ALBERT

Description: Introduction. AML standard intensive induction chemotherapy ("3+7" or equivalent) combined with wide spectrum antibiotics can dramatically alter the composition of the gut microbiota, leading to dysbiosis which is characterized by loss of microbial diversity. Such dysbiosis status can promote a pathological condition involving uncontrolled local immune responses, systemic inflammation and increased incidence of adverse events. The development of FMT-based drugs to restore microbial communities could offer novel therapeutic possibilities to reduce such adverse events and potentially improve outcomes in AML. We therefore conducted this single arm prospective phase I/II multicenter trial (NCT02928523) to evaluate the use of a FMT-based drug in association with AML induction treatment to restore the gut microbiota diversity. Patients and methods. A total of 62 consecutive patients aged between 24 and 69 years old with a diagnosis of de novo AML were screened in 7 French sites. At time of admission and AML diagnosis (Step 1=S1), patients' faeces were collected, rigorously screened, prepared following a standardized process, and stored at -80°C until later administration. The drug was administered as an enema after hematopoietic recovery (S2) and before consolidation chemotherapy (Conso). The primary endpoint was the recovery of at least 70% of microbiota diversity (based on the Simpson index) after drug administration and the reduction of multidrug resistant bacteria carriage. Blood and feces samples were collected at S1, S2, and around 10 days post-FMT before Conso (S3). Microbiome diversity restoration was assessed by metagenomics analysis through Illumina HiSeq shotgun sequencing. Antibiotic resistance gene carriage (ARGC, also known as resistome) was evaluated through mapping of readouts on the MEGARES database. Secondary objectives included safety and analysis of host response with assessment of blood and fecal markers by ELISA and Luminex. Results. Overall, 25 patients were actually treated with FMT, and 20 were included in the per-protocol population. Induction Chemotherapy (IC) induced a dramatic shift in microbial communities, with a significant 42.3% decrease of mean α-diversity Simpson index between S1 and S2 at species level (0.85 to 0.50; p

Description: Abstract 3996 Background: AZA significantly improves OS in higher-risk MDS (including RAEB-t/AML) compared to conventional treatments (AZA 001 trial, Lancet Onc, 2009), but prognostic factors of response and OS to AZA remain largely unknown. We designed a prognostic score for OS in a cohort of AZA treated higher-risk MDS in a patient-named compassionate program (French ATU), and validated it in patients from the AZA 001 trial. Methods: Between Sept 2004 and Jan 2009, prior to AZA approval in Europe, IPSS int-2/high risk MDS (including RAEB-t) not previously treated with intensive chemotherapy (IC), allo SCT, or a hypomethylating agent were included in a compassionate program (ATU), and received AZA (planned schedule 75 mg/m2/d ×7 d every 28 d for ≥4 cycles). Independent prognostic factors of OS were individualized in a Cox model. A prognostic score was then developed based on those factors. After validation of the score as a continuous variable, pts were grouped in three distinct risk categories. We subsequently tried to validate this score in the 175 higher risk MDS pts treated with AZA at the same schedule in AZA 001 trial (4 of the 179 pts randomized to AZA in that trial did not start AZA). Results: The ATU cohort included 282 pts with de novo (74%) or therapy related (t) (26%) higher-risk MDS (IPSS int-2 in 54% high in 43%, at least int-2 in 2%). ECOG PS ≥2, RBC transfusion dependence ≥4 units/8 weeks and circulating blasts were present in 21%, 46% and 46% of pts respectively (resp). Cytogenetic risk was good, int, and poor in 31%, 17% and 47% (unknown in 5%). 10% pts had previously been treated with LD araC for their MDS. Multivariate analysis of survival retained PS ≥2 (HR= 2.0 [95% CI: 1.4–2.9]), RBC transfusion dependence ≥4 units/8 weeks (HR=1.9 [1.4-2.6]), presence of circulating blasts (HR=2.0 [1.5-2.7]), and IPSS cytogenetic risk (intermediate: HR=1.4 [0.8-2.3], poor: HR=3.0 [2.0-4.3]) as independent prognostic factors (all p

Description: Abstract 843 Background: AZA prolongs survival in higher-risk MDS including patients (pts) with 20-29 % marrow blasts, now considered WHO-AML ( Lancet Onc, 2009). However, no large AML cohorts (especially with '30% marrow blasts) treated upfront with AZA have been reported. Methods: An AZA compassionate program (ATU) was initiated in France in Dec 2004 for higher risk MDS, and AML considered not candidates or refractory to intensive chemotherapy (IC). We retrospectively analyzed WHO AML pts having received at least 1 cycle of AZA in the 42 centers with complete pt reporting, excluding those previously treated by IC, allo SCT, low dose AraC or a hypomethylating agent. Results: 138 pts were included between Dec 2004 and Dec 2008; M/F: 86/52; median age 73 years (y) (range 31-87), 117 pts (85%) were 〉 65 y and 54 (40%) 〉75y. 65 pts (47%) had prior WHO MDS and 30 pts (22%) therapy related (tAML). 44 pts (32%) had 20-29% marrow blasts. Median WBC was 3.0 G/L [0.8-111.5]. Karyotype (MRC classification), was intermediate (int) in 60 pts,( including 38 normal (NK), and 7 isolated +8 ) adverse in 67 pts (including 42 -7/ del7q, 41 del5q/-5, 45 complex karyotype, two 3q26) and failed in 11 pts. With a median follow-up of 11.3 months, pts received a median of 4.5 AZA cycles (range 1-26). Treatment was according to FDA-EMEA approved schedule for MDS in 95 pts (69%) and a less intensive schedule (5d/4w, or 10 G/L (32 pts in our cohort) carried poorer prognosis ( 1 y OS of 27% vs 44% ,p=0.01); NK had better OS (1-y OS: 66%) than adverse cytogenetics (1-y OS: 30%, p=0.01) but also other “intermediate-risk” abnormalities (1-y OS: 30%, p=0.03). Marrow blast % did not influence OS and survival, whatever the cut off chosen. In particular, pts with 20-29 % marrow blasts had 22% AML response and 1 y OS of 50%, compared to 21% and 1 y OS of 35%, respectively, in pts with 〉30% marrow blasts (p=NS and NS, respectively). Prior MDS also had no influence on survival. Overall, 33 pts required hospitalization during treatment, mainly for neutropenic fever. A landmark analysis at the time of evaluation showed that achievement of CR, CRi or PR was associated with improved OS (1y-OS 55% vs 31%,p=0.007). In pts with no AML-IWG response, however, achievement of HI also predicted better survival: 1 y-OS 55% vs 19 %, p=0.02. In the 54 pts older than 75 y (ie pts generally considered unfit for IC), 12 (22%) had AML response including CR in 9 (17%) and 3 PR (5%). 1y-OS was 41 % vs 38% for younger pts (p=NS). Hospitalisation was needed in 31% of them vs 32% in younger pts (p=NS). Conclusion: In this untreated cohort of generally older AML pts considered non candidates for intensive chemotherapy, response rate was 21% and 1 y OS 40%. Higher WBC counts and adverse karyotype were associated with poorer OS, but marrow blast %, whatever the threshold chosen, had no influence on outcome. Age above 75 y was associated with similar response and 1y OS. Finally, pts without AML IWG responses but with improved cytopenias also appeared to have improved survival. Disclosures: Off Label Use: Azacytidine is approved by FDA and EMEA in the treatment of high risk MDS and AML up to 30% of bone marrow blast.. Fenaux:CELGENE: Research Funding; AMGEN: Research Funding.

Description: Abstract 1773 Poster Board I-799 Background Patients aged ≥ 80 years account for as many as 30 to 35% of MDS in large registries (Rollison Blood 2008; Germing Ann Hematol 2008). Those patients (pts), when they have high risk MDS, are rarely candidates for chemotherapy (CT), even at low dose like low-dose araC, due to the risk of myelosuppression, and generally receive best supportive care (BSC) only, with very poor survival. Azacytidine (AZA) improves survival in higher-risk MDS pts, including RAEB-t and in pts aged 〉 75, with more limited myelosuppression than CT (Lancet Oncol 2009). Methods An AZA compassionate program (ATU) was opened in France between Dec 2004 and Dec 2008 for higher risk MDS, and for AML not candidates or refractory to intensive chemotherapy (IC). We retrospectively analyzed the outcome of MDS (including RAEB-t and CMML) pts ≥ 80 years from the 42 centers with complete patient (pt) reporting, and having received ≥ 1 cycle of AZA. Results The study population included 41 pts (M/F: 22/19; median age 83y, range 80-91) WHO diagnosis was RMCD in 2, RAEB-1 in 12, RAEB-2 in 16, and RAEB-t in 8, CMML in 3; IPSS cytogenetic risk favorable (fav) in 16, intermediate (int) in 10, and unfavorable (unfav) in 9 (karyotype failure/not done in 6); IPSS was int-1 in 8, int-2 in 18 and high in 13, undetermined in 2. Six pts had previously been treated unsuccessfully with low-dose AraC. With a median follow-up of 12 months, pts had received a median of 4 cycles (1-12) of AZA, at FDA/EMEA-approved schedule (75 mg/m2/d x7d/4 w) in 54% or a less intensive schedule (5d/4w, or

Description: Background Higher risk MDS and AML with del(5q) carry very poor prognosis, but show some response to AZA and LEN as single agents (Adès et al. Blood 2009, Itzykson, Blood, 2010). The combination of LEN and AZA has been tested in non-del 5q MDS patients with encouraging results and limited toxicity (Sekeres, Blood 2012). Sequential combination of AZA and LEN has also shown to be feasible and potentially effective in higher-risk MDS with del(5q) in a phase I study (Platzbecker et al, Leukemia 2013 ). In this phase I-II trial, we combined escalating doses of LEN to AZA in higher risk MDS and AML with del(5q). Methods Patients aged 18 or more, with IPSS int-2 or high MDS, CMML with WBC 〈 13,000/mm3 and marrow blasts 〉 10% and AML (20-30% marrow blasts) with 5q deletion with or without additional cytogenetic abnormalities could be included provided they had not previously received LEN or AZA. Patients should also have contra indication to intensive chemotherapy (IC), precluding inclusion in a GFM competing trial combining IC and LEN in higher risk MDS and AML with del 5q (results of that trial are also submitted to ASH 2013). In the present trial, patients received AZA (75 mg/m2 x5days, every 28 days) combined to escalating doses of LEN (5 mg/d x14 days in cohort 1, 5 mg/d x21 days in cohort 2 and 10 mg/d x21 days in cohort 3). For patients in hematological CR, PR , HI or marrow CR (MDS) and CR or PR (AML) after cycle 2 or 4, treatment was to be continued at the same schedule unless unacceptable toxicity or overt progression occurred. The main endpoint was response assessed after 2-4 cycles (IWG 2006 criteria). Median [IQR] are reported unless specified. Results 35 patients were enrolled in the study, including 15, 10 and 10 patients in cohort 1 (LEN 5mg/d x14d), 2 (LEN 5mg/d x21d) and 3 (LEN 10mg/d x21d) respectively. 18 were males and the median age was 68.9 (62.7-73). According to WHO classification, 1 patient had CMML, 7 RAEB1, 15 RAEB2 and 11 AML (with 20 to 30% marrow blasts). PS was 0, 1, 2 in 31%, 40%, 29% patients respectively. However, as said above, patients included in this trial were considered unfit for IC due to their age and/or comorbidities including cardiovascular events in 23 patients (still active in 19 at inclusion), pulmonary events in 7 (still active in 5), and neurological events in 6 pts. Del(5q) was isolated in only 2 pts, and 33 pts (94%) had del (5q) and at least 2 additional abnormalities. Baseline platelet count was 50 G/L (25-74), baseline Hb level was 9.15 (8.60-9.80), and baseline ANC was 1 G/l (0.545-1.66), including 38% patients with less than 0.8 G/L. IPSS was int-2 in 27% patients and high in 73% patients. With a median follow-up of 3.5 months, 98 cycles were administered (median 2 /patient, including 4 patients who received 6 or more cycles). In the three cohorts, the median number of cycles received was 2, 2 and 2 respectively. 15 (43%) patients discontinued treatment before the second cycle, due to early death (n=10), adverse events (n=2), progression (n=2), or CNS hemorrhage (n=1). They were all considered as non responders (primary endpoint). Of the 35 pts, 4 (11%) achieved CR and 2 (5.5 %) marrow CR after 2 cycles. After 4 cycles, The 2 marrow CR converted into CR and one additional patient achieved stable disease with HI leading to an overall response rate (ORR) of 7 (20%). The ORR was 13% in cohort 1, 10% in cohort 2, and 30% in cohort 3 (p=0.53). 4/6 complete responders achieved cytogenetic response, including 1 complete (CCyR) and 3 partial. The 6 CR included one of the 2 patients with isolated del(5q), who also obtained CCyR, and 5 of the 33 (15%) patients with complex karyotype. One year OS was 39%. Regarding toxicity, 31 SAEs (grade 3-4) were reported in 19 patients, including 1 cardiovascular event, 6 pulmonary infection, 5 gut events, 3 neurological events. No difference in grade 〉2 toxicity was seen in the 3 cohorts (10, 10, and 11 events, respectively). Conclusion In this elderly population of higher risk MDS or AML considered unfit for intensive chemotherapy , and with del 5q that was part of a complex karyotype in almost all cases , the combination of AZA with escalated doses of LEN was associated with early discontinuation (

Description: Background : Following FDA approval of AZA for MDS and activation of a phase III trial randomizing AZA to conventional treatment in higher risk MDS, a compassionate program for the use of AZA (ATU nominative) was started in France for MDS with exclusion criteria for this trial. Patients (pts) : IPSS int-2 and high-risk MDS (and some int-1) with contra-indication to the trial (ie therapy related (t-MDS) or already treated by cytoreductive agents or having progressed to AML or patient refusal), received AZA 75 mg/m/d (d 1–7) (SC) every 4 weeks. Results : From Sept 2004 to May 2006, 90 pts from 31 centres were included, of whom 77 had completed at least one course of AZA : M/F: 52/25, median age 71 y [42–88]. WHO at inclusion : 15 RAEB1, 30 RAEB2, 14 AML post-MDS, 7 CMML, 3 RA, 3 RAS, 2 RCMD, 3 unclassified MDS. 22 pts had previously received intensive Anth-AraC, 9 low dose AraC, 16 EPO and 13 other treatments (alkylators, Arsenic, androgens, Thal) and 1 had t-MDS. 32 (42%), 16 (21%) and 29 (37%) pts had fav, int and unfav karyotype, resp. 37 pts (48%) were IPSS high, 26 pts (34%) int-2 and 14 pts (18%) int-1. Pts received a median of 4 cycles [range 1–16]. Response was generally assessed after 4 cycles, unless pts progressed before. Thus, 16 pts were not yet evaluable for response. Of the remaining 61 pts, 10 (16%) achieved CR (IWG criteria), 15 (25%) achieved PR and 13 (21%) achieved HI (Overall response rate OR=62%). 23 pts (38%) were considered failure of whom 4 died before evaluation and 10 of them were considered failure because early evaluation after only 2 cycles showed stable disease only, and AZA was then stopped. OR was 73%, 57%, 67% and 36% for RAEB1, RAEB2, CMML and AML post-MDS resp (p

Description: Background IA is a major cause of morbidity and mortality for patients with hematological malignancies and has been mainly reported in patients with acute myeloblastic leukemia (AML) and stem cell transplantation. Much less is known about the role of IA during the treatment of lymphoproliferative diseases like ALL. Here, we retrospectively evaluated the characteristics of patients and the incidence of IA occurring during the induction course in adult ALL patients enrolled in the GRAALL-2005 trial. Methods We collected the data of 36 patients with IA during induction chemotherapy. All were included between May 2006 and October 2012 in the multicentric GRAALL-2005 phase III trial. According to ALL characteristics, these patients were treated in 3 different substudies: GRAALL, GRAALL-Rituximab (GRAALL-R) for CD20+ ALL, GRAAPH for Philadelphia (Ph) chromosome-positive ALL. IA was defined retrospectively using the EORTC modified criteria (De Pauw, CID 2008). Results Among the 969 patients enrolled, 36 (3.7%) developed IA during induction therapy. The median age was 30 years for all patients receiving induction and 47 years (range, 18 to 59) for patients with IA. We observed 18 IA (3%) by the GRAALL protocol (593 patients enrolled), 16 (8.3%) by the GRAALL-R protocol (191 patients enrolled), and 2 (0.7%) by the GRAAPH protocol (270 patients enrolled). In the GRAALL-R protocol, IA was diagnosed in 6 patients randomly assigned to receive rituximab and in 10 patients treated in the control group. The median time between first day of induction therapy and IA diagnosis was 20 days (range, -2 to 71). The median time between the first day of neutropenia and IA diagnosis was 18 days (range, 0 to 76). At the time of IA diagnosis, 13 patients were hospitalized in laminar airflow rooms, 10 patients in rooms with overpressure, 1 patient in a room with high-efficiency particulate filter, 5 patients in conventional rooms, 1 patient received home care and the type of hospitalization was unknown for the 6 remaining patients. Four patients with IA (11%) had received antifungal drug for invasive fungal infection (IFI) prophylaxis: one patient received fluconazole, one received caspofungin, and two received liposomal amphotericin B. All patients with IA presented pulmonary symptoms associated with a sinusal or cutaneous localization in 1 and 2 patients respectively. The diagnosis of IA was classified as possible in 7 episodes (19 %), probable in 22 episodes (61%), proven in 4 episodes (11%), and indeterminate in the remaining 3 episodes. Detection of Aspergillus antigen in serum by latex agglutination was positive in 24 cases (67%). Chest CT scans were taken for 33 patients (92%): nodules were found in 19 patients, halo sign in 20 patients, and “air crescent sign” in 1 patient. Bronchoalveolar lavage was performed in 11 patients (31%): culture was positive in 7 of them and Aspergillus antigen was positive in 2 of them. Biopsies where positive in 4 cases: in pulmonary biopsy in 3 patients and in cutaneous biopsy in 1 patient. Of all the Aspergillus isolates identified to the species level, Aspergillus fumigatus was isolated from 4 patients and Aspergillus flavus from 1 patient. Overall and IA-attributable 12-week mortality was 8 (0.8%) and 6 (16.7%) patients respectively. Conclusion IA is less frequently observed during induction therapy in adult ALL as compared to adult AML patients. However, the attributable mortality appears to be high in these patients. They are as at risk patients for IA and should be included in prophylactic and empirical antifungal clinical trials. Disclosures: No relevant conflicts of interest to declare.

Description: Purpose: Hyper-CVAD developed by the MD Anderson group a few years ago, is one of the standard salvage regimen used for younger relapsed/refractory ALL patients. Recently, targeted therapies using monoclonal antibodies directed against such surface antigens as CD19, CD20 or CD22 have allowed to obtain complete remission (CR) in B ALL expressing these markers. We hypothesized that combining Hyper-CVAD and an anti-CD22 monoclonal antibody could improve the response of such patients. Materials and Methods: This study evaluated the Cheprall salvage regimen, where epratuzumab, a humanized therapeutic monoclonal antibody against CD22 with mainly ADCC property, was associated to Hyper-CVAD, in younger patients (18-59 years old) with relapsed/refractory CD22+ (〉30% of expression) B-ALL. Cheprall consisted of epratuzumab 360 mg/m²/d iv on days 1, 8, 15 and 22, cyclophosphamide 300 mg/m²/12h iv on days 1 to 3, vincristine 2 mg iv on days +4 and +11, doxorubicin 50 mg/m² iv on day +4 and dexamethasone 40 mg po on days 1 to 4 and 11 to 14. The main objective of the study was the overall response rate (CR + CR with incomplete platelets recovery (=50% of bone marrow (BM) blasts decrease or CR with persistent extramedulladory disease) evaluated between 4 and 6 weeks from day+1. Secondary objectives were overall (OS) and leukemia free (LFS) survivals and minimal residual disease (MRD) evaluated by flow cytometry. Results: Between January 2011 and April 2016, 31 patients from 11 French centres were enrolled in the study. A combination of epratuzumab + vincristine and dexamethasone (EVD) only was given to one patient subsequently excluded from the analysis. Among the 30 patients ultimately considered for analyses, 19 were males and the median age was 35 years (range: 21-59). The median time between diagnosis and Cheprall was 14.5 months (range: 4-130) and 13 patients had been allotransplanted. Disease status at time of Cheprall was as follows: primary refractory n=3; first relapse non treated n=13; refractory first relapse n=6, second relapse non treated n=7 and fourth relapse n=1. Median percentage of white blood cells and BM blasts were 4525/mm3(range: 90-86790) and 60% (range: 15-100), respectively. The median CD22 expression of BM blasts was 100% (range: 36-100). Four patients had extramedullary disease: breast n=2, parotid n=1, nervous central system n=1 (deviation). Cheprall was overall well tolerated including mostly pancytopenia as grade ¾ toxicities. Three patients died during aplasia (septis n=1; cerebral haemorrhage n=1, fusariosis n=1) and were not evaluable for response. The overall response rate was 50% (n=15) including 9 CR (30%), 1 CRp (3%) and 5 PR (17%). The number of CR/CRp was higher for patients in first non-treated relapse (54% vs 18%) with an age below 36 years (50% vs 14%), with 18 months (54% vs 17%). Four out of 9 evaluated CR/CRp patients (45%) were documented with negative MRD. All patients in CR/CRp and 1 patient in PR received a consolidation consisting of a second cycle of Cheprall n=5, EVD n=5 or blinatumomab n=1. At the time of analysis (July 2016), all patients have died (during aplasia n=3, progression n=23, multiple organ failure n=1), except three responders still in CR, but yet recently enrolled (2015 n=1, 2016 n=2). Six patients received allogeneic transplant after Cheprall: 4 in CR2, 1 as salvage treatment and 1 in CR3. The last patient included and who achieved CR2 should be allografted in August 2016. Median OS was 3 months (range: 0.2-34.8). Median LFS for those achieving CR/CRp was 4.5 months (range: 1-12). Conclusion: Hyper-CVAD + epratuzumab allowed to obtain 50% of response in this cohort of patients at high risk of failure with refractory/relapsed younger CD22+ B-ALL. Disease improvement was however short-lived, which could be explained either by an insufficient disease load decrease and/or by escape of the blast cells to epratuzumab. This partial efficacy in a population of poor prognosis may suggest that epratuzumab should be tested within first-line chemotherapies as it may participate to decrease MRD level, especially before transplantation. The trial was registered at http://clinicaltrials.gov/ct no.NCT01219816. This study was supported by a grant from the French National Cancer Institute (PHRC 2010). Disclosures Huguet: Pfizer, Novartis, BMS, Ariad, Jazz, Amgen: Membership on an entity's Board of Directors or advisory committees. Thomas:Pfizer: Consultancy. Goldenberg:Immunomedics: Employment, Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Wegener:Immunomedics: Employment, Honoraria.

Description: Purpose: Pediatric-like protocols have yielded significant advances in younger adults with Ph-negative ALL. Nonetheless, the 5-year cumulative incidence of relapse was still estimated at 32% in the GRAALL-2003/2005 trials, approximately 25% of the relapses occurring after allogeneic stem cell transplantation (SCT). We report here on the outcome of these relapsing patients. Patients and Methods: Among 880 GRAALL-2003/2005 patients(18-60 years) with Ph-negative ALL in first complete remission (CR1), 264 relapsed. Data were available for 229 of them (151 B-cell precursor [BCP] ALL, 78 T-ALL; 45 standard-risk, 165 high-risk, and 19 unclassified ALL according to the risk classification used in these trials). Relapse site was bone marrow (BM), isolated CNS, combined BM/CNS and other in 181, 20, 17 and 11 patients, respectively. At relapse, median age was 35.7 years (range, 17-63). Median CR1 duration was 10 months (range, 0.5-74), 50 patients (22%) having CR1 〉 18 months. Fifty-four patients (24%) had received allogeneic SCT during CR1. First salvage treatments were classified as follows: standard curative therapy, 194 (85%); low-intensity therapy, 21 (9%); allogeneic SCT, 6 (2.5%); and best supportive care (BSC), 8 (3.5%). Post-relapse allogeneic SCT was analyzed as a time-dependent event using Mantel-Byar estimations. Results: A total of 121 patients (53%) achieved CR2, including 100/194 patients after standard salvage, 7/21 patients after low-intensity salvage, and 14 patients after SCT (6 as first salvage, 8 as subsequent salvage after standard salvage failure). Thus, 107/215 patients (50%) treated with standard or low-intensity first salvage achieved CR2 and in multivariable analysis (including age, ALL lineage, ALL risk classification, CR1 duration, prior SCT, relapse site and salvage type), a younger age and a longer CR1 duration were associated with CR2 achievement in these patients. Of note, few patients with t(4;11) BCP-ALL reached CR2 (19%). A total of 77 patients received allogeneic SCT after relapse, including 55 patients in CR2 after standard salvage (52 in CR2 at SCT time), 4 patients in CR2 after low-intensity salvage (all in CR2 at SCT time), the 6 patients transplanted as first salvage (all reaching CR2), and 12 patients transplanted as subsequent salvage (8 reaching CR2). The median time between relapse and SCT was 111 days (range, 5-311). With a median post-relapse follow-up of 3.1 years, post-relapse overall survival (OS) was 19.3% (14-25%) at 2 years and 13.3% (9-19%) at 5 years (median OS, 6.7 months). In landmark analysis, OS was significantly longer in patients who achieved CR2 (HR, 0.19; p 18 months (HR, 0.43; p