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Antunovic, Petar
Publications (10 of 16) Show all publications
Schober, S. J., von Luettichau, I., Wawer, A., Steinhauser, M., Salat, C., Schwinger, W., . . . Thiel, U. (2018). Donor lymphocyte infusions in adolescents and young adults for control of advanced pediatric sarcoma. OncoTarget, 9(32), 22741-22748
Open this publication in new window or tab >>Donor lymphocyte infusions in adolescents and young adults for control of advanced pediatric sarcoma
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2018 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 9, no 32, p. 22741-22748Article in journal (Refereed) Published
Abstract [en]

Allogeneic stem cell transplantation (allo-SCT) and donor lymphocyte infusions (DLI) may induce a graft-versus-tumor effect in pediatric sarcoma patients. Here, we describe general feasibility, toxicity and efficacy of DLI after allo-SCT.

Keywords
Ewing sarcoma; allogeneic stem cell transplantation; alloimmunity and transplantation; donor lymphocyte infusion; rhabdomyosarcoma
National Category
Hematology
Identifiers
urn:nbn:se:liu:diva-155846 (URN)10.18632/oncotarget.25228 (DOI)29854312 (PubMedID)
Available from: 2019-03-29 Created: 2019-03-29 Last updated: 2019-10-09
Hulegardh, E., Nilsson, C., Lazarevic, V., Garelius, H., Antunovic, P., Rangert Derolf, A., . . . Lehmann, S. (2015). Characterization and prognostic features of secondary acute myeloid leukemia in a population-based setting: A report from the Swedish Acute Leukemia Registry. American Journal of Hematology, 90(3), 208-214
Open this publication in new window or tab >>Characterization and prognostic features of secondary acute myeloid leukemia in a population-based setting: A report from the Swedish Acute Leukemia Registry
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2015 (English)In: American Journal of Hematology, ISSN 0361-8609, E-ISSN 1096-8652, Vol. 90, no 3, p. 208-214Article in journal (Refereed) Published
Abstract [en]

Patients with secondary acute myeloid leukemia (AML) often escape inclusion in clinical trials and thus, population-based studies are crucial for its accurate characterization. In this first large population-based study on secondary AML, we studied AML with an antecedent hematological disease (AHD-AML) or therapy-related AML (t-AML) in the population-based Swedish Acute Leukemia Registry. The study included 3,363 adult patients of which 2,474 (73.6%) had de novo AML, 630 (18.7%) AHD-AML, and 259 (7.7%) t-AML. Secondary AML differed significantly compared to de novo AML with respect to age, gender, and cytogenetic risk. Complete remission (CR) rates were significantly lower but early death rates similar in secondary AML. In a multivariable analysis, AHD-AML (HR 1.51; 95% CI 1.26-1.79) and t-AML (1.72; 1.38-2.15) were independent risk factors for poor survival. The negative impact of AHD-AML and t-AML on survival was highly age dependent with a considerable impact in younger patients, but without independent prognostic value in the elderly. Although patients with secondary leukemia did poorly with intensive treatment, early death rates and survival were significantly worse with palliative treatment. We conclude that secondary AML in a population-based setting has a striking impact on survival in younger AML patients, whereas it lacks prognostic value among the elderly patients.

Place, publisher, year, edition, pages
Wiley: 12 months, 2015
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:liu:diva-116506 (URN)10.1002/ajh.23908 (DOI)000349889300014 ()25421221 (PubMedID)
Note

Funding Agencies|Stockholm County Council; Swedish Cancer Foundation

Available from: 2015-03-27 Created: 2015-03-27 Last updated: 2017-12-04
Lazarevic, V., Horstedt, A.-S., Johansson, B., Antunovic, P., Billstrom, R., Derolf, A., . . . Juliusson, G. (2015). Failure matters: unsuccessful cytogenetics and unperformed cytogenetics are associated with a poor prognosis in a population-based series of acute myeloid leukaemia. European Journal of Haematology, 94(5), 419-423
Open this publication in new window or tab >>Failure matters: unsuccessful cytogenetics and unperformed cytogenetics are associated with a poor prognosis in a population-based series of acute myeloid leukaemia
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2015 (English)In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 94, no 5, p. 419-423Article in journal (Refereed) Published
Abstract [en]

Unsuccessful cytogenetics (UC) in patients with acute myeloid leukaemia (AML) treated on different SWOG trials was recently reported to be associated with increased age and dismal outcome. To ascertain whether this holds true also in unselected patients with AML, we retrieved all cytogenetic reports in cases from the population-based Swedish AML Registry. Between 1997 and 2006, 1737 patients below 80yr of age without myelosarcoma or acute promyelocytic leukaemia received intensive treatment. The frequencies of UC and unperformed cytogenetics (UPC) were 2.1% and 20%, respectively. The early death rates differed between the cytogenetic subgroups (P=0.006) with the highest rates in patients with UC (14%) and UPC (12%) followed by high-risk (HR) AML, intermediate risk (IR) and standard risk (SR) cases successfully karyotyped (8.6%, 5.9%, and 5.8%, respectively). The complete remission rate was lower in UC and UPC and HR compared with the other risk groups (Pless than0.001). The overall five-year survival rates were 25% for UC and 22% for UPC, whereas the corresponding frequencies for SR, IR and HR AML patients without UC and UPC were 64%, 31% and 15%, respectively. In conclusion, lack of cytogenetic data translates into a poor prognosis.

Place, publisher, year, edition, pages
Wiley: 12 months, 2015
Keywords
unsuccessful metaphase analysis; unperformed cytogenetics; acute myeloid leukaemia; karyotype; survival
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-117785 (URN)10.1111/ejh.12446 (DOI)000352633000007 ()25200361 (PubMedID)
Note

Funding Agencies|Swedish Cancer Society; Swedish Research Council; Regional Cancer Centers; Swedish Association of Local Authorities and Regions (SKL)

Available from: 2015-05-11 Created: 2015-05-08 Last updated: 2017-12-04
Lazarevic, V., Rosso, A., Juliusson, G., Antunovic, P., Rangert-Derolf, A., Lehmann, S., . . . Johansson, B. (2015). Prognostic significance of high hyperdiploid and triploid/tetraploid adult acute myeloid leukemia. American Journal of Hematology, 90(9), 800-805
Open this publication in new window or tab >>Prognostic significance of high hyperdiploid and triploid/tetraploid adult acute myeloid leukemia
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2015 (English)In: American Journal of Hematology, ISSN 0361-8609, E-ISSN 1096-8652, Vol. 90, no 9, p. 800-805Article in journal (Refereed) Published
Abstract [en]

To ascertain the clinical implications of high hyperdiploid (HH; 49-65 chromosomes) and triploid/tetraploid (TT; greater than65 chromosomes) adult acute myeloid leukemia (AML), all such cases were retrieved from the Swedish AML Registry. Of the 3,654 cytogenetically informative cases diagnosed between January 1997 and May 2014, 68 (1.9%) were HH (n=50)/TT (n=18). Patients with HH/TT were older than those with intermediate risk (IR) AML (median 71 years vs. 67 years; P=0.042) and less often had de novo AML (63% vs. 79%; P=0.004); no such differences were observed between HH/TT and complex karyotype (CK) AML. The overall survival (OS) was similar between patients with HH/TT and CK AML (median 0.9 years vs. 0.6 years; P=0.082), whereas OS was significantly longer (median 1.6 years; P=0.028) for IR AML. The OS was shorter for cases with HH than with TT (median 0.6 years vs. 1.4 years; P=0.032) and for HH/TT AMLs with adverse abnormalities (median 0.8 years vs. 1.1 years; P=0.044). In conclusion, HH/TT AML is associated with a poor outcome, but chromosome numbers greater than65 and absence of adverse aberrations seem to translate into a more favorable prognosis. Thus, HH/TT AMLs are clinically heterogeneous and should not automatically be grouped as high risk.Am. J. Hematol. 90:800-805, 2015. (c) 2015 Wiley Periodicals, Inc.

Place, publisher, year, edition, pages
WILEY-BLACKWELL, 2015
National Category
Hematology
Identifiers
urn:nbn:se:liu:diva-121425 (URN)10.1002/ajh.24091 (DOI)000360218000023 ()26088289 (PubMedID)
Note

Funding Agencies|Swedish Cancer Society; Swedish Research Council; Regional Cancer Centers; Swedish Association of Local Authorities and Regions (SKL); Governmental Funding of Clinical Research within the National Health Service

Available from: 2015-09-18 Created: 2015-09-18 Last updated: 2017-12-04
Lazarevic, V., Horstedt, A.-S., Johansson, B., Antunovic, P., Billstrom, R., Derolf, A., . . . Juliusson, G. (2014). Incidence and prognostic significance of karyotypic subgroups in older patients with acute myeloid leukemia: the Swedish population-based experience. Blood Cancer Journal, 4(e188)
Open this publication in new window or tab >>Incidence and prognostic significance of karyotypic subgroups in older patients with acute myeloid leukemia: the Swedish population-based experience
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2014 (English)In: Blood Cancer Journal, ISSN 2044-5385, E-ISSN 2044-5385, Vol. 4, no e188Article in journal (Refereed) Published
Abstract [en]

The Swedish population-based acute myeloid leukemia registry contains data from 3251 patients (excluding acute promyelocytic leukemia) diagnosed between 1997 and 2006. Informative cytogenetic data from 1893 patients were retrospectively added, including 1054 patients aged between 60 and 79 years. Clonal abnormalities were found in 57% of the informative karyotypes. Karyotypic patterns differed by age: t(8; 21), inv(16) and t(11q23) were more common in younger patients, whereas loss of 5q, 7q and 17p, monosomal karyotype (MK) and complex karyotypes were more common in older patients. Loss of 5q, 7q and 17p often occurred together within MK. Patients with greater than= 5 chromosome abnormalities had worse overall survival than those with fewer abnormalities or normal karyotype in all age groups. Loss of 5q, 7q and/or 17p had, in contrast to MK, a further negative impact on survival. Multivariable Cox regression analyses on risk factors in patients less than80 years with cytogenetic abnormalities and intensive treatment revealed that age and performance status had the most significant impact on survival (both Pless than0.001), followed by sex (P = 0.0135) and a karyotype including - 7/del(7q) (P = 0.048).

Place, publisher, year, edition, pages
Nature Publishing Group: Open Access Journals - Option B / Nature Publishing Group, 2014
National Category
Hematology
Identifiers
urn:nbn:se:liu:diva-105903 (URN)10.1038/bcj.2014.10 (DOI)000332631700008 ()
Available from: 2014-04-14 Created: 2014-04-12 Last updated: 2017-12-05
Thiel, U., Koscielniak, E., Blaeschke, F., Grunewald, T. G., Badoglio, M., Diaz, M. A., . . . Burdach, S. (2013). Allogeneic stem cell transplantation for patients with advanced rhabdomyosarcoma: a retrospective assessment. British Journal of Cancer, 109(10), 2523-2532
Open this publication in new window or tab >>Allogeneic stem cell transplantation for patients with advanced rhabdomyosarcoma: a retrospective assessment
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2013 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 109, no 10, p. 2523-2532Article in journal (Refereed) Published
Abstract [en]

Background: Allogeneic haematopoietic stem cell transplantation (allo-SCT) may provide donor cytotoxic T cell-/NK cell-mediated disease control in patients with rhabdomyosarcoma (RMS). However, little is known about the prevalence of graft-vs-RMS effects and only a few case experiences have been reported. less thanbrgreater than less thanbrgreater thanMethods: We evaluated allo-SCT outcomes of 30 European Group for Blood and Marrow Transplantation (EBMT)-registered patients with advanced RMS regarding toxicity, progression-free survival (PFS) and overall survival (OS) after allo-SCT. Twenty patients were conditioned with reduced intensity and ten with high-dose chemotherapy. Twenty-three patients were transplanted with HLA-matched and seven with HLA-mismatched grafts. Three patients additionally received donor lymphocyte infusions (DLIs). Median follow-up was 9 months. less thanbrgreater than less thanbrgreater thanResults: Three-year OS was 20% (s. e.+/- 8%) with a median survival time of 12 months. Cumulative risk of progression was 67% (s. e.+/- 10%) and 11% (s. e.+/- 6%) for death of complications. Thirteen patients developed acute graft-vs-host disease (GvHD) and five developed chronic GvHD. Eighteen patients died of disease and four of complications. Eight patients survived in complete remission (CR) (median: 44 months). No patients with residual disease before allo-SCT were converted to CR. less thanbrgreater than less thanbrgreater thanConclusion: The use of allo-SCT in patients with advanced RMS is currently experimental. In a subset of patients, it may constitute a valuable approach for consolidating CR, but this needs to be validated in prospective trials.

Place, publisher, year, edition, pages
Cancer Research UK, 2013
Keywords
rhabdomyosarcoma, allogeneic haematopoietic stem cell transplantation, graft-vs-tumour effect, reduced intensity conditioning, myeloablative conditioning, donor lymphocyte infusion
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-102497 (URN)10.1038/bjc.2013.630 (DOI)000327128200003 ()
Note

Funding Agencies|Wilhelm Sander-Stiftung|2006.109.1|Else Kroner-Fresenius-Stiftung|P31/08//A123/07|BMBF (TranSarNet FK)|01GM087001GM1104B|Deutsche Forschungsgemeinschaft (DFG)|GR3728/2-1|AmGen and Chugai and the Deutsche Kinderkrebsstiftung|DKS 2010.07|

Available from: 2013-12-12 Created: 2013-12-12 Last updated: 2017-12-06
Lehmann, S., Ravn, A., Carlsson, L., Antunovic, P., Deneberg, S., Mollgard, L., . . . Juliusson, G. (2011). Continuing high early death rate in acute promyelocytic leukemia: a population-based report from the Swedish Adult Acute Leukemia Registry. Leukemia, 25(7), 1128-1134
Open this publication in new window or tab >>Continuing high early death rate in acute promyelocytic leukemia: a population-based report from the Swedish Adult Acute Leukemia Registry
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2011 (English)In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 25, no 7, p. 1128-1134Article in journal (Refereed) Published
Abstract [en]

Our knowledge about acute promyelocytic leukemia (APL) patients is mainly based on data from clinical trials, whereas population-based information is scarce. We studied APL patients diagnosed between 1997 and 2006 in the population-based Swedish Adult Acute Leukemia Registry. Of a total of 3897 acute leukemia cases, 3205 (82%) had non-APL acute myeloid leukemia (AML) and 105 (2.7%) had APL. The incidence of APL was 0.145 per 100 000 inhabitants per year. The median age at the time of diagnosis was 54 years; 62% were female and 38% male. Among younger APL patients, female sex predominated (89% of patients less than 40 years). Of the 105 APL patients, 30 (29%) died within 30 days (that is, early death (ED)) (median 4 days) and 28 (26%) within 14 days from diagnosis. In all, 41% of the EDs were due to hemorrhage; 35% of ED patients never received all-trans-retinoic acid treatment. ED rates increased with age but more clearly with poor performance status. ED was also associated with high white blood cells, lactate dehydro-genase, creatinine, C-reactive protein and low platelet count. Of non-ED patients, 97% achieved complete remission of which 16% subsequently relapsed. In total, 62% are still alive at 6.4 years median follow-up. We conclude that ED rates remain very high in an unselected APL population.

Place, publisher, year, edition, pages
Nature Publishing Group, 2011
Keywords
acute promyelocytic leukemia; incidence; early mortality; hemorrhagic death; population based
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-69804 (URN)10.1038/leu.2011.78 (DOI)000292682600008 ()
Available from: 2011-08-10 Created: 2011-08-08 Last updated: 2017-12-08
Juliusson, G., Karlsson, K., Lj Lazarevic, V., Wahlin, A., Brune, M., Antunovic, P., . . . Hoglund, M. (2011). Hematopoietic Stem Cell Transplantation Rates and Long-Term Survival in Acute Myeloid and Lymphoblastic Leukemia Real-World Population-Based Data From the Swedish Acute Leukemia Registry 1997-2006. Cancer, 117(18), 4238-4246
Open this publication in new window or tab >>Hematopoietic Stem Cell Transplantation Rates and Long-Term Survival in Acute Myeloid and Lymphoblastic Leukemia Real-World Population-Based Data From the Swedish Acute Leukemia Registry 1997-2006
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2011 (English)In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 117, no 18, p. 4238-4246Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Allogeneic stem cell transplantation (alloSCT) reduces relapse rates in acute leukemia, but outcome is hampered by toxicity. Population-based data avoid patient selection and may therefore substitute for lack of randomized trials. METHODS: We evaluated alloSCT rates within the Swedish Acute Leukemia Registry, including 3899 adult patients diagnosed from 1997 through 2006 with a coverage of 98% and a median follow-up of 6.2 years. RESULTS: AlloSCT rates and survival decreased rapidly with age andgt;55 years. The 8-year overall survival (OS) was 65% in patients andlt;30 years and 38% in patients andlt;60 years and was similar for acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Among 1073 patients andlt;60 years, alloSCT was performed in 42% and 49% of patients with AML and ALL, respectively. Two-thirds of the alloSCTs were performed in first complete remission, and half used unrelated donors, the same in AML and ALL. Regional differences in management and outcome were found: 60% of AML patients andlt;40 years received alloSCT in all parts of Sweden, but two-thirds of AML patients 40-59 years had alloSCT in one region compared with one-third in other regions (Pandlt;.001), with improved 8-year OS among all AML patients in this age cohort (51% vs 30%; P = .005). CONCLUSIONS: More Swedish AML patients received alloSCT, and long-term survival was better than in recently published large international studies, despite our lack of selection bias. There was no correlation between alloSCT rate and survival in ALL. In adult AML patients andlt;60 years of age, a high alloSCT rate was associated with better long-term survival, but there was no such correlation in ALL.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2011
Keywords
acute myeloid leukaemia, acute lymphoblastic leukaemia, allogeneic stem cell transplantation, population based, performance status, nonrelapse mortality, survival
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-71382 (URN)10.1002/cncr.26033 (DOI)000295186000020 ()
Note
Funding Agencies|Swedish Association of Local Authorities and Regions (SKL)||Available from: 2011-10-14 Created: 2011-10-14 Last updated: 2017-12-08
Nilsson-Ehle, H., Birgegard, G., Samuelsson, J., Antunovic, P., Astermark, J., Garelius, H., . . . Hellstrom-Lindberg, E. (2011). Quality of life, physical function and MRI T2*in elderly low-risk MDS patients treated to a haemoglobin level of andgt;= 120 g/L with darbepoetin alfa +/- filgrastim or erythrocyte transfusions. European Journal of Haematology, 87(3), 244-252
Open this publication in new window or tab >>Quality of life, physical function and MRI T2*in elderly low-risk MDS patients treated to a haemoglobin level of andgt;= 120 g/L with darbepoetin alfa +/- filgrastim or erythrocyte transfusions
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2011 (English)In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 87, no 3, p. 244-252Article in journal (Refereed) Published
Abstract [en]

Objective: Anaemia in low-risk myelodysplastic syndromes (MDS) is associated with reduced quality of life (QoL). Response to treatment with erythropoietin +/- granulocyte colony-stimulating factor (G-CSF) is associated with improved QoL, but whether transfusion therapy with higher haemoglobin (Hb) target levels has similar effects is unknown. The objective for this prospective phase II Nordic multicentre trial was to assess QoL, response rate and physical function in elderly anaemic MDS patients treated to a target Hb level of andgt; 120 g /L. Methods: Thirty-six elderly patients with low-and intermediate-1 risk MDS received darbepoetin (DA) 300 mu g/wk, with the addition of G-CSF if no response. If the Hb target was reached at 16 wk, treatment was maintained until week 26. Remaining patients were transfused to reach the target level for at least 8 wk. Results: Twenty-seven patients completed the study. Response rate to DA +/- G-CSF was 67% in evaluable patients and 56% according to intention to treat. Eighteen patients reached the target Hb level according to protocol. QoL scores for fatigue, dyspnoea, constipation, and physical, role and social functioning improved significantly during study, with similar results for transfused and untransfused patients. Maintaining Hb andgt; 120 g /L did not confer a higher transfusion rate, once the target was reached. In two of fourteen patients, magnetic resonance imaging T2* indicated cardiac iron overload, however, without association with ferritin levels. Conclusions: In elderly anaemic MDS patients, an increment in haemoglobin is associated with improved QoL, whether induced by growth factor treatment or transfusion therapy.

Place, publisher, year, edition, pages
John Wiley and Sons, 2011
Keywords
elderly, myelodysplasia, anaemia, erythropoietin, transfusion
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-70323 (URN)10.1111/j.1600-0609.2011.01654.x (DOI)000294022000006 ()
Note
Funding Agencies|Nordic Cancer Union||Swedish Cancer Society||Amgen Inc||Swedish Orphan Inc||Available from: 2011-09-02 Created: 2011-09-02 Last updated: 2017-12-08
Grovdal, M., Karimi, M., Khan, R., Aggerholm, A., Antunovic, P., Astermark, J., . . . Hellstrom-Lindberg, E. (2010). Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy. British Journal of Haematology, 150(3), 293-302
Open this publication in new window or tab >>Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy
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2010 (English)In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 150, no 3, p. 293-302Article in journal (Refereed) Published
Abstract [en]

Pgreater thanThis prospective Phase II study is the first to assess the feasibility and efficacy of maintenance 5-azacytidine for older patients with high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia and MDS-acute myeloid leukaemia syndromes in complete remission (CR) after induction chemotherapy. Sixty patients were enrolled and treated by standard induction chemotherapy. Patients that reached CR started maintenance therapy with subcutaneous azacytidine, 5/28 d until relapse. Promoter-methylation status of CDKN2B (P15 ink4b), CDH1 and HIC1 was examined pre-induction, in CR and 6, 12 and 24 months post CR. Twenty-four (40%) patients achieved CR after induction chemotherapy and 23 started maintenance treatment with azacytidine. Median CR duration was 13 center dot 5 months, greater than 24 months in 17% of the patients, and 18-30 center dot 5 months in the four patients with trisomy 8. CR duration was not associated with CDKN2B methylation status or karyotype. Median overall survival was 20 months. Hypermethylation of CDH1 was significantly associated with low CR rate, early relapse, and short overall survival (P = 0 center dot 003). 5-azacytidine treatment, at a dose of 60 mg/m2 was well tolerated. Grade III-IV thrombocytopenia and neutropenia occurred after 9 center dot 5 and 30% of the cycles, respectively, while haemoglobin levels increased during treatment. 5-azacytidine treatment is safe, feasible and may be of benefit in a subset of patients.

Place, publisher, year, edition, pages
Blackwell Publishing Ltd, 2010
Keywords
myelodysplastic syndrome; azacytidine; clinical studies; maintenance therapy; DNA-methylation
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-58201 (URN)10.1111/j.1365-2141.2010.08235.x (DOI)000279836800004 ()
Available from: 2010-08-11 Created: 2010-08-09 Last updated: 2017-12-12
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