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1.
Ann Oncol ; 18(6): 1085-9, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17363838

ABSTRACT

BACKGROUND: Secondary central nervous system (CNS) involvement by aggressive lymphoma is a well-known and dreadful clinical complication. The incidence and risk factors for CNS manifestation were studied in a large cohort of elderly (>60 years) patients with aggressive lymphoma. PATIENTS AND METHODS: In all, 444 previously untreated patients were randomized to receive 3-weekly combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone or cyclophosphamide, mitoxantrone, vincristine and prednisone (CNOP) (doxorubicin substituted by mitoxantrone) chemotherapy with or without filgrastim. Prophylactic intrathecal methotrexate was given to patients with lymphoma involvement of bone marrow, testis and CNS near sites. RESULTS: In all 29 of 444 (6.5%) developed CNS disease after a median observation time of 115 months. CNS was the only site of progression/relapse in 13 patients while part of a systemic disease manifestation in 16 patients. In univariate risk factor analysis, CNS occurrence was associated with extranodal involvement of testis (P = 0.002), advanced clinical stage (P = 0.005) and increased age-adjusted International Prognostic Index score (aaIPI; P = 0.035). In multivariate analysis, initial involvement of testis remained significant and clinical stage was of borderline significance. The median survival time was 2 months after presentation of CNS disease. CONCLUSION: A significant proportion of elderly patients with advanced aggressive lymphoma will develop CNS disease. CNS occurrence is related to testis involvement, advanced clinical stage and high aaIPI and the prognosis is dismal.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Central Nervous System Neoplasms/epidemiology , Lymphoma, Non-Hodgkin/pathology , Aged , Cohort Studies , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Female , Follow-Up Studies , Humans , Incidence , Lymphoma, Non-Hodgkin/drug therapy , Lymphoma, Non-Hodgkin/mortality , Male , Neoplasm Staging , Prednisone/administration & dosage , Survival Analysis , Survivors , Time Factors , Vincristine/administration & dosage
2.
Blood ; 96(12): 3712-8, 2000 Dec 01.
Article in English | MEDLINE | ID: mdl-11090051

ABSTRACT

High serum concentrations of vascular endothelial growth factor (S-VEGF) and basic fibroblast growth factor (S-bFGF) are associated with unfavorable clinical characteristics in cancer. The combined effect of S-VEGF and S-bFGF on the survival of 200 patients with non-Hodgkin lymphoma (NHL) was studied. High S-VEGF and S-bFGF at diagnosis were associated with poor survival with the medians, the highest tertiles, or the highest quartiles as the cutoff values. The highest prognostic power was obtained when S-VEGF and S-bFGF were examined as a combination. Patients who had both S-VEGF and S-bFGF within the highest quartiles had only a 21% 5-year survival rate in contrast to a 64% 5-year survival rate among patients with both factors within the 3 lowest quartiles (P <.0001). Simultaneous elevation of S-VEGF and S-bFGF was associated with poor survival in different grades of lymphomas and in the largest histologic subgroup, the large-cell diffuse and immunoblastic lymphomas. S-VEGF (relative risk [RR], 1.83; P =.019) and S-bFGF (RR, 2.02; P =.0049) had independent influences on survival in multivariate models when tested together with the components of the International Prognostic Index (IPI). Patients with both S-VEGF and S-bFGF within the highest quartiles had nearly 3 times higher risk for death (RR, 2.90; 95% confidence interval [CI], 1.56-5.40; P =.0008) than the rest of the patients. This RR was higher than the relative risks associated with any of the components of the IPI in the same model. The authors conclude that the combination of S-VEGF and S-bFGF is a powerful prognostic variable in NHL. (Blood. 2000;96:3712-3718)


Subject(s)
Endothelial Growth Factors/blood , Fibroblast Growth Factor 2/blood , Lymphokines/blood , Lymphoma, Non-Hodgkin/blood , Lymphoma, Non-Hodgkin/diagnosis , Adult , Aged , Biomarkers/blood , Cohort Studies , Drug Resistance , Endothelial Growth Factors/adverse effects , Fibroblast Growth Factor 2/adverse effects , Follow-Up Studies , Humans , L-Lactate Dehydrogenase/blood , Lymphokines/adverse effects , Middle Aged , Multivariate Analysis , Prognosis , Survival Analysis , Survival Rate , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
3.
Cancer Causes Control ; 11(3): 197-205, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10782653

ABSTRACT

BACKGROUND: Some epidemiological investigations suggest that higher intake or biochemical status of vitamin E and beta-carotene might be associated with reduced risk of colorectal cancer. METHODS: We tested the effects of alpha-tocopherol and beta-carotene supplementation on the incidence of colorectal cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a double-blind, placebo-controlled trial among 29,133 50-69-year-old male cigarette smokers. Participants were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), both agents, or a placebo daily for 5-8 years. Incident colorectal cancers (n = 135) were identified through the nationwide cancer registry, and 99% were histologically confirmed. Intervention effects were evaluated using survival analysis and proportional hazards models. RESULTS: Colorectal cancer incidence was somewhat lower in the alpha-tocopherol arm compared to the no alpha-tocopherol arm, but this finding was not statistically significant (relative risk (RR) = 0.78, 95% confidence interval (CI) 0.55-1.09; log-rank test p = 0.15). Beta-carotene had no effect on colorectal cancer incidence (RR = 1.05, 95% CI 0.75-1.47; log-rank test p = 0.78). There was no interaction between the two substances. CONCLUSION: Our study found no evidence of a beneficial or harmful effect for beta-carotene in colorectal cancer in older male smokers, but does provide suggestive evidence that vitamin E supplementation may have had a modest preventive effect. The latter finding is in accord with previous research linking higher vitamin E status to reduced colorectal cancer risk.


Subject(s)
Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/prevention & control , Dietary Supplements , Vitamin E/administration & dosage , beta Carotene/administration & dosage , Aged , Colorectal Neoplasms/mortality , Double-Blind Method , Finland/epidemiology , Humans , Incidence , Male , Middle Aged , Risk Factors , Smoking
4.
Blood ; 94(10): 3334-9, 1999 Nov 15.
Article in English | MEDLINE | ID: mdl-10552942

ABSTRACT

Basic fibroblast growth factor (bFGF) is a secreted multifunctional cytokine and a potent stimulator of angiogenesis in vivo. Elevated bFGF concentrations have been detected in the serum and urine of cancer patients. We measured bFGF by enzyme-linked immunosorbent assay from sera taken from 160 non-Hodgkin's lymphoma (NHL) patients before treatment and stored at -20 degrees C. The patients had been observed for at least 5 years or until death. Serum bFGF concentrations (S-bFGF) ranged from undetectable to 34.7 pg/mL (median, 3.3 pg/mL). S-bFGF was detectable with a similar frequency in all subtypes of NHL. A high pretreatment S-bFGF was associated with poor overall survival. The 5-year survival rate of the patients within the highest quartile of S-bFGF concentrations (S-bFGF = 5.5 pg/mL) was only 39%, in contrast to a 60% survival rate of the patients with lower S-bFGF (P =.019). A high S-bFGF (within the highest quartile) was associated with poor outcome also in large-cell diffuse and immunoblastic lymphomas (5-year survival rates of 28% v 56%, respectively; P =.027), which was the largest histologic subgroup (n = 66) within the series. In multivariate analyses, S-bFGF was an independent prognostic factor, both when the highest quartile was used as a cut-off value (P =.0079) and when S-bFGF and the other parameters were entered into the model as continuous variables (P =.024). In the multivariate analyses, S-bFGF had a noticeably stronger prognostic value than serum lactate dehydrogenase and the number of extranodal tumor sites, both of which are currently included as components in the International Prognostic Index.


Subject(s)
Biomarkers, Tumor/blood , Fibroblast Growth Factor 2/blood , Lymphoma, Non-Hodgkin/diagnosis , Biomarkers, Tumor/metabolism , Fibroblast Growth Factor 2/metabolism , Humans , Lymphoma, Non-Hodgkin/blood , Lymphoma, Non-Hodgkin/metabolism , Lymphoma, Non-Hodgkin/mortality , Middle Aged , Multivariate Analysis , Prognosis , Survival Analysis
5.
Oncology ; 56(2): 103-9, 1999.
Article in English | MEDLINE | ID: mdl-9949294

ABSTRACT

Escalating doses of cyclophosphamide were given every 3 weeks as adjuvant treatment for women operated for breast cancer to determine the maximum tolerated dose of cyclophosphamide that can be given with constant doses of methotrexate (40 mg/m2) and 5-FU (600 mg/m2; CMF) as an outpatient treatment without the routine use of granulocyte colony-stimulating growth factor (G-CSF). The dose of cyclophosphamide was increased by 250 mg/m2 starting from the dose of 1,000 mg/m2. Mesna was given to prevent cystitis. The criteria for dose-limiting toxicity were grade IV granulocytopenia lasting for longer than 48 h, granulocytopenic infection or other grade IV toxicities. G-CSF and ofloxacin were used if grade IV granulocytopenia continued for longer than 48 h or if granulocytopenic infection occurred. At the dose level of 1,500 mg/m2 (500 mg/m2/week) 22 (92%) of the 24 patients had grade IV granulocytopenia during the 6 CMF cycles given, but only 3 (13%) had granulocytopenic fever. G-CSF was used in 28% of the cycles at this dose level. Other toxicities included complete alopecia (79%), nausea and vomiting. Sixteen (80%) of the premenopausal women became postmenopausal. At the dose level of 1,750 mg/m2 all 3 patients treated had to be hospitalized after the first cycle due to neutropenic infection (n = 2) or intractable vomiting even though prophylactic G-CSF was used. We conclude that intravenous CMF with a cyclophosphamide dose of 1,500 mg/m2 given at 3-week intervals with the selective use of prophylactic G-CSF is feasible as adjuvant treatment for patients with breast cancer.


Subject(s)
Agranulocytosis/chemically induced , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/drug therapy , Adult , Aged , Agranulocytosis/prevention & control , Alopecia/chemically induced , Ambulatory Care , Conjunctivitis/chemically induced , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Drug Administration Schedule , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Gastrointestinal Diseases/chemically induced , Granulocyte Colony-Stimulating Factor/therapeutic use , Humans , Methotrexate/administration & dosage , Methotrexate/adverse effects , Middle Aged , Neutropenia/chemically induced , Treatment Outcome , Urinary Bladder/drug effects
6.
Eur J Cancer ; 34(3): 329-36, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9640217

ABSTRACT

Mantle cell lymphoma (MCL) is a subtype of B-cell non-Hodgkin's lymphoma recently recognised as a distinct disease entity. Little is known about the prognostic factors and optimal treatment of MCL. The aim of this study was to analyse retrospectively the clinical features and effect of treatment in 94 MCL patients diagnosed and treated in one centre between 1980 and 1996, and to find out different factors influencing the treatment results and prognosis. The median age of the patients was 66 years, and 77% were over 60 years old. Of the patients, 76% had advanced disease, the performance status (PS) was WHO 0-1 in 86%, and B symptoms were present in 35% of the cases. Bone marrow infiltration was found in 61% and overt leukaemia in 12% of the patients. Of the patients, 47% achieved complete remission with first- or second-line therapy. The median duration of remission, time to treatment failure (TTF), and survival were 28, 18, and 41 months, respectively. In multivariate analyses, age, stage and leukaemic disease were significantly associated with TTF, and age, stage, leukaemic disease and lactate dehydrogenase (LDH) with survival. Long-term prognosis is poor in MCL. None of the conventional chemotherapies seems curative. A prospective randomised trial should be made to evaluate the benefit of anthracycline-containing regimens in MCL.


Subject(s)
Lymphoma, Non-Hodgkin , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Neoplasm Staging , Remission Induction , Retrospective Studies , Survival Analysis , Survival Rate , Treatment Outcome
7.
J Natl Cancer Inst ; 90(6): 440-6, 1998 Mar 18.
Article in English | MEDLINE | ID: mdl-9521168

ABSTRACT

BACKGROUND: Epidemiologic studies have suggested that vitamin E and beta-carotene may each influence the development of prostate cancer. In the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a controlled trial, we studied the effect of alpha-tocopherol (a form of vitamin E) and beta-carotene supplementation, separately or together, on prostate cancer in male smokers. METHODS: A total of 29133 male smokers aged 50-69 years from southwestern Finland were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), both agents, or placebo daily for 5-8 years (median, 6.1 years). The supplementation effects were estimated by a proportional hazards model, and two-sided P values were calculated. RESULTS: We found 246 new cases of and 62 deaths from prostate cancer during the follow-up period. A 32% decrease (95% confidence interval [CI] = -47% to -12%) in the incidence of prostate cancer was observed among the subjects receiving alpha-tocopherol (n = 14564) compared with those not receiving it (n = 14569). The reduction was evident in clinical prostate cancer but not in latent cancer. Mortality from prostate cancer was 41% lower (95% CI = -65% to -1%) among men receiving alpha-tocopherol. Among subjects receiving beta-carotene (n = 14560), prostate cancer incidence was 23% higher (95% CI = -4%-59%) and mortality was 15% higher (95% CI = -30%-89%) compared with those not receiving it (n = 14573). Neither agent had any effect on the time interval between diagnosis and death. CONCLUSIONS: Long-term supplementation with alpha-tocopherol substantially reduced prostate cancer incidence and mortality in male smokers. Other controlled trials are required to confirm the findings.


Subject(s)
Anticarcinogenic Agents/therapeutic use , Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/prevention & control , Vitamin E/therapeutic use , beta Carotene/therapeutic use , Double-Blind Method , Humans , Incidence , Male , Prostatic Neoplasms/mortality , Treatment Outcome
8.
Genes Chromosomes Cancer ; 21(4): 298-307, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9559341

ABSTRACT

We used comparative genomic hybridization (CGH) to screen for DNA copy number changes in 34 specimens from 27 cases of mantle cell lymphoma (MCL). The most common gains were detected at 3q (52%), 8q (30%), and 15q (26%), whereas the most frequent losses involved 13q (41%), 1p (33%), 6q (30%), 9p (30%), and 11q (30%). The gain of 3q, with a minimal common region at 3q26.1-27, appeared in more than half of the lymphomas, suggesting the location of an important oncogene here. A common deleted region at 11q22 was found in one-third of the patients, which suggests that this region may harbor a tumor suppressor gene important in the tumorigenesis of MCL. The mean number of changes was higher in more aggressive blastoid variants of MCL than in lymphomas with typical morphology. Our results show that the chromosomal regions affected in MCL are highly consistent and are different from those seen in other types of non-Hodgkin's lymphoma.


Subject(s)
Chromosome Aberrations/genetics , Chromosome Deletion , Chromosomes, Human, Pair 11/genetics , Chromosomes, Human, Pair 3/genetics , Lymphoma, Non-Hodgkin/genetics , Aged , Aged, 80 and over , Female , Gene Dosage , Humans , Loss of Heterozygosity/genetics , Lymphoma, Non-Hodgkin/therapy , Male , Middle Aged , Neoplasm Recurrence, Local , Ploidies
9.
Blood ; 90(10): 4039-45, 1997 Nov 15.
Article in English | MEDLINE | ID: mdl-9354673

ABSTRACT

CD44 molecule is a cell surface glycoprotein involved in many cell-cell and cell-matrix interactions. Circulating serum CD44 (s-CD44) levels have been found to change in parallel with response to therapy, but little is known about the predictive or prognostic significance of s-CD44. In the present study, we measured s-CD44 levels in sera taken before treatment from 194 patients with non-Hodgkin's lymphoma using a chemiluminescence-enzyme immunoassay method. All except 1 patient were regularly followed-up after therapy at least for 60 months (range, 33 to 143 months). The median pretreatment s-CD44 level was 440 ng/mL (range, 13 to 1,220 ng/mL). Only 32% of the 92 patients with an International Prognostic Index (IPI) score of 0 or 1 had an s-CD44 concentration higher than the median as compared with 67% of the patients with an IPI score >/=2 (P < .0001). Patients with lower than the median s-CD44 achieved more often a complete remission to therapy (P = .0002) and had better survival (P = .007) than those with higher s-CD44 levels. However, in a multivariate analysis, only the IPI score had independent prognostic value (P < .001). The findings were similar if only the patients with diffuse large-cell lymphoma (n = 51) were included in the analysis, but among patients with low-grade lymphoma, the median s-CD44 level was not significantly associated with the IPI or survival. In conclusion, a high s-CD44 level at diagnosis is associated with a high IPI score, poor response to treatment, and unfavorable outcome in non-Hodgkin's lymphoma.


Subject(s)
Biomarkers, Tumor , Hyaluronan Receptors/blood , Immunoassay/methods , Lymphoma, Non-Hodgkin/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Lymphoma, Non-Hodgkin/blood , Lymphoma, Non-Hodgkin/physiopathology , Male , Middle Aged , Predictive Value of Tests , Prognosis
10.
Blood ; 90(8): 3167-72, 1997 Oct 15.
Article in English | MEDLINE | ID: mdl-9376599

ABSTRACT

Vascular endothelial growth factor (VEGF) is a secreted endothelial cell-specific mitogen, which is induced by hypoxia and is angiogenic in vivo. Recently, elevated serum concentrations of VEGF (S-VEGF) have been reported in patients with cancers of various histologies. However, the prognostic significance of S-VEGF in human cancer is unknown and the origin of S-VEGF remains unsettled. We measured S-VEGF by enzyme-linked immunosorbent assay from sera taken from 82 patients with non-Hodgkin's lymphoma before treatment and stored for 9 to 15 years at -20 degrees C. All but one of the patients had been followed-up for at least 5 years or until death. S-VEGF ranged from 15 to 964 pg/mL; median, 228 pg/mL; mean, 291 pg/mL. A higher than the median S-VEGF level was associated with a poor World Health Organization performance status, a high International Prognostic Index, a high serum lactate dehydrogenase level, and a large cell histology. Patients with lower than the median S-VEGF at diagnosis had a 71% 5-year survival rate in comparison with only 49% among those with a higher than the median S-VEGF. We conclude that a high pretreatment S-VEGF level is associated with poor outcome in non-Hodgkin's lymphoma.


Subject(s)
Endothelial Growth Factors/blood , Lymphokines/blood , Lymphoma, Non-Hodgkin/blood , Adult , Blood Specimen Collection , Female , Freezing , Humans , Lymphoma, Non-Hodgkin/physiopathology , Male , Middle Aged , Prognosis , Retrospective Studies , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
11.
Article in English | MEDLINE | ID: mdl-9127375

ABSTRACT

OBJECTIVE: Patients treated for Hodgkin's disease and non-Hodgkin lymphomas were followed for 5 years after start of therapy. The patients received combinations of anticancer drugs for curative intent for 6 months (Hodgkin's disease) or 7 months (non-Hodgkin lymphomas). STUDY DESIGN: Cumulated data of 22 surviving patients (mean age, 49 years) were compared with that of 17 patients (mean age, 52 years) who had died or were terminally ill at the 5-year examination. Saliva samples were taken at baseline, and 4, 6, 12, and 60 months after start of chemotherapy. Salivary flow rate and a variety of biochemical constituents were analyzed. RESULTS: The results showed no long-term effect of anticancer treatment on salivary flow rates. Neither was there any difference between the surviving or deceased patients' baseline values (1.5 +/- 0.7 mL/minute versus 1.5 +/- 0.8 mL/minute) and after chemotherapy. Lysozyme, IgA, IgG, and IgM concentrations decreased after chemotherapy. Significantly lower values were observed at the 5-year examination than at baseline. This was particularly evident in IgA, which is the major immunoglobulin in saliva; mean IgA was 70.5 +/- 52.8 mg/mL at baseline, 35.8 +/- 15.0 mg/mL 5 years later (p < 0.001). Salivary total protein and amylase concentrations were significantly decreased (p < 0.001 and p < 0.05, respectively), whereas albumin concentration was significantly increased at the 5-year examination (p < 0.05). When the salivary biochemical results were compared between the surviving and deceased patients, no statistically significant differences were observed. At baseline, however, the mean immunoglobulin values were lower in patients who later died, in comparison with those who survived. CONCLUSIONS: These results showed that modern anticancer therapy need not cause severe side effects on salivary flow rates and composition. In addition, apart from the long-term immunosuppression, no significant decreases were expressed in salivary defensive factors.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Lymphoma/drug therapy , Saliva/drug effects , Adult , Aged , Aged, 80 and over , Albumins/analysis , Amylases/analysis , Analysis of Variance , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bleomycin/administration & dosage , Cyclophosphamide/administration & dosage , Dacarbazine/administration & dosage , Dexamethasone/administration & dosage , Doxorubicin/administration & dosage , Epirubicin/administration & dosage , Female , Follow-Up Studies , Hodgkin Disease/drug therapy , Humans , Immunoglobulin A, Secretory/analysis , Leucovorin/administration & dosage , Lymphoma, Non-Hodgkin/drug therapy , Male , Mechlorethamine/administration & dosage , Methotrexate/administration & dosage , Middle Aged , Muramidase/analysis , Prednisone/administration & dosage , Procarbazine/administration & dosage , Saliva/chemistry , Saliva/metabolism , Salivary Proteins and Peptides/analysis , Salivary Proteins and Peptides/drug effects , Secretory Rate/drug effects , Statistics, Nonparametric , Vinblastine/administration & dosage , Vincristine/administration & dosage
12.
Acta Oncol ; 36(6): 619-24, 1997.
Article in English | MEDLINE | ID: mdl-9408153

ABSTRACT

Seventy-six patients with stage I or IE intermediate-grade or immunoblastic non-Hodgkin's lymphoma were treated with a short course of doxorubicin-containing chemotherapy with (n = 58) or without (n = 18) involved field radiotherapy. Chemotherapy consisted of 3 or 4 cycles of M-BACOD or (bleo-)CHOP. Seventy-two (97%) of the 74 evaluable patients achieved a complete response. The 3-year overall survival was 89%, recurrence-free survival 94%, and lymphoma-specific survival 93%. Patients older than 60 years also had a 3-year lymphoma-specific survival rate of as high as 92%. The International Prognostic Index was associated with overall survival (p = 0.04), but not with lymphoma-specific survival (p = 0.18). We conclude that stages I and IE intermediate-grade or immunoblastic non-Hodgkin's Hodgkin's lymphoma is highly curable if treated with short doxorubicin-containing chemotherapy and involved field radiotherapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Large-Cell, Immunoblastic/drug therapy , Lymphoma, Large-Cell, Immunoblastic/radiotherapy , Lymphoma, Non-Hodgkin/drug therapy , Lymphoma, Non-Hodgkin/radiotherapy , Adult , Aged , Aged, 80 and over , Bleomycin/administration & dosage , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Dexamethasone/administration & dosage , Doxorubicin/administration & dosage , Female , Humans , Leucovorin/administration & dosage , Male , Methotrexate/administration & dosage , Middle Aged , Neoplasm Staging , Prednisone/administration & dosage , Retrospective Studies , Vincristine/administration & dosage
13.
Oral Oncol ; 33(6): 389-97, 1997 Nov.
Article in English | MEDLINE | ID: mdl-9509121

ABSTRACT

This article reviews papers dealing with oral infections of adult septicaemia patients, searched from MEDLINE, Current Contents and Core Biomedical Collection databases from January 1966 to November 1996. Case reports were excluded. The systematic review of literature revealed that our knowledge of the topic is mostly based on very small patient material. There are no multicentre studies on the effects of various oral health treatment modes on the prevention of septicaemia of oral origin. The number of controlled and comparative studies on the efficacy of the different treatment protocols of oral infections is also small. Current recommendations in this respect are mainly empirical and not evidence based. Clinical practice guidelines are therefore urgently needed. Nevertheless, close co-operation between oncological and oral health units is emphasised because many studies have shown that the oral cavity is indeed an important source of bacteraemia. Life-threatening infections may follow if maintenance of oral health is neglected during anticancer therapy and if potential oral infection foci are left untreated before immunosuppressive therapy.


Subject(s)
Mouth Diseases/complications , Neoplasms/complications , Sepsis/etiology , Adult , Dental Care , Dental Plaque , Humans , Immunocompromised Host , Mouth/microbiology , Mouth Diseases/therapy , Neoplasms/immunology , Neoplasms/therapy , Oral Hygiene , Saliva , Sepsis/prevention & control
14.
Oral Oncol ; 33(6): 439-43, 1997 Nov.
Article in English | MEDLINE | ID: mdl-9509129

ABSTRACT

Twenty-two patients out of the 79 that were originally included were examined 5 years after beginning anticancer therapy for lymphomas. The patients' cumulative data on salivary flow rate, buffering capacity and acidogenic microbial counts were compared with respective data of 17 patients who died during the follow-up. Stimulated saliva samples had been taken at baseline and during the cytostatic treatment with combination chemotherapy, and 1 year and 5 years later. Chair-side kits were used at the hospital ward for the assessment of the study parameters. Mean saliva flow at baseline was 1.5 +/- 0.7 ml/min in the surviving group and 1.5 +/- 0.8 ml/min in the deceased. Salivary flow rates were not affected by the anticancer treatment and there was no statistically significant difference between the groups in this respect. A significant difference was observed between the groups in salivary buffering capacity values at baseline: only 32% of the survived had low buffering capacity in comparison to 69% of those who later died (P < 0.02). Buffering capacity values remained low in 50% of the surviving patients 5 years later. Higher mutans streptococci and lactobacilli counts were seen among the deceased than in the survived patients but mutans streptococci decreased significantly in both groups after the start of the anticancer therapy (P < 0.05). The number of positive yeast counts increased consistently during the chemotherapy in both groups, being higher in the survived when compared with the deceased patients. Yeast counts remained positive 5 years later in 73% of the survived patients, while the mean mutans streptococci and lactobacilli counts decreased below baseline values. The results showed that persistently high salivary microbial counts and low buffering capacity may be linked with poor prognosis.


Subject(s)
Lymphoma/microbiology , Saliva/microbiology , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Female , Follow-Up Studies , Humans , Hydrogen-Ion Concentration/drug effects , Lactobacillus/isolation & purification , Lymphoma/drug therapy , Male , Middle Aged , Prognosis , Salivation/drug effects , Streptococcus mutans/isolation & purification , Survival Rate , Yeasts/isolation & purification
15.
Eur J Cancer ; 31A(13-14): 2406-8, 1995 Dec.
Article in English | MEDLINE | ID: mdl-8652277

ABSTRACT

The aim of the study was to define the maximum tolerated dose (MTD) of vinorelbine given as one or two weekly doses in combination with epirubicin 60 mg/m2 every third week. The MTD was defined as the dose resulting in a WHO grade III or IV leucopenia exceeding 50% of patients. Patients were treated in groups of 10 at escalating doses of vinorelbine. The number of patients at the final dose level was expanded to 20. The dose of epirubicin was kept constant at 60 mg/m2 every third week. At dose level 1, 15 mg/m2 vinorelbine was given on day 1 at level 2, 20 mg/m2 was given on day 1 and at level 3, 20 mg/m2 was given on days 1 and 8. The MTD was reached at dose level 3. WHO haematological toxicity grade IV occurred in 0, 10 and 45% and grade III at 60, 30 and 30% of patients at dose levels 1, 2 and 3, respectively. Despite the common occurrence of grade IV haematological toxicity, only two serious infections were noted. Non-haematological toxicity of vinorelbine included neurotoxicity, manifesting as muscle weakness, constipation and paresthesias in the majority of patients. Neurotoxicity was usually mild and did not require treatment discontinuation. Phlebitis at the injection site was troublesome in many patients. Alopecia and nausea, probably due to epirubicin, occurred in most patients. The response rates were 22% (95% CI (confidence interval) 3-60%), 40% (12-74%) and 60% (36-81%) at levels 1, 2 and 3, respectively (non-significant).


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Breast Neoplasms/drug therapy , Aged , Antibiotics, Antineoplastic/administration & dosage , Antibiotics, Antineoplastic/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Epirubicin/administration & dosage , Epirubicin/adverse effects , Female , Humans , Leukopenia/chemically induced , Remission Induction , Vinblastine/administration & dosage , Vinblastine/adverse effects , Vinblastine/analogs & derivatives , Vinorelbine
16.
Genes Chromosomes Cancer ; 10(2): 95-102, 1994 Jun.
Article in English | MEDLINE | ID: mdl-7520272

ABSTRACT

Analysis of most hematologic neoplasms indicates the involvement of one or more cell lineages in the bone marrow and/or the blood but rules out the involvement of all lineages in any one neoplasm. It is important to detect lineage involvement in order to clarify which stem cells are involved in leukemia, to predict prognosis, and to select appropriate treatment. Our aim was to study the cell lineage involvement of some of the recurrent chromosomal abnormalities seen in hematological neoplasms. The direct morphology-antibody-chromosomes (MAC) method was used. The deletion 20q in myeloproliferative diseases (MPD), the deletion of 5q and t(1;7) in myelodysplastic syndromes (MDS), and t(3;3) in acute myeloid leukemia subtype M7 (AML-M7) were seen in all or at least in two myeloid lineages. These were interpreted as stem cell abnormalities. Deletion 13q in MPD, t(8;21) in AML-M2 and t(15;17) in AML-M3 were seen in granulocytic lineages only; t(14;18) in non-Hodgkin's lymphoma and trisomy 12 as the sole abnormality in chronic lymphocytic leukemia (B-CLL) were seen only in immunoglobulin light chain clonal B cells; inversion 14 in T-CLL was seen only in T cells, whereas t(15;14) in acute lymphocytic leukemia with eosinophilia (ALL-EO) was seen in lymphoid stem cells but not in mature granulocytes or lymphocytes. Additional abnormalities (in addition to the Philadelphia chromosome) in chronic myeloid leukemia (CML) were seen in all myeloid cell lineages and also in mature granulocytes, B cells, and large granular lymphocytes. Abnormalities in Hodgkin's disease were restricted to CD30-positive Reed-Sternberg cells. Trisomy 8 and monosomy 7 are abnormalities that may be present in either stem cells or any of the single cell lineages.


Subject(s)
Chromosome Aberrations , Chromosome Disorders , Leukemia/genetics , Lymphoma/genetics , Myelodysplastic Syndromes/genetics , Blast Crisis/genetics , Blast Crisis/pathology , Cell Line , Chromosome Deletion , Hodgkin Disease/genetics , Humans , Leukemia/pathology , Lymphoma/pathology , Megakaryocytes/pathology , Reed-Sternberg Cells/pathology , Stem Cells/pathology , Translocation, Genetic , Tumor Cells, Cultured
17.
Eur J Cancer B Oral Oncol ; 30B(3): 204-8, 1994 May.
Article in English | MEDLINE | ID: mdl-7920168

ABSTRACT

We reported earlier that despite the well-known cytolytic effect of anticancer drugs, mean stimulated salivary flow rates were not significantly affected during a 12-month follow-up of patients undergoing treatment for lymphomas (Laine et al. Oral Oncol, Eur J Cancer 1992, 28B, 125-128). Therefore, we set out to investigate in more detail the flow rates and composition of salivas in these patients, but now grouped according to their initial flow rate values, which had been assessed before the start of treatment. 49 patients of the original material (30 men and 19 women, mean age 49.9 years) were divided into hyposalivation and normal flow rate groups, according to their baseline values. Stimulated saliva flow > or = 0.8 ml/min was regarded as the limit for a normal flow rate. 11 patients were found to have reduced flow at baseline (hyposalivation group), while 38 patients had normal flow rate. Analysis of repeated saliva samples taken during the 12-month follow-up showed that flow rates remained significantly lower in the hyposalivation group compared with those of the other group (P < 0.001). Further, the concentrations of total protein, albumin, lysozyme, amylase, IgG, IgA and IgM were, and remained, all significantly higher in patients of the hyposalivation group. Counts for salivary mutans streptococci and yeasts were higher and remained significantly so among patients with hyposalivation than among those with normal flow rate while lactobacilli counts were higher in patients with normal initial flow rate.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Lymphoma/physiopathology , Saliva/drug effects , Salivation/drug effects , Xerostomia/physiopathology , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Female , Follow-Up Studies , Humans , Lymphoma/drug therapy , Male , Middle Aged , Saliva/chemistry , Saliva/microbiology , Xerostomia/microbiology
18.
Eur J Haematol ; 52(2): 65-72, 1994 Feb.
Article in English | MEDLINE | ID: mdl-8119385

ABSTRACT

Two B-cell lines, designated as HF-1 and HF-4, were characterised. The cell lines have complicated karyotype abnormalities including a 14;18 translocation and an 8q24 breakpoint originating from t(2;8)(p11;q24) (HF-1) or t(1;8)(p21;q24) (HF-4). The lines have BCL2 rearrangement and they are positive for CD19, CD20, CD22, CD39. HF-1 is also positive for IgG, and HF-4 is positive for IgM and IgD. On Northern blot analyses, the 2.6-kb and 4.2-kb transcripts corresponding to the major transcripts of CMYC and BCL2, respectively, were seen. In Western blot as well as in FACS (fluorescence-activated cell sorting) analysis the presence of BCL2 protein in the both HF-1 and HF-4 cells was demonstrated. The cell lines are expected to serve as an important tool in the study of the chromosomal mechanism activating cellular oncogenes, the somatic hypermutation mechanism of antigen-activated B cells and the apoptosis of B cells.


Subject(s)
Lymphoma, B-Cell/pathology , Base Sequence , DNA Primers/chemistry , Gene Expression , Gene Rearrangement , Genes, Immunoglobulin , Genes, myc , Humans , Immunophenotyping , Karyotyping , Lymph Nodes/pathology , Molecular Sequence Data , Oncogenes , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins c-bcl-2 , RNA, Messenger/genetics , Translocation, Genetic , Tumor Cells, Cultured
19.
J Clin Periodontol ; 20(9): 628-34, 1993 Oct.
Article in English | MEDLINE | ID: mdl-8227449

ABSTRACT

This double-blind study was undertaken to evaluate the effect of twice-daily use of a mouthwash containing 0.025% of fluoride as amine fluoride-stannous fluoride (AmF + SnF) or 0.05% of fluoride as sodium fluoride (NaF) on visible plaque index (VPI) and gingival bleeding index (GBI) and on some salivary micro-organisms in patients suffering from non-Hodgkin or Hodgkin lymphomas. 79 patients were allocated at random to the two mouthwash groups. Mouthwashing began at the start of cancer chemotherapy. Results relating to 45 patients who completed a 1-year rinsing protocol showed a significant decrease in VPI and GBI in the AmF + SnF group. An increase was found in the NaF group. Mean values for stimulated salivary secretion rates and buffering capacities mostly did not differ significantly from baseline values during the study. In both groups, mutans streptococci counts decreased significantly after the study began and remained low in the AmF + SnF group. No corresponding effect was seen in relation to lactobacilli and yeast counts. In the NaF group, lactobacilli counts increased significantly over a year. Significantly more patients reported adverse or unpleasant effects in the AmF + SnF group (52%) than in the NaF group (6%), although both solutions had the same colour and taste. However, all patients continued with rinsing.


Subject(s)
Amines/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bacteria/isolation & purification , Hodgkin Disease/drug therapy , Lymphoma, Non-Hodgkin/drug therapy , Mouthwashes , Periodontal Index , Saliva/microbiology , Tin Fluorides/therapeutic use , Adult , Amines/administration & dosage , Buffers , Colony Count, Microbial , Dental Plaque Index , Double-Blind Method , Drug Combinations , Female , Humans , Male , Middle Aged , Mouthwashes/administration & dosage , Patient Compliance , Patient Satisfaction , Saliva/drug effects , Saliva/metabolism , Secretory Rate/drug effects , Sodium Fluoride/administration & dosage , Sodium Fluoride/therapeutic use , Tin Fluorides/administration & dosage
20.
Eur J Cancer B Oral Oncol ; 29B(4): 291-4, 1993 Oct.
Article in English | MEDLINE | ID: mdl-11706423

ABSTRACT

The 1-year incidence of oral mucosal lesions during cytostatic therapy was investigated in 67 patients [34 men and 33 women (mean age 49 years)] out of 79 original patients, being treated for non-Hodgkin lymphoma or Hodgkin's disease. The incidence of lesions during examinations was 43.4%. Recurrent lesions were observed in 19.4% of cases. Mean leukocyte counts were statistically significantly lower (P < 0.01) during lesion periods than before cytostatic therapy in all lesion groups. Leukocytopenia was found in 85.4% of patients with hairy leukoplakia-like lesions (HLL), and in 81.8% of the patients with angular cheilitis. 5 out of 14 patients with oral ulcers (35.7%) had episodes of septicaemia. Mean thrombocyte counts of patients in various lesion groups were normal (< 140 x 10/1). However, low thrombocyte counts were more statistically significant (P < 0.05), when haemorrhages or HLL were present. Clinical candidiasis was diagnosed in 28.4% of patients during the treatment. However, cultivation revealed that 62.3% of salivary yeast cultures were positive. The study reported here shows a correlation between mucosal ulcers and septicemia, and between leukocytopenia, angular cheilitis and HLL. The disparity between clinically diagnosed candidiasis and the occurrence of salivary yeast counts suggests that antifungal drugs might be of prophylactic value during cytostatic therapy.


Subject(s)
Antineoplastic Agents/adverse effects , Hodgkin Disease/drug therapy , Lymphoma, Non-Hodgkin/drug therapy , Mouth Diseases/chemically induced , Mouth Mucosa/drug effects , Mouth Mucosa/pathology , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Candidiasis/chemically induced , Female , Hemorrhage , Humans , Male , Middle Aged , Sepsis/chemically induced , Sepsis/complications
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