Comorbidities and FLT3‐ITD abnormalities as independent prognostic indicators of survival in Elderly acute myeloid leukaemia patients

Breccia, Massimo; Frustaci, Anna Maria; Cannella, Laura; Stefanizzi, Caterina; Latagliata, Roberto; Cartoni, Claudio; Diverio, Daniela; Guarini, Anna; Nanni, Mauro; Rago, Angela; Cimino, Giuseppe; Alimena, Giuliana

doi:10.1002/hon.889

Cited by 37 publications

(32 citation statements)

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“…On the basis of the information collected we retrospectively calculated the modified CCI and ACE27 (Table 1). 9 Analyses were conducted of the impact of stratification according to the CCI and the hematologic and non-hematologic toxicities experienced during dasatinib treatment. A complete ACE27 data form is available on …”

Section: Design and Methodsmentioning

confidence: 99%

“…Comorbidities may affect survival and choice of treatment among cancer patients: in fact they have been identified as significant determinants of response to therapy in older patients with acute myeloid leukemia, female breast cancer, head and neck cancer or lung cancer. 9,10 The Charlson comorbidity index (CCI) is a list of 19 comorbid conditions: each condition has a weight assigned from 1 to 6, which was derived from relative risk estimates of a proportional hazard regression model using clinical data. The adult comorbidity evaluation-27 (ACE27) is a new 27-item comorbidity index for patients with cancer.…”

Section: Introductionmentioning

confidence: 99%

“…The adult comorbidity evaluation-27 (ACE27) is a new 27-item comorbidity index for patients with cancer. 9 The ACE27 was developed through modification of the KaplanFeinstein Comorbidity Index. ACE27 includes comorbid conditions of various organ systems such as cardiovascular, respiratory, gastrointestinal, renal, endocrine, neurological, psychiatric, rheumatological, and immunological systems, as well as malignancy, substance abuse, and body weight.…”

Section: Introductionmentioning

confidence: 99%

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Charlson comorbidity index and adult comorbidity evaluation-27 scores might predict treatment compliance and development of pleural effusions in elderly patients with chronic myeloid leukemia treated with second-line dasatinib

Breccia¹,

Latagliata²,

Stagno³

et al. 2011

Haematologica

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BackgroundComorbidities may affect survival and choice of treatment among cancer patients. In fact, comorbidities have been identified as significant determinants of response to therapy in older patients with acute myeloid leukemia, breast cancer, head and neck cancer, and lung cancer. The Charlson comorbidity index and adult comorbidity evaluation-27 are lists of comorbidities with a weight assigned from 1 to 6 for the former and from 0 to 3 for the latter score, derived from relative risk estimates of a proportional hazard regression model using clinical data. Design and MethodsWe retrospectively evaluated the Charlson index and adult comorbidity evaluation-27 score in a cohort of 125 elderly (> 60 years) patients with chronic phase chronic myeloid leukemia who received dasatinib after showing resistance or intolerance to imatinib with the aim of establishing associations between comorbidities and the development of pleural effusions or compliance with the drug treatment. ResultsWe found a significant association between the Charlson index as well as the adult comorbidity evaluation-27 score and the rate of drug reduction or suspension: with regards to the Charlson index, 49% of score 0 patients had a dose reduction compared to 63% of patients with score 1, 74% of those with score 2 and 100% of patients with score 3-5 (P=0.03); with regards to the adult comorbidity evaluation-27 score, 45% of patients had score 0-1 and 69% of patients with score 2-3 had a dose reduction. Of the 65 patients with Charlson score 0, 29% had at least one suspension of treatment (79% for hematologic and 21% for non-hematologic toxicity), compared to 46% of patients with score 1 (37% for hematologic and 69% for non-hematologic toxicity), 58% of patients with score 2 (36% for hematologic and 64% for non-hematologic toxicity) and 100% of patients with score 3 or 4 (all patients for both types of toxicity). High adult comorbidity index-27 scores identified patients at high risk of grade 3/4 hematologic toxicity. Forty-one patients (32.8%) experienced pleural effusion during treatment: the highest scores for both indices were associated with an increased risk of pleural effusions. ConclusionsIn elderly patients with chronic myeloid leukemia treated with dasatinib, the rate of drug reduction or suspension and the incidence of pleural effusions seem to be associated with the presence of comorbidities: stratification according to the Charlson index and adult comorbidity evaluation-27 score before dasatinib therapy may enable the identification of patients at risk of major toxicities.Key words: chronic myeloid leukemia, dasatinib, Charlson comorbidity index, adult comorbidity evaluation 27 (ACE-27).Citation: Breccia M, Latagliata R, Stagno F, Luciano L, Gozzini A, Castagnetti F, Fava C, Cavazzini F, Annunziata M, Russo Rossi A, Pregno P, Abruzzese E, Vigneri P, Rege-Cambrin G, Sica S, Pane F, Santini V, Specchia G, Rosti G, and Alimena G. Charlson comorbidity index and adult comorbidity evaluation-27 scores might predict treatment complia...

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Section: Design and Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Charlson comorbidity index and adult comorbidity evaluation-27 scores might predict treatment compliance and development of pleural effusions in elderly patients with chronic myeloid leukemia treated with second-line dasatinib

Breccia¹,

Latagliata²,

Stagno³

et al. 2011

Haematologica

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“…45,47,52,58,62,[77][78][79][80][81][82][83][84] At least five other studies reported on the ability of the HCT-CI to provide good prediction of conventional treatment outcomes among patients with AML or MDS, which adds another layer to the generalizability of this index. [85][86][87][88] One study found the HCT-CI to be a sole independent predictor of outcomes among patients receiving relative or cord blood grafts, but of less strength in smaller samples of subgroup analyses. 89 Only four studies disagreed with the validity of the HCT-CI for outcome prediction.…”

Section: Validity and Reliability Of The Hct-ctmentioning

confidence: 99%

Comorbidities and Hematopoietic Cell Transplantation Outcomes

Sorror

2010

Hematology

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Conventional allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment option for various hematological diseases due, in part to high-dose conditioning and, in part, to graft-versus-tumor effects. Reduced-intensity or non-myeloablative conditioning regimens have relied mostly on graft-versus-tumor effects for disease control, and their advent has allowed relatively older and medically infirm patients to be offered allo-HCT. However, both HCT modalities have been associated with organ toxicities and graft-versus-host disease, resulting in substantial non-relapse mortality. It has become increasingly important to optimize pre-transplant risk assessment in order to improve HCT decision making and clinical trial assignments. Single-organ comorbidity involving liver, lung, heart, or kidney before HCT has been traditionally found to cause organ toxicity after HCT. Recent efforts have resulted in the advent of a weighted scoring system that could sensitively capture multiple-organ comorbidities prior to HCT. The HCT-comorbidity index (HCT-CI) has provided better prediction of HCT-related morbidity and mortality than other non-HCT-specific indices. Subsequent studies, with the exception of a few studies with modest numbers of patients, have confirmed the prognostic importance of the HCT-CI. Further, the HCT-CI has been consolidated with various disease-specific and patient-specific risk factors to refine assignments of patients to the appropriate HCT setting. Ongoing studies are addressing prospective validation of the HCT-CI, furthering our understanding of biological aging, and enhancing the applicability of the HCT-CI comorbidity coding. Future knowledge of the impacts of multiple comorbidities on post-HCT toxicities might guide new prophylactic and therapeutic interventions to lessen the procedure's mortality.

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“…15 Higher HCT-CI scores are associated with higher mortality. 12,[16][17][18][19] An MDACC study in 177 elderly AML patients (age 460) showed that early date rates were 3%, 11%, and 29% in patients with HCT-CI scores of 0 (n ¼ 39), 1-2 (n ¼ 53) and X3 (n ¼ 85) (Po0.001), respectively. Median OS was inversely affected by higher HCT-CI scores (median OS was 45, 31 and 19 weeks in these three groups, P ¼ 0.04).…”

Section: Induction Therapymentioning

confidence: 99%

To transplant or not: a dilemma for treatment of elderly AML patients in the twenty-first century

Üstün

Lazarus

Weisdorf

2013

Bone Marrow Transplant

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AML treatment presents significant challenges in the elderly, who more often have poor risk cytogenetic and molecular markers, comorbidities and compromised performance status. Although population-based studies indicate that treated patients' survival is better than those who are not treated, there is an understandable reluctance of physicians to choose aggressive therapy. Even in this older population 40-60% CR rates are achievable. Several scoring systems and web-based programs help to predict TRM and CR rates. These sources can assist physicians in the difficult decision-making process of aggressive therapy in an individual patient. Clofarabine and hypomethylating agents are reasonable options and can induce CR in patients who cannot receive standard induction with anthracyclines and cytarabine. Despite encouraging CR rates, median survival remains short (o12 months) in elderly AML patients. Even those patients achieving CR have limited long-term survival (B20% at 3 years) without allogeneic hematopoietic cell transplantation (alloHCT). AlloHCT is feasible and can provide approximately 40% survival at 2 years in appropriately selected patients. Although increased age is associated with poorer survival, higher comorbidities and poor performance status have more negative impact than age per se. The short duration of CR demands that leukemia and transplant physicians collaborate immediately after diagnosis to move quickly toward alloHCT. This collaboration is also essential to choosing the right individuals to transplant and to bridging post-remission therapy (intermediate-dose cytarabine, a hypomethylating agent or FLT-3 inhibitor) in this sometimes frail population. Future studies should be designed not only to address who should receive alloHCT, but also to improve our understanding of AML biology and the process of its cure.

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Comorbidities and FLT3‐ITD abnormalities as independent prognostic indicators of survival in Elderly acute myeloid leukaemia patients

Cited by 37 publications

References 25 publications

Charlson comorbidity index and adult comorbidity evaluation-27 scores might predict treatment compliance and development of pleural effusions in elderly patients with chronic myeloid leukemia treated with second-line dasatinib

Charlson comorbidity index and adult comorbidity evaluation-27 scores might predict treatment compliance and development of pleural effusions in elderly patients with chronic myeloid leukemia treated with second-line dasatinib

Comorbidities and Hematopoietic Cell Transplantation Outcomes

To transplant or not: a dilemma for treatment of elderly AML patients in the twenty-first century

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