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  • 1
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 4547-4547
    Abstract: Abstract 4547 Introduction: The 2005 NIH consensus criteria (NCC) for acute and chronic graft-versus-host disease (aGVHD, cGVHD) are the gold standard for classifying GVHD in trials but they are not routinely used in the clinic, in part due to uncertainty about their prognostic value. To address this limitation we analyzed NIH-defined GVHD in 147 consecutive acute lymphoblastic leukemia (ALL) patients who received a first myeloablative transplant at our center between 1995 and 2009. Methods: Median age was 31 years (range: 17–56). Disease status was CR1 (50%), CR 〉 1 (22%) or no CR (28%). Myeloablative conditioning consisted of 12 Gy TBI ± etoposide ± cyclophosphamide. Donors were HLA-matched related (42%), -matched unrelated (46%) or -mismatched (12%) and peripheral blood stem cells (74%) or bone marrow (26%) were given. GVHD-prophylaxis consisted of CSA/MTX (72%), CSA/prednisolone (19%) or other CSA-based regimens (9%). ATG was given in HLA-mismatched transplants (12%) and since 2005 also in matched unrelated transplants (11%), according to GMALL study protocols. Preemptive donor lymphocyte infusions (DLI) were a treatment option in case of mixed chimerism or minimal residual disease. Results: Median follow-up was 60 months (8–185). Projected overall survival (OS) at 1, 2 and 5 years was 64%, 56% and 49%. 5-year cumulative incidence of relapse was 33% and of non-relapse mortality (NRM) 25% (7% infections, 9% aGVHD, 7% cGVHD, 2% other). Median time until onset of classic aGVHD was 20 days (5–95). Cumulative incidence of classic aGVHD was 41% for grade I/II and 29% for grade III/IV. Among patients with classic aGVHD, skin, liver or gut involvement was seen in 94%, 32% and 34%. Late aGVHD was observed in 12% at a median of 100 days (range 100–240). Among late aGVHD cases 82% were subclassified as persistent or recurrent classic aGVHD. Median time until onset of chronic GVHD was 115 days (14–294) measured from transplant or DLI with a cumulative incidence for mild, moderate and severe forms of 13%, 15% and 25%. Mouth, skin, eyes, liver, joints and fascia, gut, lung and other organs were involved in 91%, 70%, 61%, 48%, 27%, 19%, 10% and 6% of cGVHD cases. cGVHD was subclassified as classic cGVHD and overlap syndrome in 40% and 60% of cases. 62% had progressive or quiescent type of onset. In multivariate Cox regression analysis with GVHD as time-dependant covariate (table 1) classic aGVHD grade III/IV was associated with inferior OS due to higher NRM. Comparable effects were seen for late aGVHD. In contrast, moderate and severe cGVHD were associated with superior OS due to lower relapse incidence. Classic and overlap cGVHD had no differential prognostic impact. 34 patients without GVHD after cessation of immunosuppression received preemptive DLI. In this subgroup cumulative incidence of classic aGVHD, late aGVHD or cGVHD was 62%, 6% and 62%. Organ involvement was comparable to non-DLI associated GVHD. In a time-dependant multivariate analysis, patients who developed NIH-defined cGVHD after DLI had improved OS (HR 0.21, 95%CI: 0.054–0.81, P=0.023) due to lower relapse incidence (HR 0.26, 95%CI: 0.043–0.91, P=0.048) compared to patients without cGVHD after DLI. Conclusions: This is the first study on the natural history and prognostic impact of NIH-defined GVHD in ALL patients. We found that severe classic aGVHD leads to higher NRM and inferior OS with similar effects seen for late aGVHD. cGVHD had a positive impact on OS and relapse rate, both after transplant and after preemptive DLI, indicating a potent graft-versus-leukemia effect. Although our cohort contains some heterogeneity we believe that this data supports the use of the NCC as diagnostic and prognostic tool in ALL patients. Multivariate Cox regression analysis for OS, relapse and NRM with GVHD as time-dependant covariate. Only results for GVHD are shown. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
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  • 2
    In: Biology of Blood and Marrow Transplantation, Elsevier BV, Vol. 20, No. 10 ( 2014-10), p. 1522-1529
    Type of Medium: Online Resource
    ISSN: 1083-8791
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2014
    detail.hit.zdb_id: 3056525-X
    detail.hit.zdb_id: 2057605-5
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  • 3
    In: European Journal of Haematology, Wiley, Vol. 95, No. 6 ( 2015-12), p. 498-506
    Abstract: For patients with refractory acute myeloid leukemia ( AML ), allogeneic stem cell transplantation (allo SCT ) represents the only curative approach. We here analyzed the long‐term outcome of 131 consecutive patients with active AML , which was either primary refractory or unresponsive to salvage chemotherapy, transplanted at our center between 1997 and 2013. After a median follow‐up of 48 months for the surviving patients, disease‐free survival ( DFS ) at 5 yr post allo SCT was 26% (94% CI : 17–35). Relapses, most of which occurred within the first 2 yr from transplant, were the predominant cause of treatment failure affecting 48% (95% CI : 40–58) of patients, whereas non‐relapse mortality was 26% (95% CI : 20–36) at 5 yr and thereafter. A marrow blast count ≥20% before allo SCT was an independent prognosticator associated with an inferior DFS ( HR : 1.58, P  = 0.027), whereas the development of chronic graft‐ versus ‐host disease ( cGvHD ) predicted an improved DFS ( HR 0.21, P   〈  0.001) and a decreased relapse incidence ( HR : 0.18, P  = 0.026), respectively. These results indicate that allo SCT represents a curative treatment option in a substantial proportion of patients with refractory AML . A pretransplant blast count 〈 20% before allo SCT and the development of cGvHD are the most important predictors of long‐term disease control.
    Type of Medium: Online Resource
    ISSN: 0902-4441 , 1600-0609
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2015
    detail.hit.zdb_id: 2027114-1
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  • 4
    In: International Journal of Hematology, Springer Science and Business Media LLC, Vol. 91, No. 3 ( 2010-4), p. 436-445
    Type of Medium: Online Resource
    ISSN: 0925-5710 , 1865-3774
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2010
    detail.hit.zdb_id: 2028991-1
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  • 5
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 899-899
    Abstract: Abstract 899 Introduction: The classic definition of acute (aGVHD) and chronic graft-versus-host disease (cGVHD) was based on a cut-off day 100 after transplantation, but this did not reflect that aGVHD can occur later and that symptoms of aGVHD and cGVHD can occur simultaneously. In 2005 a NIH consensus classification was proposed which included 1) classic aGVHD, occurring before day 100, 2) persistent, recurrent or late aGVHD occurring thereafter, 3) classic cGVHD and 4) an overlap syndrome with simultaneous features of aGVHD and cGVHD. Only few studies have evaluated this classification and no studies have determined the differential impact of reduced intensity (RIC) and myeloablative conditioning (MAC). Method: We retrospectively analyzed 202 AML patients who were transplanted between 1999 and 2008. 102 patients received RIC (generally 6×30 mg/m2 FLU, 4×4 mg/kg BU, 4×10 mg/kg ATG) and immunosuppression with CSA/MMF and 100 patients received MAC (generally 6×2 Gy TBI and 2×60 mg/kg CY) and CSA/MTX. Donors were HLA-matched related (n=82), -matched unrelated (n=88) or -mismatched (n=32). Result: Leukocyte recovery was faster after RIC than after MAC (14 vs. 19 days, P 〈 0.001) but time to reach full donor chimerism was similar (60 vs. 56 days, P=0.12). The cumulative incidence of classic aGVHD was lower after RIC than after MAC (40 vs. 67%, P 〈 0.001) and it occurred later (31 vs. 23 days, P=0.041). No difference was seen in organ manifestations and in the overall aGVHD grade. The cumulative incidence of late aGVHD was low and did not differ between RIC and MAC (9 vs. 7%, P=NS). 13/16 patients with late aGVHD had persistent or recurrent classic aGVHD and 3/16 had de novo late aGVHD. Late aGVHD was less severe after RIC (grade III/IV 22 vs. 86%, P=0.041). The first signs of cGVHD were observed on days 86 after RIC and 97 after MAC with median onset on days 167 and 237, respectively (P=NS). The cumulative incidence of cGVHD tended to be lower after RIC (36 vs. 51%, P=0.088) and it tended to be less severe. Organ manifestations were similar except for cGVHD of the joints and fascia which affected 11% of MAC but no RIC patients (P=0.0021). More than half of cGVHD cases were subclassified as overlap cGVHD with no significant differences between RIC and MAC (51 vs. 65%, P=0.26). In multivariate Cox regression analysis of the whole cohort the only significant risk factor for aGVHD was MAC (HR 2.33, 95%CI 1.51–3.59, p 〈 0.001). In RIC patients the administration of bone marrow lead to less aGVHD (HR 0.13, 95%CI 0.016–0.98, P=0.047). The only relevant risk factor for late aGVHD was prior aGVHD (HR 3.65, 95%CI 1.040–12.81, P=0.043). The most important risk factors for cGVHD were prior aGVHD (HR 2.77, 95%CI 1.64–5.67, P 〈 0.001), female-to-male transplantation (HR 1.94, 95%CI 1.12–3.35, P=0.017) and advanced disease (HR 1.95, 95%CI 1.2–3.1, P=0.018). In multivariate Cox regression analysis with GVHD as time-dependant covariate aGVHD grade III/IV (HR 2.41, 95%CI: 1.51–3.87, P=0.001) and late aGVHD grade III/IV (HR 3.037, 95%CI 1.29–7.18, P=0.011) were associated with inferior overall survival (OS) while moderate cGVHD had a positive effect (HR 0.42, 95%CI 0.18–0.97, P=0.043). Classic and overlap cGVHD had no differential prognostic impact. Conclusion: This study in AML patients shows that previously established GVHD risk factors remain valid for the new NIH classification. It also confirms the major impact of conditioning intensity on GVHD incidence, the negative prognostic impact of severe aGVHD and the benefit of moderate cGVHD. The new category late aGVHD may only include few patients but will allow more adequate allocation to therapies or clinical trials. Whether the subgroups classic and overlap cGVHD are clinically relevant remains to be determined. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 6
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 3470-3470
    Abstract: Abstract 3470 Introduction: Allogeneic stem cell transplantation (alloSCT) represents a curative treatment option for the post-remission therapy of patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). The presence or absence of distinct karyotypic abnormalities has a substantial impact on the risk of relapse and overall outcome. In particular, complex, i.e. ≥3, chromosomal aberrations are associated with a poor outcome. Patients and Methods: We retrospectively analyzed 91 patients (47 female, 44 male) with secondary AML or therapy-related AML (n=50; CR1: n=22, CR 〉 1: n=2, no CR: n=24) or MDS (n=41; RA/RCMD: n=14, RAEB-1: n=11, RAEB-2: n=16) who underwent alloSCT at our center between 1995 and 2008. An intermediate-risk karyotype was present in 47 patients, whereas 38 patients had a poor-risk karyotype. Among those, 22 patients had aberrations of chromosome 5 and/or 7. 45 patients were treated with standard myeloablative conditioning (MAC) (12 Gy total body irradiation, 2×60 mg/kg cyclophosphamide) prior to alloSCT, whereas 46 patients received reduced intensity conditioning (RIC) (fludarabine 6×30 mg/m2, busulfan 2×4 mg/kg, anti-thymocyte globulin 4×10 mg/kg). 35 patients had a matched-related donor (MRD) and 37 or 13 patients had a matched-unrelated (MUD) or a mismatched-unrelated (MMUD) donor. Results: After a median follow-up of 58 (12-170) months, 42/91 patients (46%) are alive and in CR. 20/91 patients (22%) succumbed to relapse and 27/91 patients (30%) died from treatment-related mortality (TRM). Projected OS (DFS) at 1, 3, or 5 years was 60% (55%), 52% (53%), or 50% (48%) and TRM was 27%, 27%, or 31%. Patients with a poor-risk cytogenetic profile had a significantly lower DFS as compared to patients with an intermediate-risk cytogenetics, i.e. 57% versus 36% at 5 years (p=0.04). However, within the group of patients with a poor-risk karyotype, those with aberrations of chromosome 5 and/or 7 had significantly lower OS (30% versus 50% at 5 years; p=0.03), or DFS (26% versus 50%; p=0.01) as compared to patients with complex aberrations. In contrast, the OS of patients with complex chromosomal aberrations excluding those who have chromosome 5 and/or 7 aberrations had a similar OS, DFS, or probability of relapse as compared to patients with an intermediate risk karyotype. Of note, in this subgroup there was no statistically significant difference in OS or DFS between patients conditioned with either standard MAC or RIC. Likewise, there was no statistically significant difference between patients transplanted from a MRD or a MUD. Conclusions: Taken together, these results indicate that the presence of a poor-risk karyotype has a substantial prognostic impact in patients with secondary AML, therapy-related AML or MDS undergoing alloSCT. In particular, patients with aberrations of chromosome 5 and/or 7 are highest risk of relapse. Nonetheless, a substantial proportion of these patients may achieve durable remissions following either standard or RIC-alloSCT. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
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  • 7
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 3276-3276
    Abstract: Purpose: The hematopoietic cell transplantation-specific comorbidity index (HCT-CI) is used to assess the impact of comorbidities on the outcome of patients following alloSCT. Nonetheless, in AML patients leukemia-associated risk factors, i.e. cytogenetics, the presence of secondary (sAML) or therapy-related AML (tAML), or disease status prior to alloSCT, are highly relevant with regards to the long-term outcome. We therefore investigated whether the HCT-CI combined with the analysis of a defined set of AML-specific high risk factors may be used to predict the overall outcome of AML patients after alloSCT following RIC. Patients and Methods: 90 patients with high-risk AML (median age 51 (17 – 68) years) who underwent alloHSCT at our institution between 1999 and 2007 were retrospectively analyzed (median follow-up of the surviving patients: 16 (range 2 – 113) months). 50/90 patients (56%) were in CR1, 12/90 (13%) were in CR2, 2/90 (2%) were 〉 CR2, and 26/90 (29%) had refractory or relapsed disease at the time of transplantation. 57/90 patients (63%) had de novo AML and 33/90 patients (37%) had either secondary AML (sAML) or therapy-related AML (tAML). Whereas 4/90 patients (4%) had a favorable risk karyotype, 51/90 patients (57%) or 29/90 patients (32%) had an intermediate risk or a poor risk karyotype as defined by the SWOG/ECOG criteria (Slovak et al., Blood 2000). Notably, 18/90 (20%) patients had an intermediate risk HCT-CI (1–2 points) and 72/90 patients (80%) had an unfavorable score ( 〉 2 points). As a preparative regimen all patients received RIC, which consisted of fludarabine 180 mg/m2 + oral busulfane 8 mg/kg + anti-thymocyte globulin 30 mg/kg. As stem cell source peripheral blood stem cells (PBSC) were used in 85/90 patients (94%), whereas 5/90 patients (6%) received bone marrow (BM). 38/90 patients (42%) were transplanted from a matched related donor. A matched unrelated or a mismatched unrelated donor was available in 36/90 patients (40%) or in 16/90 patients (18%). Graft-versus-host disease (GvHD) prophylaxis consisted of cyclosporin (CSA) + mycophenolate mofetil (MMF). Results: Projected overall survival (OS) or disease-free survival (DFS) of the whole cohort at 1, 3, and 5 years was 60%, 44%, and 44% or 56%, 46%, and 46%. 49/90 patients (54%) are in CCR. Causes of death were relapse (23/90 patients (26%)) or TRM (18/90 patients (20%)). Notably, the HCT-CI alone was not sufficient to predict the overall outcome our cohort of patients after RIC-alloSCT. Therefore, depending on the presence or absence of at least one additional leukemia-specific high-risk factor, i.e. disease status prior to alloSCT 〉 CR1, tAML, or poor risk karyotype, patients were grouped into four subgroups: group I (HCT-CI 〈 4, no high risk), group II (HCT-CI 〉 4, no high risk), group III (HCT-CI 〈 4, high risk), and group IV (HCT-CI 〉 4, high risk). Projected OS in at 1, 2, and 3 years after alloSCT was 73%, 59%, and 59% (group I), 86%, 57%, and 57% (group II), 56%, 46%, and 37% (group III), or 33%, 16%, and 16% (group IV), which differed statistically significant between the 4 subgroups (p = 0.04). In turn, there was no statistically significant difference in TRM between groups I – IV (p = 0.61). Conclusions: These results indicate that the combined analysis of TRM-related factors, as assessed by the HCT-CI, and a limited set of leukemia-specific risk factors, i.e. cytogenetic risk, disease status before alloSCT, and the presence of tAML, may be useful in predicting the overall outcome of patients with AML after alloSCT following RIC.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    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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  • 8
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 2302-2302
    Abstract: Abstract 2302 Poster Board II-279 Purpose: The presence of comorbidities was shown to have a substantial impact of the outcome of patients undergoing cancer treatment. In chronic myeloid leukemia (CML) the EBMT risk score proofed to be highly valuable in predicting the outcome of patients following allogeneic stem cell transplantation (alloSCT). We therefore investigated, whether a slightly modified EBMT risk score may be used to predict the outcome of patients with AML following alloSCT. Patients and Methods: We retrospectively analyzed 233 patients with AML (median age: 47 years, range: 17 – 68 years) who underwent alloSCT at our institution between 1994 and 2007. 180 patients (77%) had de novo AML and 53 patients (23%) had secondary or therapy-related AML. A favorable karyotype was present in 11 patients (5%) whereas 101 (43%) or 82 patients (35%) had an intermediate risk or a poor risk karyotype. 131 patients (56%) received myeloablative conditioning (MAC) whereas 102 patients (44%) were conditioned using reduced intensity conditioning (RIC). The EBMT risk score was calculated analogous to the original score established by Gratwohl et al. (Lancet 352, 1998) and included the following variables: age ( 〈 20, 20-40 or 〉 40 years), interval from diagnosis to alloSCT ( 〈 1 year or ≥1 year), disease stage (CR1, 〉 CR1 or no CR), donor/recipient gender match (female donor/male recipient or other), and donor type (HLA-identical sibling or other). Altogether, 6 patients (3%) were younger than 20 years, 82 patients (35%) were between 20-40 years, and 145 patients (62%) were older than 40 years. The interval from diagnosis to alloSCT was 〈 1 year in 180 patients (77%) and ≥1 year in 53 patients (23%). 121 patients (52%) were transplanted in CR1, 41 patients (18%) underwent alloSCT 〉 CR1, and 71 patients (30%) had active (relapsed/refractory) disease at the time of alloSCT. A female donor/male recipient transplantation was performed in 59 patients (25%). Transplants were from a matched-related donor (MRD) in 103 patients (44%). A matched-unrelated or a mismatched-unrelated donor was chosen in 101 (44%) or in 28 patients (12%). Only 1 patient was transplanted from a haplo-identical donor. Results: After a median follow-up of 48 months (range: 6 – 170 months) for the surviving patients, 108 patients (46%) are alive, 101 (43%) of which are in continuous CR. Causes of death (total 125 patients (54%)) were relapse in 70 patients (30%), infections/graft versus host-disease in 54 patients (23%), or other (1 patient (0.5%)). At 10 years after alloSCT, projected overall survival (OS) or disease-free survival (DFS) were 41% or 39%. Non-relapse mortality (NRM) or incidence of relapse were 32% or 43%. Of the 233 patients, 30 (13%) had an EBMT risk score of 0-1, 48 (21%) had a score of 2, 50 (21%) had a score of 3, 40 (17%) had a score of 4, 51 (22%) had a score of 5, and 14 (6%) had a score of 6-7. OS in the different score groups were 67% (score 0-1), 50% (score 2), 48% (score 3), 33% (score 4), 23% (score 5), or 21% (score 6-7) and differed significantly between the groups (p=0.0005). NRM in patients with an EBMT risk score 〉 4 as an abritary cut-off was significantly higher as compared to patients with a score ≤4 (53% versus 25%; p=0.009). Likewise, the incidence of relapse was significantly lower in patients with an EBMT risk score ≤3 as an abritary cut-off when compared those with a score 〉 3 (31% versus 57%; p 〈 0.0001). In univariate analysis, disease stage had a negative prognostic impact on OS (CR1: 54%, 〉 CR1: 32%, no CR: 25%; p 〈 0.0001). Likewise, OS in patients with a MRD was significantly higher as compared to patients with other donor types (MRD: 50%, other: 34%; p= 0.003). In contrast, age, interval from transplantation to alloSCT, and donor/recipient gender match did not influence OS in our analysis. Conclusions: These data indicate that a modified EBMT risk score may be used to predict the outcome of patients with AML following alloSCT. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 9
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 1998-1998
    Abstract: Abstract 1998 Purpose: In patients with newly diagnosed acute myeloid leukemia (AML) rapid achievement of remission by induction chemotherapy is an important predictor for long-term disease control. In turn, patients who fail to attain early blast clearance after the first chemotherapy course have an inferior outcome. Here, we investigated the impact of early blast clearance on the overall outcome of patients with AML undergoing allogeneic stem cell transplantation (alloSCT) in first complete remission (CR1) as consolidation therapy. Patients and Methods: 169 (90 female, 79 male) patients with AML who underwent alloSCT in CR1 at our center between 1994 and 2011 were included. Data were prospectively recorded in our transplant data base and retrospectively analyzed as of December 31st, 2011. In detail, 107 patients (64%) had de novo AML, 31 patients (18%) had AML evolving from myelodysplastic syndrome (MDS), and 31 patients (18%) had therapy-related AML. According to the criteria of the SWOG/ECOG, cytogenetic risk was either favorable (6 patients, 4%), intermediate (104 patients, 62%), or poor (47 patients, 27%). Prior to alloSCT all patients were treated in a German multicenter AML trial and received at least two courses of induction chemotherapy, i.e. either standard “7+3” (daunorubicin 60 mg/m2, day 3–5 and Ara-C 100 mg/m2, day 1–7) or a “high-dose Ara-C” containing regimen (Ara-C 1–3 g/m2). In 98 patients (58%) induction chemotherapy resulted in blast clearance after the first course, whereas 71 patients (42%) failed to achieve early remission, but entered remission after 1 or 2 subsequent courses. Median age at transplantation was 47 years (range: 17–69 years). In 146 patients (86%) alloSCT was performed using peripheral blood stem cells (PBSCs), whereas 23 patients (14%) received a bone marrow (BM) graft. Conditioning consisted of standard myeloablative conditioning (MAC: 6 × 2 Gy TBI and 2 × 60 mg/m2 cyclophosphamide) in 81 patients (48%), whereas 86 patients (52%) received reduced intensity conditioning (RIC: busulfan 2 × 4 mg/kg, fludarabine 6 × 30 mg/m2 and ATG 4 × 10 mg/kg). A matched related donor was available in 82 patients (49%), whereas 68 patients (40%) or 19 patients (11%) were transplanted from a matched-unrelated or mismatched unrelated donor. Results: After a median follow-up of 45 months (range: 3–196 months) for the surviving patients, 91 patients (54%) are alive and in continuous remission. Causes of death were relapse in 38 patients (22%) or NRM in 33 patients (19%). At 1, 3 or 5 years projected overall survival (OS) was 72±6%, 58±6%, or 54±8% for all patients. Probability of relapse or non-relapse mortality (NRM) at 1, 3, and 5 years was 20±10% (20±11%), 31±12% (20±11%), and 34±12% (20±11%). Although there was no statistically significant difference in OS at 3 and 5 years between patients who achieved early blast clearance as compared to patients who failed to do so (p=0.09), disease-free survival (DFS) and probability of relapse differed significantly between the two groups at 3 years (77±8% vs 55±14%) or 5 years (75%±9% vs 52%±14%) following alloSCT (p=0.02). There was no significant difference in NRM between the two subgroups. Likewise, there was no statistically significant difference between patients conditioned with either MAC or RIC. In multivariate analysis cytogenetic risk group and remission status were identified as independent prognostic factors for DFS and probability of relapse. Conclusions: These results suggest that in patients with AML undergoing alloSCT in CR1 early blast clearance, i.e. following the first course of induction chemotherapy, predicts a very favorable outcome. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 10
    In: Acta Haematologica, S. Karger AG, Vol. 133, No. 2 ( 2015), p. 237-241
    Abstract: The presence of a Philadelphia chromosome with a corresponding 〈 i 〉 BCR-ABL1 〈 /i 〉 rearrangement is the hallmark of chronic myeloid leukemia, but is considered a very rare event in de novo acute myeloid leukemia (AML). Here, we report the first case in which a dominant Philadelphia chromosome-positive subclone was detected upon relapse in a formerly Philadelphia chromosome-negative 〈 i 〉 MLL-AF6 〈 /i 〉 〈 sup 〉 〈 i 〉 + 〈 /i 〉 〈 /sup 〉 AML. Due to refractory disease under salvage chemotherapy, the patient was started on nilotinib treatment. As a result, the Philadelphia chromosome-positive subclone was eradicated within 1 month; however, disease progressed and was again dominated by the Philadelphia chromosome-negative founding clone, demonstrating rapid clonal expansion under nilotinib-induced selection pressure. © 2014 S. Karger AG, Basel
    Type of Medium: Online Resource
    ISSN: 0001-5792 , 1421-9662
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2015
    detail.hit.zdb_id: 1481888-7
    detail.hit.zdb_id: 80008-9
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