ALBERT

Description: Background Invasive fungal infections (IFIs) are of great concern after allogeneic hematopoietic stem cell transplantation (HSCT), the risk of which is considered to be particularly prominent among cord blood transplantation (CBT) recipients. Patients and Methods We retrospectively analysed the records of 749 adult patients who underwent CBT or unrelated bone marrow transplantation (uBMT) for the first time at the Toranomon Hospital between 2002 and 2012, and who had neither prior history nor suspicious findings of IFIs. As prophylaxis for IFIs, fluconazole (FLCZ) or itraconazole (ITCZ) capsules were conventionally used until around 2006, which were then changed to newer mold-active agents including ITCZ oral solution, voriconazole or micafungin after their approval in Japan, the choice of which was subjected to physician's discretion. Results Engraftment achieved in 418 CBT patients and 198 uBMT patients with a significantly longer neutropenic period in CBT patients (median 20 days vs 18 days, P

Description: Abstract 3132 Introduction: In year 2008 version of WHO classification for myeloid malignancies, a category of AML with myelodysplasia-related changes (AML-MRC) was defined which included both de novo AML with dysplasia and AML secondary to MDS. It is characterized by poor chemosensitivity for which allogeneic transplantation (allo-SCT) has been a viable option to cure. Umbilical cord blood transplantation (UCBT) is a possible treatment strategy that can be performed for those who lack suitable donors due to rapid availability and less stringent HLA matching required. So far, there have been sparse reports available on UCBT for those with AML-MRC. This study was conducted to see the current update in our institute and to see whether the presence of induction chemotherapy before transplant is better for the outcome. Design and Methods: We retrospectively reviewed patients diagnosed as AML-MRC who underwent UCBT at our institute from Mar. 2002 to Mar. 2011 consecutively. Patients who lacked appropriate adult PB/BM donors underwent UCBT. Patients who had prior history of transplantation, were in poor performance status (ECOG PS 〉3), had active bacterial or fungal infections at the time of conditioning were excluded. Results: Eighty-one patients were included. 52 (64%) were males, and median age was 61 years (range, 17–72). 35 (43%) were de novo AML, and 46 (57%) were AML secondary to MDS. Median time from diagnosis to transplantation was 346 days (range, 42–7997). 39 (48%) did not receive induction chemotherapy before transplant. 76 (94%) were not in remission, 29 (36%) were in high, and 52 (64%) were in very high WPSS risk group, just before transplant. 54 (67%) received reduced-intensity conditionings. 65 received GVHD prophylaxis of tacrolimus-based, while 16 did cyclosporine alone. Median observation time for survivors was 646 days (range 32–2456). Median days of neutrophil recovery (〉 500/ul) was 20 days (range, 11–45), and cumulative incidence of engraftment was 76.5 % up to day 50 post-transplant. Cumulative incidences of relapse and non-relapse mortality at 2 years post-transplant were 37.8 % and 33.3 %, respectively. Higher incidence of relapse was observed in those with prior history of MDS in univariate analysis (51.8 % vs. 21.2 % at 2 years post-transplant, P = 0.004), which was the only significant factor associated with higher relapse rate in multivariate analysis (P = 0.020). More NRM was observed in those received transplant early period from 2002 to 2005 vs. those who did from 2006 to 2010 (45.1 % vs. 25.5 % at 2 years post-transplant, P = 0.001), and in those received GVHD prophylaxis using CsA alone vs. others (72.0 % vs. 24.8 % at 2 years post-transplant, P = 0.0002). In multivariate analysis, higher degree of HLA mismatch (2 antigens vs. less than 2) and GVHD prophylaxis using CsA alone were associated with higher incidence of NRM (P = 0.024 and P = 0.00047, respectively). Overall survival (OS) was estimated as 42.1 % at 2 years post-transplant. Better OS was observed in those who received conditioning containing 12.8mg/kg of iv busulfan (60.8% vs. 32.4% at 2 years post-transplant, P = 0.0337), in those received tacrolimus-based GVHD prophylaxis vs CsA alone (47.9 % vs. 17.0 % at 2 years post-transplant, P = 0.0024), and in those received transplant in recent period from 2006 to 2010 vs. those who did from 2002 to 2005 (52.1 % vs. 26.1 % at 2 years post-transplant, P = 0.0248). In multivariate analysis, GVHD prophylaxis using CsA alone and poor WPSS risk category just before transplant were the factors significantly asssociated with poor OS (P 〈 0.0001 and P = 0.001, respectively). There were no significant differences between presence or absence of prior induction chemotherapy in terms of cumulative incidence of neutrophil recovery (71.4 % vs. 82.1% up to day 50 post-transplant, P = 0.88), relapse (38.0 % vs. 36.1%, P = 0.94), NRM (30.7 % vs. 35.4 %, P = 0.87), and OS (47.7 % vs. 36.2%, P= 0.72) at 2 years post-transplant. Conclusions: These data indicate that CBT is a feasible and promising treatment approach for those with AML-MRC, including elderly patients. More intensive GVHD prophylaxis was beneficial in reducing NRM and improving OS for the population studied. Presence of prior induction chemotherapy before transplant was not associated with higher rate of engraftment or better OS, suggesting tumor reduction before pre-transplant conditioning may not be necessary for successful outcome in our transplant settings. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 4705 [Background] Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by abnormal accumulation of alveolar surfactant protein within alveoli. Acquired PAP has been sub-classified into autoimmune and secondary PAP according to the presence of serum anti-granulocyte macrophage colony-stimulating factor (GM-CSF) autoantibody. Hematological diseases including myelodysplastic syndrome (MDS) are the most frequent causes for secondary PAP with unclear pathogenesis independent of anti-GM-CSF antibody.[Objective and method] To assess the clinical effect of HSCT for PAP, we retrospectively analyzed 4 patients with MDS who received allogeneic transplantation at Toranomon Hospital. [Case report] Case 1 is a 35-year-old male with pancytopenia. He was diagnosed with MDS-RA with trisomy 8 abnormality in January 2008. In January 2009, he had productive cough and chest X-ray and CT revealed opaque consolidation in the bilateral lower lung fields. The diagnosis of PAP was made by transbronchial lung biopsy findings. In April 2010, he underwent unrelated bone marrow transplantation (BMT). But idiopathic pneumonia syndrome as a transplant-related complication developed and died on day 55. Case 2 was a 42-year-old female who had a history of aplastic anemia with normal karyotype from March 2007. In March 2009, she had cough and abnormal chest X-ray and CT findings. The diagnosis of PAP was made by bronchoalveolar lavage (BAL) findings. At this time, the diagnosis of MDS-RAEB with trisomy 8 was made. In September 2009, she underwent unrelated cord blood transplantation. But she died by sepsis and pneumonia of Stenotrophomonas maltophilia on day 12. Case 3 was a 58-year-old female with stomatitis who was diagnosed with Behcet's disease in 2001. In May 2001, she developed fever and productive cough. She was diagnosed with PAP by abnormal chest X-ray and BAL findings. In July 2009, she developed pancytopenia, and the diagnosis of MDS-RAEB with trisomy 8 was made. In March 2010, she underwent unrelated BMT. After transplantation, PAP was gradually improved. Case 4 was a 47-year-old male with dyspnea who was diagnosed with PAP by CT and BAL findings. At the same time, he was diagnosed with MDS-RCMD with trisomy 8. In June 2011, he underwent peripheral blood stem cell transplantation from a HLA-identical brother. His transplant clinical course was uneventful and PAP was completely improved by day 42 in CT findings.[Discussion &Conclusion] Case 1 and 2 died of pulmonary complication developed after HSCT, one is pneumonia and another was idiopathic pneumonia syndrome. In case 3 and 4, both transplant clinical course was relatively uneventful and PAP disappeared with the improvement of MDS after HSCT. It is suggested that HSCT might be the effective treatment of secondary PAP with hematological disease, but secondary PAP itself may be the risk of pulmonary complication after HSCT. As we reported the possible association of trisomy 8 MDS with PAP development in 3 cases1, all 4 MDS cases presented here revealed trisomy 8 abnormality of bone marrow cells. Disclosures: Off Label Use: Mycophenolate mofetil was off-lable use for GVHD prophylaxis.

Description: Abstract 4553 Introduction Acute graft versus host disease (GVHD) remains the most frequent complication after allogeneic hematopoietic stem cell transplantation (SCT). In reduced intensity cord blood transplantation (CBT) previous studies have reported a lower incidence of severe acute GVHD compared with conventional allo-SCT. However, in these studies the incidences of grade II-IV acute GVHD varied widely from 26% to 51% (H.Narimatsu Stem cell int. 2011: 607569). In particular, post transplant immune disorders, including early immune reactions (PIR) and acute GVHD, are potential complications following CBT in adult patients. Such reactions might increase the risk of organ dysfunction, leading to high rates of transplantation-related mortality, particularly in patients who do not respond to primary therapy, which usually consists of steroids. Infliximab, a chimeric monoclonal antibody against tumor necrosis factor alpha, has shown activity against steroid refractory acute GVHD. Patients and Methods We retrospectively reviewed 275 patients who underwent single-unit reduced intensity cord blood transplantation consecutively from March 2007 to December 2011 at our institute. Patients in whom PIR or acute GVHD developed received methylprednisolone 1–2 mg/kg per day. If no partial or complete resolution of symptoms occurred, they were considered steroid-refractory and proceeded to infliximab treatment. The dose of infliximab was 5 mg/kg/day once weekly for at least 1 course. An antifungal drug, itraconazole or micafungin or voriconazole was used until all immunosuppressive drus were withdrawn. Results In this study we retrospectively evaluated 54 patients who had steroid refractory acute GVHD. Of these, 21 who received infliximab were analyzed. GVHD prophylaxis was with only tacrolimus(n=15) and mycophenolate mofetil+tacrolimus(n=6). All of them developed grade III to IV GVHD. Median follow-up time of survivors was 548 days (range, 222–1152). The overall response rate was 62% (n=13), and 9 patients (43%) experienced complete response (CR). 5 patients (24%) did not respond and 3 (14%) had progressive GVHD. The Kaplan-Meier estimate of overall survival was 31%, with no signs of chronic GVHD (n=2). Four patients who responded subsequently died, one of exacerbation of GVHD, three of infections. All the 8 unresponsive patients died of GVHD or infections. Five patients (21%) had non-Candida invasive fungal infections. Sixteen patients(79%) had bacterial infections. Conclusion Infliximab was well tolerated and active for the treatment of steroid-resistant acute GVHD even following reduced intensity cord blood transplantation. However, it is associated with a high rate of infections. Controlled studies to assess the pharmacokinetics and most effective dosing regimen of infliximab for the treatment of steroid refractory acute GVHD are warranted. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 461 Background: Human herpes virus 6 (HHV-6) encephalitis is a growing concern after cord blood transplantation (CBT), which leads to permanent neurological sequelae that do not allow patients to get back into society. The pathogenic mechanism remains unknown and appropriate preventative strategies have not been established. Patients and methods: To evaluate incidences, risk factors and outcomes of HHV-6 encephalitis after CBT, we reviewed the medial records of 496 adult patients who underwent CBT for the first time at the Toranomon Hospital between 2002 and 2011, and who survived more than 7 days. Over the entire period, routine prophylaxis with acyclovir against reactivation of herpesviruses and pre-emptive therapy with ganciclovir or foscarnet (FCV) against cytomegalovirus disease were performed. From January 2006, prophylactic administration of FCV with monitoring of serum HHV-6 viral load against HHV-6 disease was introduced, the indication of which was decided at a physician's discretion. Plasma HHV-6 DNA copy numbers were measured using real-time PCR method, and the detection limit was 200 copies/mL. Immune reaction prior to neutrophil engraftment characterized by unexplained fever in the absence of documented infection with skin eruption, peripheral edema and body-weight gain was defined as pre-engraftment immune reaction (PIR), which was categorized as mild and severe, according to the degree of concomitant organ dysfunctions. HHV-6 encephalitis was defined as the neurological symptoms with positive PCR results for HHV-6 in cerebrospinal fluid (CSF) and the absence of other identified etiologies of encephalitis. Results: Forty-two patients developed HHV-6 encephalitis with a cumulative incidence of 8.5%. The incidence was significantly higher in the period from 2006 to 2011 compared to the period from 2002 to 2005 in spite of the introduction of prophylactic FCV after 2006 (11.1% vs. 4.3%, P=0.01), probably owing to more vigorous investigation. Among the 308 patients who received CBT after 2006, engraftment was achieved in 239 at a median of 20 (10–66) days after CBT, and PIR occurred in 133 patients at a median of 10 (4–24) days, the severity of which was classified into mild in 114 and severe in 19. 132 patients developed grade II-IV acute graft-versus-host disease (GVHD) at a median of 31 (9–91) days, and 182 received high-dose corticosteroids at 〉= 0.5mg/kg with a median starting point of 19.5 (0–1363) days. Serum HHV-6 PCR measurement was performed in 280 patients, 122 of who showed positive test results at a median of 20 (8–193) days. Prophylactic FCV was given in 234 patients from a median of 11 (0–35) days, with a median duration of 23 (2–79) days. HHV-6 encephalitis occurred in 34 of the 308 patients at a median of 22 (11–49) days, with a cumulative incidence of 11.2%. The median peak level of HHV-6 DNA was 20,000 (200–400,000) copies/mL in CSF, in contrast with 200 (0–89,300) copies/mL in plasma. PIR was identified as an independent significant risk factor for HHV-6 encephalitis (HR 3.13(1.52–6.44), P=0.002), which occurred more frequent in patients with severe PIR compared to those with mild one (HR 2.82(1.11–7.18), P=0.029). Another significant risk factor was high-level of HHV-6 DNA in plasma at 〉=10,000 copies/mL (HR 3.29(1.17–9.30), P=0.024), which was, however, observed in only 7 of the 34 patients with encephalitis. Neither grade II-IV acute GVHD nor the use of high-dose steroids influenced an incidence of the encephalitis (HR 2.2(0.90–5.37), P=0.083, and HR 0.98(0.47–2.03), P=0.95). Prophylactic FCV at 〉=60mg/kg showed a significant benefit in preventing HHV-6 encephalitis (HR 0.27(0.09–0.77), P=0.015), which substantially reduced the incidence to 1.6% if PIR was completely suppressed, whereas the incidence reached 23.4% in the presence of PIR if the FCV was not given (P=60mg/kg combined with the optimal suppression of PIR might provide a further reduction of HHV-6 encephalitis after CBT. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 4498 Background: Unrelated cord blood transplantation (uCBT) using reduced-intensity conditioning (RIC) is increasingly used for older and medically unfit patients. Data on the efficiency of hematopoietic stem cell transplantation (HCT) after RIC in younger and standard-risk patients are limited relative to myeloablative conditioning (MAC). Objective and method: To compare the outocomes of RIC to MAC in uCBT for adult patients with standard-risk hematological diseases, we retrospectively reviewed medical records of 57 standard risk hematological disease patients who underwent first uCBT at Toranomon Hospital from Jan. 2005 to December.2011. The definition of standard risk disease is severe aplastic anemia (SAA), myelodysplastic syndrome (MDS) in RA, RARS, and RCMD, acute myeloid or lymphoid leukemia (AML, ALL) in complete remission (CR) 1 or 2, chronic myeloid leukemia (CML) in chronic phase, malignant lymphoma (ML) and adult T-cell leukemia (ATL) in CR. RIC and MAC are defined according to previously reported criteria. Result: The median age of the studied patients was 55 years (range; 26–70). Twenty nine of patients received RIC and 28 MAC. Eleven patients of SAA, 7 MDS, 17 AML, 12 ALL, 5 CML, 2 ML, and 3 ATL were included in this study. Median follow-up days of survivors was 299 (11–2522). Cumulative incidence of neutrophil engraftment was 89.2% and the median days of engraftment is 20 days (11–51). Cumulative incidence of grade 2 to 4 acute graft versus host disease (aGVHD) was 42.9%. The 5-year disease-free and overall survival (DFS and OS) rates were 49.1% and 42.6%, respectively. The 5-years OS was comparable between MAC and RIC (RIC= 52.1% versus MAC= 44.2%; P=0.90). The 5-years OS of the elderly patients 〉54 years (n=27, 47%) were significantly lower than that in the younger patients (n=30, 53%) (35.1% versus 63.7%; P=0.042). The 5-years transplant-related mortality (TRM) was comparable between MAC and RIC (RIC= 35.0% versus MAC= 28.6%; P=0.56). The relapse rate was also comparable in two groups (RIC=11.9% versus MAC=33.6%; P=0.2) Conclusion: This study showed that uCBT with RIC for standard risk disease patients with median age of 55 years old had the similar results as MAC regimens in the 5-years OS, DFS, TRM and relapse rate. Disclosures: No relevant conflicts of interest to declare.

Description: Background EBV-associated post-transplant lymphoproliferative disorder (EBV-PTLD) is uncommon but one of serious complications after allogeneic stem cell transplantation (SCT). However, there has been little literature published on clinicopathological feature of it. Method We retrospectively investigated 825 cases of allogeneic SCT (unrelated bone marrow (uBM) 159, related peripheral blood (rPB) 94, cord blood (CB) 572) at Toranomon Hospital between January 2006 to November 2012. EBV-PTLD was defined as histologically confirmed Epstein-Barr virus (EBV) positive lymphoproliferative disorder developed after allogeneic SCT. Results We identified 12 cases of EBV-PTLD in our cohort. Cumulative incidence of EBV-PTLD at 2 years was 1.5%. Median time from allogeneic SCT to the diagnosis of EBV-PTLD was 6.4 (2.5-26) months. Eight patients were male and median age at the diagnosis of EBV-PTLD was 58.5 years (28-66). Underlying diseases were acute myeloid leukemia (n=5), myelodysplastic syndrome (1), acute lymphoblastic leukemia (2), adult T cell leukemia-lymphoma (1), aplastic anemia (2) and chronic myeloid leukemia in blastic phase (1). Conditioning regimens were fludarabine-based (n=10) and TBI/CY (n=2). None had an antithymocyte globulin-containing regimen. Donor sources were uBM (n=1) and CB (11). EBV serology before allogeneic SCT was tested in 11 and all were positive. Patients who received CB showed higher incidence of EBV-PTLD compared to those in non-CB cohort (2.2% vs 0.6%, p 〈 0.01), although patients characteristics was different between them. One patient developed PTLD after third allogeneic SCT. All but one patients had a history of acute graft-versus-host disease (aGVHD) of grade I (n=2), grade II (6) and grade III (3), respectively. Chronic GVHD was observed in 6 patients. Eight patients were on immunosuppressive therapy (IST) with calcineurin inhibitors and/or steroids when EBV-PTLD was suspected for the first time. Although lymphadenopathy was detected by CT scan in 7 patients, surface lymph nodes were swollen in only 3 patients. Initial manifestations were fever in 8, and diarrhea in 5 patients. EBV-PTLD was diagnosed from lymph nodes (n=3), skin (3), bone marrow (2), stomach/duodenum (1), colon (2), and lung (1), respectively. Histological feature was monomorphic (n=4), polymorphic (2), early lesion (4), and unknown (2), respectively. LMP1 and EBNA2 was positive in 40% (4/10) and 30% (3/10), suggesting latency status of I in 50% (6/12), II in 8.3% (1/12), III in 25% (3/12), and unknown in 16.7% (2/12). EBV DNA of 100 copies/microL or above was detected in peripheral blood in all of the EBV-PTLD cases. The treatment for EBV-PTLD were rituximab alone (n=3), rituximab plus reduction of IST (6), rituximab plus cytotoxic chemotherapy (1), and observation alone(2). Although 8 patients achieved response, 2 patients suffered a relapse of EBV-PTLD. With a median follow up of 27.5 (4.1-47.7) months, 2-year overall survival was 46.9% after diagnosis of EBV-PTLD. Eight patients died and 4 are alive without relapse of EBV-PTLD. Causes of death were EBV-PTLD (n=2), relapse of underlying disease(3), infectious disease(2), and aGVHD(1). Conclusion Twelve cases of EBV-PTLD were identified in 825 transplants. Cumulative incidence of EBV-PTLD at 2 years was 1.5%. The incidence of EBV-PTLD after CB transplant was higher than that after non CB transplant, although we have to take into consideration that patients feature was different between them. Response to rituximab and/or reduction of IST was observed in 8 patients with a 2-year overall survival rate of 46.9%. Patients with prior aGVHD and with longer duration of immunosuppressive therapy may have an increased risk of developing EBV-PTLD. Since the initial manifestations were often equivocal, and survival rate after diagnosis is not high, having EBV-PTLD in mind as one of the possibilities is critical for prompt diagnosis. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 3043 Introduction HLA-mismatched unrelated cord blood transplantation (UCBT) is feasible and, in retrospective comparative analyses, allows survival rates similar to conventional unrelated HLA-matched adult-derived grafts. Although it is clear that the degree of UCB HLA mismatch in patients has a negative effect on outcomes, the biologic implications of HLA haplotype itself have not been explored for UCBT. In unrelated bone marrow transplantation, an effect of HLA haplotype matching on GVHD has been clarified. (S.Morishima. et al. Blood 2010). This study was conducted to determine the impact of HLA haplotype matching in reduced intensity UCBT. Patients and Methods To determine the impact of HLA haplotype matching with outcomes after UCBT, We retrospectively reviewed patients with hematologic malignancies who underwent reduced intensity CBT at Toranomon Hospital from August 2006 and December 2010 consecutively. Patients who had prior history of transplantation, were in poor performance status (ECOG PS 〉3), had active bacterial or fungal infections at the time of conditioning were excluded. Then, the remaining 164 consecutive patients were reviewed. The most frequently used conditioning regimens were fludarabine, alkylating agent (melphalan or busulfan) with total body irradination (TBI), tacrolimus plus mycophenolate mofetil for GVHD prophylaxis. DNAs of 164 pairs were analysed for HLA-A, -B, and -DRB1 based on High Resolution typing, and we have determined the HLA haplotype based on Japanese common HLA haplotypes referred from the previous reports. Results For A, B, DR based on high resolution typing the following mismatch occurred: no mismatch 3(2%), one mismatch 12(7%), two mismatch 58(35%), three mismatch 60(37%), four mismatch 28(17%), five mismatch 3(2%) in the GvH direction, and: no mismatch 2(1%), one mismatch 16(10%), two mismatch 55(34%), three mismatch 56(34%), four mismatch 32(20), five mismatch 3(2%) in the HvG direction. Then 37 among 164 pairs were defined as the HLA haplotype matched group. The number of total nucleated cells and CD34+ cells were not significantly different between HLA haplotype matched group and non-matched group. The cumulative incidence of neutrophil recovery was higher in HLA haplotype matched group than in non-matched group.( 94.6% vs. 80.3% up to day 60, p=0.0027). Lower incidence of pre-engraftment immune reaction(PIR) and acute GVHD were observed in haplotype matched group (37.8 % vs. 47.9 % up to day 60 post-transplant, P = 0.32), III to IV acute GVHD( 18.9% vs. 27.7% up to day 100 post-transplant, p=0.29). The cumulative incidences of relapse tended to be lower in haplotype matched group than in non-matched group (21.5% vs. 31.5%, P=0.28).Overall survival (OS) was estimated as 36.0 % at 3 years post-transplant. There were no significant differences between mathed and non-matched group in the cumulative incidence of OS (36.8 % vs. 34.3% at 3 years post-transplant, P = 0.84). Conclusion HLA haplotype matching in UCBT was found to have a significant impact on engraftment in this analysis. Disclosures: No relevant conflicts of interest to declare.

Description: Comparable 2-year overall and progression free survival among unrelated cord blood, unrelated bone marrow, and related peripheral blood stem cell transplantation in adult patients with standard-risk hematological diseases; A single center retrospective analysis Background Cord blood has become one of the major alternative donor sources for those who lack identical related donors in recent years. In Japan, an annual number of unrelated cord blood transplantation (uCBT) has been increasing and it reached 1179 cases in 2012, which is comparable to those of unrelated bone marrow transplantation (uBMT) and related peripheral blood stem cell transplantation (rPBSCT). So far, there is still limited data available on the comparative outcomes of adult standard risk patients receiving uCBT, uBMT and rPBSCT. Objectiv and method To compare the outcome of uCBT with those of uBMT and rPBSCT for adult patients with standard-risk hematological diseases, we retrospectively reviewed medical records of 142 patients with standard risk hematological diseases who underwent first allogeneic hematopoietic stem cell transplantation (allo-HSCT) at Toranomon Hospital from Jan 2005 to December 2011. The definition of standard risk disease is severe aplastic anemia (SAA), myelodysplastic syndrome (MDS) in refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), and refractory cytopenia with multilineage dysplasia (RCMD), acute leukemia in complete remission (CR) 1 or 2, chronic myeloid leukemia in chronic phase, non-Hodgkin lymphoma (NHL) in CR, and adult T-cell leukemia/lymphoma (ATL) in CR. Patients with active infection were excluded. Result The median follow-up day of survivors was 654 (19-2745). The characteristics of patients are summarized in Table 1. Forty-six patients performed uCBT, 66 did uBMT, and 30 did rPBSCT. The median age of the patients was 50 years (range, 16-70). There were more elderly patients in uCBT group than uBMT and rPBSCT groups (p=0.009). Cumulative incidence of neutrophil recovery at 50 days after transplantation was lowest in uCBT group and highest in rPBSCT group (uCBT= 87.1%, uBMT= 94.7%, rPBSCT=100%; P

Description: Abstract 4563 Introduction: Cord blood transplantation with fludarabine-containing toxicity-reduced conditioning (RT-CBT) has been widely applied to adult patients who have advanced hematologic diseases and are not eligible for conventional conditioning. Severe immune-mediated reactions early after transplant (preengraftment immune reactions, PIR) have been the major cause of early non-relapse mortality particularly for elderly patients. Mycophenolate mofetil (MMF) has been administered since late December 2005 at our institute and was shown to be effective in reducing early toxicity (Transplantation 92:366,2011). However, disease relapse has been the issue hampers successful outcomes, and the optimal GVHD prophylaxis has still not been established. We conducted a retrospective analysis of those who received RT-CBT at our institute using tacrolimus + MMF focusing on the impact of MMF dosing on the outcome. Design and Methods: We retrospectively reviewed patients aged 55 and older who underwent single-unit RT-CBT and GVHD prophylaxis using tacrolimus + MMF consecutively. Median dose of MMF was 33 mg/kg recipient body weight per day, ranging from 13 to 80 mg/kg, divided by 2 or 3 times at each physician’s determination. MMF was started on day -1 and continued until neutrophil recovery (〉500/μl). Patients who had prior history of transplantation, were in poor performance status (ECOG PS 4 and greater), had active bacterial or fungal infections at the time of conditioning, had diagnosed as multiple myeloma were excluded. Results: From December 2005 to April 2011, 134 patients underwent RT-CBT at our institute. Twenty-seven were excluded due to active infection at the day of transplant or poor performance status, and 107 patients were subjected to the following analysis. The diagnoses included were AML/MDS (n=87), ALL (n=2) CML/MPD (n=4), ML (n=11), and SAA (n=3). Eighty-six (80%) had high risk diseases, and 29 (27%) and 6 (6%) were in ECOG PS 2 and 3, respectively. Cumulative incidence of neutrophil recovery 〉500/μl were 81 %. Median follow-up time of survivors was 521 days (range, 83 – 1847). Cumulative incidences of non-relapse mortality were 21.4 % and 27.3 % at day 100 and 1 year post-transplant, respectively. Overall survival and event-free survival at 1 year post-transplant were estimated as 47.7 % and 31.7 %, respectively. The patients were subdivided into 2 groups according to MMF dosing (≥30 vs.