| 1. |
|
|
| 2. |
|
|
| 3. |
- Christiansson, Lisa, et al.
(författare)
-
The Tyrosine Kinase Inhibitors Imatinib and Dasatinib Reduce Myeloid Suppressor Cells and Release Effector Lymphocyte Responses
- 2015
-
Ingår i: Molecular Cancer Therapeutics. - : American Association for Cancer Research. - 1535-7163 .- 1538-8514. ; 14:5, s. 1181-1191
-
Tidskriftsartikel (refereegranskat)abstract
- Immune escape mechanisms promote tumor progression and are hurdles of cancer immunotherapy. Removing immunosuppressive cells before treatment can enhance efficacy. Tyrosine kinase inhibitors (TKI) may be of interest to combine with immunotherapy, as it has been shown that the inhibitor sunitinib reduces myeloid suppressor cells in patients with renal cell carcinoma and dasatinib promotes expansion of natural killer-like lymphocytes in chronic myeloid leukemia (CML). In this study, the capacity of dasatinib and imatinib to reduce myeloid suppressor cells and to induce immunomodulation in vivo was investigated ex vivo. Samples from CML patients treated with imatinib (n = 18) or dasatinib (n = 14) within a Nordic clinical trial (clinicalTrials.gov identifier: NCT00852566) were investigated for the presence of CD11b(+)CD14(-)CD33(+) myeloid cells and inhibitorymolecules (arginase I, myeloperoxidase, IL10) as well as the presence of natural killer cells, T cells (naive/memory), and stimulatory cytokines (IL12, IFN gamma, MIG, IP10). Both imatinib and dasatinib decreased the presence of CD11b(+)CD14(-)CD33(+) myeloid cells as well as the inhibitory molecules and the remaining myeloid suppressor cells had an increased CD40 expression. Monocytes also increased CD40 after therapy. Moreover, increased levels of CD40, IL12, natural killer cells, and experienced T cells were noted after TKI initiation. The presence of experienced T cells was correlated to a higher IFNg and MIG plasma concentration. Taken together, the results demonstrate that both imatinib and dasatinib tilted the immunosuppressive CML tumor milieu towards promoting immune stimulation. Hence, imatinib and dasatinib may be of interest to combine with cancer immunotherapy. (C) 2015 AACR.
|
|
| 4. |
- Ejerblad, Elisabeth, et al.
(författare)
-
Diagnosis according to World Health Organization determines the long-term prognosis in patients with myeloproliferative neoplasms treated with anagrelide : Results of a prospective long-term follow-up
- 2013
-
Ingår i: Hematology. - 1024-5332 .- 1607-8454. ; 18:1, s. 8-13
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES:During long term follow-up of a cohort of patients with essential thrombocythemia (ET) and polycythemia vera (PV) a higher than expected incidence of myelofibrosis (MF) was noted. In order to test if the explanation could be found in the diagnostic criteria a re-evaluation of diagnosis using the 2008 WHO diagnostic criteria for ET and MF was performed.METHODS: This prospective study of 60 patients with ET and PV was set up in 1998 to evaluate the long-term efficacy and tolerability of anagrelide treatment. Bone marrow trephine biopsies were requested from study start, after 2 and 7 years of follow-up. A blinded re-evaluation of the bone marrow trephines was performed. The 2008 WHO bone marrow criteria were used for diagnosis and fibrosis grading.RESULTS: Of 40 patients with an initial diagnosis of ET, 21 were confirmed as 'true ET' whereas 17 were reclassified as primary myelofibrosis (PMF) (12 PMF-0, 3 PMF-1, 2 PMF-2) and 2 as myeloproliferative neoplasms of uncertain origin. After 7 years of follow-up, 19 of 21 patients with 'true ET' were alive, none had transformed to MF, leukemia, or myelodysplastic syndrome. In contrast, 4/17 patients reclassified as PMF had died, two patients transformed to myelodysplastic syndrome and 7 patients progressed to overt MF.DISCUSSION:We conclude that a blinded re-evaluation of bone marrow trephines from study start and after 7 years of follow-up using 2008 World Health Organization criteria was able to differentiate between true ET and PMF with a marked difference in follow-up outcome.
|
|
| 5. |
- Flygt, Hjalmar, et al.
(författare)
-
Long-term tolerability and efficacy after initial PegIFN-α addition to dasatinib in CML-CP : Five-year follow-up of the NordCML007 study
- 2021
-
Ingår i: European Journal of Haematology. - : John Wiley & Sons. - 0902-4441 .- 1600-0609. ; 107:6, s. 617-623
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTreatment-free remission (TFR) has emerged as a treatment goal in chronic myeloid leukemia in the chronic phase (CML-CP). Attempts to increase proportion of patients achieving TFR include combination of tyrosine kinase inhibitors (TKI) and other drugs. Interferon-α in addition to TKI has shown promising efficacy but with dose-dependent toxicity and discontinuations. NordCML007 was initiated to study the efficacy and safety of low dose pegylated IFN-α (PegIFN-α) in combination with dasatinib (DAS) in CML-CP.MethodsForty patients with newly diagnosed CML-CP were given DAS upfront. After month 3 (M3) 15 μg/wk of PegIFN-α was added and increased to 25 μg/wk from M7 until M15. DAS treatment was continued and adverse events and BCR-ABL1 qRT-PCR values were reported yearly after M24. Results from M1 to M18 have previously been published, and here we present long-term data.ResultsAfter 5 years of follow-up, there were no suspected unexpected serious adverse reactions, no increase in serosal effusions, no disease progressions and no CML-related deaths. Rates of MR3.0 (MMR), MR4.0 and MR4.5 were 84.6%, 64.1% and 51.3% respectively at M60, and 95% of patients reached MMR at some point during the study.ConclusionInitial addition of PegIFN-α to DAS shows good long-term efficacy without increased toxicity.
|
|
| 6. |
- Flygt, Hjalmar, et al.
(författare)
-
Successful tyrosine kinase inhibitor discontinuation outside clinical trials - data from the population-based Swedish chronic myeloid leukaemia registry
- 2021
-
Ingår i: British Journal of Haematology. - : John Wiley & Sons. - 0007-1048 .- 1365-2141. ; 193:5, s. 915-921
-
Tidskriftsartikel (refereegranskat)abstract
- Clinical trials show that tyrosine kinase inhibitor (TKI) treatment can be discontinued in selected patients with chronic myeloid leukaemia (CML). Although updated CML guidelines support such procedure in clinical routine, data on TKI stopping outside clinical trials are limited. In this retrospective study utilising the Swedish CML registry, we examined TKI discontinuation in a population-based setting. Out of 584 patients diagnosed with chronic-phase CML (CML-CP) in 2007-2012, 548 had evaluable information on TKI discontinuation. With a median follow-up of nine years from diagnosis, 128 (23%) discontinued TKI therapy (>= 1 month) due to achieving a DMR (deep molecular response) and 107 (20%) due to other causes (adverse events, allogeneic stem cell transplant, pregnancy, etc). Among those stopping in DMR, 49% re-initiated TKI treatment (median time to restart 4 center dot 8 months). In all, 38 patients stopped TKI within a clinical study and 90 outside a study. After 24 months 41 center dot 1% of patients discontinuing outside a study had re-initiated TKI treatment. TKI treatment duration pre-stop was longer and proportion treated with second-generation TKI slightly higher outside studies, conceivably affecting the clinical outcome. In summary we show that TKI discontinuation in CML in clinical practice is common and feasible and may be just as successful as when performed within a clinical trial.
|
|
| 7. |
- Flygt, Hjalmar, et al.
(författare)
-
Treatment-free remission after a second TKI discontinuation attempt in patients with Chronic Myeloid Leukemia re-treated with dasatinib - interim results from the DAstop2 trial.
- 2024
-
Ingår i: Leukemia. - : Springer. - 0887-6924 .- 1476-5551.
-
Tidskriftsartikel (refereegranskat)abstract
- Tyrosine kinase inhibitor (TKI) discontinuation in chronic myeloid leukemia (CML) has become part of routine care for patients with a sustained deep molecular response (DMR). Approximately 50% experience a molecular relapse upon TKI cessation. Most of them quickly regain DMR upon TKI resumption. Whether these patients can achieve a second treatment-free remission (TFR) remains unclear. DAstop2 (ClinicalTrials.gov ID: NCT03573596) is a prospective study including patients with a failed first TFR attempt re-treated with any TKI for ≥ one year. Upon entering the study, patients received the TKI dasatinib for additional two years. Patients with sustained DMR for ≥1 year qualified for a second TKI stop. Ninety-four patients were included between Oct 2017-Dec 2021. At the time of data analysis, 62 patients had attempted a 2nd stop. After a median follow-up of 27 months from 2nd stop, TFR rates were 61, 56 and 46% at 6, 12 and 24 months respectively. No progression to advanced stage disease was seen and 87% had re-achieved MR4 within a median of 3 months from TKI re-initiation. In summary, we show that a 2nd TFR attempt after dasatinib treatment is safe, feasible and TFR rates seem in the range of those reported in trials of a first TKI stop.
|
|
| 8. |
- Geelen, Inge G. P., et al.
(författare)
-
Switching from imatinib to nilotinib plus pegylated interferon-α2b in chronic phase CML failing to achieve deep molecular response : clinical and immunological effects
- 2023
-
Ingår i: Annals of Hematology. - : Springer. - 0939-5555 .- 1432-0584. ; 102:6, s. 1395-1408
-
Tidskriftsartikel (refereegranskat)abstract
- In order to improve molecular response for a discontinuation attempt in chronic myeloid leukemia (CML) patients in chronic phase, who had not achieved at least a molecular response <0.01% BCR-ABL1IS (MR4.0) after at least 2 years of imatinib therapy, we prospectively evaluated whether they could attain MR4.0 after a switch to a combination of nilotinib and 9 months of pegylated interferon-α2b (PegIFN). The primary endpoint of confirmed MR4.0 at month 12 (a BCR-ABL1IS level ≤ 0.01% both at 12 and 15 months) was reached by 44% (7/16 patients, 95% confidence interval (CI): 23- 67%) of patients, with 81% (13/16 patients, 95% CI: 57-93%) of patients achieving an unconfirmed MR4.0. The scheduled combination was completed by 56% of the patients, with premature discontinuations, mainly due to mood disturbances after the introduction of PegIFN, questioning the feasibility of the combination of nilotinib and PegIFN for this patient population and treatment goal. A comprehensive clinical substudy program was implemented to characterize the impact of the treatment changes on the immunological profile.
|
|
| 9. |
|
|
| 10. |
- Gunnarsson, Niklas, et al.
(författare)
-
Second malignancies following treatment of chronic myeloid leukaemia in the tyrosine kinase inhibitor era
- 2015
-
Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 169:5, s. 683-688
-
Tidskriftsartikel (refereegranskat)abstract
- Given that tyrosine kinase inhibitors (TKIs) have dramatically improved the survival of patients with chronic myeloid leukaemia (CML), we were interested in examining the possible risk of long-term adverse events, such as the emergence of other neoplasms. Therefore, we studied the development of second malignancies in 868 patients diagnosed with CML between 2002 and 2011 using the Swedish CML register, cross-linked to the Swedish Cancer register. With a median follow-up of 37 (range 0-99)years, 65 (75%) patients developed 75 second malignancies (non-haematological), 52 of which were of the invasive type. Compared to expected rates in the background population, the risk of second malignancies was higher in the CML cohort, with a standardized incidence ratio (SIR) of 152 (95% CI 113-199). The SIR before and after the second year following diagnosis of CML was 158 and 147, respectively. Among specific cancer types, gastrointestinal and nose and throat cancer were significantly increased. Founded on a population-based material, our results indicate that CML patients treated in the TKI era are at an increased risk of developing a second malignancy, with indications that this risk may more likely be linked to CML itself rather than to the TKI treatment.
|
|
| 11. |
|
|
| 12. |
- Gupta, Manu, et al.
(författare)
-
Expression of BCR-ABL1 oncogene relative to ABL1 gene changes overtime in chronic myeloid leukemia
- 2008
-
Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 366:3, s. 848-851
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Using a quantitative single nucleotide polymorphism (SNP) assay we have investigated the changes in the expression of the BCR-ABL1 oncogene relative to the wild-type ABL1 and BCR alleles in cells from chronic myeloid leukemia (CML) patients not responding to therapy. The results show a progressive increase in the BCR-ABL1 oncogene expression at the expense of decreased expression of the ABL1 allele, not involved in the fusion. No relative changes in the expression of the two BCR alleles were found. These results demonstrate that allele-specific charities in gene expression, with selective, progressive silencing of the wild-type A BL1 allele in favor of the oncogenic BCR-ABL1 allele occur in CML patients with therapy-resistant disease.
|
|
| 13. |
- Huuhtanen, Jani, et al.
(författare)
-
IFN-alfa with dasatinib broadens the immune repertoire in patients with chronic-phase chronic myeloid leukemia
- 2022
-
Ingår i: Journal of Clinical Investigation. - : AMER SOC CLINICAL INVESTIGATION INC. - 0021-9738 .- 1558-8238. ; 132:17
-
Tidskriftsartikel (refereegranskat)abstract
- In chronic myeloid leukemia (CML), combination therapies with tyrosine kinase inhibitors (TKIs) aim to improve the achievement of deep molecular remission that would allow therapy discontinuation. IFN-alpha is one promising candidate, as it has long-lasting effects on both malignant and immune cells. In connection with a multicenter clinical trial combining dasatinib with IFN-alpha in 40 patients with chronic-phase CML (NordCML007, NCT01725204), we performed immune monitoring with single-cell RNA and T cell receptor (TCR) sequencing (n = 4, 12 samples), bulk TCR beta sequencing (n = 13, 26 samples), flow cytometry (n = 40, 106 samples), cytokine analyses (n = 17, 80 samples), and ex vivo functional studies (n = 39, 80 samples). Dasatinib drove the immune repertoire toward terminally differentiated NK and CD8+ T cells with dampened functional capabilities. Patients with dasatinib-associated pleural effusions had increased numbers of CD8(+) recently activated effector memory T (Temra) cells. In vitro, dasatinib prevented CD3-induced cell death by blocking TCR signaling. The addition of IFN-alpha reversed the terminally differentiated phenotypes and increased the number of costimulatory intercellular interactions and the number of unique putative epitope-specific TCR clusters. In vitro IFN-alpha had costimulatory effects on TCR signaling. Our work supports the combination of IFN-alpha with TKI therapy, as IFN-alpha broadens the immune repertoire and restores immunological function.
|
|
| 14. |
- Höglund, Martin, et al.
(författare)
-
Tyrosine kinase inhibitor usage, treatment outcome, and prognostic scores in CML: report from the population-based Swedish CML registry
- 2013
-
Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 122:7, s. 1284-1292
-
Tidskriftsartikel (refereegranskat)abstract
- Clinical management guidelines on malignant disorders are generally based on data from clinical trials with selected patient cohorts. In Sweden, more than 95% of all patients diagnosed with chronic myeloid leukemia (CML) are reported to the national CML registry, providing unique possibilities to compile population-based information. This report is based on registry data from 2002 to 2010, when a total of 779 patients (425 men, 354 women; median age, 60 years) were diagnosed with CML (93% chronic, 5% accelerated, and 2% blastic phase) corresponding to an annual incidence of 0.9/100 000. In 2002, approximately half of the patients received a tyrosine kinase inhibitor as initial therapy, a proportion that increased to 94% for younger (andlt;70 years) and 79% for older (andgt;80 years) patients during 2007-2009. With a median follow-up of 61 months, the relative survival at 5 years was close to 1.0 for patients younger than 60 years and 0.9 for those aged 60 to 80 years, but only 0.6 for those older than 80 years. At 12 months, 3% had progressed to accelerated or blastic phase. Sokal, but not European Treatment and Outcome Study, high-risk scores were significantly linked to inferior overall and relative survival. Patients living in university vs nonuniversity catchment areas more often received tyrosine kinase inhibitors up front but showed comparable survival.
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
- Mustjoki, S, et al.
(författare)
-
Impact of malignant stem cell burden on therapy outcome in newly diagnosed chronic myeloid leukemia patients
- 2013
-
Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 27:7, s. 1520-1526
-
Tidskriftsartikel (refereegranskat)abstract
- Chronic myeloid leukemia (CML) stem cells appear resistant to tyrosine kinase inhibitors (TKIs) in vitro, but their impact and drug sensitivity in vivo has not been systematically assessed. We prospectively analyzed the proportion of Philadelphia chromosome-positive leukemic stem cells (LSCs, Ph+CD34+CD38=) and progenitor cells (LPCs, Ph+CD34+CD38+) from 46 newly diagnosed CML patients both at the diagnosis and during imatinib or dasatinib therapy (ClinicalTrials.gov NCT00852566). At diagnosis, the proportion of LSCs varied markedly (1-100%) between individual patients with a significantly lower median value as compared with LPCs (79% vs 96%, respectively, P = 0.0001). The LSC burden correlated with leukocyte count, spleen size, hemoglobin and blast percentage. A low initial LSC percentage was associated with less therapy-related hematological toxicity and superior cytogenetic and molecular responses. After initiation of TKI therapy, the LPCs and LSCs rapidly decreased in both therapy groups, but at 3 months time point the median LPC level was significantly lower in dasatinib group compared with imatinib patients (0.05% vs 0.68%, P = 0.032). These data detail for the first time the prognostic significance of the LSC burden at diagnosis and show that in contrast to in vitro data, TKI therapy rapidly eradicates the majority of LSCs in patients.
|
|
| 20. |
- Palmblad, Jan, et al.
(författare)
-
TPO, but not soluble-IL-6 receptor, levels increase after anagrelide treatment of thrombocythemia in chronic myeloproliferative disorders
- 2008
-
Ingår i: International Journal of Medical Sciences. - Lake Haven : Ivyspring international publishers. - 1449-1907. ; 5:2, s. 87-91
-
Tidskriftsartikel (refereegranskat)abstract
- Anagrelide is often used in the treatment of thrombocythemia in myeloproliferative disease (MPD), but information concerning effects of treatment on cytokines involved in regulation of blood platelet levels is limited. Here, we investigated serum levels of thrombopoietin (TPO) and soluble IL-6 receptor (sIL-6R) in relation to response to treatment with and plasma concentrations of anagrelide. Samples from 45 patients with thrombocythemia due to MPD (ET=31, PV=14), being treated with anagrelide for 6 months, were analyzed for TPO, sIL-6R and anagrelide levels. The mean baseline platelet count was 983x10(9)/L. A reduction of platelets to <600 in asymptomatic or <400 x 10(9)/L in symptomatic patients was defined as a complete remission (CR), a reduction with >50% of baseline as partial remission, and <50% reduction as failure. At 6 months, 35 patients were in CR, 1 had a partial remission and 9 were treatment failures. For all patients, there was an increase in TPO of 44% from baseline; this change was more pronounced for patients with partial remission and failure. sIL-6R levels did not change significantly. There was no correlation between levels of anagrelide and cytokine levels at 6 months, and changes of cytokine levels did not relate to changes of platelet counts. Thus, a pronounced increase of TPO levels after 6 months of anagrelide treatment indicated that this treatment affected a major regulatory mechanism for megakaryocyte and platelet formation in MPD.
|
|
| 21. |
|
|
| 22. |
- Simonsson, Bengt, et al.
(författare)
-
Combination of pegylated IFN-alpha 2b with imatinib increases molecular response rates in patients with low- or intermediate-risk chronic myeloid leukemia
- 2011
-
Ingår i: Blood. - Washington D.C. : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 118:12, s. 3228-3235
-
Tidskriftsartikel (refereegranskat)abstract
- Biologic and clinical observations suggest that combining imatinib with IFN-alpha may improve treatment outcome in chronic myeloid leukemia (CML). We randomized newly diagnosed chronic-phase CML patients with a low or intermediate Sokal risk score and in imatinib-induced complete hematologic remission either to receive a combination of pegylated IFN-alpha 2b (Peg-IFN-alpha 2b) 50 mu g weekly and imatinib 400 mg daily (n = 56) or to receive imatinib 400 mg daily monotherapy (n = 56). The primary endpoint was the major molecular response (MMR) rate at 12 months after randomization. In both arms, 4 patients (7%) discontinued imatinib treatment (1 because of blastic transformation in imatinib arm). In addition, in the combination arm, 34 patients (61%) discontinued Peg-IFN-alpha 2b, most because of toxicity. The MMR rate at 12 months was significantly higher in the imatinib plus Peg-IFN-alpha 2b arm (82%) compared with the imatinib monotherapy arm (54%; intention-to-treat, P = .002). The MMR rate increased with the duration of Peg-IFN-alpha 2b treatment (andlt; 12-week MMR rate 67%, andgt; 12-week MMR rate 91%). Thus, the addition of even relatively short periods of Peg-IFN-alpha 2b to imatinib markedly increased the MMR rate at 12 months of therapy. Lower doses of Peg-IFN-alpha 2b may enhance tolerability while retaining efficacy and could be considered in future protocols with curative intent.
|
|
| 23. |
- Söderlund, Stina, et al.
(författare)
-
Advanced phase chronic myeloid leukaemia (CML) in the tyrosine kinase inhibitor era : a report from the Swedish CML register
- 2017
-
Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 98:1, s. 57-66
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The primary goal in management of chronic phase (CP) chronic myeloid leukaemia (CML) is to prevent disease progression to accelerated phase (AP) or blast crisis (BC). We have evaluated progression rates in a decentralised healthcare setting and characterised patients progressing to AP/BC on TKI treatment.METHODS: Using data from the Swedish CML register, we identified CP-CML patients diagnosed 2007-2011 who progressed to AP/BC within 2 yrs from diagnosis (n = 18) as well as patients diagnosed in advanced phase during 2007-2012 (n = 36) from a total of 544 newly diagnosed CML cases. We evaluated baseline characteristics, progression rates, outcome and adherence to guidelines for monitoring and treatment.RESULTS: The cumulative progression rate at 2 yrs was 4.3%. All 18 progression cases had been treated with imatinib, and six progressed within 6 months. High-risk EUTOS score was associated to a higher risk of progression. Insufficient cytogenetic and/or molecular monitoring was found in 33%. Median survival after transformation during TKI treatment was 1.4 yrs. In those presenting with BC and AP, median survival was 1.6 yrs and not reached, respectively.CONCLUSION: In this population-based setting, progression rates appear comparable to that reported from clinical trials, with similar dismal patient outcome. Improved adherence to CML guidelines may minimise the risk of disease progression.
|
|
| 24. |
- Wahlin, Anders, et al.
(författare)
-
Improved outcome in adult acute myeloid leukemia is almost entirely restricted to young patients and associated with stem cell transplantation
- 2002
-
Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 68:1, s. 54-63
-
Tidskriftsartikel (refereegranskat)abstract
- Prognostic factors were studied in a series of 318 patients with acute myeloid leukemia (AML), 17-90 yr old, treated at a single centre during 1982-98, and representing 79% of the total number of cases registered in the area during this period. Risk group stratification based on cytogenetics, occurrence of antecedent hematological disorder, and leukocyte count could be performed in 93%. Five percent were allocated to the favourable risk group, 40% to standard risk, and 55% to adverse risk. Complete remission (CR) was attained in 52%. The CR rate was higher in the favourable (80%) and standard risk groups (69%) than in the adverse risk group (37%). The CR rate increased from 44% in the 1980s to 60% in the 1990s. The 5-yr survival rate for all patients was only 12%. Low age, promyelocytic leukaemia, treatment in the 1990s, high induction treatment intensity, and non-adverse risk group were favourably associated with survival. The median survival time increased from 115 to 349 d between the 1980s and the 1990s, but the 5-yr survival rate was only 11% for patients over 55 yr of age even in the last decade. For the younger patients, the 5-yr overall survival rate increased from 9% to 35% in the last decade. The median time in first remission was 365 d. Age below 56 yr, allogeneic and autologous transplants, and non-adverse risk group were associated with prolonged response duration. The duration of response among all patients increased from 250 d in the 1980s to 451 d in the 1990s, but event-free survival time did not improve significantly in patients above 55 yr of age. Among patients below 56 yr of age, overall survival and event-free survival were significantly better for those who received allogeneic or autologous transplants in first remission than for those who were treated with chemotherapy only. Overall survival times did not improve from the 1980s to the 1990s among those patients below 56 yr who were treated with chemotherapy only in first remission, in spite of the use of transplants in second remission.
|
|
| 25. |
- Wahlin, Anders, et al.
(författare)
-
Prognostic significance of risk group stratification in elderly patients with acute myeloid leukaemia.
- 2001
-
Ingår i: British Journal of Haematology. - 0007-1048 .- 1365-2141. ; 115:1, s. 25-33
-
Tidskriftsartikel (refereegranskat)abstract
- Prognostic factors were studied in a series of 211 acute myeloid leukaemia (AML) patients over 60 years of age, treated at a single centre. The patients were allocated into three risk groups based on cytogenetics, occurrence of antecedent haematological disorder and leucocyte count. Only 3% had low-risk features, 39% had intermediate- and 58% had adverse-risk features. Complete remission (CR) was achieved in 43% of all patients. In multivariate analyses, the number of cycles needed to achieve CR and the risk group were significantly associated with the duration of CR. Median survival time for the entire cohort of patients was only 107 d. Advanced age, low induction treatment intensity, treatment during earlier years and adverse-risk group were associated with shorter overall survival times. Risk group classification may help selection of elderly patients with a good chance of benefiting from intensive treatment to actually receive such treatment, while sparing others with a low probability of survival benefit from toxic treatment. Low intensity induction treatment reduces the chance of obtaining complete remission, produces inferior survival times and should consequently be avoided when the aim is to obtain complete remission. In elderly AML patients, introducing age and re-evaluation of intermediate and good prognosis patients regarding response to induction treatment may improve the risk group classification.
|
|
