Search PubMed⌕ Search

Biomedical subjects

R S Neiman

Publications and source records attributed to R S Neiman.

At least 55 records · Page 3Linked to original sources

A comparison between the Rappaport Classification and Working Formulation in cooperative group trials: the ECOG experience.

The Working Formulation (WF) for the classification of non-Hodgkin's lymphomas was shown to be reproducible and clinically relevant in the original study. However, it has not yet been tested by an NCI-supported cooperative clinical oncology group. As a result, the Hematopathology Subcommittee of the Eastern Cooperative Oncology Group (ECOG) undertook a retrospective study to compare concordance and practical utility between the WF and the Rappaport Classification (RC). Data indicate that with appropriate modifications to minimize unclassifiable lymphomas, the WF can be effectively utilized in cooperative clinical oncology groups.

Humans↗

The predictive value of bone marrow morphologic characteristics and immunostaining in primary (AL) amyloidosis.

The authors previously demonstrated that bone marrow plasmacytosis in primary (AL) amyloidosis may be monoclonal or polyclonal. However, the clinical implications of the degree of plasmacytosis and its clonality have not been studied. The authors evaluated 62 patients with AL amyloidosis, 40 of whom had monoclonal medullary plasma cells. There was complete concordance between the light chain class of the plasma cells in the monoclonal cases and that of the circulating paraprotein in the 22 cases associated with a paraprotein. The remaining 22 patients had polyclonal plasma cells, although a paraprotein was detected in 6. The degree of plasmacytosis was significantly higher among patients with monoclonal plasma cells and correlated inversely with length of survival. The authors' findings indicate that the quantitation of bone marrow plasma cells in AL amyloidosis by immunoperoxidase studies may predict the clinical course.

Adult↗

Pentostatin induces durable remissions in hairy cell leukemia.

Fifty patients with hairy cell leukemia were treated with pentostatin (2'-deoxycoformycin; dCF) for a median of 3 months; 32 (64%) patients achieved complete remission (CR), and 10 (20%) patients achieved partial remission (PR), for an overall response rate of 84%. After reaching maximal response, no maintenance therapy was administered. The median duration of follow-up is now 39 months, and only four of 32 patients in CR and two of 10 patients in PR have relapsed. dCF therapy produces durable long-term, disease-free survival in patients with hairy cell leukemia.

Humans↗

Phase II trial of pentostatin in refractory lymphomas and cutaneous T-cell disease.

Thirty-seven patients with refractory lymphoma or cutaneous T-cell lymphoma were treated with 2'-deoxycoformycin (pentostatin; dCF), 5 mg/m2 intravenous (IV) bolus for 3 consecutive days of every 3-week cycle in this Eastern Cooperative Oncology Group (ECOG) trial. Included were 25 with the diagnosis of non-Hodgkin's lymphoma, three with Hodgkin's disease, eight with cutaneous T-cell lymphoma (CTCL), and one with unknown subtype, of whom 31 were considered eligible. The majority had failed at least two, but no more, conventional chemotherapy regimens. Ten (32%) of the eligible patients had a partial response (PR), including patients with nodular poorly differentiated lymphocytic (NPDL), nodular mixed (NM), diffuse poorly differentiated lymphocytic (DPDL), or diffuse histiocytic (DH), lymphoma mixed-cellularity (MC), Hodgkin's disease, and unknown subtype, and in four patients with CTCL. The overall median time to treatment failure (TTF) was only 1.3 months, but the range extended to 57.3 months. The overall response duration was 16.0 months, and the range extended to 53.4 months. Overall median survival was 2.7 months, with the range extending to 63.2 months. The majority of patients had no toxicity, but there were some instances of severe or life-threatening events. Four fatal toxicities occurred, in two patients with underlying pulmonary conditions and two with prior cardiac histories. From this study, we conclude that dCF is active in refractory lymphomas and CTCLs, should be avoided in patients with a history of serious pulmonary or cardiac diseases, and warrants consideration for incorporation of a low-dosage schedule into conventional combination chemotherapy regimens, including its use with biologic response modifiers.

Adult↗

Prognostic correlation of HLA-DR expression in large cell lymphoma as determined by LN3 antibody staining. An Eastern Cooperative Oncology Group (ECOG) study.

Several previous studies employing surface-marker techniques suggest that HLA-DR antigen expression may correlate with prognosis in diffuse large cell lymphoma. Control studies in the authors' laboratory indicated that LN3 positivity in paraffin-embedded tissue correlates well with HLA-DR antigen expression. Accordingly they examined 212 cases of diffuse large cell lymphoma from one of Eastern Cooperative Oncology Group's (ECOG) high-grade malignant lymphoma treatment protocols. All patients studied had careful clinical follow-up of between 5 and 11 1/2 years from diagnosis and initiation of therapy. There was no correlation of strongly positive, positive, weakly positive, equivocal, or negative staining with survival. Cases that were LN3 negative had a median survival of 18.8 months versus a median survival of 39.4 months for all LN3-positive cases. However this difference was not statistically significant when using a log-rank test. The authors were unable to confirm that HLA-DR antigen expression, as defined by LN3, is prognostically valuable in diffuse large cell lymphoma in a multi-institutional study.

Antibodies, Monoclonal↗

Non-Hodgkin's lymphomas of the gastrointestinal tract. An evaluation of paraffin section immunostaining.

Although the gastrointestinal (GI) tract is the most common site of primary extranodal lymphomas, the lineage of these tumors has been controversial. The authors used paraffin-reactive antibodies detecting markers of B-, T-, histiocytic, and epithelial cells to study 34 non-Hodgkin's lymphomas of the GI tract for which unequivocal frozen-section immunophenotypine was available as a control to determine whether these antibodies are reliable in the study of these tumors. Frozen-section studies revealed 31 tumors of B-cell origin and three T-cell tumors. Paraffin-reactive antibodies confirmed B-cell lineage in 28 of the 31 cases, with equivocal results in the remaining three. Only one of the T-cell lymphomas was identified in paraffin studies. Our results indicate that paraffin-reactive antibodies can reliably identify most B-cell lymphomas in the GI tract but may be unreliable in the detection of lymphomas of T-cell origin.

Adult↗

An evaluation of immunohistologic stains for immunoglobulin light chains in bone marrow biopsies in benign and malignant plasma cell proliferations.

Bone marrow specimens from 226 patients with a variety of benign and malignant plasma cell proliferations were studied to assess the reliability of immunohistologic studies in their evaluation. The clonality of the bone marrow plasma cells was compared with results of serum and urine electrophoreses. Discordance was observed most frequently in cases in which a paraprotein was demonstrated, but no monoclonality was detected by immunoperoxidase (16 cases). Of these 16 cases, 9 had 5% or less bone marrow plasma cells. In only one case was the light chain class of the bone marrow plasma cells different from that of the paraprotein. If discordant cases with 5% or less plasma cells are eliminated, the overall concordance was 97%. The authors' findings indicate that immunohistologic studies for immunoglobulin light chains in Zenker-fixed decalcified bone marrow biopsy sections are reliable in the evaluation of patients with plasma cell proliferations when the marrow contains more than 5% plasma cells.

Biopsy↗

The detection of Epstein-Barr virus in hairy cell leukemia cells by in situ hybridization.

Epstein-Barr virus (EBV) has been implicated in the pathogenesis of several B-cell lymphoid proliferations. Because patients with hairy cell leukemia (HCL) have a high incidence of seropositivity for EBV antigens, we studied the cells of HCL for evidence of EBV infection using in situ hybridization techniques. EBV mRNA was detected in the tumor cells in four of six cases using a radiolabeled RNA probe. Confirmatory serologic data were available in three cases in which the viral DNA was detected and in one negative case. Our results suggest that EBV infection may have a pathogenetic role in this disorder.

Adult↗

Paraffin section markers for Reed-Sternberg cells. A comparative study of peanut agglutinin, Leu-M1, LN-2, and Ber-H2.

Hodgkin's disease (HD) is sometimes difficult to distinguish from non-Hodgkin's lymphomas, and a reliable marker for Reed-Sternberg and related (R-S) cells in paraffin sections would be useful. Ninety-one cases of HD with PNA, anti-Leu M1, and LN-2, and 90 cases with Ber-H2 were studied. The staining results were evaluated independently. R-S cells stained positively with one or more of the reagents in all cases. PNA staining was positive in 78 cases (85.7%); Leu M1, 63 (69.2%); LN-2, 71 (78.0%); and Ber-H2, 80 cases (88.9%). Positively stained cells were readily recognized in 71 cases (91.0%) of PNA+, 51 (80.9%) of Leu M1+, and 51 (71.8%) of LN-2+ and 71 (88.7%) of Ber-H2+ cases; the cells were found only after careful search in the remaining cases. Sixteen cases of peripheral T-cell lymphoma (large cell type, ten; mixed, five; unclassifiable, one) were also stained. Tumor cells did not stain with PNA or anti-Leu M1 in any of the 16 cases but did stain positively with LN-2 in four and with Ber-H2 in five. Thus, the detection rate of R-S cells was the highest with Ber-H2, closely followed by PNA. PNA, however, stained the largest number of R-S cells per case, and the results were least affected by the type of fixative employed. Staining of peripheral T-cell lymphoma appeared to be nil or extremely rare with PNA and Leu M1, whereas it was not uncommon with Ber-H2 and LN-2. In conclusion, to facilitate the detection of R-S cells in paraffin sections, the application of a panel of three markers, PNA, Leu M1, and Ber-H2, appears to be necessary at this point in time.

Antigens, Differentiation↗

The pathogenesis of splenic extramedullary hematopoiesis in metastatic carcinoma.

Splenic extramedullary hematopoiesis (EMH) is a characteristic finding in agnogenic myeloid metaplasia (AMM) and in the spent phase of polycythemia vera (PV). Evidence from our laboratory has suggested that splenic EMH in these conditions results from the filtration of circulating hematopoietic cells from the peripheral blood and does not arise de novo from splenic stem cells. To further test this hypothesis, 31 autopsy and 26 surgical cases of carcinoma metastatic to the bone marrow were studied. The presence of leukoerythroblastosis (LEB) correlated with intravascular hematopoiesis (IVH) in the bone marrows associated with reticulin fibrosis, and with splenic EMH in the autopsy cases. These studies provide evidence that stromal changes in the bone marrow with resulting IVH, LEB, and splenic EMH are not unique to AMM and PV but also occur in such unrelated conditions as metastatic carcinoma, and suggest that these phenomena are causally related.

Adult↗

Evaluation of pathology review of malignant lymphomas and Hodgkin's disease in cooperative clinical trials. The Eastern Cooperative Oncology Group experience.

Although central expert pathology review for quality assurance in cooperative clinical trials involving malignant lymphomas and Hodgkin's disease was put in place by the NCI two decades ago, its impact upon patient eligibility for given treatment protocols has never been assessed. We reviewed diagnoses from contributing pathologists, the Eastern Cooperative Oncology Group (ECOG) review pathologists and the Pathology Panel for Lymphoma Clinical Studies in 2019 cases from 14 ECOG protocols. Although we found high rates of disagreements in diagnoses, the vast majority of these represented differences which did not impact on protocol eligibility. A total of 221 cases (10.9%) were excluded from protocols, representing a range of 2.8 to 36.7% of cases per protocol. Eighty-six percent of the exclusions resulted from the initial review by the ECOG hematopathologists. Our data indicate that while central pathology review is mandatory for quality assurance in malignant lymphoma (ML) and Hodgkin's disease (HD) protocols, a two-tier review mechanism is not necessary for adequate quality control.

Clinical Trials as Topic↗

Statistical and empirical evaluation of histopathologic reviews for quality assurance in the Eastern Cooperative Oncology Group.

Central pathology review for quality assurance in cooperative clinical cancer trials has been an accepted practice for over a decade. However, the actual value of such pathology review has never been statistically evaluated or the need defined in a comprehensive manner. Pathology exclusions in 35 completed and ongoing Eastern Cooperative Oncology Group (ECOG) trials were analyzed. Ineligibility rates ranged from 0% to 16.9%. The lowest ineligibility rates occurred in breast cancer, small cell and non-small cell lung cancer, squamous cell carcinoma of head and neck, and gastrointestinal carcinoma protocols. The highest rates occurred in rare cancers such as malignant thymoma, endocrine carcinomas, and in the sarcoma-mesothelioma area. Simulated prototypical trials involving an aggressive and an indolent cancer were examined to evaluate the precision with which treatment differences would be measured when pathologically ineligible cases were included. Analysis of these models indicated that in trials in which the pathology exclusion rate is greater than 10%, slide review is prudent. When the exclusion rate is 5% to 10%, the necessity for pathology confirmation depends on the scientific objective of the trial. If less than 5% pathology exclusions characterize a clinical trial, routine pathology review is not justified. Routine histopathologic review for quality assurance in cooperative groups is not always necessary and may be eliminated in studies of the more common cancers. The practical value of reallocating limited pathology resources for investigative studies in cooperative groups is significant.

Costs and Cost Analysis↗

Chemotherapy followed by consolidation radiation therapy for the treatment of clinical stage II aggressive histologic type non-Hodgkin's lymphoma.

Sixty-three eligible patients with Ann Arbor clinical Stage II or IIE aggressive histologic type non-Hodgkin's lymphomas received combination chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone [COPA]) as the primary treatment technique. Moderate-dose radiation therapy (2500 to 3000 cGy in 2 to 3 weeks) was given to anatomic areas involved initially by lymphoma in patients demonstrated to be in complete remission after chemotherapy. Fifty-seven percent of the patients were free of lymphoma clinically after induction chemotherapy. The minimum patient follow-up from the start of chemotherapy is 3.7 years, and the median follow-up for patients still alive is 4.7 years. The progression-free survival is projected to be 62% at 4 years, and 86% of the patients achieving a complete response are projected to be in continuous remission at 4 years from the completion of all therapy. There were no treatment-related fatalities. This treatment sequence has produced durable tumor control in the majority of patients with acceptable toxicity. The need for consolidation radiation therapy is being studied currently in a controlled clinical trial.

Antineoplastic Combined Chemotherapy Protocols↗

Inflammatory pseudotumor of the spleen: a clinicopathology study of three cases.

The clinical and pathologic findings of three cases of splenic inflammatory pseudotumor are described, and differential diagnostic features are discussed. This benign lesion is extremely rare, only four having been previously reported. Inflammatory pseudotumors often pose diagnostic difficulties because they form infiltrative masses which have clinical and gross pathologic features that suggest malignancy. Although these lesions are usually easily recognizable microscopically as benign processes, the admixed component of lymphoid and other hematopoietic cells may sometimes raise the question of a lymphoreticular malignancy, requiring immunohistologic studies for resolution in some cases. Alternatively, pseudotumors may be mistaken for infectious granulomatous processes, sarcoidosis, or hamartomas.

Adult↗

Splenic hematopoiesis in polycythemia vera. A morphologic and immunohistologic study.

Spleens from 42 patients with polycythemia vera were studied with immunohistologic technics to assess the degree of hematopoietic cellularity in an attempt to clarify the pathogenesis of the splenomegaly characteristic of this disorder. The 22 spleens obtained in the erythrocytotic phase showed striking congestion with mature erythrocytes but no significant extramedullary hematopoiesis. However, the 20 spleens obtained in the spent phase showed prominent trilinear extramedullary hematopoiesis. Increasing splenomegaly with extramedullary hematopoiesis correlated with the development of increased medullary reticulin and peripheral blood leukoerythroblastosis. Splenic myeloid metaplasia is not a feature of uncomplicated polycythemia vera, and its presence indicates progression to the spent phase, or postpolycythemic myeloid metaplasia. The authors' findings indicate that the presence of hematopoietic precursors in the spleen in the spent phase of polycythemia vera and in agnogenic myeloid metaplasia is a result of their filtration from the peripheral blood.

Adult↗

The bone marrow in myeloproliferative and dysmyelopoietic syndromes.

The myeloproliferative and dysmyelopoietic syndromes are complex disorders that are interrelated and not always easily diagnosed on morphologic grounds alone. In particular, in the case of the myeloproliferative diseases, the diagnostic pathologist should avoid the pitfall of attempting to make a definite diagnosis in the absence of appropriate laboratory and clinical data. The morphologic features in given myeloproliferative diseases are not always specific; and, as the disorders evolve, they may closely mimic one another. With respect to the dysmyelopoietic syndromes, care must be taken not to confuse them with megaloblastic anemias or other conditions that do not have the same ominous prognosis. Distinction between the varying syndromes may frequently also be difficult, and on occasion one may have difficulty placing them within the appropriate context. Only careful correlation with clinical laboratory findings and history will result in accurate diagnoses.

Bone Marrow↗

Morphology of cells grown in the CFU-GEMM tissue culture assay from mononuclear cells obtained from peripheral blood and bone marrow of normal volunteers.

In ten healthy volunteers studies were done to assess the morphology, immunocytology, and cytochemical properties of mononuclear hematopoietic stem cells isolated from normal human peripheral blood and bone marrow grown in semisolid matrix mixed lineage colony-forming unit (CFU-GEMM) culture. In three volunteers, peripheral blood and bone marrow samples were collected simultaneously; the progeny were remarkably similar in each of the three paired cultures, although macrophages were more numerous in the bone marrow cultures. Three peripheral blood samples were cultured following frozen storage with 10% DMSO at-150 degrees C for approximately 5 months. Megakaryopoiesis was present in each case, demonstrating the full hematopoietic potential of previously frozen peripheral blood mononuclear cells. Four other peripheral blood samples and one bone marrow sample were cultured and, in each case, cells of all hematopoietic cell lines were present. Bone marrow, peripheral blood mononuclear cells, and previously frozen peripheral blood mononuclear cells grown in the CFU-GEMM tissue culture assay showed the presence of granulocyte-macrophage, erythroid, and megakaryocytic cell lines.

Adult↗