Fulminant late onset cold hemagglutinin disease after allogeneic bone marrow transplantation.
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Adult↗
Biomedical subjects
A K Lie
Publications and source records attributed to A K Lie.
[Suffering of the heart, song of the lips--some examples from the history of melancholia].
Melancholy--the word has many and varied significations. It has more or less disappeared from the medical vocabulary; in ICD-10 it is only used for depressions with somatic symptoms. However, the concept continues to live on in cultural contexts; in the newspaper as a classification of an artist or his work as a distinguished form of moody creativity, or in cultural theory as an existential or philosophical category. In this article, the historical basis for this remarkable variety of significations is traced. From its beginnings in antiquity with Hippocrates and the humoral theory, through the renaissance focus on the genius, to the separation of humanist and medical disciplines, the concept lives on and takes on new meanings on its way.
Concept Formation↗
[Freedom in a little box].
What are the implications for health of freedom as a community value? This article focuses on the fact that both health and freedom are complex concepts that elude a concise definition. Depending on how you define them, the answer to the question above will vary. Different conceptions of health and freedom are described initially, and then their interdependence is illustrated by means of examples. One issue examined is how the breakdown of the communist regime in the former Soviet Union influenced life expectancy, another the positive and negative aspects of the Cuban health system. Finally, the importance of a questioning attitude to the two concepts is underlined.
Attitude to Health↗
Outcome of Chinese patients with chronic myeloid leukaemia (CML) underwent allogeneic bone-marrow transplantation (BMT).
UNLABELLED: Clinical studies have shown that patients with chronic myeloid leukaemia (CML) treated with allogeneic bone-marrow transplantation (BMT) experience not only prolonged disease-free survival but also complete cure in some. Therefore, we followed a cohort of 81 Chinese patients who received allogeneic BMT. PATIENTS AND METHODS: The donors were either relatives (65 siblings, 1 parent) or unrelated volunteers (15). BMT was performed at a median interval of 11.6 months from diagnosis of CML, and the stages of disease before BMT were: first chronic phase (60 patients), accelerated or second chronic phase in (10 patients), and blastic crisis (11 patients). Three conditioning regimens were employed: Bu-Cy, Cy-TBI, or Bu-Cy-TBI. Standard cyclosporin and short methotrexate protocol were used for acute graft-versus-host disease (GvHD) prophylaxis. RESULTS: There were five graft failures with three after related BMT. Patients after related or unrelated BMT had a comparable rate of neutrophil recovery (median = 22 days), but significant delay in platelet recovery occurred after unrelated BMT (median = 34 vs. 20 days, P < 0.05). The latter also had higher incidence of acute GvHD (73% vs. 41%, P < 0.05), although the incidence of chronic GvHD was not different between groups. At a median follow-up of 43.5 months, patients after related BMT had a significantly better rate of disease-free survival (68% vs. 37.3%, P < 0.05) and overall survival (81% vs. 38.9%, P < 0.05) at 4 years. Subgroup analysis of patients after related BMT showed the outcome was better when they were transplanted at first chronic phase. Multivariate analysis showed that advanced disease (RR = 2.01, 95% CI = 1.48-2.73) significantly worsened the outcome of BMT, whereas the presence of chronic GvHD had a protective effect against relapse and survival (RR = 0.09, 95% CI = 0.02-0.38). CONCLUSION: Allogeneic BMT is a curative form of treatment for patients with CML. Treatment outcome is best for those who undergo transplants from HLA-matched siblings during the first chronic phase.
Acute Disease↗
Advanced stage and unfavorable Hodgkin's disease in the Chinese-a 20-year experience.
We retrospectively analyzed 57 patients with advanced stage (stage III/IV) or unfavorable (presence of B symptoms or bulky disease) Hodgkin's disease from January 1977 to December 1997. There were 29 male and 28 female patients. The median age was 27 years old (range, 13-59). Lactate dehydrogenase levels ranged from 104 units/l to 2320 units/l (median, 433). Eighteen (31.6%), 13 (22.8%), and 26 (45.6%) patients had stage II bulky, stage III, and stage IV disease, respectively. Twenty-five (44%) patients had B symptoms. One (1.8%), 3 (5.3%), 36 (63.2%), and 17 (29.8%) had lymphocyte predominant, lymphocyte depleted, nodular sclerosis, and mixed cellularity histology, respectively. Chemotherapy regimens included mechlorethamine, vincristine, procarbazine, prednisone (MOPP) (n = 9), adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) (n = 23), MOPP alternating with ABVD (n = 13), and COPP-ABV hybrid (n = 12). Complete remission was achieved in 47 (82.4%) patients. Eleven patients (23%) relapsed after the first complete remission and four (36%) attained a second complete remission with salvage chemotherapy. Projected overall survival was 69.0% at 10 years and 20 years. Disease-free survival rates were 71% at 10 years and 20 years. Of the potential prognostic factors analyzed (age, sex, stage, lactate dehydrogenase, serum albumin level, regimen, B symptoms and bulky disease) by using the Cox regression model, only a low albumin level was found to adversely affect overall survival (P = 0.003). In conclusion, despite the relative low incidence of Hodgkin's disease in Hong Kong Chinese, the treatment outcomes in patients with advanced stage or unfavorable Hodgkin's disease is comparable to Caucasian patients.
Adolescent↗
Extra-medullary relapse of leukemia following allogeneic bone marrow transplantation.
The curative effect of allogeneic bone marrow transplantation (BMT) for acute and chronic leukemia is attributed to the intensive conditioning chemotherapy with or without radiotherapy, as well as an immune-mediated graft versus leukemia (GVL) effect. A different pattern of relapse has been observed after allogeneic BMT for patients with leukemia. Compared with treatment using conventional chemotherapy alone, isolated extra-medullary relapse of disease appears to be seen more commonly after allogeneic BMT. While a full donor's hematopoiesis may be retained, prolonged morphological remission has been observed in the recipient's bone marrow. There appears to be a population of leukemic cells with an affinity to extra-medullary tissues. The failure of the leukemic clone to repopulate the recipient's marrow suggests the presence of a more profound GVL effect in the marrow environment. The optimal treatment for extra-medullary relapse of leukemia following allogeneic BMT remains uncertain. In the case of isolated extra-medullary relapses following BMT, the leukemia may still be responsive to further treatment with chemotherapy and/or radiotherapy. The prognosis is poor in general, but prolonged survival has been observed in some of these patients. With the preservation of donor's hematopoiesis in the recipient's marrow, the use of intensive chemotherapy followed by donor lymphocyte or stem cell re-infusion is a promising option.
Bone Marrow Transplantation↗
Aberrant expression of the cell cycle associated proteins TP53, MDM2, p21, p27, cdk4, cyclin D1, RB, and EGFR in cervical carcinomas.
OBJECTIVE: The aims of this study were to study aberrant expression and coexpression of the cell cycle associated proteins TP53, p21, p27, cyclin D1, cdk4, RB, EGFR, and MDM2 in cervical carcinomas, to correlate protein alterations with histopathological and clinical parameters, and to evaluate whether these alterations provide prognostic information. METHODS: Seventy-four cervical carcinomas and 10 cases of normal cervical epithelium from patients with benign uterine leiomyomas were investigated immunohistochemically for aberrant expression of the cell cycle associated proteins using the biotin-streptavidin-peroxidase method and the OptiMax Plus automated cell staining system. RESULTS: In normal cervical epithelium p27 immunostaining was identified in more than 50% of the cells, cdk4 in 5-50% of the cells, and EGFR in less than 5% of the cells, whereas no immunostaining for TP53, p21, MDM2, or cyclin D1 was detected. Positive RB protein staining was identified in all cases of normal cervical epithelium. RB protein staining was also identified in all carcinomas of the cervix uteri. Overexpression of p21 was found in 96% of the tumors, MDM2 in 35%, cdk4 in 69%, cyclin D1 in 3%, and EGFR in 20% of the tumors. A low level of p27 was observed in 65% of the cases. In a previous study, the TP53 protein level has been found to be elevated in 41 of the 74 (55%) cases included in this work. Significant coexpression was seen for TP53 and MDM2 (P = 0. 001); concording results were observed in 67% of the cases. There was no difference in aberrant expression or coexpression of any of the cell cycle regulatory proteins related to histological type, grade of differentiation, FIGO stage, or relapse-free survival. CONCLUSION: The high number of cases showing increased levels of p21 and cdk4 and decreased levels of p27 suggests that these proteins may be important in the pathogenesis of cervical carcinoma. Furthermore aberrant expression of MDM2 in a smaller but significant fraction of cases indicates that these proteins could also be involved in the development of these cancers. Finally our results indicate that MDM2 may protect against HPV-induced TP53 protein degradation.
Adult↗
Computed tomography features of primary pulmonary non-Hodgkin's lymphoma.
AIM: To characterize computed tomography (CT) features of primary pulmonary lymphoma (PPL). METHODS: The CT films of six patients (five men, one woman; 63.2 +/- 14.5 years) with low grade non-Hodgkins PPL were evaluated for alveolar opacities (lobar consolidation, masses or nodules, and ill-defined consolidations), peribronchial disease or bronchial wall thickening, mediastinal nodes and pleural effusion. RESULTS: Multilobar bilateral, multilobar unilateral, and unilobar unilateral involvement were present in three, one and two cases respectively. CT features were: ill-defined mainly subpleural consolidations (n = 4), mass-like consolidation (n = 1), lobar consolidation (n = 1), and pleural effusion (n = 1). Minor peribronchial disease was seen in two patients, heterogeneous enhancement in four patients, and CT-angiogram sign in one patient. There were no lymphadenopathy or lung nodules. Although the pleura were inseparable from subpleural disease, pleural enhancement was noted on magnetic resonance imaging (MRI) of a patient with lobar lymphoma. CONCLUSION: PPL is characterized by ill-defined alveolar opacities that are usually multifocal. Peribronchial disease, proximal bronchiectasis and positive CT-angiogram sign are ancillary features. MRI may be useful in further evaluation with respect to pleural or chest wall involvement.
Adult↗
Donor lymphocyte infusion induced molecular remission in relapse of acute myeloid leukaemia after allogeneic bone marrow transplantation.
Donor lymphocyte infusion (DLI) has been used successfully to induce remissions in relapse of acute myeloid leukaemia (AML) after bone marrow transplantation (BMT), but molecular eradication of leukaemia has rarely been documented. A patient with AML-M4Eo relapsed after HLA-identical sibling BMT in first complete remission (CR). Cytogenetic and molecular genetic investigations confirmed inv(16) and CBFbeta/MYH11 fusion characteristic of M4Eo. A second remission was obtained with chemotherapy. Full donor chimerism was demonstrated by fluorescence in situ hybridisation. However, molecular evidence of minimal residual disease still persisted, and donor lymphocyte infusion (DLI) was administered. This resulted in molecular eradication, and the patient remained in clinical and molecular remission 16 months from DLI. Our observations showed that, for AML relapse after BMT, molecular leukaemia eradication could be achieved by DLI so that, in cases where genetic markers are available, molecular monitoring should be performed to assess the efficacy of treatment.
Adult↗
Isolated extramedullary relapse of acute lymphoblastic leukaemia after allogeneic bone marrow transplantation.
Isolated extramedullary relapse of acute lymphoblastic leukaemia (ALL) with sparing of the marrow after allogeneic bone marrow transplantation (BMT) is a rare occurrence, and the mechanisms underlying the selective involvement of extramedullary sites remain undefined. These might be due to relapse in sanctuary sites where the leukaemic cells are resistant to chemotherapy, or a stronger putative graft-versus-leukaemia (GVL) effect in the marrow as compared with peripheral tissues. We report two ALL patients with repeated episodes of extramedullary relapse after BMT in whom both mechanisms might be operating. In the first patient, the marrow was in morphologic and molecular remission before isolated leukaemic relapse in the central nervous system (CNS) occurred. Subsequent secondary infiltration of leukaemic cells into the marrow was only evident molecularly but not morphologically, implying that the relapse had arisen in a sanctuary CNS site. In the second patient, a first relapse in the marrow, which was induced into morphologic and molecular remission by chemotherapy and donor lymphocyte infusion, was followed by extramedullary relapses without any subsequent involvement of the marrow. This suggested that factors, likely to be due to a GVL effect, were stronger in the marrow than in peripheral tissues.
Adult↗
Human papillomavirus (HPV) in high-grade cervical intraepithelial neoplasia (CIN) detected by morphology and polymerase chain reaction (PCR)-- a cytohistologic correlation of 277 cases treated by laser conization.
The aims of this study were to evaluate the cytohistologic correlation in women treated for high-grade lesions of the cervix uteri (HG CIN), to assess the distribution of HPV features and finally to test the validity of the morphological criteria of HPV infection. The smears and biopsy specimens from 277 women treated for HG CIN by laser conization were re-evaluated blindly. Tissue blocks (n = 188) and 52 archival smears were examined for HPV DNA using PCR. HPV changes were detected with equal frequency in the smears and biopsy specimens by light microscopy; 63% and 65%, respectively. The prevalence of HPV DNA in biopsies was 88% and in archival smears 85%; agreement was found in 89% of the cases. Using PCR as the gold standard, we found a sensitivity of 63% for cytology and 70% for histology; the specificity was 41% and 37%, respectively. The positive predictive value was > 80%, but the negative predictive value was < 20%. Our study confirms that HPV features are frequently associated with HG CIN and that morphology is a non-specific method of identifying HPV infection and should be followed by PCR, also allowing detection of oncogenic HPV types and latent infections.
Conization↗
Expression of p53, MDM2, and p21 proteins in high-grade cervical intraepithelial neoplasia and relationship to human papillomavirus infection.
The relationship between human papillomavirus (HPV) infection and cell cycle regulators p53, MDM2, and p21 in cervical intraepithelial neoplasia (CIN) has not been investigated. p53, MDM2, and p21 immunoreactivity were analyzed with respect to HPV DNA status in high-grade CIN (CIN II-III). Formalin-fixed, paraffin-embedded tissue sections from 169 biopsy specimens with high-grade CIN were examined for HPV DNA by polymerase chain reaction with the L1 and E1 consensus primers Gp5+/6+ and CpI/CpIIG. HPV-positive specimens were typed with the E6 type-specific primers for HPV 16 and 18. The biopsy specimens were stained with the monoclonal antibodies p53, MDM2, and p21. The interpretation of nuclear staining was regarded as focal (< 5%), regional (5% to 50%), or diffuse (> 50%). HPV DNA was found in 156 cases (92%); 122 (78%) were positive for HPV 16, 18, or both. Immunohistochemically, p53 was detected in 50 specimens (30%); nuclear staining was mainly focal. Focal nuclear staining for MDM2 was found in 6 specimens (4%), and regional and diffuse nuclear staining for p21 was present in 137 (81%). Significant correlation was found only between p53 and MDM2 immunoreactivity. These results indicate that there is no correlation between HPV status and expression of the cell cycle regulators p53, MDM2, and p21. Inactivation of p21 and p53 protein may be important, and MDM2 abnormalities seem to play a minor role in the development of high-grade CIN.
Cyclin-Dependent Kinase Inhibitor p21↗
Association between the HLA DQB1*0301 gene and human papillomavirus infection in high-grade cervical intraepithelial neoplasia.
This study describes the distribution of DQB1genes in Norwegian women treated for high-grade cervical intraepithelial neoplasia (CIN). Formalin-fixed, paraffin-embedded tissue sections from 170 biopsy specimens with diagnoses of CIN II (n = 54) or CIN III (n = 116) were DQB1-typed using allele-specific polymerase chain reaction. The follow-up period for cases was 13 to 15 years. The control material comprised blood samples and endocervical brushes from 213 women without CIN. Both cases and controls had previously been human papillomavirus (HPV)-typed. The DQB1*0301 allele was overrepresented among cases compared with controls (odds ratio [OR] = 1.8). Presence of CIN was related to HPV infection, and HPV 16 positivity was significantly associated with the presence of DQB1*0301 (OR 1.8). The DQBI*0301 allele was significantly more prevalent in CIN III than in CIN II cases. The lesions in two women recurred in the follow-up period, one of whom was carrying the DQB1*0301 allele. Women carrying the HLA-DQB1*0301 allele have an increased risk of developing CIN when infected by HPV 16, although there was not an increased frequency of recurrent disease among women carrying this allele.
Adult↗
Treatment of de novo acute myeloid leukaemia in Hong Kong: a twenty-year experience (1975 to 1996).
BACKGROUND: Small patient numbers and short follow-up are common in some acute myeloid leukaemia (AML) studies and data on secondary malignancies after treatment of AML are rare. AIMS: To determine the prognostic factors and long-term treatment results. METHODS: A retrospective study of patients with de novo AML under the age of 60 over a 20-year period in which two induction therapy regimens: 7:3 (1975-1983) and 7:3:7 (1984-1996) and three consolidation chemotherapy regimens: 5:2 (1975-1983), 5:2:5 (1984-1990) and Ara-C/mitoxantrone (1991-1996) were used. Disease-free (DFS), overall survivals (OS) and prognostic factors were analysed. RESULTS: Two-hundred and two of 276 (73%) patients attained complete remission (CR). The CR rates of 7:3 and 7:3:7 regimens were 70.5% and 74.5% respectively (p=0.92). The median DFS was 12 months and the projected DFS at 10- and 20-years were 23% and 21% respectively. For patients consolidated with 5:2, 5:2:5 and Ara-C/mitoxantrone, the median DFS was 15 m, 12 m and 11 m respectively and the projected ten-year DFS were 27%, 21% and 18% respectively (p=0.2). Ninety per cent of relapses occurred within two years from remission but there were two late relapses at 109 m and 120 m respectively. Young age and FAB M3 subtype were favourable prognostic factors to OS (p=0.04) and DFS (p=0.006) respectively. There was no secondary solid tumour in the long-term survivors. CONCLUSION: Our experience confirmed the efficacy of standard-dose Ara-C/daunorubicin and the prognostic value of age and FAB subtype. Median and projected DFS were similar to western studies.
Acute Disease↗
Synchronous occurrence of carcinoid tumour of the appendix and T-cell lymphoma of the ileum. A case report with review of the literature.
Carcinoid tumours of the gastrointestinal tract are often associated with other tumour types at various sites. However, only rarely has a lymphoma constituted the second tumour. In the present paper, we report the case of a 62-year-old woman who was operated on for a perforated T-cell lymphoma of the ileum and in whom an appendicular carcinoid tumour was incidentally discovered at surgery. It was possible to completely remove both tumours and postoperatively the patient underwent CHOP treatment. Ten months after surgery the patient is well, with no tumour manifestations. We also discuss problems concerning classification of the lymphoma on account of loss of the T-cell antigen CD45RO (UCHL-1).
Appendiceal Neoplasms↗
Acute myeloid leukemia relapsing as gynecomastia.
Granulocytic sarcoma (GS) is an increasingly common relapse feature of acute myeloid leukemia (AML), late in the disease course or post bone marrow transplantation (BMT). Any solid organ can be affected, and there have been a number of reports of GS in breast tissue in female patients. We present a unique case of GS in a male AML patient, presenting as painless gynecomastia immediately before BMT at advanced disease. Aberrant expression of CD56 was found in the relapsed GS tissue but not in the original AML clone. Twelve months after allogeneic BMT, leukemia relapsed again in the same breast, with normal marrow morphology and full donor chimerism. The lesion failed to respond to donor lymphocyte infusion, chemotherapy and radiotherapy, and disseminated to other subcutaneous tissues.
Adult↗
Mantle cell lymphoma in the Chinese: clinicopathological features and treatment outcome.
We report the clinical, molecular, and immunohistological findings of 20 Chinese patients with mantle cell lymphoma diagnosed over a 10-year period. The disease affected mainly elderly patients (median age, 65.5 years) with a male predominance (M/F, 3/1). Eighty percent presented with advanced stage III/IV disease but only 25% had B symptoms. Eighty-five percent had extranodal disease at presentation. Complete remission (CR) and partial remission (PR) were achieved in 45% and 40% of the patients, respectively. There was no difference in the CR rate for patients treated with anthracycline-containing or nonanthracycline-containing regimens (43% and 50%, P = 0.67). Disease progression or relapse was observed after a median of 26 months in patients who initially responded to treatment. Extranodal relapse occurred in the central nervous system (n = 1), bone marrow (n = 1), pleura (n = 2), orbit (n = 2), and the gastrointestinal tract (n = 3). The median overall survival (OS) was 52 months but there were no long-term survivors. This was not different from the median OS of 53 months of patients with diffuse large cell (DLC) lymphoma treated in the same center over the same period (log rank, P = 0.76). Of the 12 patients who were tested for bcl-1 rearrangement by polymerase chain reaction (PCR), five (42%) were positive for rearrangement in the major translocation cluster (MTC) region. The median OS rates were 45 months and 63 months for PCR positive and negative patients, respectively (P = 0.97). In conclusion, MCL is a disease mainly of the elderly in the Chinese with a male predominance and most had advanced-stage disease and extranodal involvement at presentation. Clinicopathologic features and treatment outcome were similar to Caucasian patients, in that the disease combined the aggressive nature of DLC lymphoma and the incurability of low-grade lymphoma.
Aged↗
Allogeneic bone marrow transplantation for severe aplastic anemia: the Hong Kong scenario.
Severe aplastic anemia (SAA) is a disease associated with high mortality. For young patients with HLA identical siblings, allogeneic bone marrow transplantation (BMT) offers the best chance of cure. Favourable results have also been reported using immunosuppressive therapy (IST). Transplantation is usually favoured for patients below 45 years of age. We report our experience of 11 allogeneic and one syngeneic BMT for adult Chinese patients with SAA, over a 4-year period from 1991 to 1995. Ten of the 12 (83 per cent) patients had received and failed prior IST including anti-thymocyte globulin (ATG) before being referred for BMT. Neutrophil and platelet engraftment was successful in 11 of them (92 per cent) and nine were completely transfusion independent after transplantation. Their overall 3-year survival was 67 per cent. The compromised overall result was due to a number of cases transplanted after a long time delay. No patient transplanted beyond 3 years from the initial time of diagnosis of SAA achieved long-term marrow engraftment, and they all eventually succumbed. On univariate analysis, a longer time delay and hence a larger amount of blood products exposure, were highly significantly statistically associated with inferior marrow engraftment and patient survival. Other factors including age, iron status, infused cell dose and the conditioning protocol were not found to significantly affect engraftment and survival. Graft versus host disease was clinically mild or absent in most patients. This may be related to ethnicity or previous ATG exposure. In conclusion, early allogeneic BMT was a safe and effective treatment in our small series of patients with SAA failing IST.
Adolescent↗