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Biomedical subjects

A K Lie

Publications and source records attributed to A K Lie.

At least 73 records · Page 4Linked to original sources
PubMed1998

CEOP treatment results and validity of the International Prognostic Index in Chinese patients with aggressive non-Hodgkin's lymphoma.

From 1991 to 1997, we have treated 78 newly diagnosed patients with aggressive non-Hodgkin's lymphoma with a modified CHOP regimen in which epirubicin (60 mg/m2) was used in place of doxorubicin (50 mg/m2), i.e. CEOP (cyclophosphamide, epirubicin, vincristine and prednisolone). The median age was 41 years (range: 17 to 67). Sixty-four (82 per cent) had diffuse large cell (Working Formulation category G) histology. The median LDH level was 453 u/l. Thirty-three (42.3 per cent) and 45 (57.7 per cent) had stage I/II and stage III/IV disease, respectively. Fifty-five of 78 (71 per cent) CEOP-treated patients achieved CR, and the projected DFS and OS were both 65 per cent. In an earlier cohort of patients (from 1985-1991) treated with second or third-generation chemotherapy regimens (m-BACOD, MACOP-B, ProMACE-CytaBOM), CR was achieved in 95/123 (77 per cent) patients and the projected DFS and OS were 62 per cent and 55 per cent. There was no significant difference in the clinical characteristics, CR rates (p = 0.26), DFS (p = 0.38) or OS (p = 0.68) between patients who received CEOP or second/third-generation chemotherapy regimens. Of the patients treated with CEOP, 37.9 per cent, 28.8 per cent, 24.2 per cent and 9.1 per cent were in the age-adjusted International Index L, LI, HI and H risk groups, with CR rates of 82 per cent and 57 per cent in the L/LI and HI/H risk groups (p = 0.03). Moreover, patients in the L, LI and HI/H risk groups had significantly different projected DFS (87 per cent, 62 per cent and 39 per cent, p = 0.02) and OS (85 per cent, 80 per cent and 36 per cent, p = 0.006). In conclusion, CEOP is an effective regimen and the age-adjusted International Index is valid for Chinese patients with aggressive NHL.

Adolescent↗
PubMed1998

Allogeneic bone marrow transplantation for adult acute lymphoblastic leukemia: a single-centre experience.

Between 1990 and 1997, we performed 29 allogeneic BMTs for acute lymphoblastic leukemia (ALL) patients with HLA-identical sibs. Their median age was 31 years (range 15 to 43); there were 15 males and 14 females. The conditioning protocol was Cy-TBI (n = 15), VP16-Cy-TBI(n = 12), CBV (n = 1) and Bu-Cy (n = 1). Cyclosporin and methotrexate were used for GVHD prophylaxis. The median disease-free survival (DFS) was 12 months (range 1 to 92) with an actuarial 4-years DFS of 42.3 per cent. Three patients died of transplant-related complications before 100 days. Relapse occurred in 11 cases at a median time of 5 months (range 3 to 14). All nine patients relapsing within one year died form resistant leukemia. Three patients died of late treatment-related complications. There were 13 survivors (median follow-up 38 months, range 12-98), with 12 in remission. Only four had limited cGVHD, and all had 100 per cent performance scores. One patient also cleared her chronic hepatitis B carrier status due to acquired immunity. The DFS rates amongst CR1 cases and R1/CR2 cases were comparable (p = 0.39). No long-term DFS is obtained from patients with resistant disease (n = 4). The survival results for BMT at CR1 were superior to those using intensive chemotherapy consolidation (p = 0.29), mainly due to poor late results in the chemotherapy arm. For young ALL patients with HLA-matched siblings, the option of BMT should be considered in light of local consolidation survival results.

Adolescent↗
PubMed1998

Recurrent isolated extramedullary relapses as granulocytic sarcomas following allogeneic bone marrow transplantation for acute myeloid leukemia.

Isolated extramedullary relapses as granulocytic sarcomas (GS) following allogeneic bone marrow transplantation (BMT) for acute myeloid leukemia (AML) are rare events. We describe three such patients who presented with a unique pattern of GS relapse post-BMT. The clinical features included repeated relapses in multiple sites, absence of marrow involvement, and prolonged survival. Fluorescence in situ hybridization (FISH) demonstrated persistence of donor hematopoiesis despite disseminated GS. The findings indicated that a graft-versus-leukemia (GVL) effect might operate more strongly in the marrow than in peripheral sites. Finally, our observations suggest that isolated GS relapses after BMT might be compatible with long survivals, and that in patients with marrow hematopoiesis of donor origin, augmentation of the GVL effect might be of use.

Adult↗
PubMed1998

Unique risk factors for bacteraemia in allogeneic bone marrow transplant recipients before and after engraftment.

A study of the risk factors associated with bacteraemia in 191 allogeneic bone marrow transplant (BMT) recipients (1991-1996) was performed. In contrast to risk factors commonly cited for cancer chemotherapy, mucositis, degree of conditioning toxicity of the gut and lungs, duration of neutropenia, and severity of neutropenia and monocytopenia were not associated with bacteraemia in the pre-engraftment period, during which the only significant risk factor was late stage underlying disease (P < 0.05). After engraftment, Hickman catheter infection, and severe acute and chronic graft-versus-host disease (GVHD) were found to be independently associated with bacteraemia by multivariate analysis (P < 0.001, <0.05 and <0.05, respectively). This might be explained by intense antimicrobial prophylaxis, early empirical treatment, and non-routine use of haemopoietic growth factors. No significant difference in mortality was detected between bacteraemic and non-bacteraemic patients in both periods. Allogeneic BMT recipients are therefore a group of patients distinct from other cancer patients receiving chemotherapy at risk of developing bacteraemia. The study findings prompt consideration of a management protocol incorporating early and routine use of haemopoietic growth factors before engraftment in high-risk patients with late stage underlying malignancies, routine antimicrobial prophylaxis for acute GVHD with intense immunosuppression, and intravenous immunoglobulin therapy for chronic GVHD. Further cost-benefit analyses are warranted.

Adolescent↗
PubMed1998

Isolated extramedullary relapse after allogeneic bone marrow transplantation for chronic myeloid leukemia.

Relapse of chronic myeloid leukemia (CML) as extramedullary granulocytic sarcoma (GS) after allogeneic bone marrow transplantation (BMT) is a rare occurrence. We report two patients who developed spinal GS as the first indication of relapse after allogeneic BMT for CML. In both cases, the marrow was in morphologic and karyotypic remission. However, fluorescence in situ hybridization (FISH) successfully demonstrated the presence of a minor Ph-positive clone in the marrow, as well as an occult clone with an additional Ph chromosome detected in one case. The results indicated a stronger graft-versus-leukemia effect in the marrow than in the peripheral tissues.

Adult↗
PubMed1998

Granulocyte colony-stimulating factor (G-CSF) dose-dependent efficacy in peripheral blood stem cell mobilization in patients who had failed initial mobilization with chemotherapy and G-CSF.

For 10 consecutive patients in our unit who did not show a significant rise in blood progenitor cells within 14 days following chemotherapy and G-CSF, we increased the G-CSF dose from 5 to 10 microg/kg/day (n = 9) or from 10 to 15 microg/kg/day (n = 1). As a result, there were significant increases in total yield as well as yield per apheresis of mononuclear cells, CD34+ cells and CFU-GM (P < 0.025, <0.01 and <0.005, respectively). After G-CSF dose escalation, six of the 10 patients had sufficient CD34+ cells for performing transplantation. These results demonstrate a dose-dependent response of progenitor cell mobilization by G-CSF when used in combination with chemotherapy. Moreover, increasing the dose of G-CSF as late as the third week of mobilization may still provide sufficient cell yield even with patients who did not show a significant mobilization with conventional doses of G-CSF.

Adolescent↗
PubMed1998

Clonorchiasis in bone marrow transplant recipients.

Among 380 bone marrow transplant (BMT) recipients, five cases (1.3%) of clonorchiasis were observed from 1991 to 1996. Clonorchis sinensis infection was evident in the results of stool examinations performed for screening purposes 7 days before bone marrow transplantation. Salmonella species were isolated concomitantly from the stools of two of the five patients. None of the patients had symptoms due to clonorchiasis. Ultrasonography did not show dilated hepatobiliary ducts, stones, or periportal fibrosis. Fatty liver changes were detected in one patient. All five patients received praziquantel (25 mg/kg po t.i.d. for 1 day) before bone marrow transplantation. Only two patients who underwent allogeneic transplantation had mild venoocclusive disease of the liver with transient hyperbilirubinemia and mildly elevated liver enzyme levels, whereas hyperbilirubinemia or elevated serum alanine aminotransferase levels, related to conditioning toxicity, occurred in two other patients. After treatment with praziquantel, stool examination for all five patients were negative for C. sinensis ova. In addition, Salmonella species were not detected after ciprofloxacin prophylaxis. All five patients survived for > 300 days. Given the availability of effective therapy and in the absence of excessive complications, clonorchiasis is not a contraindication to bone marrow transplantation.

Adult↗
PubMed1998

CO2 laser conization for cervical intraepithelial neoplasia grade II-III: complications and efficacy.

AIMS: To examine per- and postoperative complication rates and efficacy of laser conization in the treatment of cervical intraepithelial neoplasia (CIN) grade II-III. MATERIAL AND METHODS: Eligible for analyses were all women treated with their first laser conization because of CIN II-III during the time-period January 1, 1983 to December 31, 1992. The study population comprises 1081 women who were permanent residents of one Norwegian county (Sør-Trøndelag). All analyses were performed in SPSS applying chi-square for trend, Mann-Whitney test, survival analyses and logistic regression. RESULTS: In total 86 women (8.0%) were observed with one or two (4:86) complications. Bleeding was most frequent (n = 66) followed by symptomatic cervical stenosis (n = 18). Most bleeding complications (74.2%) occurred one to two weeks postoperatively. Both bleeding complications and the occurrence of cervical stenosis were associated with cone height. Three emergency hysterectomies, two for bleeding and one for bladder perforation, were performed. Persistent disease was diagnosed in 1.9% (20:1053) of the women. All women with persistent disease were diagnosed among those with CIN III. Persistent disease was more than 20 times more common among women with disease-involved resection margins compared to those with free resection margins. CONCLUSIONS: Our evaluation of ten years' consistent use of conization by CO2 laser in the treatment of CIN II-III in an unselected population showed a low overall complication rate (8%) and very high efficacy (CIN II 100%, CIN III 98.1%) of the treatment.

Adult↗
PubMed1997

Residual and recurrent disease after laser conization for cervical intraepithelial neoplasia.

OBJECTIVE: To assess the risk of residual and recurrent disease after carbon dioxide laser conization treatment for high-grade lesions of the cervix uteri, and thus to refine intervals for follow-up. METHODS: The study population comprised all women treated for cervical intraepithelial neoplasia grade II-III over a 10-year period (1983-1992). All women who resided within the county for the entire follow-up period were followed for residual or recurrent disease, verified histologically until the closure date of January 31, 1996. The cumulative incidence of recurrent disease was assessed by survival analyses, and logistic regression was used to predict clinical features at initial treatment that were associated with the risk of residual or recurrent disease. RESULTS: Only 19 of 1081 women (1.8%) were lost to follow-up. Residual disease was diagnosed in 20 (1.9%) study participants. The cumulative incidence of recurrent disease was extremely low, increasing nearly linearly with an annual incidence of three per 1000 woman-years observed. Involved resection margins were associated significantly with both residual disease (crude odds ratio [OR] 18.1; 95% confidence interval [CI] 5.2, 64.0) and recurrent disease (adjusted OR 3.0; 95% CI 1.2, 7.5) when compared with disease-free resection margins as reference. CONCLUSION: We recommend a differential follow-up interval depending upon the histologic evaluation of cone margins. If there is no residual disease, women who have free resection margins should return at a 3-year interval for follow-up. Women who have disease extended to the cone margins are recommended Papanicolaou smears at annual intervals through the fourth postoperative year before returning at a 3-year interval as practiced in the general screening program.

Adolescent↗
PubMed1997

Autoantibody formation after allogeneic bone marrow transplantation: correlation with the reconstitution of CD5+ B cells and occurrence of graft-versus-host disease.

Manifestations of autoimmune diseases are common in patients who have received allogeneic bone marrow transplantation (BMT). Autoantibodies have been reported in these patients but the source and clinical significance of these autoantibodies are still obscure. In the present study the kinetics of autoantibody formation and the reconstitution of CD5+ B cells was followed in 21 patients who were submitted to allogeneic BMT. Anti-nuclear, anti-smooth muscle, anti-neutrophil cytoplasmic antibodies, anti-reticulin and rheumatoid factor were found at a frequency of 25%, 17%, 24%, 22% and 10% respectively after BMT. Anti-double stranded DNA levels were mildly elevated in 15% of samples. The screening for anti-extractable nuclear antigen, anti-mitochondrial, anti-gastric parietal cell, anti-proteinase III, anti-myeloperoxidase, anti-lactoferrin antibodies was negative. The percentage and absolute count of CD5+ B cells increased with time after allogeneic BMT. Those patients with anti-nuclear or anti-smooth muscle antibodies had significantly higher CD5+ B cell counts than those without these two antibodies. Correlations of CD5+ B cell counts with other autoantibodies were negative. Acute graft-versus-host disease (GVHD) occurred in eight of the patients and chronic GVHD in four patients, but the frequency of autoantibodies had no relationship with the occurrence of acute or chronic GVHD.

Autoantibodies↗
PubMed1997

Comparison of light microscopy, in situ hybridization and polymerase chain reaction for detection of human papillomavirus in histological tissue of cervical intraepithelial neoplasia.

The aims of the study were to estimate the prevalence of HPV infection in patients treated for high grade lesions of the cervix uteri (HG CIN), and to evaluate the validity of the histological criteria used for detection of HPV infection. The study comprised 203 women treated for HG CIN by laser conization. Forty-three preoperative biopsies and 160 cone specimens were examined for HPV infection using light microscopy (LM), in situ hybridization (ISH), and polymerase chain reaction (PCR). ISH was performed using commercial biotinylated probes for HPV types 6/11, 16/18, and 31/33/35 (Vira-Type In Situ Kits, Digene Diagnostics, Silver Spring, MD). HPV-PCR was performed with the L1 consensus primers Gp5+/6+. The prevalence of HPV detected by LM was 70%; by ISH 48% and by PCR 83%. Using PCR as the gold standard, LM had a sensitivity of 0.71 and specificity of 0.41. The corresponding results for ISH were 0.51 and 0.65, respectively. The positive predictive value for both tests reached over 80%, but the negative predictive value was less than 25%. This study demonstrates that morphology is an unspecific method of identifying HPV infections. LM identification of HPV infections has no clinical implications. Our analyses comparing test performances of LM, ISH and PCR show that PCR is the superior method.

Adult↗
PubMed1996

Progenitor cell yield in sequential blood stem cell mobilization in the same patients: insights into chemotherapy dose escalation and combination of haemopoietic growth factor and chemotherapy.

Between April 1988 and March 1994 a total of 23 patients with haematological or non-haematological malignancies received serial peripheral blood stem cell (PBSC) mobilization to attain sufficient harvest for PBSC transplant at our institution. There was no improvement in yield with the second mobilization for group A patients (n = 12) who had the same dose of cyclophosphamide twice as mobilizing agent. For group B patients (n = 6). who had a higher dose of cyclophosphamide with the second mobilization, there was significant increase in CFU-GM yield. CD34+ cell yield was not measured. For group C patients, who received interleukin-3 plus granulocyte-macrophage colony-stimulating factor (GM-CSF) with the first mobilization and chemotherapy plus GM-CSF with the second, there was significant increase in CFU-GM as well as CD34+ cell yield. Our results demonstrate that, at the doses studied, chemotherapy dose escalation and combining haemopoietic growth factor with chemotherapy improve progenitor cell yield in PBSC mobilization.

Adult↗
PubMed1995

Essential thrombocythemia: a retrospective analysis of 39 cases.

Thirty-nine Chinese patients presenting as essential thrombocythemia (ET) were analyzed retrospectively. The median age at presentation was 69 years and the M:F ratio was 1.35:1. At diagnosis, 33 cases (84%) were asymptomatic and the diagnosis was made incidentally, while 3 cases (8%) presented with small vessel, and 2 cases (5%) with large vessel, thrombosis. One patient (3%) presented with minor bleeding. The platelet count ranged from 0.9-34 x 10(12)/l. Of 12 karyotypes done, 2 cases were abnormal, both showing the Philadelphia (Ph) chromosome. First-line therapy was radiophosphorus (32P) in 3 cases, melphalan in 20 cases, and hydroxyurea in 12 cases; 4 cases did not receive specific therapy. During the follow-up (mean = 4 years), no thrombotic or bleeding episodes were observed. One patient with the Ph chromosome underwent blastic transformation. These results indicate that bleeding and thrombosis occur significantly less in Chinese patients than in Western patients. The Ph chromosome appears to be a bad prognostic indicator. Because of the very low incidence of complications and good prognosis, the authors believe that cytoreductive therapy is best achieved by the use of hydroxyurea instead of alkylating agents or radiophorphours, as the latter agents are potentially leukemogenic.

Adult↗
PubMed1995

Neuronal degeneration in subacute necrotizing encephalomyelopathy (Leigh's disease). Case report.

We report clinical, radiological and pathological findings in a 5-year-old girl who died of subacute necrotizing encephalomyelopathy (SNE) after 4 weeks of illness. Autopsy revealed endothelial swelling and vacuolar degeneration of the neuropil in the brain, brain stem and cerebellum. In addition, the affected areas showed degeneration of the neurons which was different from anoxic nerve cell damage both with regard to morphological picture and topographical distribution. This neuronal degeneration was probably due to the underlying metabolic defect in SNE per se and resembled in several aspects the nerve cell changes seen in the thalami and inferior olives in active Wernicke's encephalopathy. It is our opinion that more attention should be paid to the nerve cell degeneration in SNE rather than focusing on the relative preservation of these cells.

Autopsy↗
PubMed1995

Incidence of graft-versus-host disease in Hong Kong Chinese and its influence on survival after bone marrow transplantation from HLA-identical siblings.

Graft-versus-host disease (GVHD) is an important complication of allogeneic bone marrow transplantation (BMT). To assess its influence on transplant outcome, we studied 90 Chinese patients with hematologic disorders with BMT from HLA-identical siblings. GVHD prophylaxis consisted of a combination of methotrexate (MTX) and cyclosporine A (CsA). The incidence of grade II-IV acute GVHD was 29% (95% CI 19-38%). The incidence of limited and extensive chronic GVHD was 30% (95% CI 20-40%). For patients transplanted for early hematologic malignancy (n = 40), those with GVHD (acute and/or chronic) had lower relapse rate (17% (95% CI 0-36%) vs. 54% (95% CI 26-82%), P = 0.043). They had higher transplant-related mortality (12% (95% CI 0-28%) vs. 6% (95% CI 0-18%), P = 0.715) and event-free survival (EFS) (73% (95% CI 53-93%) vs. 43% (95% CI 17-69%), P = 0.104) that had not reached statistical significance. For patients transplanted for advanced hematologic malignancy (n = 37), those with GVHD also had lower relapse rate (5% (95% CI 0-15%) vs. 72% (95% CI 50-94%), P = 0.002) and higher transplant-related mortality (50% (95% CI 27-73%) vs. 8% (95% CI 0-24%), P = 0.006) than those without any GVHD. They had higher EFS (47% (95% CI 24-70%) vs. 26% (95% CI 5-47%), P = 0.609) that had not reached statistical significance. Therefore, the incidence of acute and chronic GVHD in Chinese was similar to that of their Caucasian counterparts using MTX and CsA for GVHD prophylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1995

Occurrence of human papillomavirus infection in cervical intraepithelial neoplasia. A retrospective histopathological study of 317 cases treated by laser conization.

The aim of the study was to compare the histological outcome of the cone specimens with the diagnoses of the preoperative biopsies, to assess the distribution of histological features consistent with human papillomavirus (HPV) infection and, finally, to analyse the impact of cellular HPV features on classification of cervical intraepithelial neoplasia (CIN). The study comprised a population of 317 women treated for CIN by laser conization during the period 1983-85. A total of 634 cervical specimens (317 preoperative biopsies and their corresponding cones) were studied retrospectively for CIN classification and examined for morphological signs of HPV infection. For presentation of the results, we used a modified terminology for CIN. Low-grade (LG) CIN included borderline lesions and CIN I, while high-grade (HG) CIN included CIN II and CIN III. The blinded histopathological review revealed HG CIN both in the preoperative biopsies and the cones in 71% of the cases. LG CIN or benign lesions were found in the preoperative biopsies and their corresponding cone specimens in 6% of the study population. HPV features were present in 65% of the preoperative biopsies, and were most prevalent in women under 29 years of age (p < 0.001). Thirteen percent of the total biopsy material was downgraded. The downgrading was most prevalent among original CIN II (p = 0.009) and HPV-negative biopsies (p < 0.001). This study demonstrates that CIN lesions are frequently associated with HPV features, which are significantly more prevalent in the youngest women. Concomitant HPV features do not influence the CIN classification.

Biopsy↗
PubMed1994

Differentiation-linked changes in tyrosine phosphorylation, functional activity, and gene expression downstream from the granulocyte-macrophage colony-stimulating factor receptor.

The HL-60 model of myeloid maturation was used to test whether changes in signaling from the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor accompany maturation-related changes in cellular responses to GM-CSF. Receptor expression, tyrosine phosphorylation, functional activity, and c-fos gene expression were measured. Functional GM-CSF receptors were present throughout differentiation as both uninduced and dimethyl sulfoxide (DMSO)-induced HL-60 cells responded to GM-CSF, albeit in different ways. Uninduced promyelocytes proliferated in response to GM-CSF, whereas DMSO-induced cells lost the capacity to proliferate but did respond with increased expression of beta 2-integrins, enhanced respiratory burst activity, and metabolism of arachidonic acid. GM-CSF-stimulated upregulation of c-fos mRNA expression was not detected in immature cells but developed after 2 to 4 days with DMSO in line with a marked increase in responsiveness to stimulation with phorbol ester, showing that increased expression of c-fos is predominantly a feature of mature phagocytes. GM-CSF stimulated the tyrosine phosphorylation of a broadly similar range of proteins in both uninduced and DMSO-treated HL-60 cells, but protein bands were more heavily phosphorylated in DMSO-induced cells. Phosphorylation was rapid in onset and very transient in immature cells. Phosphorylation of several proteins, in particular a 130-kD band, was more sustained in DMSO-induced cells. These differences in signaling were not because of numerical differences in receptors, because reduction of GM-CSF concentration to trigger equivalent numbers of high-affinity receptors delayed the onset of phosphorylation in DMSO-induced cells. We conclude that there are maturation-related changes in signaling downstream from the GM-CSF receptor.

Arachidonic Acid↗