ALBERT

Description: Leukemic blasts from 774 children with newly diagnosed acute lymphocytic leukemia (ALL) have been phenotyped by microcytotoxicity testing with a panel of monoclonal antibodies and heteroantisera as part of a Pediatric Oncology Group classification study of acute leukemia. One hundred twenty-two cases, or 16% were designated as T cell leukemia based on the reactivity of blast cells with previously well-characterized antisera (PT) against a T lymphocyte-associated antigen. Using this antisera-based definition as a standard, we looked for a monoclonal antibody combination that would be a suitable substitute. An algorithm calling for reactivity with either monoclonal antibody 3A1 or Leu-1 was a 92% sensitive and 97% specific predictor of PT reactivity. Only 27 of 755 cases of leukemia were incorrectly classified using this algorithm. Subsequently, Ficoll-Hypaque-separated bone marrow cells from 118 additional patients with ALL (21 of whom had T cell ALL) were stained by immunofluorescence using a combination of directly fluoresceinated 3A1 and Leu-1. Reactivity of 20% or more of the cells with this antibody combination was a 100% sensitive and 94% specific indicator of T cell ALL defined by PT positivity; with a higher cutoff value for positive values, or the use of supplemental tests, even this small number of false-positives could be eliminated. We conclude that this monoclonal antibody combination is a satisfactory replacement for our heteroantisera definition of T cell ALL.

Description: The comparative effectiveness of intrathecal (IT) combination chemotherapy using two agents, methotrexate (MTX) and hydrocortisone (HDC), and three agents, MTX, HDC, and cytosine arabinoside (CA), in treating meningeal leukemia was determined in a randomized Southwest Oncology Group study. Following central nervous system (CNS) remission induction the same regimen was used for periodic maintenance until CNS relapse supervened. Complete CNS remission was achieved in 100% of 43 children given two-agent therapy and in 96% of 48 children given three- agent therapy. Length of CNS remission for two-agent therapy was 1-150+ wk, median 47.2 wk; for three-agent therapy, remissions were 1-190+ wk, median 64.6 wk. Differences in length of remission curves were not of statistical significance (p=0.71). Toxicity of combination IT chemotherapy in the two- and three-agent regimens was reduced compared to that of IT MTX alone for CNS remission induction and maintenance. The additive effects of the IT drug combinations have been less than expected. The cytocidal activity of these agents when administered simultaneously of sequentially is not fully understood. Further studies are clearly indicated to determine optimum doses, schedules, and sequences for the chemotherapeutic agents which can be given intrathecally in combination.

Description: In an attempt to improve the poor outlook for children with T-cell leukemia (T-ALL), the Southwest Oncology Group, Pediatric Division, used a modified LSA2-L2 multidrug regimen to treat 53 patients with E- rosette-positive T-ALL. This regimen was chosen because of its demonstrated efficacy in T-cell (mediastinal) non-Hodgkin's lymphoma. Complete remission (CR) rate was 88%. Range of follow-up for those patients remaining in CR is 24–49 mo (median 39 mo). Life table analysis estimates that 40% (SE 8.3%) of all patients who started induction therapy will remain failure-free at 3 yr. For patients achieving CR, 46% (SE 9%) are projected to remain in both marrow and extramedullary CR at 3 yr. Median failure-free duration was 13 mo, but only 1 patient has relapsed beyond 16 mo. Twenty-nine percent of initial relapses were isolated CNS relapses. The following presenting factors did not relate significantly to outcome: hemoglobin, platelet count, uric acid, race, and mediastinal mass. Age greater than 10 yr was a poor prognosis indicator only in the less than 50,000/microliter WBC group. Sex was not a significant factor after adjusting for WBC. WBC was the most important prognostic factor: 19% (SE 8%) of patients with WBC greater than 50,000/microliter are projected to remain failure- free at 3 yr as compared to 67% (SE 11%) of patients with WBC less than 50,000/microliter. Although the overall results are better than those previously reported for pediatric patients with T-ALL, the long-term failure-free rate remains low for patients presenting with greater than 50,000/microliter WBC.

Description: In an attempt to improve the poor outlook for children with T-cell leukemia (T-ALL), the Southwest Oncology Group, Pediatric Division, used a modified LSA2-L2 multidrug regimen to treat 53 patients with E- rosette-positive T-ALL. This regimen was chosen because of its demonstrated efficacy in T-cell (mediastinal) non-Hodgkin's lymphoma. Complete remission (CR) rate was 88%. Range of follow-up for those patients remaining in CR is 24–49 mo (median 39 mo). Life table analysis estimates that 40% (SE 8.3%) of all patients who started induction therapy will remain failure-free at 3 yr. For patients achieving CR, 46% (SE 9%) are projected to remain in both marrow and extramedullary CR at 3 yr. Median failure-free duration was 13 mo, but only 1 patient has relapsed beyond 16 mo. Twenty-nine percent of initial relapses were isolated CNS relapses. The following presenting factors did not relate significantly to outcome: hemoglobin, platelet count, uric acid, race, and mediastinal mass. Age greater than 10 yr was a poor prognosis indicator only in the less than 50,000/microliter WBC group. Sex was not a significant factor after adjusting for WBC. WBC was the most important prognostic factor: 19% (SE 8%) of patients with WBC greater than 50,000/microliter are projected to remain failure- free at 3 yr as compared to 67% (SE 11%) of patients with WBC less than 50,000/microliter. Although the overall results are better than those previously reported for pediatric patients with T-ALL, the long-term failure-free rate remains low for patients presenting with greater than 50,000/microliter WBC.

Description: In 35 of 191 patients with acute lymphocytic leukemia (ALL) malignant cells were similar in phenotype to B-lymphocyte precursors. Both these patients' lymphoblasts and normal pre-B-cells contain cytoplasmic immunoglobulin (Ig) mu heavy chains, but have no surface Ig. In patients with pre-B leukemias, lymphoblasts containing cytoplasmic mu chains alone were often accompanied by cells of identical morphology that expressed no Ig and less frequently by lymphoblasts bearing scant amounts of surface mu. This spectrum of cellular Ig expression suggests that “null”, pre-B, and intermediate pre-B/B ALLs represent closely related malignancies with complete or partial arrests at different stages of maturation. When pre-B, B, T, and “null” cell categories of ALL were compared for 22 different clinical and laboratory features, including remission rate and short-term remission duration, no statistical differences were observed between the pre-B and “null” groups. These early results suggest that pre-B-cell leukemias represents a relatively good prognostic subclass of ALL, do not require more intensive treatment than that proven to be effective for “null” cell ALL, and should be distinguished from the less common, but more clinically aggressive, B-cell subclass of ALL. Longer follow-up will be required to confirm these preliminary conclusions.

Description: The comparative effectiveness of intrathecal (IT) combination chemotherapy using two agents, methotrexate (MTX) and hydrocortisone (HDC), and three agents, MTX, HDC, and cytosine arabinoside (CA), in treating meningeal leukemia was determined in a randomized Southwest Oncology Group study. Following central nervous system (CNS) remission induction the same regimen was used for periodic maintenance until CNS relapse supervened. Complete CNS remission was achieved in 100% of 43 children given two-agent therapy and in 96% of 48 children given three- agent therapy. Length of CNS remission for two-agent therapy was 1-150+ wk, median 47.2 wk; for three-agent therapy, remissions were 1-190+ wk, median 64.6 wk. Differences in length of remission curves were not of statistical significance (p=0.71). Toxicity of combination IT chemotherapy in the two- and three-agent regimens was reduced compared to that of IT MTX alone for CNS remission induction and maintenance. The additive effects of the IT drug combinations have been less than expected. The cytocidal activity of these agents when administered simultaneously of sequentially is not fully understood. Further studies are clearly indicated to determine optimum doses, schedules, and sequences for the chemotherapeutic agents which can be given intrathecally in combination.

Description: In 35 of 191 patients with acute lymphocytic leukemia (ALL) malignant cells were similar in phenotype to B-lymphocyte precursors. Both these patients' lymphoblasts and normal pre-B-cells contain cytoplasmic immunoglobulin (Ig) mu heavy chains, but have no surface Ig. In patients with pre-B leukemias, lymphoblasts containing cytoplasmic mu chains alone were often accompanied by cells of identical morphology that expressed no Ig and less frequently by lymphoblasts bearing scant amounts of surface mu. This spectrum of cellular Ig expression suggests that “null”, pre-B, and intermediate pre-B/B ALLs represent closely related malignancies with complete or partial arrests at different stages of maturation. When pre-B, B, T, and “null” cell categories of ALL were compared for 22 different clinical and laboratory features, including remission rate and short-term remission duration, no statistical differences were observed between the pre-B and “null” groups. These early results suggest that pre-B-cell leukemias represents a relatively good prognostic subclass of ALL, do not require more intensive treatment than that proven to be effective for “null” cell ALL, and should be distinguished from the less common, but more clinically aggressive, B-cell subclass of ALL. Longer follow-up will be required to confirm these preliminary conclusions.

Description: Leukemic blasts from 774 children with newly diagnosed acute lymphocytic leukemia (ALL) have been phenotyped by microcytotoxicity testing with a panel of monoclonal antibodies and heteroantisera as part of a Pediatric Oncology Group classification study of acute leukemia. One hundred twenty-two cases, or 16% were designated as T cell leukemia based on the reactivity of blast cells with previously well-characterized antisera (PT) against a T lymphocyte-associated antigen. Using this antisera-based definition as a standard, we looked for a monoclonal antibody combination that would be a suitable substitute. An algorithm calling for reactivity with either monoclonal antibody 3A1 or Leu-1 was a 92% sensitive and 97% specific predictor of PT reactivity. Only 27 of 755 cases of leukemia were incorrectly classified using this algorithm. Subsequently, Ficoll-Hypaque-separated bone marrow cells from 118 additional patients with ALL (21 of whom had T cell ALL) were stained by immunofluorescence using a combination of directly fluoresceinated 3A1 and Leu-1. Reactivity of 20% or more of the cells with this antibody combination was a 100% sensitive and 94% specific indicator of T cell ALL defined by PT positivity; with a higher cutoff value for positive values, or the use of supplemental tests, even this small number of false-positives could be eliminated. We conclude that this monoclonal antibody combination is a satisfactory replacement for our heteroantisera definition of T cell ALL.

Description: Two hundred fifty-three children with newly diagnosed T-cell acute lymphoblastic leukemia (ALL), who were treated uniformly with modified LSA2L2 therapy, were evaluated using univariate and recursive partition analyses to define clinical or biologic features associated with risk of treatment failure. Overall event-free survival (EFS) at 4 years was 43% (SE = 4%). Factors examined included white blood cell (WBC) level, age, gender, race (black v other), presence of a mediastinal mass, hepatomegaly, splenomegaly, marked lymphadenopathy, hemoglobin level, platelet count, blast cell expression of antigens such as the common acute lymphoblastic leukemia antigen (CALLA, CD10), HLA-DR, and T-cell- associated antigens (CD3, CD4, CD8, CD7, CD5, and THY). Univariate analysis showed that age less than or equal to 5 or less than or equal to 7 years, WBC level less than 10, less than 25, less than 50 or less than 100 x 10(3)/microL, and blast cell expression of CD4, CD8, or CALLA were associated with significantly better EFS, while hepatomegaly and splenomegaly were associated with worse EFS. Recursive partitioning analysis showed that the most important single favorable prognostic factor was a WBC level less than 50 x 10(3)/microL and, for patients with WBC counts below this level, the most important predictor of EFS was blast cell expression of the pan-T antigen defined by the monoclonal antibody (MoAb), L17F12 (CD5). For patients with higher WBC levels, the most important predictor of EFS was blast cell expression of THY antigen. The recursive partitioning analysis defined three groups of patients with widely varied prognoses identified as follows: (1) those with a WBC count less than 50 x 10(3)/microL who lacked massive splenomegaly and had blasts expressing CD5 had the best prognosis (66%, SE = 7%, EFS 4 years, n = 84); (2) those with (b1) WBC counts less than 50 x 10(3)/microL with either massive splenomegaly or who had blasts lacking CD5 expression, or (b2) WBC counts greater than 50 x 10(3)/microL with expression of the THY antigen had an intermediate prognosis (39%, SE = 7% EFS at 4 years, n = 94); (3) those with WBC counts greater than 50 x 10(3)/microL and whose blasts lacked expression of THY antigen had the poorest outcome (EFS = 19% at 4 years, SE = 8%, n = 63). A three-way comparison of EFS according to these groupings showed significant differences among the three patient groups (P less than .001). The recursive partitioning was able to classify 241 (95%) of the patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Description: Two hundred fifty-three children with newly diagnosed T-cell acute lymphoblastic leukemia (ALL), who were treated uniformly with modified LSA2L2 therapy, were evaluated using univariate and recursive partition analyses to define clinical or biologic features associated with risk of treatment failure. Overall event-free survival (EFS) at 4 years was 43% (SE = 4%). Factors examined included white blood cell (WBC) level, age, gender, race (black v other), presence of a mediastinal mass, hepatomegaly, splenomegaly, marked lymphadenopathy, hemoglobin level, platelet count, blast cell expression of antigens such as the common acute lymphoblastic leukemia antigen (CALLA, CD10), HLA-DR, and T-cell- associated antigens (CD3, CD4, CD8, CD7, CD5, and THY). Univariate analysis showed that age less than or equal to 5 or less than or equal to 7 years, WBC level less than 10, less than 25, less than 50 or less than 100 x 10(3)/microL, and blast cell expression of CD4, CD8, or CALLA were associated with significantly better EFS, while hepatomegaly and splenomegaly were associated with worse EFS. Recursive partitioning analysis showed that the most important single favorable prognostic factor was a WBC level less than 50 x 10(3)/microL and, for patients with WBC counts below this level, the most important predictor of EFS was blast cell expression of the pan-T antigen defined by the monoclonal antibody (MoAb), L17F12 (CD5). For patients with higher WBC levels, the most important predictor of EFS was blast cell expression of THY antigen. The recursive partitioning analysis defined three groups of patients with widely varied prognoses identified as follows: (1) those with a WBC count less than 50 x 10(3)/microL who lacked massive splenomegaly and had blasts expressing CD5 had the best prognosis (66%, SE = 7%, EFS 4 years, n = 84); (2) those with (b1) WBC counts less than 50 x 10(3)/microL with either massive splenomegaly or who had blasts lacking CD5 expression, or (b2) WBC counts greater than 50 x 10(3)/microL with expression of the THY antigen had an intermediate prognosis (39%, SE = 7% EFS at 4 years, n = 94); (3) those with WBC counts greater than 50 x 10(3)/microL and whose blasts lacked expression of THY antigen had the poorest outcome (EFS = 19% at 4 years, SE = 8%, n = 63). A three-way comparison of EFS according to these groupings showed significant differences among the three patient groups (P less than .001). The recursive partitioning was able to classify 241 (95%) of the patients.(ABSTRACT TRUNCATED AT 400 WORDS)