Childhood T-cell acute lymphoblastic leukemia: the Dana-Farber Cancer Institute acute lymphoblastic leukemia consortium experience.

PURPOSE: T-cell acute lymphoblastic leukemia (T-ALL) accounts for 10% to 15% of newly diagnosed cases of childhood acute lymphoblastic leukemia (ALL). Historically, T-ALL patients have had a worse prognosis than other ALL patients. PATIENTS AND METHODS: We reviewed the outcomes of 125 patients with T-ALL treated on Dana-Farber Cancer Institute (DFCI) ALL Consortium trials between 1981 and 1995. Therapy included four- or five-agent remission induction; consolidation therapy with doxorubicin, vincristine, corticosteroid, mercaptopurine, and weekly high-dose asparaginase; and cranial radiation. T-ALL patients were treated the same as high-risk B-progenitor ALL patients. Fifteen patients with T-cell lymphoblastic lymphoma were also treated with the same high-risk regimen between 1981 and 2000. RESULTS: The 5-year event-free survival (EFS) rate for T-ALL patients was 75% +/- 4%. Fourteen of 15 patients with T-cell lymphoblastic lymphoma were long-term survivors. There was no significant difference in EFS comparing patients with T-ALL and B-progenitor ALL (P =.56), although T-ALL patients had significantly higher rates of induction failure (P <.0001), and central nervous system (CNS) relapse (P =.02). The median time to relapse in T-ALL patients was 1.2 years versus 2.5 years in B-progenitor ALL patients (P =.001). There were no pretreatment characteristics associated with worse prognosis in patients with T-ALL. CONCLUSION: T-ALL patients fared as well as B-progenitor patients on DFCI ALL Consortium protocols. Patients with T-ALL remain at increased risk for induction failure, early relapse, and isolated CNS relapse. Future studies should focus on the identification of and treatment for T-ALL patients at high risk for treatment failure.     

Anti-GD3 monoclonal antibody analysis of childhood T-cell acute lymphoblastic leukemia: detection of a target antigen for antibody-mediated cytolysis

We have demonstrated in previous studies significant quantitative differences in the ganglioside content of leukemia cell membranes within immunological subclasses of acute lymphoblastic leukemia (ALL): The disialoganglioside GD3 (disialolactosylceramide) is increased in lymphoblasts with a T-cell immunophenotype compared to non-T-ALL blasts. Utilizing an indirect immunofluorescence assays with a monoclonal antibody to GD3(R24), pretreatment leukemic lymphoblasts from 80 children with ALL were assayed for GD3 expression. GD3 was observed in 75% of leukemic samples in which lymphoblasts exhibited a T-cell phenotype, whereas none of the 33 non-T-ALL samples tested exhibited GD3. Correlation between the expression of GD3 and various antigenic determinants of T-cell differentiation was restricted to CD2; 75% of CD2-negative T-cell ALL blasts failed to express GD3. Anti-GD3 immunoreactivity to T-ALL samples was not restricted to R24 in that two other monoclonal anti-GD3 antibodies were similarly reactive to T-ALL blasts. In vitro incubation of T-cell lymphoblasts with the anti-GD3 antibodies, R24 and C281 and human serum resulted in significant cytotoxicity, and R24 also mediated antibody-dependent cellular cytotoxicity by normal effector cells. Cytotoxicity was specific for those T-ALL blast cell populations which reacted with anti-GD3 as assessed by immunofluorescence microscopy. Since immunoreactivity with monoclonal antibody to GD3 was exclusively observed in a large population of immunophenotypically defined T-cell leukemic lymphoblasts, these studies suggest a possible immunodiagnostic and immunotherapeutic potential for anti-GD3 monoclonal antibodies in T-cell lymphoblastic malignancies.     

成人急性淋巴细胞白血病免疫表型特点分析

目的研究成人急性淋巴细胞白血病(ALL)患者中不同亚型的各种白血病细胞免疫表型分布特点。方法采用当前国际通用的四色流式细胞术图像分析系统检测并综合分析76例ALL患者的免疫表型及其发生规律与特点。结果①76例ALL免疫表型系列来源可分为三种不同亚型,其中T-ALL亚型5例(占6.57%)、B-ALL亚型68例(89.48%)、T和B细胞混合型(T/B-ALL)亚型3例(3.95%)②ALL早期抗原表达特点:在B-ALL亚型中CD38、CD34、HLA-DR呈高表达;在T-ALL亚型中,CD38和CD34呈高表达,但HLA-DR不表达;在T/B-ALL亚型中,HLA-DR表达,CD34和CD38不表达。③按免疫分型相关抗原的敏感性和特异性分析:在B-ALL中,特异性抗原cCD79a占91.18%,敏感性抗原CD19表达占97.06%;在T-ALL中,特异性抗原cCD3和敏感性抗原CD7均表达为100%;在T/B混合型ALL中,cCD3、cCD79a、CD19均表达,CD7表达2例;④伴髓系抗原交叉表达分析:在B-ALL中,伴髓系抗原表达占21例(30.88%);在T-ALL中,伴髓系抗原表达1例(20%);T/...     

Subpopulations of human T lymphocytes. VI. Analysis of cell markers in acute lymphoblastic leukemia with special reference to Fc receptor expression on E-rosette-forming blasts

A variety of surface markers, terminal deoxynucleotidyl transferase (TdT) activity, morphologic appearance, and cytochemical composition were studied in a group of 16 patients (13 children, 3 adults) with acute lymphoblastic leukemia (ALL). In 9 children, no surface markers were detected on lymphoblasts (null-type ALL). Leukemic blasts of 4 children formed E-rosettes. These E-rosette-forming blasts from 3 adult patients with ALL, were studied for the presence of Fc receptors. Of the leukemic blasts from these 7 patients, 2--76% expressed receptors for IgG Fc. Only 3 of 7 patients showed 9--42% receptors for IgM Fc. In addition, complement receptors were investigated in 6 of those 7 patients with T-cell ALL. Complement receptors were detected on 9--70% of the E rosette forming blasts from all 6 patients. TdT activity was elevated in T-cell ALL and in children with null-type ALL. The heterogeneity of Fc receptor expression on leukemic blasts in these patients demonstrates a malignant proliferation of T cells in different stages of differentiation or maturation. This observation might be helpful in subclassifying T-cell leukemias with regard to prognosis and the response to therapy.     

Immunological subtypes of childhood T-cell acute lymphoblastic leukemia and their prognostic significance

The data on examination and treatment of 39 children with T-cell acute lymphoblastic leukemia (T-ALL) were assessed; all patients received ALL BFM-90-M treatment. The fraction of children with T-ALL among ALL patients in Belarus was 12.2% (pre-T-ALL--15, cortical T-ALL--46 and mature T-ALL--23%). Also, a subtype of T-ALL with atypical expression of markers was identified (13%). Overall 7-year survival in T-ALL patients was 47(20%). The worst prognosis was recorded in the T-ALL subgroup with atypical expression of markers (p < 0.001 as compared with the other subgroups). As for outcome--from best to worst, T-ALL subtypes ranged as follows: cortical T-ALL, mature T-ALL, pre-T-ALL and T-ALL with atypical expression of markers.     

Unfavorable presenting clinical and laboratory features are associated with CALLA-negative non-T, non-B lymphoblastic leukemia in children

Twenty-four (5.7%) of 424 children with newly diagnosed acute lymphoblastic leukemia (ALL) were found to have blast cells that expressed HLA-DR antigens but not the common ALL antigen (CALLA), E-rosette receptors, T-cell antigens, or cytoplasmic or surface immunoglobulins. Each of the eight cases tested expressed the B-cell associated antigen B4, but not B1 or B2 antigen. Myeloid-associated antigens were not present in any of the 10 cases tested. By comparison with common (CALLA+ B-cell precursor) ALL, patients having this immunophenotype were more likely to be children less than 2 yr of age (p less than 0.001), to have higher initial leukocyte counts (p less than 0.001), and to have blast cells with a DNA index less than 1.16 (p = 0.05), a pseudodiploid karyotype (p = 0.01) and a chromosomal translocation (p = 0.003). The presence of any chromosomal translocation in these CALLA- ALL was related to measures of increased leukemic cell burden including higher leukocyte counts, larger liver and spleen sizes and higher serum lactic dehydrogenase levels. While the patients were entered into several treatment arms of two protocols, the CALLA- cases appeared to have lower remission rate (p = 0.06) and shorter event-free survival time (p = 0.05) than did those with common ALL. The association with clinical and laboratory features of known adverse prognostic significance provides some explanation for the poor treatment outcome of CALLA- ALL.     

Prognostic significance of CD34 expression in childhood B-precursor acute lymphocytic leukemia: a Pediatric Oncology Group study.

We studied the blasts from 795 children greater than 1 year of age with newly diagnosed, untreated B-precursor acute lymphoblastic leukemia (ALL) for expression of the hematopoietic stem cell-associated antigen CD34. All cases were confirmed as B-lineage lymphoblastic leukemia by virtue of expression of CD19 and/or CD22, lack of T-cell antigens, and lack of surface-membrane immunoglobulin (Ig). The CD34 antigen was present in at least 10% of blast cells in 587 (73.8%) of the patients. There was no significant difference in presenting clinical characteristics between CD34+ and CD34- patients save for an increased incidence of CNS involvement at diagnosis in the latter. Patients with CD34+ leukemia were more likely to have blasts expressing CD22, CD9, and CD13 antigens but were less likely to coexpress CD20. Patients with pre-B (cytoplasmic mu) ALL were significantly more likely to lack CD34 on their blasts, while children with hyperdiploid ALL were more likely to be CD34+. Although remission induction rates were not significantly different between patients with CD34+ and CD34-ALL (P = .23), event-free survival was shorter for patients with CD34- leukemia (P = .0014). Even though CD34 expression was associated with certain other known prognostically favorable variables including hyperdiploidy and lack of cytoplasmic Ig, it had an independent favorable effect on treatment outcome, even after adjusting for competing prognostic factors.     

Granulocyte-Colony Stimulating Factor, Granulocyte-Macrophage Colony Stimulating Factor, PIXY-321, Stem Cell Factor, Interleukin-3, and Interleukin-7: Receptor Binding and Effects on Clonogenic Proliferation in Acute Lymphoblastic Leukemia

Cytokines are frequently used after chemotherapy of leukemias and solid tumors to augment recovery of normal hematopoiesis. While the regulation of normal and leukemic myelopoiesis is well investigated, little is known about effects of cytokines on growth and differentiation of lymphoblastic leukemia. In this study, we investigated the expression of receptors for G-CSF, GM-CSF, SCF, IL-3, and IL-7 on acute lymphoblastic leukemia (ALL) blasts and the effects of these growth factors (GF) on ALL blast colony formation. The binding of fluorescence-tagged cytokines to receptors on ALL blasts was studied by flow-cytometry in 27 cases of ALL (24 precursor B-ALL, 3 T-ALL). Receptor-binding for myeloid-associated GF was observed in the majority of precursor B-ALL (G-CSF = 100%, GM-CSF = 65%, IL-3 = 83%, SCF = 74%), but not in T-ALL. Binding of labelled IL-7 was detected in both precursor B- (92%) and T-ALL (100%). The presence of receptors for SCF in ALL was confirmed by polymerase chain reaction for c-kit mRNA in 19/21 cases tested. Expression of receptors for G-CSF, GM-CSF, IL-3, and SCF was not associated with expression of myeloid antigens, or with specific cytogenetic abnormalities. The effects of these GF on clonogenic cells were tested in the ALL blast colony assay and varied between samples, but all cytokines were able to increase clonogenic growth. The GM-CSF/IL-3 fusion molecule PIXY-321 was most effective in promoting colony growth. In some cases inhibition of colony formation was found. We conclude that ALL blast cells have receptors not only for IL-7, but also for G-CSF, GM-CSF, SCF, and IL-3. ALL precursors can respond to these GF with changes in their clonogenic growth indicating the presence of functional receptors. Results may have implications, for therapeutic approaches combining cytokines and chemotherapy.     

Prognostic impact of CD45 antigen expression in high-risk, childhood B-cell precursor acute lymphoblastic leukemia.

To evaluate the clinical implications of CD45 expression in acute childhood lymphoblastic leukemia (ALL), we measured the CD45 expression of blast cells from 133 untreated patients with childhood B-precursor ALL (n = 118) or T-ALL (n = 15). CD45 expression (> or = 20%) was detected in all 15 cases (100%) of T-ALL, and 101 cases (86%) of B-precursor ALL. In 122 cases, the fluorescence intensity of the CD45 expression was measured as a relative value; the ratio of average linear values (RALV) of CD45 on the blasts to that on CD3-positive T-lymphocytes from the same specimen. The expression was more intense in the T-ALL cases than in the B-precursor ALL cases (RALV, mean +/- SE: T-ALL 0.230 +/- 0.04 vs. pro-B ALL 0.150 +/- 0.012/pre-B ALL 0.153 +/- 0.019, p < 0.05). However, the intensity of the CD10, CD19, CD20 and CD34 antigen immunoreactivity did not correlate with the CD45 expression. Patients with hyperdiploidy (chromosome number > 50) showed significantly lower levels of CD45 expression than patients with t(1;19) or normal karyotypes (RALV, mean +/- SE: 0.081 +/- 0.022 vs. 0.133 +/- 0.03/0.143 +/- 0.019, p < 0.05). Other clinical features such as age, gender and WBC count did not correlate with CD45 expression. The prognostic implications of CD45 expression were studied in non-high-risk (low-risk + intermediate-risk) (n = 60) and high-risk patients (n = 52) with B-precursor ALL who had been treated with the risk-directed protocol of ALL-941 trial. Although CD45 expression did not correlate with the event-free survival (EFS) of the non-high-risk patients, there was a significant correlation between the expression levels and the EFS of the high-risk patients: the 3-year EFS rate of the CD45low group (n = 26, RALV = 0.017-0.132) was 88 +/- 7% versus the CD45high group (n = 26, RALV = 0.133-0.450) at 34 +/- 24% (p < 0.05). These results show that the levels of expression of the CD45 antigen on leukemic lymphoblasts are significantly correlated with the clinical features and prognosis of childhood ALL.     

T-cell acute lymphoblastic leukemia in Israel: clinical and laboratory features

T-cell acute lymphoblastic leukemia (ALL) comprises a third of the cases of childhood ALL in Israel. This high proportion of T-ALL is most probably due to a deficiency in pre-B/common ALL. The T-ALL patients had significantly worse 4-yr survival compared to standard risk or non-T high risk patients. In view of these special epidemiologic and clinical features a study of the immunophenotype of all consecutive cases of T-ALL and T-non Hodgkin's lymphoma (NHL) observed in our medical center was performed. Twenty-eight ALL and 3 NHL patients were studied and their cells characterized using a panel of monoclonal antibodies, TdT reactivity and E-rosette formation. Assays of the activities of adenosine deaminase (ADA) and purine nucleoside phosphorylase (NP) were also performed. Based on the surface antigen expression, the tumor cells could be classified into one of the three known developmental stages of T cells. It was found that the immunophenotype of the T-ALL cases in Israel was similar to that observed in other countries. Considerable heterogeneity of surface antigen expression was found and in a number of cases the phenotype analysis was not easily reconciled with models of T-cell ontogeny. The activities of ADA and NP were correlated with the developmental stage, as defined by the surface antigenic expression. Contrary to observations on normal T-cells, where ADA activity decreases and NP activity increases as T-cells mature and differentiate, this was not found in the malignant T cells. These findings as well as the existence of atypical immunophenotypes suggest that the leukemic T cell has an abnormal gene expression.     

Expression of GD3 ganglioside in childhood T-cell lymphoblastic malignancies

Lymphoblasts from seven children with T-cell lymphoblastic malignancies and three children with non-T, non-B acute lymphoblastic leukemia (ALL) were analyzed for ganglioside content. Nonmalignant T-cells from thymus served as controls. Both ganglioside and glycoprotein sialic acid were increased approximately 3-3.5-fold in T-cell disease compared to thymic tissue when expressed on a per cell basis, but not on a per milligram protein basis. Thin-layer chromatography of the isolated ganglioside fraction from T-cell lymphoblasts revealed two major resorcinol-positive bands. One ganglioside comigrated with II3-alpha-N-acetylneuraminosyllactosylceramide (GM3), the major ganglioside in normal lymphoid tissue, and the other ganglioside comigrated with authentic II3-alpha-N-acetylneuraminosyl-alpha 2----8-N-acetylneuraminosyllactosylceramide (GD3) in three different solvent systems. Neuraminidase treatment of the latter ganglioside yielded GM3 and lactosyl ceramide, hydrolysis products of GD3. Scanning densitometry revealed that whereas thymus cells contained 97% GM3 and 3% GD3, T-cell lymphoblasts contained from 22 to 86% GD3 and a corresponding decrease in GM3. The shift to increased GD3 was observed in the blasts from all seven T-cell patients, but not in the blasts from the non-T, non-B patients studied. Only trace quantities of GD3 were detected from two continuous T-ALL cell lines, HSB2 and RPMI 8402. The results demonstrate a consistently significant increase in ganglioside GD3 in uncultured, patient-derived T-cell ALL lymphoblasts when compared to non-T-cell ALL and normal lymphoid tissue. Therefore, GD3 may represent a tumor-associated antigen for the T-cell subclass of childhood lymphoblastic malignancy.     

Classification,subtype discovery,and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling

Treatment of pediatric acute lymphoblastic leukemia (ALL) is based on the concept of tailoring the intensity of therapy to a patient's risk of relapse. To determine whether gene expression profiling could enhance risk assignment, we used oligonucleotide microarrays to analyze the pattern of genes expressed in leukemic blasts from 360 pediatric ALL patients. Distinct expression profiles identified each of the prognostically important leukemia subtypes, including T-ALL, E2A-PBX1, BCR-ABL, TEL-AML1, MLL rearrangement, and hyperdiploid >50 chromosomes. In addition, another ALL subgroup was identified based on its unique expression profile. Examination of the genes comprising the expression signatures provided important insights into the biology of these leukemia subgroups. Further, within some genetic subgroups, expression profiles identified those patients that would eventually fail therapy. Thus, the single platform of expression profiling should enhance the accurate risk stratification of pediatric ALL patients.     

Efficient formation of cytosine arabinoside-5'-triphosphate in leukemic blasts of human T-cell acute lymphoblastic leukemia

The potential usefulness of cytosine arabinoside (ara-C) in the treatment of T-cell acute lymphoblastic leukemia (T-ALL) was studied by measuring the influx of ara-C into the lymphoblasts and the conversion of ara-C to its triphosphate form (ara-CTP) in lymphoblasts from the bone marrow of eighteen patients of T-ALL. Intracellular accumulation of ara-CTP was 3.5 times greater in T-cell lymphoblasts than in non-T or AML blasts. The increased formation of ara-CTP in T-ALL cell may be correlated with the good clinical response of T-ALL patients to the treatment with ara-C in combination with mitoxantrone.     

Biologic and cytogenetic characteristics of leukemia in infants

Clinical features, leukemic cell characterization, chromosomal findings, and treatment outcome were analyzed in a retrospective study of 30 cases with acute leukemia of infancy, 24 infants with acute lymphoblastic leukemia (ALL), and six cases with acute nonlymphoblastic leukemia (ANLL). Extensive bulky disease with organomegaly, central nervous system (CNS), and skin involvement were prominent features at diagnosis with a higher frequency in ANLL as compared to ALL. Four of six ANLL patients were classified as monocytic or myelomonocytic. In the ALL group nine of 24 (36%) were non-L1 morphology and six of 17 (33%) were common ALL antigen (CALLA) negative, the majority of them (five of six) were included in the non-L1 group. Immunophenotyping revealed four cases with early B-cell (three patients: Ia+B4+, and one patient: Ia+) and two cases with T-cell. Mixed lineage leukemia was found in five infants. Heavy chain immunoglobulin gene rearrangement was present in six cases tested, two CALLA+, two with Ia+B4+, and two were undifferentiated mixed lineage leukemia. Chromosomal aberrations were detected in ten of 18 patients, mostly in ANLL and CALLA negative ALL. Translocations were detected in six patients, involving 4q21-23 and 11q23 in three and two cases, respectively. The probability of five-year DFS were 27% for the whole group. The worst prognosis was observed in infants younger than 6 months of age, in whom the leukemia cell characteristics was compatible with stem cell: ANLL, very early pre-B, or undifferentiated mixed type. The chromosomal aberrations found in all cases included translocation with the seemingly nonrandom breakpoints at 4q21 and 11q23, and breakpoints that corresponded to known fragile sites. This finding may be suggestive of an underlying genetic predisposition associated with the poor prognosis of leukemia of infancy.     

Immunoreactivity of leukemic lymphoblasts of T-cell and B-cell precursor origin with monoclonal anti-GD3 and anti-GM3 antibodies.

The glycosphingolipids GD3, GM3, and alpha 2, 3-sialosylparagloboside (SPG) are major gangliosides of lymphoid leukemia cells. The reactivity of two monoclonal anti-ganglioside antibodies, an anti-GD3 (R24) and an antibody cross-reactive to GM3 and SPG (M2590), to blasts of patients with T-cell acute lymphoblastic leukemia (ALL) and B-cell precursor ALL (pre-B-ALL), were compared using indirect immunofluorescence and flow cytometry. Results from 23 patients with T-ALL and eight with pre-B-ALL yielded four subclasses of T-ALL and two subclasses of pre-B-ALL. Blasts from most of the patients with T-ALL were R24+M2590- whereas most of the patients with pre-B-ALL were R24-M2590-. Seven of 23 patients with T-ALL had ganglioside immunophenotypes similar to that of pre-B-ALL, i.e. R24-M2590- or R24-M2590+. These subclasses could not be further characterized by additional cell surface immunophenotypic markers or by gene (immunoglobulin and T-cell receptor) rearrangement analysis. The ratio R24/M2590 was less than 1.0 in all patients with pre-B-ALL, and was greater than 1.0 in all patients with T-ALL who were R24 positive, but was not useful in characterizing the double negative T-ALL subclass. To assess whether cryptogenicity of gangliosides due to cell surface protein could account for the low binding of either R24 or M2590, blasts were treated with trypsin before antibody analysis. Whereas the binding of R24 was unchanged after trypsin treatment, binding of M2590 was increased in a number of samples, particularly in those samples which were originally M2590-positive. The results show that comparative staining of T-ALL and pre-B-ALL cells with both anti-GD3 and anti-GM3/SPG antibodies results in a further subclassification of ALL and provides a quantitative assessment of the expression of tumor-associated gangliosides on the blasts of this disease.     

Heterogeneity of non-T,non-B acute lymphocytic leukemia defined by the quantitative expression of Ia and common all antigens

The Ia antigens and the common acute lymphoblastic leukemia antigens (CALLA) accessible on the cell surface were quantitated in newly diagnosed patients with non-T, non-B ALL using monoclonal antibodies and a cellular radioimmunoassay. The levels of both antigens expressed in molecules of RAM-Fc bound per cell exhibited a wide range of variation amongst patients. Ia levels, measured with monoclonal antibody 21w4 which recognizes a monomorphic epitope of human Ia molecules, were between 5.0 × 10⁴ and 87 × 10⁴ molecules per cell in 37 patients. CALLA levels measured with BA-3 or J-5 antibody varied from 3.4 × 10⁴ to 22 × 10⁴ molecules per cell in 13 patients.In $\text{12}\text{13}$ cases for which Ia and CALLA were quantitated simultaneously, the amount of Ia was found to be higher than that of CALLA. A positive correlation (p < 0.02) between the levels of these two antigens was observed suggesting that ALL cells with the highest levels of Ia also had the highest levels of CALLA. In addition, our results suggest a possible correlation (0.05 < p < 0.1) between the amount of Ia expressed on the leukemic cells and the white blood cell count of the patient at the time of diagnosis.The data indicate that non-T, non-B ALL are heterogenous with respect to their expression of Ia and CALLA antigens. A longitudinal study of non-T, non-B ALL patients will allow us to assess if the levels of Ia and CALLA at diagnosis are correlated with prognosis of the disease in these patients.     

Differential miRNA expression in childhood acute lymphoblastic leukemia and association with clinical and biological features

The present study aimed to analyze the expression profile of the microRNAs previously described as associated with childhood ALL, miR-92a, miR-100, miR-125a-5p, miR-128a, miR-181b, miR-196b and let-7e, and their association with biological/prognostic features in 128 consecutive samples of childhood acute lymphoblastic leukemia (ALL) by quantitative real-time PCR. A significant association was observed between higher expression levels of miR-196b and T-ALL, miR-100 and patients with low white blood cell count at diagnosis and t(12;21) positive ALL. These findings suggest a potential activity of these microRNAs in pediatric ALL biology.     

Prognostic implication of ecto-5'-nucleotidase activity in acute lymphoblastic leukemia

Ecto-5'-nucleotidase (5'-N) activity was determined in 191 patients (71 children and 120 adults) with acute leukemia. Elevated values for 5'-N were registered in common acute lymphoblastic leukemia (ALL), but blast cells of T-cell ALL (T-ALL) and common ALL antigen-negative non-T-ALL had low enzyme activity comparable with the values of acute non-lymphocytic leukemia. Dependence of remission duration on 5'-N activity was analyzed in 74 adults with ALL, treated similarly in a prospective multicenter trial. The remission curves for ALL patients with 5'-N activity lower than 10 nmol/h x 10(6) cells were substantially and significantly better than those of patients with high activity (greater than 10 nmol/h x 10(6) cells). This difference was also evident in the immunologic subclass common ALL. Statistical evaluation showed that an interaction between immunologic subtype of the blast cells and their 5'-N activity had prognostic significance for remission duration. In addition to the independent factor, initial age, this interaction was also prognostic for survival.     

Cytological and immunological study of 139 patients with acute leukemia

Sixty-six children with acute lymphatic leukemia (ALL), 26 adults with ALL and 47 adults with acute myeloid leukemia (AML) were subclassified according to the classifications French-American-British (FAB) and World-Health-Organization (WHO). Nine immunological markers and 6 cytochemical stains were also used. The reproducibility of the WHO classification of the smears performed independently twice by one observer was 93%, but that between two observers only 78%. Three patients considered ALL by A were called AML by B, but all three had the common acute leukemia antigen, CALLA. In the group of 87 patients considered ALL by B, only 74 were classified ALL by A, but of the 13 non-ALL B, none had the CALLA. Ten of these thirteen patients had myeloid markers such as Philadelphia chromosomes, peroxidase or Sudan Black B positive reactions, or Fc and C3 receptors. The remaining 3 patients were non-Hodgkin lymphoma with B-cell markers. None of the 47 cases classified as AML had CALLA. Seventeen of nineteen myeloblastic leukemias (M2, FAB) had a myeloid antigen (Mag) and 13 of 15 myelomonocytic leukemias (M4, FAB) had, in addition, Fc and C3 receptors.     

Immunodiagnosis of childhood ALL with monoclonal antibodies to myeloid and lymphoid associated antigens

Sixty-five cryopreserved leukemic samples from children diagnosed and treated as having acute lymphocytic leukemia (ALL) were retrospectively examined for the presence of lymphoid and myeloid associated antigens by indirect immunofluorescence using monoclonal antibodies. Expectedly, the majority of these specimens expressed antigens known to be expressed on lymphoid, and not myeloid malignancies. These included the common acute lymphoblastic leukemia antigen (CALLA), the p32 B-cell associated antigen, and T-cell associated antigens. Leukemic cells from the 8 remaining patients expressed antigens known to be present on both myeloid and lymphoid leukemias. These included HLA/DR, and the antigens identified by BA-1 and BA-2. Cells from 2 of these 8 patients reacted with antibodies that define antigens present on normal and malignant myeloid cells. Both specimens reacted with 1G10, an anti-granulocyte antibody, and one reacted with 5F1 which reacts with monocytes, nucleated red blood cells, megakaryocytes and platelets. One of these patients relapsed while receiving ALL therapy, and the morphology of her leukemic cells became characteristic of acute monocytic leukemia (AMoL). The second patient failed ALL therapy but responded to standard acute nonlymphocytic leukemia (ANLL) therapy, clearing her peripheral blasts. Thus these studies confirm that cell surface phenotyping with monoclonal antibodies can recognize ALL cells that express myeloid rather than lymphoid associated antigens and demonstrate that the malignant cells display a clinical behavior consistent with the diagnosis of ANLL.