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Recent progress in genetic analysis technology has helped researchers understand the pathogenesis of acute myeloid leukemia (AML). Considering this progress, AML karyotype is still one of the most significant prognostic factors that provides risk-adapted treatment approaches. Karyotype changes during treatment have been observed at times, but their prognostic impact is sparse, especially on allogeneic stem cell transplantation (allo-SCT). Here, we retrospectively investigated the effect of chromosomal changes between diagnosis and pretransplantation on the prognosis of allo-SCT by analyzing the outcomes of 212 consecutive patients who underwent allo-SCT for the first time at Toranomon Hospital, Tokyo, Japan, between 2008 and 2018. Cytogenetic abnormalities at diagnosis and pretransplantation were categorized based on the 2017 European Leukemia Net risk stratification. Genetic abnormalities such as FLT3-ITD and NPM1 were not considered in this study due to lack of genetic information in most patients. We defined cytogenetic evolution as chromosomal changes classified from lower category to higher category. Seventeen patients (8%) had cytogenetic evolution between diagnosis and pretransplantation, and they showed a significantly worse relapse rate than those who were categorized in the intermediate group based on the karyotype at diagnosis (3-year confidence interval [CI] of relapse, 57.4% versus 24.9%; P.01). In multivariate analysis, cytogenetic evolution before allo-SCT had a significant impact on the CI of relapse (hazard ratio [HR], 3.89; CI, 1.75 to 8.67; P.01), as well as the high score of the hematopoietic cell transplantation-specific comorbidity index (HR, 0.54; CI, 0.31 to 0.94; P = .03), but had no significant impact on overall survival or nonrelapse mortality. These results indicate that cytogenetic evolution has a significant impact after allo-SCT and should be considered during AML treatment.

The impact of anti-HLA antibodies, except for donor-specific anti-HLA-A, -B, -DRB1 antibodies, on engraftment was retrospectively evaluated in 175 single cord blood transplantations (CBT). Patients and donors had been typed at HLA-A, -B, and -DRB1 antigens, and anti-HLA antibodies had been screened before transplantation to avoid the use of cord blood (CB) units with corresponding antigens. The median age was 59 (range, 17 to 74) years. Overall, 61% were male, 89% had high-risk disease status, 77% received myeloablative conditioning regimens, and over 80% were heavily transfused patients. Sixty-nine of the 175 (39.4%) were positive for anti-HLA antibodies. Thirty-nine patients had antibodies only against HLA-A, -B, or -DRB1, 13 had antibodies only against HLA-C, -DP, -DQ, or -DRB3/4/5, and 17 had antibodies both against HLA-C, -DP, -DQ, or -DRB3/4/5 and against HLA-A, -B, or -DRB1. Because CB units had not been typed at HLA-C, -DP, -DQ, or -DRB3/4/5, it was possible that antibodies against them were unrecognized donor-specific antibodies. Patients with antibodies only against HLA-A, -B, or -DRB1 showed comparable neutrophil engraftment rates to those without antibodies (89.7% versus 83%, P = .65), whereas patients having antibodies against C, DP, DQ, or -DRB3/4/5 showed lower engraftment rate (66.7%, P = .12), which became statistically significant in a subgroup of HLA-mismatched donor-recipient pairs (50%, P = .01). Our results demonstrated that the presence of donor nonspecific anti-HLA-A, -B, -DRB1 antibodies had no significant influence on engraftment, whereas anti-HLA-C, -DP, -DQ, or -DRB3/4/5 antibodies adversely affect engraftment, possibly because of unrecognized donor-specific anti-HLA antibodies against them, especially in HLA-mismatched CBT.

BACKGROUND: The prognosis of chronic myeloid leukemia (CML) in advanced stages (accelerated phase, AP or blast crisis, BC) is still extremely poor even with tyrosine kinase inhibitors (TKIs) and allogeneic hematopoietic cell transplantation (allo-HCT) is the only curative treatment for them. METHOD: Using our database, we retrospectively collected CML patients transplanted at Toranomon Hospital between June 2004 and March 2014, after the introduction of TKIs in Japan. RESULT: Twenty-nine consecutive patients were extracted. The median age was 52 years (range; 16-70). The disease status at diagnosis was chronic phase (CP, n=11), accelerated phase (AP, n=5) and blast crisis (BC, n=13). All the patients were treated with TKIs before transplantation, including imatinib (n=15), nilotinib (n=1), dasatinib (n=6), imatinib/dasatinib (n=4), nilotinib/dasatinib (n=1) and imatinib/nilotinib/dasatinib (n=2). All the 11 patients in CP at diagnosis progressed into AP/BC in their course and only 3 patients achieved second CP (MinorCyR, n=1; PCyR, n=1; MMR, n=1) at transplantation. On the other hand, 11 of 18 patients in AP/BC at diagnosis achieved CP (MinorCyR, n=1; PCyR, n=4; CCyR, n=3; MMR, n=3) at transplantation and the remaining 7 patients did not achieve CHR (Fig. 1). The median HCT-CI and EBMT score at transplantation was 2 (range, 0-5) and 5 (range, 0-7), respectively. Additional cytogenetic abnormalities developed until transplantation in 8 of 11 patients (73%) in CP at diagnosis and in 11 of 18 (61%) in AP/BC at diagnosis. Point mutations in ABL gene were detected in 9 of 20 patients (45%) in their course. Four of 7 patients (57%) in CP at diagnosis had ABL mutations, including T315I (n=1), E255K (n=2) and L359C (n=1). Five of 13 (38%) in AP/BC at diagnosis had ABL mutations, including T315I (n=4) and V299L (n=1). Overall, 14 of 29 (48%) patients underwent transplantation in CP stage (MinorCyR, n=2; PCyR, n=5; CCyR, n=3; MMR, n=4). The donors were related PBSC (n=6), unrelated BM (n=4) or unrelated CB (n=19). The conditioning regimens were myeloablative in 20 patients and reduced-intensity in 9. Twenty-seven patients achieved neutrophil engraftment at a median day of 19 (range, 10-34). The cumulative incidence of neutrophil engraftment was 93.1% at day 42 (patients engrafted, n=27; dead before day 19, n=2). At 3 years, the cumulative incidence of relapse and non-relapse mortality was 32.3% and 14.0%, respectively. In 15 patients who did not achieve CP before transplantation, 11 patients (73.3%) achieved CR after transplantation. With a median follow-up of survivors of 1144 days (range, 127-3705), overall survival (OS) and event free survival (EFS) at 3 years was 63.2% and 56.3%, respectively. In univariate analysis, age ( Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures No relevant conflicts of interest to declare.

Abstract 4535 Incidence and clinical features of idiopathic pneumonia syndrome and diffuse alveolar hemorrhage after unrelated cord blood transplantation. Aya Nishida 1, Atsushi Wake 1, Hisashi Yamamoto 1, Kazuya Ishiwata 1, Nobuaki Nakano 1, Masanori Tsuji 1, Yuki-Asano Mori 1, Naoyuki Uchida 1, Koji Izutsu 1, Kazuhiro Masuoka 1, Akiko Yoneyama 3, Shigeyoshi Makino 4, Shuichi Taniguchi 1. 1 Department of Hematology, Toranomon Hospital, Tokyo, Japan; 2 Department of Pathology, Toranomon Hospital, Tokyo, Japan; 3 Department of Infectious Diseases, Toranomon Hospital, Tokyo, Japan; 4 Department of Transfusion Medicine, Toranomon Hospital, Tokyo, Japan [Background] Idiopathic pneumonia syndrome (IPS) and diffuse alveolar hemorrhage (DAH) are non-infectious pulmonary complications of hematopoietic stem cell transplantation (HSCT) with unclear pathogenesis and treatment. [Objective and method] To investigate the incidence and clinical features of IPS/DAH after unrelated cord blood transplantation (uCBT), we retrospectively analyzed 370 patients underwent uCBT from January 2005 to June 2010 at Toranomon Hospital. Diagnosis of IPS/DAH was made by multilobar infiltrates on CXR or CT, clinical signs of pneumonia: cough, dyspnea, or rales, abnormal physiology: increased arterial-alveolar oxygen gradient, or the needfor supplemental oxygen support, and no evidence of respiratory tract infection. [Result:] Twenty five cases of IPS/DAH were identified, with incidence of 6.8%. The median-age was 59 years (range; 26–72). Nineteen patients underwent transplantation for leukemia, 4 for malignant lymphoma, and 2 for aplastic anemia. IPS/DAH was diagnosed at a median of 34 days (range; 8–93) after uCBT. All patients were administered mPSL therapy. Nine of 25 patients were administered etanercept combined with mPSL pulse therapy. Five of 9 had not responded, while 4 responders had worse their respiratory condition after discontinuation of etanercept therapy. Twenty four of 25 died of respiratory failure. [Conclusion] IPS/DAH after uCBT are fetal pulmonary complications. It is suggested that the incidence of IPS/DAH after uCBT appears similar to that observed after transplantation using other sources. But our results suggested that the existing treatment such as etanercept combined mPSL pulse have only limited efficacy as a therapy for IPS/DAH after uCBT. Further research is needed to characterize the condition of this syndrome and to investigate the optimal therapy and prophylaxis. Disclosures: No relevant conflicts of interest to declare.

MUD 169 0.65 (0.57-0.72) 0.54 (0.45-0.62) 8/10 Loci 31 0.47 (0.29-0.64) 0.40 (0.23-0.57) 0.04 DFS 9/10 Loci 105 0.65 (0.55-0.74) 0.50 (0.40-0.60) Single DQB 18 0.78 (0.51-0.91) 0.72 (0 45-0.87) 0.29 Single C 26 0.56 (0.35-0.73) 0.37 (0.18-0.56) 0.14 Single DQB1 87 0.64 (0.53-0.73) 0.47 (0.36-0.58) 0.42 MUD 169 0.09 (0.04-0.14) 0.13 (0.08-0.19) 8/10 Loci 31 0.07 (0.01-0.19) 0.13 (0.40-0.28) 0.36 aGvHD (Gr 2-4) 9/10 Loci 105 0.14 (0.08-0.22) 0.21 (0.14-0.30)