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| 2. |
- Höglund, M., et al.
(författare)
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Dose-dependent mobilisation of haematopoietic progenitor cells in healthy volunteers receiving glycosylated rHuG-CSF
- 1996
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Ingår i: Bone Marrow Transplantation. - 0268-3369 .- 1476-5365. ; 18:1, s. 19-27
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Tidskriftsartikel (refereegranskat)abstract
- In an attempt to optimise the dose of G-CSF for mobilisation of PBPC in allogeneic donors, four groups of six healthy male volunteers received lenograstim (glycosylated rHuG-CSF) at a dose of 3, 5, 7.5 or 10 micrograms/kg/day, respectively, for 6 days (days 1-6). All subjects underwent a 10 I leukapheresis. Lenograstim was well tolerated. Maximal mobilisation was observed on days 5 or 6, with a clear dose-response for all progenitor cell types (CD34+, CFU-GM, BFU-E, CFU-mix). The peak numbers of CD34+ cells/microlitre (mean, s.e.m.) were 30 +/- 5, 49 +/- 8, 44 +/- 5 and 122 +/- 30 in the 3, 5, 7.5 and 10 micrograms/kg groups, respectively. A good correlation was observed between the number of CD34+ cells in blood and leukapheresis product (LP), respectively. Increasing the dose of lenograstim did not increase the number of T cells in the LP. A comparison of LP and steady state BM CD34+ cells in paired samples from each individual, showed a higher proportion of primitive immunophenotypes (CDw90+, HLA-DR-, CD45RA-, CD33-) among LP CD34+ cells. We conclude that increased doses of G-CSF improve the mobilisation of PBPC, and that G-CSF favours mobilisation of primitive CD34+ cell subsets. Lenograstim 10 micrograms/kg/day for 6 days should provide a sufficiently effective mobilisation of PBPC in most healthy PBPC donors.
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| 3. |
- Höglund, M., et al.
(författare)
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Mobilization of CD34+ cells by glycosylated and nonglycosylated G-CSF in healthy volunteers : a comparative study
- 1997
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 59:3, s. 177-183
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Tidskriftsartikel (refereegranskat)abstract
- In vitro studies indicate that lenograstim (glycosylated G-CSF) is more potent than filgrastim (nonglycosylated G-CSF) on a weight for weight basis. However, such a difference has not yet been shown in vivo. The primary objective of this trial was to compare the efficacy of equivalent doses (microgram) of lenograstim and filgrastim in mobilizing CD34+ cells. Thirty-two healthy male volunteers, median age 27 yr (19-44 yr), were randomized to receive either lenograstim 10 micrograms/kg followed by filgrastim 10 micrograms/kg or vice versa with a washout period of a minimum 4 wk. Both drugs were administered as s.c. injections once daily for 5 d (d 1-5). CD34+ cells were mobilized with a similar kinetics, peaking at median d 6 (5-6) for both drugs. A significant difference in favour of lenograstim was shown for peak number of CD34+ cells/microliter blood (104 +/- 38 vs. 82 +/- 35, mean +/- 1 SD, p < 0.0001, paired t-test, n = 30) and number of CFU-GM/microliter blood at d 6 (14.6 +/- 8.4 vs. 10.2 +/- 4.6, p < 0.0001), respectively. There was no difference in the d 6 number of CD3+ cells. Both drugs were generally well tolerated and did not differ with respect to number of adverse events. In conclusion, lenograstim 10 micrograms/kg/d mobilizes PBPC more efficiently than the identical dose of filgrastim, indicating a difference in in vivo potency between the two G-CSFs.
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| 5. |
- Bergfelt, Emma, et al.
(författare)
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Satisfactory outcome after intensive chemotherapy with pragmatic use of minimal residual disease (MRD) monitoring in older patients with Philadelphia-negative B cell precursor acute lymphoblastic leukaemia : a Swedish registry-based study
- 2015
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Ingår i: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 32:4
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Tidskriftsartikel (refereegranskat)abstract
- The introduction of minimal residual disease (MRD) monitoring, in the Swedish national guidelines for acute lymphoblastic leukaemia, was evaluated in 35 patients aged 46-79 years (median 61), who were diagnosed from 2007 to 2011 and treated with high-intensity, block-based chemotherapy (ABCDV/VABA induction). Both a high complete remission rate (91 %) and acceptable overall survival (OS) rate (47 %) at 5 years were achieved. MRD by flow cytometry was measured in 73 % of the patients reaching complete remission after the first course, but was omitted by the clinicians for eight patients who were either over 70 years of age or already met conventional high-risk criteria. Factors negatively influencing OS were age over 65 years and WHO status >= 2. MRD < 0.1 % after induction had positive impact on continuous complete remission but not on OS. Only five patients were allocated to allogeneic haematopoietic stem cell transplantation in first remission, mainly due to conventional high risk factors. Thus, use of intensive remission induction therapy is effective in a selection of older patients. In a population for whom the possibilities of treatment escalation are limited, the optimal role of MRD monitoring remains to be determined.
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| 6. |
- Giebel, Sebastian, et al.
(författare)
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The prophylactic use of granulocyte-colony stimulating factor during remission induction is associated with increased leukaemia-free survival of adults with acute lymphoblastic leukaemia : A joint analysis of five randomised trials on behalf of the EWALL
- 2012
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 48:3, s. 360-367
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Granulocyte-colony stimulating factor (G-CSF) is used to prevent febrile neutropenia and support intense chemotherapy. However, its impact on long-term outcome in oncological patients including adults with acute lymphoblastic leukaemia (ALL) has not been determined so far.METHODS: In the current study follow-up data from individual patients recruited in five multicentre, prospective, randomised trials were pooled to perform a joint analysis. Among 347 adults and adolescents with ALL, 185 were assigned to receive prophylactically G-CSF along with induction chemotherapy while 162 patients were treated without G-CSF support.RESULTS:With the median follow-up of 5.3years, there was a tendency towards increased 5year probability of the overall survival for the G-CSF arm compared to the controls (32%±4% versus 23%±4%, p=.07), which reached statistical significance in a subgroup of T-ALL (51%±8% versus 29%±9%, p=.01) and among patients aged 21-40years (44%±6% versus 27%±6%, p=.03). The probability of leukaemia-free survival was 38%±4% and 24%±4% (p=.01) while the median remission duration equalled 33 and 17months (p=.007), respectively. In a multivariate analysis the prophylactic use of G-CSF was independently associated with reduced risk of relapse (hazard ratio (HR)=.64, p=.007) and treatment failure (HR=.67, p=.02).CONCLUSIONS:The prophylactic use of G-CSF during induction of ALL is associated with improved long-term outcome and should be recommended especially in a setting of T-ALL and in 'young adults'. Our analysis provides the first direct evidence coming from prospective trials for the impact of primary G-CSF prophylaxis on disease-free survival of oncological patients.
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| 7. |
- Hallböök, Helene, 1963-
(författare)
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Acute Lymphoblastic Leukaemia in Adult Patients : Studies of Prognostic Factors, Treatment Results and in vitro Cellular Drug Resistance
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Treatment results and clinical characteristics in adult acute lymphoblastic leukaemia (ALL) were evaluated regarding three issues: a new treatment with cytarabine up-front, stem cell transplantation and a comparison between adult and paediatric treatment protocols. All studies were conducted on a national basis. Furthermore, activity of imatinib was investigated by in vitro cytotoxicity assay. The national protocol was evaluated in 153 adult ALL patients. A high complete remission rate, 86%, was achieved with 29% overall survival at 3-years. Favourable outcome was identified in patients < 40 years with precursor B phenotype and continuous complete remission was higher for precursor B compared to T-ALL. Stem cell transplantation was evaluated in 187 patients. No differences in outcome between allogeneic and autologous transplantation were found, with the exception of Philadelphia-positive ALL, in which allogeneic transplantation was preferable. Limited chronic graft-versus-host disease (compared to none) resulted in superior disease free survival. The paediatric NOPHO-92 and the Adult protocols were evaluated for 243 ALL-patients. Superior remission rate and survival were achieved for 10-18 year-olds treated according to the Paediatric protocol compared to both 15-25 and 25-40 year-olds treated according to the Adult protocol. Treatment protocol was a significant prognostic factor for patients aged 15-20 years. Fluorometric Microculture Cytotoxicity Assey was used to analyze 15 tumour cell samples from ALL patients. High concordance was determined between in vitro sensitivity to imatinib and presence of BCR-ABL. Daunorubicin, prednisolone and cytarabine had the greatest benefit from a combination with imatinib. The national adult treatment protocol’s results were consistent with international trials regarding precursor B ALL but may be under performing for T-ALL. Adolescents may benefit from treatment according to the Paediatric protocol. No difference in outcome between allogeneic and autologous stem cell transplantation was determined except for Philadelphia-positive patients, despite the indication of a graft-versus-leukaemia effect.
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| 8. |
- Hallböök, Helene, et al.
(författare)
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Autologous and allogeneic stem cell transplantation in adult ALL : The Swedish Adult ALL Group experience
- 2005
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Ingår i: Bone Marrow Transplantation. - London : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 35:12, s. 1141-1148
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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.
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| 9. |
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| 10. |
- Hallböök, Helene, et al.
(författare)
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Treatment outcome in young adults and children > 10 years of age with acute lymphoblastic leukemia in Sweden : A comparison between a pediatric protocol and an adult protocol
- 2006
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Ingår i: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 107:7, s. 1551-1561
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. Several studies have reported a more favorable outcome for teenagers and young adults with acute lymphoblastic leukemia (ALL) when they were treated in pediatric oncology departments compared with adult hematology departments. However, biased risk grouping and high treatment-related mortality have hampered some of those comparisons. METHODS. In Sweden during the 1990s, adolescents with ALL were treated in a pediatric oncology unit or in an adult hematologic unit, depending on the initial referral. In the current national, comparative, retrospective study, patients with ALL aged 10 years to 40 years who were treated either according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL protocol (1992-2000) (NOPHO-92 protocol) or according to the Swedish Adult ALL Group protocol (1994-2000) (Adult protocol) were included. None of the protocols had age as a high-risk criterion. RESULTS. In total, 243 patients with B-precursor and T-cell ALL were treated according to the protocols. There was a significant difference in the remission rate between the NOPHO-92 protocol (99%; n = 144 patients) and the Adult protocol (90%; n = 99 patients; P <.01), and the event-free survival (EFS) was also superior for the NOPHO-92 protocol compared with the Adult protocol (P <.01). However, EFS was higher for patients aged 15 years to 25 years compared with patients aged 26 years to 40 years within the Adult protocol group (P =.01). The treatment protocol itself was identified as an independent risk factor. CONCLUSIONS. The NOPHO-92 protocol resulted in a better outcome than the Adult protocol; therefore, adolescents may benefit from the pediatric protocol treatment strategy. Prospective trials are warranted to determine whether young adults would benefit from similar treatment.
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