Katsuji Kaida

Hyogo College of Medicine, Nishinomiya, Hyōgo, Japan

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Publications (42)106.5 Total impact

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    ABSTRACT: Human leukocyte antigen (HLA)-haploidentical stem cell transplantation (haplo-SCT) is associated with a high incidence of cytomegalovirus (CMV) infection, probably originating from the delayed reconstitution of CMV-specific T cell immunity. There have been few reports on the presence of CMV-specific cytotoxic T lymphocytes (CMV-CTLs) after haplo-SCT. We have studied CMV-specific immune reconstitution by measuring the absolute number of CMV-CTLs using a flow cytometry method with HLA-A2-restricted NLVPMVATV peptide dextramers. We examined the association between reconstitution patterns of CMV-CTLs and the duration of CMV antigenemia in 15 patients who underwent first allogeneic SCT from HLA-haploidentical-related donors with HLA-A2. In seven and eight patients, CMV antigenemia consecutively resolved for more than 4 weeks (the CMV antigenemia 'resolved' group) and intermittently persisted (the CMV antigenemia 'persistent' group) during a 100-day observation period, respectively. The group of the seven patients, in whom levels of CMV antigenemia were reduced to zero, had a significantly lower maximum level of CMV antigenemia than the CMV antigenemia persistent group. In contrast, the CMV antigenemia persistent group had a significantly higher maximum level of CMV-CTLs, but the levels took longer to peak. Despite no difference in general lymphocyte recovery between the two groups, the CMV antigenemia resolved group had significantly higher median CMV-CTL counts than the CMV antigenemia persistent group at 6 weeks after onset of CMV infection. Flow cytometry analysis of CMV-CTLs is a convenient method of monitoring reconstitution of CMV-specific lymphocyte immunity following haplo-SCT.
    Annals of Hematology 07/2015; DOI:10.1007/s00277-015-2446-4 · 2.40 Impact Factor
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    ABSTRACT: This prospective, multicenter phase I/II study of unmanipulated HLA-haploidentical RIST using a low dose of ATG and steroid was conducted in 5 institutes in Japan. Thirty-four patients with hematologic malignancies who were in an advanced stage or at a high risk of relapse at the time of transplantation were enrolled. Among them, 7 patients underwent transplantation as a second transplantation because of relapse after the previous allogeneic SCT. The conditioning regimen consisted of fludarabine, busulfan and anti-T-lymphocyte globulin (Fresenius, 8 mg/kg), and GVHD prophylaxis consisted of tacrolimus and methylprednisolone (1 mg/kg). All patients except one (97.1%) achieved donor-type engraftment. Rapid hematopoietic engraftment was achieved, with neutrophils > 0.5 x 10(9)/l on day 11 and platelets > 20 x 10(9)/l on day 17.5. Treatment was started for ≥ grade I GVHD, and the cumulative incidence of acute grade I and grade II-IV GVHDs was 27.5% and 30.7%, respectively. The incidence of chronic GVHD (extensive type) was 20%. Fourteen patients (41.2%) had a relapse. The cumulative incidence of transplantation-related mortality at 1 year after the transplantation was 26.5%. The survival rate at day 100 was 88.2%. The survival rates at 1 year for patients with CR/CP (n=8) and non-CR (n=26) status before transplantation were 62.5% and 42.3%, respectively. In the multivariate analysis, non-CR status before transplantation was the only factor significant prognostic factor of increased relapse (p=0.0424), which tended to have a lower survival rate (p=0.0524). This transplant protocol is safe and feasible, if a suitable donor is not available in a timely manner. As the main cause of death was relapse but not GVHD, more intensified conditioning or attenuation of GVHD prophylaxis and/or DLI may be desirable for patients with non-CR status. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 04/2015; DOI:10.1016/j.bbmt.2015.04.012 · 3.35 Impact Factor
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    ABSTRACT: This study investigated the differences between allogeneic haematopoietic stem cell transplantation (allo-HSCT) patients receiving HSC from human leucocyte antigen (HLA)-haploidentical donors (HID) and other donors that included HLA-matched sibling, matched unrelated, and unrelated umbilical cord blood donors in the 6 weeks after HSCT with respect to quality of life (QOL), psychological status, and physical function. The study included 126 patients (HID group, n = 100; other donor group, n = 26) who underwent allo-HSCT between July 2007 and December 2012. Patients were evaluated for health-related QOL using the Medical Outcome Study 36-item Short Form Health Survey. Psychological status was measured by Hospital Anxiety and Depression Scale. Physical function was assessed using tests for handgrip strength, knee extensor strength, and the 6-min walk test. After HSCT, the HID group showed significantly greater improvements in the general health subscale and Mental Component Summary (MCS) of QOL than the other donor group (P < 0.01). Multivariate analysis confirmed that complete remission and age were associated with changes in the general health subscale before and after HSCT (P < 0.05). With regard to physical function, the HID group showed significantly more decline than the other donor group with respect to handgrip strength and knee extensor muscle strength after HSCT (P < 0.05). Total corticosteroid dose was associated with decreased handgrip strength before and after HSCT (P < 0.05). The donor type affects QOL, psychological status, and physical function in allo-HSCT recipients; these findings may provide insights for customised rehabilitation strategies for HSCT recipients. Copyright © 2015 Elsevier Ltd. All rights reserved.
    European journal of oncology nursing: the official journal of European Oncology Nursing Society 04/2015; DOI:10.1016/j.ejon.2015.02.002 · 1.79 Impact Factor
  • Biology of Blood and Marrow Transplantation 02/2015; 21(2):S158-S159. DOI:10.1016/j.bbmt.2014.11.227 · 3.35 Impact Factor
  • Biology of Blood and Marrow Transplantation 02/2015; 21(2):S160-S161. DOI:10.1016/j.bbmt.2014.11.232 · 3.35 Impact Factor
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    ABSTRACT: Anti-human T-lymphocyte immunoglobulin, rabbit (ATG, Zetbulin(®) intravenous infusion liquid), is an immunosuppressive agent that is indicated for aplastic anemia in Japan. The "prevention of graft-versus-host disease (GVHD) for allogeneic hematopoietic stem cell transplantation in adults" indication has been added to ATG in 32 countries worldwide, but has not yet been approved for GVHD prevention in Japan. The pharmacokinetics of ATG in Japanese people has not yet been assessed. In this study, to assess ATG pharmacokinetics, ATG (2 mg/kg/day from day-4 to day-1) as a pretransplant treatment was administered to six patients who had received transplantation of HLA-haploidentical stem cells. The ATG concentration was measured using an ELISA kit for rabbit IgG. The serum ATG concentration increased with administration for 4 consecutive days, peaking at a concentration of 66.0μg/ml (±8.8 SD). Subsequently, it gradually decreased with an elimination half-life of 21.9 days (±20.4 SD) but was still detectable in serum even a few weeks after allogeneic hematopoietic stem cell transplantation. We found the pharmacokinetics of ATG in this study to be comparable to those described in previous reports from Europe.
    [Rinshō ketsueki] The Japanese journal of clinical hematology 01/2015; 56(5):475-80. DOI:10.11406/rinketsu.56.475
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    ABSTRACT: In the present study, we analyzed the kinetics of serum soluble interleukin-2 receptor (sIL-2R) using data from 77 patients undergoing HLA-haploidentical transplantation using reduced-intensity conditioning (RIC), who were at an advanced stage or at high risk for relapse, to clarify the usefulness of sIL-2R as a biomarker of acute graft-versus-host disease (GVHD). Anti-T-lymphocyte globulin and methylprednisolone were used as GVHD prophylaxis. While the median sIL-2R in 38 patients not developing GVHD was suppressed at levels <740 U/ml, sIL-2R in 25 patients developing severe GVHD peaked on day 11 (1,663 U/ml), and thereafter decreased to <1,000 U/ml after day 30. The occurrence of GVHD was not limited to times of high sIL-2R level, but occurred at any time point on the sIL-2R curve. Most patients developing GVHD, however, experienced a higher sIL-2R level early in their transplant course. The combination of RIC and glucocorticoids sufficiently suppressed sIL-2R levels after HLA-haploidentical transplantation. In a multivariate analysis to identify factors associated with GVHD, day 7 sIL-2R >810 U/ml was the only factor significantly associated with the occurrence of severe GVHD (p = 0.0101).
    International journal of hematology 03/2014; 99(4). DOI:10.1007/s12185-014-1542-x · 1.68 Impact Factor
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    ABSTRACT: Introduction: Severe peripheral neuropathy and myelopathy are rare complications after stem cell transplantation (SCT). Patients and Methods: In our institution, seven patients of precursor T lymphoblastic leukemia/lymphoma without the central nervous involvement who had been treated by nelarabine to control their diseases received SCT from HLA-haploidentical familial donor (HLA-haploidentical SCT) with the conditioning regimen including high-dose cytarabine (HDAC). Results: Three of evaluable six patients developed irreversible paresthesia and muscle weakness in both lower extremities after neutrophil engraftment. The results of nerve conduction studies and short latency somatosensory evoked potentials suggested axonal neuropathy of both lower extremities in all three patients and myelopathy in two patients. Negative findings of PET-CT, and analyses of repeated cerebrospinal fluid samples and the bone marrow also indicated that tumor involvement was improbable. In all three patients, the symptoms worsened or persisted despite administration of corticosteroid and intravenous immunoglobulin. The high frequency of the neurological symptoms in our patients previously treated by nelarabine strongly suggested the association of the nelarabine use. Furthermore, the HLA-haploidentical SCT setting and the use of a potentially neurotoxic agent, HDAC might augment the neurotoxicity of nelarabine. Conclusion: It may be desirable that HLA-haploidentical SCT candidates avoid receiving nelarabine.
    American Journal of Hematology 07/2013; 88(10). DOI:10.1002/ajh.23502 · 3.48 Impact Factor
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    ABSTRACT: OBJECTIVE: The aim of this study was to examine gender differences in quality of life (QOL), physical function and psychological status before and in the early phase after allogeneic haematopoietic stem cell transplantation (allo-HSCT). METHODS: One hundred patients (66 men, 34 women) who underwent allo-HSCT between July 2007 and June 2011 at Hyogo College of Medicine Hospital were included in this study. Patients were evaluated for health-related QOL using the Medical Outcome Study 36-item Short Form Health Survey; exercise capacity was measured with the 6-min walk test, hand grip strength and knee extensor strength. Fatigue and psychological status were measured by the Piper Fatigue Scale and Hospital Anxiety and Depression Scale, respectively. RESULTS: Women had significantly lower scores for physical function and general health on health-related QOL tests compared with men (p < 0.01). No difference between genders was found in decline of physical function. In women, exercise capacity was strongly associated with QOL (p < 0.01). In men, depression and anxiety were closely related to QOL (p < 0.01). CONCLUSIONS: Gender-appropriate rehabilitation in allo-HSCT patients is important. Women may need more endurance exercises and training for activities of daily life. Men may need rehabilitation including a psychological approach. Copyright © 2012 John Wiley & Sons, Ltd.
    Psycho-Oncology 05/2013; 22(5). DOI:10.1002/pon.3128 · 4.04 Impact Factor
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    ABSTRACT: PURPOSE: The aim of this study was to investigate the relationship between corticosteroid dose and degree of physical function decrease in allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients during the early stage of recovery. We further investigated the confounding factors affecting loss of physical function. METHODS: The study included 113 patients who underwent allo-HSCT between July 2007 and April 2012 at Hyogo College of Medicine Hospital in Japan. Physical function was assessed using tests for hand-grip strength, knee-extensor strength, and the 6-min walk test (6MWT). Fatigue was measured using the Piper Fatigue Scale. Total corticosteroid dose, frequency of physical therapy, body weight, and nutritional status were also collected from medical records. RESULTS: Total corticosteroid dose was correlated with decrease of hand-grip and knee-extensors strength (P < 0.01) but was not correlated with 6MWT performance. Results of multivariate analysis confirmed that low physical function was associated not only with high corticosteroid dose but also with low frequency of physical therapy, increase in fatigue, and body weight loss (P < 0.05). Also, hemoglobin levels were associated with 6MWT (P < 0.05). CONCLUSIONS: This study showed the relationship between corticosteroid dose and declines in physical function and also showed other clinical factors affecting loss of physical function among allo-HSCT patients. Our results indicate that the effectiveness of rehabilitation may be influenced by corticosteroid treatment.
    Supportive Care in Cancer 03/2013; 21(8). DOI:10.1007/s00520-013-1778-7 · 2.50 Impact Factor
  • Biology of Blood and Marrow Transplantation 02/2013; 19(2):S325-S326. DOI:10.1016/j.bbmt.2012.11.493 · 3.35 Impact Factor
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    ABSTRACT: Cytomegalovirus (CMV) meningoencephalitis is a rather rare complication after allogeneic stem cell transplantation. We describe here the case of a 59-year-old man with acute myeloid leukemia who developed CMV meningoencephalitis after cord blood transplantation. The patient presented with a sudden onset of neurological symptoms, such as convulsion, on day 37. The analysis of cerebrospinal fluid (CSF) sample revealed an increase in the number of cells, which were of donor (cord blood) origin, consisting mainly of T cells. No bacteria were detected in the CSF sample. Real-time PCR analysis revealed that the CSF sample was positive for CMV, but was negative for HHV-6, adenovirus, or BK virus. The patient was diagnosed with CMV meningoencephalitis and received cidofovir. His neurological symptoms were gradually improved and completely disappeared by day 60. CMV-specific dextramer-positive CD8(+) T cells were detected in the peripheral blood and CSF samples, with the frequency being much higher in the CSF. To our knowledge, this is the first report on the appearance of CMV-specific T cells in CSF samples from a patient with CMV meningoencephalitis. Cord blood-derived CMV-specific T cells may develop early after transplantation, enter the intrathecal compartment, and likely contribute to the regulation of CMV-meningoencephalitis.
    International journal of hematology 12/2012; 97(2). DOI:10.1007/s12185-012-1231-6 · 1.68 Impact Factor
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    ABSTRACT: This study aimed to investigate the safety and feasibility of physical therapy in cytopenic patients undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT), and to investigate the effect of physical therapy on physiological functions and quality of life (QOL) in allo-HSCT patients. The study cohort included 321 patients who underwent allo-HSCT. To investigate the safety and feasibility of physical therapy during cytopenia, patients were assigned to the physical therapy group (n = 227) or the control group (n = 94). To determine the effects of physical therapy, patients were divided according to the frequency with which they underwent physical therapy (n = 51 per group). Handgrip strength, knee extensor strength and a 6-min walk test were used as measures of physiological function. Short-Form 36 was used to assess QOL. The physical therapy group had higher rate of achieving engraftment and lower death rate than the control group (P < 0.05). After HSCT, the high-frequency physical therapy group showed significantly less decline than the low-frequency physical therapy group with respect to physical functioning of QOL (P < 0.01). Physical therapy is quite beneficial and can be performed safely and feasibly in cytopenic patients during allo-HSCT.
    European Journal of Cancer Care 12/2012; 22(3). DOI:10.1111/ecc.12027 · 1.76 Impact Factor
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    ABSTRACT: Hematopoietic stem cell transplantation (HSCT) from an HLA haploidentical family donor is an option for patients who do not have a full HLA matched donor and lack the time to find an unrelated one [1] and [2]. Furthermore, it may facilitate a powerful graft versus leukemia/lymphoma (GVL) effect to help combat hematological malignancies by directly targeting the mismatched HLA expressed on leukemia/lymphoma cells [3]. On the contrary, leukemia/lymphoma cells escape from the surveillance of the donor-derived GVL effect by losing the target HLA (mismatched HLA in GVH direction). This mechanism has been called loss of heterozygosity (LOH) in the HLA gene region on chromosome 6 [4,5]. Taking the above into account, in this case report, we present a case of lymphoma with monosomy 6, which means natural LOH of HLA, and suggest that selection of a haploidentical family donor matched with the missing HLA haplotype seems to be very effective.
    Transplant Immunology 12/2012; 27(4):162-165. DOI:10.1016/j.trim.2012.09.002 · 1.83 Impact Factor
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    ABSTRACT: Acute GVHD (aGVHD) is a major obstacle to allogeneic hematopoietic SCT (alloHSCT). Although it is thought that aGVHD is initiated in secondary lymphoid organs at a very early stage of alloHSCT, whether CD4(+)FOXP3(+) regulatory T-cells (Tregs) have an impact on aGVHD development during this period remains unclear. Here, we measured Tregs in peripheral blood as early as possible after HLA-mismatched alloHSCT, and assessed the incidence of aGVHD. Flow cytometric analyses revealed that at the second week after HSCT, patients with aGVHD had significantly (P=0.018) lower Treg:CD4(+)T-cell ratios than those without aGVHD. As these differences were seen before the development of aGVHD, these ratios can predict the incidence of aGVHD. The cumulative incidence of aGVHD in patients with ratios of <9% was significantly higher than that in patients with ratios of 9% (P=0.0082, log-rank test). Additionally, the specific ratio of Tregs:CD4(+)T-cells was the most significant value among all other possible lymphocyte-associated ratios and absolute cell counts. These findings suggest that the ratio of Tregs:CD4(+)T-cells at the second week post HLA-mismatched alloHSCT might be a potent predictor of aGVHD in these patients. The practical efficacy of this finding should be verified in further interventional studies.Bone Marrow Transplantation advance online publication, 19 November 2012; doi:10.1038/bmt.2012.232.
    Bone marrow transplantation 11/2012; DOI:10.1038/bmt.2012.232 · 3.47 Impact Factor
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    ABSTRACT: Mismatched human leukocyte antigens (HLAs) on leukemic cells can be targeted by donor T cells in HLA-mismatched/haploidentical stem cell transplantation. In two cases of acute myeloid leukemia with t(6;11)(q27;q23) abnormality presented here, flow cytometry analysis showed a lack of HLA-A unshared between recipients and donors in relapsing leukemic cells after HLA-haploidentical transplantation. However, high-resolution HLA genotyping showed that one case lacked a corresponding HLA haplotype, whereas the other preserved it. These cases suggest that leukemic cells, which lacked mismatched HLA expression, might have an advantage in selective expansion under donor T-cell immune surveillance after HLA-haploidentical transplantation. Most importantly, down-regulation of unshared HLA expression potentially occurs by genetic alterations other than loss of HLA alleles. © 2012 John Wiley & Sons A/S.
    European Journal Of Haematology 10/2012; 89(6). DOI:10.1111/ejh.12017 · 2.41 Impact Factor
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    ABSTRACT: HLA-haploidentical hematopoietic stem cell transplantation (haplo-SCT) in HLA-homozygous patients is accompanied by HLA mismatches only in the host-versus-graft vector, and thus theoretically could be performed with standard graft-versus-host disease (GVHD) prophylaxis. However, the risk of GVHD remains uncertain, and graft failure could be a problem. In this study, we assessed nine HLA-homozygous patients who underwent haplo-SCT. Preparative treatment was cyclophosphamide/total body irradiation-based regimen in five patients, fludarabine/busulfan-based regimen in two, and other regimens in two. GVHD prophylaxis consisted of cyclosporine and methotrexate in seven patients, cyclosporine and mycophenolate mofetil in one, and cyclosporine alone in one. Seven patients achieved neutrophil engraftment and platelet recovery. The median times to neutrophil engraftment and platelet recovery were 15 and 44 days, respectively. Two patients developed graft failure, including one who achieved engraftment with a second SCT from the same donor. Grade II GVHD was observed in half of the evaluable patients; grades III and IV were not observed. Two patients died from treatment-related causes. Five patients were alive after a median follow-up period of 563 days. The probability of overall survival at 5 years was 65 %. These findings may serve as a rationale for considering haplo-SCT as a treatment option for HLA-homozygous patients.
    International journal of hematology 05/2012; 96(1):101-8. DOI:10.1007/s12185-012-1097-7 · 1.68 Impact Factor
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    ABSTRACT: BACKGROUND: Granulocyte mobilization and harvesting, the two major phases of granulocyte collection, have not been standardized. STUDY DESIGN AND METHODS: The data on 123 granulocyte collections were retrospectively investigated for the effect of the mobilization regimen and the harvesting technique. After a single subcutaneous dose (600 µg) of granulocyte-colony-stimulating factor (G-CSF) with (n = 68) or without (n = 40) 8 mg of orally administered dexamethasone, 108 granulocyte donors underwent granulocyte collections. Moreover, 15 peripheral blood stem cell (PBSC) donors who had received 400 µg/m(2) or 10 µg/kg G-CSF for 5 days underwent granulocyte collections on the day after the last PBSC collections (PBSC-GTX donors). Granulocyte harvesting was performed by leukapheresis with (n = 108) or without (n = 15) using high-molecular-weight hydroxyethyl starch (HES). RESULTS: Granulocyte donors who received mobilization with G-CSF plus dexamethasone produced significantly higher granulocyte yields than those who received G-CSF alone (7.2 × 10(10)  ± 2.0 × 10(10) vs. 5.7 × 10(10)  ± 1.7 × 10(10) , p = 0.006). PBSC-GTX donors produced a remarkably high granulocyte yield (9.7 × 10(10)  ± 2.3 × 10(10) ). The use of HES was associated with better granulocyte collection efficiency (42 ± 7.8% vs. 10 ± 9.1%, p < 0.0001). CONCLUSION: G-CSF plus dexamethasone produces higher granulocyte yields than G-CSF alone. Granulocyte collection from PBSC donors appears to be a rational strategy, since it produces high granulocyte yields when the related patients are at a high risk for infection and reduces difficulties in finding granulocyte donors. HES should be used in apheresis procedures.
    Transfusion 04/2012; 52(12). DOI:10.1111/j.1537-2995.2012.03661.x · 3.57 Impact Factor
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    ABSTRACT: Cachexia in patients with hematological malignancies is often related to sarcopenia. We believe that allogeneic hematopoietic stem cell transplant (allo-HSCT) patients often exhibit sarcopenia prior to transplantation. Here, we aimed to investigate the prevalence of sarcopenia and its relationship with body composition, physiological function, nutrition, fatigue, and health-related quality of life (QOL) in patients before allo-HSCT. We further investigated the confounding factors associated with sarcopenia. We included 164 patients with allo-HSCT in this study. Body composition, handgrip, knee extensor strength, and 6-min walk test were evaluated. Furthermore, fatigue, nutritional status, and health-related QOL were also evaluated. Eighty-three patients (50.6 %) enrolled in our study had sarcopenia prior to allo-HSCT. Patients with sarcopenia experienced decreased muscular strength and increased fatigue compared with patients without sarcopenia (p < 0.05). Patients with sarcopenia showed significantly lower scores in physical functioning, bodily pain, and vitality in health-related QOL than those without sarcopenia. Multivariate regression analysis revealed that only gender and body mass index were significantly related to sarcopenia (gender, odds ratio, 3.09; body mass index, odds ratio, 0.70; p < 0.01). Sarcopenia is common in patients before allo-HSCT and related to low muscle strength, fatigue, and health-related QOL. Male patients may be more susceptible to sarcopenia than female patients before allo-HSCT. Further study of rehabilitation with gender insight is warranted for patients receiving allo-HSCT.
    Supportive Care in Cancer 04/2012; 20(12):3161-8. DOI:10.1007/s00520-012-1460-5 · 2.50 Impact Factor
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    ABSTRACT: Adenovirus (AdV) infection is an emerging complication in patients undergoing allogeneic stem cell transplantation (SCT) and is closely associated with delayed immune reconstitution. In particular, disseminated AdV disease accompanies a high mortality. We retrospectively examined the incidence of AdV infection in patients undergoing unmanipulated haploidentical SCT. Following 121 transplantations in 110 patients, three had asymptomatic AdV viremia, three had localized AdV disease (hemorrhagic cystitis, HC), and seven had disseminated AdV disease (HC + viremia). The median time from transplantation to the onset of AdV-associated HC was 15 days (range 4-39), and the median time to the onset of disseminated AdV disease was 23 days (range 7-38). The cumulative incidence of AdV-associated HC was 8.3 %, and that of disseminated AdV disease was 5.8 %. AdV group B (type 11, type 34, or type 35) was detected in plasma samples from all the patients with disseminated AdV disease. Among them, three patients who received either cidofovir or donor lymphocyte infusion (DLI) alone progressed to pneumonia and died. The remaining four patients were treated with the combination of cidofovir and low-dose unmanipulated DLI, and all survived. We showed that disseminated AdV disease is a significant complication after haplo-SCT and that the combination of cidofovir and DLI is a promising treatment option.
    Annals of Hematology 04/2012; 91(8):1305-12. DOI:10.1007/s00277-012-1440-3 · 2.40 Impact Factor