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  • 1
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 4563-4563
    Abstract: 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. 〈 30, n = 82 vs. 25) and were compared in terms of the incidence and severity of PIR, neutrophil recovery, NRM, RR, and OS. The cumulative incidence of total PIR was higher in low MMF group compared to high (76.0 % vs. 51.2 %, P=0.009), whereas that of severe-type PIR, defined by the presence of organ dysfunction (described in Transplantation 92:366,2011), was comparable between 2 groups (8.0 % vs. 9.8 %, P=0.83). The incidences of neutrophil recovery (88 % vs 79.3 % at 50 days post-transplant, P=0.10), grade II-IV acute GVHD (61.3 % vs 46.1 % up to day 100, P=0.09), engraftment failure & NRM (40.7 % vs 27.3 % at 1 year P=0.57), HHV6-associated limbic encephalopathy (12.3 % vs 8.6% at day 100 P=0.57), and relapse (37.9% vs 37.2 % at 1 year, P=0.58) were comparable between 2 groups. Overall (34.7 % vs 50.8 %, P = 0.60) and event-free survival (21.4 % vs 34.5 %, P = 0.38) at 1 year post-transplant were also comparable between 2 groups. Cox regression analysis did not find factors significantly affecting OS, PFS, NRM and relapase. Conclusions: These data indicated that lower MMF dosing ( 〈 30 mg/kg) does increase the incidence of total PIR, but similarly effective in reducing that of severe form nor NRM as standard dose of MMF (≥ 30 mg/kg), even for elderly population whose majorities were in advanced disease status. Prospective study is warranted to determine the optimal dose of MMF. Disclosures: Off Label Use: Mycophenolate mofetil is used in off-label for GVHD prophylaxis.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 2
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 1954-1954
    Abstract: Abstract 1954 Backgrounds: Viral infections remain serious complications after hematopoietic stem cell transplantation (HSCT), despite a remarkable progress of the prophylactic and treatment strategies. Detection of the early stage of viral reactivation and infection was extremely important as CMV antigenemia monitoring and pre-emptive therapy. In this study, we performed a prospective PCR-guided viral monitoring for 13 species and evaluate the association with actual onset of viral disease. Patients and methods: Adult patients aged ≥ 16 years old who were scheduled for allogeneic or autologus HSCT were eligible for this study. Informed consent was obtained from all patients. From a week before transplantation to the 8 weeks after, the DNA quantity of 13 viral species was weekly measured using in-house multiplex PCR assays, which enable to simultaneously determine the amount of herpes simplex virus-1 (HSV-1), human simplex virus-2 (HSV-2), varicella-zoster virus (VZV), cytomegalovirus (CMV) and Epstein-Barr virus (EBV) humanherpesvirus 6 (HHV-6), humanherpesvirus 7(HHV-7), humanherpesvirus 8 (HHV-8), parvovirus B19, hepatitis B virus (HBV), JC virus (JCV), BK virus (BKV), and adenovirus (ADV). As antiviral prophylaxis for HSV/VZV and HHV-6 diseases, oral acyclovir and intravenous foscarnet in all recipients and exclusively in those receiving unrelated cord blood, respectively, whereas antigenemia-guided preemptive therapy against CMV disease with ganciclovir or foscarnet was performed in allo-transplant settings. Results: A hundred patients who underwent HSCT at Toranomon Hospital from May to December 2010 were enrolled for this study. Median age was 52 (16–71) years old. Six patients who underwent autologous transplantation were included. In a total of 821 peripheral specimens obtained during the study period, HHV-6 was detected in 69.6%, CMV in 37.7%, BK in 13.2% and ADV in 7.7% of 471 PCR positive samples, and the detection rate of other virus was lower than 3.1%. The cumulative incidences of positive viral load due to HHV-6, CMV, BKV, ADV during the study period were 88.5%, 54.3%, 24.1%, and 11.6%. During the study period, 31 patients developed any viral infections with a cumulative incidence of 34.0%, at a median of 18 (-1-56) days after HSCT. Ten patients had 2 or more episodes of different viral infections, and a total of 45 infectious episodes were documented. HHV-6 encephalitis accounted for 33.3% of all viral infections during prophylactic foscarnet administration. Other common viruses included ADV 22.2 % (dissemination in 8, hemorrhagic cystitis (HC) in 2), and BKV 35.6 % (HC in all 22 patients). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were analyzed for common virus such as ADV, BKV and HHV-6. CMV was excluded CMV antigenemia-guided pre-emptive therapy successfully suppressed the onset of diseases. The sensitivity, specificity, PPV, and NPV for diagnosing ADV infections were 85.7%, 100.0%, 100.0% and 98.9%. These data suggest ADV monitoring is a useful strategy for predicting the onset of disease. The sensitivity, specificity, PPV, and NPV for diagnosing BKV associated HC were 61.1%, 86.6%, 50.0% and 91.0%, whereas those of the PCR assay with use of a threshold of 10000 copies/ml were 46.6%, 71.8%, 29.1% and 88.4% for diagnosing HHV-6 encephalitis. Conclusion: Our multiple viral monitoring system using multiplex PCR assay was useful for detecting viral load kinetics for 13 species early after HSCT. As for ADV, viral load in blood detected in our assay had a high sensitivity and specificity for developing ADV infectious diseases. The sensitivity and specificity level for HHV-6 and BK was not as high as ADV because definite threshold level was not determined yet and HHV-6 encephalitis might be suppressed due to prophylactic foscarnet, these findings suggested that the multiplex PCR assay could be applied to the routine monitoring for viral infections in the early period after HSCT. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
    In: Bone Marrow Transplantation, Springer Science and Business Media LLC, Vol. 56, No. 7 ( 2021-07), p. 1625-1634
    Type of Medium: Online Resource
    ISSN: 0268-3369 , 1476-5365
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2004030-1
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  • 4
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 651-651
    Abstract: Abstract 651 Backgrounds: Engraft failure remains a critical issue to be solved especially after cord blood transplantation (CBT). The factors such as limited doses of infused total nucleated (TNC) and CD34+ cells, HLA disparity, and anti-HLA antibodies are considered to induce engraftment failure. We studied the patterns and mechanisms of engraftment failure for patients who failed engraftment after CBT. Patients/methods: Medical charts on 429 transplant recipients of single unit CB with hematological diseases as the first allogeneic HSCT at Toranomon Hospital between January 2002 and May 2011 were retrospectively reviewed. Patients who did not meet the criteria of engraftment were subjected to the following analysis. Engraftment was defined when the neutrophil counts exceeded 0.5 × 109/L for 3 consecutive tests. Patients who died or had progressive disease before day 28 post-transplant were excluded. Result: Among 429 recipients, 67 were excluded due to early death before day 28 (n=52) and disease progression (n=15). In remaining 362 patients, 31 were diagnosed as engraftment failure. Median age was 62 years (range, 17–71). Underlying diseases were AML (n=16), ALL (n=5), MDS (n=2), NHL (n=6), and SAA (n=2). Twenty-three (74%) were in high risk disease status (MDS RAEB and beyond, or AL, NHL not in remission). Conditioning regimens mainly comprised of purine analogue-based reduced-toxicity regimens with fludarabine phosphate (125-180 mg/m2), melphalan (80-140 mg/m2) or busulfan (8-16 mg/kg) and 0–4 Gy of total body irradiation (TBI), and others. Graft-versus-host disease (GVHD) prophylaxis comprised of tacrolimus (TAC) (n=13) or cyclosporine alone (n=8), and TAC + mycophenolate mofetil (MMF) (n=10). Median number of total nucleated cells (TNC) and CD34+ cells were 2.45×106 /kg (range, 1.94 – 4.20), and 0.76×105 /kg (range, 0.21 – 1.35), respectively. Three had 1 antigen mismatch and 28 had 2 antigen mismatches in serological HLA typing, and 15 had allelic mismatches in more than 3 loci between host and graft. Twenty-two (71%) showed recipient-dominant chimerism (donor type 〈 5%) at the diagnosis of engraftment failure, which were designated as graft rejection, and the other 9 (29%) showed donor-dominancy (donor type 〉 90%), designated as poor graft function. Anti-HLA antibodies were present in 7 of the 13 patients tested (54%), including 2 (28%) who had a donor-specific antigen that targeted against UCB unit used. All these 7 patients who had anti-HLA antibody showed the graft rejection pattern. T-cell donor-recipient chimeric status was assessed in 14 patients. Nine who showed complete recipient dominant chimerism in T-cell fraction (donor type 〈 5%) at early transplant phase (median day15, range, 8–17) developed graft rejection. In 9 patients who achieved complete donor chimerism, 4 complicated persistent infection (sepsis, invasive pulmonary aspergillosis), and the other 5 developed hemophagocytic syndrome (HPS). There were no statistically significant differences between graft rejection group versus poor graft function group in terms of TNC, CD34+ cell dose, HLA disparity, disease type (myeloid vs. lymphoid), disease status (standard vs. high), pretransplant conditioning (presence vs. absence of melphalan, or TBI), and GVHD prophylaxis (presence vs. absence of MMF) in this study. Discussion: These data demonstrated that the graft rejection pattern comprised 70% of engraftment failure. Presence of anti-HLA antibody showed close correlation with graft rejection, suggesting antigen-mediated graft rejection mechanism following CBT. Recipient dominant T-cell chimerism at early transplant phase (around day 15) strongly indicates impending graft rejection. All patients who showed poor graft function pattern accompanied by severe infection and/or HPS. This pattern is rarely seen in HSCT of other stem cell sources, suggesting unique characteristics of immune cells in CB graft as we reported. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 5
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 5747-5747
    Abstract: Background & Aim: Recombinant human soluble thrombomoduline alpha (rhTM) is a novel anticoagulant agents and approved for disseminated intravascular coagulation (DIC) in Japan. Although several case reports suggested its therapeutic potential for sinusoidal obstructive syndrome/hepatic veno-occlusive disease (SOS/VOD), no information is available in large cohort. The aim of the study is to evaluate the therapeutic potential of rhTM for SOS/VOD. Patients & Methods: We retrospectively studied 878 times of allogeneic hematopoietic cell transplantation (HCT) in Toranomon Hospital from June 2008 to June 2015. We extracted the patients who used rhTM for DIC and satisfied the diagnostic criteria of SOS/VOD around the same time, because the use of rhTM for SOS/VOD alone is off-label. We excluded the patients who were already treated with rhTM before the emergence of the first symptom or sign of SOS/VOD, who used rhTM only in the short period (within 2 days), and who started rhTM over 30 days after the emergence of the first symptom or sign of SOS/VOD. To diagnose classical SOS/VOD (≤ 21 days after transplantation), we used two classical criteria of the modified Seattle (McDonald et al. Ann Intern Med 1993) and the Baltimore (Jones et al. Transplant 1987). For late-onset SOS/VOD ( 〉 day 22 of transplantation), we used the criteria which was recently published from the EBMT group (Mohty et al, Bone Marrow Transplant 2016). We considered the atrophic change of the liver in a long-term clinical course as an evidence of SOS/VOD, in a patient who was not evaluated the portal flow. We defined as severe SOS/VOD, if the patients had renal (Cr ≥ 2 times of baseline at transplant), respiratory (SpO2 ≤ 90% and/or the need for positive pressure) or central nervous system failure (confusion, lethargy and/or delirium) until 2 weeks after the diagnosis of SOS/VOD. Complete response (CR) of SOS/VOD was defined as the resolution of all the symptoms and the signs of SOS/VOD diagnostic criteria. We prioritized the date of Baltimore criteria, when we fixed the date of diagnosis. Results: A total of 39 patients used rhTM for DIC and concurrent SOS/VOD. The median age was 60 years (range, 27 - 72) and 27 patients (69%) was male. Hematologic diseases were as follows; AML (n=25), ALL (n=5), lymphoma (n=3), CML (n=2), MDS (n=2) and CMML (n=2). Donor cell sources were UCB (n=34) and UBM (n=5). Most of the prophylaxis regimen at the time of transplantation was the combination of ursodeoxycholic acid and dalteparin in 36 patients (92%). Classical SOS/VOD was diagnosed in 3 (8%) and 8 patients (21%) by the criteria of the modified Seattle and the Baltimore at the median day of 14 (range, 11 - 14) and 16 (range, 11 - 20), respectively. Twenty-eight patients (72%) were diagnosed as late-onset SOS/VOD at the median day of 44 (range, 22 - 89). In a total of 39 patients, severe SOS/VOD developed in 33 patients (85%) (renal, n=32; respiratory, n=7; central nervous system, n=15). The elevation of transaminase (2x upper limit of normal range) was observed in 18 patients (46%). The median interval from the emergence of the first symptom or sign of SOS/VOD to rhTM administration was 7 days (range, 0 - 23). The median duration of rhTM administration was 11 days (range, 3 - 63). RTM was used alone in 20 patients (51%), in combination with dalteparin in 7 (18%), with antithrombin III (ATIII) in 5 (13%), with dalteparin & ATIII in 3 (8%), with ATIII & prostaglandin E1 (PGE1) in 2 (5%), and with PGE1 in 2 (5%). Corticosteroid was used with rhTM concomitantly in 32 patients (82%). Finally, 13 patients achieved CR of SOS/VOD. The cumulative incidence of CR of SOS/VOD was 33.3 % at 1 year after the administration of rhTM (95% confidence interval, 18.5 - 48.9%) (Figure 1). The median interval from the administration of rhTM to CR of SOS/VOD was 51 days (range, 6 - 141). At 1 year after transplantation, overall survival was 25.6% (95% confidence interval, 13.3 - 69.9%) (Figure 2). From the administration of rhTM to 2 weeks after the cessation of rhTM, 23 hemorrhagic adverse events were observed. Seven out of 23 events were at grade 3-5, and 5 out of 7 events were fatal (intra-abdominal n=2, gastro-intestinal n=1, lung n=1, and brain n=1). Conclusion: We concluded that rhTM had a possible therapeutic potential for SOS/VOD. Its safety and efficacy should be evaluated in a prospective study in the future. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Izutsu: Abbvie: Research Funding; Gilead: Research Funding; Celgene: Research Funding; Janssen Pharmaceutical K.K.: Honoraria; Eisai: Honoraria; Kyowa Hakko Kirin: Honoraria; Chugai Pharmaceutical: Honoraria, Research Funding; Takeda Pharmaceutical: Honoraria; Mundipharma KK: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
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    detail.hit.zdb_id: 80069-7
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  • 6
    In: Mycopathologia, Springer Science and Business Media LLC, Vol. 182, No. 9-10 ( 2017-10), p. 847-853
    Type of Medium: Online Resource
    ISSN: 0301-486X , 1573-0832
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2003647-4
    SSG: 12
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  • 7
    In: Biology of Blood and Marrow Transplantation, Elsevier BV, Vol. 19, No. 2 ( 2013-02), p. S150-
    Type of Medium: Online Resource
    ISSN: 1083-8791
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2013
    detail.hit.zdb_id: 3056525-X
    detail.hit.zdb_id: 2057605-5
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  • 8
    In: Biology of Blood and Marrow Transplantation, Elsevier BV, Vol. 21, No. 2 ( 2015-02), p. S299-S300
    Type of Medium: Online Resource
    ISSN: 1083-8791
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2015
    detail.hit.zdb_id: 3056525-X
    detail.hit.zdb_id: 2057605-5
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  • 9
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 461-461
    Abstract: 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 〈 0.001). Although no patient directly died of HHV-6 encephalitis, the encephalitis tended to affect non-relapse mortality after CBT (HR 1.75(0.99–3.07), P=0.053). Conclusions: PIR seems to bring at least similar or more risk for HHV-6 encephalitis compared to high-level HHV-6 viral load. Prophylaxis with FCV at 〉 =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.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 10
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 4705-4705
    Abstract: 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-ra y 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.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
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    detail.hit.zdb_id: 80069-7
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