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  • 1
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 607-607
    Abstract: We treated 520 patients ≤60 years with de novo (n=414) or secondary (n=106) AML. Patients with CBF-leukemias [t(8;21) or inv(16)] or normal karyotype and good response (GR) to induction I (≤5% blasts in d15 BM) were considered standard risk (SR), all others as high risk (HR). Patients with t(15;17) were excluded. Induction I consisted of standard dose araC, idarubicine and etoposide (IVA-I). Patients with GR to IVA-I continued with IVA–II on d21. In patients with bad response ( & gt;5% BM blasts on d15), the second cycle consisted of either IVA–II or FlAG/Ida. Induction was followed by early consolidation with intermediate dose araC. As late consolidation, SR patients with normal karyotype and an HLA-matched sibling received matched related donor (MRD) transplantation. The remaining SR patients were randomized between high dose (HD) araC (12 x 3g/m2)/daunorubicine (3 x 45mg/m2) or an autologous peripheral blood stem cell transplantation (autoPBCSCT) with PBSC mobilized after early consolidation. 90% of the 262 SR patients achieved CR in contrast to only 59% of the 249 HR patients (overall CR rate 74%). After 75 months, overall survival (OS) and relapse free survival (RFS) was significantly better for SR than for HR patients. Within the SR group, OS for patients with CBF leukemia (n=62) at 56 months was significantly better than for patients with normal karyotype (n=200). RFS was similar for both groups. 57 SR patients (14 with CBF leukemia) were randomized to receive HD araC and 62 (16 with CBF leukemia) to undergo autoPBSCT. At 70 months, OS and RFS was not different for the patients treated with autoPBSCT and for those receiving HD araC. This was true for patients with normal karyotype as well as CBF leukemias. Median duration of neutropenia ( & lt;500/μl) was 9 days for autoPBSCT and 19 days for HD araC (p & lt;0.01) with a significantly higher rate of septicemia (21% vs. 11%) and pneumonia (14% vs. 3%) after HD araC. Duration of thrombocytopenia was 21 days for HD araC and 11 days for autoPBSCT (p & lt;0.01). In SR patients with normal karyotype, OS and RFS after MRD transplantation did not significantly differ from HD araC or autoPBSCT. However, when looking at the FLT3 status in patients with normal karyotype (n=49), chemoconsolidation resulted in an inferior survival (17%) in patients with mutated FLT3 as compared to autotransplantation (67%). In conclusion, outcome is similar in SR AML patients after autoPBSCT, HD araC or MRD transplantation. In SR patients without an HLA-identical sibling donor, autoPBSCT instead of HD araC as used in our study is recommended for late consolidation due to the reduced treatment related toxicity and should be studied prospectively in patients with mutated FLT3.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
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  • 2
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 433-433
    Abstract: In this prospective multicenter trial, we treated 520 patients with AML ≤60 years (414 with de novo and 106 with secondary AML). Patients with CBF-leukemias [t(8;21) or inv(16)] or normal karyotype and good response (GR) to induction I (≤5% blasts in day 15 BM) were considered standard risk (SR), all other patients as high risk (HR). Patients with t(15;17) were excluded. Induction course I consisted of standard dose araC, idarubicine and etoposide (IVA-I). Patients with GR to IVA-I continued with IVA-II on day 21. In patients with bad response (BR; & gt;5% BM blasts on day 15), the second cycle consisted of either IVA-II or FlAG/Ida. Double induction was followed by early consolidation with intermediate dose araC. As late consolidation, HR patients with an HLA-matched sibling were scheduled for a matched related donor (MRD) transplantation; patients without a family donor should undergo autologous peripheral blood stem cell transplantation (autoPBSCT). PBSC were mobilized after early consolidation. An interim analysis showed superior results for allogeneic transplants compared to patients who had undergone autoPBSCT. Therefore, since 2003 all HR patients without a sibling donor were scheduled for matched unrelated donor (MUD) transplantation. 147 of 249 HR patients (59%) achieved complete remission. 33 (13%) of the HR patients died during induction. After 75 months, overall survival (OS) was significantly worse for HR patients (24%) than for SR patients (53%). For HR patients, there was no difference in OS and relapse-free survival (RFS) between patients classified as HR because of BR to IVA-1 (n = 83), unfavourable karyotype (n = 87) or both characteristics (n = 79). RFS was neither different between HR patients with de novo or secondary AML nor between HR patients with normal karyotype, complex karyotype or other high risk cytogenetics. Regarding late consolidation, the “as treated” analysis revealed that OS and RFS was significantly better after an MRD transplantation (n=41, OS 67%, RFS 62%) than after autoPBSCT (n=27, OS 14%, RFS 7%). Patients who received a MUD transplantation (n=32) showed a significantly better RFS (52%) than after autoPBSCT. RFS and OS after MUD transplantation did not differ significantly from MRD transplants. OS of patients after autoPBSCT was not significantly different from patients who received no transplant at all after entering CR. Of the 69 HR patients who did not enter CR after induction, 44 received an MRD or MUD transplantation. 15 of these patients (35%) are alive in CR. In conclusion, HR patients as defined in our study do not benefit from an autologous PBSCT and an allogeneic MRD or MUD transplantation should be performed. Moreover, allogeneic transplants are a viable salvage option for HR patients not entering CR.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 618-618
    Abstract: In our prospective multicenter AML 01/99 trial for risk-adapted therapy of patients aged up to 60 years with acute myeloblastic leukemia, patients with CBF-leukemias [t(8;21) or inv(16)] or normal karyotype and good response (GR) to induction I (up to 5% blasts in day 15 BM) were considered standard risk (SR), all other patients as high risk (HR). Patients with acute promyelocytic leukemia were excluded. Between January 1999 and May 2004, 421 patients (328 with with de novo and 93 with secondary AML) were treated. Induction course I consisted of standard dose araC, idarubicine and etoposide (IVA-I). Patients with GR to IVA-I continued with IVA-II on day 21 as double induction. In patients with bad response ( 〉 5% bone marrow blasts on day 15), the second cycle consisted of either IVA-II or FlAG/Ida. Double induction was followed by an early consolidation with intermediate dose araC. As late consolidation, HR patients were allo- [HLA-matched sibling or matched unrelated donor (MUD)] or autotransplanted. Matched sibling allotransplantation was done in all participating centers whereas MUD transplantation was favoured by only two centers. The remaining centers performed autologous PBSCT if there was no sibling donor available. 199 patients were classified as HR, of whom 118 (59%) achieved CR, and 25 (13%) of the HR patients died during induction. After 55 months, overall survival was significantly worse for HR patients (25%) than for SR patients (49%). This was also true for the relapse-free survival (32% vs. 42%; p = 0.049). In the HR group, there was no difference in overall and relapse-free survival between those patients classified as HR because of bad response to IVA-1 (n = 65), unfavourable karyotype (n = 71) or both characteristics (n = 63). Regarding the different regimens for late consolidation, the “as treated” analysis of the HR patients revealed that overall (59% vs. 20%) and relapse-free survival (59% vs. 20%) was significantly better after an allogeneic HLA-matched sibling transplantation (n = 26) than after autoPBSCT (n=24). Overall and relapse-free survival for the 23 patients who underwent MUD transplantation were 59% and 45% respectively. In conclusion, in HR patients with an HLA-identical sibling donor an allotransplantation should be performed. The results obtained with MUD transplantation in this particular patient group are encouraging. Therefore, in HR patients without an HLA-identical sibling allografting from unrelated donors should be considered in first CR. On the other hand, HR patients as defined by our risk stratification do not seem to benefit from autografting even after intensive induction and consolidation therapy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
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    detail.hit.zdb_id: 80069-7
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  • 4
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 344-344
    Abstract: In the prospective multicenter AML 295 and 01/99 trials, we treated 825 adult patients with acute myeloid leukemia (AML) up to 60 years. 719 patients had de novo disease and 106 had a secondary AML. Median age was 46 years. Patients with t(15;17) were excluded. Induction course I consisted of standard dose araC, idarubicine and etoposide (IVA-I). Patients with good response to IVA-I ( & lt;5% bone marrow blasts on day 15) continued with IVA-II on day 21 as double induction. Patients with bad response received an intensified second induction course with intermediate dose AraC (1g/m2, 8 doses) combined with mAMSA or fludarabine/idarubicine/G-CSF (FlAG-Ida). Double induction was followed by an early consolidation with intermediate dose AraC. Late consolidation was stratified according to risk factors (karyotype and response to IVA-I) and consisted of high dose AraC (3g/m2, 12 doses) + daunorubicine, autoPBSCT or an allogeneic stem cell transplantation. Overall complete remission (CR) rate was 75%. 278 patients relapsed after a median duration of first CR of 9 months. Of these 278 patients, 135 (48%) received an allogeneic stem cell transplantation (alloSCT) from related (n=65) or unrelated (n=70) donors. Median time from relapse to alloSCT was 3 months. 55% of the transplanted patients had achieved a second CR as best response to salvage therapy before alloSCT. Patients who received an alloSCT after relapse were younger (median 40 vs. 50 years) and had a longer duration of first CR (10 vs. 7.5 months) than those who did not. Patients with CBF-leukemias or normal karyotype were significantly more likely to receive an alloSCT after relapse than patients with other karyotypic aberrations. Median overall survival after alloSCT was 12 months and 5-year overall survival was 30%. Results did not differ between transplants from matched related or unrelated donors. In univariate and multivariate analysis, age above the median (HR 2.1, 95% CI 1.3 –3.2) and best response to salvage therapy (CR vs. no CR; HR 0.5, 95% CI 0.3 –0.9) were the only independent prognostic factors for overall survival after alloSCT. Patients aged below 46 years who achieved a CR as best response to salvage therapy had a 5-year overall survival after alloSCT of 53% (median not reached). All other patients had a 16% 5-year overall survival (median 7 months). There was no independent prognostic effect of WBC, platelets, peripheral blasts or extramedullary disease at initial diagnosis. Also, de novo vs. secondary AML, response to induction I, karyotype (CBF vs. normal vs. others), duration of CR1 (≥6 vs. & lt;6 months) and type of consolidation did not affect outcome after alloSCT in relapse. In conclusion, alloSCT from related or unrelated donors offers cure to selected patients with relapsed AML. Age and disease status after salvage therapy are critical prognostic factors for transplantation success. Strategies to increase the number of patients eligible for an alloSCT after relapse and age adapted transplantation protocols are required.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
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    detail.hit.zdb_id: 80069-7
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  • 5
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 145-145
    Abstract: 421 patients (pts.) up to 60 years with de novo (n=328) or secondary (n=93) AML were treated with risk-adapted therapy. Pts. with CBF-leukemias [t(8;21) or inv(16)] or normal karyotype and good response (GR) to induction I (up to 5% blasts in day 15 BM) were consider ed standard risk (SR), all others as high risk (HR). Induction I consisted of standard dose araC, idarubicine and VP16 (IVA-I). Pts. with GR to IVA-I continued with IVA-II on day 21. In pts. with bad response, the second cycle consisted of either IVA-II or FlAG/Ida. Double induction was followed by early consolidation with intermediate dose araC. As late consolidation, SR patients were randomized between high dose (HD) araC (12 x 3g/m2)/daunorubicine (3 x 45mg/m2) or an autologous PBSCT with PBSC mobilized after early consolidation except SR pts. with normal karyotype and an HLA-matched sibling who were allotransplanted. 214 pts. were classified as SR and 199 as HR. 91% of the SR and 59% of the HR pts. achieved CR (overall CR rate 75%) and 1% of the SR pts. died during induction. After 55 months, overall survival was significantly better for SR (49%) than for HR pts. (25%). Within the SR group, relapse free survival at 46 months was 63% for 21 pts. with inv(16), 58% for 25 pts. with t(8;21), and 37% for 148 pts. with normal karyotype (p = 0.13). Overall survival at 48 months was significantly better (p=0.014) for pts. with inv(16) (93%) than for those with t(8;21) (60%) or normal karyotype (44%). 48 SR pts. (12 with CBF leukemia) were randomized to receive HDaraC and 53 (14 with CBF leukemia) to undergo autoPBSCT. At 55 months, the overall survival was 52% for the autotransplanted pts. and 65% for those receiving HDaraC (p=0.71, intent-to-treat analysis). Median duration of neutropenia ( 〈 500/ μl) was 8 days for autoPBSCT and 19 days for HDaraC. Eleven pts. died in the HDaraC group (4 in CR and 7 from relapse) and 12 autotransplanted pts. died (1 in CR and 11 from relaspe). In pts. with normal karyotype, overall survival at 55 months for the allotransplanted SR pts. (n = 29) was 58% with no significant difference to HDaraC (62%) or autoPBSCT (43%). Relapse free survival for SR pts. with normal karyotype was 56% after allotransplantation, and 36% after autoPBSCT and HDaraC respectively (p = n.s.). In conclusion, overall survival is similar in SR AML pts. after autoPBSCT, HDaraC or allotransplantation. In SR pts. without an HLA-identical sibling donor, the reduced treatment related toxicity recommends autoPBSCT as late consolidation. In standard risk pts. with normal karyotype, allotransplantation from an HLA-identical sibling seems to have the highest antileukemic activity.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
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    detail.hit.zdb_id: 80069-7
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  • 6
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 172-172
    Abstract: In the prospective multicenter AML 01/99 trial, 484 patients with acute myeloid leukemia up to 60 years (385 with de novo and 99 with secondary AML) were treated with risk-adapted therapy. Patients with CBF-leukemias [t(8;21) or inv(16)] or normal karyotype and good response (GR) to induction I (≤5% blasts in day 15 BM) were considered standard risk (SR), all other patients as high risk (HR). Patients with t(15;17) were excluded. Induction course I consisted of standard dose araC, idarubicine and etoposide (IVA-I). Patients with GR to IVA-I continued with IVA-II on day 21 as double induction. In patients with bad response ( & gt;5% bone marrow blasts on day 15), the second cycle consisted of FlAG/Ida. Double induction was followed by an early consolidation with intermediate dose araC. As late consolidation, HR patients with an HLA-matched sibling were scheduled for a matched related donor (MRD) transplantation whereas patients without a family donor should undergo autologous peripheral blood stem cell transplantation (autoPBSCT). PBSC were mobilized after early consolidation. A pilot study within the 01/99 trial showed superior results for matched unrelated donor (MUD) transplantation compared to patients who had undergone autoPBSCT. Therefore, since 2003 all HR patients without a sibling donor were scheduled for MUD transplantation. 234 patients were classified as HR, of whom 137 (58%) achieved complete remission. 31 (13%) of the HR patients died during induction. After 70 months, overall survival (OS) was significantly worse for HR patients (28%) than for SR patients (51%). For HR patients, there was no difference in OS and relapse-free survival (RFS) between those patients classified as HR because of bad response to IVA-1 (n = 76), unfavourable karyotype (n = 83) or both characteristics (n = 75). Moreover, RFS was neither different between HR patients with de novo or secondary AML nor between HR patients with normal karyotype, complex karyotype or other high risk cytogenetics. Regarding the different regimens for late consolidation, the “as treated” analysis of the HR patients revealed that OS and RFS was significantly better after an MRD transplantation (n=34, OS 68%, RFS 65%) than after autoPBSCT (n=26, OS 23%, RFS 7%). OS and RFS for the 29 patients who received MUD transplantation was also significantly better than after autoPBSCT with 56% and 52% respectively. In conclusion, HR patients as defined in our study do not benefit from an autologous PBSCT even after intensive double induction and early consolidation. Therefore, an allogeneic transplantation from a related or unrelated donor should be performed.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 7
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 151-151
    Abstract: 484 patients aged ≤60 years with de novo (n=385) or secondary (n=99) acute myeloid leukemia (AML) were treated with risk-adapted therapy. Patients with t(8;21), inv(16) or normal karyotype and good response (GR) to induction I (≤5% blasts in day 15 BM) were considered standard risk (SR), all others as high risk (HR). Induction I consisted of standard dose araC, idarubicine and etoposide (IVA-I). Patients with GR to IVA-I continued with IVA-II on day 21 as double induction. Patients with bad response ( & gt;5% blasts in day 15 BM) received FlAG/Ida as second cycle. Double induction was followed by early consolidation with intermediate dose araC. As late consolidation, SR patients with normal karyotype and an HLA-matched sibling received matched related donor (MRD) transplantation. The remaining SR patients were randomized between high dose araC (HD-araC; 12 x 3g/m2)/daunorubicine or an autologous peripheral blood stem cell transplantation (autoPBCSCT) with PBSC mobilized after early consolidation. 90% of SR patients (n=250) achieved complete remission (CR) in contrast to 58% of HR patients (n=234) (overall CR rate 75%). 4% of the SR patients died during induction. At 70 months, overall survival (OS) was significantly better for SR (51%) than for HR patients (28%). Within the SR group, relapse free survival at 50 months was not different between patients with normal karyotype (n=165), inv(16) (n=30) or t(8;21) (n=30). 55 SR patients were randomized to receive HD-araC and 59 to autoPBSCT. Distribution of the main characteristics were well balanced (age, performance status, cytogenetics, FLT3 mutation status, de novo or secondary AML). At 63 months, OS was 62% for patients treated with autoPBSCT and 59% for those receiving HD-araC (p=0.91, intent-to-treat). Median duration of neutropenia ( & lt;500/μl) was 8 days for autoPBSCT and 20 days for HD-araC (p & lt;0.05). This corresponded to a significantly higher rate of septicemia (20% vs. 10%) and pneumonia (13% vs. 3%) after HD-araC. The duration of thrombocytopenia was 22 days after HD-araC and 11 days after autoPBSCT (p & lt;0.01). 14 patients died in the HD-araC group (4 in CR and 10 from relapse) and 14 patients died after autoPBSCT (1 in CR and 13 from relapse). In patients with normal karyotype, OS at 67 months for the SR patients receiving MRD transplantation (n = 37) was 61% with no significant difference to HD-araC or autoPBSCT. In conclusion, OS is similar in SR AML patients after autoPBSCT, HD-araC or MRD transplantation. In SR patients without an HLA-identical sibling donor, autoPBSCT instead of HD-araC is recommended for late consolidation due to the reduced treatment related toxicity.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 8
    In: Biology of Blood and Marrow Transplantation, Elsevier BV, Vol. 25, No. 10 ( 2019-10), p. 1975-1983
    Type of Medium: Online Resource
    ISSN: 1083-8791
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2019
    detail.hit.zdb_id: 3056525-X
    detail.hit.zdb_id: 2057605-5
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  • 9
    In: APMIS, Wiley, Vol. 116, No. 1 ( 2008-01), p. 66-73
    Type of Medium: Online Resource
    ISSN: 0903-4641 , 1600-0463
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2008
    detail.hit.zdb_id: 2098213-6
    SSG: 12
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  • 10
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 1129-1129
    Abstract: Trisomy 8 (+8) is one of the most common chromosomal abnormality encountered in acute myeloid leukemia (AML), occurring in about 10 to 15% of cases. Currently, data assessing specifically the role of allogeneic hematopoietic stem cell transplantation (allogeneic-HSCT) in the setting of AML with +8 are still relatively sparse. The aim of this multicenter retrospective analysis was to perform a survey on overall outcomes after allogeneic-HSCT of AML patients harboring +8 as a sole chromosomal abnormality or associated with other abnormalities. We have identified 182 de novo AML patients who underwent allogeneic-HSCT between 1990 and 2007 exhibiting isolated +8 (n=136) or +8 associated to other favorable (n=8), intermediate (n=30), high-risk (n=7) or unknown (n=1) group cytogenetics reported to the EBMT. Median age was 37 years. At transplant 108 (59%) patients were in first complete remission (CR). The donor was HLA identical sibling in 115 (63%) and peripheral blood HSCT was used in 54% (n=98). Conditioning regimen was myeloablative in 82%. With a median follow-up of 48 months, 5-year non-relapse mortality (NRM), relapse rate (RR), LFS and OS were 25%, 30%, 45% and 47%, respectively. Five-years OS and LFS was not significantly different between AML patients with isolated or associated +8 (44% vs. 56% P=0.14 and 41% vs. 55%, P=0.11). In a multivariate analysis, LFS rate was improved when patients were female and transplanted in CR with an HLA identical sibling donor. LFS rate were 62% and 64% when using an HLA identical sibling donor in patients in CR1 and CR2/CR3, respectively. Isolated or associated +8 were not a risk factor for any outcomes (OS, LFS, RR, NRM). We conclude that allo-HSCT, from an HLA identical sibling donor, appears to be the treatment of choice for AML patients in CR at transplant with isolated or associated +8.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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