scholarly journals High fludarabine exposure and relationship with treatment-related mortality after nonmyeloablative hematopoietic cell transplantation

2010 ◽  
Vol 46 (1) ◽  
pp. 20-26 ◽  
Author(s):  
J R Long-Boyle ◽  
K G Green ◽  
C G Brunstein ◽  
Q Cao ◽  
J Rogosheske ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Treatment Related Mortality ◽  
Related Mortality

scholarly journals Adolescents and Young Adults with Acute Myeloid Leukemia Are Associated with Higher Treatment-Related Mortality and Inferior Overall Survival after Allogeneic Hematopoietic Cell Transplantation Compared with Children

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4702-4702
Author(s):  
Daisuke Tomizawa ◽  
Shiro Tanaka ◽  
Tadakazu Kondo ◽  
Yoshiko Hashii ◽  
Yasuyuki Arai ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Gvhd Prophylaxis ◽  
Treatment Related Mortality ◽  
Related Mortality ◽  
Acute Myeloid

Abstract BACKGROUND : There have been few reports on outcome of adolescent and young adults (AYAs) with acute myeloid leukemia (AML) who received allogeneic hematopoietic cell transplantation (allo-HCT). We performed a retrospective analysis of nationwide registration data of the Japan Society of Hematopoietic Cell Transplantation collected between 1990 and 2013 to assess the allo-HCT outcomes of AYA patients with AML in Japan. PATIENTS & METHODS : 2973 patients with de novo AML (excluding acute promyelocytic leukemia, myeloid leukemia associated with Down syndrome, and secondary AML) whose age was 0-29 years old at their first allo-HCT either in first or second remission (CR), primary induction failure, or first relapse were identified. Outcomes including overall survival rate (OS), disease-free survival rate (DFS), cumulative incidence of relapse (CIR), and treatment-related mortality (TRM) were compared between children (0-14 years old at HCT, N=1123) and AYAs (15-29 years old, N=1850). RESULTS : AYA patients had male predominance, higher incidence of intermediate risk cytogenetics but lower incidence of high-risk cytogenetics [-7/7q-, -5/5q-, complex karyotype, t(6;9), or t(16;21)], and higher prevalence of French-American-British M0, M1, and M2 morphology, while M5 and M7 were lower. Compared to children, AYA patients were transplanted more frequently by HLA-matched-related or unrelated donors, while less frequently by HLA-mismatched related or unrelated cord blood donors. As for conditioning regimen, proportion of myeloablative conditioning (MAC) using total-body-irradiation (TBI) was higher in the AYAs, while that of non-TBI MAC and reduced-intensity-conditioning (RIC) were lower. Cyclosporine was more frequently used than tacrolimus as graft-versus-host-disease (GVHD) prophylaxis in the AYAs. Five-year OS and DFS rates were significantly poorer in the AYAs: 58% vs 54% (p<0.01) and 53% vs 48% (p=0.03), respectively. Five-year CIR did not differ between the two groups; 33% vs 34% (p=0.99). However, 5-year TRM was significantly higher in the AYAs; 13% vs 16% (p=0.02). Multivariate analysis for both OS and TRM showed significant negative impact of AYAs, but not for DFS or CIR. Subgroup analyses showed that impact of AYAs for OS was greater in male, patients with low-risk cytogenetic abnormalities [t(8;21) or inv(16)], transplanted in CR, transplanted from HLA-matched related donor, received non-TBI MAC conditioning, or received cyclosporine-based GVHD prophylaxis. Finally, we analyzed the impact of transplant center types on HCT outcomes among the 317 adolescent patients (15-18 years old) who were transplanted at 1CR or 2CR, because they could be transplanted either by pediatricians or by adult hematologists according to their referral pattern. 92 cases were transplanted in pediatric centers, 203 in adult centers, and 22 in combined pediatric and adult centers. Basic characteristics and method of HCT did not differ significantly among the three groups. Interestingly, there was no difference in OS, DFS, CIR, or TRM. CONCLUSIONS : AYAs with AML showed inferior post-transplant survival, which was mainly due to higher TRM in the AYAs. Disclosures No relevant conflicts of interest to declare.

scholarly journals Trends in allogeneic stem cell transplantation for multiple myeloma: a CIBMTR analysis

Blood ◽  
2011 ◽  
Vol 118 (7) ◽  
pp. 1979-1988 ◽  
Author(s):  
Shaji Kumar ◽  
Mei-Jie Zhang ◽  
Peigang Li ◽  
Angela Dispenzieri ◽  
Gustavo A. Milone ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Unrelated Donor ◽  
Recent Cohort ◽  
Over Time ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Allogeneic hematopoietic cell transplantation in multiple myeloma is limited by prior reports of high treatment-related mortality. We analyzed outcomes after allogeneic hematopoietic cell transplantation for multiple myeloma in 1207 recipients in 3 cohorts based on the year of transplantation: 1989-1994 (n = 343), 1995-2000 (n = 376), and 2001-2005 (n = 488). The most recent cohort was significantly older (53% > 50 years) and had more recipients after prior autotransplantation. Use of unrelated donors, reduced-intensity conditioning and the blood cell grafts increased over time. Rates of acute graft-versus-host (GVHD) were similar, but chronic GVHD rates were highest in the most recent cohort. Overall survival (OS) at 1-year increased over time, reflecting a decrease in treatment-related mortality, but 5-year relapse rates increased from 39% (95% confidence interval [CI], 33%-44%) in 1989-1994 to 58% (95% CI, 51%-64%; P < .001) in the 2001-2005 cohort. Projected 5-year progression-free survival and OS are 14% (95% CI, 9%-20%) and 29% (95% CI, 23%-35%), respectively, in the latest cohort. Increasing age, longer interval from diagnosis to transplantation, and unrelated donor grafts adversely affected OS in multivariate analysis. Survival at 5 years for subjects with none, 1, 2, or 3 of these risk factors were 41% (range, 36%-47%), 32% (range, 27%-37%), 25% (range, 19%-31%), and 3% (range, 0%-11%), respectively (P < .0001).

scholarly journals Impact of prior imatinib mesylate on the outcome of hematopoietic cell transplantation for chronic myeloid leukemia

Blood ◽  
2008 ◽  
Vol 112 (8) ◽  
pp. 3500-3507 ◽  
Author(s):  
Stephanie J. Lee ◽  
Manisha Kukreja ◽  
Tao Wang ◽  
Sergio A. Giralt ◽  
Jeffrey Szer ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Imatinib Mesylate ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Phase ◽  
Hematopoietic Cell ◽  
Free Survival ◽  
Treatment Related Mortality ◽  
Related Mortality

AbstractImatinib mesylate (IM, Gleevec) has largely supplanted allogeneic hematopoietic cell transplantation (HCT) as first line therapy for chronic myeloid leukemia (CML). Nevertheless, many people with CML eventually undergo HCT, raising the question of whether prior IM therapy impacts HCT success. Data from the Center for International Blood and Marrow Transplant Research on 409 subjects treated with IM before HCT (IM+) and 900 subjects who did not receive IM before HCT (IM−) were analyzed. Among patients in first chronic phase, IM therapy before HCT was associated with better survival but no statistically significant differences in treatment-related mortality, relapse, and leukemia-free survival. Better HLA-matched donors, use of bone marrow, and transplantation within one year of diagnosis were also associated with better survival. A matched-pairs analysis was performed and confirmed a higher survival rate among first chronic phase patients receiving IM. Among patients transplanted with advanced CML, use of IM before HCT was not associated with treatment-related mortality, relapse, leukemia-free survival, or survival. Acute graft-versus-host disease rates were similar between IM+ and IM− groups regardless of leukemia phase. These results should be reassuring to patients receiving IM before HCT.

scholarly journals Donor IFNL4 Genotype Is Associated with Transplant-Related Mortality after Unrelated Donor Myeloablative Hematopoietic Cell Transplantation in Patients with Acute Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 968-968
Author(s):  
Shahinaz M Gadalla ◽  
Tao Wang ◽  
Olusegun Onabajo ◽  
Youjin Wang ◽  
Michael D. Haagenson ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Cell Transplantation ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Taqman Assay ◽  
Unrelated Donor ◽  
Karnofsky Performance Score ◽  
Related Mortality

Abstract Introduction. Interferon Lambda 4 gene (IFNL4) encodes IFN-λ4 protein, a new member of the type-III interferon family. IFNL4 genotype (rs368234815-dG allele), defines the genetic ability to produce IFN-λ4 and has been associated with reduced clearance of hepatitis C virus (HCV) infection. Given antiviral activity and immune modulation properties of IFN-λ4, we hypothesized that IFNL4 genotype of recipient and/or donor may modulate post-transplant survival outcomes, possibly through control of viral infections, and/or alloreactivity. Methods. From the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we randomly selected 627 patients who received unrelated hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML, N=449) or acute lymphocytic leukemia (ALL, N=178). The patients had to match the following criteria: 1) HCT between 2004 and 2012, 2) available pre-HCT blood sample for the donor and recipient, 3) 8/8 HLA matching, and 3) myeloablative conditioning. IFNL4 genotyping was completed for 619 donors and 522 recipients using a custom-designed TaqMan assay for rs368234815. Multivariable Cox proportional hazard models were used for statistical analyses. Follow-up ended in November 2017. Results. Median age at HCT was 40 years (range=<1-68). Most patients (66%, N=411) were in first complete remission, had a Karnofsky Performance Score (KPS) between 90-100% (70%, N=436), and received peripheral blood stem cell grafts (70%, N=439). The median post-HCT follow-up was 68 months (range=5-122). Donor IFNL4 genotype was associated with risk of transplant-related mortality (TRM); with 5 years probabilities=19%, 27%, and 30% for donor TT/TT (n=286), TT/dG (n=267), and dG/dG (n=64) genotypes, respectively, p=0.02. The results remained significant in multivariable analysis (p=0.002); compared with patients receiving HCT from donors with TT/TT genotype, with the HR=1.59 (95% CI=1.13-2.23, p=0.007) for TT/dG donors and HR=1.95 (95% CI=1.18-3.23, p=0.009) for dG/dG donors. The data suggested that donor IFNL4 genotype may also predict risk of disease-free survival (DFS; HR=1.43, 95% CI=1.02-2.00, p=0.03), and overall survival (OS; HR=1.40 (95% CI=0.98-1.99, p=0.06) for donor dG/dG genotype (Table1). No association between recipient genotype and any survival outcome was observed (p>0.05 for OS, DFS, and TRM) Conclusions. Donor IFNL4 genotype is associated with risk of transplant-related mortality in patients with acute leukemia. The data suggest that avoiding donors with dG/dG genotype will improve HCT outcomes without limiting the potential donor pool. A validation study is needed; if confirmed, IFNL4 genotype may provide an added value to donor selection criteria. Disclosures Lee: Onyx: Research Funding; Kadmon: Research Funding; Amgen: Consultancy, Research Funding; Mallinckrodt: Honoraria; Incyte: Consultancy; Pfizer: Consultancy; Takeda: Research Funding.

Sign in / Sign up

Export Citation Format

Share Document