Impact of age on outcome of pediatric acute myeloid leukemia
Bassem I. RazzoukElihu H. EsteyStanley PoundsShelly LensingSherry PierceMark BrandtJeffrey E. RubnitzRaul C. RibeiroMichael RyttingChing‐Hon PuiHagop M. KantarjianSima Jeha
58
Citation
50
Reference
10
Related Paper
Citation Trend
Abstract:
Abstract BACKGROUND The prognostic significance of age among pediatric patients with acute myeloid leukemia (AML) was investigated. METHODS The authors reviewed the outcome of 424 patients who were ≤21 years of age at the time of diagnosis of AML (excluding acute promyelocytic leukemia) between 1983 and 2002 at St. Jude Children's Research Hospital ( n = 288) or the M. D. Anderson Cancer Center ( n = 136). Two treatment eras (1983‐1989 and 1990‐2002) were examined because of the greater intensity of treatment during the recent era. RESULTS After controlling for the effects of cytogenetics, white blood cell (WBC) count, French–American–British (FAB) subtype, and treatment era, they observed that age and treatment era interacted significantly in relation to event‐free survival (EFS) ( P = .033). Patients 10 years of age or older were at greater risk of an adverse event than younger patients in the recent era (hazard ratio = 1.8; 95% confidence interval [CI]: 1.3‐2.6; P = .005) but not in the early era. The rate of adverse events (death or recurrence) increased significantly with each year of age in the recent era (4.3%/year; 95% CI: 1.9‐6.8%; P = .001) but not in the early era. The rate of death increased significantly with each year of age in both eras (4.4%/year; 95% CI: 2.3‐6.5%; P <.001). EFS and survival showed no association with study site, and the effects of age were similar at the 2 sites. CONCLUSIONS These results suggest that age is an independent prognostic factor in childhood AML and that children younger than 10 years benefit more than older children from newer intensive therapies. Cancer 2006. © 2006 American Cancer Society.Keywords:
White blood cell
The present study retrospectively analyzed 96 newly diagnosed acute promyelocytic leukemia (APL) patients with low-intermediate mortality risk to identify the optimum timing to initiate cytotoxic chemotherapy following all-trans retinoic acid (ATRA) administration. Based on white blood cell (WBC) at chemotherapy initiation, the patients were divided into three groups: low WBC (WBC count ≤4×109/l), intermediate WBC (WBC count >4×109/l and <15×109/l) and high WBC group (WBC count ≥15×109/l). According to the period from ATRA commencement to chemotherapy, 96 patients were further divided into two groups: ≤3 days group (chemotherapy within 3 days of ATRA) and >3 days group (chemotherapy >3 days after ATRA). Clinical effects were compared by univariate analysis and multivariate analyses. The incidence rate of differentiation syndrome (DS; also termed retinoic acid syndrome) was 0.0, 11.1 and 40.0% in the low, intermediate and high WBC groups, respectively (P<0.001); complete remission (CR) rate was 90.5, 100.0 and 73.3%, respectively (P<0.001); and the rate of early mortality (defined as fatality during induction treatment) was 4.8, 0.0 and 26.7%, respectively (P<0.001). No differences were identified in clinicolaboratory parameters between the ≤3 days and >3 days groups, except in time to achieve CR (P=0.004) and rate of bleeding related to chemotherapy (P=0.009), both being higher in the >3 days group. Multivariate analyses indicated WBC count at chemotherapy was the only independent risk factor for the occurrence of DS [P=0.002; odds ratio (OR) =1.058, 95% confidence interval (CI) =1.021-1.095] and early mortality (P=0.036; OR =1.036, 95% CI =1.002-1.070). For newly diagnosed APL patients with low-intermediate risk, chemotherapy initiation should be recommended until WBC count rises to between 4×109/l and 15×109/l during induction treatment.
White blood cell
Univariate analysis
Case fatality rate
Cite
Citations (5)
Cite
Citations (7)
Animal model
Cite
Citations (1)
Key Clinical Message t(11;17) is a rare but recognized finding usually found in Acute Promyelocytic Leukemia with variant RARA translocation (APLv). We present a case of Acute Myeloid Leukemia with t(11;17) that has different break points than those occurring in APLv. The diagnosis of acute myeloid leukemia, not otherwise specified, acute monoblastic leukemia was reached after a thorough investigation. Reaching the correct diagnosis and distinguishing these two entities are essential as they have different management, prognosis, and overall survival.
Promyelocytic leukemia protein
Cite
Citations (3)
Objective:To explore the possibility of secondary neoplasia following long term combined chemotherapy.Methods:Sister chromatid exchanges(SCE)were investigated in 44 patients with adult leukemia.Rusults:Frequencies of SCE in patients with de novo leukemia,relapsed leukemia and chronic myeloid leukemia(CML)were significant higher than health controls.The five patients(5/16)with complete remission showed higher SCE frequencies,those were mainly the patients received more than nine courses of combined chemotherapeutic regimens received more than nine courses of combined chemotherapeutic regimens.Conclusion:The patients with de novo leukemia,relapsed leukemia and CML have DNA damage in diagnosis,long term combined chemotherapy may cause the DNA instability in partial patients.
Sister chromatid exchange
Cite
Citations (0)
Objective: To analyze the interfering factors of the induced remission in acute leukemia. Methods: The treatment in 64 patients with acute leukemia were summarized and the relationship between the complete remission (CR) and factors, including age, the types of leukemia, bone marrow primary (or promyelocyte) cell ratios, white blood cell (WBC) counts in peripheral blood, with or without hepatosplenomegaly were analyzed. Results: There was significant difference in the CR ratios between the different ages and WBC counts (P0. 05). There was no significant difference among the CR ratios in the types of leukemia, bone marrow primary (or promylocyte) cell ratios and with or without hepatosplenomegaly (P0. 05). Conclusion: The old age (≥60) and high WBC counts in acute leukemia (WBC counts in peripheral blood ≥100×109/L) may have low CR rate, and the prognosis will be poor.
Hepatosplenomegaly
White blood cell
Promyelocyte
Cite
Citations (0)
Promyelocytic leukemia protein
Cite
Citations (0)
Acute promyelocytic leukemia (APL) is a disease described as definite morphological and cytogenetical abnormalities and leads to coagulopathy leaving the patient in a life-threatening condition. A specific chromosomal translocation of 15 and 17 chromosomes leads to retinoic acid receptor-α (RARα) and promyelocytic leukemia (PML) genes fusion that produces an abnormal gene mutation forming an oncogenic protein which is (PML-RARα). Those APL patients, who have been treated with all-trans retinoic acid (ATRA) or arsenic trioxide (ATO) commonly lead a complicated condition called differentiation syndrome which is rarely severe. This case report explains the 37-years old male diagnosed with acute promyelocytic leukemia and later developed a differentiation syndrome after initiation of all-trans retinoic acid and arsenic trioxide induction therapy.
Arsenic Trioxide
Promyelocytic leukemia protein
Differentiation Therapy
Tretinoin
Cite
Citations (0)
To evaluate factors predictive for relapse in a cohort of adult patients with acute promyelocytic leukemia monitored by molecular methods during consolidation and during at least one month of maintenance therapy. The charts and laboratory data of 65 adult patients with acute promyelocytic leukemia treated according to the International Consortium on Acute Promyelocytic Leukemia 2006 protocol were reviewed. The identification of the promyelocytic leukemia-retinoic acid receptor-alpha gene rearrangement at diagnosis, post-induction, post-consolidation and during maintenance treatment was performed by qualitative and quantitative reverse transcription polymerase chain reaction. Eighty-nine patients were diagnosed with acute promyelocytic leukemia over a seven-year period and of these 65 were eligible for treatment with the protocol. Among the 45 patients who received consolidation and maintenance treatment, six (13%) relapsed, three of whom presented hematologic and three presented molecular relapse. The first relapses occurred at a median of 39 months. Relapsed patients were from all risk groups (low, intermediate and high) and both morphological types (M3 and M3variant) were found. Three of these patients are alive and in molecular remission after salvage treatment. There were no statistically significant differences regarding gender, age, risk group, morphology, promyelocytic leukemia breakpoint cluster region, use of all-trans retinoic acid, development of differentiation syndrome and number of days to complete remission between the patients who relapsed and those who did not. Our results reinforce the importance of prolonged monitoring of acute promyelocytic leukemia patients using molecular methods to detect relapse early.
Promyelocytic leukemia protein
Tretinoin
Maintenance therapy
Cite
Citations (0)