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  • 1
    Online Resource
    Online Resource
    Progressive Decline in Late Mortality after Hematopoietic Cell Transplantation (HCT) over 40 Years - a Report from BMTSS
    American Society of Hematology ; 2016
    In:  Blood Vol. 128, No. 22 ( 2016-12-02), p. 691-691
    Details
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 691-691
    Abstract: Background: The high intensity of therapeutic exposures (for autologous and allogeneic HCT) and chronic GvHD and its management (in allogeneic HCT) increase the risk for late mortality. Significant changes in transplantation strategies have been instituted over the past 4 decades, with the overarching goal of improving outcomes. The impact of these changes on late mortality remains unknown. Methods: We evaluated late mortality in 5,566 patients who had survived at least 2y after HCT performed between 1974 and 2010. Vital status information was ascertained as of May 2016, using medical records, National Death Index and Accurint databases. Separate analyses were conducted for allogeneic and autologous HCT. For all-cause mortality, relapse-related (RRM) and non-relapse-related (NRM) mortality, we examined trends over 4 time periods: 〈 1990 (n=656); 1990-1999 (n=1650); 2000-2004 (n=1292) and 2005-2010 (n=1968). Multivariable Cox regression analysis was used to identify predictors of all-cause mortality. Proportional subdistribution hazards model (Fine-Gray) for competing risks was used for RRM and NRM. Multivariable analysis included demographics, primary disease, conditioning regimens, disease status at HCT, stem cell source (for allogeneic and autologous HCT recipients); for allogeneic HCT recipients, it also included transplant intensity, GvH prophylaxis, chronic GvHD. Results: Allogeneic HCT:The cohort included 2,999 2y survivors followed for a median of 12.4y (range, 2.0-40.7) from HCT. Significant differences in HCT strategies (p 〈 0.0001) observed over time in the cohort included increases in age at HCT (median: 21.7y to 40.4y); use of peripheral blood stem cells (PBSCs: 0% to 62%) and cord blood stem cells (0% to 21%); reduced intensity HCTs (0% to 54%); GvH prophylaxis with tacrolimus (0% to 57%), sirolimus (0% to 49%), MMF (0% to 27%); prevalence of chronic GvHD (43% to 60%); and decreases in GvH prophylaxis with methotrexate (71% to 32%), steroids (63% to 0.3%). Multivariable analysis revealed a 44% reduction over the 4 decades in risk of all-cause late mortality (Figure 1, 〈 1990: HR=1.0; 1990-1999: HR=0.77, p=0.01; 2000-2004: HR=0.53, p=0.0003; 2005-2010: HR=0.56, p=0.005). The reduction in risk was more marked in NRM (80% reduction over 4 decades: 〈 1990: HR=1.0; 1990-1999: HR=0.52, p 〈 0.001; 2000-2004: HR=0.41, p=0.0005; 2005-2010: HR=0.2, p 〈 0.0001) than RRM (51% decline over 4 decades: 〈 1990: HR=1.0; 1990-1999: HR=0.74, p=0.02; 2000-2004: HR=1.06, p=0.7; 2005-2010: HR=0.49, p 〈 0.0001) (Figure 1). Autologous HCT: The cohort included 2,567 2y survivors followed for a median of 9.3y (2-31) from HCT. Significant (p 〈 0.0001) changes in transplantation strategies observed over time included increases in: median age at HCT (29.3y to 53.1y); use of PBSCs (39% to 100%); and decreases in: HCT for AML/MDS (18% to 5%), conditioning with TBI (43% to 12%). Multivariable analysis revealed a 75% reduction in risk of all-cause late mortality over 4 decades (Figure 2, 〈 1990: HR=1.0; 1990-1999: HR=0.55, p 〈 0.0001; 2000-2004: HR=0.35, p 〈 0.0001; 2005-2010: HR=0.25, p 〈 0.0001). The decline in risk of NRM was pronounced (96% decline over 4 decades; Figure 2, 〈 1990: 1.0; 1990-1999: HR=0.41, p 〈 0.0001; 2000-2004: HR=0.22, p 〈 0.0001; 2005-2010: HR=0.04, p 〈 0.0001). The decline in risk of RRM was 83% over 4 decades, and was statistically significant only after 2000 (Figure 2, 〈 1990: HR=1.0; 1990-1999: HR=0.77, p=0.3; 2000-2004: HR=0.46, p 〈 0.0001; 2005-2010: HR=0.17, p 〈 0.0001). Analyses restricted to autologous and allogeneic HCT recipients transplanted between 1974 and 2004 with follow-up for all for the first 10y after HCT (to ensure comparable follow-up across all time periods) showed similar findings (data not shown). Conclusions: Changes in transplantation strategies have contributed to a progressive decline in late mortality for both allogeneic and autologous HCT. The all-cause mortality has declined 44% for allogeneic HCT recipients and 75% for autologous HCT recipients over the 4 decades examined in this study. The decline in risk, while evident for relapse-related mortality, is more prominent for non-relapse mortality. Disclosures Forman: Mustang Therpapeutics: Other: Construct licensed by City of Hope.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V128.22.691.691
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
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  • 2
    Online Resource
    Online Resource
    Late mortality after bone marrow transplant for chronic myelogenous leukemia in the context of prior tyrosine kinase inhibitor exposure: A Blood or Marrow Transplant Survivor Study (BMTSS) report
    Wiley ; 2019
    In:  Cancer Vol. 125, No. 22 ( 2019-11-15), p. 4033-4042
    Details
    In: Cancer, Wiley, Vol. 125, No. 22 ( 2019-11-15), p. 4033-4042
    Abstract: Conditional on surviving for 2 years after bone marrow transplant (BMT), 10‐year overall survival is comparable for patients with chronic myelogenous leukemia (CML) who undergo transplant with and without pre‐BMT tyrosine kinase inhibitors (TKI). Non–CML‐related causes are the primary causes of death among patients with CML who survive for ≥2 years from BMT, irrespective of pre‐BMT TKI exposure.
    Type of Medium: Online Resource
    ISSN: 0008-543X , 1097-0142
    URL: Issue
    URL: Article
    DOI: 10.1002/cncr.v125.22
    DOI: 10.1002/cncr.32443
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 1479932-7
    detail.hit.zdb_id: 1429-1
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  • 3
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    Online Resource
    Long-Term Morbidity and Mortality Experienced By Chronic Myeloid Leukemia (CML) Patients after Allogeneic Hematopoietic Cell Transplantation (HCT) - a Report from BMTSS-2
    American Society of Hematology ; 2016
    In:  Blood Vol. 128, No. 22 ( 2016-12-02), p. 823-823
    Details
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 823-823
    Abstract: Background: Tyrosine kinase inhibitors have become the treatment of choice for CML. However, the high cost and need for life-long treatment contribute to non-adherence and represent a major challenge in their use. Allogeneic HCT is potentially curative, but the very long-term health of the survivors is not known. It is also not clear whether a subgroup of CML patients carries a relatively low risk of long-term morbidity. Methods: We addressed these gaps by studying long-term outcomes in 637 CML patients treated with allogeneic HCT between 1981 and 2010 at City of Hope or Univ MN, and surviving for at least 2y after HCT (median follow-up: 16.7y from HCT); 80% of the cohort was 〈 45y at HCT; 68% received HCT in 1st chronic phase (CP); 63% received matched related [MRD], 34% matched unrelated donor (MUD) and 3% non-myeloablative HCTs; 79% received TBI; 65.8% developed chronic GvHD. Vital status information was collected as of May, 2016, using medical records, National Death Index and Lexis Nexis. US mortality rates were obtained from CDC's National Center for Health Statistics. Thirty percent (n=192) died after having survived at least 2 years after HCT; median time between HCT and death was 8.3y. Of the 445 patients alive at study, 288 (65%) completed the BMTSS health questionnaire used to examine the risk of CTCAE grade 3 (severe) or 4 (life-threatening) chronic health conditions. A sibling comparison group (n=404) also completed the BMTSS questionnaire. Results: Late Mortality: Overall survival was 72.1% at 20y and 69.9% at 30y from HCT. The 20y cumulative incidence of relapse-related mortality was 3.9% (95% CI, 2.6-5.8%) and of non-relapse-related mortality was 18.2% (95% CI, 19.8-28.1%) (Figure 1). 20y cumulative incidence of mortality by cause of death was as follows: infection (7%), chronic GvHD (6%), subsequent malignant neoplasms (SMNs: 3%). HCT recipients were at 4.4-fold increased risk of death (95% CI, 3.8-5.1, p 〈 0.0001) than age-, race-, and sex-adjusted normal populations. For patients transplanted in 1st CP and surviving 15y, mortality rates became comparable with the general population (SMR, 1.5, 95% CI, 0.9-2.3, p=0.1). Among CML patients receiving HCT at 〈 45y with Bu/Cy (n=70), overall survival was 81.5% at 20y from HCT; the 20y cumulative incidence of relapse-related mortality was 2.9% and of non-relapse-related mortality was 14%. This cohort was at 3.3-fold higher risk of death when compared with the general population (95% CI=1.7-5.7, p 〈 0.0001). Late Morbidity: The 20y cumulative incidence of a severe/life-threatening chronic health condition among HCT survivors was 47.2% (95% CI, 39.0-54.9%); the incidence was higher (p=0.0006) for MUD vs. MRD recipients (Figure 2). After adjusting for age, sex, race and SES, HCT survivors were at 2.7-fold higher risk for severe/life-threatening chronic health conditions as compared with siblings (95% CI, 1.8-3.9, p 〈 0.0001). The 20y cumulative incidence of specific conditions experienced by survivors and siblings were: SMNs (10.1% vs. 1.7%, p 〈 0.001); diabetes (11.1% vs. 1.5%, p 〈 0.001) and coronary artery disease (6.9% vs. 3.2%, p 〈 0.001). CML patients receiving MRD HCT at 〈 45y with Bu/Cy were not at increased risk of severe/life-threatening chronic health conditions when compared with the sibling comparison group (HR=0.81, 95% CI, 0.26-2.54, p=0.7). Conclusions: Conditional on surviving the first 2y after HCT, the overall survival exceeds 70% at 20y and remains stable at 70% at 30y after HCT. Non-relapse related mortality (infections, chronic GvHD, SMNs) is by far the major contributor to the late mortality. Conditional on surviving the first 15y, mortality rates are similar to those observed in the general population. HCT survivors are at a 2.7-fold higher risk of severe/life-threatening morbidity when compared with siblings. The more common morbidities include SMNs, diabetes and coronary artery disease. However, CML patients receiving HCT at 〈 45y with Bu/Cy conditioning enjoy survival rates exceeding 81% at 20y from HCT, and their burden of long-term morbidity is comparable to that experienced by siblings. These findings could help inform decisions regarding therapeutic options for management of CML. Disclosures Snyder: BMS: Membership on an entity's Board of Directors or advisory committees; Ariad: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees. Forman:Mustang Therpapeutics: Other: Construct licensed by City of Hope.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V128.22.823.823
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
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    Online Resource
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