease (HD), particularly HD of the mixed cellularity subtype (HDMC), can be difficult at times using current morphologic criteria. This study assessed the value of using mitotic activity and pericapsular invasion in discriminating between the two diseases. Mitotic activity was evaluated in 64 cases of HDNS (nodular sclerosis), 51 of HDMC, 14 of HDLP (lymphocyte predominant), 7 of HDLD (lymphocyte depleted), and 28 cases of PTCL. The number of mitoses in random high-power fields (hpf) was counted independently by two observers. Interobserver agreement on mitotic counts was achieved with a 0.97 coefficient of correlation. Statistical analyses demonstrated significant differences in mitotic counts between HD and PTCL (p less than 0.01), but not within the subtypes of HD. A value of greater than 20 mitoses/20 hpf was obtained in only 10% of HD, in contrast to 70% of PTCL. The mitotic rate was greater than 40/20 hpf in 43% of PTCL, but in no case of HD. In addition, perinodal extension of disease was a significant differentiating feature between PTCL and HD, especially HDMC (p less than 0.001). There was also a significant difference in the age distribution between patients in the two disease groups, with PTCL being seen more frequently in the older age group. The results of this study confirm that counting of mitoses is reproducible, and that mitotic activity and the presence of pericapsular disease are two additional morphologic criteria that are helpful in making the distinction between HD and PTCL.

Adolescent↗

PubMed1987

High-grade mantle zone lymphoma.

A 66-year-old man with a 6-month history of sweating at night, generalized lymphadenopathy, hepatosplenomegaly, and paraproteinemia was diagnosed to have a Stage IV mantle zone lymphoma (MZL), which behaved aggressively. The neoplasm rapidly disseminated to extranodal sites--the skin, lungs, pleural cavity, and the central nervous system. The neoplasm did not respond to initial double-agent chemotherapy, but it did partially respond to multi-agent chemotherapy. In addition, the neoplasm had histopathologic features not reported previously in MZL--vascular invasion, massive extranodal infiltration, high mitotic count, and convoluted nuclei.

Aged↗

PubMed1987

Mitotic counts in follicular lymphomas.

Increased mitotic activity is associated with significantly shorter patient survival in some of the subtypes of diffuse non-Hodgkin's lymphomas. This study on 105 cases of follicular lymphoma was undertaken to determine the clinical significance of mitotic activity in follicular lymphomas. For each case, two pathologists independently counted mitotic figures in 20 random high-power fields. The difference of the average mitotic counts over 20 high-power fields for the two pathologists showed a Gaussian distribution with a median difference of -0.26 counts per high-power field and a standard error of 0.10 per cent. In 94 cases (91 per cent), the difference was less than two mitotic counts per high-power field, indicating good interobserver agreement. There was a statistically significant difference in mitotic counts between subtypes of follicular lymphoma as well as a gradient among subtypes, with the lowest mitotic activity in the poorly differentiated lymphocytic subtype and highest in the undifferentiated subtype. A multivariate statistical analysis of clinical and pathologic variables showed that mitotic figures were not of prognostic significance.

Humans↗