scholarly journals Treatment-related mortality in children with cancer: Prevalence and risk factors

2019 ◽  
Vol 121 ◽  
pp. 113-122 ◽  
Author(s):  
Erik A.H. Loeffen ◽  
Rutger R.G. Knops ◽  
Joren Boerhof ◽  
E.A.M. (Lieke) Feijen ◽  
Johannes H.M. Merks ◽  
...  
Keyword(s):  
Risk Factors ◽  
Children With Cancer ◽  
Cancer Prevalence ◽  
Treatment Related Mortality ◽  
Related Mortality

Treatment-Related Mortality in Patients With Advanced-Stage Hodgkin Lymphoma: An Analysis of the German Hodgkin Study Group

2013 ◽  
Vol 31 (22) ◽  
pp. 2819-2824 ◽  
Author(s):  
Diana Wongso ◽  
Michael Fuchs ◽  
Annette Plütschow ◽  
Beate Klimm ◽  
Stephanie Sasse ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hodgkin Lymphoma ◽  
Individual Risk ◽  
Tumor Control ◽  
Poor Performance Status ◽  
Study Group ◽  
Advanced Stage ◽  
German Hodgkin Study Group ◽  
Treatment Related Mortality ◽  
Related Mortality

Purpose The introduction of BEACOPPescalated (escalated-dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) has significantly improved tumor control and overall survival in patients with advanced-stage Hodgkin lymphoma. However, this regimen has also been associated with higher treatment-related mortality (TRM). Thus, we analyzed clinical course and risk factors associated with TRM during treatment with BEACOPPescalated. Patients and Methods In this retrospective analysis, we investigated incidence, clinical features, and risk factors for BEACOPPescalated-associated TRM in the German Hodgkin Study Group trials HD9, HD12, and HD15. Results Among a total of 3,402 patients, TRM of 1.9% (64 of 3,402) was mainly related to neutropenic infections (n = 56; 87.5%). Twenty of 64 events occurred during the first course of BEACOPPescalated (31.3%). Higher risk of TRM was seen in patients age ≥ 40 years with poor performance status (PS) and in patients age ≥ 50 years. PS and age were then used to construct a new risk score; those with a score ≥ 2 had TRM of 7.1%, whereas patients who scored 0 or 1 had TRM of 0.9%. Conclusion The individual risk of TRM associated with BEACOPPescalated can be predicted by a simple algorithm based on age and PS. High-risk patients should receive special clinical attention.

scholarly journals The risk factors associated with treatment-related mortality in 16,073 kidney transplantation—A nationwide cohort study

PLoS ONE ◽  
2020 ◽  
Vol 15 (7) ◽  
pp. e0236274 ◽  
Author(s):  
Hyunji Choi ◽  
Woonhyoung Lee ◽  
Ho Sup Lee ◽  
Seom Gim Kong ◽  
Da Jung Kim ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cohort Study ◽  
Kidney Transplantation ◽  
Factors Associated ◽  
Treatment Related Mortality ◽  
Related Mortality

Mortality during Treatment of Patients with Advanced Hodgkin’s Lymphoma Undergoing Dose Escalated BEACOPP Chemotherapy: An Analysis of the German Hodgkin Study Group (GHSG).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2668-2668 ◽  
Author(s):  
Michael Fuchs ◽  
Jeremy Franklin ◽  
Beate Klimm ◽  
Andreas Josting ◽  
Beate Pfistner ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hodgkin’S Lymphoma ◽  
Mediastinal Mass ◽  
Hodgkin's Lymphoma ◽  
Outpatient Basis ◽  
Extranodal Involvement ◽  
Study Population ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Introduction: Due to substantial clinical progress over the past decades, the outcome of patients with Hodgkin’s Lymphoma (HL) has improved with a long-term disease free survival of nearly 80%. Even patients with advanced-stage HL show a five year freedom from treatment failure (FFTF) of 87% and overall survival (OS) of 91% when treated with 8 cycles of BEACOPPescalated (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbacine, prednisone). However, BEACOPPescalated has been associated with some acute and long-term treatment related mortality (TRM). We thus analysed the incidence, clinical features and risk factors for TRM of patients treated with BEACOPPescalated in the HD12 multicenter trial of the GHSG performed between 1998 and 2002. The HD12 was conducted for advanced HL patients (Stage IIB with large mediastinal mass and/or extranodal involvement, stage III/IV). All patients received 8 cycles of chemotherapy either 8x BEACOPPescalated (Arm A/B) or 4xBEACOPPescalated + 4xBEACOPPbaseline (Arm C/D) +/− 30Gy radiation on bulk and residual tumor. Results: In this study, 43 patients (3.1%) from a total of 1392 included died from TRM. 5 patients were excluded from this analysis because of various reasons (change of fist-line therapy due to toxicity, TRM in BEACOPPbaseline) 38 patients were eligible for this analysis. 30 patients (79%) had infectious complications, 6 (16%) cardiac events such as arrhythmia or heart failure, 1 patient died due to bleomycin-related toxicity and 1 case remained unclear. 25 patients (66%) were older than 50 years in contrast to the whole HD12 study population with only 17% of patients being older than 50. There was no statistical difference between those cases with treatment related mortality and the whole study population in terms of other clinical risk factors such as gender, B-symptoms, extranodal involvement, stage of disease, large mediastinal mass or elevated ESR. There was also no difference between the 4 study arms. Most events occurred during the first 4 courses of BEACOPPescalated (79%) with the majority during the first cycle (n = 12; 32%). 23/26 (89%) of patients who died during cycles 2 – 8 had prior WHO grade III/IV leucopenia or infection. Conclusion: Patient age and toxicity in previous cycles are the most obvious risk factors for TRM in patients with advanced HL undergoing BEACOPPescalated chemotherapy. In the HD12 study, the use of G-CSF was mandatory and most patients received their treatment on an outpatient basis. Thus, possible measures to reduce toxicity with this treatment include the prophylactic use of antibiotics as well as treating those with risk factors at least for the first course as inpatients.

Iron Overload Strongly Correlates with Acute Graft-Versus-Host-Disease of the Liver and Treatment Related Mortality after Allogeneic Hematopoetic Cell Transplantation (HCT).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1812-1812
Author(s):  
Ann-Kathrin Eisfeld ◽  
Ralph Burkhardt ◽  
Daniel Teupser ◽  
Sabine Schroeder ◽  
Rainer Krahl ◽  
...  
Keyword(s):  
Risk Factors ◽  
Iron Overload ◽  
Retrospective Analysis ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Hfe Gene ◽  
Strongly Correlated ◽  
Body Iron ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Risk factors for morbidity and treatment related mortality (TRM) following HCT have been well defined in retrospective analysis and prospective validations. These include disease-, recipient- and donor-specific characteristics, but not treatment related factors. Considering that patients undergoing HCT usually receive multiple blood transfusions (BT) and that mutations of the HFE gene are common in the European population, we asked the question if iron overload and HFE mutations were risk factors for complications following HCT. Patients and methods: From January 2001 to December 2004, 265 consecutive patients (142 m/123 f; median age 47 y) received HCT at the University of Leipzig. Patients suffered from acute leukaemia (n=113; 43%), chronic leukaemia (n=75; 28%), lymphoma (n=37; 14%), multiple myeloma (n=21; 8%), and others (n=19; 7%). Preparative regimen consisted of Cyclophosphamid 120 mg/kg and 12 Gy TBI in 145 (55%) patients. The remaining 120 (45%) patients were conditioned with Fludarabin 30 mg/m2/day for 3 days and 2 Gy TBI. HCT was performed from matched related donors in 85 (32%) and matched unrelated donors (MUD) in 180 (68%) patients. Patients and donors were screened for mutant HFE genes by PCR using LightCycler, Roche. Serum ferritin (reference values 30–400 ng/ml) was measured at a median of 1 month after HCT. At the time of measurement, patients had to be in good clinical condition with normal C-reactive protein. Results: Elevated iron stores were present in 86% of patients (median ferritin 1697 ng/ml). At a median of 25 (range 7–55) months after HCT, 92 (35%) patients have died from relapse (n= 27; 29%) or TRM (n= 65; 71%). TRM occurred at a median of 4 months after HCT. Median ferritin in patients who died (measured at a median of 3 months prior to death) and in surviving patients were 3815 and 1146 ng/ml respectively (p<0.0001). The median number of BT at HCT in the 2 groups were 34, and 16 unit respectively (p<0.0001). MUD, CMV-serological status and the gender of the donor did not correlate with TRM. In multivariate analysis, ferritin and BT strongly correlated with TRM (p<0.0001). Mutant HFE genes were found in 98 (37%) patients prior to HCT [heterozygous (het; n=82, 84%), compound (n=9; 9%), homozygous (homo; n=7; 7%). Similarly, 99 (37%) donors showed mutant HFE genes [het, n=86 (87%), compound, n=8 (8%), and homo, n=5 (5%)]. After HCT, all patients expressed donor HFE genotype. HFE genotype of patients and donors did not correlate with TRM. Acute GvHD > grade II was significantly more in pts who died (p=0.0002). Acute GvHD of the liver strongly correlated with excess body iron (p=0.009). Interestingly, chronic GvHD of the skin and liver tended to be more frequent in patients with mutant HFE genes prior to HCT (p=0.03). Conclusions: This is, to our knowledge, the first retrospective analysis where excess body iron and the number of BT at HCT strongly correlated with acute GvHD of the liver and TRM after HCT. These data must be confirmed in prospective studies. Whether morbidity and TRM after HCT can be reduced by iron chelation needs to be evaluated.

Risk factors for treatment related mortality in childhood acute lymphoblastic leukaemia

2010 ◽  
Vol 56 (4) ◽  
pp. 551-559 ◽  
Author(s):  
Bendik Lund ◽  
Ann Åsberg ◽  
Mats Heyman ◽  
Jukka Kanerva ◽  
Arja Harila-Saari ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Lymphoblastic Leukaemia ◽  
Lymphoblastic Leukaemia ◽  
Childhood Acute Lymphoblastic Leukaemia ◽  
Treatment Related Mortality ◽  
Related Mortality

Early Deaths and Treatment-Related Mortality in Children Undergoing Therapy for Acute Myeloid Leukemia: Analysis of the Multicenter Clinical Trials AML-BFM 93 and AML-BFM 98

2004 ◽  
Vol 22 (21) ◽  
pp. 4384-4393 ◽  
Author(s):  
Ursula Creutzig ◽  
Martin Zimmermann ◽  
Dirk Reinhardt ◽  
Michael Dworzak ◽  
Jan Stary ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Clinical Trials ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Fungal Infections ◽  
Adequate Treatment ◽  
Treatment Related Mortality ◽  
Related Mortality ◽  
Acute Myeloid

Purpose The rates of early death (ED) and treatment-related mortality (TRM) are unacceptably high in children undergoing intensive chemotherapy for acute myeloid leukemia (AML). Better strategies of supportive care might help to improve overall survival in these children. Patients and Methods In a retrospective study, we analyzed incidence, clinical features, and risk factors for lethal complications of 901 children enrolled onto the multicenter trials Acute Myeloid Leukemia-Berlin-Frankfurt-Muenster (AML-BFM) 93 and AML-BFM 98. Results One hundred four patients (11.5%) enrolled onto the clinical trials AML-BFM 93 and AML-BFM 98 died shortly after diagnosis or as a result of treatment-related complications. Thirty-two patients (3.5%) died before (six patients) or during (26 patients) the first 14 days of treatment, mainly as a result of bleeding or leukostasis. Low performance status, hyperleukocytosis, and French-American-British type M5 were the main risk factors for a lethal event before day 15. After day 15, the predominant causes of death were complications caused by infections, particularly bacterial and fungal infections. The incidence of lethal infections was highest during induction therapy and decreased thereafter. When comparing both clinical trials, significantly fewer patients died within the first 6 weeks in AML-BFM 98 than in AML-BFM 93 (14 [3.5%] of 430 patients v 35 [7.4%] of 471 patients; P = .01). Conclusion To reduce the high incidence of ED and TRM in children with AML, early diagnosis and adequate treatment of complications are needed. Children with AML should be treated in specialized pediatric cancer centers only. Prophylactic and therapeutic regimens for better treatment management of bleeding disorders and infectious complications have to be assessed in future trials to ultimately improve overall survival in children with AML.

NOD2/CARD15 Mutations Associate with Transplant Related Mortality and GvHD in HLA-Identical Sibling Transplants: Detailed Analysis of Single SNPs in 211 Recipient/Donor Pairs.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 424-424
Author(s):  
Ernst Holler ◽  
Gerhard Rogler ◽  
Joachim Hahn ◽  
Hans Herfarth ◽  
Julia Brenmoehl ◽  
...  
Keyword(s):  
Risk Factors ◽  
Detailed Analysis ◽  
Intestinal Inflammation ◽  
Ex Vivo ◽  
Strong Association ◽  
Pcr Analysis ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Recently, our group reported a strong association of the most frequent single nucleotide polymorphisms (SNPs) in the antibacterial defense gene NOD2/CARD15 with GvHD and outcome following allogeneic stem cell transplantation (SCT). We now extended our analysis in HLA-identical sibling transplants by adding a second cohort of 133 donor /recipient pairs collected in 3 centers to our previously analyzed group of 78 consecutive transplants. PCR analysis for major SNPs 8,12, and 13 of the NOD2/CARD15 gene was performed in DNA samples from recipients and their donors after receiving informed consent, and occurrence or absence of mutations was correlated with major outcome variables. Heterozygous NOD2/CARD15 mutations were observed in 54/211 (25,6%), whereas only 1 patient and 2 donors revealed homozygous mutations. Analysis of the second cohort confirmed the significant association of occurrence of any NOD2/CARD15 mutation with treatment related mortality (TRM) and graft-versus-host disease (GvHD): Incidence of severe GvHD rose from 13% (cohort1 + 2) to 48% (cohort1, p <0.001) and 30% (cohort 2, p=0.02), and 6 months treatment related mortality (TRM) increased from 11% (cohort1) and 8% (cohort2) to 44% (cohort1, p =0.004) and 30% (cohort 2, p=0.002). By combining the data from both cohorts, we now were able to ask for the relevance of individual mutated SNPs: Detailed analysis of SNPs revealed an increased TRM in recipients bearing mutations for SNP8 or SNP12 (50% as compared to 15.6.% in wildtype recipients, p 0.005). Furthermore, our analyses showed an increased carriage of heterozygous mutations of SNP8 and 12 in healthy HLA-identical sibling donors resulting in a high number of pairs with simultaneous recipient and donor mutations for SNP8 and 12. As TRM was also strongly increased in these pairs (56%, p 0.001) but not at all in transplants with donor mutations alone, our data suggest a predominant role of recipient mutations in HLA-identical sibling transplants. This was also confirmed in a multivariate analysis of risk factors associated with TRM and overall survival where recipient and combined recipient and donor SNP8 or 12 mutations remained independent and highly significant (p 0.001) factors when compared with established risk factors such as age at Tx or stage at Tx. Even inclusion of possible interfering strategies such as use of in vivo/ex vivo T cell depletion or reduced intensity conditioning had no impact on the unique role of NOD2/CARD15 mutations. The strong association of recipient mutations points to a major role of NOD2/CARD15 mutations in intestinal inflammation, and otherwise asymptomatic heterozygous mutations might become symptomatic in the context of additional epithelial damage induced in the course of SCT.

Risk Factors of Treatment Related Mortality during Autologous Stem Cell Transplant in Patients with Light Chain Associated Amyloidosis (AL).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3082-3082
Author(s):  
Nelson Leung ◽  
Angela Dispenzieri ◽  
Martha Q. Lacy ◽  
Suzanne R. Hayman ◽  
Shaji Kumar ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alkaline Phosphatase ◽  
Stem Cell ◽  
Light Chain ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Septal Thickness ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Background: High dose melphalan followed by autologous stem cell transplant (ASCT) is an effective treatment of immunoglobulin light chain amyloidosis (AL). However, the high treatment related mortality (TRM, death before day 100) remains a serious concern and is the major drawback of this therapy. A better understanding the risk factors contributing to TRM could help physicians choose the most appropriate therapy for these patients. We performed a retrospective study to identify risk factors that contribute to TRM after ASCT in AL patients. Methods: All patients who underwent ASCT for AL at our institution from 7/96 to 12/04 were studied. Data were collected on age, sex, septal thickness, glomerular filtration rate (GFR), B2M, CRP, proteinuria, albumin, cardiac troponin T (cTnT) and alkaline phosphate. Results: A total of 218 patients underwent ASCT for AL during this time period. One patient refused consent for this study. Pretransplant cTnT was available on 161 (73.9%) patients. The overall TRM rate for the 217 patients was 12.4%. By univariate analysis, septal thickness, GFR, albumin, alkaline phosphatase and cTnT were found to be associated with TRM. In the multivariate analysis, only albumin, alkaline phosphatase and cTnT remained independent predictors of TRM. Cutoffs were identified using receiver-operator characteristic (ROC) curve. The cutoff for albumin was 2.85 g/dL, 249 U/L for alkaline phosphatase and 0.02 ng/mL for cTnT. The percentage of patients with low albumin, elevated cTnT and alkaline phosphatase were 51.1%, 20.5% and 12.4% respectively. The TRM rate of patients with low albumin was 18.0%, 27.3% for elevated cTnT and 29.6% for high alkaline phosphatase. Risk of TRM increased significantly with each additional risk factor (Table). Discussion: In our AL population, low serum albumin, elevated alkaline phosphatase and cTnT were independent risk factors of TRM after ASCT. Patients with 2 or more risk factors are at significant risk of TRM during ASCT. In these high risk patients, alternative therapy should be considered in order to avoid excessively high incidence of TRM. Treatment Related Mortality by Number of Risk Factors Risk Factors 0 1 2 3 Rate of TRM 1.8% 8.4% 35.0% 66.0% Odds Ratio 5.0 29.1 108.0

Early death and treatment‐related mortality: A report from SUCCOUR ‐ Supportive Care for Children with Cancer in Africa

2021 ◽  
Author(s):  
Trijn Israels ◽  
Glenn Mbah Afungchwi ◽  
George Chagaluka ◽  
Peter Hesseling ◽  
Francine Kouya ◽  
...  
Keyword(s):  
Supportive Care ◽  
Early Death ◽  
Children With Cancer ◽  
Treatment Related Mortality ◽  
Related Mortality
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