Monitoring of 1,3-Beta-D-Glucan (BGL) Antigenemia in Neutropenic Patients with Acute Leukemia at High Risk for Invasive Fungal Infections (IFI).

Abstract Invasive candidiasis (IC) and aspergillosis (IA), the most frequent IFI in leukemic patients, are associated with high morbidity and mortality. As early diagnosis of IFI is difficult, empirical antifungal therapy is recommended in persistently febrile neutropenic patients. This standard of care results in a broad use of antifungals. New non-invasive diagnostic tests such as circulating BGL, a fungal cell wall component, are thus needed to optimize management of patients with IFI. The objective of the current study was to evaluate the utility of monitoring BGL antigenemia in neutropenic patients at high risk for IFI. We conducted a prospective study of 189 episodes of neutropenia (median duration 22 days, range 7–113) following induction (n=107) or consolidation chemotherapy (n=82) in 99 consecutive patients with acute leukemia (85 AML, 14 ALL). Blood was collected 2× weekly before onset of fever and daily thereafter until resolution of fever. BGL was measured by colorimetric assay (Wako, Japan). Two cut-off values (5 or 11 pg/ml) were studied. A positive result was defined by 2 consecutive samples with BGL higher than the cut-off value. A median of 2 (0–4) febrile episodes occurred per neutropenic episode. Among 320 febrile episodes, 31 IFI were diagnosed according to EORTC-MSG criteria: 17 IC (4 proven, 13 probable) and 14 IA (5 proven, 9 probable). A median of 15 samples (4–47) per episode of neutropenia were analyzed over a median period of 34 days (19–121). The diagnostic performance of BGL was evaluated in patients with proven or probable IFI compared with febrile patients without IFI (Table). In patients with IC, the median time between onset of fever as first sign of IFI and BGL positivity (>= 5) was 0 (−3 to 17 days) as compared with 16 (0 to 51 days) until diagnosis of infection using conventional microbiological and imaging techniques (p=0.03). In IA patients, it was 3 (−9 to 14 days) vs. 7 (1 to 21 days) (p=0.07). In IC and IA, median peak BGL (21 [6–111] and 15 [7–51] pg/ml) occurred on day 13 (1 to 41) and on day 7 (3 to 20) after fever onset, respectively. Median time to initiation of antifungal therapy after fever onset was similar in IC (2.5, range: 1 to 10 days) and IA (5, range: 0 to 10 days). BGL antigenemia decreased or cleared in patients responding to therapy (n=19) and continued to increase (peak 111 and 66 pg/ml) in 2 cases of IC, in whom therapy failed. BGL was negative (< 5 pg/ml) in 100/102 episodes of bacteremia. In conclusion, monitoring of 1,3-beta-D-glucan antigenemia provides a new tool for early diagnosis and follow-up of IFI in neutropenic patients with acute leukemia. Diagnostic Performance of BGL BGL Cut-off (pg/ml) 2 × 5 2 × 5 2 × 5 2 × 11 2 × 11 2 × 11 Type of proven/probable IFI IC IA All IFI IC IA All IFI Sensitivity % 65 93 76 35 43 38 Specificity % 89 89 89 99 99 99 PPV % 48 52 65 86 86 92 NPV % 94 99 93 91 93 86 Positive Likelihood Ratio 5.9 8.5 6.9 35 43 38 Negative Likelihood Ratio 0.4 0.1 0.3 0.7 0.6 0.6

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Validation of scoring systems and (1, 3)-beta-D-glucan assay for early diagnosis of invasive candidiasis in high-risk non-neutropenic patients in Siriraj Hospital: a prospective cohort study

10.26226/morressier.56d6be7cd462b80296c958d4 ◽

2016 ◽

Author(s):

Supitcha Ongkittikul

Keyword(s):

Cohort Study ◽

High Risk ◽

Early Diagnosis ◽

Prospective Cohort Study ◽

Invasive Candidiasis ◽

Prospective Cohort ◽

Scoring Systems ◽

Siriraj Hospital ◽

Neutropenic Patients

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Busulfan (Bu) in Combination with Double Nucleoside Analogues Fludarabine (Flu) and Clofarabine (Clo) Plus Vorinostat As a Novel Reduced Toxicity Conditioning Regimen for Allogeneic Hematopoietic Cell Transplantation (HCT) in Patients (pts) with Acute Leukemia

Blood ◽

10.1182/blood.v128.22.64.64 ◽

2016 ◽

Vol 128 (22) ◽

pp. 64-64

Author(s):

Partow Kebriaei ◽

Wei Wei ◽

Peter F Thall ◽

Celina Ledesma ◽

Benigno C. Valdez ◽

...

Keyword(s):

High Risk ◽

Acute Leukemia ◽

Disease Control ◽

Median Time ◽

Acute Gvhd ◽

Conditioning Regimen ◽

Nucleoside Analogues ◽

Unrelated Donor ◽

Equity Ownership

Abstract The combination of IV Bu and Flu is an effective and well-tolerated HCT conditioning regimen for patients with advanced acute leukemia. However, relapse remains the main reason for treatment failure. We combined two nucleoside analogues Flu and Clo, and showed cytotoxic synergy when combined with Bu, first in pre-clinical models, and subsequently in a randomized clinical study (Andersson BBMT 2011). We selected the optimized regimen from Andersson et al, and combined with escalating doses of the histone deacetylase inhibitor vorinostat in attempts to augment disease control without increasing toxicity. Herein, we describe our initial experience with this novel regimen for patients with advanced acute leukemia or MDS undergoing allogeneic HCT. Methods: Vorinostat (200mg to 1200mg) was escalated in cohorts of 3 patients, and administered 1 hour prior to the fixed regimen of Flu 10 mg/m2 followed by Clo 40 mg/m2 followed by Bu. The nucleoside analogs were infused over 1 hour once daily for 4 days, followed on each day by Bu, infused over 3 hours to a pharmacokinetically targeted daily area under the curve (AUC) of 5500 μMol-min ± 5%. Dilantin was given for seizure prophylaxis. GVHD prophylaxis was based on tacrolimus andmini-MTX, with the addition of rabbit anti-thymocyte globulin (4 mg/kg total dose) for unrelated donor transplants. The presence of minimal residual disease (MRD) was determined by multiparameter flow cytometry. Results: 21 patients (7 AML, 14 ALL) with median age 43 years (range 19-60) received an allogeneic matched sibling (n=10) or unrelated donor (n=11) HCT in CR1 (n=13), CR2 (n=1), primary induction failure (n=5), or relapse (n=2). Twelve patients had MRD or overt disease present at time of HCT. Ten patients had high-risk karyotype defined by t(9;22) (n=3), t(4;11) (n=2), complex (n=2), or del 5 or 7 (n=3). Median time from diagnosis to HCT was 5 months (range 3-48). Median time to ANC > 0.5 x 109/L and platelets > 20 x 109/L were 11 (range 10-15) and 12 days (5-30), respectively. Excluding grade 1 toxicities, the most commonly reported toxicities were nausea with maximum grade 2 (71%), followed by grade 2 or 3 mucositis (64%). Grade 2 or 3 reversible elevation of liver function tests was noted in 54% of pts, including 1 case of reversible VOD. No renal toxicities were noted. Two patients with prior systemic treatment for acute GVHD died of infections (disseminated adenovirus and E.coli sepsis). Ten patients achieved CR and clearance of MRD by day +30 after HCT; one patient had progressive disease and on patient died before disease restaging. Eighteen patients achieved 100% donor chimerism at 30 days following HCT, 2 patients remain with mixed chimerism by 100 day assessment following HCT, and 1 patient died before assessment. The incidence of grades II-IV acute GVHD is 43% and chronic extensive GVHD among 18 evaluable patients is 24%. With a median follow-up of 10 months among surviving patients (1-22), overall and progression-free survival at 6 months is 95% and 71%, respectively. Early results suggest excellent disease control in MRD negative patients (Figure). Conclusion: The Vorinostat-Flu-Clo-Bu combination is well-tolerated and did not add appreciable toxicity in these patients with high-risk leukemia. Longer follow-up is needed to better assess disease control. Figure Figure. Disclosures Ciurea: Spectrum Pharmaceuticals: Other: Advisory Board; Cyto-Sen Therapeutics: Equity Ownership. Patel:Ziopharm Oncology: Equity Ownership, Patents & Royalties; Intrexon: Equity Ownership, Patents & Royalties.

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Pilot Study on Septifast PCR for the Early Diagnosis of Invasive Fungal Infections in Neutropenic Patients with Acute Leukemia

International Journal of Infectious Diseases ◽

10.1016/s1201-9712(08)60077-6 ◽

2008 ◽

Vol 12 ◽

pp. S32

Author(s):

Frederic Lamoth ◽

Katia Jaton-Ogay ◽

Jacques Bille ◽

Guy Prodhom ◽

Laurence Senn ◽

...

Keyword(s):

Pilot Study ◽

Early Diagnosis ◽

Acute Leukemia ◽

Fungal Infections ◽

Invasive Fungal Infections ◽

Neutropenic Patients

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Antifungal Therapy in Neutropenic Oncohemopatic Patients. A Single Centre Retrospective Analysis.

Blood ◽

10.1182/blood.v106.11.5334.5334 ◽

2005 ◽

Vol 106 (11) ◽

pp. 5334-5334

Author(s):

Alessandro Bonini ◽

Alessia Tieghi ◽

Simona Bulgarelli ◽

Luigi Gugliotta

Keyword(s):

High Risk ◽

Adverse Events ◽

Renal Insufficiency ◽

Acute Leukemia ◽

Fungal Infection ◽

Amphotericin B ◽

Antifungal Therapy ◽

Secondary Prophylaxis ◽

Antifungal Treatment ◽

Empiric Treatment

Abstract Infections are the most frequent complication during chemotherapy-induced neutropenia and fungal infections are a cause of morbility and mortality. We have retrospectively analysed our patients who received an antifungal treatment for a possible, probable or proven fungal infection. Between April 1998 and July 2005 we analysed 750 consecutive phases of treatment for 309 patients admitted at our Institution. The treatment phases were for: acute leukemia 253, lymphoma 168, multiple myeloma 215, chronic leukemia 19, severe aplastic anemia 12, solid tumors (breast, renal, testis cancer) 44, multiple sclerosis 5, others 34. Among them 474 (63.2%) were at high risk for infections (the risk was considered high for lenght of neutropenia, diagnosis of acute leukemia, allogeneic BMT). There were 31 allo-BMT and 145 autologous BMT. The antifungal therapy was for a first short period (until mid-1999) an empirical treatment (when fever persisted more than 4 days despite antibiotic therapy during neutropenia); after, only when another sign (clinical or radiological or microbiological) of fungal infection was present, the patients received an antifungal treatment. We treated also a small cohort of patients with a secondary prophylactic regimen (they were patients who developed a fungal infection during a previous treatment). Seventy-four patients received an antifungal treatment (10% of all phases and 15.6% of high-risk phases). The infection was possible (empiric treatment) in 4 cases, probable (presumptive therapy) in 37 cases, proven in 16 cases; 17 cases of secondary prophylaxis. The first administered drug was Amphotericin B deoxycholate (AMB) in 31/74 cases (41.9%), Abelcet (ABCT) in 6/74 (8%), Liposomal Amphotericin B (LAMB) in 18/74 cases (24.4%), Voriconazole (VCZ) in 3/74 cases (4%) and Caspofungin (Caspo) in 16/74 cases (21.7%). The schedule of treatment was: AMB 0.7–1 mg/Kg in 6 hours, ABCT 5 mg/Kg in 3 hours, LAMB 3 mg/Kg in 1 hour, VCZ 6 mg/Kg bid iv in 2 hours for 3 days then 4 mg/Kg bid orally, Caspo 70 mg iv on the first day and then 50 mg in 1 hour. For the empiric treatment the first drug was AMB 3 and Caspo 1; for presumptive therapy AMB 18, ABCT 4, LAMB 4, VCZ 1 and Caspo 10. For proven infections AMB 8, ABCT 1, LAMB 5, VCZ 1, Caspo 1; for secondary prophylaxis AMB 2, ABCT 1, LAMB 9, VCZ 1 and Caspo 4. The isolated fungi were Candida albicans 4, Aspergillus spp 4, Scedosporium 2, Fusarium solani 1, others (only histological isolation) 5. The days of treatment were 7.64 for AMB, 6.88 for ABCT, 14.22 for l-AMB, 14.1 for Caspo and 30 for VCZ. Adverse events with AMB and ABCT were similar: mild to moderate renal insufficiency (50%), fever (50%), ipokalemia (75%), chills (30%); with VCZ visual disturbances (80%) and mild hepatic insufficiency (20%); with LAMB mild renal insufficiency (10%) and low back pain (5%); no adverse events with Caspo were noted. AMB was discontinued 9/31 times (29%), ABCT 1/6 (17%) for adverse events. Our conclusions are that AMB and ABCT are problematic drugs for their poor tolerability, they need an important premedication, a hyperhydration regimen and a long-time administration; moreover for a great cohort of patients we have had to discontinue the drug. The other drugs seems to be better tolerated; no organ failures were seen and the treatment duration was longer for Caspo and LAMB. Even if the cost of these two drugs is major than others the lack of adverse events and the new mechanism of action of Caspo make these drugs probably better than ABCT, AMB and VCZ.

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Galactomannan and Computed Tomography-Based Preemptive Antifungal Therapy in Neutropenic Patients at High Risk for Invasive Fungal Infection: A Prospective Feasibility Study

Clinical Infectious Diseases ◽

10.1086/496927 ◽

2005 ◽

Vol 41 (9) ◽

pp. 1242-1250 ◽

Cited By ~ 432

Author(s):

J. Maertens ◽

K. Theunissen ◽

G. Verhoef ◽

J. Verschakelen ◽

K. Lagrou ◽

...

Keyword(s):

Computed Tomography ◽

High Risk ◽

Fungal Infection ◽

Feasibility Study ◽

Antifungal Therapy ◽

Invasive Fungal Infection ◽

Neutropenic Patients

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Classical Empiric Antifungal Therapy Vs. D-Index Guided Early Therapy Using Micafungin for Persistent Febrile Neutropenia (CEDMIC trial): A Randomized Controlled Trial from Japan FN Study Group

Blood ◽

10.1182/blood-2018-99-111154 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 816-816

Author(s):

Shun-Ichi Kimura ◽

Yoshinobu Kanda ◽

Masaki Iino ◽

Takahiro Fukuda ◽

Emiko Sakaida ◽

...

Keyword(s):

High Risk ◽

Febrile Neutropenia ◽

Fungal Infection ◽

Antifungal Therapy ◽

Invasive Fungal Infection ◽

Research Funding ◽

Controlled Trial ◽

Pharmaceutical Research ◽

Randomized Controlled ◽

Neutropenic Patients

Abstract Introduction: Empiric antifungal therapy (EAT) is recommended for persistent or recurrent febrile neutropenia based on an old randomized controlled trial, but such treatment is apparently overtreatment for the majority of patients. On the other hand, preemptive therapy triggered by positive blood tests for fungal antigens and/or imaging study findings was shown to increase the incidence of invasive fungal infection, and thus, a risk-based approach is important. The D-index, which is defined as the area over the neutrophil curve during neutropenia and hence reflects both the duration and depth of neutropenia (Figure 1A), enables real-time monitoring of the risk of invasive fungal infection. Previous studies showed that the cumulative D-index (c-D-index), which was calculated as cumulative D-index from the onset of neutropenia (Figure 1B), had high negative predictive values for invasive mold infection or pulmonary infection with cutoff values of 5,800 or 5,500 in high-risk neutropenic patients [J Clin Oncol 2009; 27: 3849-54. Biol Blood Marrow Transplant 2010; 16: 1355-61]. Methods: We investigated a novel approach, called D-index-guided early antifungal therapy (DET) and compared it to EAT in high-risk neutropenic patients. In the EAT group, empiric antifungal therapy was started for persistent (>=4 days) or recurrent febrile neutropenia. For patients with persistent or recurrent febrile neutropenia in the DET group, preemptive antifungal therapy was applied until c-D-index reached 5,500, but antifungal agent was initiated after c-D-index exceeded 5,500, even if there was no significant finding in serum fungal makers or imaging studies, to prevent excessive invasive fungal infection. Micafungin at 150 mg/day was administered as EAT or DET in this study. We randomized 423 patients who underwent chemotherapy or hematopoietic stem cell transplantation for hematological malignancies, in which predicted period of neutropenia exceeded 7 days, into the EAT group or the DET group, and 413 were eligible for intent-to-treat analyses (201 patients in the EAT group, 212 patients in the DET group). The prophylactic use of fluconazole or itraconazole was allowed. Primary endpoint was the development of proven/probable invasive fungal infection. Results: Backgrounds of the patients were similar between the 2 groups (Table 1). Invasive fungal infection (proven/probable/possible) was observed in 12 patients (6.0%) of the EAT group and 5 patients (2.4%) of DET group, respectively. Proven/probable invasive fungal infection was identified in 5 patients (2.5%) of the EAT group and 1 patient (0.5%) of DET group, which fulfilled the predetermined criteria of non-inferiority of the DET group. Regarding the pathogens, the EAT group included 1 case of candidemia and 4 cases of invasive pulmonary aspergillosis, and the DET group included one fusariosis. The survival rate of the EAT and DET group was 98.0% vs. 98.6% at day 42 and 96.4% vs. 96.2% at day 84, respectively. During the observation period, 31 patients died due to disease progression (n=19), infection (n=5) or other causes (n=7). Causes of infection related mortality included Pseudomonas aerginosa infection (n=2), fusariosis (n=1), toxoplasmosis (n=1) and septic shock by unknown pathogen (n=1). The frequency of micafungin use was significantly lower in the DET group than the EAT group (32.5% vs. 60.2%, P<0.001). Similar results were obtained in per-protocol set analyses. Conclusions: DET successfully reduced the use of antifungal agents without increasing invasive fungal infection or mortality compared to EAT. This randomized controlled study revealed the feasibility of DET in high-risk neutropenic patients. Disclosures Kimura: Astellas: Honoraria; Pfizer: Honoraria; Sumitomo Dainippon Pharma: Honoraria; MSD: Other: Investigator in the institute; Nippon Kayaku: Honoraria; Celgene: Honoraria; Kyowa Hakko Kirin: Honoraria; Takeda: Honoraria. Kanda:Chugai: Consultancy, Honoraria, Research Funding; Shionogi: Consultancy, Honoraria, Research Funding; Nippon-Shinyaku: Research Funding; Ono: Consultancy, Honoraria, Research Funding; MSD: Research Funding; Pfizer: Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria; CSL Behring: Research Funding; Kyowa-Hakko Kirin: Consultancy, Honoraria, Research Funding; Asahi-Kasei: Research Funding; Tanabe-Mitsubishi: Research Funding; Novartis: Research Funding; Astellas: Consultancy, Honoraria, Research Funding; Eisai: Consultancy, Honoraria, Research Funding; Otsuka: Research Funding; Dainippon-Sumitomo: Consultancy, Honoraria, Research Funding; Sanofi: Research Funding; Taisho-Toyama: Research Funding; Taiho: Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria; Mochida: Consultancy, Honoraria; Alexion: Consultancy, Honoraria; Takara-bio: Consultancy, Honoraria. Fujiwara:Shire: Consultancy; Pfizer: Consultancy; Chugai: Consultancy; Kirin: Consultancy; Kyowa-Hakko: Consultancy; Astellas: Consultancy. Suzumiya:Celltrion: Research Funding; Taiho: Research Funding, Speakers Bureau; SymBio: Research Funding; Toyama Chemical: Research Funding; Takeda: Research Funding, Speakers Bureau; Eisai: Research Funding, Speakers Bureau; Chugai-Roche: Research Funding, Speakers Bureau; Kyowa Hakko Kirin: Research Funding, Speakers Bureau; Zenyaku Kogyo: Consultancy; Abbvie: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Pfizer: Research Funding; Sumitomo Dainioppon: Research Funding, Speakers Bureau; Astellas: Research Funding, Speakers Bureau; Bristol Myers Squibb: Speakers Bureau; Nippon Shinyaku: Speakers Bureau; Ono: Speakers Bureau; Ohtsuka: Speakers Bureau; Shire Japan: Speakers Bureau. Takamatsu:Taisho Toyama Pharmaceutical: Research Funding; TAIHO Pharmaceutical: Research Funding; Pfizer: Research Funding; Bristol-Myers Squibb: Research Funding; Ono Pharmaceutical: Research Funding; Astellas Pharma: Research Funding; Kyowa Hakko Kirin: Research Funding; Chugai Pharma: Research Funding; Takeda Pharmaceutical: Research Funding; Celgene: Honoraria. Tamura:Astellas Phrma: Research Funding; Eisai: Speakers Bureau; Kyowa Hakko Kirin: Speakers Bureau; Ono Pharmaceutical: Speakers Bureau.

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Phase II Prospective Multicentre Study Testing The Efficacy and Safety Of a Clofarabine (Clo), I.v. Busulfan (Bu) and Antithymocyte Globulins (ATG)-Based Reduced-Intensity Conditioning Regimen (RIC) Before Allogeneic Stem Cell Transplantation (allo-SCT) For High-Risk Myelodysplastic Syndrome Or Acute Leukemia: The Cloric Trial

Blood ◽

10.1182/blood.v122.21.413.413 ◽

2013 ◽

Vol 122 (21) ◽

pp. 413-413

Author(s):

Patrice Chevallier ◽

Myriam Labopin ◽

Gérard Socié ◽

Stephane Vigouroux ◽

Sabine Furst ◽

...

Keyword(s):

High Risk ◽

Acute Leukemia ◽

Myelodysplastic Syndrome ◽

Median Time ◽

Multicentre Trial ◽

Conflicts Of Interest ◽

Single Case ◽

Lymphoblastic Leukemia ◽

Conditioning Regimen ◽

Prospective Comparison

Abstract Introduction Clofarabine (Clo) is a purine analogue which was developed to overcome limitations and to incorporate the favorable pharmakokinetic properties of fludarabine and cladribine. This agent has also a significant antileukemic activity. Thus, can one exploit both the antileukemic and immunosuppressive effects of Clo for further improving outcome after RIC allo-SCT for patients with high-risk myelodysplastic syndrome (MDS) or acute leukemia. Here we report the results of a prospective multicentre trial testing the use of Clo in replacement of fludarabine in combination with i.v. Busulfan (Bu) and ATG in 30 patients with high-risk MDS/acute leukemia (clinicaltrials no. NCT00863148). Patients and Methods Thirty patients (male n=18, female n=12) from 6 centres were included in this study between October 2009 and August 2012. Sixteen patients were diagnosed with high-risk MDS (n=5) or acute myeloid leukemia (AML, n=11), while 13 patients had high-risk acute lymphoblastic leukemia (ALL, Ph+ n= 2, Ph- n=11) and 1 patient a biphenotypic leukemia. All patients were in first (AML/MDS, n= 10; ALL/biphenotypic n=10) or second (AML n= 3; ALL n= 4) complete remission, or in stable disease (MDS n=3) at time of transplant. Median age at transplant was 58.8 years (range: 20.5-64.5). The median interval between diagnosis and transplant was 6 months (range: 3.8-124). Karnofsky’s performans status at transplant was: 100% (n=19); 90% (n=6); and 80% (n=4).The RIC regimen consisted of: i.v. Clo 30 mg/m²/day for 4 days (day-8 to day-5), i.v. Bu 3.2 mg/Kg/day for 2 days (day-4 and day-3) and ATG (Thymoglobuline) 2.5 mg/kg/day for 2 days (day -2 and day-1). All patients received G-CSF-mobilized PBSCs and cyclosporine alone for GVHD prophylaxis, irrespective of the type of donor (sibling donors n=14; 10/10 MUD, n=16). For the purpose of this study, the single case of binephotypic leukemia was considered as ALL for comparison between AML/MDS and ALL patients. The primary endpoint of the trial was the assessment of leukemia-free survival (LFS) at one year after allo-SCT. Results Engraftment was observed in all patients (100%). Median time for neutrophils (>500 /µL) and platelets (>50.000/µL) recovery was 18 (range: 14-26) and 12 (range: 0-23) days, respectively. With a median follow-up of 23 months (range: 12-37), the 1-year and 2-year overall survival (OS), leukemia-free survivals (LFS), relapse incidence (RI) and non relapse mortality (NRM) rates were 63±9% and 58+-10%, 57±9% and 53+-9%, 40±9% and 44+-9%, and 3.3±3% and 3.3±3%, respectively. Thirteen patients relapsed (43%) at a median time of 3.5 months (range: 2.3-13.1) after allo-SCT. Overall, 13 patients died, with the cause of death being relapse in 11 and GVHD in 2 (including one after donor lymphocyte injection). 1-year and 2-year OS were significantly higher for AML/MDS patients compared to ALL patients (75±10% vs 50±13%, and 75±10% vs 37±14%, p=0.04). There were trends for higher 1-year and 2-year LFS (69±12% vs 43±13%, and 69±12% vs 34±13%, p=0.08) and lower RI (57±14% vs 25±11%, and 66±14% vs 25±11%, p=0.05) for AML/MDS patients compared to ALL patients. Finally, 1-year and 2-year NRM were similar between both groups (AML/MDS: 6±6% vs 0%, p=0.36). Conclusion This phase 2 prospective multicentre trial shows that a Clo-i.v. Bu-ATG RIC regimen prior to allo-SCT in high-risk MDS/leukemia is feasible allowing for full engraftment and very low toxicity. Disease control appears to be satisfactorily, especially in AML/MDS, warranting a prospective comparison with other widely used fludarabine-based RIC regimens (e.g. Fludarabine, i.v. Bu, ATG versus Clo, i.v. Bu, ATG). Genzyme/Sanofi provided clofarabine and financial support for the study. Disclosures: No relevant conflicts of interest to declare.

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