| 1. |
- Grövdal, Michael, et al.
(författare)
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Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy
- 2010
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 150:3, s. 293-302
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Tidskriftsartikel (refereegranskat)abstract
- This 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 13.5 months, >24 months in 17% of the patients, and 18-30.5 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 = 0.003). 5-azacytidine treatment, at a dose of 60 mg/m(2) was well tolerated. Grade III-IV thrombocytopenia and neutropenia occurred after 9.5 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.
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| 3. |
- Kozlowski, Piotr, 1969-, et al.
(författare)
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High curability via intensive reinduction chemotherapy and stem cell transplantation in young adults with relapsed acute lymphoblastic leukemia in Sweden 2003-2007
- 2012
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Ingår i: Haematologica. - : Ferrata Storti Foundation. - 0390-6078 .- 1592-8721. ; 97:9, s. 1414-1421
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Tidskriftsartikel (refereegranskat)abstract
- Background less thanbrgreater than less thanbrgreater thanA minority of patients with adult acute lymphoblastic leukemia who relapse are rescued. The aim of this population-based study was to assess the results of reinduction treatment and allogeneic stem cell transplantation in patients in second complete remission. less thanbrgreater than less thanbrgreater thanDesign and Methods less thanbrgreater than less thanbrgreater thanBetween 2003-2007, 76 adults (andlt;66 years) with relapsed acute lymphoblastic leukemia (Burkitts leukemia excluded) were prospectively reported to The Swedish Adult Acute Leukemia Registry and later evaluated. less thanbrgreater than less thanbrgreater thanResults less thanbrgreater than less thanbrgreater thanReinduction with: (i) mitoxantrone, etoposide, and cytarabine (MEA); (ii) fludarabine, cytarabine, pegylated-asparaginase plus granulocyte colony-stimulating factor (FLAG-Asp); and (iii) cytarabine, betamethasone, cyclophosphamide, daunorubicin, and vincristine (ABCDV) resulted in complete remission in 6/9 (67%), 10/16 (63%) and 9/21 (43%) of the patients, respectively. Allogeneic stem cell transplantation was performed during second complete remission in 29 patients. Multivariate analysis regarding overall survival after relapse revealed that age over 35 years at diagnosis and relapse within 18 months were negative prognostic factors. Overall survival rates at 3 and 5 years were 22% (95% CI: 13-32) and 15% (95% CI: 7-24). Of 19 patients less than 35 years at diagnosis who underwent allogeneic stem cell transplantation in second remission, ten (53%) are still alive at a median of 5.5 years (range, 4.2-8.3) after relapse, whereas all patients over 35 years old at diagnosis have died. less thanbrgreater than less thanbrgreater thanConclusions less thanbrgreater than less thanbrgreater thanAllogeneic stem cell transplantation remains the treatment of choice for young adults with relapsed acute lymphoblastic leukemia. Both (i) mitoxantrone, etoposide, and cytarabine and (ii) fludarabine, cytarabine, pegylated-asparaginase plus granulocyte colony-stimulating factor seem effective as reinduction treatments and should be further evaluated. New salvage strategies are needed, especially for patients over 35 years old at diagnosis.
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| 4. |
- Kozlowski, Piotr, 1969-, et al.
(författare)
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High relapse rate of T cell acute lymphoblastic leukemia in adults treated with Hyper-CVAD chemotherapy in Sweden
- 2014
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Ingår i: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 92:5, s. 377-381
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Tidskriftsartikel (refereegranskat)abstract
- Background Hyper-CVAD is widely used to treat acute lymphoblastic leukemia (ALL) and aggressive lymphomas. This multicenter, population-based study assessed the efficacy of Hyper-CVAD as first-line therapy in patients with T-cell ALL (T-ALL). Patients and methods Between October 2002 and September 2006, 24 patients were diagnosed with T-ALL in Sweden; 19 were eligible for treatment with the protocol. Results The median age was 32yr (range 18-72yr). Complete remission (CR) was obtained in 17 of 19 (89%) patients, and the treatment was relatively well tolerated. Allogeneic stem cell transplantation (SCT) was recommended in high-risk disease and was performed in four patients upfront. Two- and 5-yr leukemia-free survivals (LFS) in 17 patients with CR achievement were identical, at 29% (95% confidence interval [CI]: 8-51). Two- and 5-yr overall survival (OS) in whole cohort was 63% (95% CI: 42-85) and 47% (95% CI: 26-69), respectively. The 5-yr LFS for 15 patients who did not receive allogeneic SCT upfront were 20% (95% CI: 0-40), although 14 of 15 completed the protocol (eight cycles). Relapse occurred in 2 of 4 upfront-transplanted patients and in 12 of 15 patients treated with chemotherapy alone, six of whom received allogeneic SCT in CR2. Age >= 35yr influenced OS negatively in univariate analysis (HR 5.1, 95% CI: 1.55-16.7). Conclusions Hyper-CVAD treatment resulted in a high CR rate and appeared safe, but it showed poor efficacy at preventing relapse. Therefore, this treatment is no longer recommended for adults with T-ALL in Sweden.
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| 5. |
- Toft, Nina, et al.
(författare)
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Risk group assignment differs for children and adults 1-45 years with acute lymphoblastic leukemia treated by the NOPHO ALL-2008 protocol
- 2013
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 90:5, s. 404-412
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The prognosis of acute lymphoblastic leukemia is poorer in adults than in children. Studies have indicated that young adults benefit from pediatric treatment, although no upper age limit has been defined.DESIGN AND METHODS:We analyzed 749 patients aged 1-45 years treated by the NOPHO ALL-2008 protocol. Minimal residual disease (MRD) on days 29 and 79, immunophenotype, white blood cell count (WBC), and cytogenetics were used to stratify patients to standard, intermediate, or high risk treatment with or without hematopoietic stem cell transplantation.RESULTS: Adults aged 18-45 had significantly lower WBCs at diagnosis compared to children aged 1-9 and 10-17 years, but significantly more adults were stratified to high-risk chemotherapy (8%, 14%, 17%; p < 0.0001) or high risk chemotherapy with transplantation (4%, 13%, 19%; p < 0.0001). This age dependent skewing of risk grouping reflected more T-ALL (11%, 27%, 33%, p < 0.0001), poorer MRD response day 29 (MRD < 0.1%: 75%, 61%, 52%; p < 0.0001), and more MLL gene rearrangements (3%, 3%, 10%; p = 0.005) in older patients.CONCLUSIONS:Even if identical diagnostics, treatment, and risk stratification are implemented, more adults will be stratified to high risk therapy, which should be considered when comparing pediatric and adult outcomes.
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