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  • 1
    Online Resource
    Online Resource
    Elsevier BV ; 2014
    In:  Biology of Blood and Marrow Transplantation Vol. 20, No. 11 ( 2014-11), p. 1852-1856
    In: Biology of Blood and Marrow Transplantation, Elsevier BV, Vol. 20, No. 11 ( 2014-11), p. 1852-1856
    Type of Medium: Online Resource
    ISSN: 1083-8791
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2014
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  • 2
    In: Biology of Blood and Marrow Transplantation, Elsevier BV, Vol. 19, No. 1 ( 2013-01), p. 82-86
    Type of Medium: Online Resource
    ISSN: 1083-8791
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2013
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  • 3
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 5456-5456
    Abstract: Before allogeneic transplantation, an extensive workup is generally performed to evaluate disease status, prior organ damage and ability to tolerate intensive treatment. Due to lack of specific guidelines, the extent of the workup varies substantially among centers. In an attempt to understand the significance of the different components of pretransplant workup, we evaluated 150 consecutive transplants at our center. Furthermore, we analyzed reasons for delaying or cancelling transplants after admission for workup. Patients and methods Between May 2010 and October 2012, 157 allogeneic transplants were planned in 99 men and 58 women with a median age of 51 y (19-70). Diagnoses were acute leukemia (n=80), myelodysplastic syndrome (n=23), multiple myeloma (n=15), lymphoma (n=25), myeloproliferative disease (n=10) or aplastic anemia (n=4). 26 transplants were not performed as initially scheduled but were delayed for a median of 21 days (4-146). Seven transplants were cancelled due to progressive disease (n=6) or lack of indication upon reevaluation (n=1) and were excluded from further analysis. At the time of analysis, the pretransplant workup consisted of an MRI of the head, a CT-scan of the chest and upper abdomen, gynecology, ophthalmology, ears nose and throat (ENT), and dental evaluation, pulmonary function testing (PFT) and an echocardiography, as well as microbiological tests not included in this analysis. All patients received a history and thorough physical examination, as well as disease staging. Some examinations were cancelled due to scheduling issues. We assessed the results of the various examinations, categorizing these into “normal or minor finding”, “major finding”, meaning the result had significant consequences such as further testing or therapy, or “delay”, meaning scheduled transplant was postponed due to a major finding. In case of a major finding or delay, we also considered whether this was incidental, or whether the patient had clinical symptoms or a previous history indicating the patient was at risk for the given finding. Results The number of major findings and delayed transplants are shown in Table 1 for the respective examinations, along with the number of findings that were incidental. The majority of findings in CT were pulmonary infiltrates, and 4 cases of new liver lesions. Major ENT findings consisted of sinusitis or rhinitis in most cases; the majority of dental findings were severe caries or periodontitis. Of note is the fact that sanitation of dental or ENT foci before transplant was recommended in 4 cases, but not performed due to time constraints. Disease staging revealed unexpected progression in 7 patients, so that transplant was delayed for reinduction therapy. Clinical evaluation showed signs of infection leading to postponement of transplant in 8 patients, while in 2 patients planned conditioning intensity was reduced due to poor general health. Finally in 4 patients, transplant was delayed for reasons unrelated to the pretransplant workup, including donor issues (n=3) and unexpected toxicity of the conditioning regimen (n=1). In summary, while extensive testing seems justified before allogeneic transplant, only a minority of exams performed in our center led to a significant number of major findings that necessitated further testing or therapy, or to postponement of the transplant. Furthermore, many of the major findings were not incidental but were either symptomatic or previously known. CT-scan of the chest and upper abdomen and dental evaluation had the highest yield of incidental major findings (in 9% of screened patients, each), and led to delay of several transplants. Furthermore, the significant number of transplants delayed at short notice suggest that the pretransplant workup should possibly be performed at an earlier timepoint, allowing time for necessary interventions. In a next step, we will perform a cost efficiency analysis of the pretransplant workup, based on the results presented here. 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: 2013
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  • 4
    Online Resource
    Online Resource
    American Society of Hematology ; 2009
    In:  Blood Vol. 114, No. 22 ( 2009-11-20), p. 3337-3337
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 3337-3337
    Abstract: Abstract 3337 Poster Board III-225 In the past decade there has been a significant increase in the use of reduced intensity conditioning (RIC) regimens for allogeneic hematopoietic stem cell transplantation (HSCT). RIC HSCT is associated with reduced transplant related mortality, but also with an increased risk of relapse and graft rejection. Little is known about factors associated with graft rejection. Based on early animal models, intensified cyclosporine (CyA) administration is considered an essential component of RIC HSCT with minimal conditioning. We were interested in analyzing the role of CyA in graft rejection following RIC HSCT. Between October 1999 and December 2008, 85 patients received an allogeneic RIC HSCT with fludarabine 3 × 30 mg/m2 and 2 Gy TBI as conditioning at our institution. 6 patients were excluded from the analysis due to graft loss associated with relapse or progressive disease, 2 were excluded for missing data. Diseases were acute leukemia (N=19), MDS (N=11), CML/MPN (N=10), lymphoma (N=24), multiple myeloma (N=12), and pure white cell aplasia (N=1). Donors were HLA-identical siblings (N=54) or unrelated donors (N=23). Graft source was peripheral blood (N=74) or bone marrow (N=3). Graft-versus-host disease (GvHD) prophylaxis consisted of CyA and mycophenolate mofetil (MMF). CyA was started at a dose of 6.25mg/kg p.o. twice daily and adjusted according to trough levels (measured weekly) and toxicity. MMF was administered at a dose of 15mg/kg twice daily; trough levels were not analyzed systematically. For the analysis of impact on graft rejection, CyA levels between day 1 and 28 where summarized as mean trough levels. Graft rejection was defined as 〈 5% donor cells at any time on day 28 or later or application of donor lymphocyte infusion for declining donor chimerism. Of the 77 evaluable patients, 16 (21%) experienced graft rejection at a median of 69 days after transplantation. There was no significant difference in disease stage (early vs. advanced), median age at transplant (56 and 57 years, respectively), EBMT risk score, graft cell count (nucleated and CD34+ cells) and history of previous transplants between patients with or without rejection. In contrast, there was a significant difference in underlying disease, with a higher proportion of CML/MPN and a lower proportion of multiple myeloma in rejecting patients. Mean CyA trough levels were clearly associated with graft rejection with a cumulative incidence of rejection of 8%, 29% and 56% with trough levels of 〈 300 ng/ml (N=40), 300-600 ng/ml (N=28) and 〉 600 ng/ml (N=9) (p=0.002) (Figure A) and a median donor chimerism at day 28 of 99%, 84%, and 72% respectively (p=0.004). In a multivariate analysis, two factors remained significantly associated with graft rejection: unrelated donor (HR vs. sibling donor 4.52, p = 0.03), and mean trough level of CyA for days 1-28 (HR 1.006 per ng/ml increase, p=0.001). Patients with CML/MPN had an increased risk of rejection (HR 1.36 versus other patients combined, p=0.65) which did not reach statistical significance. The overall survival of the entire patient group was 55% at five years; patients with stable engraftment had a five-year survival rate of 61%, those rejecting their graft 36% (p=0.04). These data indicate that elevated CyA levels during the first month posttransplant might be associated with an increased risk of graft rejection. The potentially detrimental effects of high CyA levels have been described previously in the myeloablative setting, where a correlation between CyA levels and risk of relapse has been shown. Further studies will be needed to better define the exact role of CyA following RIC regimens. Disclosures Gratwohl: Amgen: Research Funding; Bristol Myers Squibb: Research Funding; Pfizer: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
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  • 5
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 2268-2268
    Abstract: Abstract 2268 Poster Board II-245 Busulfan-cyclophosphamide (BU-CY) is the established non total body irradiation based myeloablative conditioning regimen for allogeneic hematopoietic stem cell transplantation (HSCT). The introduction of intravenous busulfan has facilitated its application and reduced toxicity. Theoretical considerations and pharmacological data indicate that previous application of busulfan may trigger liver toxicity of subsequent cyclophosphamide. A reverse order of cyclophosphamide-busulfan (CY-BU) would be preferable. Recent animal data confirmed this hypothesis, showing less liver toxicity and better outcomes in mice treated with CY-BU. While CY-BU was not feasible in patients with oral busulfan, it has become a possibility with the introduction of i.v. busulfan. We were therefore interested in exploring this concept and changed the order of drug application to CY-BU in 2003 in those patients not on a multicentre standardized BU-CY protocol. We now retrospectively analyzed in this single centre cohort study liver toxicity and transplantation outcome in patients receiving BU and CY as conditioning regimen for allogeneic HSCT. We analyzed 93 consecutive patients between 1993 and 2008, 52 male (55.9%), median age 46 years (range 16 to 70) with hematological malignancies (AML 41 [44.1%], ALL 11 [11.8%] , CML 12 [12.9%], myelodysplastic syndrome and myeloproliferative neoplasia 22 [23.7%] , lymphoproliferative disorders 4 [4.3%]) or other diseases (3 [3.2%] ), receiving an allogeneic HSCT from an HLA- identical sibling (52 [55.9%]), other family member (3 [3.2%] ) or a matched unrelated donor (38 [40.9%]) after conditioning regimen with BU-CY (34 patients; 18 patients with oral, 16 patients since 2003 with i.v. busulfan) or CY-BU (59 patients). Outcomes were analyzed using a Cox regression model, adjusting for disease, stage, donor type, stem cell source, previous total body irradiation (TBI) and busulfan administration (oral vs. intravenous). Pretransplant patient characteristics were comparable in the two cohorts for age, gender, underlying disease, stem cell source, donor type and EBMT risk score, but differed in stage (advanced disease BU-CY 28 [84,8%] vs. CY-BU 40 [66.7%]) and previous TBI (BU-CY 16 [48.5%] vs. CY-BU 9 [15.0%]). Liver function as measured by levels of bilirubin and liver enzymes (aspartate amino transferase [AST] , alanine amino transferase [ALT], gamma glutamyl transpeptidase [GGT] and alkaline phosphatase [AP]) was not different between the groups before starting conditioning regimen. In contrast liver function differed significantly at day 20, with higher levels of ALT (median 51.0 vs 27.0 IU/l; p=0.012) and a higher incidence of veno-occlusive disease (VOD) (5/34 vs. 1/59, p=0.036) in the BU-CY group (Figure 1A). The cumulative incidence of transplant-related mortality (TRM) at 2 years was significantly higher in patients receiving BU-CY (BU-CY 0.48, CY-BU 0.24, p=0.024; hazard ratio 4.594 for BU-CY, 95% CI 1.382-15.268, p=0.013) (Figure 1B). The cumulative incidence of TRM with BU i.v.-CY was lower (0.44) than with BU oral-CY (0.56) but still higher than CY-BU. This did translate into a higher overall survival in patients after conditioning regimen with CY-BU (hazard ratio for mortality 0.426 for CY-BU, 95% CI 0.184-0.987, p=0.047). Time to engraftment (BU-CY median 13 days vs. CY-BU median 14 days), cumulative incidence of acute GVHD and relapse were similar between patients receiving BU-CY or CY-BU. These data support the concepts derived from Sadeghi et al in their mouse model in favor of CY-BU compared to the traditional BU-CY. They form the basis for prospective controlled studies. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
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  • 6
    In: Cytotherapy, Elsevier BV, Vol. 23, No. 4 ( 2021-04), p. 329-338
    Type of Medium: Online Resource
    ISSN: 1465-3249
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
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  • 7
    In: Biology of Blood and Marrow Transplantation, Elsevier BV, Vol. 16, No. 9 ( 2010-09), p. 1309-1314
    Type of Medium: Online Resource
    ISSN: 1083-8791
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2010
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  • 8
    In: Biology of Blood and Marrow Transplantation, Elsevier BV, Vol. 19, No. 6 ( 2013-06), p. 973-980
    Type of Medium: Online Resource
    ISSN: 1083-8791
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2013
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    detail.hit.zdb_id: 2057605-5
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