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E Juvonen

Publications and source records attributed to E Juvonen.

At least 19 recordsLinked to original sources

Autologous stem cell transplantation in patients with chronic lymphocytic leukaemia: the Finnish experience.

Although autologous stem cell transplantation (ASCT) has gained some popularity as a treatment option in patients with chronic lymphocytic leukaemia (CLL), limited multicentre data are available on the feasibility and efficacy of this approach. Between January 1995 and June 2005, 72 patients with CLL received ASCT in five Finnish centres. There were 45 men and 27 women with a median age of 57 years (38-69). The median time from diagnosis to ASCT was 32 months (6-181) and the median number of prior regimens 1 (1-4). All patients received blood stem cell grafts and CD34+ selection had been performed in 44 patients (61%). The most common high-dose regimen was a total body irradiation plus cyclophosphamide (38 patients, 53%). No early treatment-related deaths were observed. With a median follow-up of 28 months from ASCT, a relapse or progression has been observed in 27 patients (37%). The projected progression-free survival is 48 months (confidence interval (CI) 30-66). The projected median overall survival is 95 months (CI 74-101) from ASCT and is not influenced by graft selection or conditioning regimen used. Autologous stem cell transplantation is a feasible treatment option for CLL. Randomized trials against alternative treatments are needed to assess the impact of ASCT on the clinical course of CLL.

Adult↗

Early treatment-related mortality in adult autologous stem cell transplant recipients: a nation-wide survey of 1482 transplanted patients.

OBJECTIVES: To evaluate early (<100 d) treatment-related mortality (TRM) in autologous stem cell transplant (ASCT) recipients. PATIENTS: Altogether 1482 adult patients received ASCT in six Finnish centres 1990-2003. The most common diagnoses were non-Hodgkin's lymphoma (NHL) (n = 542), multiple myeloma (MM) (n = 528), breast cancer (BC) (n = 132), Hodgkin's lymphoma (n = 86) and chronic lymphocytic leukaemia (CLL) (n = 63). RESULTS: Forty-two patients (2.8%) died from treatment-related reasons <100 d from ASCT. The median time to death was 38 d from ASCT (0-99). The risk of TRM varied according to the diagnoses. The highest risk was observed in patients with AL amyloidosis (24%) followed by NHL (4.4%) and MM (1.9%). No early TRM was observed in patients transplanted for BC or CLL. Infections were the cause of death in 16 patients (fungal 7, bacterial 6, viral 3). Organ toxicity was responsible for early death in 26 patients (heart 9, lungs 7, other 10). CONCLUSIONS: This nation-wide survey indicated a low early TRM in ASCT recipients in general, but higher risks in patients with AL amyloidosis or NHL. In addition to patient selection, also optimization of transplant procedure may be needed in these patient groups to reduce early TRM.

Amyloidosis↗

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↗

Late non-relapse mortality among adult autologous stem cell transplant recipients: a nation-wide analysis of 1,482 patients transplanted in 1990-2003.

Data on the incidence and causes of late (>100 d) non-relapse mortality (NRM) in autologous stem cell transplant (ASCT) recipients is limited. We have analysed NRM in a cohort of 1,482 adult patients who received ASCT in 1990-2003 in six Finnish transplant centres. The most common diagnoses included non-Hodgkin's lymphoma (NHL) (n = 542), multiple myeloma (MM) (n = 528), breast cancer (n = 132); Hodgkin's lymphoma (HL) (n = 86) and chronic lymphocytic leukaemia (CLL) (n = 63). Until September 2005, 646 patients (44%) have died. Late NRM was observed in 68 patients (4.6% of ASCT recipients; 11% of all deaths). There were 38 males and 30 females with a median age of 58 yr (20-69) at the time of ASCT. The median time to NRM was 27 months from ASCT (3-112). The risk of NRM was highest in patients with CLL (9.5%) and those with HL (8.1%) followed by MM and NHL (4.9% and 4.8%, respectively). The risk of late NRM was comparable in patients who received total body irradiation (TBI) and those who received chemotherapy-only regimens (6.7% vs. 4.3%). Another malignancy was the most common cause of late NRM (24 patients, 35% of late NRM). Twelve patients (0.8% of ASCT recipients) have died due to secondary haematological malignancy. Altogether 22 patients (32% of late NRM) died from infectious causes. Malignancies and late infections are important causes of NRM after ASCT. These facts point out the importance of prolonged follow-up in ASCT recipients.

Adult↗

Collection of autologous blood for bone marrow donation: how useful is it?

The hospital charts of 495 adult bone marrow (BM) donors to adult patients were reviewed to determine how necessary it is to collect autologous blood for marrow donation. An autologous transfusion was given to 79% of the donors. The median total volume of marrow harvested was 900 ml (range 450-1350 ml). The median number of nucleated cells harvested was 3.2 x 10(8)/kg patient weight (range 0.9-7.4 x 10(8)/kg patient weight). On the morning following the harvest, the median haemoglobin (Hb) concentrations were 104 g/l (79-135 g/l) in the female and 122 g/l (89-151 g/l) in the male donors autotransfused, and 96 g/l (75-127 g/l) in the female and 119 g/l (88-141 g/l) in the male donors not autotransfused. The post-donation Hb was lower than 85 g/l in four and lower than 90 g/l in 25 donors. Of the 25 donors with post-harvest Hb lower than 90 g/l, 23 were females and 14 had received an autologous transfusion. This study shows that, with a few exceptions, it is not necessary to collect autologous blood from healthy BM donors before the marrow harvest. The post-donation Hb concentrations do not decrease to levels detrimental to healthy persons whether autologous blood is transfused or not.

Adolescent↗

Autologous stem cell transplantation in patients with high-risk plasmacytoma.

Although autologous stem cell transplantation (ASCT) is considered standard treatment in patients with multiple myeloma (MM), limited experience is available on this approach in patients with plasmacytoma (PC). Twelve patients with high-risk PC received ASCT in Finland 1994-2002. There were nine males and three females with a median age of 50 yr (32-64). Ten patients had a PC of bone, whereas two patients had extramedullary PCs. The median time from the diagnosis to ASCT was 9 months (5-100). At the time of ASCT six patients were in first complete remission (CR) or partial remission (PR), in four patients the disease was refractory to the first line therapy and two patients had relapsed. High-dose therapy consisted of melphalan (MEL)200 (n = 7), MEL200 x 2 (n = 3) or total body irradiation (TBI)-MEL140 (n = 2). No transplant-related deaths occurred. After ASCT eight patients (67%) were in CR, one patient in very good PR and one patient in PR; two patients were non-responders. With a median follow-up of 48 months from ASCT, 11 patients (92%) are alive. Six patients (50%) have relapsed or progressed 3-81 months from ASCT. ASCT is feasible in this patient population resulting in promising overall survival. A randomised trial is needed to assess the real value of ASCT when compared with other treatment options in patients with high-risk PC.

Adult↗

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↗

Candidaemia in allogeneic stem cell transplant recipients: low risk without fluconazole prophylaxis.

Invasive fungal infections (IFI) are common in allogeneic SCT recipients. We have reviewed our experience of IFI with special reference to candidaemia in 685 adult patients transplanted in 1983-2002. The donor was a matched sibling in 505 patients and an unrelated donor in 180 patients. A BM graft was used in 561 patients and a PB graft in 124 patients. Fluconazole prophylaxis was not used during the study period. Definite or probable IFI was observed in 60 patients (8.7%) with a dominance of Aspergillus infections (46 patients, incidence 6.7%). Candidaemia was found only in nine patients (1.3%). The causative agents were Candida albicans (n=8), C. krusei (n=2), and C. glabrata (n=1); in two patients, two causative agents were found. The median time to the diagnosis of candidaemia was 53 days (range 6-249 days) post transplant. Seven patients were neutropaenic at diagnosis, and four patients had experienced acute GVHD. All patients received antifungal therapy, but only one patient was cured. According to this study, candidaemia was a rare event in allogeneic SCT recipients. Thus, systematic prophylaxis against Candida infections might not be indicated. The prognosis of established infections is still poor due to comorbid conditions, notably GVHD.

Adolescent↗

Autologous stem cell transplantation in patients with primary amyloidosis: a nation-wide survey.

Due to poor prognosis with conventional therapy, high-dose therapy (HDT) with autologous stem cell transplantation (ASCT) is considered for treatment in patients with primary amyloidosis (AL). Only single centre series are available on the feasibility and efficacy of this approach. Altogether 20 AL patients (11 males, 9 females, median age 54 years) were included in HDT protocols in 5 Finnish transplant centres between 1997 and 2003. Twelve patients were mobilized with granulocyte colony-stimulating factor (G-CSF) alone and 8 patients with a combination of cyclophosphamide and G-CSF. Sixteen patients (80%) went on to high-dose melphalan. Early transplant-related mortality was 25%. Nine out of 11 evaluable patients showed improvement or stabilization of AL. The overall survival of the transplanted patients is 69% (median follow-up 13 months). After a median follow-up of 26 months for the living patients, only 2 patients (18%) have shown progression of AL. This retrospective nation-wide analysis shows that HDT with ASCT leads to improvement or stabilization of AL in the majority of the patients who survive the immediate posttransplant period. A randomized multicentre trial is needed to show whether ASCT is superior to conventional therapy in patients with AL.

Adult↗

Invasive fungal infections in autologous stem cell transplant recipients: a nation-wide study of 1188 transplanted patients.

UNLABELLED: Based on small single-centre series, the risk of invasive fungal infections (IFI) has been considered small in autologous stem cell transplant (ASCT) recipients. PURPOSE: To analyse epidemiological and clinical features of (IFI) among ASCT recipients in Finland 1990-2001. PATIENTS: During the study period, 1188 adult patients received high-dose therapy supported by ASCT in six centres. Altogether, 1112 patients (94%) received blood progenitor cells. The graft was CD34+ selected in 261 patients (22%). The major diagnostic groups were non-Hodgkin's lymphoma (n = 417), multiple myeloma (n = 395), breast cancer (n = 132) and Hodgkin's lymphoma (n = 53). RESULTS: Eighteen patients (1.5%) with IFI were identified. The incidence of proven or probable invasive aspergillosis was 0.8%, followed by candidaemia with an incidence of 0.3%. The median time to the diagnosis of IFI was 35 d (6-162) from the progenitor cell infusion. In fourteen patients (78%) IFI was diagnosed during lifetime and they were treated with antifungal therapy for a median of 50 d. Nine patients (64%) were cured. CONCLUSIONS: IFI appears to be a rare event after ASCT and Aspergillus infections seem to be predominant. These epidemiological features have an impact in planning prophylactic and empirical antifungal strategies in ASCT recipients.

Antineoplastic Combined Chemotherapy Protocols↗

High incidence of PTLD after non-T-cell-depleted allogeneic haematopoietic stem cell transplantation as a consequence of intensive immunosuppressive treatment.

The occurrence of post-transplant lymphoproliferative disorder (PTLD) in relation to immunosuppressive treatment was determined in 257 patients treated with non-T-cell-depleted allogeneic stem cell transplantation from an HLA-matched sibling (173 patients) or unrelated donor (84 patients). The conditioning consisted of total body irradiation and cyclophosphamide (myeloablative conditioning, 250 patients), or fludarabine combined with cyclophosphamide or a single 2 Gy dose of TBI (nonmyeloablative conditioning, seven patients). In transplantations from an unrelated donor, the patients also received antithymocyte globulin (ATG). The prophylaxis against graft-versus-host disease (GVHD) consisted of cyclosporine A, methotrexate, and methylprednisolone. The autopsy reports of deceased patients were systematically reviewed, and the autopsy materials of cases suggestive of PTLD were re-examined histologically for Epstein-Barr virus (EBV). Nineteen patients with EBV-positive PTLD were identified, of whom six had been transplanted from a sibling donor and 13 from an unrelated donor. All the patients who developed PTLD had been given ATG either for the treatment of steroid-resistant acute GVHD (all PTLD patients with a sibling donor and one with an unrelated donor), or as part of the conditioning (all patients with an unrelated donor). In conclusion, in transplantations from an HLA-identical donor with a non-T-cell-depleted graft, the risk of PTLD correlated strongly with the intensity of the immunosuppressive treatment.

Adult↗

Standard-dose anti-CD20 antibody rituximab has efficacy in chronic lymphocytic leukaemia: results from a Nordic multicentre study.

OBJECTIVES: This prospective multicentre study was conducted to assess the efficacy of the monoclonal anti-CD20 antibody rituximab in patients with chronic lymphocytic leukaemia (CLL). Secondary objectives were defined as the tolerability and feasibility of rituximab in patients with CLL. METHODS: Twenty-four heavily pretreated patients with CLL were treated with a standard dose of 375 mg m-2 of rituximab given once weekly for four doses. RESULTS: The overall response rate was 35% and all the responses were partial as defined by the revised NCI criteria. In 17 (85%) of 20 patients with initially measurable peripheral lymph nodes the size of lymph nodes decreased by at least 50%, while an improvement of the bone marrow infiltration was observed only in two (11%) of 18 evaluable patients. The median duration of the overall response was 12.5 wk. Rituximab was relatively well tolerated. Although side-effects were common (75%) they were usually mild or moderate. There was only one grade 3 adverse event and no grade 4 events. CONCLUSIONS: Standard-dose rituximab has activity in heavily pretreated patients with CLL, although the response is mainly limited to the lymph nodes and of short duration. Since rituximab has in vitro synergism with chemotherapeutic agents and is well tolerated by CLL patients, it is reasonable to investigate rituximab in combination with other treatments.

Adolescent↗

Allogeneic blood stem cell transplantation following non-myeloablative conditioning for hypereosinophilic syndrome.

A male patient with hypereosinophilic syndrome (HES) underwent an allogeneic blood stem cell transplantation from a female donor following non-myeloablative conditioning consisting of a 2 Gy dose of TBI and fludarabine 30 mg/m(2) intravenously on three days. Before transplantation 100% of the mitotic bone marrow cells of the patient showed a clonal karyotype abnormality. Three months after the transplantation eosinophilia had resolved and a chromosome analysis revealed normal female karyotype. The present study shows that stem cell transplantation after non-myeloablative conditioning may have curative potential for HES.

Adult↗

The predictive value of vascular risk factors and gender for the development of thrombotic complications in essential thrombocythemia.

The impact of the cardiovascular risk factors smoking, hypertension, hypercholesterolemia, and diabetes mellitus on the risk of thrombotic complications was evaluated retrospectively in 132 patients with essential thrombocythemia (ET). The median age at diagnosis was 51 years, and the median follow-up time was 65 months. Sixty-three out of 132 patients (48%) had one or more vascular risk factors, whereas 69 patients (52%) had no risk factors. Thirty-two patients were smokers, 27 had hypertension, 21 hypercholesterolemia, and four diabetes mellitus. During the follow-up, 53 patients (40%) had 98 arterial thrombotic events, half of which were disturbances of cerebral circulation. Fifteen patients (11%) experienced 27 venous thrombotic events. The presence of one or more vascular risk factors increased the risk of arterial thrombotic complications. Of the patients, 52% with one or more vascular risk factors and 29% of those without any risk factors had arterial thrombosis (P = 0.01). In multivariate analysis the only independent risk factor was smoking (P = 0.01). Male gender increased the risk of arterial thrombosis significantly. Thirty-six out of 62 men (58%) but only 17 out of 70 women (24%) had an arterial complication (P < 0.001). Smoking had a strong predictive value for the development of arterial complications in women but not in men. Among women 9/15 (60%) of the smokers and 12/82 (15%) of the non-smokers experienced arterial thrombosis (P = 0.002), whereas among men no difference between smokers and non-smokers could be found. According to the present findings, the male gender should be regarded as a risk factor when deciding about the indication for treatment. Smoking should be discouraged especially among women with ET.

Adult↗

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↗

Anemia in children with cartilage-hair hypoplasia is related to body growth and to the insulin-like growth factor system.

Cartilage-hair hypoplasia (CHH) is a metaphyseal chondrodysplasia characterized by severe short-limbed short stature, hypoplastic hair, and defective immunity. The patients also have anemia. As GH may regulate both body growth and erythropoiesis, we used CHH as a clinical model to study their interrelationships. Retrospective analysis of hematological data of 114 patients showed that the severity of the anemia and macrocytosis in CHH varies with age. The anemia was most severe in early childhood. A prospective study of 21 patients with CHH showed that height correlates with hemoglobin (P = 0.006) and mean corpuscular volume of red blood cells (P < 0.0001). The individual hemoglobin levels correlated with the GH parameters [P = 0.035 for insulin-like growth factor I (IGF-I) and P = 0.002 for IGF-binding protein-3], and the mean corpuscular volume of red blood cell values correlated with fetal hemoglobin. Bone marrow cultures obtained from six patients with CHH showed reduced or totally absent erythroid colony formation, which was not influenced by GH or IGF-I in vitro or by GH treatment in vivo. In patients with CHH, we observed an association between erythropoiesis and growth. We conclude that body growth and erythropoiesis share common regulators. One of these is the GH-IGF-I axis; other factors, as not yet identified, may also be important.

Adolescent↗