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M Sato,
H Nakasone,
K Oshima,
Y Ishihara,
H Wada,
K Sakamoto,
K Kawamura,
M Ashizawa,
T Machishima,
K Terasako,
S Kimura,
M Kikuchi, S Okuda,
A Tanihara,
R Yamazaki,
Y Tanaka,
J Kanda,
S Kako,
J Nishida,
Y Kanda
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ABSTRACT: Various biomarkers have been investigated with regard to their ability to predict the outcome of allogeneic hematopoietic SCT (HSCT). In this study, we retrospectively reviewed 90 recipients who received HSCT between 2007 and 2011 in our institution, and evaluated the predictive value of the baseline serum C-reactive protein (CRP) levels just before the initiation of conditioning for transplant-related complications after allogeneic HSCT. A receiver-operating characteristic curve revealed that the baseline serum CRP levels had an excellent predictive value for non-relapse mortality (NRM), with an area under the curve of 0.83. The sensitivity and specificity for NRM were 80% and 87%, respectively, with a cutoff of 0.6 mg/dL. With this cutoff value, multivariate analyses revealed that a higher baseline CRP level was an independent risk factor for NRM (HR 6.21, P<0.01), grade III-IV acute GVHD (HR 3.91, P=0.03) and poor overall survival (HR 3.27, P=0.0018). On the other hand, the baseline CRP level did not predict infectious events. These findings suggested that CRP levels before conditioning may be a useful predictive biomarker for poor survival.Bone Marrow Transplantation advance online publication, 8 October 2012; doi:10.1038/bmt.2012.193.
Bone marrow transplantation 10/2012; · 3.00 Impact Factor
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M Ashizawa,
K Oshima,
H Wada,
Y Ishihara,
K Kawamura,
K Sakamoto,
M Sato,
K Terasako,
T Machishima,
S Kimura,
M Kikuchi,
H Nakasone, S Okuda,
S Kako,
J Kanda,
R Yamazaki,
A Tanihara,
J Nishida,
Y Kanda
[show abstract]
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ABSTRACT: Hyperbilirubinemia in the early phase after allogeneic hematopoietic SCT (HSCT) is due to various causes. One of the most important causes of hyperbilirubinemia is veno-occlusive disease/sinusoidal obstructive syndrome (VOD/SOS). However, the prognosis of patients who are clinically diagnosed as SOS varies. We retrospectively evaluated 82 patients who underwent their first allogeneic HSCT. GVHD prophylaxis was a combination of short-term MTX and CsA (n=77) or tacrolimus (n=5). Thirty-three patients developed hyperbilirubinemia, with a bilirubin level of at least 2 mg/dL, within 20 days after HSCT. Of these patients, 24 were diagnosed as VOD/SOS using the modified Seattle criteria. Twenty-six recovered to a bilirubin level of <2 mg/dL. We focused on the serum alkaline phosphatase/total bilirubin ratio (ALP/TB) at the onset of hyperbilirubinemia and found that it significantly predicted the recovery from hyperbilirubinemia. OS was significantly higher in patients with a lower ALP/TB ratio (P=0.00056). In addition, a lower ALP/TB ratio was associated with better survival even in patients who were clinically diagnosed as SOS (P<0.001). The ALP/TB ratio at the onset of hyperbilirubinemia may be a useful predictor for the prognosis of hyperbilirubinemia and SOS early after HSCT.Bone Marrow Transplantation advance online publication, 2 July 2012; doi:10.1038/bmt.2012.130.
Bone marrow transplantation 07/2012; · 3.00 Impact Factor
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S-I Kimura,
H Wada,
K Sakamoto,
M Ashizawa,
M Sato,
K Terasako,
H Nakasone,
M Kikuchi, S Okuda,
S Kako,
R Yamazaki,
K Oshima,
Y Tanaka,
A Tanihara,
J Nishida,
Y Kanda
[show abstract]
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ABSTRACT: We retrospectively investigated L-index, which evaluates both the intensity and duration of lymphopenia after allogeneic hematopoietic stem cell transplantation (HSCT) (n = 50). L-index was defined as the area over the lymphocyte curve during lymphopenia (absolute lymphocyte count < 700/μL). We calculated the L-index from the start of conditioning to day 30 - L-index(30) - and to day 100 - L-index(100) - after HSCT. Multivariate analysis revealed that human leukocyte antigen mismatched donor, female gender, and non-lymphoid disease were significantly associated with high L-index(30). Grade III-IV acute graft-versus-host disease, alemtuzumab-containing regimen, and non-lymphoid disease were identified as independent significant factors for high L-index(100). Cytomegalovirus (CMV) antigenemia was detected > 3 cells/2 slides by C10/11 method in 30 patients (CMV-AG ≥ 3 group) and was not detected in 20 patients (CMV-AG < 3 group). Although no significant difference was seen in absolute lymphocyte count on day 30 between the 2 groups, the L-index(30) was significantly higher in the CMV-AG ≥ 3 group than in the CMV-AG < 3 group (P = 0.050). L-index(30) was identified as an independent factor on CMV reactivation in multivariate analysis, when it was treated as a dichotomous variable with a cut-off value of 22,318, determined by receiver operating characteristic curve analysis. In conclusion, both the intensity and duration of lymphopenia in early phase after HSCT evaluated on the basis of L-index(30) showed significant association with CMV reactivation.
Transplant Infectious Disease 04/2012; 14(4):364-73. · 2.22 Impact Factor
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J Suzuki,
M Ashizawa, S Okuda,
H Wada,
K Sakamoto,
K Terasako,
M Sato,
S-I Kimura,
M Kikuchi,
H Nakasone,
S Kako,
R Yamazaki,
K Oshima,
J Nishida,
Y Kanda
[show abstract]
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ABSTRACT: Although the reactivation of varicella zoster virus (VZV) is a common complication after allogeneic hematopoietic stem cell transplantation (HSCT), VZV meningoencephalitis is a rare life-threatening infectious disease after HSCT. We describe here a patient who developed VZV meningoencephalitis 2 years after human leukocyte antigen-matched unrelated HSCT for acute myeloblastic leukemia. She developed chronic graft-versus-host disease, and cyclosporine (CSA) was continued until 17 months after HSCT. Low-dose acyclovir (ACV) at 200 mg/day was administered to prevent the reactivation of VZV from day -7 to the termination of CSA. At 22 months, she suddenly developed fever, loss of consciousness, and seizure, with generalized skin rash. A high level of VZV DNA was detected in her cerebrospinal fluid (CSF). She was diagnosed to have VZV meningoencephalitis. Intravenous ACV at 30 mg/kg/day was given for 2 months. Although loss of consciousness was quickly resolved, some neurologic symptoms persisted. She did not have any known risk factors for VZV reactivation. Therefore, we should keep in mind that any HSCT recipient may develop VZV meningoencephalitis, and examination of CSF for VZV infection with an empiric administration of ACV may be recommended for HSCT recipients with central nervous system symptoms, even in the absence of skin manifestations.
Transplant Infectious Disease 02/2012; 14(4):E7-12. · 2.22 Impact Factor
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H Wada,
K Terasako,
Y Kamiya,
M Sato,
S-i Kimura, S Okuda,
S Kako,
R Yamazaki,
K Oshima,
J Nishida,
M Moriguchi,
C Terai,
Y Kanda
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ABSTRACT: Autologous hematopoietic SCT (ASCT) has been investigated as salvage therapy for refractory systemic lupus erythematosus (SLE). Although immune recovery after ASCT with in vitro purging of lymphocytes has been extensively studied, little information is available about immune recovery after ASCT without in vitro purging. Therefore, we analyzed the immune recovery of a patient who successfully underwent ASCT without in vitro purging for refractory SLE. In addition to the numbers of PBL subsets, T-cell receptor rearrangement excision circles (TRECs) and the T-cell receptor repertoire diversity of both CD4+ and CD8+ T cells were sequentially analyzed. All SLE-related symptoms disappeared within 3 months after ASCT and the serum anti-dsDNA Ab became undetectable. The number of CD4+CD45RO+ memory T cells remained lower than that in healthy adult controls, but the number of CD4+CD45RA+ naïve T cells showed a rapid increase after ASCT. TRECs of both CD4+ and CD8+ T cells were strongly suppressed before ASCT, but consistently increased after ASCT. The T-cell receptor repertoire of CD8+ T cells was skewed before ASCT, but the diversity recovered after ASCT. ASCT with the reinfusion of a large number of autologous T cells did not impair the recovery of naive T cells or resetting of the immune system.
Bone marrow transplantation 01/2011; 46(11):1450-4. · 3.00 Impact Factor
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Bone marrow transplantation 10/2010; 46(8):1145-7. · 3.00 Impact Factor
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S Kimura,
K Oshima, S Okuda,
K Sato,
M Sato,
K Terasako,
H Nakasone,
S Kako,
R Yamazaki,
Y Tanaka,
A Tanihara,
T Higuchi,
J Nishida,
Y Kanda
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[hide abstract]
ABSTRACT: We investigated the serial changes in the blood CsA concentration during the switch from continuous intravenous infusion to twice-daily oral administration in allogeneic hematopoietic stem cell transplant recipients (n=12). The microemulsion form of CsA, Neoral, was started at twice the last dose in intravenous infusion in two equally divided doses. The area under the concentration-time curve during oral administration (AUC(PO)) was significantly higher than the AUC during intravenous infusion (AUC(IV)) (median 7508 vs 6705 ng/ml x h, P=0.050). The median bioavailability of Neoral, defined as (AUC(PO)/DOSE(PO)) divided by (AUC(IV)/DOSE(IV)), was 0.685 (range, 0.45-1.04). Concomitant administration of oral voriconazole (n=4) significantly increased the bioavailability of Neoral (median 0.87 vs 0.54, P=0.017), probably due to the inhibition of gut CYP3A4 by voriconazole. Although the conversion from intravenous to oral administration of CsA at a ratio of 1:2 seemed to be appropriate in most patients, a lower conversion ratio may be better in patients taking oral voriconazole. To obtain a similar AUC, the target trough concentrations during twice-daily oral administration should be halved compared with the target concentration during continuous infusion.
Bone marrow transplantation 11/2009; 45(6):1088-94. · 3.00 Impact Factor
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Bone marrow transplantation 09/2009; 45(4):781-2. · 3.00 Impact Factor
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Bone marrow transplantation 10/2008; 43(3):261-2. · 3.00 Impact Factor
