Biomedical subjects

M Abromowitch

Publications and source records attributed to M Abromowitch.

43 records · Page 3Linked to original sources

PubMed1985

Serum lactic dehydrogenase level has prognostic value in childhood acute lymphoblastic leukemia.

Serum lactic dehydrogenase (LDH) levels were measured at diagnosis in 293 children with "standard-risk" acute lymphoblastic leukemia (ALL) to determine the prognostic value of this biologic feature. Standard risk assignment was based on an initial leukocyte count of less than 100 X 10(9)/L, the absence of a mediastinal mass, the absence of meningeal involvement, and the presence of lymphoblasts lacking sheep erythrocyte receptors or surface immunoglobulin. Serum LDH levels ranged from 97 to 6,595 U/L, with a mean of 547 U/L. Higher LDH levels were associated with higher leukocyte counts, lower blast cell DNA indices, lower platelet counts, a larger spleen size, and nonwhite race. LDH levels were not related to the percentage of marrow S-phase cells, liver size, French-American-British (FAB) classification, hemoglobin levels, age, sex, or the presence of the common ALL antigen on marrow blasts. Patients with the highest LDH levels (greater than 1,000 U/L) were most likely to fail treatment, whereas those with the lowest levels (less than 300 U/L) had the lowest risk of failure (P less than .0001). The prognostic significance of serum LDH level was retained in a subset of patients that included only those with leukocyte counts less than 25 X 10(9)/L (P = .0018). When 11 presenting characteristics were subjected to multivariate analysis, serum LDH level was found to have independent prognostic strength, contributing clinically important information to that gained from leukocyte count. Early measurement of serum LDH could be useful in identifying a group of standard-risk ALL patients with a high relapse hazard.

Analysis of Variance↗

PubMed1984

Seizures in childhood lymphoblastic leukaemia patients.

Features of seizures in children with acute lymphoblastic leukaemia were examined in relation to the type of treatment received for central nervous system prophylaxis. Of the 1289 patients in the study, 132 (10%) had experienced one or more seizures. In 96 the seizures had not been associated with any recognisable aetiology and, with 3 exceptions, had been generalised or focal motor in type. Status epilepticus had occurred in one-third of the group with seizures. Initial seizure rates among patients in continuous complete remission were significantly related to the method of central nervous system prophylaxis. Those who had received intrathecal methotrexate repeatedly with or without moderate doses of methotrexate intravenously or prior prophylactic cranial irradiation had a 20-fold higher seizure risk during remission induction, and a 37-fold higher risk during the 6th to 12th month of therapy, than did those who had received irradiation and only five intrathecal injections of methotrexate early in the course of treatment. Other clinical factors associated with an increased frequency of seizures were escalation of intravenous methotrexate dosage following cranial irradiation and treatment of meningeal leukaemia with intrathecal methotrexate. Parenterally administered methotrexate thus seems to increase susceptibility to seizure development in childhood leukaemia patients.

Central Nervous System↗

PubMed1984

Methotrexate systemic clearance influences probability of relapse in children with standard-risk acute lymphocytic leukaemia.

108 children with standard-risk acute lymphocytic leukaemia (ALL) were randomised to a post-induction treatment protocol including 15 doses of intermediate-dose methotrexate (1000 mg/m2) in addition to conventional oral therapy of mercaptopurine and low-dose methotrexate. After median follow-up of 26 months, 22 patients have had relapses. Among the 108 patients, rates of methotrexate systemic clearance ranged from 44.7 to 132 ml/min/m2. When the group was divided into three subgroups according to the patients' rates of methotrexate clearance, statistical analysis of the Kaplan-Meier curves estimating the probability of complete remission showed significant differences (p = 0.016) among the subgroups, patients with faster clearance having higher probability of relapse. Multivariate Cox's regression analysis incorporating other potential prognostic variables identified three significant variables influencing the risk of relapse--methotrexate clearance and white-blood-cell count and haemoglobin level at diagnosis (p = 0.0015). This study has demonstrated the potential clinical importance of the rate of drug clearance in children with ALL.

Bone Marrow Examination↗

PubMed1984

Identification and characterization of a human thymus-leukemia antigen (43-kDa/513TL) bearing a structural relationship to HLA.

A human thymus-leukemia-like antigen has been identified that is antigenically distinct from T6/HTA-1. This was accomplished with a rabbit antiserum (513) which was prepared against lymphoblasts that were E rosette negative (E-), human thymus antigen positive (HuTA+), cALLA-, DR-, SmIg- from a patient who presented with a mediastinal mass and a WBC count of 130 X 10(9) cells/1. Following absorption with B cell and "null" cell lines, 513 exhibited prominent reactivity with a membrane antigen that was present on normal thymocytes and lymphoblasts from 11 of 13 patients with T cell ALL and 1 of 16 patients with common ALL, but was not detected on normal peripheral blood lymphocytes, normal bone marrow cells and leukemic lymphoblasts with an undifferentiated phenotype. SDS-PAGE analysis of this antigen indicated that it was composed of two subunits, 43-kDa and 12-kDa. Sequential absorption experiments revealed that: (1) the 12-kDa subunit was antigenically similar to beta 2 microglobulin; (2) the intact molecule did not exhibit HLA-A, B or C "framework" determinants; (3) the molecule was antigenically distinct from a human thymus-leukemia antigen HTA-1 (recognized by monoclonal antibodies NA1/34 and OKT6); and (4) the molecule was antigenically distinct from adenosine deaminase. It is concluded that 513 reacts with a membrane protein (designated 513TL) which exhibits properties characteristic of a histocompatibility-like antigen whose expression is restricted to thymocytes and some leukemias (TL antigen). Its antigenic distinction from another recently characterized human TL antigen, HTA-1, suggests polymorphism among this family of alloantigens.

Adenosine Deaminase↗

PubMed1984

Evidence for clonal evolution in pre-B-cell leukaemia.

This case study provides evidence for clonal evolution in pre-B-cell leukaemia. At diagnosis, the lymphoblasts from a 3-year-old boy were morphologically subtyped as L1 (French-American-British classification). Their immunophenotype was CALLA+, CIgM+, SIg-, TdT+, and the karyotype was pseudodiploid with a 1;19 translocation. Striking shifts were apparent when the child relapsed 16 months later. The morphologic subtype had changed to L3, CALLA and TdT had disappeared, and a consistent karyotype was lacking. The modal chromosome number had increased through clonal evolution to 85, the 1;19 translocation was retained, and a new marker, a 14q+ (partial duplication) appeared and was present in a majority of cells. These cytogenetic findings are characteristic of a transforming state. However, despite the loss of TdT, the appearance of classic L3 morphology and the acquisition of a 14q+ marker, the cells retained a predominantly pre-B phenotype.

Antigens, Neoplasm↗

PubMed1984

Failure of late intensification therapy to improve a poor result in childhood lymphoblastic leukemia.

This clinical study, begun in 1975, tested the efficacy of early and delayed intensification treatments in children with acute lymphoblastic leukemia. Regardless of presenting features, all patients received 4 weeks of conventional induction therapy with daily prednisone and weekly vincristine and daunorubicin. One-third were randomized to receive, in addition, two doses of asparaginase during induction therapy, while another one-third received four doses of both asparaginase and cytarabine after remission induction. Preventive central nervous system therapy uniformly included 2400 rads cranial irradiation and five doses of intrathecal methotrexate. Remissions were maintained with daily p.o. mercaptopurine and weekly i.v. methotrexate. Of the 277 assessable patients, 254 (92%) entered complete remission, and 102 (37%) remain clinically free of leukemia for 4.6 to 8.0 years (median, 6.3 years). The three treatment groups showed no significant differences in either remission induction rate or outcome, even when the analysis was based on risk assignment. A "late intensification" phase of therapy, added to the maintenance protocol for 65 patients who had been in continuous complete remission for 14 to 30 months, failed to extend remission durations, as judged from statistical comparison with matched controls (p = 0.84). When tested as a time-dependent covariate in the Cox proportional-hazards model, delayed intensification again showed no important effect on duration of complete remission. We conclude that limited early or aggressive late intensification of therapy, as described here, does not improve outcome in childhood acute lymphoblastic leukemia.

Adolescent↗

PubMed1983

Sequential changes in platelet function and coagulation in leukemic children treated with L-asparaginase, prednisone, and vincristine.

Coagulation and platelet function in 13 children with acute lymphoblastic leukemia were studied sequentially during a remission induction with L-asparaginase, prednisone, and vincristine. In the first weeks of therapy, which included four doses of L-asparaginase coagulation was characterized by significant decreases in plasma concentrations of plasminogen, antithrombin III alpha 2-macroglobulin, and fibrinogen. All measures gradually returned to normal after complication of L-asparaginase therapy. In the latter part of induction treatment, clotting times, especially partial Thromboplastin time, decreased significantly, while levels of factors V and VIII increased with recovery of platelet counts. At this time, 6 patients had an increased in vitro platelet aggregation response to adenosine diphosphate, and their partial thromboplastin times were significantly shorter than those of patients without increased aggregation. Concurrent abnormalities in coagulation and platelet function may account for the thrombotic complications that develop in some children receiving induction therapy with these agents.

Acute Disease↗