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Biomedical subjects

I A Cooper

Publications and source records attributed to I A Cooper.

At least 19 recordsLinked to original sources
PubMed1998

Prognostic markers of disease activity in Hodgkin's disease.

The erythrocyte sedimentation rate (ESR), liver alkaline phosphatase (ALP), serum copper (Cu) and urinary nucleoside excretion (UNs) have been proposed as independent prognostic markers in Hodgkin's Disease (HD). However, their prognostic value has not satisfactorily been directly compared to recognised clinical prognostic factors. One hundred and sixty-eight patients with HD had the above markers performed prior to initial treatment. At a median follow-up of 10.9 yrs, the predicted 10 year relapse free survival (RFS) and overall survival (OS) for the entire cohort is 64% and 66%, respectively. In general, patients with elevated markers were significantly less likely to achieve CR, remain in CR and survive. However, multivariate analysis revealed this was due to the association of elevated markers with stage and constitutional symptoms. Following therapy, elevated markers were also correlated with evidence of clinically detectable disease. We conclude that although UNs, Cu, ALP and ESR reflect disease activity, they do not provide independent information beyond that of clinical assessment.

Adult↗
PubMed1997

Long-term survival advantage of MACOP-B over CHOP in intermediate-grade non-Hodgkin's lymphoma. The Australian and New Zealand Lymphoma Group.

BACKGROUND: The initial publication of the results of the Australian and New Zealand Lymphoma Group (ANZLG) randomized controlled trial comparing MACOP-B and CHOP in patients with intermediate-grade non-Hodgkin's lymphoma (NHL) showed equivalent complete response rates, time to treatment failure, and survival. Here we report the long-term follow-up of the 236 patients entered on that study to determine if there were any long-term advantages or disadvantages associated with MACOP-B. PATIENTS AND METHODS: Two hundred thirty-six eligible patients were randomized between October 1986 and June 1991. The median duration of follow-up has been extended from 3.2 years in our previous publication to 6.5 years. RESULTS: As previously reported, the complete response (CR) rate for MACOP-B and CHOP chemotherapy was 51% and 59%, respectively. The estimated failure-free survival rate for MACOP-B and CHOP patients was 42% and 30%, respectively, at 5 years (P = 0.045) and 37% and 25%, respectively, at 8 year (P = 0.057). The estimated overall survival rate at 5 years was 54% for MACOP-B and 41% for CHOP patients (P = 0.035) and at 8 years was 45% and 36%, respectively (P = 0.16). CONCLUSION: With this extended follow-up, we have shown a long-term survival advantage for MACOP-B chemotherapy over standard CHOP in patients with intermediate-grade non-Hodgkin's lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Interaction between a murine myeloma cell line and bone marrow stromal cells.

Intravenous transplantation of an in vitro maintained murine myeloma cell line, 5T33, results in progressive growth in the bone marrow of C57Bl/KaLwRiJ mice. Concurrent with the growth of the tumor in vivo, the bone marrow stromal cells are inhibited, as assayed by their ability to form stromal cell foci and long-term monolayers in vitro. Inhibition of normal mouse marrow stromal cell growth also occurs when 5T33 cells are added to the marrow cells in vitro, and contact between the marrow and 5T33 cells is not necessary to achieve inhibition, indicating secretion of one or more diffusible inhibitory factors.

Animals↗
PubMed1994

Oncology.

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Antibodies, Monoclonal↗
PubMed1994

Randomized comparison of MACOP-B with CHOP in patients with intermediate-grade non-Hodgkin's lymphoma. The Australian and New Zealand Lymphoma Group.

PURPOSE: To compare complete response rates, time to failure, survival, and toxicity for patients with intermediate-grade non-Hodgkin's lymphoma (NHL) treated with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) versus those treated with a regimen consisting of methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisolone, and bleomycin (MACOP-B), in a multicenter, randomized controlled trial performed by 22 centers of the Australian and New Zealand Lymphoma Group (ANZLG). PATIENTS AND METHODS: Between October 1986 and June 1991, 304 patients were randomized, of whom 236 were eligible for analysis. Eligibility criteria included diffuse small cleaved-cell, diffuse mixed small- and large-cell, follicular large-cell, diffuse large-cell, and large-cell immunoblastic, stages I bulky or II to IV. RESULTS: There was no significant difference in complete response rates (51% for MACOP-B v 59% for CHOP), failure-free survival, or overall survival in the two treatment arms. The rate of death of MACOP-B patients relative to CHOP patients was estimated to be 0.91 (P = .64) when stratified by prognostic group. There were no significant differences between the two regimens in any of the prognostic subgroups. Toxicity was significantly more severe with MACOP-B, particularly cutaneous toxicity, stomatitis, and gastrointestinal ulceration. The average relative dose-intensity (RDI) of MACOP-B was 0.91 and of CHOP was 0.90, indicating good dose delivery in this multicenter group setting. CONCLUSION: CHOP chemotherapy produced results equivalent to those of MACOP-B in patients with intermediate-grade NHL and with significantly fewer toxic complications. Despite relatively poor results in some patient subgroups, CHOP remains the standard chemotherapy for this disease, against which all new regimens should be compared.

Adolescent↗
PubMed1992

A randomised double-blind study of high-dose intravenous prochlorperazine versus high-dose metoclopramide as antiemetics for cancer chemotherapy.

High-dose prochlorperazine 0.8 mg/kg administered intravenously 30 min pre and 7 h 30 min post the initial dose of emetogenic chemotherapy was compared to high-dose metoclopramide 2 mg/kg over 20 min every 2 h for five doses starting 30 min prior to chemotherapy in a randomised, double-blind, parallel subjects design study. On the prochlorperazine arm intravenous dextrose placebos every 2 h maintained blinding. Complete suppression of vomiting occurred in 42% on metoclopramide (53% with non-cisplatin regimens) and 36% on prochlorperazine (52% with non-cisplatin-containing regimens) while major responses (2 or less vomits) occurred in 58% on metoclopramide and 54% on prochlorperazine. In patients who vomited after cisplatin, prochlorperazine achieved a significantly shorter duration of vomiting, a median of 5 h compared to 15 h on metoclopramide (P = 0.03). The response rate to prochlorperazine for cisplatin-induced emesis between 12 and 24 h was significantly better than for metoclopramide (prochlorperazine = 0.02). Toxicities were equivalent except for significantly greater sedation and dry mouth on prochlorperazine. Extrapyramidal reactions were recorded equally on both arms but were only severe enough to stop treatment on metoclopramide. The metoclopramide regimen was five times as expensive as prochlorperazine. High-dose prochlorperazine is an active and cost-effective antiemetic.

Adolescent↗
PubMed1992

Failure of intensive chemotherapy in poor prognosis non-Hodgkin's lymphoma.

In an attempt to improve response and survival rates in patients with non-Hodgkin's lymphoma, a relatively intense six drug regimen MATCOP was developed comprising four-weekly cycles of methotrexate (100 mg/m2, IV, day 8), Adriamycin (30 mg/m2, IV, days 1,2), teniposide (75 mg/m2, IV, day 1), cyclophosphamide (300 mg/m2, po, days one to five), Oncovin (1.4 mg/m2, IV: maximum 2 mg, days 8, 15) and prednisolone (100 mg, po, days one to five). A randomised trial was conducted comparing MATCOP with the standard CHOP regimen, comprising three-weekly cycles of cyclophosphamide (750 mg/m2, IV, day 1), Adriamycin (50 mg/m2, IV, day 1), Oncovin (1.4 mg/m2 IV: maximum 2 mg, day 1) and prednisolone (100 mg, po, days two to six). Eighty patients with large cell lymphoma, diffuse mixed small cleaved and large cell lymphoma or diffuse small cleaved cell lymphoma were randomised, 47 to MATCOP and 33 to CHOP. MATCOP patients experienced increased granulocytopenia, thrombocytopenia (p less than 0.0001), mucositis (p = 0.002) and infections (p = 0.01) compared to CHOP patients. Complete response rates were similar: 66% for MATCOP patients and 61% for CHOP patients. There were no apparent differences in the time to relapse for patients achieving CR, the time to treatment failure or the overall survival time. Thus despite an increase in toxicity, the more intense regimen MATCOP failed to confer any therapeutic benefit compared with the standard CHOP regimen. Survival was not influenced but toxicity was increased by dose intensification.

Adolescent↗
PubMed1991

Etoposide in leukemia.

Etoposide (VP16-213, NSC 141540) induces a complete response (CR) in 15% to 25% of previously treated patients with acute nonlymphocytic leukemia (ANLL) when used as a single agent. Etoposide has been used successfully in combination with cytarabine, daunorubicin, and amsacrine for salvage and consolidation therapies. Previously untreated ANLL patients 15 to 70 years of age were randomly assigned to cytarabine (100 mg/m2) on days 1 to 7 plus daunorubicin (50 mg/m2) on days 1 to 3 (7-3) or to the same drugs plus etoposide (75 mg/m2) on days 1 to 7 (7-3-7). Patients achieving a CR received two consolidation courses (5-2, attenuated 7-3 or 5-2-5). Among 264 eligible patients, there was a 56% CR rate with 7-3 therapy and a 59% CR rate with 7-3-7 therapy. Remission duration was significantly improved with 7-3-7 (median, 12 months with 7-3 and 18 months with 7-3-7; P = 0.01), but survival was not. Subset analysis in patients younger than 55 years of age revealed prolonged remission (median, 12 months with 7-3 and 27 months with 7-3-7; P = 0.01) and survival (median, 9 months with 7-3 and 17 months with 7-3-7; P = 0.04) with the 7-3-7 regimen. Hematologic toxicity was similar for both regimens during induction, but significantly more severe for 7-3-7 during consolidation therapy. Etoposide is active in ANLL and prolongs remission when used in induction therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Infradiaphragmatic Hodgkin's disease, long term follow-up of a rare presentation.

Hodgkin's disease limited to the infradiaphragmatic region was seen in 30 of 306 (9.8%) of all Stage I and II patients referred to the Peter MacCallum Cancer Institute between 1968 and 1980. The male:female ratio was 2.3:1 with median age of 43.5 years at presentation. Of the seven patients with clinical stage (CS) IA-IIA disease who had staging laparotomy and splenectomy only one CSIIA patient had splenic involvement. The patients were staged as pathological stage (PS) IA 2, PSIIA 5, CSIA 4, CSIIA 10, CSIIB 9. Primary treatment was by radiation in 24 patients, combination chemotherapy in five and surgical excision in one. Twenty-five patients achieved complete response. Relapse free survival (RFS) at five and ten years was 59% and the five and ten-year survival was 75% and 67% respectively. On univariate analysis the significant prognostic factors for RFS and survival were stage, constitutional symptoms and presence of bulky disease. Using Cox regression analysis the only significant variable for RFS and survival was bulky disease (p = 0.01, 0.02). A treatment policy for patients with infradiaphragmatic Hodgkin's disease is recommended.

Abdominal Neoplasms↗
PubMed1990

Value of bilateral bone marrow biopsy specimens in non-Hodgkin's lymphoma.

A study of 260 patients with non-Hodgkin's lymphoma (NHL) who underwent bilateral bone marrow biopsy at initial diagnosis showed marrow disease in 99 (38%) cases. The highest incidence of disease (83%) was seen in small lymphocytic lymphoma (SLL) and the lowest (19%) in diffuse large cell lymphoma (DLCL). Among cases with positive marrows, disease was bilateral in all 15 cases of SLL but in only 10 of 20 (50%) of the DLCL cases. In 30 of 99 (30%) positive marrows disease was unilateral. Follicular lymphomas were strongly associated with a paratrabecular pattern, with 40 of 45 positive cases showing this. Discordant histology was seen in six of 20 positive cases of DLCL and two of 37 positive cases of follicular small cleaved cell lymphomas (FSCCL). A bone marrow aspirate was positive in only 56 of the 99 (57%) cases. Peripheral blood disease was present in 15% of the bone marrow positive cases and in 6% of the cases overall. The incidence of marrow disease varies with the histological subtype of lymphoma. The paratrabecular pattern is associated with follicular lymphoma, and bilateral biopsy specimens increase the positivity rate in most subtypes of NHL.

Bone Marrow↗
PubMed1989

A study of splenic irradiation in chronic lymphocytic leukemia.

A retrospective study was performed to assess the effect of splenic irradiation (SI) on splenomegaly, splenic pain, anemia, and thrombocytopenia in patients with chronic lymphocytic leukemia. Twenty-two patients received 32 courses of SI. Of 31 courses of SI given for splenomegaly there were 19 responders (61%). Ten courses of SI were given for splenic pain resulting in partial relief of pain in 4 courses and complete relief in 4 courses. Only 4 of 16 courses given for anemia resulted in elevations of hemaglobin of 2 g/dL or more. Of the 14 courses of SI given for thrombocytopenia there were only 2 responses with platelet counts decreasing further in another 9 courses. The median duration of response was 14 months (range: 3-116 months). There was no dose-response relationship detected for SI in CLL. Treatment related toxicity was hematologic and secondary to leucopenia and thrombocytopenia. We recommend the use of small fraction sizes of 25 cGy to 50 cGy and close monitoring of hematological parameters. Splenic irradiation effectively palliates splenomegaly and reduces spleen size in CLL. It was of limited value in correcting anemia and thrombocytopenia in this patient population.

Adult↗
PubMed1988

Nitrogen mustard, vincristine, procarbazine, and prednisolone for relapse after radiation in Hodgkin's disease. An analysis of long-term follow-up.

One hundred and sixty-one patients who were treated with nitrogen mustard, vincristine, procarbazine, and prednisolone (MOPP) chemotherapy for Hodgkin's disease have been observed for a median of 10.2 years. Eighty-two percent of those patients received MOPP after relapse from previous irradiation. The complete response (CR) rate was 71%. For the 116 patients achieving CR the relapse-free survival at 5 years was 83% and at 10 years, 79%. The overall survival was 72% at 5 years and 64% at 10 years. In a stepwise logistic regression analysis the most important clinical factors influencing response were B symptoms at presentation (fever greater than 38 degrees C, night sweats, weight loss greater than 10% of body weight), histologic subtype, and lung or pleural involvement. Patients who received MOPP as first-line therapy had a significantly worse response rate than those who received MOPP upon relapse after radiotherapy. This difference is reduced when adjustments are made for the presence of the above prognostic factors. A Cox regression analysis showed that Stage IV at presentation and lymphocyte-depleted histology were the most important factors indicating reduced survival. Patients who achieved a CR to MOPP had a significantly improved survival. Of the 65 patients who had died at the time of the analysis of this series, 46 died of progressive Hodgkin's disease. All four patients who developed secondary acute nonlymphocytic leukemia had received radiation as well as MOPP.

Adolescent↗
PubMed1988

Clinical factors influencing the efficacy of pooled platelet transfusions.

To determine the relative importance of clinical factors on the efficacy of platelet transfusions, 941 pooled platelet transfusions from HLA-unmatched donors were studied prospectively in 133 patients with bone marrow failure. Multiple linear regression analyses identified the major factors influencing one-hour-corrected increments (CI) as prior splenectomy, bone marrow transplantation, disseminated intravascular coagulation, concurrent intravenous amphotericin B, splenomegaly, and HLA antibody grade. The relative impact of these factors on CI has been quantitated by using a formula developed from these data. A linear relationship was demonstrated between increasing percentage of HLA antibody grade and decreasing CI. A number of other factors were less important in the linear regression model than the aforementioned major factors. These included platelet-specific antibodies, concurrent antibacterial antibiotics, clinical bleeding grade, and temperature. Factors that did not influence CI included the number of prior platelet transfusions, prior granulocyte transfusions, prior red cell transfusions, infection, age, blood group, diagnosis, sex, pretransfusion platelet count, prior pregnancies, and concurrent antineoplastic drugs. This study identified major clinical factors that significantly influenced CI and were major causes of refractoriness to pooled platelet transfusions.

Antibodies↗
PubMed1987

Expression of leucocyte-common antigen and large sialoglycoprotein on leukemic cells in B-cell chronic lymphocytic leukemia and non-Hodgkin's lymphoma.

Patterns of leucocyte-common antigen (L-CA) and large sialoglycoprotein (LSGP) expression on leukemic peripheral blood lymphocytes of 13 patients with chronic lymphocytic leukemia (CLL), 17 with non-Hodgkin's lymphoma (NHL) in leukemic phase and one with hairy cell leukemia (HCL) have been examined by means of surface labelling and electrophoresis in 5% polyacrylamide gels. The 13 CLL, 10 of the 11 diffuse NHL and the six nodular poorly differentiated lymphocytic lymphoma (PDLL) patients fell into three groups according to expression of 210, 198 and 185k forms of L-CA. Group 1 (210 less than 198 less than 185k L-CA) included eight CLL and one diffuse NHL; Group 2 (210 greater than or equal to 198 and 185k L-CA) included four CLL, three diffuse NHL and four nodular PDLL; Group 3 (mainly 210k L-CA) included one CLL, six diffuse NHL and two nodular PDLL. A patient with diffuse large cell lymphoma and the HCL patient both had patterns of multiple, diffuse, very high Mr labelled glycoproteins. LSGP on these cells varied from nil to very high and levels were not related to L-CA patterns. Lymph node cells from five patients were also studied and were found to express larger numbers of L-CA forms and less LSGP than corresponding peripheral blood lymphocytes. Possible relationships of L-CA forms and LSGP to lymphocyte function and disease patterns are discussed.

B-Lymphocytes↗
PubMed1987

Nocardia infection in splenectomized patients: case reports and a review of the literature.

Opportunistic infections are increasingly becoming a problem in cancer patients amongst whom infection with Nocardia species is particularly difficult to detect due to the capricious natural history of the disease. Three cases of Nocardia infection in patients who had undergone splenectomy for haematological malignancy are presented. These cases illustrate the diverse mode of presentation, the natural history and the difficulties in early and accurate diagnosis of Nocardia infection. Despite the difficulties in arriving at the correct diagnosis, these cases highlight the importance of early institution of appropriate antibiotic therapy. Antibiotics should be given in adequate doses to control the initial infection and be maintained for a prolonged period to prevent relapses.

Adult↗
PubMed1987

Randomized, double-blind, cross-over study comparing prochlorperazine and lorazepam with high-dose metoclopramide and lorazepam for the control of emesis in patients receiving cytotoxic chemotherapy.

To further define optimal combinations of antiemetics, high-dose metoclopramide and lorazepam (M+L) were compared with prochlorperazine and lorazepam (P+L) in a randomized, double-blind, cross-over study. Both patient and observer assessments were documented in 66 patients receiving cisplatin and noncisplatin chemotherapy. M+L significantly reduced the severity of vomiting (P = 0.01), duration of vomiting (P = 0.05), and number of vomiting episodes (P = 0.003). Comparing the severity or duration of nausea, M+L and P+L were not significantly different. M+L significantly reduced severity of vomiting (P = 0.005) and number of vomiting episodes (P = 0.03) in the cisplatin subset. The number of vomiting episodes was also reduced in the noncisplatin subset (P = 0.03). When asked to nominate a preferred regimen, 41% of patients preferred P+L, 35% preferred M+L, and 24% rated them equally. M+L was associated with significantly more anxiety and less sedation than P+L. Patient assessments produced similar results to observer assessments but gave a broader understanding of our patients' tolerance to chemotherapy. M+L is a superior regimen in controlling vomiting induced by chemotherapy.

Adult↗