Population-based disparities in survival among patients with core-binding factor acute myeloid leukemia: A SEER database analysis

We performed a retrospective population-based study using the SEER database to assess survival trends in CBF-AML between 2000 and 2010. Median OS increased from 16 months in 2000–2002 to 25 months in 2006–2008 (P = 0.002). The 3-year OS rate for patients with inv(16) was 57.3%, but in t(8;21) was only 35.5%. Patients aged 75–84 had worse survival than patients aged 15–44 (HR 5.61, P = 0.0002). Black race was associated with higher mortality (HR 1.50, P = 0.03). Compared to clinical trial outcomes, CBF-AML survival is poorer in the general population, particularly among African Americans and the elderly, and in t(8;21) compared to inv(16) AML.     

Treatment-related leukemia in Hodgkin's disease: a multi-institution study on 75 cases

Hematological and cytogenetic characteristics of 75 cases of therapy-related acute non lymphoid leukemia (t-ANLL) occurring in Hodgkin's disease (HD) are analysed in this multi-institution study. Combined radio and chemotherapy had been given in 88 per cent of patients, either as adjuvant (44 per cent) or as salvage modality (44 per cent). Radiotherapy alone and chemotherapy alone had been given in 3 per cent and 9 per cent respectively. Eighty per cent of patients were in remission of HD and 71 per cent off-therapy while developing leukemia. The median latent time from remission of HD to leukemia was 34 months. The myeloblastic variety of leukemia accounted for 43 per cent of total cases; the myelomonocytic and monocytic for 17 per cent and 4 per cent, the promyelocytic and erythroblastic variants for 5 per cent and 7 per cent of t-ANLL. Twenty four per cent of cases were unclassifiable; one of these was TdT-positive. Dysplastic features of erythrocytic line were invariably present with circulating erythroblasts; defects of granulocytes, circulating megathrombocytes and micromegakaryocytes were also present. Bone marrow hypoplasia and marked fibrosis were documented in 47 per cent and 30 per cent of cases. Preleukemia heralded overt leukemia in 73 per cent of cases; 37 per cent had refractory anemia with no excess of blasts; 16 per cent of preleukemias were unclassifiable. Cytogenetics revealed chromosome abnormalities in 83 per cent of cases; 72 per cent presented chromosome 5 and/or 7 monosomy or partial deletion (5q- or 7q-) of the long arm (94 per cent in the combined modality therapy group). In 3 cases, a pure monosomy 7 was observed; in none 5q-alone. Response rate to conventional therapy was 14 per cent; low and high-dose cytarabine were of little benefit. Long-term CR (28 + and 16 + months) was achieved in 2 cases with allogeneic bone marrow transplantation (BMT) as first-line therapy. A better knowledge of t-ANLL in HD and new therapies, including BMT, may improve the prognosis of this late complication of intensive HD treatment.     

Race and intensity of post-remission therapy in acute myeloid leukemia

Background

In many cancers, including AML, blacks have poorer overall survival. We investigated whether differences in post-remission therapy (PRT) were a contributing factor.

Methods

We compared PRT cycle number and intensity and time to PRT in blacks and whites, among 460 patients with newly diagnosed AML.

Results

Blacks and whites had PRT of equal cycle intensity and number, but black patients experienced a significant delay in starting PRT (2.73 months in blacks vs. 1 month in whites, p = 0.047). Overall survival was equivalent in blacks and whites.

Conclusion

PRT is delayed in blacks but does not explain differences in survival.     

Family history of cancer in children with acute leukemia, Hodgkin's lymphoma or non-Hodgkin's lymphoma: the ESCALE study (SFCE)

The role of a family history of cancer in the etiology of childhood hematopoietic malignancies was investigated using the data from the ESCALE study. ESCALE, a population-based case-control study, was carried out in France over the period, 2003-2004. A total of 773 cases of acute leukemia (AL), 130 of Hodgkin's lymphoma (HL), 163 of non-Hodgkin's lymphoma (NHL) and 1,681 population-based controls were included. The controls were randomly selected from the French population and were frequency matched with the cases on age and gender. Cancer history in first- and second-degree relatives was reported by the mothers in a structured telephone questionnaire that was the same for the cases and controls. Odds ratios (ORs) were estimated using an unconditional regression model taking into account the stratification variables and potential confounders. A family history of cancer was associated with an increased risk of HL (OR = 1.5 [1.0-2.2]) and NHL (OR = 1.8 [1.3-2.5]), but not AL (OR = 1.0 [0.9-1.2]). The ORs were higher when at least 2 relatives had a history of cancer or when 1 case occurred before age 46 years. Only HL was significantly associated with a family history of hematopoietic malignancies (OR = 2.0 [1.0-3.8]), mainly because of a significant association with a history of HL (OR = 5.4 [1.3-22]). In conclusion, the study findings support the hypothesis of familial susceptibility to childhood lymphoma, but do not suggest familial susceptibility to childhood AL.     

Treatment of acute myeloid leukemia in the elderly: a clinical dilemma

Fifty-four patients representing all the cases of acute myeloid leukemia in patients aged over 60 years, presenting to three adjacent hospitals, were studied. Only 26 of the 54 patients were considered suitable for remission induction with intensive combination chemotherapy which produced seven complete remissions (CR) (26 per cent). Eighteen of the 54 patients survived longer than three months--11 of these had received remission induction chemotherapy (five CRs), two low dose cytarabine, one vincristine and vitamin A and four supportive treatment alone. By six months all the patients who had received supportive treatment had died. Patients who received intensive chemotherapy spent 77 per cent of the first 90 days in hospital and half died in hospital. Patients receiving differentiating agents or supportive care spent more time at home (37 per cent, 34 per cent of the first 90 days, respectively) but had shorter overall survival. Assessment of clinical characteristics in an attempt to predict response to treatment and survival indicated that poor performance status and the presence of infection were the most important factors. Analysis was limited by the statistically small number in the group. At present there is no reliable method of predicting which patients will respond well to treatment with intensive chemotherapy. The clinical dilemma is whether to treat more intensively to benefit a minority, or to use supportive treatment to allow more time to be spent at home albeit with a shorter overall survival.     

Dynamics of procalcitonin and bacteremia in neutropenic adults with acute myeloid leukemia

Sensitive markers of infection are rare or of limited validity in neutropenic patients. Procalcitonin (PCT), a precursor protein of calcitonin, is a specific and sensitive marker of severe bacterial infections during short-term neutropenia. Because the value of PCT measurements among patients undergoing long periods of neutropenia remains uncertain and because several mechanisms, such as bacterial or fungal infections, reactions to drugs or blood products or tumor-associated events, can cause fever, we described the dynamics of PCT in 29 acute myeloid leukemia (AML) patients with 39 instances of chemotherapy-induced neutropenia. Plasma levels of PCT were determined prospectively by an immunoluminometric assay every four days starting at the onset of chemotherapy and continuing until the resolution of fever. We found that bacteremia did increase PCT levels above 0.5 ng/mL and these levels predicted bacteremia at day 15 of chemotherapy. This finding may be relevant in the decision to alter antibiotic regimens to decrease toxicity and cost when patients remain febrile at day 15.     

Molecular evidence for transferrin receptor 2 expression in all FAB subtypes of acute myeloid leukemia

We examined transferrin receptor (TfR) 1 and TfR2 mRNA expression in 50 acute myeloid leukemia (AML) patients by RT-PCR, with primers specific for exons 15–17 (TfR1), 3–5 (TfR2-alpha) and 4–5 (TfR2-beta) of the corresponding gene. There were 4/50 TfR1-negative (−), 3/50 TfR2-alpha mRNA (−) and 13/50 TfR2-beta mRNA (−) cases; only three cases were TfR1/2 mRNA (−). No significant correlations were identified between TfR2-beta mRNA negativity and specific FAB subtypes, karyotype or attainment of complete remission. These findings suggest that: (i) TfR2 expression is not restricted to erythroid cells, and (ii) iron import proteins might complement each other in AML cells.     

急性髓系白血病16号染色体倒位的研究进展

 inv(16)是急性髓系白血病（AML）M4Eo的特征性的异常核型,是预后较好的一个标志。inv(16)的结果是16q22上的CBFb基因和 16p13上的MYH11基因重排,产生CBFb-MYH11融合基因,可能在白血病的发病机制中起重要作用。本文就inv(16) AML的临床、血液学特点及分子生物学特征等方面的研究进展作一综述。     

A risk factor for relapse in Hodgkin's disease: Female gender?

A retrospective study of 163 patients with Hodgkin's disease treated between 1969 and 1987 was performed to identify adverse prognostic factors. One hundred and thirty-five patients (83 per cent) attained a complete remission and 42 (31 per cent) of these have relapsed (median follow-up--43 months). Using multivariate analysis, no independent factors predicted for the event of relapse. However, analysis of disease-free survival revealed that females fared significantly worse than males (p less than 0.05) and this was independent of other prognostic variables. Female sex has not been recognized as an independent prognostic factor predictive of inferior survival and inferior disease-free survival.     

Impact of remission induction chemotherapy on survival in older adults with acute myeloid leukemia

BACKGROUND: Significant controversy surrounds the use of remission induction chemotherapy (IC) in older adults with acute myeloid leukemia (AML). Earlier clinical trials have yielded conflicting results and possibly a minor survival benefit, often offset by a longer hospitalization time. METHODS: To evaluate the role of IC in patients with AML, a case control study of patients 60 years or older treated at the Cleveland Clinic Taussig Cancer Center between 1997 and 2005 was conducted. Forty-four patients who did not receive IC were matched by a propensity analysis to 138 patients who received an anthracycline-based regimen. RESULTS: The unadjusted median survival of patients who did not receive IC was 53 days, compared with 197 days (P < .001) for those who did. After further adjusting for age, gender, race, leukocyte count at presentation, AML cytogenetics, history of prior hematologic disorder, and assessing for comorbidities, not receiving IC was still associated with worse survival (hazards ratio of 1.88; 95% confidence interval, 1.15-3.05 [P = .01]). Additional predictors of poor outcomes in older adults with AML included higher leukocyte count at presentation, poor-risk cytogenetics, and African-American race (compared with Caucasians). CONCLUSIONS: The study suggests improved outcomes in older adults with AML who undergo remission induction therapy.     

组织蛋白酶G在急性髓系白血病诊断及免疫治疗中的作用

组织蛋白酶G (CG)在中性粒细胞早幼粒阶段特异性升高,在多种急性髓系白血病(AML)中表达异常,是极具免疫活性的白血病相关抗原之一,为AML免疫治疗提供重要靶点,文章就CG在AML诊断及免疫治疗中的作用进行综述.     

Epigenetic modifications of splicing factor genes in myelodysplastic syndromes and acute myeloid leukemia

Somatic mutations in splicing factor genes have frequently been reported in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Although aberrant epigenetic changes are frequently implicated in blood cancers, their direct role in suppressing one or both alleles of critical splicing factors has not been previously examined. Here, we examined promoter DNA hypermethylation of nine splicing factors, SF3B1, SRSF2, U2AF1, ZRSR2, SF3A1, HNRNPR, MATR3, ZFR, and YBX3 in 10 leukemic cell lines and 94 MDS or AML patient samples from the Australasian Leukemia and Lymphoma Group Tissue Bank. The only evidence of epigenetic effects was hypermethylation of the YBX3 promoter in U937 cells in conjunction with an enrichment of histone marks associated with gene silencing. In silico analysis of DNA methylation data for 173 AML samples generated by the Cancer Genome Atlas Research Network revealed promoter hypermethylation of the gene encoding Y box binding protein 3, YBX3, in 11/173 (6.4%) AML cases, which was significantly associated with reduced mRNA expression (P < 0.0001). Hypermethylation of the ZRSR2 promoter was also detected in 7/173 (4%) cases but was not associated with decreased mRNA expression (P = 0.1204). Hypermethylation was absent at the promoter of seven other splicing factor genes in all cell lines and patient samples examined. We conclude that DNA hypermethylation does not frequently silence splicing factors in MDS and AML. However, in the case of YBX3, promoter hypermethylation‐induced downregulation may contribute to the pathogenesis or maintenance of AML.     

Racial,ethnic and socioeconomic disparities in the treatment of brain tumors

Disparities in American health care based on socially-defined patient characteristics such as race, ethnicity, and socioeconomic position are well-documented. We review differences and disparities in incidence, pathobiology, processes and outcomes of care, and survival based on social factors for brain tumors of all histologies. In the US, black patients have lower incidences of most brain tumor types and lower-income patients have lower incidences of low grade glioma, meningioma and acoustic neuroma; ascertainment bias may contribute to these findings. Pathogenetic differences between malignant gliomas in patients of different races have been demonstrated, but their clinical significance is unclear. Patients in disadvantaged groups are less often treated by high-volume providers. Mortality and morbidity of initial treatment are higher for brain tumor patients in disadvantaged groups, and they present with markers of more severe disease. Long term survival differences between malignant glioma patients of different races have not yet been shown. Clinical trial enrollment appears to be lower among brain tumor patients from disadvantaged groups. We propose future research both to better define disparities and to alleviate them.     

Invasive fungal diseases during first induction chemotherapy affect complete remission achievement and long-term survival of patients with acute myeloid leukemia

We retrospectively evaluated, in a logistic-regression-model, the role of proven/probable invasive fungal diseases (PP-IFD), occurring during first induction chemotherapy, on the achievement of complete remission (CR) and overall survival (OS) in 198 acute myeloid leukemia (AML) patients. A PP-IFD was documented in 34 (17.2%) patients. Younger age, good performance status at AML diagnosis and no development of a PP-IFD (OR 4.09, 95% CI 1.71–9.81, p < 0.0001) were independent factors associated to CR achievement. Younger age, good performance status, favorable genetic risk and no development of PP-IFD (HR 1.86, 95% CI 1.20–2.88, p = 0.005) were independent factors associated to OS at 3 years.     

Allogeneic and autologous bone marrow transplantation for acute leukemia and malignant lymphoma: current status

The current status of autologous and allogeneic marrow transplantation for acute leukemias and malignant lymphoma is reviewed and compared to the current status of conventional chemotherapy. Based on the reviewed literature, it is concluded that marrow transplantation and conventional chemoradiotherapy are not mutually exclusive and that for most young patients with acute hematological malignancies the question is not if, but rather when to intervene with a marrow transplant treatment. Thus marrow transplantation and conventional chemoradiotherapy can work as complimentary units in the complex therapeutic approach needed to cure most patients with hematological malignancies.     

Leukocyte count as a predictor of death during remission induction in acute myeloid leukemia

Acute myeloid leukemia (AML) presenting with a high leukocyte count has been associated with an increase in induction mortality and poor results in a number of other survival measures. However, the level at which an elevated leukocyte count has prognostic significance in AML remains unclear. In this report on a series of 375 adult (non-M3) AML patients undergoing induction chemotherapy at a single institution, leukocyte count analyzed as a continuous variable is shown to be a better predictor of induction death (ID) and overall survival (OS) than a leukocyte count of ≥100×10⁹/L, a value characteristically associated with “hyperleukocytosis” (HL). In this patient cohort, a presenting leukocyte count of ≥30×10⁹/L had high sensitivity and specificity for predicting ID, and both performance status (PS) and leukocyte count more accurately predicted for ID than age. Considering these parameters in newly-diagnosed AML patients may facilitate the development of strategies for reducing induction mortality.