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B Barlogie

Publications and source records attributed to B Barlogie.

At least 199 records · Page 11Linked to original sources
PubMed1987

HLA-associated invariant chain gene expression in human B cell neoplasia.

The expression of the gene encoding the HLA-DR associated invariant chain (In-gene) in human B lymphocytes was analyzed by determining the level of invariant chain, mRNA in peripheral blood and bone marrow cells of several patients affected by hematological malignancies. In B cell neoplasms representative of different stages of B lymphocyte differentiation, In-gene activation was an early event that may occur in pre-B cells before immunoglobulin gene transcripts are detectable. The highest level of invariant chain mRNA were observed at an intermediate maturation stage corresponding to sIg, Ia, and B1 positive peripheral blood lymphocytes. At the terminal stage of B lymphocyte differentiation, the In-gene was turned off. In leukemic cell populations, the pattern of temporal activation of the In-gene corresponded to the pattern of activation of the genes encoding the HLA-DR alpha and beta chain.

Antigens, Differentiation↗
PubMed1987

Characterization of hematologic malignancies by flow cytometry.

The quantitative assessment of cellular DNA and RNA content by flow cytometry to provide useful information for both diagnosis and prognosis of patients with hematologic malignancies is reviewed. While the characterization of cell surface antigens seems to be more germane to questions of the normal cell counterpart (stage) of malignant transformation and the biology of regulation of proliferation and differentiation by cell-cell contact and humoral factors, DNA-derived and RNA-derived parameters were surprisingly sensitive in the distinction of major morphologic groups, drug sensitivity and long-term prognosis. Our findings to date in the study of leukemias, lymphomas and myelomas are summarized.

DNA, Neoplasm↗
PubMed1987

High-dose chemoradiotherapy and autologous bone marrow transplantation for resistant multiple myeloma.

Seven patients with advanced multiple myeloma, refractory to therapy with alkylating agent-VAD (vincristine-adriamycin-dexamethasone), received a regimen combining high-dose melphalan with total body irradiation supported by autologous bone marrow transplantation. Very rapid, usually greater than 90% tumor mass reduction was achieved in six patients, regardless of prior chemotherapy responsiveness and marrow plasmacytosis up to 30%. Despite signs of early relapse in three patients (median remission duration of all patients, 15 months), five remain alive and well without further cytotoxic therapy from 2 to 21 months (median, 9+ months). Two patients died, one from surgical complications after transplantation and a second due to persistent neutropenia with fatal pneumonia. This treatment provides meaningful disease control for selected patients with resistant myeloma and a poor prognosis.

Blood Cells↗
PubMed1987

Flow cytometry of transitional cell carcinoma of the urinary bladder: influence of prior local therapy.

A review of acridine-orange DNA and RNA flow cytometry (FCM) histograms of 249 bladder irrigation specimens from 129 patients with a previous history of transitional cell carcinoma (TCC) reveals that aneuploidy and tetraploidy (greater than 10% of total cell population) are reliable markers to detect the presence of bladder tumor in patients treated by surgical resection of tumor only. Tetraploidy is unreliable when the patient received intravesical chemotherapy or radiation therapy but aneuploidy remains accurate. A comparison of the reliability of FCM compared with cytology indicates an overall lower sensitivity and specificity for FCM (respectively, 52% and 73%) as opposed to cytology (respectively, 62% and 92%). Sensitivity is improved and raised to 77% if FCM and cytology are used in conjunction and reaches 82% in patients treated by surgery only and 88% in those who received radiation therapy. The lowest sensitivity and specificity obtained with FCM are in patients treated by intravesical chemotherapy (respectively, 44% and 58%) and the highest are in those treated by surgery without additional therapy (56% and 83%). This study demonstrates that FCM criteria for diagnosis of TCC of urinary bladder on bladder irrigation specimens depends on patient's treatment history. It also indicates that sensitivity and specificity of cytology to detect bladder tumor are superior to those obtained with FCM but both methods may be considerably improved if they are used in conjunction.

Aneuploidy↗
PubMed1986

Fusarium. A newly recognized fungal pathogen in immunosuppressed patients.

Two cases of disseminated fungal infection due to Fusarium species, that occurred during a 4-month period, are reported. Both patients had a myeloproliferative disorder for which they had received intensive cytotoxic and immunosuppressive therapy, and both died despite treatment with amphotericin B. This report and review of the recent literature suggest that Fusarium is emerging as a newly recognized fungal pathogen in immunosuppressed patients.

Adult↗
PubMed1986

Chromosomal abnormalities in lymphoma and their correlations with nucleic acid flow cytometry.

Cytogenetic studies were performed on 25 samples obtained from 25 patients with lymphoma. Fourteen of these were also simultaneously studied with nucleic acid flow cytometry to determine percent S-phase and DNA content (ploidy). In 17 cases (68%), evaluable metaphases were obtained. The evaluable metaphase rate was higher in previously untreated patients (15/19 or 79%). All but two cases showed abnormal karyotype. All five cases showing either the t(8;14) or t(8;22) abnormality were associated with extremely high percent S-phase values, ranging from 36% to 47%, which is in the range of high-grade lymphomas according to our previous experience. Four of these cases were diagnosed as Burkitt's lymphoma and one as diffuse large cell lymphoma. Further review of this latter case resulted in the pathologic diagnosis being changed to Burkitt's lymphoma. Three patients had either numerical or structural abnormalities of chromosome #21 [two cases of extra chromosomes and one i(21q)]. All three cases were diagnosed as diffuse large cell lymphoma. Four instances of trisomy 12 were identified. Only one of these was diagnosed as diffuse well-differentiated lymphocytic lymphoma. The remaining three were Burkitt's lymphoma in two and diffuse large cell lymphoma in one. Two instances of t(14;18) were observed. This is the characteristic abnormality of follicular lymphomas. One of these cases was a follicular large cell lymphoma. The second case had possibly originated from a follicular mixed lymphoma and had evolved into a diffuse mixed cell type. Both of these cases had low S-phase values in the range of low-grade lymphomas. The correlation between ploidy as determined by flow cytometry and cytogenetic analysis was good whenever the DNA index was elevated. However, when the DNA index was 1.0 (diploid), concordant measurements were observed in only five of eight cases. Flow cytometry detected one instance of clearly abnormal ploidy, which was thought to be diploid by cytogenetics. This case most likely represents a "false negative" cytogenetic determination.

Adolescent↗
PubMed1986

Biclonal and hypodiploid multiple myeloma.

Plasma cell DNA and RNA content was measured by flow cytometry of acridine orange-stained bone marrow cells from 72 untreated patients with multiple myeloma. Biclonal or hypodiploid DNA stemlines were identified in 10 patients, nine of whom had a low RNA content and did not have response to chemotherapy. Biclonal tumors often showed atypical myeloma protein changes with chemotherapy, suggesting that one clone was reduced whereas the other remained unchanged. These findings suggest a genetic basis for the resistance of low RNA tumors to chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Analysis of nuclear m-AMSA content by DNA fluorochrome competition.

Spectrofluorometry and flow cytometry were used to measure cellular uptake of the anti-leukemic drug 4'-(9-acridinylamino) methane sulfon-m-anisidide (m-AMSA). Because of its very low intrinsic fluorescence, we used m-AMSA to quench DNA-fluorescence induced by the vital DNA fluorochrome Hoechst 33342. Maximum fluorescence was obtained with cells incubated in the fluorochrome alone. Subsequent incubation of cells in increasing concentrations of m-AMSA resulted in a gradual decrease in fluorescence. Upon incubation in drug-free medium, the quenching phenomenon was reversible, consistent with rapid exit of m-AMSA from the cells. The novel competitive fluorescence assay for cellular uptake for m-AMSA showed a better correlation to nuclear accumulation of the drug, than to its overall cellular accumulation, which may be important in assessment of cellular resistance to m-AMSA, with possible low nuclear accumulation of the drug. When this competitive fluorescence technique for measurement of cellular m-AMSA concentration was applied in flow-cytometric setting, subpopulations of normal human white blood cells were detected with distinctly different fluorescence patterns, indicating differences in cellular m-AMSA uptake. The potential use of this technique is to detect differences between cell subpopulations with different drug uptake abilities.

Amsacrine↗
PubMed1986

Phase II trial of acivicin in patients with advanced colorectal carcinoma.

Acivicin, an amino acid antibiotic, was administered to 36 adult patients with previously treated metastatic colorectal cancer. The starting dose for good-risk patients was 15 mg/m2/day day given as a short intravenous infusion on 5 consecutive days every 3 weeks. Patients previously treated with radiation therapy, mitomycin, or nitrosoureas and those with inadequate bone marrow reserve received 12 mg/m2 on the same schedule. In 33 evaluable patients, one partial response occurred. Sixteen patients had stable disease with a median time to disease progression of 15 weeks (range 9-27) and a median survival of 8 months. The median survival of the whole group was, however, less than 6 months. Myelotoxicity was mild and resulted in no significant complications. Nonhematological toxicity primarily consisted of nausea, vomiting, drowsiness, depression, and altered mentation. Acivicin given by this schedule is inactive at these dose levels in previously treated patients with colorectal carcinoma.

Adult↗
PubMed1986

Therapy of primary resistant and relapsed multiple myeloma.

This article reports the efficacy of two salvage programs for primary resistant and relapsed multiple myeloma. Employing high dose dexamethasone alone or combined with continuous infusions of vincristine and adriamycin (VAD) in 83 patients, 1/3 achieved a greater than or equal to 75% tumor cytoreduction. The highest response rate of 65% was observed among previously responding patients receiving VAD compared to approximately 1/4 among those receiving VAD for primary resistant disease or dexamethasone alone regardless of prior response status. Tumor halving times were short with values of 0.5 months for VAD and 1.3 months for dexamethasone alone. The single most important pretreatment variable associated with failure to achieve remission was a low RNA content of myeloma plasma cells in the bone marrow. The second program evaluated high dose melphalan with or without autologous bone marrow transplantation in 23 patients resistant to VAD salvage treatment. Ten of 23 patients responded for at least 2 months, and 4 others had a comparable anti-tumor effect but died between 4-6 weeks from disseminated infection. Unlike the VAD regimen, responses occurred regardless of prior response or plasma cell RNA content, and tumor halving times were extremely short with a median of 0.3 months. With autologous bone marrow support, the higher melphalan dose (140 vs. 100 mg/m2) could be more safely administered to an older patient population (median of 63 vs. 44 years) with 1 of 7 vs 6 of 16 drug-related deaths in the absence of marrow support.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

High-dose glucocorticoid treatment of resistant myeloma.

Intermittent, high-dose dexamethasone treatment was given to 49 consecutive patients with refractory multiple myeloma. In patients who were unresponsive to previous treatment, the response rate of 27% was similar to that achieved with the VAD regimen, which combines the same schedule of dexamethasone with vincristine and doxorubicin given by continuous infusion. Among patients with relapses, VAD chemotherapy induced remissions in 11 of 17 patients (65%), whereas dexamethasone alone induced remissions in 4 of 19 (21%). The median survival of all patients responding to either treatment, 22 months, was longer than that from any previous program for treatment of resistant myeloma. These findings indicate the value of frequent dexamethasone administration in patients unresponsive to standard therapy and show the major role of vincristine and doxorubicin given by continuous infusion in patients with relapses. They also suggest different mechanisms for primary and secondary resistance to chemotherapy.

Aged↗
PubMed1986

Nucleic acid cytometry of homosexual-associated lymphoproliferative disease.

Twenty-six reactive lymph nodes and 5 malignant lymphomas from homosexual males were studied by acridine orange flow cytometry (AO-FCM) for determination of ploidy, proliferation, and RNA characteristics. Two reactive lymph nodes showed ploidy abnormalities as compared with none of 27 reactive lymph nodes from nonhomosexual patients. The homosexual-associated (HA) lymphadenopathy had a higher mean proliferative activity (11.2% versus 5.6%) and higher ribonucleic acid (RNA) content (1.11 versus 0.96) than non-HA counterparts. The proliferative activity of HA lymphadenopathy was also higher than follicular small cleaved cell lymphoma, and not dissimilar to that of follicular large cell lymphoma. These findings indicate that HA-reactive lymphadenopathy is a hyperproliferative state associated with high cellular RNA content and rare DNA-abnormal stemlines. One HA lymphoma had an abnormal stemline by AO-FCM, compared with 9 of 15 (63%) non-HA high grade lymphomas. This lymphoma also demonstrated an abnormal karyotype (47,XY, +12, t[8;22]) by classic cytogenetic studies. The mean proliferative activity and RNA content of HA lymphomas was higher than non-HA counterparts (37% versus 22.5% and 2.48 versus 1.73, respectively). The proliferation and RNA features of HA lymphoma were on higher planes than non-HA lesions histologically comparable. Thus, in addition to differences in clinical presentation, histologic subtype, stage distribution, and therapeutic response, HA lymphomas have DNA/RNA characteristics different from those of counterparts in the general population.

Adult↗
PubMed1986

HLA-DR-associated invariant chain is highly expressed in chronic lymphocytic leukemia.

Total RNA extracted from peripheral blood lymphocytes of a patient with B-cell chronic lymphocytic leukemia (CLL) and the poly (A+) RNA was purified. A cDNA library was constructed and approximately 4,000 clones were screened in order to identify genes preferentially expressed in CLL. A relatively low repetition frequency characterizes the majority of the abundant mRNA species present in CLL lymphocytes. One clone, corresponding to the mRNA encoding the HLA-DR-associated invariant chain, was selected and its expression was examined in different leukemic cell populations and in normal tissues. DNA-RNA hybridization studies showed that the invariant chain mRNA (In-mRNA) is detectable in RNA preparations from human blood cells and their precursors, whereas no In-mRNA is found in several other tissues examined. Among various normal and leukemic leukocyte populations, the highest levels of In-mRNA are found in CLL. Therefore, a role of In-chain mRNA as a marker of CLL is proposed. Our data support a relationship between high levels of invariant chain mRNA and the out of cycle condition of CLL peripheral blood lymphocytes.

Clone Cells↗
PubMed1986

High-dose melphalan with autologous bone marrow transplantation for multiple myeloma.

A large dose of melphalan was given to 23 patients with advanced multiple myeloma that was refractory to multiple prior treatments. Sixteen patients received a dose of 80 to 100 mg/m2, and seven were given 140 mg/m2 followed by autologous bone marrow infusion. Tumor mass was reduced by more than 75% in 14 patients, including four who died of bone marrow aplasia. Serious infections were prevented in six of seven patients who received autologous bone marrow. The marked cytoreduction in patients with previously refractory disease indicated the apparent drug resistance could be overcome by dose escalation. However, short remission times in most responding patients were consistent with rapid regrowth of primordial tumor cells with high proliferative activity. Although high-dose melphalan was of limited benefit to patients with refractory myeloma, further studies are necessary to clarify its role during earlier phases of disease.

Adult↗
PubMed1986

Treatment of multiple myeloma with recombinant alpha-interferon.

Thirty-two patients with multiple myeloma were treated with recombinant alpha-interferon clone A (rIFN alpha A) daily by intramuscular injection with an initial dose of 12 X 10(6) U/m2. Of 27 patients evaluable for response, tumor responses were obtained in seven of 14 previously untreated patients (50%) and two of 13 who had relapsed or failed prior chemotherapy (15%). In all patients who had tumor response, there was restoration from subnormal levels of serum immunoglobulins, an effect infrequently observed with chemotherapy. The median duration of tumor responses exceeded 14 months (range, 6 to 20). Moderate-to-severe fatigue was the predominant side effect and necessitated dose reductions in all patients. We conclude that treatment of early stages of multiple myeloma with rIFN alpha A is beneficial because of the substantial response rate and the improvement in the synthesis of serum immunoglobulins. rIFN alpha A has a potential role in combination with other agents in the treatment of multiple myeloma.

Female↗
PubMed1985

Immune thrombocytopenia following alpha-interferon therapy in patients with cancer.

Immune thrombocytopenia occurred in five patients with cancer receiving alpha-interferon. The median pretreatment platelet count was 217,000/cu mm, which fell to a median of 12,000/cu mm after a median of 25 days of interferon therapy. All had normal numbers of megakaryocytes, with dysplasia noted in three; all four who were tested had platelet-associated immunoglobulin. All had normalization of platelet counts with prednisone therapy. Four tolerated re-treatment with interferon, two with concurrent prednisone administration and two others following splenectomy. Immune thrombocytopenia should be considered in patients who become thrombocytopenic during interferon therapy.

Adult↗
PubMed1985

Beta 2 microglobulin in multiple myeloma.

Serum beta 2 microglobulin levels (B2M) were evaluated before and during chemotherapy in 97 previously untreated patients with multiple myeloma. Pretreatment values were useful in confirming tumor mass grade, and marked reductions following chemotherapy correlated well with the onset of remission. No gain was evident from correcting the B2M for the level of serum creatinine. A pretreatment B2M value greater than 6 mg/L correlated with a low response rate and was the most important variable that predicted a short survival time.

Aged↗