Kooperativer Bibliotheksverbund

In: mBio, American Society for Microbiology, Vol. 5, No. 6 ( 2014-12-31)

Abstract: Several cases of rapidly fatal infections due to the fungus Saprochaete clavata were reported in France within a short period of time in three health care facilities, suggesting a common source of contamination. A nationwide alert collected 30 cases over 1 year, including an outbreak of 18 cases over 8 weeks. Whole-genome sequencing (WGS) was used to analyze recent and historical isolates and to design a clade-specific genotyping method that uncovered a clone associated with the outbreak, thus allowing a case-case study to analyze the risk factors associated with infection by the clone. The possibility that S. clavata may transmit through contaminated medical devices or can be associated with dairy products as seen in previous European outbreaks is highly relevant for the management of future outbreaks due to this newly recognized pathogen.

Type of Medium: Online Resource

ISSN: 2161-2129 , 2150-7511

URL: Article

DOI: 10.1128/mBio.02309-14

Language: English

Publisher: American Society for Microbiology

Publication Date: 2014

detail.hit.zdb_id: 2557172-2

In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 28, No. 18 ( 2010-06-20), p. 3028-3034

Abstract: No significant improvement in treatment outcome has been seen in elderly patients with acute myeloid leukemia (AML) over the past 20 years. This retrospective analysis investigated the prognostic factors for complete remission (CR) and survival in older patients with AML. Patients and Methods The study involved 847 patients older than 60 years enrolled onto three trials carried out in France between 1995 and 2005. Induction therapy consisted of idarubicin (8 mg/m 2 , days 1 through 5) and cytarabine (100 mg/m 2 , days 1 through 7; group I, 339 patients) or the same drugs plus lomustine (200 mg/m 2 orally on day 1; group II, 508 patients). Consolidation therapy consisted of anthracycline and cytarabine courses at lower doses, preceded or not by a first course of intermediate-dose cytarabine. Results The rate of CR was significantly higher in patients in group II compared with group I (68% v 58%; P = .002). The rate of toxic death was similar in the two groups. In multivariate analysis, two prognostic factors were linked to CR: nonadverse cytogenetic (P 〈 .003) and addition of lomustine to induction chemotherapy (P = .002). Median overall survival was significantly improved in patients treated with lomustine (median and SE, 12.7 ± 2.2 months v 8.7 ± 2.7 months; P = .004). In multivariate analysis, five prognostic factors positively affected overall survival: addition of lomustine (P = .002), age ≤ 69 years (P 〈 .001), Eastern Cooperative Oncology Group performance status lower than 2 (P = .002), French-American-British subgroup 1/2 (P = .02), and nonadverse cytogenetic (P 〈 .001). Conclusion Lomustine improves the rate of CR and survival in elderly patients with de novo AML when added to standard induction therapy.

Type of Medium: Online Resource

ISSN: 0732-183X , 1527-7755

URL: Article

DOI: 10.1200/JCO.2009.26.4648

Language: English

Publisher: American Society of Clinical Oncology (ASCO)

Publication Date: 2010

detail.hit.zdb_id: 2005181-5

In: European Journal of Haematology, Wiley, Vol. 98, No. 5 ( 2017-05), p. 443-449

Abstract: Anthracyclines and cytarabine are cornerstones for intensive chemotherapy in acute myeloid leukemia (AML). The goals of this study were to comprehensively assess deviations from theoretical doses and the impact of body‐surface area (BSA) on patients’ characteristics, physicians’ strategy, dose adjustment, and clinical outcome. Methods The GOELAMS 2001 phase III trial included 823 AML patients below 60 years of age. In the course of treatment, anthropomorphic parameters and chemotherapy doses were prospectively registered. Results Very high BSA (≥2.15 m 2 ) was the factor most significantly associated with the physician's decision to reduce chemotherapy doses during induction and postremission therapy. Despite similar AML characteristics and therapeutic strategies, the very high BSA group exhibited a significantly worse survival (5‐years OS of 27%) compared to the low (BSA≤1.5 m 2 ), intermediate (1.5 m 2 〈 BSA≤2.0 m 2 ), or high (2 m 2 〈 BSA 〈 2.15 m 2 ) BSA groups (46%, 47%, 56%, respectively) ( P =.009). In the very high BSA group, dose capping was associated with worse overall survival, although not significantly ( P =.09). Conclusion The presence of a very high BSA is the main reason prompting physicians to reduce chemotherapy doses in adult AML. Furthermore, these patients display a poor outcome and could benefit from full doses calculated on actual BSA.

Type of Medium: Online Resource

ISSN: 0902-4441 , 1600-0609

URL: Issue

URL: Article

DOI: 10.1111/ejh.2017.98.issue-5

DOI: 10.1111/ejh.12850

Language: English

Publisher: Wiley

Publication Date: 2017

detail.hit.zdb_id: 2027114-1

In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 844-844

Abstract: Abstract 844 Introduction: intensive chemotherapy (IC) in AML post-MDS (here AML) or High Risk-MDS (here MDS) is associated with lower CR rate, shorter response duration and poor overall survival compared to de novo AML. Upfront treatment of MDS with AZA delays time to AML evolution and prolongs overall survival (OS). The low toxicity profile of AZA should also allow its use in IC responders in an outpatient setting. Preliminary results with this approach by the Nordic MDS group in 23 pts (ASH 2008, abstr n°223) showed its feasibility. We used it in AML or MDS patients (pts), who had achieved response after IC. Methods: Inclusion criteria were: (1) de novo MDS patients and IPSS int-2 or high risk (including CMML if WBC 〈 13G/l), or AML preceded by a documented MDS phase (2) who had reached CR, CRi or PR after IC (IWG-AML criteria) with anthracyclin and AraC in the 28 days preceding study entry (3) ECOG ≤2, absence of ongoing infection or renal and liver toxicities from IC. (4) with no identified donor for allo SCT at entry. Dosing of AZA was 60mg/m2/d for 5 days, every 28 days for the first two cycles. In the absence of grade ≥ 3 toxicities, dosing of subsequent cycles could be increased to 75mg/m2/d. Dosing of AZA had to be reduced in case of grade ≥3 toxicities, persistent cytopenias beyond day 42 of each cycle, or if cytopenias were associated with re-hospitalization. AZA post-remission therapy was to be continued until relapse (according to IWG-AML and MDS criteria) or toxicity. Results: From July 06 to June 09, 51 pts (M31/F20) were included but 5 were not evaluable (2 IWG failures upon review, 1 protocol violation, 1 therapy-related MDS, 1 patient too early). The 46 evaluable pts had achieved CR (n=33), CRi (n=11) and PR (n=2) before study entry. Median age was 66y (55-78). Diagnosis at IC onset was MDS (N=13) and AML (N=33), IPSS cytogenetics was normal (N= 28), intermediate (N=10), high (N= 6), and failed (N=2). Median time from diagnosis of MDS to IC was 8 months (0.5-101). Median number of AZA maintenance cycles was 5.5 (0-32+)in CR pts ( 〉 23 cycles in 4 of them) and 2 (0-11) in CRi or PR pts. Median follow-up was 24 months (m). Median DFS was 6.5 m and 18-m DFS was 20% (95% CI 9-35); median and 18 month OS from response were 15 m and 43% (95% CI 27-58), respectively. 18-m-DFS and OS were 30 % (95% CI 13-48) and 56% (95% CI 35-72), in the 33 CR pts (median OS 24m), compared to O% and 17% (95% CI 3-41), in the 11 PR/CRi pts, ( P= .0001 and .04, respectively) . 21 of the 33 CR pts had relapsed and 3 had CR duration 〉 24 months. None of the pts in CRi/PR after IC improved their response with AZA. Only initial response to IC (ie CR vs CRi/PR), but not cytogenetics (normal vs. others), diagnosis at IC onset (MDS vs AML), % bone marrow blasts (using 20 or 30 % cut-off), age or time from MDS diagnosis to treatment, significantly predicted DFS or OS in this cohort. AZA dosing in CR patients was escalated in 9 pts but had to be reduced in 6 other pts, due to GI tract intolerance (n=1) and cytopenias (n=5). Only 2/33 CR pts, developed severe infection or febrile neutropenia while in persistent response, compared to 4/11 pts in CRi or PR (including 1 fatal case). We finally compared outcome of the 22 AML study pts in CR to that of 46 similar AML post MDS pts from our ALFA group elderly AML 9803 study (Gardin, Blood 2007), in which pts in CR received DNR/IDA–AraC post-remission therapy. Cumulative incidence of relapse did not differ between the present AZA cohort in AML patients and the ALFA cohort (18-m CIR at 41% (95% CI 18-63) and 25% (95% CI 13-40), respectively; P=0.92). OS from CR was also identical between the 2 cohorts (18-m OS of 56% (95% CI 31-76) and 54% (95% CI 37-69), respectively; P=0.84) Conclusion: In this study, post–CR therapy with AZA alone was associated with a 30% DFS rate and 56% OS at 18m and a median OS of 24m, while pts in CRi or PR did not benefit from AZA. Although selection biases may exist between cohorts, DFS and OS of AML post MDS in CR were identical to those observed in similar pts treated after CR by anthracyclin and AraC consolidation. Hematological toxicity of AZA, however, was minimal. Combinations of AZA with other drugs may be of further interest in those patients at high–risk of relapse. Disclosures: Gardin: Celgene: Consultancy, Honoraria, Research Funding. Off Label Use: azacitidine as post-remission therapy in AML patients. Dombret:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Fenaux:Celgene: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Ortho Biotech: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Cephalon: Honoraria, Research Funding; Merck: Honoraria, Research Funding; Novartis: Honoraria, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V114.22.844.844

Language: English

Publisher: American Society of Hematology

Publication Date: 2009

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 1-2

Abstract: Background: Results of the phase III QUAZAR trial suggest that post-remission treatment with an oral form (CC-486) of azacitidine (AZA) can prolong CR duration and overall survival(OS) in AML patients reaching at least PR with intensive chemotherapy (IC) (Wei et al, ASH 2019). Maintenance treatment with subcutaneous (SC) AZA was recently shown to improve DFS in elderly AML (Huls et al, Blood 2019, a study that also included 10% MDS). We report very long term results of a study evaluating SC AZA as post-remission treatment in patients with AML post-MDS or high-risk MDS (HR-MDS) who achieved at least PR after IC, a population known to have short responses with IC. Methods: Inclusion criteria were (1) HR-MDS according to IPSS, or AML after a documented phase of MDS(2) who entered CR, CRi or PR after IC with anthracycline and AraC within 28 days of inclusion (3) ECOG & lt;= 2, absence of infection or organ toxicity from IC (4) no identified donor for allo SCT at inclusion. Dosing of SC AZA was 60mg/m2/d for 5 days every 28 days, with adjustments according to tolerance, and until relapse or toxicity. Results: From July 2006 to June 2009, 51 pts (M:31/F:20) were included. The 46 evaluable pts had achieved CR (n=28), CRi (n=11), and PR (n=7) before study entry. Median age was 66y (range 55-78). Diagnosis at IC onset was MDS (n=13) and AML (n=33), IPSS cytogenetics was normal (n= 28), intermediate (n=10), high (n= 6), and failed (n=2). Median time from diagnosis of MDS to IC was 8 months (range 0.5-101). Median number of AZA maintenance cycles was 7.5 (1-76) in CR pts ( & gt;23 cycles in 5 of them) and 4.5 (1-24) in CRi or PR pts ( & gt; 23 cycles in 1). Two patients were allografted and censored at allo SCT. Median follow-up was 16.5 months As of May 2020 (cut off date of analysis) median DFS and OS from response were 6.9 m and 16.9 m, respectively (figure). In CR patients, median and 18 months OS were 18.9 months and 58%, versus 12.8 months and 50% in CRi-PR patients (p=0.33) All non allografted patients eventually relapsed. 7 had a response duration & gt;18 months (6 CR patients: 22, 23, 25, 36, 40, and 84 months; 1 CRi patient: 24 months) OS from inclusion was & gt;3 years in 7 patients (CR pts: 150, 126,74, 51, 50,40 months; CRi pt:58 months), in addition to the 2 allografted pts who remained alive in CR at 156+ and 159+ months No baseline factor including cytogenetics, diagnosis at IC onset (MDS vs AML), % bone marrow blasts, age or time from MDS diagnosis to treatment, significantly predicted DFS or OS. AZA dosing in CR patients was escalated in 9 pts to 75mg/m2/d due to good tolerance but had to be reduced in 6 pts, due to GI toxicity (n=1) and cytopenias (n=5). During SC AZA maintenance, 2/28 CR pts developed febrile neutropenia, compared to 4/18 pts in CRi or PR (including 1 fatal case). In the 22 AML post MDS pts who reached CR, DFS and OS were similar to those observed in 46 AML post AML pts included in a previous ALFA study where pts in CR after IC received DNR/IDA-AraC post-remission therapy (Gardin, Blood 2007). Conclusion: In the very long term analysis of this trial in AML post MDS and HR-MDS treated with induction intensive chemotherapy, post-remission therapy with SC AZA alone was associated with a median DFS and OS of 6.9 and 16.9 months, respectively, with some prolonged response. Results appeared similar to those we had reported with intensive consolidation chemotherapy, but using an ambulatory treatment with limited myelosuppression. Figure Disclosures Braun: Daiichy-Sankyo: Honoraria; Servier: Research Funding. Bouabdallah:Takeda: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Gilead Sciences: Consultancy, Honoraria. Ades:Celgene/BMS: Research Funding; novartis: Research Funding; takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; jazz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding. Fenaux:Abbvie: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Jazz: Honoraria, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-137012

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 1839-1839

Abstract: Introduction. The prognosis of AML in patients over 60 years of age remains very poor. As in younger patients karyotype is a major prognostic factor. Elderly patients with poor risk cytogenetics have a dismal outcome and complete remission (CR) rates with conventional chemotherapy are usually & lt; 45% (and & lt; 25% if complex abnormalities). GO has been used in combination with chemotherapy in relapsed or newly diagnosed AML, but with reduced doses in order to decrease hepatic toxicity. Methods. In this multicentric open-label Phase II study we have evaluated the combination of I (8 mg/m2/D × D1-5) + C (100 mg/m2/D × D1-7) with GO (6 mg/m2 on D3) in AML patients aged 60–75 years with poor risk cytogenetics and fit enough to undergo cytotoxic chemotherapy. Other inclusion criteria were: CD33+ AML, PS 2, de novo or secondary AML (excluding M3 and Ph1 + AML), no cardiac, renal or hepatic dysfunction. Results. 44 pts aged 60–74 (median 68) were treated in 13 GOELAMS centers. Karyotype results were: chromosome (chr) 5 abnormalities 22, chr 7 abnormalities 26, chr 5+7 abnormalities 14, complex abnormalities 26. In 13 cases (30%) AML was secondary (chemoinduced 9, prior myeloproliferative or myelodysplastic syndrome 4). Median duration of hospitalisation was 31 D (4–51). In CR patients median duration of neutropenia was 19 D (14–28) and median duration of thrombocytopenia was 15D (5–29). Bacterial or fungal infections were documented in 71% of cases. 7 patients had severe bleeding including 3 deaths, (2 cerebral hemorrhage, 1 intestinal bleeding). Grade 2 hepatic dysfunction was seen in 30% of patients including 3 (7%) pts with veino-occlusive disease (one death). There were 17 (38%) CR (16 CR, 1 CRp), 6 (14%) toxic deaths and 21 (48%) failures. The CR rates was 41% (7/17) for patients aged 70–75 and 37% (10/27) for patients & lt; 70 years. While CR rate was 50% (6/12) in patients with isolated chr 5 or 7 abnormalities, it was 35% (9/26) in patients with complex abnormalities. Conclusion. In this population of elderly but relatively fit patients with poor risk cytogenetics AML the addition of GO 6 mg/m2 to conventional chemotherapy did not appear to increase the CR rate mostly because of leukemic resistance. The incidence of aplasia-related toxicities and of hepatic complications does not encourage to use higher doses of GO.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V110.11.1839.1839

Language: English

Publisher: American Society of Hematology

Publication Date: 2007

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 31-31

Abstract: Background. Tyrosine kinase inhibitors (TKI) are standard front-line therapy for patients with BCR-ABL1/Philadelphia positive ALL (Ph+ ALL), but the relative merits of available TKIs remain uncertain. Nilotinib is a potent inhibitor of BCR-ABL1 with broader activity against ABL kinase domain mutations than imatinib and greater selectivity than dasatinib or ponatinib. As there is a paucity of data on nilotinib as first-line therapy for Ph+ ALL, the EWALL (European Working Group for Adult ALL) conducted an international clinical trial to evaluate efficacy and safety of the combination of nilotinib with low intensity chemotherapy. Patients and Methods. After a prephase with dexamethasone (DEX) and cyclophosphamide, nilotinib (400 mg BID) was given concurrently with the same chemotherapy backbone employed in the EWALL-PH01 assessing the combination with dasatinib (Rousselot et al, Blood 2016;128:774-82). Induction consisted of nilotinib combined with weekly vincristine (VCR, 1mg iv) and oral dexamethasone 40mg 2 days (20 mg over 70y). Nilotinib was continued throughout six consolidation cycles, followed by 24 months maintenance therapy with nilotinib, 6-MP, MTX and DEX/VCR boosts. Stem cell transplantation (SCT) was permitted as considered appropriate. BCR-ABL1 RTQ-PCR and kinase domain resistance mutations were centrally monitored. Primary endpoint was event-free survival (EFS) at 12 months, secondary endpoints included rates of CR, major and complete molecular response, relapse free survival (RFS), EFS and overall survival (OS). Results. 72/79 enrolled pts. were evaluable for response, 3 withdrew consent, 4 did not meet eligibility criteria. Median age was 65.5 (55-85) years, male/female ratio 0.85, ECOG status 0 or 1 in 89% of pts., median CIRS comorbidity score 5(0-19). Baseline vascular risk factors including high blood pressure (grade ≥2) were present in 36% of pts.. Sixty-eight of 72 pts. (94.4%) achieved CR, one died during induction and one was refractory, 2 pts. discontinued study therapy. Non-hematologic adverse events (AE) grades 3/4 during induction (in ≥ 5% of pts. irrespective of causality) included infections (n=20), elevated transaminases or bilirubin (n=18) and gastrointestinal AEs (n=12). The spectrum of AEs was similar during consolidation, without concerns related to cardiovascular events. 24 pts. (61y; 55-69y) underwent allogeneic (9 MUD, 12 SIB, 3 Haplo) and 3 autologous SCT. 21 pts. received reduced intensity conditioning (including 8Gy TBI, n=11) regimens. Among all pts., relapse was the main cause of treatment failure (n=23; 17 BM, 2 CNS, 3 other sites, 1 na), 11 pts. died in CR (6 after HSCT), 34 are in ongoing CR. Based on Kaplan Meier analysis, EFS (events being resistant disease, relapse or death) at 12 months was 74%, with median follow-up of 39 (24-66) months for surviving pts., EFS and OS at 4 years was 42%, and 47%, respectively. By landmark analyses using median time to HSCT as cutoff, cumulative incidence of relapse in transplanted vs. non-transplanted pts. was 32% and 47%, OS at 4 years was 61% and 39%, median OS was not reached versus 3.6 years, respectively (p=ns). The proportion of pts. with a BCR-ABL1/ABL1 ratio ≤0.1% increased from 41% after induction to 86% after consolidation 2; that of pts. with undetectable or non-quantifiable BCR-ABL1 transcripts (sensitivity ≥10-4) increased from 14% to 58%. Conclusions. Nilotinib combined with low-intensity chemotherapy is well tolerated and highly effective in elderly pts. with Ph-positive ALL. OS and EFS compare favorably with previous similar studies testing imatinib or dasatinib. With 32% of pts. undergoing allogeneic HSCT and 61% survival at 4 years, transplantation is a viable option in this elderly cohort of pts.. Disclosures Ottmann: Celgene: Consultancy, Research Funding; Novartis: Consultancy; Incyte: Consultancy, Research Funding; Takeda: Consultancy; Amgen: Consultancy; Pfizer: Consultancy; Fusion Pharma: Consultancy, Research Funding. Pfeifer:Novartis: Research Funding. Cayuela:Cepheid: Other: financial sponsor to attend John Goldman Conference 2017. Viardot:Roche: Consultancy, Honoraria; Amgen: Consultancy; Gilead Kite: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Sanhes:Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Goekbuget:Pfizer: Consultancy, Other: Travel support, Research Funding; Novartis: Consultancy, Other: Travel support, Research Funding; Celgene: Consultancy; Kite / Gilead: Consultancy; Amgen: Consultancy, Other: Travel support, Research Funding. Dombret:Jazz Pharma: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Menarini: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Sunesis: Consultancy, Honoraria; Ambit (Daiichi Sankyo): Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Agios: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Abbvie: Consultancy, Honoraria; Roche/Genentech: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Ariad (Incyte): Consultancy, Honoraria, Other: Travel expenses, Research Funding, Speakers Bureau; Shire-Baxalta: Consultancy, Honoraria; Immunogen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Other: Travel expenses, Speakers Bureau; Cellectis: Consultancy, Honoraria, Other: Travel expenses; Otsuka: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Other: Travel expenses, Research Funding, Speakers Bureau.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2018-99-114552

Language: English

Publisher: American Society of Hematology

Publication Date: 2018

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 2603-2603

Abstract: Abstract 2603 Purpose Although CBF-AML (i.e. with t(8;21) or inv(16)/t(16;16)) represents a favorable cytogenetic AML subgroup (Döhner, Blood 2010), 35–45% of these patients still relapse after standard intensive chemotherapy. The immunoconjugate gemtuzumab ozogamicin (GO) was shown to be effective in patients with relapsed AML in non randomized studies and has been recently demonstrated in a Phase 3 trial as associated with a significant benefit in younger adults with CBF-AML (Burnett, JCO 2011). In this study, we thus investigated the impact of GO-based salvage at first relapse in this specific subgroup of patients with CBF-AML. Patients and Methods We retrospectively analysed the medical records of 84 patients aged 60 years or less with CBF-AML in first relapse after intensive chemotherapy and treated in 18 French centers. None of these patients received allogeneic (alloSCT) or autologous (autoSCT) hematopoietic stem cell transplantation in first complete remission (CR). As salvage, 27 patients received GO, combined with high-dose cytarabine in most of them; 21 patients received high-dose cytarabine and anthracycline without GO; 36 patients received conventional chemotherapy based on standard-dose cytarabine and anthracycline. Post-remission therapy was alloSCT in 49 patients, autoSCT in 17 patients, and chemotherapy alone in 11 patients. Results Among 84 patients with a median age of 39 years [16–58], 36 patients had t(8;21) AML and 48 patients had inv(16)/t( 16;16) AML. Median CR1 duration was 12.9 months [2.6–55.3]. Second complete remission (CR2) rate was 92% (77/84), and early death rate was 1% (1/84). The median follow up was 4.0 years. The 5-year overall survival (5y-OS) and relapse-free survival (5y-RFS) was 52% [39–64%] and 48% [36–60%] respectively. Patients receiving alloSCT in CR2 had a better outcome (5y-OS, 56% versus 43%; p=0.05). In patients not allografted in CR2, RFS was similar after autoSCT and chemotherapy alone (5y-RFS, 44% versus 47%, respectively). Patients treated with GO had similar CR rate but a lower risk of second relapse and a better survival than other patients (5y-RFS, 89% versus 55%; p=0.05 and 5y-OS, 90% versus 45%; p=0.03). In univariate analysis, other factors associated with a better OS were younger age, longer CR1 duration, but not CBF subtype (p=0.03, 0.01, and 0.20, respectively). In multivariate analysis adjusted on age, CR1 duration, and CBF subtype, GO salvage was still associated with a significant benefit in OS (HR=0.16 [0.04–0.69] , p=0.01) and RFS (HR=0.19 [0.04–0.80], p=0.02). With a median post-relapse follow-up of 2.2 years, no relapse nor death were observed in the 19 patients who received GO salvage followed by alloSCT in CR2 (p=0.007 for RFS; p=0.008 for OS). Moreover, in patients who received alloSCT, previous GO therapy significantly improved post-transplantation outcome. Conclusion Younger patients with CBF-AML in first relapse had a high second complete remission rate regardless the intensive chemotherapy salvage. More interestingly, the outcome of these patients was significantly improved by the addition of GO-based salvage, especially when followed by alloSCT. Disclosures: Off Label Use: GO is available in Europe as a compassionate treatment for relapsed AML.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V118.21.2603.2603

Language: English

Publisher: American Society of Hematology

Publication Date: 2011

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Journal de Mycologie Médicale, Elsevier BV, Vol. 27, No. 3 ( 2017-09), p. e26-e27

Type of Medium: Online Resource

ISSN: 1156-5233

URL: Article

DOI: 10.1016/j.mycmed.2017.04.062

Language: French

Publisher: Elsevier BV

Publication Date: 2017

detail.hit.zdb_id: 2049532-8

SSG: 12

In: American Journal of Hematology, Wiley, Vol. 90, No. 9 ( 2015-09), p. 811-818

Abstract: Purpose : The GRASPALL/GRAALL‐SA2‐2008 Phase II trial evaluated the safety and efficacy of L‐asparaginase encapsulated within erythrocytes (GRASPA®) in patients ≥ 55 years with Philadelphia chromosome‐negative acute lymphoblastic leukemia. Findings : Thirty patients received escalating doses of GRASPA ® on Day 3 and 6 of induction Phases 1 and 2. The primary efficacy endpoint was asparagine depletion  〈  2 µmol/L for at least 7 days. This was reached in 85 and 71% of patients with 100 and 150 IU/kg respectively but not with 50 IU/kg. Grade 3/4 infection, hypertransaminasemia, hyperbilirubinemia and deep vein thrombosis occurred in 77, 20, 7, and 7% of patients, respectively. No allergic reaction or clinical pancreatitis was observed despite 17% of Grade 3/4 lipase elevation. Anti‐asparaginase antibodies were detected in 50% of patients and related to a reduction in the duration of asparagine depletion during induction Phase 2 without decrease of encapsulated L‐asparaginase activity. Complete remission rate was 70%. With a median follow‐up of 42 months, median overall survival was 15.8 and 9.7 months, in the 100 and 150 IU/kg cohorts respectively. Conclusions : The addition of GRASPA ® , especially at the 100 IU/kg dose level, is feasible in elderly patients without excessive toxicity and associated with durable asparagine depletion. ( clinicaltrials.gov identifier NCT01523782). Am. J. Hematol. 90:811–818, 2015. © 2015 Wiley Periodicals, Inc.

Type of Medium: Online Resource

ISSN: 0361-8609 , 1096-8652

URL: Issue

URL: Article

DOI: 10.1002/ajh.v90.9

DOI: 10.1002/ajh.24093

Language: English

Publisher: Wiley

Publication Date: 2015

detail.hit.zdb_id: 1492749-4