ALBERT

Description: Rationale: Inotuzumab ozagomicin (IO) has been linked to an increased incidence of veno-occlusive disease (VOD) and liver alterations. Most VOD events occurred during hematopoietic stem cell (HSCT) transplantation after IO therapy. We have previously described that the measurement of liver stiffness can anticipate the diagnosis of VOD in the context of HSCT. The mechanisms underlying the increased risk of VOD and liver damage in patients receiving IO are not well understood; in the pathogenesis endothelial damage, ozagomicin release and on-target off-tumor effects may be involved. Here, we aimed to assess the effects of IO on the changes of liver, vascular and biochemistry parameters. Methods: Intensive monitoring of the liver was incorporated into the standard of care of patients who received IO for relapsed or refractory (R / R) acute lymphoblastic leukemia (ALL). Upper abdomen ultrasound with Doppler was performed at baseline and at the end of therapy; liver stiffness measurement (LSM) by Fibroscan® (Echosens, Paris, France) at every IO course or at every IO infusion. With the exception of ursodeoxycholic acid, the patients did not receive prophylaxis for VOD. Data was collected after anonymous aggregation, in accordance with GCP and Helsinki declaration. Results are reported as median with interquartile ranges (IQR). Results: At data cut-off, 1st Apr 2019, 16 patient received baseline assessment and at least a post-IO assessment in our monitoring program. In our patent set, median age was 44.5 (IQR 30.7 - 64.0); 12/16 (75 %) patients relapsed after the last treatment and 4/16 (25 %) patients were refractory to the last treatment; patients received a median of 3 (IQR 2 - 3.7) lines before IO; 6/16 (37.5 %) patients undergone HSCT before IO, of which a patient had 1st and 2nd HSCT before IO; 5/16 (31.25 %) undergone HSCT after IO therapy (no patients had second HSCT after IO). Patients received a median of 2 (IQR 2.0 - 3.7) IO administration according to the schedule of the phase 3 trial. The median duration of the therapy was 61.5 days (IQR 43.2 - 114.0) and median progression-free survival in our population was 278.0 days (95% C.I. 264.0 - 292.0). In our patient set, we performed 113 biochemistry determination, 30 liver ultrasounds with Doppler and 116 LSM examination. One patient received a liver biopsy. Among the biochemical exams (AST, ALT, GGT and alkaline phosphatase) only the AST values significantly increased after 1st course of IO (from the median value of 21 U/L to 53 U/L after course 3). Liver ultrasound with Doppler revealed portal hypertension signs in half of the patients during IO monitoring program. Among these patients 7/16 (44%), 3/16 (17%), 5/16 (33.3%) and 3/16 (17%) showed splenomegaly, recanalization of the paraumbilical vein, dilatation of portal vein and ascites, respectively. Median LSM significantly increased from a baseline value of 6 kPa to 7.8 kPa after last post-IO assessment (p-value 7.1 kPa). With a median follow up of 387.5 days (IQR 182.8-524.5) we observed one VOD event (7%); the VOD was graded severe and occurred after HSCT post-IO. Conclusions: Our clinical experience represents the first step to better understand the IO-related liver alterations, as we described the frequency and relevance of quantitative markers. Most of the patients in our set developed ultrasound and/or elastography alteration during IO therapy. Furthermore, these alterations do not seem to correlate with biochemistry. Even if most of the patients had sub-clinical vascular and parenchymal alterations of the liver portal-hypertension related, VOD incidence in our set is comparable with literature. Long-term follow-up results are expected to test whether alterations return or evolve over time. Stratifying the tailored risk liver complications with prospective non-invasive and marker-driven strategies in term of IO dosing and HSCT timing could be a great benefit for patients. * FR and GM contributed to this manuscript equally # AC and CP contributed to this manuscript equally Figure Disclosures Martinelli: Roche: Consultancy; BMS: Consultancy; Novartis: Consultancy; Pfizer: Consultancy; ARIAD: Consultancy. Cavo:janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau; bms: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; novartis: Honoraria; takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau. Papayannidis:Amgen: Honoraria; Novartis: Honoraria; Teva: Honoraria; Pfizer: Honoraria; Incyte: Honoraria; Shire: Honoraria.

Description: Several groups have reported the results of Allo-SCT following a RIC regimen in relapsed and refractory lymphomas. However, the long-term efficacy of this strategy is still unknown. We report herein the results of a prospective multicenter phase II trial at median follow-up of 5 years. A total of 194 relapsed/refractory lymphomas received the same RIC regimen (thiotepa, cyclophosphamide and fludarabine) followed by Allo-SCT from sibling donors. Histologies were non-Hodgkin’s lymphomas (NHL) [indolent (LG-NHL, n=68), including follicular lymphoma (FL, n=29), chronic lymphocytic leukemia (CLL, n=35), other (n=4); aggressive (HG-NHL, n=87), including B-cell phenotype (n=43), T-cell phenotype (n=28), mantle cell lymphoma (MCL, n=16)] and Hodgkin’s lymphoma (HL, n=39). 133 (68%) of 194 patients (pts) had chemosensitive disease and 100 (52%) of 194 failed a previous autologous transplantation. Median follow-up was 60 months (range, 15–113). At last follow-up, 116 pts are alive (59%) and 78 died from any cause [n=47 for disease progression, n= 30 for non-relapse mortality (NRM), n=1 not assessable]. The 5-year overall survival (OS) and progression-free survival (PFS) were 62% and 70% for LG-NHL, 61% and 59% for HG-NHL, and 42% and 19% for HL, respectively. The median time to relapse was 7 (range, 2–30), 4.5 (range, 1.6–33), and 5.5 (range, 0.4–42) months for LG-NHL, HG-NHL, and HL respectively. Pts with chemosensitive disease at Allo-SCT had 5-year OS and PFS of 69% and 61%, while those with refractory disease had 5-year OS and PFS of 35% and 45%, respectively. Status of disease at Allo-SCT influenced significantly long-term outcome in HG-NHL and HL [chemosensitive versus chemorefractory: 73% versus 32% (p

Description: Host dendritic cells (DC) are thought to be essential in the induction of acute GVHD after allogeneic HSCT. Human peripheral blood contains various circulating DC precursors including CD11c+ myeloid preDC (mDC), CD14+ monocytic DC precursors (CD14+ preDC) and plasmacytoid preDC (pDC). In this study we employed flow cytometry to enumerate both mDC (lin-, HLA-DR+ and CD11c+), mono-DC (CD14+, CD45 bright) and pDC (lin-, HLA-DR+ and CD123+) numbers in the blood of patients receiving an allogeneic HSCT. Fifty consecutive patients undergoing HSCT from HLA-matched either related (n=28) or unrelated (n=22) donors were enrolled in the study. The stem cell source was bone marrow in all unrelated donors, and G-CSF mobilized PBSC in related donors. Indications to transplant were AML (n=12), ALL (n=11), MM (n=10), CML (n=7), NHL (n=6) and HD (n=4). 13 patients (26%) received reduced dose conditioning regimens (RIC). All patients received CsA and MTX as GVHD prophylaxis. Moreover, 26 patients (52%) received ATG before transplant. mDC and pDC PB counts were significantly lower in patients as compared to 28 age-matched healthy controls [8.8 cells/microL (25th to 75th percentile 3.5–14.5) mDC, and 2.8 (1.3–5.5) pDC, vs 15.5 (12.1–25.1) and 8.6 (5.6–13.1), respectively] (p 310/mL (median value) had a higher actuarial probability of developing acute GVHD grade II–IV than patients with lower CD14+ preDC counts (61% vs 15%). No correlation was observed between pretransplant recipient PB mDC, pDC or CD14+ preDC counts and chronic GVHD. These findings demonstrate that blood levels of DC precursors may represent an important biomarker correlating with a higher risk of developing aGVHD. Based on these results, future studies will exploit clinical strategies aimed at depleting or inactivating host preDC before allotransplant as a means of GVHD prophylaxis.

Description: We analyzed clinical and molecular follow-up of 16 patients with chronic myeloid leukemia (CML) relapsing after allogeneic stem cell transplantation (SCT). The median interval between allogeneic SCT and relapse was 26 months (7–162). Two patients had failed treatment with donor lymphocyte infusions prior to Imatinib; four patients had received therapy with IFN alpha. All patients were treated with Imatinib (400 or 600 mg/daily). One patient had received Imatinib before allogeneic SCT. The overall complete hematological (CHR) and cytogenetic responses (CCyR) were 100% for all patients either relapsed in CP or AP. All patients achieved complete molecular response (CMR), intended as 3 logs reduction of BCR-ABL/B2M within 18 months; 8/16 patients obtained a CMR within three months, independently of the phase of the disease at of relapse. Median follow-up after start of Imatinib therapy was 24 months (range 6–36). Chimerism status evaluated in 9 patients showed conversion to full donor chimerism after therapy in all but one of them. Imatinib has significant activity against CML in relapse after allogeneic bone marrow transplantation with durable cytogenetic and molecular remissions obtainable in all patients.

Description: The primary end point of the study was the successful mobilization of a target cell dose of 2 x 106 CD34+ cells/kg in lymphoma patients receiving ifosfamide, epirubicin and etoposide (IEV) chemotherapy and a fixed dose (6 mg) of pegfilgrastim given as single subcutaneous injection. An open-label phase II study including 25 relapsed or refractory patients (Hodgkin’s disease=4; aggressive non-Hodgkin’s lymphoma=21) was conducted to evaluate the efficacy of pegfilgrastim, in combination with salvage chemotherapy, mobilizing CD34+ stem cells into peripheral blood. Following chemotherapy, all patients had grade 4 neutropenia with a median duration of 1.5 days (1–3). Pegfilgrastim treatment was well tolerated and only 2/25 patients required pain-control medication. CD34+ cells were mobilized in all patients. The median (range) peak value of peripheral blood CD34+cells after IEV chemotherapy and pegfilgrastim was 141/microL (12.8–386) and occurred almost invariably on day +14 (13–16). Twenty three/25 patients underwent a single apheresis to collect a median of 8.7 CD34+cells/Kg (1.8–17.3). Twenty four/25 patients (96%) reached the target cell dose of 2 x 106 CD34+ cells/kg. High concentrations of circulating CD34+ cells (〉 50/microL) were observed for several days after the achievement of the peak value. All patients have been transplanted with pegfilgrastim-mobilized CD34+ cells and all of them showed a rapid and sustained engraftment after high-dose chemotherapy. Our results show that pegfilgrastim as adjunct to chemotherapy is a predictable and highly effective mobilization regimen in lymphoma patients

Description: Achieving a complete cytogenetic response (CCgR) is a major target in the treatment of chronic myeloid leukemia (CML) with interferon-α (IFN-α), but CCgRs are rare. The mean CCgR rate is 13%, in a range of 5% to 33%. A collaborative study of 9 European Union countries has led to the collection of data on 317 patients who were first seen between 1983 and 1997 and achieved CCgRs with IFN-α alone or in combination with hydroxyurea. The median time to first CCgR was 19 months (95% CI, 17-21; range, 3-84 months). At last contact, 212 patients were still alive and in continuous CCgR; 105 patients had lost CCgR, but 53% of them were still alive and in chronic phase. IFN-α treatment was discontinued permanently in 23 cases for response loss, in 36 cases for chronic toxicity (15 are still in unmaintained continuous CCgR), and in 8 cases because it was believed that treatment was no longer necessary (7 of these 8 patients are still in unmaintained continuous CCgR). The 10-year survival rate from first CCgR is 72% (95% CI, 62%-82%) and is related to the risk profile. High-risk patients lost CCgR more frequently and more rapidly and none survived more than 10 years. Low-risk patients survived much longer (10-year survival probability 89% for Sokal low risk and 81% for Euro low risk). These data point out that a substantial long-term survival in CCgRs is restricted mainly to low-risk and possibly intermediate-risk patients and occurs significantly less often in high-risk patients.

Description: Abstract 2009 To evaluate the role of allografting from unrelated donors in the treatment of myeloma we conducted a retrospective study through the Italian Bone Marrow Transplantation Donor Registry. Overall, from 2000 through 2009, 196 myeloma patients, median age 51 years (32–67), for a total of 199 allografts, were transplanted from an unrelated donor at 34 Centers in Italy. Fifty-two (28.1%%), 69 (37.3%), and 64 (34.6%) patients were prepared for transplant with a myeloablative, a reduced-intensity and a non-myeloablative conditioning respectively. Patient characteristics of the 3 cohorts are reported in Table 1.ConditioningMyeloablativeReduced-intensityNon-myeloablativePatient number (%)52/185 (28)69/185 (37)64/185 (35)Median Age455355Previous therapy lines 〈 2 (%)23 (27)33 (38)30 (35)Previous therapy lines ≥ 2 (%)29 (29)36 (37)34 (34)Stem Cell Source BM (%)24 (57)18 (43)0 (0)Stem Cell Source PBSC (%)28 (19)51 (36)64 (45) Cumulative incidence of acute grade II-IV graft-versus-host-disease (GVHD) was 46.4% whereas chronic GVHD was 45.1%. There was no difference in GVHD incidence among the 3 cohorts defined by type of conditioning. Complete and partial remissions in patients who survived at least 3 months post-transplant were 27% and 28% for an overall response rate of 55%. At a median follow up of 32 (0–118) months post-transplant, in the entire study population, median OS from diagnosis was 70.6 months while OS and EFS from the allograft were 18.9 and 14.9 months. Overall, the cumulative incidence of transplant related mortality (TRM) was 29.6% at 1 year and 32.4% at 5 years post-transplant. OS from diagnosis and EFS from transplant were 70.6 and 28.2 months; 66.8 and 9.1 months; and 111.9 and 22.4 months in patients who respectively underwent a myeloablative, a reduced-intensity and a non-myeloablative transplant. One-year and 5-year TRM was 33.3% and 35.7%, 32.2% and 34.4%, and 22.1% and 26.5% respectively. Univariate and multivariate analyses, assessed by multivariate Cox proportional hazards models, were performed for the following variables: number of previous chemotherapy lines (1,2 vs. ≥3), disease status at transplant, HLA- matched antigens (10/10 vs. 9/10 vs. ≤8/10), recipient/donor gender combinations, hematopoietic cell source (peripheral blood vs. bone marrow), conditioning (myeloablative vs. reduced-intensity vs. non-myeloablative), use of anti-thymoglobulin in the conditioning, acute GVHD, chronic GVHD, best response post-transplant, year of transplant (2000–02 vs. 2003–05vs. 2006–09). By univariate analysis, lower number of chemotherapy lines before the allograft, disease status at transplant, a fully HLA-identical donor, the use of peripheral hematopoietic cells rather than bone marrow were statistically significant variables for better OS whereas disease status at transplant, a fully HLA-identical donor, chronic GVHD (either limited or extensive) were statistically significant for better EFS. However, by multivariate analysis, only the development of chronic GVHD (HR 0.50; p

Description: Abstract 4577 Patients with therapy-related acute myeloid leukemia (tAML) and myelodysplastic syndromes (tMDS) have a bad prognosis. Allogeneic stem cell transplantation (alloSCT) is potentially curative, but the majority of these patients die because of the high incidence of relapse (RI) and non relapse mortality (NRM). Since it is critical to understand which patients should receive alloSCT, we designed this retrospective study to assess which patients’ characteristics may predict the alloSCT outcome in tAML/tMDS. All the patients affected by tAML or tMDS and allografted in 4 Italian hematology units between 1998 and 2009 were included. Total patients were 28: 24 (86%) had tAML, 4 (14%) had tMDS. Patients had a median age of 49 years (range 21–65) at transplant; 15 patients were female (54%). Previous neoplasia was lymphoma in 23 patients (82%, 15 Hodgkin and 8 non-Hodgkin), or non-hematologic cancer (5, 18%) like breast carcinoma (2), seminoma (1), testicular embryonal carcinoma (1), and osteosarcoma (1). Previous cancer had been treated with chemotherapy (CT, 7 patients, 25%), radiotherapy (RT, 4 patients, 14%), or both (17, 61%). Fourteen patients (50%) had received 〉=2 therapy lines, 6 (21%) had received autologous stem cell transplant. tAML/tMDS occurred after a median time of 86 months (range 13–253) after the previous cancer treatment. Cytogenetic analysis was performed in 24 patients (86%): 8 patients (33%) had intermediate risk and 16 (57%) high risk cytogenetics according to Medical Research Council AML10 Trial definitions. Twenty-three patients (82%) received induction CT for tAML/tMDS, 19 (68%) received consolidation; 5 patients (18%) received upfront alloSCT. Induction consisted of idarubicin+cytarabine+/−etoposide (12 patients, 43%) or fludarabine+cytarabine+/−idarubicin (11 patients, 39%); 15 patients (54%) had an infection after induction. Median time from tAML/tMDS diagnosis to alloSCT was 5.7 months (range 0–25). At transplant, 10 patients (36%) had a Karnofsky Performance Status (KPS)1. Donor was identical sibling for 9 patients (32%), and alternative for 19 patients (68%): mismatched related (1, 3%), matched unrelated (15, 54%) or haploidentical (3, 11%). Disease status of patients at transplant was as following: 12 patients (43%) were in CR (11 in CR1), 4 (14%) in PR and 7 (25%) in PD; 5 patients (18%) received alloSCT at diagnosis. Patients underwent reduced intensity (11 RIC, 39%) or myeloablative (17, 61%) alloSCT. Myeloablative conditioning was mainly busulfan-based (15 patients, 54%); the majority of RIC patients received thiotepa+cyclophosphamide-based conditioning (9, 32%). Twelve patients (43%) are alive at last follow-up, 7 patients (25%) died of disease, 9 (32%) died of NRM. The main reason of death by NRM was infection (8 patients, 29%). Median follow-up of surviving patients was 528 days (55-1704). One- and 2-years overall survival (OS) was 50% and 36%, progression free survival (PFS) was 42% and 38%. RI was 28% at both 1 and 2 years, NRM was 18% at 100 days, 30% at 1 year and 35% at 2 years. Nine (32%) patients had acute GVHD of grade 〉=2, 8 patients had chronic GVHD (cGVHD, 29%), 3 patients (11%) had extensive cGVHD. OS and PFS were reduced in patients with high-risk cytogenetics (p=0.03 and p=0.01, respectively) and KPS

Description: Background Thiotepa is an alkylating compound with an effective antineoplastic activity that was used in the past mainly for solid tumors and lymphoma, partially due to its ability to penetrate the blood-brain-barrier. Moreover, beside its myelosupressive activities, thiotepa has immunosuppressive properties making it an attractive agent to be used in the conditioning pre-transplantation. In the current retrospective registry study, we analyzed thiotepa-based conditioning regimen for allo-HSCT in adult patients with ALL using the EBMT ALWP database. Methods Inclusion criteria were: adults with de novo or secondary ALL who underwent first allo-HSCT between 2000 and July 2014 with a thiotepa-based regimen. Donors were either HLA-matched siblings or matched unrelated donors. Haploidentical and cord blood transplantations were excluded as well as patients who received a previous allo-HSCT. Results A total of 323 patients with adult ALL were identified. Median age was 43 years (range, 18 - 76); 59% were males and 41% females. Disease status at allo-HSCT was CR1 in 48.9%, CR2 in 21.7%, CR3 in 6.2% and 23.2% of the patients had an active disease at time of transplant. Transplantation was performed from a HLA-matched sibling (49.8%) or a matched unrelated donor (51.2%). Sixty-five per cent of patients received a myeloablative and 35% a reduced-intensity conditioning regimen, respectively. Stem cell source was peripheral blood stem cells in 84% of the transplants, while 16% received bone marrow grafts. Neutrophil engraftment (defined as 〉0.5x109/L) was 98% with a median day of 15 (range, 2 - 41). Platelets engraftment (defined as 〉20x109/L) was 92% with a median day of 14 (range, 7 - 98). Incidence of acute GvHD (Grade〉 II) was 26.6%, while chronic GvHD occurred in 35.9% at one year (24.6% with extensive disease). With a median follow-up of 16.8 months, the non-relapse mortality was 12.4% and 25.3% at 100 days and one year, respectively. Relapse incidence at 1 year was 33.3%.The one-year leukemia-free survival and overall survival incidences were 57% and 66%. Table 1 shows the outcome according to donor and disease status at time of allo-HSCT. When looking for conditioning regimen more precisely, comparing thiotepa / busulfan ± melphalan (n=213) to thiotepa / other (n=110), higher relapse incidence at one year (34.9% vs 30.3%, p=0.016) and lower leukemia-free survival (38.8% vs 45.9%, p=0.0203), respectively were observed, without difference in non-relapse mortality (23.8% vs 26.3 %, n.s.) and overall-survival (59.6% vs 51.1%, p=0.109). Conclusion This large survey suggests that TTP-based conditioning therapy in adult ALL is feasible and effective, with main outcomes being comparable to literature published results achieved with other regimens. Table 1. Donor LFS,1 year p-value OS,1 year p-value Relapse,100 days Relapse,1 year p-value NRM,100 days NRM,1 year p-value HLA-matchedsibling 49% 0.0262 62% 0.0133 13.1% 31.9% 0.4641 8.7% 18.3% 0.0042 matchedunrelateddonor 33% 46% 15.2% 34.7% 16.2% 32.1% Table 2. Disease status at allo-HSCT LFS,1 year p-value OS,1 year p-value Relapse,100 days Relapse,1 year p-value NRM,100 days NRM,1 year p-value CR1 49%

Description: Allogeneic stem cell transplantation (allo-SCT), which provides a tumor-free graft, is an alternative approach to autologous transplantation for multiple myeloma (MM) that offers the possibility of cure through a graft vs myeloma effect (GVM). However, the inherent non relapse mortality (NRM) and the high post-transplant relapse rate are the major shortcomings of this strategy which continues to have a controversial role in MM treatment. To highlight the long-term clinical outcomes of allo-SCT, we performed a retrospective analysis on 102 patients (pts) with MM who received at our Institution either a myeloablative (MA) (74 pts) or a non-myeloablative (NMA) (28 pts) conditioning regimen between 1990 and 2014. The MA regimen consisted in low dose TBI and cyclophosphamide (cyclo) ± melphalan (mel) or busulfan-cyclo. The NMA regimen was mel-fludarabine. Graft versus host disease (GVHD) prophylaxis consisted in cyclosporine + methotrexate (83%) or mycophenolate (17%), with the addition of thymoglobulin for unrelated or related female vs male recipient donors. The median age was 42 yrs (IQR 38-47), 60% pts were male. The hematopoietic cell donors were sibling in 77 pts and unrelated in 25, while the source of stem cells was peripheral blood in 65 and bone marrow in 37 pts. Fifty-six pts received allo-SCT as first-line therapy, 31 as second-line and 13 as third or fourth-line. Median time from diagnosis to allo-SCT was 22 months. Response status at the time of transplant was at least PR in 63% of the pts, including ≥ VGPR in 36% and CR in 12%. Overall, the response rate after allo-SCT was as follows: CR 58%, VGPR 19%, PR 18%. Median CR duration was 10 years (44% at 15 years). The incidence of acute grade II-IV and III-IV GVHD was 25% and 15%, respectively. The incidence of all grades chronic cGVHD was 48%, grade ≥2: 24%, with a median onset time of 178 days. By competitive risks analysis, the cumulative incidence of cGVHD at 1 and 3 years was 20% and 32%, respectively. On univariate analysis, the gender combination of female donor-male patient resulted in significantly higher incidence of cGVHD (sub hazard ratio, SHR, 2.3, P= 0.03). The cumulative incidence of NRM was 6.6% at 100 days, 11% at 1 year and 14.4% at 3 years, with lack of statistically significant relationship with the conditioning regimen. By univariate analysis, 〈 PR prior to allo-SCT (SHR 2.8) and all grades cGVHD (SHR 4.6) were significantly associated with an increased NRM. By competitive risks analysis, the cumulative incidence of relapse was 50% at 5 years, 58% at 10 years and 59% at 15 years. On univariate analysis, sibling donor (SHR 0.54, P=0.047), all grades cGVHD (SHR 0.5, P=0.011) and ≥VGPR after allo-SCT (SHR 0.38, P=0.001) were significantly associated with extended time to progression. All grades cGVHD (SHR 0.43, P=0.005) and ≥VGPR after allo-SCT (SHR 0.36, P= 0.001) were independent predictors for a lower risk of progression on multivariate analysis. With a median follow-up of 13 years, overall survival (OS) was 43% at 5 years and 34% at 10 years. In univariate analysis, low ISS stage at diagnosis, sibling donor, absence of female donor-male patient gender combination, ≥VGPR prior to allo-SCT and first-line allo-SCT were significantly related to OS. Multivariate analysis confirmed an OS benefit for having a sibling donor (HR 0.30, P