An international collaboration was set up to prospectively evaluate the role of allogeneic transplantation for adults with acute lymphoblastic leukemia (ALL) and compare autologous transplantation with standard chemotherapy. Patients received 2 phases of induction and, if in remission, were assigned to allogeneic transplantation if they had a compatible sibling donor. Other patients were randomized to chemotherapy for 2.5 years versus an autologous transplantation. A donor versus no-donor analysis showed that Philadelphia chromosome-negative patients with a donor had a 5-year improved overall survival (OS), 53% versus 45% (P ؍ .01), and the relapse rate was significantly lower (P < .001). The survival difference was significant in standard-risk patients, but not in high-risk patients with a high nonrelapse mortality rate in the highrisk donor group. Patients randomized to chemotherapy had a higher 5-year OS (46%) than those randomized to autologous transplantation (37%; P ؍ .03). Matched related allogeneic transplantations for ALL in first complete remission provide the most potent antileukemic therapy and considerable survival benefit for standard-risk patients. However, the transplantation-related mortality for highrisk older patients was unacceptably high and abrogated the reduction in relapse risk. There is no evidence that a single autologous transplantation can replace consolidation/maintenance in any risk group. This study is registered at http:// clinicaltrials.gov as NCT00002514. (Blood.
The international acute lymphoblastic leukemia (ALL) study was designed to prospectively define the optimal therapy for adults 60 years of age or younger with newly diagnosed ALL. All patients received identical induction therapy, and 91% achieved complete remission (CR). Patients 50 years of age or younger with a compatible sibling were assigned to undergo allogeneic transplantation; the others were randomly assigned to autologous transplantation or to consolidation/maintenance therapy for 2.5 years. Patients who did not achieve CR after induction had an overall survival rate of 5% compared with 45% for patients who achieved CR. Factors at diagnosis predictive of overall survival and diseasefree survival were age (P ؍ .001), white blood cell count less than 30 ؋ 10 9 /L for B lineage or less than 100 ؋ 10 9 /L for T lineage (P ؍ .001) and immunophenotype, T lineage versus B lineage (P ؍ .001). The data demonstrate that achieving CR with induction therapy is indispensable for long-term survival in adult patients with ALL. Furthermore, with a response rate greater than 90%, the induction regimen was highly efficacious as remissioninducing therapy. This large database has validated several previously identified independent prognostic factors in ALL, such as age, white blood cell count at presentation, cytogenetics, and immunophenotype. However, the achievement of CR within 4 weeks does not appear to be an independent prognostic factor. (Blood. 2005;106:3760-3767)
Summary. Cytogenetic classification of 350 adults with acute lymphoblastic leukaemia on MRC UKALL XA trial showed the following statistically significant associations: t(9;22) (11%) increased with increasing age and leucocyte counts (WBC) and most had a C/pre-B immunophenotype. t(4;11) (3%) was associated with higher WBCs, increasing age and null immunophenotype. Other abnormalities of 11q (abn11q) (4%) were associated with male sex and T-cell ALL. High hyperdiploidy (7%) and abn9p (5%) decreased with increasing WBC. High hyperdiploid patients were younger and tended to have C/pre-B ALL. Triploidy/tetraploidy (3%) decreased and pseudodiploidy (11%) increased with increasing WBC. Cytogenetic classification was prognostically important (chi-square for heterogeneity of classification ¼ 53 : 56; P < 0 : 0001) and added significance to age, sex and WBC. A poor prognosis for patients classed as t(9;22) (13% disease-free survival at 3 years), as t(4;11) 24% at 3 years) and hypodiploid (11% at 3 years), and good prognosis for abn12p (4% of subjects) and high hyperdiploidy (74% and 59% at 3 years respectively) were statistically significant, but the 54% 3-year disease-free survival for patients with t(1;19) was not. The prognosis of patients classed as t(9;22) was independent of other single variables. Abn12p, abnormalities of 11q (including t(4;11) cases) and hypodiploidy added prognostic significance to all other variables combined.
The purpose of the study was to examine the influence of age on outcome in a large cohort of children and adults with lymphoblastic leukaemia who were treated on two similar trials. Factors influencing outcome were examined in 2204 patients aged over 1 year treated between 1985 and 1992 on the parallel Medical Research Council Trials UKALL X and Xa, for children and adults, respectively. There was a progressive worsening in survival with increasing age from 85% (95% CI 83-87) at 5 years for children aged 1-9 to 24% (CI 17-31) for patients over 40. Induction failures, deaths in remission and bone marrow relapses increased significantly with age. Analysis of clinical and biological features showed dominance of early B-ALL in childhood and increasing incidence of the PhЈ chromosome with age. Over 80% of eligible children, but a much lower proportion of adults especially those over 40, was entered. Compliance was stricter in the paediatric trial but most deviations in adults involved giving more treatment. Analysis of results in a proportional hazards model confirmed the overwhelming independent influence of age; with all other factors equal a 10 year old had half the risk of treatment failure of a 20 year old and a 44 year old double the risk. Selective entry to therapeutic trials and increased treatment-related toxicity are features of adult ALL but age itself remains a dominant prognostic factor. While improved supportive care and refinements of conventional therapy may have some effect on prognosis, new understandings and treatment approaches to adult ALL are needed.
Fourteen cases of philadelphia chromosome (Ph1) positive chronic myeloid leukaemia in blast transformation have been investigated using cell surface markers. Morphologically eight cases were lymphoid and the remainder myeloid in appearance. All cases were negative with surface markers for thymocytes and T and B lymphocytes. Five of the lymphoid cases reacted with an antiserum specific for acute lymphoid leukaemia )ALL) of non-T non-B type and were also weakly reactive with a lymphocyte reactive antiserum. A sixth patient, whose blast cells were anti-ALL negative (ALL-) at presentation, subsequently developed central nervous system leukaemia with anti-ALL positive (ALL+) blast cells in the CSF. In all cases the leukaemic blast cells showed greatly diminished expression of cholera toxin receptors when compared to granulocytic cells from the chronic phase of CML. This parallels weak or negligible expression of the cholera toxin receptor in ALL and AML. These results suggest that the blastic phase of CML may involve different cellular derivatives of a pluripotential stem cell in which the primary malignant/genetic changes reside. The blast crisis of CML can therefore be heterogeneous with respect to cellular expression and in a significant proportion of patients involves a cell which is by membrane markers and morphological criteria indistinguishable from that seen in the common form of ALL. In these cases the Philadelphia chromosome may be the only distinguishing cellular characteristic.
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