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S Stass

Publications and source records attributed to S Stass.

35 records · Page 2Linked to original sources
PubMed1986

Chromosomal translocations play a unique role in influencing prognosis in childhood acute lymphoblastic leukemia.

Certain types of chromosomal abnormalities have been shown to exert strong independent influence on treatment outcome in acute lymphoblastic leukemia (ALL). To identify the changes most closely associated with prognosis, we analyzed the completely banded blast cell karyotypes of 161 children with this disease. One hundred twenty-five cases had one or more chromosomal abnormalities, with 45 showing translocations. The frequency of translocations was highest (58%) among patients with pseudodiploid karyotypes and lowest (0%) in the hyperdiploid group defined by 51 or more chromosomes. During the maximum 6-year follow-up period, 30 of the 45 patients with a translocation failed therapy, compared with only 27 of the 116 who lacked this feature. Life-table estimates of event-free survival indicate that only 14% of the translocation group will be in complete remission at 3 years. The percentages of failures associated with random and nonrandom translocations were virtually identical (68% v 65%). When entered in a Cox proportional hazards model with seven other types of chromosomal abnormalities, and then with 11 clinical and laboratory variables of known prognostic value in ALL, translocation emerged as the strongest single predictor of treatment outcome (P less than 0.0001). The model indicated that translocation increases the risk of treatment failure six times by comparison with the absence of this feature. These findings offer an explanation for the majority of early treatment failures in childhood ALL, including those previously attributed to ploidy classification.

Child↗
PubMed1985

Bone marrow necrosis in children with malignant disease.

The authors reviewed the case records of 1419 children with acute leukemia and other types of malignant disease involving the bone marrow to define the clinical and laboratory features associated with marrow necrosis as well as the prognostic significance of this complication. Only seven patients were found to have this abnormality: four with newly diagnosed acute lymphoblastic leukemia (ALL), one with relapsed ALL, and two with disseminated neuroblastoma. All patients presented with severe bone pain, bone tenderness, and fever. Levels of serum lactic dehydrogenase were uniformly increased, being especially high in patients with ALL. There was no evidence of severe infection or disseminated intravascular coagulation, complications that have been causally related to marrow necrosis. Four of the five children with ALL remain in complete remission for 10+ to 48+ months. Both patients with neuroblastoma are off therapy, in remission, for 9+ to 15+ months. In contrast to earlier reports, bone marrow necrosis does not appear to confer a poor prognosis in children with malignancy.

Bone Marrow↗
PubMed1985

The E rosette-associated antigen of T cells can be identified on blasts from patients with acute myeloblastic leukemia.

Monoclonal antibody T-11, considered specific for the sheep erythrocyte rosette-associated antigen of T cells, reacted with leukemic blasts from four of 23 patients with morphologic and cytochemical criteria for acute myeloblastic leukemia (AML). Although 83%, 87%, 88%, and 96% of the blasts from these patients reacted with T-11, only one patient demonstrated a small percentage of heat-stable E rosettes (5%). Antibody 9.6, which also reacts with the E rosette-associated antigen, was tested on blasts from two of the T-11-positive patients and was also strongly reactive (96% and 98%). Dual staining of blasts from these two patients demonstrated a small number of cells that simultaneously expressed the E rosette-associated antigen and myeloid-associated cytochemistries (myeloperoxidase [MPO] and Sudan black B). Additionally, leukemic blasts were identified that simultaneously expressed the E rosette-associated antigen and contained Auer rods. Antibody OKT-11 immunoprecipitated a 48,100-dalton glycoprotein from these leukemic blasts that is similar in molecular weight to that previously determined for the T cell surface protein (Tp50), thus providing strong evidence that this molecule can be found in some cases of AML. Because cells simultaneously expressing both the E rosette-associated antigen and MPO were identified, it would appear likely that leukemic blasts with only the E rosette-associated antigen or only MPO arose from the same progenitor. Our findings further demonstrate that the epitopes identified by antibodies OKT-11, T-11, and 9.6 are not always associated with, or sufficient for, 37 degrees C E rosette formation and can be found on blasts from patients with AML.

Antibodies, Monoclonal↗
PubMed1985

Rearrangement of immunoglobulin heavy chain genes in T cell acute lymphoblastic leukemia.

We studied the arrangement of the immunoglobulin heavy chain genes by Southern blot analysis of DNA freshly obtained from marrow blast cells of 14 children with T cell acute lymphoblastic leukemia (T-ALL) using probes to the C mu and JH gene segments: At least one of the C mu-gene alleles was rearranged in three cases. In two of these, one C mu gene had the germ-line configuration and one was rearranged, whereas both alleles were rearranged in the third case. In one case, a rearranged heavy chain gene hybridized to the C mu-region probe, but not to the JH probe, indicating that the entire JH region had been deleted. These results demonstrate that immunoglobulin heavy chain gene rearrangements are not restricted to B lineage lymphoproliferative diseases in humans.

Adolescent↗
PubMed1985

Acute megakaryoblastic leukemia. Blast cell aggregates simulating metastatic tumor.

Acute megakaryoblastic leukemia is a rare leukemia that can present diagnostic problems. We describe two children who have this disease and had clumps of blast cells in their bone marrow, a finding usually attributed to metastatic tumor. The megakaryocytic origin of the cells was supported by their cytochemical staining pattern (positive alpha-naphthyl acetate esterase resistant to sodium fluoride inhibition and negative alpha-naphthyl butyrate esterase) and by the presence of factor VIII-related antigen. Ultrastructural studies of blast cells from one patient demonstrated platelet peroxidase. The mechanism of blast cell clump formation in these cases is unknown; nevertheless, awareness that this feature can occur in acute megakaryoblastic leukemia may avoid a misdiagnosis of metastatic solid tumor.

Acute Disease↗
PubMed1985

Acute mixed lineage leukemia: clinicopathologic correlations and prognostic significance.

The frequency and clinical significance of acute leukemia displaying both lymphoid and myeloid characteristics was determined in 123 consecutive children using a panel of lineage-associated markers. The leukemic blasts from 18 of 95 children (19%) with the diagnosis of acute lymphoblastic leukemia (ALL) by standard diagnostic criteria expressed myeloid-associated cell surface antigens. Despite immunological evidence of lymphoid differentiation (17 CALLA + and one T cell-associated antigen +) and findings of immunoglobulin gene rearrangement, blasts from these patients reacted with one to five monoclonal antibodies identifying myeloid-associated cell surface antigens (My-1, MCS.2, Mo1, SJ-D1, or 5F1). Dual staining with microsphere-conjugated antibodies and analysis by flow cytometry confirmed that some blasts were simultaneously expressing lymphoid- and myeloid-associated antigens. Conversely, blasts from seven of 28 patients (25%) with acute nonlymphocytic leukemia (ANLL), diagnosed by otherwise standard morphological and cytochemical criteria, expressed lymphoid-associated surface antigens. Dual staining of individual blasts demonstrated simultaneous expression of myeloperoxidase (MPO) (including Auer rods) in association with either T-11, CALLA, or terminal deoxynucleotidyl transferase. Blasts from one patient with ANLL demonstrated T cell receptor gene rearrangement, while blasts from another patient demonstrated characteristics associated with T (T-11), B (CALLA and heavy-chain immunoglobulin gene rearrangement), and myeloid (MPO) lineage. There were no consistent cytogenetic abnormalities, and no patient demonstrated independent leukemic clones. Each patient with typical ALL, except for myeloid-associated antigens, achieved complete remission with conventional induction therapy for ALL. By contrast, three of the seven children with ANLL whose blasts expressed the T-11 surface antigen failed ANLL induction therapy. These three patients subsequently achieved remission with ALL therapy.

Acute Disease↗
PubMed1984

New chromosomal translocations correlate with specific immunophenotypes of childhood acute lymphoblastic leukemia.

Cytogenetic analysis of leukemic cells obtained at diagnosis from 122 patients with childhood acute lymphoblastic leukemia (ALL) disclosed chromosomal translocations in 36 cases. Two new nonrandom translocations were identified and found to be associated with specific immunophenotypes of the disease. The first, identified in 4 of 16 cases of T-cell ALL positive for sheep erythrocyte receptors (E+), involved the short arm (p) of chromosome 11 and the long arm (q) of chromosome 14 and was designated t(11;14) (p13;q13). The second, found in 7 of 23 cases with a pre-B-cell phenotype, involved the long arm of chromosome 1 and the short arm of chromosome 19; it was designated t(1;19) (q23;p13.3). A third abnormality involving a common breakpoint on chromosome 12 (band p 12) was also identified. These two new differentiation-specific translocations suggest a mechanism for aberrant expression of genes that influence lymphoid cell growth and development, as well as leukemogenesis.

Adolescent↗
PubMed1984

Acute leukaemia with mixed lymphoid and myeloid phenotype.

Three children with acute leukaemia had blasts that expressed both lymphoid and myeloid markers. The blasts met immunological criteria for acute lymphoblastic leukaemia (ALL)--common ALL antigen+, HLA-DR+, terminal deoxynucleotidyl transferase+--but their cytochemical features, including positive myeloperoxidase and Sudan black B, were those of acute nonlymphoblastic leukaemia (ANLL) as defined by the French-American-British Group. 30% of the blasts from one of two patients tested reacted with a monoclonal antibody specific for nonlymphoid cells (MCS-2). The wide overlap in the percentages of blasts expressing lymphoid or myeloid markers indicates that some leukaemic cells in each child had a mixed phenotype. There were no consistent cytogenetic findings, and the Philadelphia chromosome was not present. Complete remission was induced by treatment effective for either ALL (two patients) or ANLL. These three cases appear to represent a rare leukaemia subtype that we have designated acute leukaemia with mixed lymphoid and myeloid phenotype. Its recognition may be important in treatment, since two patients achieved remission with standard therapy for ALL. These cases demonstrate further the phenotypic heterogeneity that may be seen in leukaemic cell differentiation.

Acute Disease↗
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

Heavy chain immunoglobulin gene rearrangement in acute nonlymphocytic leukemia.

Samples of leukemic cell DNA from 14 children with acute nonlymphocytic leukemia (ANLL) and 4 human myeloid leukemia cell lines were analyzed for rearrangement in the heavy chain region of the immunoglobulin gene. The diagnosis of ANLL was confirmed in all patients by morphological, cytochemical, and immunologic studies. By restriction endonuclease digestion and hybridization with cloned heavy chain immunoglobulin gene probes for the constant (Cmu) and joining (JH) regions, the DNA of 2 patients and 1 cell line (ML-1) was found to contain rearrangements. The DNA from the remaining 12 patients and 3 cell lines was not rearranged (germline configuration). Both patients with apparent immunoglobulin gene rearrangement achieved complete remission on therapy for ANLL. Immunoglobulin gene rearrangement in phenotypically defined ANLL suggests (1) that such changes may not be limited to lymphoid leukemia of B cell lineage, or (2) that, in some patients, the leukemic transforming event may involve stem cells capable of both B cell and myeloid differentiation.

Acute Disease↗
PubMed1984

Lineage switch in acute leukemia.

Conversions of leukemic cell lineage (lymphoid or myeloid) have been reported only rarely. Our review of the cytochemical and immunophenotypic features of 89 cases of childhood leukemia in marrow relapse indicated lineage switch (lymphoid to myeloid or the reverse) in six patients (6.7%). Five patients with acute lymphoblastic leukemia (ALL) at diagnosis had converted to acute nonlymphoblastic leukemia (ANLL), and one had converted from ANLL to ALL. Each child received lineage-specific multiagent chemotherapy when initially diagnosed, and all achieved a complete remission. After conversion, four patients readily achieved second remissions with treatment for the phenotype evident at lineage switch. Two patients with ANLL at conversion failed ALL-directed reinduction, while one of the two responded to high-dose cytarabine but died during bone marrow hypoplasia, emphasizing the importance of prompt recognition of lineage switch and selection of an appropriate plan of retreatment. Cytogenetic studies disclosed evidence of clonal selection in one patient and clonal stability in two. These findings indicate an unexpectedly high frequency of lineage switch in patients who relapse in the bone marrow after intensive chemotherapy. Although specific causative factors could not be identified, our observations suggest at least two general mechanisms for lineage switch in acute leukemia. In one, chemotherapy appears to eradicate the dominant clone present at diagnosis, permitting expansion of a secondary clone with a different phenotype. In the second, drug-induced changes in the original clone may either amplify or suppress differentiation programs so that phenotypic shift is possible.

Acute Disease↗
PubMed1983

Granular acute lymphoblastic leukemia.

Granules in blasts are most typical of acute myeloblastic leukemia. However, there have been scattered reports of patients with acute lymphoblastic leukemia (ALL) that have lymphoblasts with azurophilic cytoplasmic granules. These reports do not describe immunologic markers or cytogenetics. We report five additional cases with detailed cytologic, immunologic, and cytogenetic studies. At diagnosis one of these patients had central nervous system disease, while the others had no unusual features. Four of the five patients attained remission. The blasts of all five patients contained distinct cytoplasmic azurophilic granules. The granules were negative for peroxidase and chloroacetate esterase and positive for PAS, acid phosphatase, alpha-naphthyl acetate esterase incompletely fluoride inhibited, alpha-naphthyl butyrate esterase, and in one case, Sudan black B. In the one patient studied by electron microscopy, characteristic lymphoblasts contained membrane-bound electron lucent inclusions, which stained positively with non-specific esterase. Immunologic markers showed a common ALL phenotype. Different cytogenetic abnormalities were seen in all cases. It is important to recognize the characteristics of this morphologic subtype of ALL in order to avoid a misdiagnosis of acute nonlymphocytic leukemia.

Adolescent↗
PubMed1983

Phenotypic conversion of acute leukaemia from T-lymphoblastic to myeloblastic induced by therapy with 2'-deoxycoformycin.

A 6-year-old boy with T-cell acute lymphoblastic leukaemia (ALL) in relapse was treated with the adenosine deaminase inhibitor, 2'-deoxycoformycin (DCF). Remarkably, his residual leukaemia underwent an abrupt phenotypic shift, coincident with a massive anti-leukaemic effect of DCF. Both at diagnosis and prior to therapy with DCF, blast cells had typical lymphoblastic morphology and T-cell characteristics (terminal transferase +, T-antigen +, Ia -, cALLa -, myeloperoxidase -, and high in adenosine deaminase content). After four courses of DCF by constant infusion, the blast cells were myeloid in appearance and reactivity to a variety of tests (terminal transferase -, myeloperoxidase +, Sudan black B +, esterase +, My-1 +). We hypothesize that DCF therapy created a selection pressure, blocking pathways of T-cell differentiation and proliferation, permitting the emergence of a newly dominant myeloid subclone of a multipotential leukaemic cell progenitor with the innate capacity for both T-lymphocytic and myeloid differentiation.

Adenosine Deaminase Inhibitors↗