scholarly journals High Post-Transplant Ferritin Level Associates with Adverse Survival and Higher Mortality Rate following Allogeneic Hematopoietic Stem Cell Transplant, whereas Pre-Transplant Ferritin Level Does Not

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3454-3454
Author(s):  
Warren Fingrut ◽  
Arjun Law ◽  
Wilson Lam ◽  
Fotios V. Michelis ◽  
Santhosh Thyagu ◽  
...  
Keyword(s):  
Prognostic Marker ◽  
Serum Ferritin ◽  
Research Funding ◽  
Serum Ferritin Level ◽  
Acute Gvhd ◽  
Ferritin Level ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Independent Prognostic Marker

Abstract Background: Allogeneic hematopoietic stem cell transplantation (HCT) is a curative therapy for many hematologic and non-hematologic diseases; however, it is associated with significant morbidity and mortality. Many studies have shown that elevated pre-transplant ferritin levels are associated with increased risk of morbidity and mortality following HCT. Given ferritin's association with systemic inflammation, it is a plausible potential prognostic marker in the post-HCT period, including in patients with graft-versus-host disease (GVHD). The present study attempts to determine whether post-transplant serum ferritin level is an independent prognostic marker for outcomes post-HCT, especially in the subgroups of patients with acute or chronic GVHD. Methods and patients: A total of 229 patients who had serum ferritin level data available within one-year post HCT were enrolled into this retrospective study. These patients underwent HCT at Princess Margaret Cancer Centre, Toronto, Canada between 2001-2013. Patients' characteristics and transplant procedures were: median age: 51 (range:19-70); refined disease risk index: low (n=70), intermediate (n=108), high (n=51); donor type: HLA-matched related donors (n=94), HLA-matched or partially-matched unrelated donors (n=135); conditioning regimen: myeloablative (n=120), reduced intensity (n=109). Acute and chronic GVHD were respectively classified using the 1994 consensus conference and NIH consensus criteria. Primary outcomes were overall survival (OS), non-relapse mortality (NRM), and relapse. Kaplan-Meier method was used for OS; cumulative incidences were used for NRM and relapse, considering competing risks. Multivariate analysis employed Cox or Fine-Gray proportional hazard regression model. Factors evaluated included recipient age and CMV status, donor-recipient sex, comorbidity score, performance index, GVHD prophylaxis, post-transplant serum ferritin level (ferritinPost-HCT), and serum ferritin level prior to HCT (ferritinPre-HCT). Recursive partitioning was used to stratify patients into low or high risk groups based on ferritinPost-HCT (≤3,169 vs >3,169 ng/mL) and ferritinPre-HCT (≤669 vs >669 ng/mL). Results: Median follow-up duration among survivors was 46 months post-HCT (range:2.8-147.2 months). Median ferritinPost-HCT was 2,178 ng/mL (range: 45-30,647; Figure A), measured at a median of 137 days post-HCT. There was a weak correlation between ferritinPost-HCT and ferritinPre-HCT (Pearson's correlation r=0.242, p=0.002). Compared to the group with low ferritinPost-HCT, the high ferritinPost-HCT group had lower three-year OS (40.0% vs 66.7%, p<0.001; Figure B) and higher NRM (48.6% vs 17.8%, p<0.001 Figure C), but no difference in cumulative incidence of relapse (10.5% vs 19.7%, p=0.079; Figure D). A landmark analysis was performed where the day of ferritinpost-HCT measurement was considered day 0. Results of this landmark analysis showed consistent findings: high ferritinPost-HCT showed lower three-year OS (38.3% vs 65.4%; p<0.001) and higher NRM (50.6% vs 17.7%; p<0.001) compared to low ferritinPost-HCT, but no difference in relapse (10.7% vs 21.3%, p=0.077). In multivariate analysis, ferritinPost-HCT was found to be an independent prognostic factor for OS (p=0.001, HR 2.323) and NRM (p<0.001, HR 3.905). However, pre-transplant ferritin level (ferritinPre-HCT) did not stratify well for OS (57.0% vs 61.8%, p=0.636) or NRM (30.8% vs 22.7%, p=0.247). Out of 229 patients, 171 (74.6%) developed any grade of acute GVHD, and 61 (26.6%) developed chronic GVHD. Median onset of acute and chronic GVHD were, respectively, 33.5 days and 145 days. Level of ferritinPost-HCT was significantly higher in the group that developed acute GVHD than in those without acute GVHD. However, there was no difference in ferritinPost-HCT between patients with or without chronic GVHD. FerritinPost-HCT was found to be an independent prognostic marker in the subgroup with acute GVHD for OS (p=0.001, HR 2.531) and NRM (p<0.001, HR 3.584), and in the subgroup with chronic GVHD for OS (p=0.042, HR 3.226) and NRM (p=0.009, HR 14.130). Conclusions: In our cohort, high ferritinPost-HCT levels were significantly associated with decreased OS and increased NRM, independent of other prognostic factors including ferritinPre-HCT or GVHD. Further prospective study including larger number of patients is warranted. Figure. Figure. Disclosures Lipton: ARIAD: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding. Kim:BMS: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy; Novartis: Consultancy, Honoraria, Research Funding; Paladin: Consultancy.

Hematologic Improvement with Iron Chelation using therapy Deferasirox in Patients with Aplastic Anemia: A Subgroup Analysis of KAMS0112 Prospective Study,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3424-3424
Author(s):  
Yoo-Hong Min ◽  
Sung-Soo Yoon ◽  
Hyeoung Joon Kim ◽  
Kyoo-Hyung Lee ◽  
Jae Hoon Lee ◽  
...  
Keyword(s):  
Platelet Count ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Research Funding ◽  
Serum Ferritin Level ◽  
Ferritin Level ◽  
Iron Chelation ◽  
Hemoglobin Level ◽  
Hematopoietic Stem ◽  
Wbc Count

Abstract Abstract 3424 Patients with aplastic anemia (AA) are suffered from various complications related to bone marrow failure and peripheral cytopenia. Although immunosuppressive therapy or hematopoietic stem cell transplantation has been performed for curative purpose, the majority of patients have been treated only by supportive cares including repeated transfusion. However, because continued transfusion eventually induces iron overload in many tissues and organs, transfusional iron overload and its consequences are another life-threatening problems for AA patients. Previous reports about iron chelation therapy (ICT) have mainly shown its efficiency for decreasing tissue iron and safety. However, improvement in hematopoiesis after iron chelation therapy has been limitedly reported as case reports or trials involving small number of patients without objective tools for measuring tissue iron content. In the KAMS0112 study (a multi-center, open label, prospective study evaluating the efficacy of ICT with deferasirox in transfusional iron overload with myelodysplastic syndrome or AA using quantitative R2-MRI, Ferriscan), a total of 54 patients with AA showing serum ferritin level over 1,000 ng/ml were enrolled from 19 institutes, and further analyzed for the changes in hemogram during ICT as well as efficacy and safely of deferasirox. During the study, the specific treatments for AA, such as immunosuppressive therapy or hematopoietic stem cells transplantation, were not undertaken. During 1 year prior to study, patients received 23.7±16.9 units of red blood cell (RBC) product, and the baseline serum ferritin level and liver iron content (LIC) were 4,164±447 ng/ml and 20.1±12.0 mg Fe/g DW, respectively. Deferasirox was given orally at a dose of 20 mg/kg/day for at least 6 months to all patients. If the serum ferritin level falls below 500 ng/ml, treatment was withheld. In spite of continued transfusional support during the study, serum ferritin level and LIC were significantly decreased after 1 year of ICT with deferasirox (Ds-ferritin=−3,076.7±489.9 ng/ml, p=0.0003; DLIC=−7.73 mg/Fe/g DW, p=0.001). To evaluate the improvement of each parameter in hemogram by ICT, patients with baseline hemoglobin level less than 8.0 g/dl (n=28), with baseline WBC count less than 4/ml (n=43), and with baseline platelet count less than 20/ml (n=31) were selected separately. At the end of study, hemoglobin level and platelet count (8.2±3.0 g/dl and 22.2±31.4/ml, respectively) was significantly increased from the baseline value (6.1±1.1 g/dl, p=0.001; 12.5±12.4/ml, p=0.05, respectively). WBC count was also slightly increased (from 2.1±0.9/ml to 2.3±0.9/ml, p=0.457). Considering the relatively uniform criteria of transfusion, the finding that hemoglobin level and platelet count could increase above 8 g/dl and 20/ml, respectively, after 1 year of deferasirox treatment is clinically significantly. Due to gradual improvement of anemia, requirement of RBC transfusion had continuously decreased during the study period (R2=0.31). This subanalysis of KAMS0112 study demonstrates that ICT using deferasirox can be effective in improving anemia and thrombocytopenia in the transfusional iron overload patients with AA, as well as reducing serum ferritin level and LIC. Further studies might be required to elucidate the mechanism involved in the improvement of hematopoiesis associated with correction of deranged intracellular iron homeostasis. Disclosures: Min: Novartis: Research Funding. Yoon:Novartis: Research Funding. Kim:Novartis: Research Funding. Lee:Novartis: Research Funding. Lee:Novartis: Research Funding. Won:Novartis: Research Funding. Shim:Novartis: Research Funding. Kim:Novartis: Research Funding. Seung:Novartis: Research Funding. Kim:Novartis: Research Funding. Lee:Novartis: Research Funding. Chung:Novartis: Research Funding. Hyun:Novartis: Research Funding. Jo:Novartis: Research Funding. Jung:Novartis: Research Funding. Sohn:Novartis: Research Funding. Yoon:Novartis: Research Funding. Kim:Novartis: Research Funding. Joo:Novartis: Research Funding. Cheong:Novartis: Research Funding.

Impact of Serum Ferritin Levels on the Incidence of Chronic Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1248-1248
Author(s):  
Soichiro Sakamoto ◽  
Hiroshi Kawabata ◽  
Junya Kanda ◽  
Tatsuki Uchiyama ◽  
Chisaki Mizumoto ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Serum Ferritin ◽  
Relapse Rate ◽  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Proportional Hazards ◽  
Ferritin Level ◽  
Chronic Gvhd ◽  
Hematopoietic Stem

Abstract Abstract 1248 Background: Iron overload is an important adverse prognostic factor in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-SCT). Many studies have shown that elevated pre-transplant serum ferritin levels are associated with an increased risk of morbidity and mortality after allo-SCT. Conversely, a couple of other studies have suggested that elevated pre-transplant ferritin levels are associated with a low incidence of the chronic graft-versus-host disease (GVHD). To verify these apparently paradoxical findings, we analyzed the association between pre-transplant serum ferritin levels and clinical outcomes of allo-SCT. Patients and methods: We retrospectively studied 161 consecutive patients (age, 16–65 years; median age, 46 years) who underwent their first allo-SCT for hematologic diseases at the Kyoto University Hospital between September 2004 and April 2010. The primary diseases were myeloid (n = 87) and lymphoid malignancies (n = 68), and non-malignant diseases (n = 6). Patients with acute leukemia in complete remission, untreated MDS, CML in the chronic phase, or non-malignant diseases were considered to have standard-risk diseases (n = 96), whereas those with any other hematologic disease status were considered to have high-risk diseases (n = 65). Stem cells were obtained from the bone marrow (BM) or peripheral blood (PB) of HLA-matched related donors (n = 56) and partially matched related donors (n = 18), BM of unrelated donors (n = 65), and cord blood of unrelated donors (n = 22). Conventional myeloablative regimens were used in 99 patients while reduced-intensity regimens were used in 62. The primary endpoint was the cumulative incidence of chronic GVHD, which is defined according to the Seattle criteria, while the secondary endpoints were overall survival, acute GVHD, treatment-related mortality (TRM), and relapse rate. For statistic analyses, cumulative incidence curves were used in a competing-risks setting to determine the incidence of GVHD, TRM, and relapse rate, whereas the Kaplan–Meier method was used to determine survival rate. The Fine and Gray proportional-hazards model for the sub-distribution of a competing risk and the Cox proportional-hazards regression model were used as appropriate. Factors evaluated in the analysis included the recipient's age, sex, diagnosis, disease status at the time of transplant, source of stem cells, conditioning regimen, GVHD prophylaxis, serum ferritin levels (<900 vs. ≥900 ng/mL), and serum CRP levels (<0.2 vs. ≥0.2 mg/dL). Only ferritin levels, CRP levels (which is associated with ferritin levels), and those factors with P-values of <0.10 in the univariate analysis were included in the multivariate analysis. Result: There was no significant difference in patient characteristics between the low-ferritin group (n = 105) and the high-ferritin group (n = 56). The median follow-up period among survivors was 38 months (range, 2–113 months). The cumulative incidence of chronic GVHD was lower in the high-ferritin group (32%) than in the low-ferritin group (49%) (P = 0.080) (Figure 1). In the multivariate analysis, serum ferritin level was significantly associated with the incidence of chronic GVHD (hazard ratio, 0.59; P = 0.045). Even when the serum ferritin level was treated as a continuous variable, this association remained significant. A trend toward a higher incidence of grade 3–4 acute GVHD was observed in the high-ferritin group; however, this association was not statistically significant. TRM was significantly higher in the high-ferritin group, but the relapse rate was not different between the 2 groups. High serum ferritin levels, the male sex, and high-risk diseases were significantly associated with a lower overall survival in the multivariate analysis. Conclusion: In our cohort, elevated pre-transplant ferritin levels were significantly associated with a lower incidence of chronic GVHD. Conversely, patients in the high-ferritin group tended to have a high incidence of severe acute GVHD. These patients had lower overall survival probably due to a higher incidence of TRM. Further clinical and biological studies on the immunomodulatory effects of iron or iron-related molecules, such as ferritin, may provide clues on the prophylaxis and management of acute and chronic GVHD. For this purpose, studies on post-transplant iron status in association with acute and chronic GVHD should also be conducted. Disclosures: No relevant conflicts of interest to declare.

Safety and Efficacy of Iron Chelation with Deferasirox in Adult Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5539-5539
Author(s):  
Young-Woo Jeon ◽  
Byung-Sik Cho ◽  
Hee-Je Kim ◽  
Jae-Ho Yoon ◽  
Seung-Hwan Shin ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Serum Ferritin ◽  
Myeloid Leukemia ◽  
Serum Ferritin Level ◽  
Ferritin Level ◽  
Chronic Gvhd ◽  
Iron Chelation ◽  
Hematopoietic Stem ◽  
Safety And Efficacy ◽  
Acute Myeloid

Abstract Background The prognostic impact of serum ferritin level has been well established in patients with myelodysplastic syndrome and acute myeloid leukemia (AML) in the context of allogeneic hematopoietic stem cell transplantation (Allo-HSCT). However, the clinical safety and efficacy of iron-chelation therapy (ICT) for adult AML with hyperferritinemia post-Allo-SCT has not been evaluated. Materials and methods We retrospectively evaluated 320 consecutive patients with de novo AML who received Allo-HSCT at complete remission in a single institution between January 2007 and February 2012. Serum ferritin levels were monitored from initial diagnosis to the several time points during the post-transplantation period in both the ICT group (n=113) and the non-treated group (NT, n=191). In the ICT group, ICT was started at least a month after transplantation when serum ferritin levels over 1,000 ng/mL, and continued to the ferritin level lower than 500 ng/ml unless serious adverse effects and/or relapse. Sixteen patients treated less than one month with ICT due to early complications, such as infection(n= 10, 62.5%), liver toxicity (n=4, 25%), and poor compliance (n=2, 12.5%) were excluded in the ICT group. The baseline characteristics between two groups were not significantly different. Results The median treatment duration in ICT group was 6.4 months (range, 1.0-49.2) with dosage of 20-40 mg/kg/day. Deferasirox treatment was discontinued at least one time in 43 patients (38%) in ICT group due to toxicities and/or poor compliance, but almost patients (n=40, 93%) could be treated again with deferasirox without further toxicities. High serum ferritin level of pre-Allo-HSCT over 1,000 ng/ml was significantly associated with poor overall survival (OS, 52.2% vs. 75.4%, HR 0.78, P <0.001) and lower chronic graft-versus-host disease (GVHD, 53.3% vs. 74.6%, HR 0.83, P =0.001). With a median follow up of 40.2 months, OS, disease-free survival (DFS), and cumulative incidence of relapse (CIR), non-relapse mortality, acute (over grade II) and chronic GVHD were 62.7%, 63.7%, 11.6%, 5.9%, 24.4% and 42.8%, respectively. On multivariate analyses, ICT group had significantly lower CIR (25.9% vs. 37%, HR 0.65, P=0.011) and higher cumulative incidence of chronic GVHD (46% vs. 20.1%, HR 1.88 P<0.001), with a trend of superior survival (OS, 72.0% vs 63.4%, P=0.053; DFS, 70.3% vs 61.4 %, P=0.058), whereas no association with acute GVHD (P=0.473) Conclusion Our data demonstrate that ICT with deferasirox was well tolerable in AML with hyperferritinemia after Allo-SCT, and suggest the independent association of ICT with increased incidence of chronic GVHD and decreased relapse. Iron chelation may modulate of immunobiologic properties during the period of immune reconstitution (low level of Treg cells and higher CD16+ NK cells, 2014 ASH Abstract #2543) and/or induce direct anti-leukemia effect by iron depletion, which need to be further evaluated. Disclosures No relevant conflicts of interest to declare.

Azacitidine (Vidaza®, Aza) and Donor Lymphocyte Infusions (DLI) In Patients with Acute Myeloid Leukemia (AML) or Myelodysplastic Syndromes (MDS) Relapsing After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT): Interim-Analysis From the AZARELA-Trial (NCT-00795548).

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1294-1294
Author(s):  
Thomas Schroeder ◽  
Akos Gabor Czibere ◽  
Nicolaus Kröger ◽  
Uwe Platzbecker ◽  
Gesine Bug ◽  
...  
Keyword(s):  
Overall Survival ◽  
Missing Data ◽  
Salvage Therapy ◽  
Interim Analysis ◽  
Research Funding ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Significant Activity ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct

Abstract Abstract 1294 Background: Patients with AML or MDS who relapse after allogeneic HSCT have a poor prognosis and therapeutic options are limited. The DNA hypomethylating agent Aza has significant activity in patients (pts) with AML and MDS and retrospective analyses have recently shown encouraging results with the use of Aza +/− DLI in patients with AML and MDS, who relapsed after allogeneic HSCT (Czibere et al., 2010; Luebbert et al., 2010). In line with these clinical observations preclinical data suggest that Aza enhances a Graft-versus-Leukemia (GvL) effect while mitigating Graft-versus-Host Disease (GvHD). Design/Methods: To evaluate the activity and safety of Aza in combination with DLI as first salvage therapy in pts with AML or MDS relapsing after HSCT, we conducted a prospective, multicenter, single-arm phase-II trial. Pts were allowed to receive up to 8 cycles Aza (100 mg/m2/d d1-5, every 28 days) and 3 DLI with increasing dosages (1-5×106 – 1–5×108 cells/kg) after every 2nd Aza treatment cycle. Additional DLI were permitted. Results: Between January 2009 and May 2010, 30 pts from 6 German transplant centres were included into this trial. So far, 25 pts (15 female/10 male) were evaluable and are presented in this analysis: Of these, 23 (92%) suffered from AML (15 de novo/8 secondary following MDS), 1(4%) from a MDS (RAEB-1) and 1 (4%) from a myelodysplastic/myeloproliferative syndrome (MDS/MPS, CMML-1). Median age was 54 years (range 29–71). Conditioning was myeloablative in 24 pts (96%) and non-myeloablative in 1 patient (4%). Eight pts (35%) received a graft from a matched sibling donor, while 15 (65%) were transplanted with a matched unrelated donor (2 pts missing data). Peripheral blood stem cells (PBSC) were used in 24 pts (96%; 1 pt missing data). At the time of transplant 6 pts (24%) had primary induction failure, another 6 (24%) suffered from first or secondary relapse, 10 pts (40%) were in first or second complete remission (CR), while 3 pts (12%) were untreated. With regard to their molecular and genetic characteristics at diagnosis, 21 pts belonged to an adverse (9 pts) or intermediate (12 pts) group, whereas 2 pts were diagnosed with a favourable genetic phenotype (2 pts not performed). Prior to relapse 9 (36%) and 3 (12%) pts had episodes of acute GvHD and/or chronic GvHD, respectively. Relapse occurred in all pts after a median of 160 days (range 19–1199) following HSCT (median BM blasts: 34%, range 5–100%, median chimerism: 63% range-1-100%). At the time of relapse, karyotype was evaluable in 13 of 25 pts (52%). Of these 13 pts, 4 pts had a normal karyotype, while 9 had chromosomal aberrations including 6 pts with a complex karyotype. Patients received a median of 3 courses Aza (range 1–8) and 18 of 25 pts (72%) received DLI (median: 1, range: 1–4, median CD3 dose 5×106/kg/DLI, range: 1–207×106). Following treatment, overall response rate was 64% with 5 pts (20%) achieving a CR or CRi, 3 (12%) a partial remission (PR) and 8 (32%) a stable disease (SD). Median response duration was 266 days. Acute GvHD occurred in 6 pts (24%) (2 skin/6 liver/ 2 gut) after a median of 65 days (range 19–179) following the first DLI, while chronic GvHD was observed in 3 pts (12 %, all limited). Hematotoxicity (grade III-IV) was observed in 64% of all evaluated patients. Common adverse events were gastrointestinal side effects as well as infections. After a median follow-up of 100 days (range 25–485) 15 of 25 pts (60%) are currently alive. Median overall survival of all pts is 184 days (range 87–281). All pts, who achieved a CR/CRi, remained in ongoing remission for a median time of 229 days. Achieving a CR (CR: not reached vs. no CR: 117 days, p .008) or any type of response (CR/CRi, PR or SD) to the combination of Aza and DLI (any response: not reached vs. no response: 79 days, p .0001) were associated with a significantly longer overall survival. Conclusion: The combination of Aza and DLI as salvage treatment for patients with AML or MDS who relapse after allogeneic HSCT seems to be safe and shows significant anti-leukemic activity. Response, including CR rates, so far match those from retrospective analyses. Data presented in this interim-analysis suggest that salvage therapy with Aza and DLI is of substantial therapeutic benefit in these challenging patients. Disclosures: Platzbecker: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Bug:Celgene: Honoraria. Luft:Celgene: Research Funding. Fenk:Celgene: Research Funding. Kobbe:Celgene: Research Funding.

Graft-Versus-Host Disease Following Myeloablative Busulfan Plus Fludarabine and Busulfan Plus Cyclophosphamide For Allogeneic Hematopoietic Stem Cell Transplantation In Acute Myeloid Leukemia In First Complete Remission

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3290-3290
Author(s):  
Qifa Liu ◽  
Hui Liu ◽  
Daihong Liu ◽  
Yongrong Lai ◽  
Jing Sun ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Research Funding ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Tnf Α ◽  
Before And After ◽  
First Complete Remission

Abstract Background Results from single institutions had shown that compared with busulfan plus cyclophosphamide (BuCy) conditioning, limiting tissue damage by myeloablative busulfan plus fludarabine (BuFlu) conditioning might decrease cytokines release, leading a lower incidence of the graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). In our prospective, multicenter and parallel-group study, further comparison was made of the incidences and severities of GVHD following BuCy and BuFlu myeloablative conditioning regimens in patients undergoing allo-HSCT for AML in first complete remission (CR1), and analyzed plasma cytokines before and after the conditioning. Methods A total of 148 patients with AML-CR1 undergoing allo-HSCT were enrolled into BuCy (busulfan1.6mg/kg, iv q12 hours, -7 ∼ -4d; cyclophosphamide 60 mg/kg.d, -3 ∼ -2d) or BuFlu (busulfan 1.6 mg/kg, iv q12 hours, -5 ∼ -2d; fludarabine 30 mg/m2.d, -6 ∼ -2d) group between January 2007 and January 2013. For patients enrolled between January 2012 and January 2013, plasma concentrations of IL-6, IL-1β, TNF-α, CXCL-10 and IL-17A before and after conditioning were measured by Enzyme-linked immunosorbent assay (ELISA) and compared between the two groups. Regimen-related toxicity (RRT), incidences and severities of acute and chronic GVHD, and overall survival were compared between the two groups. Results Of the 148 patients enrolled in the study, the data of 142 cases were used to determine the endpoints in the intent-to-treat population (72 in BuFlu group and 76 in BuCy group). The levels of TNF-α and IL-6 were significantly higher after the conditioning (5.60±4.40 vs 8.94±5.50 and 2.19±1.24 vs 6.06±12.16 pg/ml, P <0.001 and P =0.045 ), however, there were no significant differences on these cytokines between the two groups. The levels of CXCL-10 in BuCy group was significantly higher than that in BuFlu group (P =0.012). The incidence of I-II° and III-IV° acute GVHD were 42.1% and 6.8%, and 36.1% and 5.7%, respectively, in BuCy and BuFlu group (P=0.363 and P=0.770, respectively). Chronic GVHD occurred in 29 of 69 (41.7%) and 30 of 72 (41.7%) patients, respectively, in BuCy and BuFlu group (P= 1.000). And the incidence of extensive chronic GVHD were 14.3% and 16.7%, respectively, in BuCy and BuFlu group (P= 0.670). The median follow up duration was 824 (range, 3–2345) days. The 5 year overall survival were 79.2 ± 4.4% and 78.6 ± 76.1% (P= 0.555), respectively in BuCy and BuFlu group Conclusion In this report, the incidences and severities of acute GVHD as well as chronic GVHD were similar between BuFlu and BuCy regimen in AML-CR1 patients undergoing allo-HSCT. Disclosures: Liu: National Natural Science Foundation of China (Grant No.81000231, No.81270647) and Science and Technology Program of Guangzhou of China (11A72121174).: Research Funding; It was supported by 863 Program (No. 2011AA020105), National Public Health Grand Research Foundation (Grant No. 201202017): Research Funding.

Influence of Pretransplantation Serum Ferritin on Children Beta-Thalassemia Major Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5520-5520
Author(s):  
Yongsheng Ruan ◽  
Xuedong Wu ◽  
Xiaoqin Feng ◽  
Yuelin He ◽  
Chunfu Li
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Serum Ferritin ◽  
Serum Ferritin Level ◽  
Ferritin Level ◽  
Conditioning Regimen ◽  
Thalassemia Major ◽  
Hematopoietic Stem

Abstract Objectives: To evaluate the influence of pretransplantation serum ferritin on children β-thalassemia major (β-TM) undergoing allogeneic hematopoietic stem cell transplantation. Methods: A retrospective analysis of 266 HLA-matched children with β-TM from January 2009 and November 2014 was performed. Transplantation conditioning regimen of these children was the NF-08-TM protocol. Median follow-up time was 28 months (3~62months). We observed the relationship between pretransplantation serum ferritin level and transplantation complications which included infection, graft versus host disease(GVHD),veno-occlusive disease(VOD) and death. Results: Transplantation-related death occurred in 18 of 266 patients (6.8%). Five-year overall survival (OS) was found to be 92.8%. Among various complications, only infection was significantly associated with the high serum ferritin level (t=-2.673, P=0.008), especially serum ferritin above 3449.5μg/L(P=0.000). Meanwhile infection was the most common complication and severe infection would be main cause of deaths. Conclusions: NF-08-TM conditioning regimen was the optimization for HLA-matched β-TM patients. High pretransplantation serum ferritin level would bring high infection occurrence. Disclosures No relevant conflicts of interest to declare.

scholarly journals Survival after T-Cell Replete Haploidentical Related Donor Transplant Using Post-Transplant Cyclophosphamide Compared with Matched Unrelated Donor (MUD) Transplant for Lymphoid Malignancies

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 194-194 ◽  
Author(s):  
Alberto Mussetti ◽  
Abraham Sebastian Kanate ◽  
Mohamed A Kharfan-Dabaja ◽  
Kwang Woo Ahn ◽  
Alyssa DiGilio ◽  
...  
Keyword(s):  
Mortality Risk ◽  
Research Funding ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Study Cohort ◽  
Platelet Recovery ◽  
Post Transplant ◽  
Gvhd Prophylaxis ◽  
Significant Difference ◽  
Conditioning Regimens

Abstract Background: The use of haploidentical hematopoietic cell transplantation (HCT) using post- transplant cyclophosphamide (PT-Cy), calcineurin inhibitors (CNI) and mycophenolate as graft-versus-host disease (GVHD) prophylaxis is rapidly increasing in patients (pts) lacking suitable HLA-matched donors. Herein we compare outcomes of haploidentical HCT using this GVHD prophylaxis with 8/8 allele-level MUD HCT. Methods: Included are 917 adult (>18) lymphoma pts who underwent allogeneic HCT between 2008 and 2013. All pts received non-myeloablative or reduced-intensity conditioning regimens. The study cohort was divided into 3 groups; haploidentical (n=185), MUD without (w/o) antithymocyte globulin (ATG; n=491) and MUD with (w/) ATG (n=291). The primary end-point was overall survival (OS). Secondary endpoints included cumulative incidence (Cum-Inc) of acute GVHD, chronic GVHD, non-relapse mortality (NRM), relapse/progression (rel/prog) and progression-free survival (PFS). The study had an 83% power to detect an 11% difference in OS. Results: The baseline characteristics are shown in Table 1. Pts in the haploidentical group received conditioning with Flu/CY/2Gy TBI and PT-Cy + CNI and mycophenolate as GVHD prophylaxis, while the two MUD cohorts received fludarabine-based (+ an alkylator or 2GyTBI) conditioning and CNI-based GVHD prophylaxis. Graft source was bone marrow in 93% of the haploidentical pts and peripheral blood in 94% and 91% of MUD w/o ATG and MUD w/ ATG pts, respectively. The 28-day neutrophil recovery and platelet recovery were 94%, 97%, 97% (p=0.32) and 63%, 89%, 84% (p<0.001) in the haploidentical, MUD w/o ATG and MUD w/ ATG groups respectively. Cum-Inc of grade II-IV acute GVHD at day100 and chronic GVHD at 1 year was 27%, 40% and 49% (p=0.07) and 13%, 51% and 33% (p<0.001) in the haploidentical, MUD w/o ATG and MUD w/ ATG groups, respectively. On multivariate analysis (MVA) higher risk of chronic GVHD was seen in MUD w/o ATG (RR=5.85, 95%CI 3.96-8.64; p<0.0001) and MUD w/ ATG (RR=3.64, 95%CI 2.37-5.59; p<0.0001) groups relative to the haploidentical cohort. The 3 year NRM was 17%, 22% and 26% in the haploidentical, MUD w/o ATG and MUD w/ ATG groups (p=0.08), respectively. On MVA a trend towards higher NRM was noted in MUD w/ ATG cohort, RR 1.54 (95%CI 0.98 - 2.41, p=0.06), relative to the haploidentical group. Among the haploidentical, MUD w/o ATG and MUD w/ ATG cohorts the 3 year Cum-Inc of rel/prog was 36% vs. 28% vs. 36%, PFS was 47% vs. 49% vs. 38% and OS was 60%, 62% and 50% (Figure), respectively. MVA demonstrated no significant difference between the three groups in terms of rel/prog (p=0.27) and PFS (p=0.07). Compared to the haploidentical group, the two MUD groups did not have a significantly different mortality risk (inverse of OS; p>0.05), but compared to MUD w/ ATG, the MUD w/o ATG pts had a reduced mortality risk (RR=0.67; p=0.001). We tested for a transplant center effect on survival and found none. Conclusion: With lower-intensity conditioning regimens the early (up to 3 years) survival outcomes are comparable between conventional MUD transplants (w/ or w/o ATG) and haploidentical HCT with PT-Cy approach. Chronic GVHD was significantly lower with haploidentical HCT. Prospective, randomized confirmation of these findings is necessary before wide spread adoption of haploidentical HCT over MUD transplants in lymphomas.Table 1.Haploidentical N=185 (%)MUD w/o ATG N=491 (%)MUD w/ ATG N=241 (%)p-valueAge @ HCT, median (range)55 (18-75)55 (19-74)55 (20-73)0.13Male sex118 (64)301 (61)163 (68)0.25White race149 (81)469 (96)227 (94)<0.001KPS ≥ 90145 (78)311 (63)153 (63)<0.001HCT-CI≥355 (30)175 (36)88 (37)<0.001Histology NHL Hodgkin139 (75) 46 (25)386 (79) 105 (21)193 (80) 48 (20)<0.001Months from diagnosis to HCT, median (range)31 (<1-255)34 (<1-342)32 (4-460)0.19High LDH @ HCT16 (31)31 (33)11 (27)<0.001BM +ve @ HCT6 (12)5 (5)2 (5)0.35Extranodal disease @ HCT18 (35)20 (21)6 (15)0.11Prior lines of therapy, median (range)3 (1-7)3 (1-12)3 (1-8)0.41Remission @ HCT CR PR Refractory Untreated / missing72 (39) 99 (54) 10 (5) 4 (2)215 (44) 215 (44) 55 (11) 6 (1)100 (41) 96 (40) 40 (17) 5 (2)0.02Disease Risk Index Low Intermediate High45 (24) 126 (68) 13 (7)199 (41) 263 (49) 48 (10)75 (31) 129 (54) 37 (15)<0.001Median follow-up, months (range)36 (5-73)35 (4-74)35 (<1-75) Figure 1. Figure 1. Disclosures Armand: Infinity: Consultancy, Research Funding; Merck: Consultancy, Research Funding; BMS: Research Funding; Sequenta, Inc.: Research Funding. Smith:Celgene: Consultancy; Pharmacyclics: Consultancy. Sureda:Seattle Genetics Inc.: Research Funding; Takeda: Consultancy, Honoraria, Speakers Bureau.

Reduced Severe aGVHD and Improved Survival Using Post Transplant Cyclophosphamide/Tacrolimus/Methotrexate Graft Versus Host Disease Prophylaxis in AML Patients Receiving Myeloablative Fractionated Busulfan Conditioning Regimen

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3296-3296
Author(s):  
Uday Popat ◽  
Rima M. Saliba ◽  
Rohtesh S. Mehta ◽  
Amanda L. Olson ◽  
Julianne Chen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Board Of Directors ◽  
Research Funding ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Similar Proportion ◽  
Myeloablative Conditioning ◽  
Advisory Committees ◽  
Post Transplant ◽  
Gvhd Prophylaxis

Background: Myeloablative conditioning can be given safely to older patients by simply administering busulfan over a longer period (fractionated busulfan regimen) than the standard four day regimen. (Popat et al Lancet Haematology 2018). Subsequently, we added post-transplant cyclophosphamide (PTCy) GVHD prophylaxis to our fractionated regimen with a hypothesis that it will reduce GVHD and improve outcomes. Herein, we report the results of our retrospective analysis comparing outcomes of patients with AML who received fractionated busulfan myeloablative conditioning and PTCy versus standard tacrolimus (Tac) and methotrexate (Mtx) GVHD prophylaxis. Methods: Patients with AML between 18-70 years of age with adequate organ function and 8/8-HLA matched related or unrelated donor, who were treated on 4 consecutive protocols using fractionated busulfan were included in the analysis. All patients received two fixed doses of busulfan 80mg/m2 as outpatient either on days -13 and -12, or on days -20 and-13 followed by busulfan on day -6 to -3 dosed to achieve target area under the curve (AUC) of 20,000 mol/min for the whole course based on pharmacokinetic studies. Fludarabine ± cladribine were given on day -6 to -3. GVHD prophylaxis was PTCy 50mg/kg on days 3 and 4 and Tac ± mycophenolate mofetil in PTCy cohort (n=53), or standard Tac+ Mtx (n=53). Patients in both the cohorts were matched 1:1 by propensity score. Results: Baseline characteristics were similar between the PTCy and Tac/Mtx cohorts. The median age was 60 (range, 18-70) and 58 (range, 24-70) years, respectively, (P=0.3). Forty-nine percent were in CR, and 30% had comorbidity index >3 in each arm. Similar proportion of patients had ELN adverse risk in both arms (43% vs 40%, respectively P=0.7). The median follow up was 19 months (range, 3-36) in the PTCy and 46 months (range, 14-73) in Tac/Mtx cohort. Overall survival at 2-year was 78% vs 58% (P=0.03), non-relapse mortality was 6% vs 13% (P=0.2), incidence of grade 3-4 acute GVHD at 1-year was 6% vs 19% (P=0.07) and chronic GVHD at 2-year was 10% vs 29% (P=0.03) [Table 1 and figure 1]. The median time to neutrophil engraftment was prolonged by 3 days (15 vs 12 days; P<0.001) and platelet engraftment by 9 days (22 vs 13 days; P<0.001) in the PTCy cohort. Full donor chimerism at day 30 was noted in 79% vs 28% in the PTCy and Tac/Mtx cohorts respectively, (P<0.001). Conclusion: As compared to Tac/Mtx, PTCy-based GVHD prophylaxis not only reduced severe acute GVHD and chronic GVHD, but also improved overall survival in AML patients up to the age of 70 years who received myeloablative fractionated busulfan conditioning. Prospective randomized trial is warranted to validate these findings. Disclosures Popat: Bayer: Research Funding; Incyte: Research Funding; Jazz: Consultancy. Bashir:Imbrium: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; StemLine: Research Funding; Acrotech: Research Funding; Celgene: Research Funding. Ciurea:Kiadis Pharma: Membership on an entity's Board of Directors or advisory committees, Other: stock holder; MolMed: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; Miltenyi: Research Funding. Kebriaei:Kite: Honoraria; Pfizer: Honoraria; Amgen: Research Funding; Jazz: Consultancy. Nieto:Astra-Zeneca: Research Funding; Affimed: Consultancy; Affimed: Research Funding; Novartis: Research Funding. Oran:Astex pharmaceuticals: Research Funding; AROG pharmaceuticals: Research Funding. Qazilbash:Genzyme: Other: Speaker; Amgen: Consultancy, Other: Advisory Board; Autolus: Consultancy; Bioclinical: Consultancy. Molldrem:M. D. Anderson & Astellas Pharma: Other: Royalties. Champlin:Johnson and Johnson: Consultancy; Actinium: Consultancy; Sanofi-Genzyme: Research Funding.

Prospective Phase II Study of Prophylactic Azacitidine and Donor Lymphocyte Infusions Following Allogeneic Hematopoietic Stem Cell Transplantation for High Risk Acute Myeloid Leukemia and Myelodysplastic Syndrome

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1162-1162 ◽  
Author(s):  
Thierry Guillaume ◽  
Ibrahim Yakoub-Agha ◽  
Reza Tabrizi ◽  
Cecile Borel ◽  
Patrice Chevallier ◽  
...  
Keyword(s):  
Heart Failure ◽  
Immune Response ◽  
Stem Cell ◽  
High Risk ◽  
Prophylactic Treatment ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Post Transplantation ◽  
Hematopoietic Stem ◽  
Post Transplant

Abstract Although allogeneic hematopoietic stem cell transplantation is presently the only curative option for many patients with AML or MDS, relapse remains the main cause of morbidity and mortality. Strategies are therefore developed to prevent relapse. Post-transplant immune intervention with administration of prophylactic or pre-emptive donor lymphocyte infusion (DLI) and/or chemotherapy maintenance using DNA-demethylating agents such as azacitidine (aza) is being investigated. The exact mechanism of action of aza remains obscure and might be due in part to tumor antigen upregulation or other gene induction by tumor cells causing an immune response. We enrolled, in a clinical trial (ClinicalTrials.gov Identifier:NCT01541280), patients (pts) with high risk AML or MDS and candidates for allo-HSCT transplantation to receive azacitidine (aza) and DLI post-transplant as prophylactic treatment with the primary objective to reduce the relapse rate at 2 years following allo-HSCT and secondary objectives to increase disease free survival at 2 years post-transplant, increase overall survival at 2 years, investigate feasibility and safety of maintenance strategy combining chemotherapy and immunotherapy and follow the incidence and severity of acute and chronic GVHD. High risk AML was defined as AML in CR1 with unfavorable cytogenetics, AML in CR2 or greater remission, refractory AML or in relapse prior allogeneic transplantation. High risk MDS was defined as MDS with intermediate-2 group and higher risk group according to IPSS criteria. Aza was scheduled to begin between d+56 and d+112 post-transplant at the doses of 32 mg/m²/d sc for 5 days every 28 days for up to a total of 12 cycles if the pt had not acute GVHD >1 or severe infection. The first DLI was started following 3 cycles of aza and discontinuation of immunosuppressive prophylaxis, and if the pt had no clinical signs of GVHD, uncontrolled infection or a recent history of gr>2 acute GVHD. Two other DLI were scheduled every 8 weeks after the 5th and 7th cycle of aza. The doses of DLI 1, 2 and 3 were respectively 5x106, 1x107, 5x107 CD3+cells/kg for related donor, and 1x106, 5x106, 1x107 CD3+cells/kg for unrelated donor. Sixty-four patients were pre-included prior transplantation, 30 pts were subsequently included, 20 pts with AML and 10 pts with MDS, median age 58 y (22-70). The status at transplantation was: CR1 = 16 pts (53%), CR2 = 6 pts (20%), refractory = 5 pts (16%), upfront transplantation for MDS = 3 pts (10%). Cytogenetics was normal or intermediate for 15 pts and unfavorable for 15 pts (namely 8 pts with complex caryotype). Conditioning was myeloablative for 11 pts, reduced for 19 pts (including 2 sequential). Donors were unrelated volunteers in 18 pts (60%).The time between allografting and first aza cycle was 66 days (38-93). The median number of cycles of aza administered was 5 (1-12) with 10 pts (33%) completing the 12 cycles. Forty one DLI were injected in 17 pts: 5 pts received one DLI, 2 pts received 2 DLI, 8 pts received 3 DLI. Two additional pts received 4 and 5 DLI because of a mixed chimerism. The first DLI was given at a median of 142 d (129-221) post transplantation. Aza was well tolerated, but was discontinued in 20 pts: because of GVHD (n=11), relapse (n=5), GVHD/infection (1pt), sudden death due to heart failure (n=1), withdrawal of consent (n=2, one after 1 cycle and another after 5 cycles). Four months following transplantation, 24 (80%) demonstrated full donor chimerism (>95%) in CD3+ cells. Nine patients developed grade 1 to 3 acute GVHD (CI 29.8±9%), 6 who did not receive DLI and 3 following DLI (grade 1 n=2, grade 2 n=3, grade 3 n=4). No grade 4 acute GVHD was observed. Nine pts developed chronic GVHD (2 limited, 7 extensive), 3 who did not receive DLI, 6 following DLI. Twenty patients are alive. With a median follow-up from the allotransplant for those alive of 36 months (range 12 - 46 months), the survival at three years is 66%. Causes of death were infection (n=1), relapse (n=8), sudden death due to heart failure (n=1). The median time to relapse was 5 months (2.5-9) and the cumulative incidence of relapse at 3 years 28.1±8.5%. These results confirm that aza is well tolerated as a prophylactic treatment to reduce the risk of post-transplantation relapse. The incidence of GVHD following aza + DLI was not overwhelming. Analysis of T cell population and immune response as well as comparison to matched-pair control are currently performed and will be presented. Disclosures Moreau: Amgen: Honoraria; Novartis: Honoraria; Janssen: Honoraria, Speakers Bureau; Takeda: Honoraria; Bristol-Myers Squibb: Honoraria; Celgene: Honoraria.

Evaluation of Graft Versus Host Disease and Relapse Free Survival As Novel Endpoint in Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective Joint Naples-Paris Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2285-2285
Author(s):  
Simona Pagliuca ◽  
Antonio M Risitano ◽  
Sylvie Chevret ◽  
Flore Sicre de Fontbrune ◽  
Alienor Xhaard ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Relapse Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Graft Versus Host

Abstract The cure of hematologic disorders by allogeneic hematopoietic stem cell transplantation (HSCT) is often associated with major complications resulting in poor outcome, including acute and chronic graft-versus-host disease (GVHD), relapse and death. Classical endpoints such as overall survival (OS), desease free survival (DFS) and non relapse-mortality (NRM) had become more and more unsuitable for transplant research because of their inability to a dynamic mesure of transplant-associated comorbidity. For this reason several composite endpoints taking into account also GVHD-associated comorbidity were proposed in the last years. GVHD free/relapse free survival (GRFS), proposed by Holtan et al (Blood 2015), includes grades 3-4 acute GVHD, systemic therapy requiring chronic GVHD, primary disease relapse , or death for any cause considered as events. This endpoint seems to completely characterize the survival without mortality or ongoing morbidity. With the intent to analyse the outcomes of our transplanted cohort, we retrospectively analysed GRFS of 959 consecutive patients receiving HSCT at Federico II University in Naples (n=119) and Saint-Louis Hospital (n=840) in Paris between 2007 and 2014, identifying prognostic factors associated with a better outcome and estimating the incidences of all components of this endpoint: rates of acute and chronic GVHD, disease relapse and death. Patient, disease and transplant characteristics are listed in table 1. Median duration of follow-up after HSCT was 22.1 months (IQR: 5.6-51 months). Cumulative incidence at day 100 of grade II-IV acute GVHD and grade III-IV were 42% and 16%, respectively. Cumulative incidence of chronic GVHD requiring systemic treatment at 1 and 5 years was 23% and 33%, respectively, diagnosed according to NIH criteria [14% of patients had score 1 (mild), 58% score 2 (moderate) and 27% score 3 (severe)cGVHD]. Cumulative incidence of relapse (considering all malignant and non-malignant diseases) was 26.7% (N=219) at 5 years. Overall survival for the whole population was 57% (95%CI, 53.3-60.8) at 5 years and Disease free survival (DFS) and non-relapse mortality (NRM) were respectively 50% (95%CI, 46.6-53.8) and 23% at 5 years. GRFS was 25% (95%CI, 21.8-28.5) at 5 years. Factors identified as influencing GRFS based on univariate analyses were age higher than 45 years (HR=1.64, 95%CI, 1.40-1.92), bone marrow (BM) as stem cell source (HR=0.40, 95%CI, 0.32-0.50); reduced intensity conditioning (RIC) (HR=0.63, 95%CI, 0.53-0.74); disease type [non-malignant disorders: HR=0.24, 95%CI, 0.17-0.33; myelodysplastic and myeloproliferative syndromes (MPN/CML/MDS): HR=1.34, 95%CI, 1.10-1.63; whereas other diagnosis did not influence GRFS] and than unrelated donor (matched: HR=1.71, 95%CI, 1.41-2.07;mismatch:HR=1.81, 95%CI, 1.48-2.23). Based on a multivariable Cox model, only diagnoses (non-malignancies, HR=0.27, 95%CI, 0.19-0.38 and MPN/CML/MDS, HR= 1.35, 95%CI, 1.11-1.65), and HLA unrelated graft (matched, HR=1.42, 95%CI, 1.17-1.73 and mismatched, HR=1.55, 95%CI, 1.26-1.92) remained associated with the outcome (Figure 1 and 2). GRFS could represent the ideal endpoint following HSCT. It differs significantly based upon type of disease and donor type, essentially. This composite indicator yields more information regarding complications of HSCT than the simpler measurement of OS or DFS. Its use willbetter compare these clinically important outcomes that accompany disparate HSCT techniques. All examined prognostic factors could enhance our ability to optimally judge the risk and the probability of true recovery after allogeneic HSCT. Our data support the use of this composite endpoint to describe HSCT outcome, and also pave the way for the investigation of novel endpoints, which may also track the dynamic changes of post-transplant events in the long-term. These retrospective data represent the background to investigate the impact of novel strategies of HSCT aiming to improve the outcome of HSCT, as detectable, by using more sensitive endpoints, tracking clinical events associated with detrimental long-term outcome. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Risitano: Alexion Pharmaceuticals: Other: lecture fees, Research Funding; Novartis: Research Funding; Alnylam: Research Funding; Rapharma: Research Funding. Peffault de Latour:Pfizer: Consultancy, Honoraria, Research Funding; Amgen: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Alexion: Consultancy, Honoraria, Research Funding.

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