The risk of early mortality in elderly patients with newly diagnosed acute myeloid leukemia

Abstract Elderly patients aged 65 or older with acute myeloid leukemia (AML) have poor prognosis. The risk stratification based on genetic alteration has been proposed in national comprehensive cancer network (NCCN) guideline but its efficacy was not well verified especially in real world elderly patients. The nutritional status assessment using controlling nutritional status (CONUT) score is a prognostic biomarker in elderly patients with solid tumors but was not examined in elderly AML patients. We performed prospective analysis of genetic alterations of 174 patients aged 65 or older with newly diagnosed AML treated without hematopoietic stem cell transplantation (HSCT) and developed simplified CONUT (sCONUT) score by eliminating total lymphocyte count from the items to adapt AML patients. In this cohort, both the NCCN 2017 risk group and sCONUT score successfully stratified the overall survival (OS) of the elderly patients. A multivariable analysis demonstrated that adverse group in NCCN 2017 and high sCONUT score were independently associated with poor 2-year OS. Both risk stratification based on NCCN 2017 and sCONUT score predict prognosis in the elderly patients with newly diagnosed AML.

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Dose Dense, High Intensity Therapy in Newly Diagnosed Elderly Patients with Acute Myeloid Leukemia Using Gemtuzumab Ozogamicin (Mylotarg™) and High Dose Cytarabine (HiDAC).

Blood ◽

10.1182/blood.v104.11.4516.4516 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4516-4516

Author(s):

Arati V. Rao ◽

David A. Rizzieri ◽

Joseph O. Moore ◽

Carlos DeCastro ◽

Amy P. Abernethy ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Elderly Patients ◽

Myeloid Leukemia ◽

The Other ◽

High Rate ◽

Hematologic Toxicity ◽

Newly Diagnosed ◽

Gram Positive ◽

Dose Dense ◽

Acute Myeloid

Abstract The failure to overcome drug resistance leads to a high rate of relapse in elderly patients with acute myeloid leukemia. We evaluated, in a Phase I study the feasibility of a dose dense regimen of HiDAC, and MylotargTM therapy for newly diagnosed elderly (≥60 years) patients with AML in terms of toxicity with two cycles of this regimen as the sole induction and consolidation therapy. HiDAC was administered in a dose escalation pattern: 3000mg/m2 intravenously given for 6, and 9 doses, and MylotargTM was administered at a dose of 6mg/m2 intravenously on days 1 and 8 of each cycle. Patients without unacceptable toxicity, defined as failure to recover counts to a minimum of ANC ≥ 500/ μl, platelets ≥ 30K and hematocrit ≥ 25%, received a second cycle of therapy, though not before day 28 following day 1 of induction. In addition, death within the first 30 days of induction (not related to disease progression) and life-threatening non-hematologic toxicity (such as cardiac or pulmonary arrest) was also considered dose-limiting. Patients with persistent disease but at least a 50% decrease in the marrow or peripheral blood blast count, or those with low blood counts and patients achieving CR without platelet recovery (CRp) at the 4–6 week examination received cycle 2 with a de-escalation of the Mylotarg dose (from 6 mg/m2 to 4 mg/m2). All patients received G-CSF 5mcg/kg/day subcutaneously from days 11–14. Eight patients (five male, three female) with a median age of 68 years (range 60–74) were enrolled. In cohort one (6 doses of HiDAC), four of six patients were able to complete both cycles of therapy and two of these have achieved CR. Two of the six patients achieved CRp with persistent thrombocytopenia and thus received a second cycle of chemotherapy off protocol. One patient in this cohort had progressive disease and persistent pancytopenia requiring transfusions and subsequently received chemotherapy using Etoposide and Cyclophosphamide. Five out of six patients are alive and remain disease free. In cohort two (9 doses of HiDAC), two patients have been enrolled thus far. One patient developed neurotoxicity after six doses of HiDAC and thus completed both cycles of therapy with six doses of HiDAC along with protocol dose of MylotargTM. The other patient was able to get all nine doses of HiDAC and both patients have achieved a CR. No unexpected hematologic toxicity was observed. All patients developed grade IV thrombocytopenia requiring platelet transfusions. One patient in cohort one died after developing aspergillus infection and multiorgan failure before he could be evaluated for response. Two patients in cohort one developed uncomplicated gram-positive bacteremia requiring antibiotics. In cohort two, one patient developed neurotoxicity and the other developed uncomplicated gram-positive bacteremia. At the time of submission of this abstract seven out of eight patients are alive with four CR and two CRp. No veno-occlusive disease was seen in these eight patients treated with two cycles of HiDAC and MylotargTM back to back. The high rate of CR and relatively good tolerance of this regimen remains encouraging.

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An External Validation Study for Current Risk Scoring Models in Elderly Patients with Newly Diagnosed Acute Myeloid Leukemia

Blood ◽

10.1182/blood-2019-129597 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3861-3861

Author(s):

Chia-Jen Liu ◽

Hong Ying-Chung ◽

Chiu-Mei Yeh ◽

Chun-Kuang Tsai ◽

Liang-Tsai Hsiao ◽

...

Keyword(s):

Risk Factors ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Group Performance ◽

Early Mortality ◽

Prognostic Models ◽

Newly Diagnosed ◽

Discrimination Ability ◽

Elderly Aml ◽

Acute Myeloid

Background Acute myeloid leukemia (AML) is a common hematologic neoplasm in the elderly. The high mortality in elderly AML patients is reported to be associated with old age, poor performance status, and several disease characteristics. Several risk stratification models have been reported. Our aims were to explore risk factors for early mortality in older AML patients and compare the discrimination ability of existing prognostic models. Methods We enrolled newly diagnosed AML patients age 60 and above at Taipei Veterans General Hospital, a national medical center in Taiwan, between July 1, 2008 and May 31, 2017. Our primary endpoint was early mortality, defined as death within two months after initial AML diagnosis. Performance of several existing scoring systems were compared by using the Akaike information criteria (AIC) and Bayesian information criterion (BIC) calculations. Model discrimination ability was also estimated by Harrell's C statistics. Results A total of 478 AML patients were diagnosed during the eight-year follow-up period. After excluding young patients (age < 60) and those without a histopathologic diagnosis, the final cohort included 277 patients. The median age was 74 (range 60-96), and 171 (61.7%) of them were male. One hundred sixteen patients (41.9%) had Eastern Cooperative Oncology Group performance (ECOG) ≥ 2 and 33.9% patients had poor/adverse cytogenetics or molecular abnormalities. The two-month mortality rate was 29.9% (95% confidence interval [CI] 24.8%-35.9%). Age ≥ 80 (adjusted HR 1.95, 95% CI 1.12-3.42), having an antecedent hematologic disorder (adjusted HR 1.86, 95% CI 1.01-3.43), ECOG ≥ 2 (adjusted HR 2.06, 95% CI 1.20-3.54), complex karyotype (adjusted HR 3.13, 95% CI 1.76-5.55), BM blasts ≥ 70% (adjusted HR 1.79, 95% CI 1.02-3.13), WBC ≥ 100 ×109/L (adjusted HR 3.27, 95% CI 1.58-6.75), and creatinine > 1.3 mg/dL (adjusted HR 2.04, 95% CI 1.23-3.39) were identified as independent predictors for early mortality in the multivariate analysis. Furthermore, we systematically reviewed existing prognostic models for elderly AML. We found five scoring models that don't require additional specific examinations beyond clinical practice and later applied them to our elderly AML cohort. The performance of the five models is shown in Table. Kantarjian's prognostic model (Kantarjian H, et. al. Blood 2010) had the highest Harrell's C statistic and the ALMA score (Ramos F, et. al.Leukemia Research 2015) had the lowest AIC and BIC compared with the other prognostic models. Conclusion We identified seven risk factors for early mortality and compared the performance of five prognostic models for elderly AML patients. The finding may help clinicians to stratify patients and initiate appropriate management. Table Disclosures No relevant conflicts of interest to declare.

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