Biomedical subjects

E Elonen

Publications and source records attributed to E Elonen.

At least 19 recordsLinked to original sources

PubMed2006

Autologous stem cell transplantation in elderly (>60 years) patients with non-Hodgkin's lymphoma: a nation-wide analysis.

Limited experience is available on the feasibility and efficacy of autologous stem cell transplantation (ASCT) in elderly patients with non-Hodgkin's lymphoma (NHL). In 1994-2004 altogether 88 NHL patients > 60 years old received ASCT in six Finnish transplant centres. There were 57 male and 31 female patients with a median age of 63 years (range 60-70 years); 17 patients were>65 years. The histology included diffuse large B cell (n = 29), mantle cell (n = 27), follicular (n = 15), peripheral T cell (n = 12) and other (n = 5). Disease status at ASCT was I complete remission/partial remission (CR/PR) in 53 patients, II CR/PR in 30 patients and other in five patients. The conditioning regimens included BEAC (n = 49), BEAM (n = 34), TBI-CY (n = 4) and other (n = 1). Eighty-four patients received PB grafts. The medians to reach neutrophils > 0.5 and platelets > 20 were 10 and 14 days, respectively. The early treatment-related mortality (TRM) (<100 days) was 11%. With a median follow-up of 21 months for all patients, 45 patients (51%) are alive. A relapse or progression after ASCT has been observed in 32 patients (36%). ASCT is feasible in selected elderly patients with NHL, but the early TRM seems to be higher than in younger patients.

Age Factors↗

PubMed2005

Outcome of progressive disease after autologous stem cell transplantation in patients with non-Hodgkin's lymphoma: a nation-wide survey.

OBJECTIVES: To analyse outcome and prognostic factors in non-Hodgkin's lymphoma (NHL) patients who progress after autologous stem cell transplantation (ASCT). PATIENTS: Altogether 115 consecutive NHL patients transplanted in 1991-2000 were studied. Histology included diffuse large B cell (n = 52), follicular (n = 26), mantle cell (n = 15), T cell (n = 16) and other subtypes (n = 6). The median time from ASCT to the progression was 7 months. Ninety-six patients (83%) received salvage treatment. RESULTS: Twenty-four patients (25%) achieved complete remission and 30 (31%) partial remission. The median overall survival was 8 months (range 0-98+) and the projected 4-year survival 21%. In multivariate analysis factors predicting treatment response after the progression included the use of rituximab (P = 0.036), histology other than diffuse large B cell (P = 0.001) and International Prognostic Index < or =2 at progression (P < 0.001). Normal lactate dehydrogenase (LDH) at progression (P = 0.002), response to salvage treatment (P < 0.001) and time from ASCT to progression > or =7 months (P = 0.022) were predictors for overall survival. CONCLUSIONS: Although the prognosis of patients who progress after ASCT is generally poor, many patients will respond to current therapies, and some may experience prolonged survival. Normal LDH at time of disease progression and longer time to progression after ASCT were the most powerful predictors for a promising outcome.

Adolescent↗

PubMed2004

Autologous stem cell transplantation in adult patients with peripheral T-cell lymphoma: a nation-wide survey.

Limited experience is available on the feasibility and efficacy of high-dose therapy (HDT) supported by autologous stem cell transplantation (ASCT) in patients with peripheral T-cell lymphoma (PTCL). Therefore, a nation-wide survey was conducted in adult patients transplanted for PTCL in Finland during 1990-2001. After histopathology review, 37 patients were identified. The median age was 46 years (16-68) at the time of ASCT. Histology included PTCL not otherwise specified in 14 patients, anaplastic large cell lymphoma (ALCL) in 14 patients, and other in nine patients. Disease status at the time of ASCT was CR/PR1 in 18 patients; CR/PR2 in 14 patients, and other in five patients. HDT consisted of either BEAC (N=22) or BEAM (N=15), supported by blood stem cells in 34 patients (92%). Early transplant-related mortality was 11%. With a median follow-up of 24 months from HDT, 16 patients (43%) have relapsed or progressed. The estimated 5-year overall survival (OS) was 54%. Patients with ALCL had superior OS when compared with other subtypes (85 vs 35%, P=0.007). OS at 5 years was 63% in patients transplanted in CR/PR1 vs 45% in those transplanted in other disease status (P=NS). Prospective studies are needed to define the role of ASCT in this lymphoma type.

Adolescent↗

PubMed2004

Oral treatment of acute myeloid leukaemia with etoposide, thioguanine, and idarubicin (ETI) in elderly patients: a prospective randomised comparison with intravenous cytarabine, idarubicin, and thioguanine in the second and third treatment cycle.

A randomised multicentre study was conducted among patients over 65 yr of age with newly diagnosed acute myeloid leukaemia (AML) to compare oral treatment with etoposide 80 mg/m(2) and thioguanine 100 mg/m(2) twice daily on 5 d and idarubicin 15 mg/m(2) on 3 d (ETI) to a mainly i.v. combination of cytarabine 100 mg/m(2) twice daily on 5 d, idarubicin 12 mg/m(2) x 1, and thioguanine (TAI). Ninety-two patients were enrolled. Their median age was 72 yr, range 65-84 yr. Sixty-five patients had de novo AML, 21 AML subsequent to myelodysplastic syndrome, and six treatment-related AML. They received at first a 6-d i.v. treatment with cytarabine and idarubicin. After the first treatment, 68 patients were randomised to receive two cycles of ETI (n = 36) or TAI (n = 32) and thereafter maintenance with mercaptopurine and methotrexate. Of the 92 patients, 52 (57%) achieved remission at some stage. The median survival was 10 months. There were no significant differences between the patients randomised to ETI or TAI in the remission rate (67% vs. 72%), survival (12 months from randomisation in both arms), event-free survival or relapse rate. The patients randomised to receive ETI spent significantly fewer days at hospital during the two randomised cycles (20 vs. 41 d, P = 0.010), and they had fewer days with infusions, shorter neutropenias and thrombocytopenias and fewer and less severe infections. In conclusion, treatment with oral ETI resulted in a similar antileukaemic effect as obtained with mainly i.v. TAI, with less toxicity and reduced need for hospitalisation.

Administration, Oral↗

PubMed2003

Predictive factors for blastoid transformation in the common variant of mantle cell lymphoma.

Approximately 20% of the mantle cell lymphoma (MCL) patients present with the blastoid variant at diagnosis. Blastoid changes may occur also during the course of the disease, but factors related to blastoid transformation are poorly understood. In the present study, the incidence and predictive factors for blastoid transformation were analysed among 52 patients who primarily had the common variant of MCL and one or more biopsies taken at the time of disease progression. Blastoid transformation occurred in 18 (35%) patients. The minimum estimated risk of transformation was 42% at 5 years of follow-up. At the time of transformation, all except two patients had systemic lymphoma with lymphatic blasts in the blood. The median survival time after blastoid transformation was 3.8 months compared with 26 months in patients without transformation (P<0.001). The respective survival times as calculated from the initial diagnosis of MCL were 31 and 60 months. Leucocytosis, an elevated serum lactate dehyrdogenase (LDH) level, and a high proliferative activity at diagnosis as assessed by the mitotic count and Ki-67 staining were associated with an increased risk of blastoid transformation, and elevated serum LDH and blood leucocytosis with a short time interval to transformation. We conclude that blastoid transformation is not uncommon during the course of MCL, and is associated with a poor outcome. An elevated serum LDH level, a high cell proliferation rate, and leucocytosis are predictive for a high risk of blastoid transformation in MCL.

Adult↗

PubMed2003

Multiple organ failure and outcome of critically ill patients with haematological malignancy.

BACKGROUND: The number of failing organs systems in ICU patients with haematological malignancy is associated with outcome. The objective of this study was to assess short and long-term survival in these patients with special reference to multiple organ failure reflected by the SOFA (Sequential Organ Failure Assessment) score. METHODS: Retrospective chart review of haematological patients admitted to the 10-bed intensive care unit (ICU) of a tertiary level academic teaching hospital from 1994 to 1998. Of 31 admitted patients with the diagnosis of haematological malignancy, the charts of 30 were available for analysis. RESULTS: Univariate logistic regression analysis of factors previously shown to influence survival revealed that only admission SOFA score and untreated status of haematological disease were significantly associated with survival (P < 0.05). ICU, 3-month and one-year survival rates were 57% (17/30), 23% (7/30) and 20% (6/30), respectively. If maximal SOFA score during the ICU stay was included in a multivariate model comprising treatment status and effect, admission day SOFA and APACHE II scores, mechanical ventilation, renal replacement therapy and neutropenia, the maximal SOFA score became the only independent variable. All patients with an admission SOFA score exceeding 11 died in hospital. Leave-one-out method revealed that admission SOFA scores and the status of haematological disease (untreated or not) correctly classified 83% (25 of 30) of patients to survivors or non-survivors. CONCLUSIONS: Multiple organ failure assessed as SOFA score on admission and status of disease were associated with outcome in critically ill patients with haematological malignancy.

APACHE↗

PubMed2001

Intercellular adhesion molecule-1 in extravasation of normal mononuclear and leukaemia cells.

Interaction of intercellular adhesion molecules (ICAMs) with their receptors has a key role in normal leucocyte adhesion and migration, whereas in leukaemia this has not been well established. In this study, we have evaluated the roles of different adhesion molecules in normal and leukaemia cell extravasation in a novel organotypic model for vessel wall and measured plasma ICAM-1 and -2 levels in acute leukaemia patients at diagnosis and during chemotherapy. We found that both normal mononuclear cells and blast cells from acute leukaemia patients, as well as retinoic acid-treated promyelocytic leukaemia cells, rapidly extravasated through endothelial cell layers into the underlying collagen matrix. ICAM-1 antibody prevented the extravasation, while antibodies to other adhesion molecules showed little (CD18, ICAM-2) or no inhibition (CD11a and ICAM-3). Soluble ICAM-1 (sICAM-1) protein had no effect. We also observed increased plasma sICAM-1 and -2 levels in leukaemia patients and found that they correlated only weakly with the white blood cell count. No correlation was found between sICAM-1 or -2 levels and the response to therapy. Although elevated sICAM-2 levels decreased rapidly during chemotherapy, sICAM-1 levels did not. Because sICAM-1 protein had no effect on leukaemia cell extravasation in vitro, it is probable that the increased plasma sICAM-1 levels in leukaemia patients may not play a role in leukaemia cell infiltration. However, as we showed that ICAM-1 mediated leukaemia cell extravasation on the cell surface, it is possible that cellular ICAM-1 has an important role in disease progression.

Antigens, CD↗

PubMed2001

PPP2R1B gene in chronic lymphocytic leukemias and mantle cell lymphomas.

Deletion of chromosome bands 11q22-q23 is one of the most common structural chromosome alterations in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). The PPP2R1B gene is located very close to the minimal common deletion region of 11q22-q23 in CLL and MCL. Recently, the PPP2R1B gene was found to be mutated in human lung and colon cancers. To evaluate the role of the PPP2R1B gene in the pathogenesis of CLL and MCL, we performed RT-PCR analysis and cDNA sequencing on 10 CLL RNA samples and SSCP analysis on 26 CLL and 37 MCL genomic DNA samples. A deletion of exon 3 was found in one CLL sample. No mutation was detected in the SSCP analysis. To exclude the possibility of large genomic deletions we performed Southern blotting analysis. One MCL sample showed abnormal bands. Our results do not suggest that the PPP2R1B gene has a major pathogenic role in CLL and MCL.

Base Sequence↗

PubMed2000

Soluble urokinase receptor levels correlate with number of circulating tumor cells in acute myeloid leukemia and decrease rapidly during chemotherapy.

The importance of plasminogen activation, mediated by urokinase (uPA) and its receptor (uPAR), is well established in many physiologica and pathological processes, such as in cell migration and tumor-cell invasion. Recently, additional functions have been described for uPA and uPAR, particularly in cell adhesion and chemotaxis. The amounts of uPA and uPAR in various tumor types and in the plasma/serum samples of cancer patients have been shown to correlate with survival prognosis, indicating the relevance of these molecules in malignancy. We previously showed that in acute myeloid leukemia, a high level of plasma soluble uPAR (suPAR) at diagnosis correlates with poor response to chemotherapy. However, in this case, as in other cancers, the origin of suPAR is unknown. Therefore, we have now analyzed uPAR in cells, plasma, and urine of patients with acute leukemia (n = 35) at 0, 5, 14, 28, and 56 days after start of chemotherapy. In response to cytotoxic treatment, suPAR levels decreased rapidly, and the decreasing plasma suPAR (p-suPAR levels correlated highly with decreasing numbers of circulating tumor cells, suggesting that the elevated p-suPAR was produced by circulating tumor cells. Moreover, the p-suPAR level appeared to correlate with the amount of uPAR in tumor cell lysates at diagnosis. Our results also show for the first time that in lysates of circulating tumor cells, studied by immunoprecipitation and immunoblotting, uPAR was partly in fragmented form, whereas only full-length uPAR was found in normal leukocytes. We also detected fragmented suPAR in peripheral blood plasma, in urine, and especially in the plasma compartment of bone-marrow aspirates of acute myeloid leukemia patients, in a pattern differing considerably from that found in healthy individuals. Because proteolytic cleavage of uPAR induces a potent chemotactic response in vitro, it is possible that these fragments may play a role in the pathophysiology of acute leukemia.

Acute Disease↗

PubMed2000

Cyclosporine, methotrexate, and methylprednisolone compared with cyclosporine and methotrexate for the prevention of graft-versus-host disease in bone marrow transplantation from HLA-identical sibling donor: a prospective randomized study.

The role of corticosteroids in the prophylaxis of graft-versus-host disease (GVHD) is not well established. We have conducted a prospective, randomized, open-label, single-center study about the effect of adding methylprednisolone (MP) to the widely used prophylactic regimen consisting of cyclosporine A and methotrexate. A total of 108 consecutive patients treated with allogeneic bone marrow transplantation from an HLA-identical sibling donor for malignant blood disease were entered into the study; 53 patients were randomized to receive and 55 were randomized not to receive prophylactic MP. The dose of MP was 0.5 mg/kg on days 14 to 20, 1 mg/kg on days 21 to 34, 0.5 mg/kg on days 35 to 48, and thereafter the dose was slowly tapered and the administration discontinued on day 110. In the group given prophylactic MP, the incidence of acute GVHD was lower (19% vs 56%, P =.0001), there was a trend toward a lower incidence of chronic GVHD among low-risk patients (P =.06), and during the first 4 months the time spent at hospital was shorter and there were fewer infections. The total amount of MP given was similar in the study groups because of a higher incidence of acute GVHD and its treatment in the group of patients not given prophylactic MP. There were no significant differences between the study groups in relapse rate or survival. In conclusion, the addition of MP to the combination of cyclosporine and methotrexate markedly reduced the incidence of acute GVHD without causing untoward effects. The timing of corticosteroid administration is probably important for the efficacy.

Acute Disease↗

PubMed2000

Deletions at 11q23 in different lymphoma subtypes.

BACKGROUND AND OBJECTIVES: Chromosome band 11q23 is frequently deleted in various types of neoplasm. The region represented by yeast artificial chromosome (YAC) clone 755b11 at 11q23 has been shown to be the minimal common region of deletion in mantle cell lymphoma (MCL) and B-cell chronic lymphocytic leukemia (B-CLL). The aim of the study was to determine the frequencies of 11q23 deletion in different lymphoma subtypes. DESIGN AND METHODS: We performed fluorescence in situ hybridization (FISH) analysis with YAC755b11 on either peripheral blood or lymph node biopsy (LN) specimens of patients diagnosed as having MCL (47), CLL/small lymphocytic lymphoma (SLL) (62), diffuse large cell lymphoma (DLCL) (17), follicular lymphoma (FL) (9), and Hodgkin's disease (HD) (11). Fifteen cases of reactive or normal lymph node biopsies were studied as controls. RESULTS: Forty of the 161 (25%) samples exhibited deletions in the region represented by YAC755b11. The 11q23 deletion was found only in MCL (23, 49%), CLL / SLL (13, 21%) and DLCL (4, 24%). Three cases were classified as Richter's syndrome and they all exhibited the deletion at 11q23. The deletion frequencies in the blood specimens of typical CLL (30%) and lymph node specimens of CLL/SLL (13%) were remarkably different. INTERPRETATION AND CONCLUSIONS: Our study demonstrated that the 11q23 deletion is not common in lymphomas other than MCL, CLL and DLCL. It also showed the possible correlation of the 11q23 deletion with the transformation of localized lymphoma to CLL, and with the development of Richter's syndrome.

Adolescent↗

PubMed1999

Restriction landmark genome scanning for aberrant methylation in primary refractory and relapsed acute myeloid leukemia; involvement of the WIT-1 gene.

There is substantial evidence to suggest that aberrant DNA methylation in the regulatory regions of expressed genes may play a role in hematologic malignancy. In the current report, the Restriction Landmark Genomic Scanning (RLGS) method was used to detect aberrant DNA methylation (M) in acute myeloid leukemia (AML). RLGS-M profiles were initially performed using DNA from diagnostic, remission, and relapse samples from a patient with AML. Rp18, one of the eight spots found that was absent in the relapse sample, was cloned. Sequence analysis showed that the spot represented a portion of the WIT-1 gene on human chromosome 11p13. Rp18 was missing in the relapse sample due to a distinct DNA methylation pattern of the WIT-1 gene. Twenty-seven AML patients that entered CR after therapy (i.e., chemosensitive) were studied and only 10 (37%) of the diagnostic bone marrow (BM) samples showed methylation of WIT-1. However, seven of eight (87.5%) diagnostic BM samples from primary refractory AML (chemosensitive) showed methylation of WIT-1. The incidence of WIT-1 methylation in primary refractory AML was significantly higher than that noted in chemosensitive AML (P=0.018). Together, these results indicate that RLGS-M can be used to find novel epigenetic alterations in human cancer that are undetectable by standard methods. In addition, these results underline the potential importance of WIT-1 methylation in chemoresistant AML.

Acute Disease↗

PubMed1999

Circadian rhythm of white blood cells during clozapine treatment.

RATIONALE: The atypical antipsychotic clozapine is effective in the treatment of patients with refractory schizophrenia. It carries a well-known risk of neutropenia and agranulocytosis, which necessitates the immediate discontinuation of clozapine. OBJECTIVE: We report a patient who developed neutropenia on clozapine, but behind the cell count decrease showed to be a diurnal variation of the white blood cells (WBC). METHODS: Due to the lack of efficacy of subsequent treatment of conventional and other atypical neuroleptics, treatment with clozapine was restarted after discontinuation. When the morning count of WBC began to fall, WBC count was repeated in the afternoons. RESULTS: Careful blood cell monitoring showed a pronounced diurnal variation of WBC (2.9-4.2x10(9)/l in the morning and 3.6-7.1x10(9)/l in the afternoon) and granulocytes (0.8-1.4x10(9)/l and 2.9-5.5x10(9)/l, respectively). CONCLUSIONS: Some patients may thus have a spuriously low cell count and may be unnecessarily denied effective treatment.

Adult↗

PubMed1999

Central nervous system involvement in patients with mantle cell lymphoma.

In small cell lymphomas, central nervous system (CNS) involvement has been considered to be very rare. Mantle cell lymphoma (MCL) is a distinct subtype of non-Hodgkin's lymphomas consisting of small or intermediate lymphatic B-cells. It has a poorer prognosis than the other small cell lymphomas. Only a few MCL patients with CNS involvement have been reported in the literature to date. We analyzed retrospectively the incidence, clinical characteristics, and outcome of CNS involvement in 94 patients with confirmed MCL treated at one center from 1980 to 1997. Four of the 94 patients (4%) developed CNS lymphoma during the median follow-up of 51 months. The diagnosis was based on clinical, cytological and radiological findings. CNS involvement appeared at 4.6, 56, 66, or 86 months from the diagnosis of MCL. All patients had neurological symptoms and a leukemic disease; two cases were seen with a blastoid morphology. Malignant lymphatic cells were detected in spinal fluid in all cases and parenchymal infiltrations in brain in two. All patients were treated with intrathecal chemotherapy, without response. Survival time after diagnosis of CNS lymphoma ranged from 18 to 55 days. At diagnosis, no adverse prognostic factors predictive of CNS lymphoma were found. CNS involvement was associated with a progressive leukemic disease as a late event or a blastoid transformation. The prognosis of MCL patients with CNS involvement is poor.

Bone Marrow↗

PubMed1999

Molecular characterization of deletion at 11q22.1-23.3 in mantle cell lymphoma.

Chromosomal deletions at 11q21-23 have recently been reported to be common aberrations in mantle cell lymphoma (MCL). To characterize the structure of the deletion, we studied 41 cases of MCL by fluorescence in situ hybridization using a YAC contig, which spans the region at 11q22.1-23.3. 17 MCLs were studied using a set of 20 yeast artificial chromosomes (YACs) in a contig, and nine of these cases showed deletion of 11q22-23. The deletion spanned several megabases in all but one case, where only YAC 755b11 at 11q23.1, covering approximately a 1.6 Mb of DNA, was deleted. Analysis of additional 24 MCLs with YAC 755b11 revealed the deletion in 49% of all cases (20/41). The deleted region at 11q22.1-23.3 was discontinuous in five lymphomas and in the majority of the cases the distal breakpoint occurred between YACs 785e12 and 911f2 at 11q23.3. We conclude that the deletion of 11q22-23 and particularly the deletion of YAC 755b11 are very common in MCL and may be important in the genesis or progression of the disease.

Adult↗

PubMed1998

Rearrangement of ALL1 (MLL) in acute myeloid leukemia with normal cytogenetics.

Approximately 45% of adults with acute myeloid leukemia (AML) have normal cytogenetics and therefore lack structural abnormalities that can assist in the localization and characterization of molecular defects. The partial tandem duplication of the ALL1 (MLL) gene has been found in several such cases of AML, yet its frequency and clinical significance are unclear. We performed Southern analysis of the ALL1 gene in pretreatment samples from 98 AML patients with normal cytogenetics. Eleven of 98 such patients (11%; 95% confidence interval, 6-19%) showed rearrangement of ALL1 at diagnosis. The partial tandem duplication of ALL1 was responsible for ALL1 rearrangement in all such cases examined, making it a frequent molecular defect in adult AML patients with normal cytogenetics. Furthermore, patients with ALL1 rearrangement had a significantly shorter duration of complete remission when compared to patients without ALL1 rearrangement (P = 0.01; median, 7.1 versus 23.2 months). This defect defines for the first time a subset of AML patients with normal cytogenetics who have short durations of complete remission and thus require new therapeutic approaches.

Acute Disease↗

PubMed1998

Gain of 3q and deletion of 11q22 are frequent aberrations in mantle cell lymphoma.

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.

Aged↗

PubMed1998

Mantle cell lymphoma: clinical features, treatment and prognosis of 94 patients.

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.

Adult↗