| 1. |
- Olsson-Strömberg, Ulla, et al.
(författare)
-
Successful mobilization of Ph-negative blood stem cells with intensive chemotherapy + G-CSF in patients with chronic myelogenous leukemia in first chronic phase
- 2006
-
Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 47:9, s. 1768-73
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to investigate the feasibility of mobilizing Philadelphia chromosome negative (Ph-) blood stem cells (BSC) with intensive chemotherapy and lenograstim (G-CSF) in patients with CML in first chronic phase (CP1). During 1994-1999 12 centers included 37 patients <56 years. All patients received 6 months' IFN, stopping at median 36 (1-290) days prior to the mobilization chemotherapy. All received one cycle of daunorubicin 50 mg/m2 and 1 hour infusion on days 1-3, and cytarabine (ara-C) 200 mg/m2 24 hours' i.v. infusion on days 1-7 (DA) followed by G-CSF 526 microg s.c. once daily from day 8 after the start of chemotherapy. Leukaphereses were initiated when the number of CD 34+ cells was >5/microl blood. Patients mobilizing poorly could receive a 4-day cycle of chemotherapy with mitoxantrone 12 mg/m2/day and 1 hour i.v infusion, etoposide 100 mg/m2/day and 1 hour i.v. infusion and ara-C 1 g/m2/twice a day with 2 hours' i.v infusion (MEA) or a second DA, followed by G-CSF 526 microg s.c once daily from day 8 after the start of chemotherapy. Twenty-seven patients received one cycle of chemotherapy and G-CSF, whereas 10 were mobilized twice. Twenty-three patients (62%) were successfully (MNC >3.5 x 10(8)/kg, CFU-GM >1.0 x 10(4)/kg, CD34+ cells >2.0 x 10(6)/kg and no Ph+ cells in the apheresis product) [n = 16] or partially successfully (as defined above but 1-34% Ph+ cells in the apheresis product) [n = 7] mobilized. There was no mortality during the mobilization procedure. Twenty-one/23 patients subsequently underwent auto-SCT. The time with PMN <0.5 x 10(9)/l was 10 (range 7-49) and with platelets <20 x 10(9)/l was also 10 (2-173) days. There was no transplant related mortality. The estimated 5-year overall survival after auto-SCT was 68% (95% CI 47 - 90%), with a median follow-up time of 5.2 years.We conclude that in a significant proportion of patients with CML in CP 1, intensive chemotherapy combined with G-CSF mobilizes Ph- BSC sufficient for use in auto-SCT.
|
|
| 2. |
|
|
| 3. |
- Axelsson, Roger, et al.
(författare)
-
Vuxenutbildningens betydelse för inkomster, mobilitet och övergång till högskolestudier
- 2005
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- I början av 1990-talet befann sig Sverige i en kraftig konjunkturnedgång. Arbetslösheten hade stigit till rekordhöga nivåer. Bland de åtgärder regeringen vidtog för att motverka arbetslösheten ingick Kunskapslyftet som var en femårig sats-ning på vuxenutbildning. Kunskapslyftet startade den 1 juli 1997 och pågick till och med år 2002.Det fanns två övergripande målsättningar med Kunskapslyftet. Den första var ekonomisk och handlade om att minska arbetslösheten, öka sysselsättningen och få till stånd en snabbare ekonomisk tillväxt. Den andra målsättningen var utbildningspolitisk och handlade om att vidareutveckla och förnya vuxenutbildningen.Under den femårsperiod som Kunskapslyftet pågick uppgick statens kostnader tillcirka tre miljarder kronor per år exklusive studiestöd. Totalkostnader för hela projektetinklusive studiestöd hamnade på, i storleksordningen 40–45 miljarder kronor.På ITPS uppdrag har Institutionen för nationalekonomi vid Umeå universitetutvärderat hur Kunskapslyftet och annan kommunal vuxenutbildning påverkatdeltagarnas inkomster, rörlighet och övergång till högskolestudier.De fyra uppsatserna som sammanfattas i denna rapport bygger på deltagare i Komvuxhöstterminen 1997, i vissa fall deltagare med så kallat särskilt utbildningsbidrag(studerande i Kunskapslyftet). I de uppsatser där ett förfarande med jämförelsegrupperanvänds är dessa öppet arbetslösa i början av hösten 1997 och deltagare iarbetsmarknadsutbildning i mitten av denna höst.Den databas som har använts i projektets fyra delstudier har byggts upp vidinstitutionen för nationalekonomi vid Umeå universitet. Den omfattar samtliga stu-derande i Komvux höstterminerna 1997 t o m 1999 med tillhörande jämförelsegrupper.Jämförelsegruppen arbetslösa omfattar samtliga personer som 1 september 1997var anmälda vid arbetsförmedlingen som öppet arbetslösa. Den andra jämförelse-gruppen – deltagare i arbetsmarknadsutbildning – består av dem som den 15 okto-ber samma år var registrerade som deltagare i denna utbildning.De viktigaste resultaten i projektets fyra delstudier av kommunal vuxenutbildningär i korthet följande:1. När det gäller utbildningens effekter på bruttoarbetsinkomster efter avslutad utbildning finner vi att deltagare i Kunskapslyftet som var arbetslösa och studerade med det särskilda utbildningsbidraget hade en relativt sett gynnsammare inkomstutveckling än jämförelsegruppen öppet arbetslösa. Vi fin-ner dock en ännu bättre inkomstutveckling för deltagare i arbetsmarknadsutbildning.2. Övergång till högre utbildning var högre bland deltagare i Kunskapslyftet jämfört med övriga deltagare i kommunal vuxenutbildning när hänsyn tas till regionala arbetsmarknadsförhållanden och andra bakgrundsfaktorer.Kvinnliga studerande inom kommunal vuxenutbildning hade en relativt sett högre sannolikhet för att övergå till högskole- eller universitetsutbildning jämfört med män. Övergångssannolikheten påverkas också av regionala attribut. Den är bland annat negativt korrelerad med regional sysselsättningstillväxt och positivt korrelerad med regional arbetslöshet. Detsenare behöver dock inte nödvändigtvis tyda på negativa samhällsekonomiska effekter i form av inlåsning av arbetskraft.3. Det finns betydande regionala skillnader när det gäller deltagarnas inkomster efter utbildning. De länsvisa skillnaderna är inte obetydliga och kan överstiga 20 procent av genomsnittsinkomsten. Detta bör kanske beaktasvid den regionala fördelningen av resurser till vuxenutbildningen.4. När det gäller geografisk rörlighet finner vi lägre sannolikhet för flyttning bland deltagare i kommunal vuxenutbildning och deltagare i arbetsmarknadsutbildning jämfört med personer i öppen arbetslöshet. Detta gäller även de deltagare i Komvux som deltog i Kunskapslyftet. Jämfört med deltagare i arbetsmarknadsutbildning hade dock studerande inom Komvux högre sannolikhet för flyttning. Dock gäller detta inte deltagare i kunskapslyftet, vilka hade lägre sannolikhet för flyttning i jämförelse med deltagare i arbetsmarknadsutbildning.
|
|
| 4. |
|
|
| 5. |
- Grövdal, Michael, et al.
(författare)
-
Negative effect of DNA hypermethylation on the outcome of intensive chemotherapy in older patients with high-risk myelodysplastic syndromes and acute myeloid leukemia following myelodysplastic syndrome
- 2007
-
Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 13:23, s. 7107-7112
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Promoter hypermethylation of, for example, tumor-suppressor genes, is considered to be an important step in cancerogenesis and a negative risk factor for survival in patients with myelodysplastic syndromes (MDS); however, its role for response to therapy has not been determined. This study was designed to assess the effect of methylation status on the outcome of conventional induction chemotherapy. EXPERIMENTAL DESIGN: Sixty patients with high-risk MDS or acute myeloid leukemia following MDS were treated with standard doses of daunorubicin and 1-beta-d-arabinofuranosylcytosine. Standard prognostic variables and methylation status of the P15(ink4b) (P15), E-cadherin (CDH), and hypermethylated in cancer 1 (HIC) genes were analyzed before treatment. RESULTS: Forty percent of the patients achieved complete remission (CR). CR rate was lower in patients with high WBC counts (P = 0.03) and high CD34 expression on bone marrow cells (P = 0.02). Whereas P15 status alone was not significantly associated with CR rate (P = 0.25), no patient with hypermethylation of all three genes achieved CR (P = 0.03). Moreover, patients with CDH methylation showed a significantly lower CR rate (P = 0.008), and CDH methylation retained its prognostic value also in the multivariate analysis. Hypermethylation was associated with increased CD34 expression, but not with other known predictive factors for response, such as cytogenetic profile. CONCLUSIONS: We show for the first time a significant effect of methylation status on the outcome of conventional chemotherapy in high-risk MDS and acute myelogenous leukemia following MDS. Provided confirmed in an independent study, our results should be used as a basis for therapeutic decision-making in this patient group.
|
|
| 6. |
- Hallböök, Helene, et al.
(författare)
-
Autologous and allogeneic stem cell transplantation in adult ALL : The Swedish Adult ALL Group experience
- 2005
-
Ingår i: Bone Marrow Transplantation. - London : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 35:12, s. 1141-1148
-
Tidskriftsartikel (refereegranskat)abstract
- Adult patients with acute lymphoblastic leukaemia (ALL) have been treated according to national protocols in Sweden since 1986. Stem cell transplantation (SCT) has been recommended in first remission for patients with risk factors for relapse, and for standard risk patients only after relapse. In this retrospective study, the results of autologous and allogeneic SCT in these populations were evaluated. In total, 187 patients with a median age of 34 years (17-66 years) underwent SCT. The 5-year disease-free survival (DFS), for all patients, was 26% (Confidence intervals (CI) 20-32%). The 5-year DFS was higher for patients transplanted in first remission 32% (CI 24-40%) compared to 14% (CI 5-23%; P<0.0001) in patients transplanted beyond first remission. No significant differences in DFS (P=0.06) were determined between autologous, related donor and unrelated donor SCT in the whole cohort. A lower relapse rate was counterbalanced by higher treatment-related mortality in patients undergoing allogeneic SCT. In Philadelphia-positive ALL, allogeneic SCT was superior to autologous SCT, with a 5-year DFS of 30% (CI 12-47%) vs 0% (P=0.04). Limited chronic graft-versus-host-disease (GVHD) was associated with an improved DFS of 53% (CI 38-69%) compared to no chronic GVHD of 22% (CI 10-36%; P=0.0008), indicating a clinically important graft-versus-leukaemia effect.
|
|
| 7. |
|
|
| 8. |
- Lenhoff, Stig, et al.
(författare)
-
Intensive therapy for multiple myeloma in patients younger than 60 years. Long-term results focusing on the effect of the degree of response on survival and relapse pattern after transplantation
- 2006
-
Ingår i: Haematologica. - 0390-6078 .- 1592-8721. ; 91:9, s. 1228-1233
-
Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives. From 1994 to 1997 we conducted a population-based, prospective study on intensive therapy in newly diagnosed symptomatic myeloma patients younger than 60 years, comparing their survival to that of a conventionally treated historic population. Long-term results are presented, including the impact of the degree of response on survival and relapse pattern after transplantation. Design and Methods. The prospective population was formed of 397 patients and the historic population of 313 patients. Both populations were calculated to comprise more than 75% of the expected number of new cases. Results. After a median follow-up of 7 years survival was longer in the prospective population than in the historic one (median 60 versus 39 months; p=0.0002). When comparing only patients eligible for intensive therapy the median survival was 63 versus 44 months (p < 0.0001). Attaining a complete response was associated with prolonged event-free survival but not overall survival. The pattern of relapse after transplantation was heterogeneous but could be divided into four major groups; insidious, classical, plasmacytoma form and transformed disease. The median survival after relapse was 29 months. The relapse pattern and time to relapse predicted outcome. Patients relapsing with an insidious or classical form of disease with skeletal events only, or after a long lasting first response were likely to respond well to conventional salvage therapy. In contrast, relapse with multiple symptoms, transformed disease or a short duration of first response implied bad prognosis. Interpretation and conclusions. The relapse pattern after autologous transplantation is heterogeneous and response to salvage therapy is variable. The degree of response and event-free survival after transplantation are not reliable surrogate markers for survival.
|
|
| 9. |
- Löfgren, Christina, et al.
(författare)
-
Higher plasma but not intracellular concentrations after infusion with liposomal daunorubicin compared with conventional daunorubicin in adult acute myeloid leukemia
- 2007
-
Ingår i: Therapeutic Drug Monitoring. - New York : Raven P.. - 0163-4356 .- 1536-3694. ; 29:5, s. 626-631
-
Tidskriftsartikel (refereegranskat)abstract
- To investigate the plasma and intracellular pharmacokinetics of liposomal daunorubicin (DaunoXome) in comparison with conventional daunorubicin, 14 patients aged 28 to 60 years with newly diagnosed acute myeloid leukemia were treated for 1 day with DaunoXome (50 mg/m) and for 2 days with daunorubicin (50 mg/m) with concomitant Ara-C (7 days, 200 mg/m, continuous IV). Eleven of the 14 patients entered complete remission; 9 are still alive. Pharmacokinetic profiles were obtained by blood sampling at appropriate intervals on days 1 to 4. Daunorubicin and daunorubicinol concentrations in plasma and in peripheral leukemic blast cells were measured by high-performance liquid chromatography. Following liposomal daunorubicin administration, the peak values and plasma area under the curve (AUC) were more than 100 times higher than after administration of conventional daunorubicin (AUC, 176 vs. 0.98 micromol/L x hour), but the intracellular AUCs were comparable (759 vs. 715 micromol/L x hour). Intracellular concentrations after DaunoXome peaked later and half as high as after daunorubicin. After DaunoXome versus daunorubicin, plasma clearance was 0.001 versus 0.4 micromol/h, respectively. The volume of distribution was 5.5 L for DaunoXome, versus 3640 L for daunorubicin, indicating low tissue affinity for the liposomal formulation. The authors conclude that liposomal daunorubicin, DaunoXome, yields 2-log higher plasma concentrations but similar intracellular concentrations of daunorubicin and its metabolite daunorubicinol than does free daunorubicin.
|
|
| 10. |
|
|
