Skeletal morbidity is strongly associated with poor prognosis in adult acute lymphoblastic leukemia.
ABSTRACT The prognostic significance of skeletal morbidity in acute lymphoblastic leukemia (ALL) has been mostly studied in children and yielded disappointing results, while in adult ALL it is seldom reported, and its prognostic value is not clear. To evaluate the prognostic value of skeletal morbidity in de novo adult ALL, we identified 20 patients with ALL with skeletal morbidity and compared them with matched patients with ALL but without skeletal morbidity (n = 60). Compared with controls, patients with skeletal morbidity responded poorly to treatment, with a lower incidence of complete remission (p = 0.02) and shorter continued remission duration (p = 0.031). The overall survival (OS) (38.67% vs. 69.44%, p = 0.03) and event-free survival (EFS) (25.67% vs. 58.77%, p = 0.008) were inferior to those of controls. Allogeneic hematopoietic stem cell transplant (allo-HSCT) may be beneficial to patients with skeletal morbidity. For patients with skeletal morbidity, OS at 12 months was 72.92% in patients who underwent allo-HSCT, while it was 38.5% for patients treated with chemotherapy (p = 0.03). By multivariate analysis, skeletal morbidity was an independent prognostic factor in adult patients with ALL. These results confirm the poor prognosis of patients with ALL with skeletal morbidity and reinforce interest in evaluating the incorporation of allo-HSCT in adult patients with ALL with skeletal morbidity onset.
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ABSTRACT: The National Cancer Institute (NCI) sponsored a workshop to develop a set of standardized diagnostic and response criteria for acute myeloid leukemia (AML) clinical trials. The French-American-British (FAB) classification was retained for diagnosing AML, with the addition of patients with bone marrow morphologic features of a myelodysplastic syndrome and less than 30% bone marrow blasts, but with greater than or equal to 30% blasts in the peripheral blood. In this report, there are four important subgroups of AML not defined in the FAB classification that are discussed: undifferentiated acute leukemia, MO (AML lacking definitive myeloid differentiation by morphology or conventional cytochemistry but with ultrastructural or immunophenotypic evidence for AML), mixed lineage leukemia, and hypocellular AML. Definitions of response for clinical trials are presented to facilitate comparisons among different studies. Complete remission is considered the only response worth reporting in phase III trials, since lesser responses do not improve survival. Partial remissions may be of interest to identify active new agents in phase I and II studies. Monoclonal antibodies and cytogenetic studies are not part of the routine assessment of remission or reassessment at relapse, and their role in the evaluation of patients with AML is currently being evaluated in clinical trials. Although we recognize that some of the definitions in this report are arbitrary, generalized use of these guidelines will make results of clinical trials more comparable and interpretable.Journal of Clinical Oncology 06/1990; 8(5):813-9. · 18.04 Impact Factor
Article: Acute lymphoblastic leukaemia.[show abstract] [hide abstract]
ABSTRACT: Acute lymphoblastic leukaemia, a malignant disorder of lymphoid progenitor cells, affects both children and adults, with peak prevalence between the ages of 2 and 5 years. Steady progress in development of effective treatments has led to a cure rate of more than 80% in children, creating opportunities for innovative approaches that would preserve past gains in leukaemia-free survival while reducing the toxic side-effects of current intensive regimens. Advances in our understanding of the pathobiology of acute lymphoblastic leukaemia, fuelled by emerging molecular technologies, suggest that drugs specifically targeting the genetic defects of leukaemic cells could revolutionise management of this disease. Meanwhile, studies are underway to ascertain the precise events that take place in the genesis of acute lymphoblastic leukaemia, to enhance the clinical application of known risk factors and antileukaemic agents, and to identify treatment regimens that might boost the generally low cure rates in adults and subgroups of children with high-risk leukaemia.The Lancet 04/2008; 371(9617):1030-43. · 39.06 Impact Factor
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ABSTRACT: Chromosomal abnormalities are increasingly used to risk stratify adults with acute lymphoblastic leukemia. Published data describing the age-specific incidence of chromosomal abnormalities and their prognostic relevance are largely derived from clinical trials. Trials frequently have age restrictions and low recruitment rates. Thus we investigated these factors in a population-based cohort of 349 patients diagnosed during the course of 19 years in the northern part of England. The incidence of most chromosomal abnormalities varied significantly with age. The incidence of t(9;22)(q34;q11) increased in each successive decade, up to 24% among 40- to 49-year-old subjects. Thereafter the incidence reached a plateau. t(4;11)(q21;q23) and t(1;19)(q23;p13) were a rare occurrence among patients older than 60 years of age. In contrast, the frequency of t(8;14)(q24;q32) and t(14;18)(q32;q21) increased with age. High hyperdiploidy occurred in 13% of patients younger than 20 years of age but in only 5% of older patients. The incidence of low hypodiploidy/near-triploidy and complex karyotype increased with age from 4% (15-29 years) to 16% (>or= 60 years). Overall survival varied significantly by age and cytogenetics. Older patients and those with t(9;22), t(4;11), low hypodiploidy/near-triploidy, or complex karyotype had a significantly inferior outcome. These population-based results demonstrate the cytogenetic heterogeneity of adult acute lymphoblastic leukemia. These data will inform the delivery of routine clinical services and the design of new age-focused clinical trials.Blood 11/2009; 115(2):206-14. · 9.06 Impact Factor