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  • 1
    Publication Date: 2014-12-06
    Description: 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 (
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  • 2
    Publication Date: 2013-11-15
    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
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  • 3
    Publication Date: 2019-11-13
    Description: Delayed immune reconstitution after allogeneic transplantation increases the risk of treatment-related mortality, and chronic GVHD. Previous reports showed that absolute lymphocyte count at day 30 (ALC30) was a significant prognostic factor of transplantation, and lower numbers of total CD4+ T cells and naïve CD4+ T cells in particular were associated significantly with higher mortality. However, there is little knowledge about the factors associated with low lymphocyte recovery, especially in cord blood transplantation (CBT). The cut-off value of lymphocyte recovery for statistical significance has not been determined yet. We retrospectively analyzed the outcome of 579 consecutive patients who underwent single cord blood transplantation (CBT) for the first time at Toranomon Hospital between January 2011 and 2018. Patients with active infection at transplantation (n=40), in poor ECOG PS (3 or more) (n=36), or lacked information about CT before CBT (n=1) were excluded from this study. Five hundred and two patients (n=317 male; n=185 female) were included in this study. The median age at transplantation was 57 years (range, 16-77), with a median HCT-CI score of 2 (0-10). Underlying diseases were AML (307), MDS (43), MPN (20), ALL (50), mature lymphoid malignancies (54), and others (28). Median spleen index (SI) before transplantation was 60.2 (16.5-319.7). Three hundred and ninety eight patients (79%) were not in remission at transplant. MAC regimens were selected in 400 (80%). TAC alone was used in 132 (26%) as GVHD prophylaxis. Median number of TNC and CD34+ cells infused were 2.62 (1.57-6.85) x 107/kg and 0.86 (0.29-3.77) x 105/kg, respectively. 194 (39%) were positive for anti-HLA antibodies, but none had donor-specific. With a median follow-up of 32 (range, 3-99) months, cumulative incidence of neutrophil engraftment (NE), the 3-year probabilities of overall survival (OS), relapse rate (RR) and non-relapse mortality (NRM) for entire population were 92.8%, 40.6%, 23.5%, and 35.3%, respectively. Underlying disease (myeloid malignancy), disease status at SCT (non-CR), poor PS (PS=2), GVHD prophylaxis (TAC+MMF), low CD34-positive cell dose (
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  • 4
    Publication Date: 2007-11-16
    Description: Varicella-zoster virus (VZV) infection remains a common complication after hematopoietic stem cell transplantation (HSCT). The introduction of long-term prophylaxis with low-dose acyclovir against VZV reactivation has been investigated, because VZV-related complications including post-herpetic neuralgia and secondary infection significantly affect the patient’s quality of life. We started long-term oral acyclovir at 200 mg/day in July 2001. Acyclovir was continued until the end of immunosuppressive therapy and at least one year after transplantation. To evaluate the efficacy of this long-term prophylaxis with ultra low-dose acyclovir against VZV reactivation, we analyzed the records of 242 Japanese adult patients who underwent allogeneic HSCT for the first time from June, 1995 to November, 2006 at University of Tokyo Hospital. Sixty-six patients developed VZV reactivation at a median of 248 days after HSCT, with a cumulative incidence of 34.7%. There was no VZV-related death. Only one breakthrough reactivation occurred during long-term acyclovir, responding well to the therapeutic dose of valacyclovir. The use of long-term acyclovir was the only independent determinant that significantly decreased the overall incidence of VZV reactivation (20.4% vs 50.5%, P
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  • 5
    Publication Date: 2008-11-16
    Description: Late occurrence of viral infections beyond day 100 after hematopoietic stem cell transplantation (HSCT) was widely recognized to depend on the profound immune suppression due to severe chronic GVHD and its treatment. However, there have been few reports clarifying the direct relationships between the development of late viral infections and immune reconstitution after HSCT. To evaluate the correlation of the immune recovery with the occurrence of late cytomegalovirus (CMV) or varicella-zoster virus (VZV) infections, we retrospectively analyzed the records of 60 Japanese adult patients who underwent allogeneic HSCT for the first time from April, 2002 to February, 2007 at the University of Tokyo Hospital, and survived longer than 180 days after HSCT. Absolute lymphocyte subset counts (CD3+ T cells, CD3−CD19+ B cells, CD3+CD4+ helper T cells, CD4+CD45RO+ memory T cells, CD4+CD45RA+ naïve T cells, CD3+CD8+ cytotoxic T cells, CD3−CD56+ natural killer cells), absolute monocyte counts, serum IgG, IgA, and IgM levels were measured at 3 and 6 months after HSCT. As a prophylaxis against late CMV disease, risk-adopted preemptive therapy with ganciclovir was performed by monitoring CMV antigenemia beyond day 100 after HSCT. For late VZV disease, oral administration of acyclovir at 200 mg/day was principally continued until the end of immunosuppressive therapy and at least one year after HSCT in 52 patients, whereas valacyclovir at 500 mg/day three times a week was administered until one year after HSCT in eight patients. Two out of 60 patients have already developed CMV disease within 100 days after HSCT. Thirteen of the remaining 58 patients developed late CMV infection defined as 10 or more CMV-Ag positive cells per two slides at a median of 125 days (101 to 546 days) after HSCT. CD3+ T cells less than 400x106/L (P=0.003), CD3+CD4+ T cells less than 200 x106/L (P=0.013), CD4+CD45RO+ T cells less than 100x106/L (P
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  • 6
    Publication Date: 2012-11-16
    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.
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  • 7
    Publication Date: 2015-12-03
    Description: Background: Bloodstream infection (BSI) is one of serious complications after allogeneic hematopoietic cell transplantation (HCT). Several risk factors have been described in previous reports. They included elderly patients, myeloid malignancies, myeloablative conditioning and HLA mismatch. In recent years, the number of umbilical cord blood used as an alternative donor source is rapidly increasing. The interval between transplant and neutrophil engraftment after umbilical cord blood transplantation (UCBT) is longer than that of other stem cell sources, and bacterial infections are one of the most serious concerns after UCBT. However, studies that focus on the impact of donor source on the incidence of BSI and include sufficient number of UCBT are lacking. In the study, we aimed to analyze the impact of umbilical cord blood on the development of BSI after allogeneic HCT retrospectively. Patient and Method: We retrospectively studied the patients who received transplant as first allogeneic HCT in Toranomon Hospital between Apr 2003 and Mar 2014. We analyzed the incidence of BSI that occurred within 100 days after transplant. BSI was defined as isolation of a bacterial or fungal pathogen from at least 1 blood culture, with the exception of coagulase-negative staphylococci (CNS) and normal contaminants (Corynebacterium species, Lactobacillus species, Bacillus species and Propionibacterium species), which required 2 separate blood cultures with the same antibiogram, to be considered a true infection. BSI was considered polymicrobial, if 2 or more pathogens were isolated in a single blood culture. The patients whose blood culture was positive within 2 weeks before transplant and the patients whose performance status (PS) were 4 before transplant were excluded. Result: A total of 1032 patients were extracted. Donors were related peripheral blood stem cell and/or bone marrow (r-PB/BM) in 155 patients, unrelated BM (ur-BM) in 243, and unrelated umbilical cord blood (ur-CB) in 634. The median age of recipient was 49 years (range, 16 - 82). Underlying diseases were as follows; AML (n=458), MDS (n=83), CML (n=30), MPN (n=15), MDS/MPN (n=13), ALL/LBL (n=134), CLL (n=3), AUL (n=9), NHL (n=162), HL (n=17), ATL (n=53), MM (n=16), AA (n=35) and others (n=4). The cumulative incidence of BSI was 47.6% (95% confidence interval, 44.5 - 50.6%) at 100 days after allogeneic HCT. The median onset of first BSI was day 7 (range, 0 - 99) after transplant. In 491 patients who developed BSI, a single pathogen was isolated in 409 patients (gram-positive cocci: GPC in 257, gram-negative rod: GNR in 112, gram-positive rod: GPR in 31, fungus in 9). Of the 491 patients with BSI, two pathogens were isolated in 74 patients (two GPCs in 37, one GPC & one GNR in 20, one GPC & one GPR in 13, two GNRs in 3, one GNR & one GPR in 1) and three pathogens were isolated in 8 patients (three GPCs in 5, two GPCs & one GNR in 1, two GPCs & one GPR in 1, one GPC & two GNRs in 1). Of the 581 isolates, GPCs accounted for 66%. The most frequent isolates in GPCs and GNRs were Staphylococcus epidermidis (34% in GPCs) and Pseudomonas aeruginosa (33% in GNRs), respectively. The cumulative incidence of BSI after transplants from r-PB/BM, ur-BM, ur-CB was 31.7%, 35.0%, 56.3%, respectively (p49 vs. ≤49, p
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  • 8
    Publication Date: 2011-11-18
    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.
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  • 9
    Publication Date: 2011-11-18
    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.
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  • 10
    Publication Date: 2018-11-29
    Description: BACKGROUND: Cord blood is an established alternative donor cell source for allogeneic hematopoietic cell transplantation. However, engraftment failure is still a major concern after transplantation, especially for patients transplanted lower doses of donor cells. Higher CD34+ cell dose leads to a secure and fast engraftment, and the units of cord blood which contain CD34+ cells of 1.0 - 1.7 x 105 /kg at freezing or 1.0 - 1.2 x 105 /kg at thawing are recommended (Thomas' Hematopoietic Cell Transplantation, 5th Edition). Actually, most adult patients cannot obtain such sufficient cell dose-containing cord bloods and the feasibility of single-unit cord blood transplantation (CBT) containing lower CD34+ cell dose than 1.0 x 105 /kg is unclear. METHODS: To investigate the lower threshold of CD34+ cell dose, we studied the patients who received single-unit CBT as the first transplantation between 2009 and 2017. The patients whose ECOG performance status was 0 or 1, and who do not have donor-specific anti-HLA antibody (DSA) were analyzed. Institutional review board of Toranomon Hospital approved the study (research number #1666). RESULTS: A total of 421 patients were studied. The median age and body weight of patients was 57 years (range, 16 - 74) and 56.4 kg (32.2 - 94.6), respectively. Myeloid diseases accounted for 78% of the patients, and 83% were not in remission. Myeloablative conditioning regimens were used in 80% of the patients. All patients used Tac (26%) or Tac plus MMF (74%) as GVHD prevention. The median numbers of total nucleated cells and CD34+ cells were 2.61 x107 /kg (range, 1.57 - 5.85) and 0.86 x 105 /kg (0.29 - 3.77) at freezing, respectively. The cumulative incidence of neutrophil engraftment was 90.7% at 60 days after transplantation (95% confidence interval, 87.5 - 93.1). The median day of neutrophil engraftment was day 21 (range, 5 - 45). Multivariate analysis identified higher CD34+ cell dose, less HLA mismatch, and lymphoid disease as significant favorable factors for neutrophil engraftment (p 〈 0.05), and CD34+ cell dose was most significant among the following pre-transplant factors (HR 1.57, p 〈 0.00001): age (≤ 57 vs. 〉57 years), body weight (≤ 56.4 vs. 〉 56.4 kg), ECOG performance status (0 vs. 1), disease (myeloid vs. lymphoid), disease status (in CR vs. not in CR), anti-HLA antibody (not DSA) (positive vs. negative), total nucleated cell dose (≤ 2.61 vs. 〉 2.61 x 107 /kg), CD34+ cell dose (≤ 0.86 vs. 〉0.86 x 105 /kg), HLA antigen match (≤4/6 vs. ≥5/6), ABO match (match vs. mismatch), sex match (match vs. mismatch), GVHD prevention (Tac vs. TAC plus MMF), and the intensity of conditioning regimen (MAC vs. RIC). Then, we compared the cumulative incidence of neutrophil engraftment between 4 groups as follows: 90.2% for group A (〉 1.5 x 105 /kg, n = 41); 91.7% for group B (1.0 - 1.5 x 105 /kg, n = 109); 91.4% for group C (0.5 - 1.0 x 105 /kg, n = 255); 75.0% for group D (〈 0.5 x 105 /kg, n = 16) (p 〈 0.01). The median day of neutrophil engraftment was faster for the patients transplanted more CD34+ cell doses: day 17 for group A; day 19 for B; day 21 for C; day 26.5 for D (p 〈 0.0001). Next, we focused on group C transplanted lower CD34+ cell dose than the recommendation (0.5 - 1.0 x 105 /kg, n = 255).The patients were divided into 5 groups according to their CD34+ cell doses, and we compared their cumulative incidence of neutrophil engraftment as follows: 96.0% for group C1 (0.9 - 1.0 x 105 /kg, n = 50); 89.7% for group C2 (0.8 - 0.9 x 105 /kg, n = 39); 88.1% for group C3 (0.7 - 0.8 x 105 /kg, n = 67); 92.2% for group C4 (0.6 - 0.7 x 105 /kg, n = 51); 91.7% for group C5 (0.5 - 0.6 x 105 /kg, n = 48) (p = 0.03). The median day of neutrophil engraftment was significantly faster for the patients transplanted more CD34+ cell dose: day 20 for group C1; day 21 for C2; day 21 for C3; day 23 for C4; day 24 for C5 (p 〈 0.01). Overall survival was not significantly different between group A vs. B vs. C vs. D, nor group C1 vs. C2 vs. C3 vs. C4 vs. C5, respectively. DISCUSSION & CONCLUSION: Significantly faster neutrophil engraftment was demonstrated for patients transplanted more CD34+ cells after single-unit CBT. On the other hand, the cumulative incidences of neutrophil engraftment at day 60 were comparable among the patients who used 〉 0.5 x 105 /kg of CD34+ cells to be around 90%. The cord blood units containing 0.5 - 1.0 x 105 /kg at freezing could be alternative donor candidates for cord blood selection, if delayed engraftment was clinically acceptable for recipients. Disclosures Yamamoto: Bristol-Myers Squibb: Honoraria.
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