Abstract: Introduction In allogeneic stem cell transplantation (allo-SCT), recent reports have shown that post-transplant microbial diversity of the gastrointestinal tract is closely associated with clinical outcomes. Furthermore, pre-transplant microbial status has also been associated with the development of acute graft-versus-host disease (GVHD). These results indicate that pre-transplant microbial ecosystem may influence the immune system after allo-SCT, induce alloimmune response such as GVHD, and may finally affect the transplant outcome. Thus, we evaluate the association between pre-transplant microbial diversity and transplant outcomes. Patients and Methods Between April 2013 and March 2015, fecal samples were obtained from 107 patients in Komagome hospital. Fecal samples were collected within 2 weeks before conditioning. Microbial analysis was performed using 16S rRNA gene (hypervariable V1-2 region) sequencing. Operational taxonomic units (OTU)-based microbial diversity was estimated by calculating the Shannon index. Patients were classified into 3 groups based on the diversity index: low ( 〈 2), intermediate (2-3), and high ( 〉 3) diversity group, and we evaluated transplant outcomes such as survival, non-relapse mortality, and the cumulative incidence of GVHD, in these 3 groups. Results Among the 107 patients, there were 18 (16.8%) patients in the low diversity group, 48 (44.9%) in the intermediate diversity group, and 41 (38.3%) in the high diversity group. The median age of all patients was 49 (range: 16-72) years. The median follow-up period for survivors was 597 days (range, 23-1,046 days). We found no significant differences among 3 groups in terms of age, gender, underlying disease, disease status, performance status, hematopoietic cell transplantation comorbidity index, GVHD prophylaxis, conditioning regimen, stem cell sources, and human leukocyte antigen disparity. However, the patients in the low diversity group received intravenous antibiotics just before the conditioning more frequently compared to the patients in the intermediate /high diversity groups. The patients in the low diversity group showed poor survival (p=0.37, Figure 1a), higher non-relapse mortality (p=0.25, Figure 1b) and higher incidence of grade II-VI gastrointestinal GVHD (p=0.77, Fgiure 1c) compared with the patients in the intermediate /high diversity group although these results were not statistically significant. The cumulative incidence of relapse was similar between 3 groups. When compared between patients with and without acute GVHD, the composition of microbiota did not differ significantly between these patients. Discussion and conclusion Our results indicate that pre-transplant microbial diversity did not affect transplant outcomes. Furthermore, in contrast to previous report, the microbial composition was also irrelevant to the development of GVHD. Bacterial translocation after allo-SCT is a key trigger for the development of acute GVHD. Thus, microbial status in this period would be more important than that before allo-SCT. However, the patients in the low diversity group tended to show poor survival, higher incidence of non-relapse mortality and GVHD. Thus, further evaluation with larger sample size might be necessary to confirm the association between pre-transplant microbial ecosystem and transplant outcomes. Disclosures No relevant conflicts of interest to declare.

Abstract: FMT was safely performed in SCT patients, with 3 complete responses and 1 partial response. Temporal microbiota dynamics seem linked to gut condition and effector regulatory T cells also increased during response to FMT.

Abstract: [Background] Philadelphia chromosome positive (Ph+) leukemia is characterized by highly proliferative nature and clone instability that evokes the emergence of mutated clones, including BCR-ABL1 T315I mutated clone. Established evidence on the use of tyrosine kinase inhibitors (TKIs) after allogeneic hematopoietic stem cell transplantation (HSCT) is still lacking. The use of second-generation TKIs as a maintenance treatment after HSCT has been studied, and it is expected that their use would improve the prognosis by suppressing recurrence. The advent of ponatinib (PON), a potent inhibitor of tyrosine kinase including T315I mutated BCR-ABL1, is expected to improve clinical outcome of Ph+leukemia. However, there are few reports of a maintenance treatment using PON after HSCT. [Methods] We retrospectively reviewed data of 13 patients (pts) who received PON for Ph+leukemia after HSCT while in hematological complete remission (CR) between April 1, 2016 and July 15, 2019. Prophylactic treatment (Pro) was defined as post-transplant administration of PON while in minimal residual disease (MRD) negative CR. Pre-emptive treatment (Pre) was defined as starting PON when the bcr-abl transcript was detected by either quantitative or nested qualitative PCR after HSCT. ABL1 mutation was analyzed through the direct sequencing method. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events version 5.0. Overall survival (OS) was estimated using Kaplan-Meier method. Non-relapse mortality (NRM) and cumulative incidence of hematological relapse (CIR) were calculated using Gray's test. This study protocol was approved by the ethics committee of Tokyo Metropolitan Komagome Hospital. [Results] Underlying diseases were Ph+ALL in 8 pts (5 in CR, 3 in non-CR at HSCT), CML in 5 (all in second chronic phase). ABL1 mutations were analyzed in 12 pts and T315I mutation was detected in 4 pts with Ph+ALL and 2 with CML. Furthermore, compound mutations (CMs) in BCR-ABL1 were detected in 4 pts before HSCT. PON was used in 6 only after HSCT, and in 7 both before and after HSCT. During the median observation after HSCT of 584 days (range, 116-1,110) for survivors, no vascular occlusion event occurred. With regard to adverse events (AEs), grade 3 AEs occurred in 2 pts (15.4%) and no grade 4 AE was observed. Two had liver dysfunction and one of them discontinued PON due to grade 3 abnormalities in liver function tests. One suffered from grade 3 thrombocytopenia. Four had skin rashes lower than grade 3 that were indistinguishable from skin graft-versus-host disease, and all of them resolved through topical steroid therapy. Of all, 6 were in Pro group and 7 were in Pre group. The initial dose of PON was median 15mg (range 45mg/twice a week - 15mg/day) in Pro and median 30mg (range, 15-45mg) in Pre. The median days from HSCT to the start of PON was 107 days (range, 32-174) in Pro and 208 days (range, 50-364) in Pre. The median duration of PON treatment was 297 days (range, 20-699) in Pro and 188 days (range, 5-608) in Pre. At final observation in Pro group, 2 pts relapsed and died during the salvage therapy, 1 pt discontinued PON due to hepatic adverse event, and 3 pts were still on PON. Meanwhile, in Pre group, 5 pts achieved MRD negative CR after PON administration (1 pt also received donor lymphocyte infusion and stop PON due to liver dysfunction, 1 discontinued PON by the patient's request, and 3 of them were still on PON). One pt with CM relapsed but achieved CR through salvage therapy and 1 pt with low performance status (KPS 60) died at home of unknown cause six days after taking PON 30mg daily. For all the 13 pts receiving PON maintenance therapy, OS was 74.6% (95%CI; 39.8-91.1), CIR was 23.1% (95%CI; 5.1-48.5), and NRM was 7.7% (95%CI; 0.4-30.6) at 1 year after transplant (Figure 1). Two out of 4 pts with CMs (V299L/F317L and E255K/T315I/F317L) remains in MRD negative CR. The other 2 with CMs (E255K/T315I and D276G/T315I) had progressed to hematological relapse, suggesting the resistance to PON. In contrast, only one out of 9 without CMs relapsed on PON treatment. [Conclusion] Our results suggested that post-transplant maintenance treatment using PON was tolerable in the majority of patients with Ph+leukemia, although the optimal dose or the initiation strategy (Pre or Pro) are still undetermined. Furthermore, some patients with T315I-inclusive CMs seemed to be resistant to PON. The longer observation in a larger cohort is warranted. Disclosures No relevant conflicts of interest to declare.

Abstract: Background: Sarcopenia, the loss of muscle mass, has been recognized as a prognostic factor for cancer patients. For example, low body mass index (BMI) was reported to be a risk of poor overall survival (OS) among allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. However, low BMI was not associated with high non-relapse mortality (NRM) rate, and BMI may not directly reflect the physical condition. (Bone Marrow Transplant. 2014;49:1505-12). To evaluate the clinical impact of the muscle volume on the prognosis of allo-HSCT recipients, other biomarkers that directly reflect muscle mass may be warranted. Urinary creatinine excretion (UCE) has been reported to estimate muscle mass and have prognostic value for kidney transplant patients (Transplantation. 2008;86:391-8.). There is no report to evaluate clinical impact of UCE on the prognosis of allo-HSCT recipients. Therefore, we retrospectively analyzed the association between pre-transplant UCE and the transplant outcomes. Methods: We included 173 adult patients with acute myeloid leukemia (AML) in complete remission (CR) who underwent first allo-HSCT from 2006 to 2017 at our institute and measured UCE before allo-HSCT. Concerned the possibility of urine storage failure, two patients with low total daily urine volume ( 〈 0.5L/day) were excluded from this analysis. Therefore, we investigated the remaining 171 patients. In order to correct the physical disparities of individual patients, we evaluated the clinical impact of weight adjusted UCE (WA-UCE) ,i.e UCE / body weight [μmol/kg/day] (Intensive Care Med. 2018;44:1699-708.). We used receiver operating characteristics curve in order to determine the cutoff value of the WA-UCE and classified the patients into the high and low WA-UCE group. We evaluated transplant outcomes such as OS, progression-free survival (PFS), NRM, and cumulative incidence of relapse (CIR) between two groups. Results: The median age at allo-HSCT was 52 (range, 18-73) and there were more male patients (n=111) than female patients (n=60). Regarding cytogenetic risk, 15 (9.1%), 112 (65.8%), and 38 (23.0%) were categorized as favorable, intermediate, and poor risk, respectively (There were five patients without cytogenetic data). The median follow-up period of survivors was 704 (range, 9 to 3,857) days. We defined the cutoff value of the weight adjusted UCE as 148 μmol/kg/day in male and 128 μmol/kg/day in female. Among 171 patients, 90 patients (male = 59, female = 31) were in the high WA-UCE group and 81 patients (male = 52, female = 29) were in the low WA-UCE group. We found no significant differences between two groups in terms of the number of relapse before allo-HSCT, cytogenetic risks, conditioning regimens, hematopoietic cell transplantation comorbidity index, donor-recipient HLA matching, donor source, or estimated glomerular filtration rate. On the other hand, patient's age at allo-HSCT was significantly younger (low vs. high WA-UCE group: median, 53 [range, 18 - 73] vs. 48 [range, 19 - 68] years, P = 0.02) and BMI was lower (low vs. high WA-UCE group: median, 22.3 [range, 15.4 - 38.8] vs. 21.9 [range, 15.4 - 29.3] kg/m2, P = 0.003) in high WA-UCE group. In univariate analysis, we observed a significant difference in OS, PFS, and NRM between two groups (low vs. high WA-UCE group: 1-year OS, 60.1% vs. 80.9%, P 〈 0.01; 1-year PFS, 54.1% vs. 70.9%, P = 0.02; 1-year NRM, 24.8% vs. 12.3%, P = 0.02) (Figure1). On the other hand, there was no significant difference in 1-year CIR between two groups (low vs. high WA-UCE group: 21.1% vs. 16.8%, P = 0.63). In our cohort, the low BMI ( 〈 18.5 kg/m2) was not significantly associated with OS, PFS, CIR, and NRM (low vs. high BMI group: 1-year OS, 77.6% vs. 69.9%, P = 0.51; 1-year PFS, 74.1% vs. 60.9%, P = 0.45; 1-year CIR, 14.8% vs. 19.5%, P = 0.02, 1-year NRM, 11.1% vs. 19.5%, P = 0.70) In multivariate analysis, the low WA-UCE was an independent risk factor for OS (Hazard ratio (HR) [95% confidence interval (CI)]; 2.29 [1.38 - 3.80] , P 〈 0.01), PFS (HR [95% CI]; 1.76 [1.11 - 2.79] , P = 0.02), and NRM (HR [95% CI]; 2.22 [1.13 - 4.36] , P = 0.02) (table1). Conclusion: In allo-HSCT adult recipients with AML in CR, low WA-UCE before transplantation was associated with poor prognosis, which related to high NRM within 1 year. WA-UCE can be an independent, objective, simple, and reliable biomarker for evaluating muscle mass and predicting transplant outcome. Disclosures No relevant conflicts of interest to declare.

Abstract: Introduction Despite recent developments on various transplantation procedures and supportive therapy, nonrelapse mortality (NRM) after allogeneic stem cell transplantation (allo-SCT) remains an essential issue. In choosing the appropriate regimen for allo-SCT, decision-making information that considers the complexity of different risk factors is vital. The Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI), which was initially derived and validated by investigators at the Fred Hutchinson Cancer Research Center to predict NRM, has become a widely validated tool for predicting outcomes in many transplant settings (Sorror et al. Blood. 2005). It can also stratify patients for the risk of other outcomes, including overall survival and graft versus host disease. Patients with a high HCT-CI score tend to prefer allo-SCT with reduced-intensity conditioning. Conversely, for those who prefer allo-SCT with myeloablative conditioning (MAC) and has a low HCT-CI score, a prognostic indicator is unnecessary. Furthermore, the risk factors for NRM may differ among various conditioning regimens. Therefore, the current study aimed to establish a new prognostic model for patients specific to each MAC regimen before allo-SCT. Methods We performed a retrospective cohort study to develop prognostic models of NRM in patients conditioned with cyclophosphamide/total body irradiation (Cy/TBI) or busulfan/cyclophosphamide (Bu/Cy). We selected patients who had leukemia and lymphoma in remission or had untreated or stable myelodysplastic syndrome and experienced initial allo-SCT relapse between 2007 and 2017 in the Kanto Study of Group for Cell Therapy (KSGCT). The primary outcome measure was 2-year NRM. Furthermore, we evaluated variables such as patient age, albumin, liver function, renal function, respiratory function, ejection fraction (EF), C-reactive protein (CRP), stem cell source, donor type, antithymocyte globulin use, performance status, recipient/donor sexes, time interval from diagnosis to transplant, and HCT-CI score. To identify a set of variables for Cox proportional hazards, we used an Akaike Information Criterion (AIC)-based variable selection procedure. We assigned weights to individual parameters according to their prognostic significance in Cox proportional hazard models. The identified model's discriminative ability was assessed by Harrell's C-statistic calculated using the bootstrap method. Results Among the 555 patients analyzed, 338 received Cy/TBI, and 217 received Bu/Cy. In Cy/TBI and Bu/Cy, the median age was 39 (11-60) and 44 (18-62) years, the HCT-CI score ≤ 2 was observed in 82.1% and 87.6%, and 2-year NRM was found in 13.5% and 16.0% of the patients, respectively. Before transplantation, the most dominant parameters in Cy/TBI were abnormal liver function (AST/ALT or bilirubin & gt;upper limit of normal) and albumin value & lt; 4.5g/dL, whereas those in Bu/Cy were age & gt;40 years, EF & lt; 65 %, and CRP ≥ 0.2 mg/dL. Internal validation with bootstrap resampling showed good discrimination, with C-statistic values of 0.70 (95% CI: 0.69-0.71) in Cy/TBI and 0.68 (95% CI: 0.67-0.69) in Bu/Cy. Each of the abovementioned parameters, including age & gt;40 years, was scored as 1 point. To evaluate the 2-year NRM, we divided the total scores into three risk groups. In the Cy/TBI group, the NRM was 6.9% in low (score 0-1, n = 186), 19.5% in intermediate (score 2, n = 127), and 35.3% in high (score 3, n = 25) scores. In the Bu/Cy group, the NRM was 8.3% in low (score 0-1, n = 93), 21.7% in intermediate (score 2, n = 98), and 29.8% in high (score 3, n = 26) scores (Figure). Higher scores were strongly associated with worse NRM and survival. Conclusions Our prognostic models for NRM estimation can distinguish patients with a high NRM risk. To our knowledge, these models are the first prognostic models used to estimate NRM for standard-risk patients specific to each MAC regimen. This new simple index may help predict NRM and choose an appropriate conditioning regimen before allo-SCT. Figure 1 Disclosures Nakasone: Takeda Pharmaceutical: Honoraria; Otsuka Pharmaceutical: Honoraria; Bristol-Myers Squibb: Honoraria; Celgene: Honoraria; Pfizer: Honoraria; Novartis: Honoraria; Janssen Pharmaceutical: Honoraria; Eisai: Honoraria; Chugai Pharmaceutical: Honoraria; Nippon Shinyaku: Honoraria. Fujisawa:Takeda Pharmaceutical Company Limited.: Speakers Bureau; Astellas Pharma Inc.: Research Funding, Speakers Bureau; Otsuka Pharmaceutical: Speakers Bureau; Pfizer Japan Inc.: Research Funding, Speakers Bureau; Bristol-Myers Squibb Company: Speakers Bureau; Novartis Pharma KK: Research Funding, Speakers Bureau; Celgene: Speakers Bureau; Janssen Pharmaceutical K.K: Speakers Bureau; NIPPON SHINYAKU CO.,LTD.: Research Funding. Nakaseko:Novartis Pharma KK: Speakers Bureau; Pfizer Japan Inc.: Speakers Bureau. Kanda:Novartis: Honoraria; Kyowa Kirin: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria; Takeda Pharmaceuticals: Honoraria; Alexion Pharmaceuticals: Honoraria; Shire: Honoraria; Daiichi Sankyo: Honoraria; Ono Pharmaceutical: Honoraria; Nippon Shinyaku: Honoraria, Research Funding; Mochida Pharmaceutical: Honoraria; Mundipharma: Honoraria; Sanofi: Honoraria, Research Funding; Meiji Seika Kaisha: Honoraria; Shionogi: Research Funding; Otsuka: Honoraria, Research Funding; Celgene: Honoraria; Chugai Pharma: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Janssen: Honoraria; Astellas Pharma: Honoraria, Research Funding; Sumitomo Dainippon Pharma: Honoraria; Pfizer: Honoraria, Research Funding; Merck Sharp & Dohme: Honoraria.

Abstract: Background Constitutional partial trisomy 8 mosaicism (CT8M) is a congenital chromosomal abnormality with an estimated occurrence rate as one out of 25,000-50,000 pregnancies. CT8M has a wide variability in physical manifestation ranging from apparently normal to severe disablement. However, diagnosis of CT8M in adult without physical abnormality is difficult . Acquired trisomy 8, which is restricted to the malignant cells, is one of the most common chromosomal abnormalities in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), and clinical implication of carrying isolated trisomy 8 is considered as intermediate cytogenetic risk in MDS. However, isolated trisomy 8 without morphological dysplastic features is not definitive evidence for MDS. 15 to 20% of trisomy 8 in MDS are supposed to be derived from CT8M. We therefore diagnosed CT8M patients among patients with cytopenia and analyzed clinical and genetic features to uncover the association with MDS. Methods . Clinical features including cytogenetic analysis were analyzed regularly. Genomic DNA was extracted from whole PB cells or BM mononuclear cells. We performed targeted next-generation sequencing to identify mutations in 68 driver genes of myeloid neoplasms using AmpliSeq for Illumina Myeloid Panel and On-Demand Panel on the MiniSeq system (Illumina). Gene variants were detected by in-house analysis pipeline. The study was approved by the institutional review board and patients gave written informed consent for the study. Results We identified nine CT8M patients with cytopenia.They comprised 3 males and 6 females at a median age of 56 years (range 24-84 years) (Table). All the patients carried no physical abnormality nor conspicuous phenotypic features. Four patients (Patient #3, #4, #6 and #7) did not show apparent morphological dysplasia at the initial BM examination, and they were not diagnosed as MDS. Their cytopenia has not been exacerbated until now without any treatment, and the duration of stable cytopenia was from 2 to 12 years in these patients. By contrast, five patients with CT8M were diagnosed as MDS . Two patients (#5 and #8) were diagnosed as MDS-single lineage dysplasia (SLD), and their cytopenia has not become worse without any treatment for about 4 years. Other three patients diagnosed as MDS-multilineage dysplasia (MLD) showed various clinical courses. Patient #1 was treated with azacitidine and maintains complete hematological improvement after 34 courses of the treatment. Patient #2 was treated with erythropoietin stimulating agent and azacytidine but developed to AML 3 years after initial diagnosis but leukemic blasts has del(20), not +8. Patient #9 developed advanced pancytopenia in 3 months from initial diagnosis and received red blood cell transfusion regularly. Gene mutations were detected in five out of nine patients with CT8M. In three patients, gene mutations were detected at high (20 to 50%) variant allele frequency (VAF). Patient #2 who was analyzed at the AML phase had gene mutations of SRSF2, SF3B1, STAG2 and NOTCH1. BM sample from patient #9 showed ASXL1 mutation and two TET2 mutations. Patient #4 who did not show apparent myelodysplasia had a high VAF ASXL1 mutation, indicating clonal idiopathic cytopenias of undetermined significance. Two patients had low (2 to 5%) VAF mutations; patient #1 was analyzed after 34 courses of azacitidine had a TET2 mutation; patient #5 with MDS-SLD had a WT1 mutation and two PHF6 mutations. Four patients (#3, #6, #7 and #8) did not have any mutations. The clinical and genetic features showed that CT8M with cytopenia without MDS-related mutations were under 56 years old and did not develop to MDS or stayed at MDS-SLD. Patients with low VAF mutations were also stable. By contrast, patients with advanced diseases gained multiple MDS-related gene mutations with high VAF. One patient without dysplasia had a high VAF ASXL1 mutation. All the patients with gene mutations were age of 56 to 84 years. Conclusion Our results indicated that isolated trisomy 8 may cause cytopenia, but the cytopenia is not exacerbated without MDS-related driver gene mutations. CT8M patients with cytopenia might get gene mutations gradually with age, which leads to MDS or AML. Disclosures No relevant conflicts of interest to declare.

Abstract: Although imatinib mesylate has a highly inhibitory effect against BCR-ABL kinase, primary and secondary refractoriness have been observed. Point mutation within the kinase domain of BCR-ABL is one of the most important drug-resistant mechanisms. Of 25 reported point mutations, T315I BCR-ABL mutation might be dismal in clinical settings because it mediates clinical resistance to imatinib, nilotinib, and dasatinib, and the only established therapeutic option is hematopoietic stem cell transplantation at this moment. However, there is no information about the kinetics of this mutated clone. Here we developed quantitative Invader assay to monitor T315I BCR-ABL transcript. By using fluorescent resonance energy transfer system, the amount of released 5′ flap is measured as signal intensity, which enables us to calculate the percentage of T315I products with standard curve. Using this assay, we serially monitored T315I BCR-ABL transcript in a CML patient whose BCR-ABL transcript was still detectable (more than 100 copies/microgram RNA) 3 months after starting imatinib therapy. Although we have continued to monitor T315I BCR-ABL transcripts in 13 patients (chronic phase) up to 10 months, there was no patients who appear to be apparently resistant to imatinib due to a given T315I mutant, so far. In contrast, in a case of Ph+ ALL was being treated with chemotherapy including imatinib, we serially monitored both wild type and T315I BCR-ABL transcripts and observed the increased level of T315I transcript during relapse (0%at the time of diagnosis and 54.8% at relapse). Thus, our new strategy could be a useful tool to study the kinetics of the mutant clone and the pharmacokinetics of the drug resistant to T315I mutation.

Abstract: Introduction: Iron overload in patients who received hematopoietic cell transplantation (HCT) is one of the major clinical issues. Although deferasirox is well known to be an iron chelating agent, its safety for the patients who received HCT is unknown. Then, we designed a multicenter prospective study (phase 1) to evaluate the safety and efficacy of deferasirox in patients with iron overload after HCT. Methods: The eligibility criteria includes the duration at least 6 month after HCT, serum ferritin more than 1,000 ng/ml, red blood cell (RBC) transfusions more than 20 units, disease remission, normal renal function, performance status of 0 or 1, and the unfit of phlebotomy. The exclusion criteria were history of iron chelating therapy after HCT, presence of moderate or severe chronic graft-versus-host disease (GVHD), uncontrollable complications, and the history of hepatitis B or C virus infection. A registration target was set at 20 patients including 5 ineligibles. Safety of deferasirox was assessed by the dose escalation methods in the individual. After the registration, deferasirox was started at a dose of 5 mg/kg for four weeks. Then, the dose was increased to 7.5 mg/kg and 10 mg/kg. The patient attended every two weeks for the safety evaluation. Cessation criteria were any grade 2 to 4 of adverse event or early disease relapse. Namely, 4 weeks medication within grade 1 of adverse events was defined as tolerable and successful medication for the identical dose. Primary endpoint was the maximum tolerate dose of deferasirox and defined from the dose in which 50 to 80% of the eligible patients were tolerable. Results: A total of 16 patients were enrolled to the study from March 2013 to January 2016. One case was excluded out of analysis due to the early relapse and 15 were eligible. Median age was 42 years old (range: 22-68). Disease included acute myeloid leukemia (n=6), acute lymphoblastic leukemia (n=2), aplastic anemia (n=2), non-Hodgkin's lymphoma (n=2), and others (n=3). Median duration from HCT to deferasirox administration was 9 months (range: 6-84). Median amount of RBC transfusions was 54 units (range: 20-156). Median value of serum ferritin was 1,537 ng/ml (range: 1,027-7,655). Regarding to the dose escalation test, 9 cases succeeded in taking from the initial 5mg/kg to the final 10mg/kg and 6 resulted in withdrawal during the treatment: abnormality of clinical test in 5 mg/kg (n=3), late relapse in 7.5 mg/kg (n=1), self-cessation and gastrointestinal event in 10 mg/kg (n=2). Achievement rates of successful medication were 80% in 5 mg/kg (12 of 15), 73% in 7.5 mg/kg (11 of 15), and 60% in10 mg/kg (9 of 15), respectively. Among 10 evaluable cases, mean value of ferritin decreased from 1,605 ng/ml at pre-treatment to 1,303 ng/ml at post-treatment. The change of other markers were as follows: hemoglobin from 12.0 g/dl to 12.6 g/dl, aspartate aminotransferase (AST) from 24.9 IU/L to 28.3 IU/L, alanine aminotransferase (ALT) from 25.8 IU/L to 28.4 IU/L, creatinine (Cr) from 0.80 mg/dl to 1.05 mg/dl. Liver iron content (LIC) was examined only in 3 cases and the mean LIC was did not change before and after the treatment at 200 μmol/g. Main of grade 1 of adverse events were elevation of clinical test including Cr (60%), AST (40%), ALT (40%), and alkaline phosphatase (33%), diarrhea (27%), abdominal pain (20%), skin rash (20%), constipation (20%), nausea (13%). None of the patients developed the exacerbation of GVHD. Conclusion: This dose escalating method of deferasirox treatment for transplant patients may be feasible. Ten mg/kg of deferasirox may be maximum tolerated dose when given after HCT. The efficacy of iron chelation would be inadequate due to the low dose and short term of deferasirox. Validation of phase 2 study is warrant. Disclosures Morita: Bristol-Myers Squibb: Speakers Bureau. Kanda:Otsuka Pharmaceutical: Honoraria, Research Funding. Okamoto:Kyowa Hakko Kirin Co., Ltd.: Research Funding; Nippon Shinyaku Co., Ltd.: Research Funding; Bristol-Myers Squibb K.K.: Honoraria, Research Funding; Asahi Kasei Pharma Corp.: Research Funding; Shionogi & Co., Ltd.: Research Funding; Toyama Chemical Co., Ltd.: Research Funding; Chugai Pharmaceutical Co., Ltd.: Research Funding; Sumitomo Dainippon Pharma Co., Ltd.: Research Funding; Eisai Co., Ltd.: Research Funding; Teijin Pharma Limited: Research Funding; Astellas Pharma Inc.: Research Funding; Alexion Pharmaceuticals, Inc.: Research Funding; Otsuka Pharmaceutical Co., Ltd.: Honoraria, Research Funding; Pfizer Inc.: Honoraria, Research Funding; JCR Pharmaceuticals Co., Ltd.: Research Funding.