scholarly journals Occurrence of Treatment-Related Cardiotoxicity and Its Impact on Outcomes Among Children Treated in the AAML0531 Clinical Trial: A Report From the Children’s Oncology Group

2019 ◽  
Vol 37 (1) ◽  
pp. 12-21 ◽  
Author(s):  
Kelly D. Getz ◽  
Lillian Sung ◽  
Bonnie Ky ◽  
Robert B. Gerbing ◽  
Kasey J. Leger ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Left Ventricular Systolic Dysfunction ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Oncology Group ◽  
Late Cardiotoxicity ◽  
The Impact ◽  
Acute Myeloid

Purpose Late cardiotoxicity after pediatric acute myeloid leukemia therapy causes substantial morbidity and mortality. The impact of early-onset cardiotoxicity on treatment outcomes is less well understood. Thus, we evaluated the risk factors for incident early cardiotoxicity and the impacts of cardiotoxicity on event-free survival (EFS) and overall survival (OS). Methods Cardiotoxicity was ascertained through adverse event monitoring over the course of follow-up among 1,022 pediatric patients with acute myeloid leukemia treated in the Children’s Oncology Group trial AAML0531. It was defined as grade 2 or higher left ventricular systolic dysfunction on the basis of Common Terminology Criteria for Adverse Events (version 3) definitions. Results Approximately 12% of patients experienced cardiotoxicity over a 5-year follow-up, with more than 70% of incident events occurring during on-protocol therapy. Documented cardiotoxicity during on-protocol therapy was significantly associated with subsequent off-protocol toxicity. Overall, the incidence was higher among noninfants and black patients, and in the setting of a bloodstream infection. Both EFS (hazard ratio [HR], 1.6; 95% CI, 1.2 to 2.1; P = .004) and OS (HR, 1.6; 95% CI, 1.2 to 2.2, P = .005) were significantly worse in patients with documented cardiotoxicity. Impacts on EFS were equivalent whether the incident cardiotoxicity event occurred in the absence (HR, 1.6; 95% CI, 1.1 to 2.2; P = .017) or presence of infection (HR, 1.6; 95% CI, 1.0 to 2.7; P = .069) compared with patients without documented cardiotoxicity. However, the reduction in OS was more pronounced for cardiotoxicity not associated with infection (HR, 1.7; 95% CI, 1.2 to 2.5; P = .004) than for infection-associated cardiotoxicity (HR, 1.3; 95% CI, 0.7 to 2.4; P = .387). Conclusion Early treatment-related cardiotoxicity may be associated with decreased EFS and OS. Cardioprotective strategies are urgently needed to improve relapse risk and both short- and long-term mortality outcomes.

scholarly journals Effect of Dexrazoxane on Left Ventricular Systolic Function and Treatment Outcomes in Patients With Acute Myeloid Leukemia: A Report From the Children’s Oncology Group

2020 ◽  
Vol 38 (21) ◽  
pp. 2398-2406 ◽  
Author(s):  
Kelly D. Getz ◽  
Lillian Sung ◽  
Todd A. Alonzo ◽  
Kasey J. Leger ◽  
Robert B. Gerbing ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Group Treatment ◽  
Myeloid Leukemia ◽  
Left Ventricular Systolic Dysfunction ◽  
Left Ventricular ◽  
Cardiac Monitoring ◽  
Oncology Group ◽  
Frontline Treatment ◽  
Acute Myeloid

PURPOSE To determine whether dexrazoxane provides effective cardioprotection during frontline treatment of pediatric acute myeloid leukemia (AML) without increasing relapse risk or noncardiac toxicities of the chemotherapy regimens. PATIENTS AND METHODS This was a multicenter study of all pediatric patients with AML without high allelic ratio FLT3/ITD treated in the Children’s Oncology Group trial AAML1031 between 2011 and 2016. Median follow-up was 3.5 years. Dexrazoxane was administered at the discretion of treating physicians and documented at each course. Ejection fraction (EF) and shortening fraction (SF) were recorded after each course and at regular intervals in follow-up. Per protocol, anthracyclines were to be withheld if there was evidence of left ventricular systolic dysfunction (LVSD) defined as SF < 28% or EF < 55%. Occurrence of LVSD, trends in EF and SF, 5-year event-free survival (EFS) and overall survival (OS), and treatment-related mortality (TRM) were compared by dexrazoxane exposure. RESULTS A total of 1,014 patients were included in the analyses; 96 were exposed to dexrazoxane at every anthracycline course, and 918 were never exposed. Distributions of sex, age, race, presenting WBC count, risk group, treatment arm, and compliance with cardiac monitoring were similar for dexrazoxane-exposed and -unexposed patients. Dexrazoxane-exposed patients had significantly smaller EF and SF declines than unexposed patients across courses and a lower risk for LVSD (26.5% v 42.2%; hazard ratio, 0.55; 95% CI, 0.36 to 0.86; P = .009). Dexrazoxane-exposed patients had similar 5-year EFS (49.0% v 45.1%; P = .534) and OS (65.0% v 61.9%; P = .613) to those unexposed; however, there was a suggestion of lower TRM with dexrazoxane (5.7% v 12.7%; P = .068). CONCLUSION Dexrazoxane preserved cardiac function without compromising EFS and OS or increasing noncardiac toxicities. Dexrazoxane should be considered for cardioprotection during frontline treatment of pediatric AML.

Acute myeloid leukemia: Comparison of epidemiology and treatment outcomes between insured and uninsured patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e17012-e17012
Author(s):  
Samer Ali Srour ◽  
Michael Machiorlatti ◽  
Usman Bhutta ◽  
Namali Pierson ◽  
Mohamad Ali Cherry ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Treatment Outcomes ◽  
Myeloid Leukemia ◽  
Private Insurance ◽  
Cell Transplant ◽  
Public Insurance ◽  
Insurance Type ◽  
The Impact ◽  
Acute Myeloid

e17012 Background: The overall prognosis for most acute myeloid leukemia (AML) patients remains poor. The majority of adult patients (pts) with AML will ultimately need allogeneic stem cell transplant (allo-SCT). Limited data is available comparing epidemiology and treatment outcomes between uninsured and insured pts with AML. We describe a retrospective analysis of adult pts with AML treated at our institution. Methods: From January 2000 to June 2011 we identified 239 pts with AML, of which 185 met inclusion criteria. Patients were classified as having private insurance, public insurance (Medicaid and Medicare), or no insurance. Primary outcomes were overall survival at follow up (OS), complete remission (CR), and percent of pts receiving allo-SCT. Kaplan-Meier analysis was used to estimate survival rates. Results: Of the 185 pts studied, 146 (81%) were white, 16 (9%) African-American and 11 (6%) were Native American. The median age at diagnosis was 49 years. 75 pts had private insurance at the time of diagnosis, 70 had public insurance, and 33 were uninsured. Of those receiving allo-SCT (n=60; 38 male) 48% had private insurance, 30% public, and 22% were uninsured. Whether a patient underwent allo-SCT did not differ according to insurance source (p=0.2189) nor to status at follow-up (p= 0.6480). The proportion of patients achieving CR was higher among those undergoing allo-SCT (p=0.0002). Median OS was 920 days for those who underwent allo-SCT and 192 days for those who did not (p< 0.0001). Median OS did not differ by insurance type (p = 0.1454). The proportion of patients achieving CR did not differ by insurance type (p=0.2665) (66.7% of those with private, 62.7% of those with public, and 78.8% of those with no insurance). Conclusions: For the population referred to our institution, a tertiary referral center for the state, there were no differences in treatment outcomes or in the percent of pts receiving allo-SCT when pts were stratified according to insurance source. Further analysis of this dataset will identify the impact of pretreatment variables stratified by type of insurance.

Survival of Patients Diagnosed with Primary Refractory and Relapsed Acute Myeloid Leukemia from 2008-2012: A Single Institution Experience

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4955-4955
Author(s):  
Simon B. Zeichner ◽  
Shannon Gleason ◽  
Ana G. Antun ◽  
Amelia Langston ◽  
Leonard T Heffner ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Score ◽  
Molecular Signatures ◽  
Oncology Group ◽  
Prognostic Variables ◽  
Ecog Ps ◽  
Acute Myeloid ◽  
Refractory Aml

Abstract Introduction: Acute myeloid leukemia (AML) is one of the most lethal types of adult cancer, with 10,460 deaths among 18,860 diagnoses in 2014. Although some patients are cured with induction and consolidation chemotherapy with or without stem cell transplantation (SCT), between 50-80% of patients will either fail to obtain a complete remission (CR; primary refractory AML) or will relapse. The median overall survival (OS) for relapsed and refractory AML patients is dismal, and there is no clear consensus on the management of relapsed/refractory AML. In this study, with extended follow-up, we set out to look at our own experience with primary refractory and relapsed AML patients in order to try to identify the best therapy and factors associated with improved outcomes. Methods: This retrospective study in AML patients seen at Emory University Hospital (EUH) was IRB approved. Descriptive statistics were used to characterize the demographic and clinical variables. Cytogenetic and molecular signatures were defined based upon the European Leukemia Network and Southwest Oncology group classifications (Döhner et al. 2010, Slovak et al. 2000). Response criteria were based upon the revised recommendations of the International Working Group (Cheson et al. 2003). The combined prognostic score was created using previously validated prognostic variables including age (< 60 vs. >/= 60), Eastern Cooperative Oncology Group Performance Status (ECOG PS; 0-1 vs. >/= 2), and cytogenetic and molecular signatures (favorable vs unfavorable). A score of 0 was termed "favorable" and a score of 1 or greater was termed "unfavorable." The Kaplan-Meier and Cox proportional hazard statistical methods were used to estimate OS. Results: Review of electronic medical records identified 67 consecutive patients between January 1st 2008 and December 31st 2012 diagnosed with primary refractory or relapsed AML. Median age was 56 (range 18-81). Cytogenetic/molecular signatures were favorable in 6%, intermediate in 60%, and unfavorable in 34%, and PS was 0-1 in 34% and 2 in 66%. The majority of patients had a combined prognostic score of unfavorable (n = 53, 79%). Among the 67 patients, 17 (25%) achieved CR with salvage therapy, with 13 (76%) of those able to undergo SCT. With an extended follow-up of approximately 5.6 years, the median OS of our refractory/relapsed AML cohort was 4 months (95% CI 2.2-5.8), with 8% of patients living at least 5 years from their date of relapse. Univariate analysis identified the following factors to be associated with a significantly worse median OS: Secondary AML at initial diagnosis (2.0 vs 5.0 months; p = 0.005), unfavorable cytogenetic/molecular signature at initial diagnosis (3.0 vs 6.0 months; p = 0.014), ECOG PS of 2 or greater at relapse (2.0 vs. 7.0 months; p< 0.001), an unfavorable combined prognostic score at relapse (3.0 vs 18.0 months; p < 0.001), lack of SCT after salvage (3.0 vs. 39.0 months; p < 0.001), lack of treatment in the refractory/relapsed setting with the combination of induction chemotherapy and hypomethylating agents (1.0 vs 8.0 months; p < 0.001), and lack of attainment of CR in the refractory/relapsed setting (3.0 vs. 40.0 months; p < 0.001). In the final multivariable model, only a favorable combined prognostic score at relapse (hazard ratio, HR 0.5; 95% CI 0-0.8; p = 0.02; Figure 1) and ECOG PS of 0-1 (HR 0.42; 95% CI 0.1-0.8; p=0.04) were associated with an improved OS, while the lack of attainment of a CR in the refractory/relapsed setting (HR 15.9; 95%CI 15.2-16.6; p < 0.001; Figure 2) was associated with a worse OS. Conclusion: In our cohort, the median OS among all patients diagnosed with primary refractory/relapsed AML was dismal. Despite the incorporation of novel agents and treatment approaches among this vulnerable patient population, there remains significant heterogeneity in patient outcomes within the first year, with only a small minority having a significantly longer OS. Similarly to patients with newly diagnosed AML, the most important prognostic variables among our refractory/relapsed AML cohort appears to be their combined prognostic score and their ability to achieve a CR in the salvage setting. It may be beneficial for future studies to focus on improving both, modifiable patient prognostic factors (i.e., PS) and treatment approaches in order to achieve CR in the refractory/relapsed setting. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Kota: Pfizer: Membership on an entity's Board of Directors or advisory committees; Leukemia Lymphoma Society: Research Funding.

scholarly journals Shorter Remission Telomere Length Predicts Delayed Neutrophil Recovery After Acute Myeloid Leukemia Therapy: A Report From the Children’s Oncology Group

2016 ◽  
Vol 34 (31) ◽  
pp. 3766-3772 ◽  
Author(s):  
Robert B. Gerbing ◽  
Todd A. Alonzo ◽  
Lillian Sung ◽  
Alan S. Gamis ◽  
Soheil Meshinchi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Telomere Length ◽  
Myeloid Leukemia ◽  
Protein Structures ◽  
Telomere Maintenance ◽  
Oncology Group ◽  
Neutrophil Recovery ◽  
The Impact ◽  
Acute Myeloid

Purpose Suboptimal outcomes for children with acute myeloid leukemia (AML) necessitate maximally intensive therapy. Consequently, serious adverse events, such as prolonged periods of profound myelosuppression, contribute to AML treatment–related mortality. Telomeres, the repetitive DNA–protein structures at chromosome ends, influence cellular replicative capacity in that critically short telomeres can induce cell senescence or apoptosis. Our objective was to evaluate the impact of telomere length on duration of post-therapy neutropenia in a pediatric AML cohort. Patients and Methods Patients were diagnosed with de novo AML, enrolled in Children’s Oncology Group study AAML0531, and included those with (n = 53) and without (n = 62) significantly delayed neutrophil recovery after chemotherapy. We used quantitative polymerase chain reaction to measure telomere content (TC), a validated proxy for telomere length, from remission bone marrow samples obtained after the second induction chemotherapy course. Results Less TC was significantly associated with prolonged neutropenia after the fourth ( P < .001) and fifth chemotherapy courses ( P = .002). Cox regression adjusting for age at diagnosis confirmed that TC remained independently predictive of time to recovery of absolute neutrophil count for both the fourth and fifth courses ( P = .002 and .009, respectively). DNA from patients was analyzed for germline mutations in four telomere maintenance genes associated with telomere biology disorders. Sequence analysis revealed no enrichment of rare or novel variants in the delayed recovery group. Conclusion Our results suggest that TC at end of AML induction is associated with hematopoietic reconstitution capacity independently of age and may identify those at highest risk for markedly delayed bone marrow recovery after AML therapy.

scholarly journals Covid-19 Infection in Hematological Malignancies: Registry Data from India

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1938-1938
Author(s):  
Arihant Jain ◽  
Lingaraj Nayak ◽  
Uday Prakash Kulkarni ◽  
Nikita Mehra ◽  
Uday Yanamandra ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Hematological Malignancies ◽  
Healthcare Access ◽  
Anticancer Therapy ◽  
Cell Transplant ◽  
Access And Quality ◽  
The Impact ◽  
Acute Myeloid

Abstract Background: The impact of COVID-19 pandemic has been highly heterogeneous across the globe and different regions within the country. The differences in the outcome of these patients is related to their demographic profile, genetics, socio-economic conditions, and government health policies. Prior to the COVID-19 pandemic, the Healthcare Access and Quality (HAQ) Index for hematological malignancies (HAQ index &lt;30) in a low-middle socio-demographic index(SDI) country like India was less than the mean HAQ index for all other diseases (HAQ index 41) with a significant regional disparity.(1)Several national and international registries from high socio-demographic Index (SDI) countries have reported worse short-term outcomes of coronavirus disease (COVID-19) in patients with hematologic as compared to other solid cancers. The outcomes of COVID-19 in patients with hematologic malignancies from a low-middle SDI country are yet unknown. The COVID-19 Hematologic Cancer registry of India reports these outcomes from India. Methods: Ten tertiary referral hospitals across India reported the demographic, clinical, laboratory, treatment, and outcomes of COVID-19 infection in patients with hematological malignancies. The registry was retrospective from March 21, 2020, and prospective from November 1, 2020, till March 20, 2021. Risk factors associated with severity and mortality were evaluated using the penalised logistic regression and Cox proportional hazards model. Findings: Data from 565 patients was included in this study. Among these, 429 (76%) patients were hospitalized, 186 (33%) patients had moderate/severe COVID-19.There were 116 (20.5%) non-survivors at a mean follow up of 147 (95% CI : 142-153) days. Age &gt;60 years (HR 2·55, 1·23 - 5·27), diagnosis of acute myeloid leukemia (HR 2·85, 1·58 - 5·13), interruption or alteration of anticancer therapy (HR 2·78, 1·65 - 4·68), and post hematopoietic cell transplant status (HR 3·68, 1·82 - 7·45) predicted mortality. In contrast, increasing age [20-40 years (OR 2·54, 1·32 - 4·90), 41-60 years (OR 3·51, 1·84 - 6·71), &gt;60 years (OR 6·04, 3·01 - 12·10), comorbidities such as diabetes mellitus (OR 1·89, 1·18 - 3·04), hypertension (OR 1·94, 1·17 - 3·19), diagnosis of AML (OR 3·70, 2·06 - 6·67), indolent non-hodgkin lymphoma (OR 3·20, 1·68 - 6·09), multiple myeloma (OR 2·88, 1·64 - 5·05), malignancy not being in remission (OR 1·71, 1·12 - 2·60)were significantly associated with severe COVID-19 on univariate analysis. Of these, only increasing age [20-40 years (OR 2·60 (1·31 - 5·15), 40-60 years (OR 3·44, 1.60 - 7·41), more than 60 years (OR 5·70, 2·43 - 13·35)] , AML (OR 2·73, 1·45 - 5·12), and malignancy not being in remission (OR 1·85, 1·18 - 2·89) were significantly associated with severe COVID-19 on multivariable analysis Conclusion: The overall mortality from COVID-19 infection of the entire cohort was 20.5%; the mortality was 46.2% in patients who had moderate to severe disease COVID-19 illness. Similar to previous studies, age, diagnosis of acute myeloid leukemia and a post stem cell transplant status was associated with mortality. In addition, interruption or de-escalation of anticancer therapy during Covid-19 infection was identified as an important factor associated with higher mortality on follow up in the current study. References 1. Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: a systematic analysis from the Global Burden of Disease Study 2016. Lancet (London, England)2018; 391(10136): 2236-71.Lee AJX, Purshouse K. COVID-19 and cancer registries: learning from the first peak of the SARS-CoV-2 pandemic. Br J Cancer 2021; 124(11): 1777-84. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

AML1/RUNX1 mutations in 470 adult patients with de novo acute myeloid leukemia: prognostic implication and interaction with other gene alterations

Blood ◽  
2009 ◽  
Vol 114 (26) ◽  
pp. 5352-5361 ◽  
Author(s):  
Jih-Luh Tang ◽  
Hsin-An Hou ◽  
Chien-Yuan Chen ◽  
Chieh-Yu Liu ◽  
Wen-Chien Chou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Remission Rate ◽  
Adult Patients ◽  
Poor Prognostic Factor ◽  
The Impact ◽  
Runx1 Mutation ◽  
Acute Myeloid

AbstractSomatic mutation of the AML1/RUNX1(RUNX1) gene is seen in acute myeloid leukemia (AML) M0 subtype and in AML transformed from myelodysplastic syndrome, but the impact of this gene mutation on survival in AML patients remains unclear. In this study, we sought to determine the clinical implications of RUNX1 mutations in 470 adult patients with de novo non-M3 AML. Sixty-three distinct RUNX1 mutations were identified in 62 persons (13.2%); 32 were in N-terminal and 31, C-terminal. The RUNX1 mutation was closely associated with male sex, older age, lower lactic dehydrogenase value, French-American-British M0/M1 subtypes, and expression of HLA-DR and CD34, but inversely correlated with CD33, CD15, CD19, and CD56 expression. Furthermore, the mutation was positively associated with MLL/PTD but negatively associated with CEBPA and NPM1 mutations. AML patients with RUNX1 mutations had a significantly lower complete remission rate and shorter disease-free and overall survival than those without the mutation. Multivariate analysis demonstrated that RUNX1 mutation was an independent poor prognostic factor for overall survival. Sequential analysis in 133 patients revealed that none acquired novel RUNX1 mutations during clinical courses. Our findings provide evidence that RUNX1 mutations are associated with distinct biologic and clinical characteristics and poor prognosis in patients with de novo AML.

scholarly journals Actin cytoskeleton deregulation confers midostaurin resistance in FLT3-mutant acute myeloid leukemia

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Andoni Garitano-Trojaola ◽  
Ana Sancho ◽  
Ralph Götz ◽  
Patrick Eiring ◽  
Susanne Walz ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Actin Cytoskeleton ◽  
Myeloid Leukemia ◽  
Actin Polymerization ◽  
Cell Stiffness ◽  
Adhesion Forces ◽  
Frequent Mutations ◽  
New Perspective ◽  
The Impact ◽  
Acute Myeloid

AbstractThe presence of FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) is one of the most frequent mutations in acute myeloid leukemia (AML) and is associated with an unfavorable prognosis. FLT3 inhibitors, such as midostaurin, are used clinically but fail to entirely eradicate FLT3-ITD + AML. This study introduces a new perspective and highlights the impact of RAC1-dependent actin cytoskeleton remodeling on resistance to midostaurin in AML. RAC1 hyperactivation leads resistance via hyperphosphorylation of the positive regulator of actin polymerization N-WASP and antiapoptotic BCL-2. RAC1/N-WASP, through ARP2/3 complex activation, increases the number of actin filaments, cell stiffness and adhesion forces to mesenchymal stromal cells (MSCs) being identified as a biomarker of resistance. Midostaurin resistance can be overcome by a combination of midostaruin, the BCL-2 inhibitor venetoclax and the RAC1 inhibitor Eht1864 in midostaurin-resistant AML cell lines and primary samples, providing the first evidence of a potential new treatment approach to eradicate FLT3-ITD + AML.

Early human cytomegalovirus replication after transplantation is associated with a decreased relapse risk: evidence for a putative virus-versus-leukemia effect in acute myeloid leukemia patients

Blood ◽  
2011 ◽  
Vol 118 (5) ◽  
pp. 1402-1412 ◽  
Author(s):  
Ahmet H. Elmaagacli ◽  
Nina K. Steckel ◽  
Michael Koldehoff ◽  
Yael Hegerfeldt ◽  
Rudolf Trenschel ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Human Cytomegalovirus ◽  
Myeloid Leukemia ◽  
Homogeneous Population ◽  
Relapse Risk ◽  
Pp65 Antigenemia ◽  
Hcmv Replication ◽  
The Impact ◽  
Early Human ◽  
Acute Myeloid

Abstract The impact of early human cytomegalovirus (HCMV) replication on leukemic recurrence was evaluated in 266 consecutive adult (median age, 47 years; range, 18-73 years) acute myeloid leukemia patients, who underwent allogeneic stem cell transplantation (alloSCT) from 10 of 10 high-resolution human leukocyte Ag-identical unrelated (n = 148) or sibling (n = 118) donors. A total of 63% of patients (n = 167) were at risk for HCMV reactivation by patient and donor pretransplantation HCMV serostatus. In 77 patients, first HCMV replication as detected by pp65-antigenemia assay developed at a median of 46 days (range, 25-108 days) after alloSCT. Taking all relevant competing risk factors into account, the cumulative incidence of hematologic relapse at 10 years after alloSCT was 42% (95% confidence interval [CI], 35%-51%) in patients without opposed to 9% (95% CI, 4%-19%) in patients with early pp65-antigenemia (P < .0001). A substantial and independent reduction of the relapse risk associated with early HCMV replication was confirmed by multivariate analysis using time-dependent covariate functions for grades II to IV acute and chronic graft-versus-host disease, and pp65-antigenemia (hazard ratio = 0.2; 95% CI, 0.1-0.4, P < .0001). This is the first report that demonstrates an independent and substantial reduction of the leukemic relapse risk after early replicative HCMV infection in a homogeneous population of adult acute myeloid leukemia patients.

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