Factor In Acute Lymphoblastic Leukemia Research Articles

New definition of remission in childhood acute lymphoblastic leukemia.

The extent of clearance of leukemic cells from the blood or bone marrow during the early phase of therapy is an independent prognostic factor in acute lymphoblastic leukemia (ALL). Several methods are available to measure the minimal residual disease (MRD) remaining after initial intensive chemotherapy. The most promising are flow cytometric detection of aberrant immunophenotypes and polymerase chain reaction analysis of clonal antigen-receptor gene rearrangements. When applied together, these techniques enable one to monitor MRD in virtually all cases of ALL. Patients who achieve an 'immunologic' or 'molecular' remission (ie leukemic involvement of <0.01% of nucleated bone marrow cells at the end of remission induction therapy) are predicted to have a better clinical outcome than patients whose remission is defined solely by morphologic criteria. In studies to date, patients with MRD at a level of 10(-2) or more at the end of induction have fared almost as poorly as those with > or =5% blast cells in the bone marrow (ie induction failures). Sequential monitoring of MRD can improve the clinical utility of risk assessment still further. Additional studies are needed to determine the critical levels of MRD at various times of treatment and whether therapeutic intervention based on MRD findings can improve clinical outcome.

Expression of multidrug resistance-related genes does not contribute to risk factors in newly diagnosed childhood acute lymphoblastic leukemia

The present study was designed to evaluate the association of multidrug resistance gene (MDR1), multidrug resistance-associated protein (MRP) gene and lung resistance protein (LRP) gene expression (mRNA levels) with risk factors such as phenotype, age and leukocyte count in newly diagnosed childhood acute lymphoblastic leukemia, because biological mechanisms contributing to risk factors were not known. Expression of the MDR1, MRP and LRP genes in leukemic cells from 40 pediatric patients was quantitated using the reverse transcriptase polymerase chain reaction method. The associations of expression of these genes with age and leukocyte count, which are known as risk factors for acute lymphoblastic leukemia (ALL), were analyzed. Moreover, the associations with clinically classified risk-related groups (high-risk ALL and low-risk ALL) were also investigated. No positive correlations between expression of these genes and age or leukocyte count were found. The expression of these genes was not different among clinically classified risk-related groups. Expression (mRNA levels) of the MDR1, MRP and LRP genes did not contribute to risk factors in newly diagnosed childhood acute lymphoblastic leukemia.

Expression of multidrug resistance-related genes does not contribute to risk factors in newly diagnosed childhood acute lymphoblastic leukemia

Abstract Background: The present study was designed to evaluate the association of multidrug resistance gene (MDR1), multidrug resistance-associated protein (MRP) gene and lung resistance protein (LRP) gene expression (mRNA levels) with risk factors such as phenotype, age and leukocyte count in newly diagnosed childhood acute lymphoblastic leukemia, because biological mechanisms contributing to risk factors were not known. Methods: Expression of the MDR1, MRP and LRP genes in leukemic cells from 40 pediatric patients was quantitated using the reverse transcriptase polymerase chain reaction method. The associations of expression of these genes with age and leukocyte count, which are known as risk factors for acute lymphoblastic leukemia (ALL), were analyzed. Moreover, the associations with clinically classified risk-related groups (high-risk ALL and low-risk ALL) were also investigated. Results: No positive correlations between expression of these genes and age or leukocyte count were found. The expression of these genes was not different among clinically classified risk-related groups. Conclusions: Expression (mRNA levels) of the MDR1, MRP and LRP genes did not contribute to risk factors in newly diagnosed childhood acute lymphoblastic leukemia.

Clinical Features and Outcome of Children With First Marrow Relapse of Acute Lymphoblastic Leukemia Expressing BCR-ABL Fusion Transcripts

Although the Philadelphia chromosome (Ph1) has been identified as an adverse prognostic factor in acute lymphoblastic leukemia (ALL), little is known about the incidence and clinical course of relapsed Ph1-positive ALL in children. The incidence was determined by screening of 170 consecutive children with first bone marrow relapse of ALL using the reverse transcriptase-polymerase chain reaction (RT-PCR) and comparison, with cytogenetic analysis. Among these 170 children, 20 (12%) were found to be BCR-ABL-positive, representing a rate that is about three times higher than that reported for newly diagnosed ALL. Ten of the cases were identified by RT-PCR only. In none of the 21 patients with T-cell immunophenotypes could an expression of the BCR-ABL mRNA be detected. BCR-ABL positivity was associated with a significantly shorter duration of first remission (P = .0086) and higher white blood cell (P = .0157) and blast cell counts (P = .0304) at relapse diagnosis. All patients were treated according to the ALL-REZ BFM 87 and 90 relapse trials of the BFM Relapse Study Group. The intensive multiagent chemotherapy induced a second complete remission in only 60% of children with BCR-ABL-positive ALL compared with in 91% of those without BCR-ABL expression (P = .0023). The prognosis of BCR-ABL-positive ALL in children is poor, with a probability of event-free survival at 2 years of 8% versus 50% in those without BCR-ABL mRNA or cytogenetic analysis should become part of the routine diagnostic panel for children with newly diagnosed ALL and is fundamental for children presenting with an early bone marrow relapse.

Early cytoreduction: a major prognostic factor in adult acute lymphoblastic leukemia.

Prognostic factors in acute lymphoblastic leukemia (ALL) are used for treatment stratification of ALL. Definition of simple parameters such as the presence or absence of peripheral leukemic cells after one week of treatment could help for stratification. A retrospective study was conducted on 79 previously untreated adult patients with ALL followed in the Hematology department of Hotel Dieu from 1981 to 1991. 84% of patients achieved complete remission (CR), 7% were refractory to induction treatment, and 7 patients (9%) died during the first month after diagnosis. After multivariate analysis the only independent statistically significant factors for achieving CR were the absence of peripheral blast cells at day 7 (PBC D7) (p = 0.009) and age (< 50 years) (p = 0.03). For CR duration the same independent statistically significant factors were found (PBC D7 = 0 versus > 0, p = 0.008; and age < or > or = 30 years, p = 0.045). The PBC D7 value was more significant when circulating blast cells were present at diagnosis. In patients with more than 50,000 PBC at diagnosis, the 10- years event free disease was 62% +/- 20% when PBC were absent at day 7 versus 0% when PBC were present (p < 0.002). All 20 patients with prolonged DFS had PBC D7 = 0 achieving CR by 28 days. The persistence of PBC at Day 7 could be used as a factor to identify a subgroup of poor prognosis adults with ALL.

Chromosomes and other prognostic factors in acute lymphoblastic leukaemia: a long-term follow-up.

Cytogenetic, clinical and laboratory features at diagnosis were examined in a group of 80 children with acute lymphoblastic leukaemia (ALL) who had been followed up for a minimum of 5 1/2 years. The 17 (21%) with high hyperdiploidy tended to have low leucocyte counts and common ALL, but their favourable outcome (75% event-free survival) was independent of these factors. No patient with hypodiploidy survives while the pseudodiploid and normal groups have an intermediate prognosis. Cytogenetic analysis showed examples of patients with the well-recognized translocations and a number with apparently unique ones. Among the latter were some long-term survivors. We conclude that cytogenetic analysis identifies a good risk group of patients who remain well on long-term follow-up, but that the presence of a translocation does not necessarily imply a poor outcome.

Leukaemia and nutrition I: Malnutrition is an adverse prognostic factor in the outcome of treatment of patients with standard-risk acute lymphoblastic leukaemia

A group of 43 pediatric patients with standard-risk ALL were studied. Thirty-seven per cent of them presented with malnutrition at diagnosis. Malnourished children had a significantly worse outcome than well-nourished children. Five-year DFS was 83% for well-nourished children (WNC) and 26% for under-nourished children (UNC) ( p < 0.001). Relapses presented more frequently in the bone marrow in UNC than in WNC (56% vs 7%, p < 0.0001). The doses of maintenance chemotherapy had to be reduced in 68% of UNC and 11% of WNC ( p < 0.005); the doses of maintenance myelosuppressive chemotherapy (6-MP, oral MTX and hydroxyldaunorubicin) received by UNC were approximately 50% of those received by WNC ( p < 0.01). The correlation between malnutrition and compromised treatment was 0.92. Malnutrition might be included as an adverse prognostic factor in acute lymphoblastic leukaemia (ALL).

Prognostic factors in acute lymphoblastic leukemia in adults: the Memorial Hospital experience.

Acute lymphoblastic leukemia (ALL) has become a curable disease through the development of effective treatment strategies based on polychemotherapy with non-crossresistant drugs, effective prophylaxis of central nervous system leukemia, and prolonged maintenance chemotherapy [1–4]. Lymhoblastic leukemia in children, in particular, has been treated successfully, with the majority of children surviving 5 years [5]. It was recognized during the early studies that patients had very different responses to standard therapy, and a number of models were developed to identify patient groups with different prognoses. As a consequence, children with ALL were treated differently, based on their classification as “low,”-“standard,”- or “high”-risk patients. Risk group assignments were mainly based on age, white blood cell count (WBC), and involvement of lymph nodes, hepatomegaly or splenomegaly in some series [5].KeywordsAcute Lymphoblastic LeukemiaWhite Blood Cell CountRemission DurationBone Marrow BlastHigh White Blood Cell CountThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Analysis of prognostic factors in acute lymphoblastic leukemia.

Children with ALL who have a high probability of excellent response, long-term survival, and cure when treated with widely available standard therapy can be identified at the time of diagnosis. Others can be identified who are at high risk of failure to respond, early relapse, and death. The importance of such prognostic characteristics is so great that they should be considered in the selection of appropriate treatment for each patient. Prognostic factors also must be considered in the design and analysis of clinical trials. All prognostic factors are not equally significant and many of them are closely associated. It is possible to rank them in importance and usefulness by appropriate statistical methods. As additional prognostic factors are identified, and as more effective and more specific therapies are developed, the relative importance of prognostic factors will change.

Prognostic factors in acute lymphoblastic leukaemia--with special consideration of pre-diagnostic duration of signs (author's transl)

It is concluded from the prognostic factors of acute lymphoblastic leukaemia, as far as they have become known up to now, such as initial leukocyte count, extent of organ infiltration, etc, that the pre-diagnostic duration of signs, representing a measure of the proliferation activity of the leukaemia cells, could also represent a relevant prognostic characteristic. A check conducted in 90 children treated between 1966--1975 yields a correlation only between a very short pre-diagnostic duration of signs (less than 2 weeks) and the duration of the first complete remission (as well as the survival time). However, even those prognostic factors which are already generally recognised, possess merely limited reliability, because they do not take the individual response to therapy into account. Hence, improvement of prognosis of the course of the disease can be expected only if the continuous decrease of the remaining population of blasts during the early phase of remission can be determined with greater accuracy than before.

The effect of L‐asparaginase on plasma coagulation factors in acute lymphoblastic leukemia

Serial coagulation studies were performed in 26 pediatric patients with acute lymphoblastic leukemia during initial induction therapy with vincristine, prednisone, and L-asparaginase. Prolongation of screening coagulation tests was frequent: prothrombin time (in 16 of 26 patients), partial thromboplastin time (23/26) and thrombin time (21/26). In all 26 patients fibrinogen levels fell below .20 g/100 ml and 16 had levels below .10 g/100 ml. Sixteen patients had plasma coagulation factor assays performed. In these 16 patients, Factor XI was less than 40% in 14 and Factor XI was less than 70% in 9, with only a few scattered low levels of other factors. There were no clinical bleeding episodes. Coagulation abnormalities returned to normal at the completion of L-asparaginase therapy while the patients remained on vincristine and prednisone.

The effect of L-asparaginase on plasma coagulation factors in acute lymphoblastic leukemia

Serial coagulation studies were performed in 26 pediatric patients with acute lymphoblastic leukemia during initial induction therapy with vincristine, prednisone, and L-asparaginase. Prolongation of screening coagulation tests was frequent: prothrombin time (in 16 of 26 patients), partial thromboplastin time (23/26) and thrombin time (21/26). In all 26 patients fibrinogen levels fell below .20 g/100 ml and 16 had levels below .10 g/100 ml. Sixteen patients had plasma coagulation factor assays performed. In these 16 patients, Factor XI was less than 40% in 14 and Factor XI was less than 70% in 9, with only a few scattered low levels of other factors. There were no clinical bleeding episodes. Coagulation abnormalities returned to normal at the completion of L-asparaginase therapy while the patients remained on vincristine and prednisone.

Surface markers and prognostic factors in acute lymphoblastic leukemia.

We investigated the surface markers on lymphoblasts from 37 patients with acute lymphoblastic leukemia. Spontaneous rosette formation with sheep erythrocytes (E rosettes) identified T cells and the presence of surface immunoglobulin identified B cells. Eight patients had T-marker lymphoblasts; 28 had no markers (null lymphoblasts), and one patient had B-marker lymphoblasts. The eight patients with T-marker acute lymphoblastic leukemia had massive leukemic infiltration, frequently a mediastinal mass, and a poor prognosis. The T-marker lymphoblasts had a weak or negative periodic acid-Schiff reaction and a very low antigenic stimulation to allogeneic lymphocytes. The association of T-marker lymphoblasts and some of the conventional poor-risk factors appears to be reliable in predicting a poor prognosis.