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J Harbott

Publications and source records attributed to J Harbott.

At least 109 records · Page 6Linked to original sources
PubMed1989

Phenotypic and genotypic heterogeneity in infant acute leukemia. II. Acute nonlymphoblastic leukemia.

We have studied the immunophenotypic and genotypic characteristic of acute nonlymphoblastic leukemias (ANLL) in infants aged less than one year. Sixty-four percent of cases (16/25) showed a myeloid or myelomonocytic differentiation pattern and 10 of these were classified as FAB M5 (7 M5a, 3 M5b). Only seven of the latter cases expressed the CD14 antigen. Acute megakaryocytic leukemia with a high number of glycoprotein IIb/IIIa or IIIa positive blasts were identified in five patients. Erythroleukemia with a high percentage of rather mature glycophorin A positive erythroblasts were diagnosed in two infants. Cytogenetic studies were successfully performed in all 20 cases investigated. Abnormalities involving chromosome 11 were present in 10 of 17 patients with an abnormal karyotype including five cases with a t(9;11)(p21;q23). Immunoglobulin (Ig) and T cell receptor (TCR) gene analyses were performed in 20 patients. A rearrangement of Ig heavy chain sequences was detected in five cases (20%), one of whom exhibited multiple rearranged fragments. Three of these patients showed additional TCR delta-chain gene rearrangements, while Ig kappa, TCR beta- as well as TCR gamma-chain genes showed a germline configuration in all cases analyzed. Our study confirms the high incidence of myelomonocytic and monoblastic subtypes in infants with ANLL, which are particularly closely associated with chromosome 11 abnormalities. However, we also observed an unexpected high frequency of megakaryoblastic leukemias as well as erythroleukemias. As previously reported for ALL in infants, ANLL of infancy shows a similar heterogeneity regarding phenotypic and genotypic features.

Antigens, Differentiation↗
PubMed1988

T-cell acute childhood lymphoblastic leukemia with chromosome 14 q 11 anomaly: a morphologic, immunologic, and cytogenetic analysis of 10 patients.

Ten patients with T-cell acute lymphoblastic leukemia (ALL) and a chromosome anomaly involving band 14 q 11 are described. Mitotic index of bone marrow blasts was high in all patients (average 3.0%). Lymphoid morphology of the leukemic blasts, however, varied somewhat among the patients. The leukemic cells of 5 patients showed an immunophenotypic profile corresponding to early or common thymic differentiation stages whereas 5 children showed strong expression of CD 3 suggesting a more mature thymic phenotype. Leukemic karyotypes revealed a modal chromosome number of 46 in 9 cases, 92 in one case. A chromosome translocation t(11; 14) (p 13; q 11) was found in 5 cases, a t(1; 14) (p 32; q 11) in 2 cases, a t(10; 14) (q 24; q 11) in one case, a (hitherto undescribed) t(12; 14) (q 22; q 11) in one case, and an inv (14) (q 11 q 32) in one patient. Additional abnormalities were t(3; 10), t(7; 9), dup(7 q), del(6 q), del(10 q), and del(1 q). Of 32 cases with T-cell ALL successfully karyotyped in our laboratory 15 (= 47%) had structural aberrations involving chromosomes 1, 3, 6, 7, 9, 10, 12, 14. Ten of these 15 patients (= 67%) had a chromosome 14 q 11 anomaly. It is concluded that chromosome band 14 q 11, the gene locus of the T-cell receptor alpha-chain, is the most common site for structural chromosome aberrations in T-cell ALL.

Acute Disease↗
PubMed1988

Fragile sites and neuroblastoma: fragile site at 1p13.1 and other points on lymphocyte chromosomes from patients and family members.

Fragile sites on lymphocyte chromosomes of 20 patients with neuroblastoma of different clinical stages and histologic differentiation were studied. A hitherto unknown break in the band p13.1 of chromosome #1 was found in a frequency of 3%-15% in nine cases. The same phenomenon was observed in three members of a neuroblastoma family. In another instance, this fragile site was also seen in the mother of a patient. Fragile sites were expressed when cells were cultured in folate-deprived medium and could be slightly enhanced in frequency by aphidicolin. Additional aphidicolin induced possible fragile sites hitherto unknown or not yet accepted by the HGM 8 were detected.

Child, Preschool↗
PubMed1988

The T-ALL specific t(11;14)(p13;q11) translocation breakpoint cluster region is located near to the Wilms' tumour predisposition locus.

A breakpoint cluster region (T-ALLbcr) has been previously described on 11p13 for T-ALL carrying t(11;14)(p13;q11). One further T-ALL breakpoint is described bringing to 5 out of 6 such translocations which are found to break within a maximum of 6.7 kb on chromosome 11p13. Studies of somatic cell hybrids derived from t(11;14)(p13;q11) T-ALL placed the T-ALLbcr between the genes for catalase (CAT) and the beta-subunit of follicle stimulating hormone (FSHB). This suggested a link between the T-ALLbcr and the Wilms' tumour predisposition locus (WT) since constitutional 11p13 deletions predispose to Wilms' tumour. Utilising somatic cell hybrids from patients with Wilms' tumours and aniridia, we show that while the T-ALLbcr maps distal to the catalase gene at 11p13, it maps outside the shortest region of overlap of a series of 11p13 deletions associated with Wilms'-Aniridia. The data suggest the order of genes at 11p13 to be: centromere-CAT-T-ALLbcr-WT-aniridia-FSHB-telomere. Therefore, the T-ALLbcr must lie very close to but may be distinct from the Wilms' predisposition locus at 11p13.

Aniridia↗
PubMed1988

Ambiguous phenotypes and genotypes in 16 children with acute leukemia as characterized by multiparameter analysis.

Ambiguous phenotypes and genotypes were observed in 16 children with acute leukemia. Surface marker, cytogenetic, molecular genetic, and DNA flow cytometric analyses as well as standard morphologic and cytochemical studies were used to divide the patients into three groups. The first group comprised five children with acute leukemia whose blast cells were morphologically lymphoid, while immunophenotyping disclosed simultaneous expression of early pre-B cell and myeloid features. Molecular genetic studies showed evidence of heavy-chain immunoglobulin (Ig) gene rearrangements in all patients. Cytogenetic data, available in three of these children, revealed t(4;11). In five of the 16 patients, morphologic and surface marker analyses indicated the coexistence of two separate cell populations, one with myeloid and the other with early pre-B cell features. Further evidence of B cell commitment in these patients was provided by demonstration of Ig heavy-chain gene rearrangements in all five patients. Surprisingly, one of the five patients showed oligoclonal Ig heavy-chain as well as monoclonal gene rearrangement for the beta chain of the T cell receptor (beta-TCR). The last group consisted of four cases with otherwise typical acute lymphoblastic leukemia (ALL), early pre-B cell phenotype, and coexpression of myeloid or T cell-associated antigens, and two children with unequivocal acute myeloid leukemia (AML) and coexpression of T cell antigens. Gene rearrangement of Ig heavy-chain could be demonstrated in five of six patients, additional Ig light-chain gene rearrangement in two children with ALL, and bigenotypic features (Ig heavy-chain and beta-TCR gene rearrangement) in one patient. In none of the 16 patients did flow cytometry disclose clonal abnormalities of leukemic cell DNA content. Based on these findings, we suggest that malignant transformation in the first and second group of patients took place at a stage ontogenetically close to the pluripotent stem cell, whereas ambiguous phenotypes in the third group resulted from aberrant gene expression or insufficient reagent specificity.

Acute Disease↗
PubMed1987

Alteration of blast phenotype after low-dose cytarabine in children with acute myeloid leukemia.

Two children with acute myeloid leukemia (FAB M1 and M2) experienced bone marrow relapse during maintenance chemotherapy 7 and 10 months after diagnosis. Low-dose ARA-C monotherapy (2 X 10 mg/m2 per day s.c. for 14 days) was then initiated, as suggested by others reporting induction of differentiation and achievement of remission without toxic side effects. In contrast to these reports, remission induction was not observed in the two children after low-dose ARA-C but was achieved by subsequent high-dose chemotherapy. However, blast cell characteristics revealed some alterations. Blast count and chromosome pattern remained unchanged. Cytochemistry revealed the appearance of esterase- (0----11%), 0----21%) and PAS- (0----74%, 0----45%) positive cells in the patients and a remarkable increase (patient 1: 0----71%) and decrease (patient 2: 90----12%) in acid phosphatase positivity. Expression of myeloid marker VIM D5 decreased distinctly (70----4%, 77----11%). However, the biologic relevance of these alterations remains in question. The failure to respond clinically to low-dose ARA-C in both children is discouraging.

Antigens, Ly↗
PubMed1987

Acute leukemia with chromosome translocation (4;11): 7 new patients and analysis of 71 cases.

Clinical and laboratory features of seven patients with acute leukemia associated with the (4;11) chromosome translocation are presented. Leukemic blasts of these patients showed lymphoid morphology in 6 (although 1 was treated for monoblastic leukemia 3 years earlier) and monocytoid morphology in 1, were positive for TdT and HD 37 (CD 19) in 6 patients, whereas weak expression of CALLA was seen in only 1 patient and T-lineage-associated antigens in none. Leukemic blasts from four patients showed the simultaneous expression of B-lymphoid and myeloid antigens, suggesting leukemogenesis in a very early multipotent progenitor cell. In 2 patients an isochromosome of the long arm of No. 7 chromosome was found in the leukemic karyotypes in addition to t (4; 11) (q 21; q 23); in one instance present at diagnosis, in the other one occurring at relapse. In one other patient leukemia karyotype also demonstrated trisomy 8. Leukemic cells of three patients were investigated by molecular genetics and demonstrated immunoglobulin gene rearrangements for the Ig heavy chain sequences but not for the light chain constant regions and T cell receptor sequences. All patients were treated by intensive chemotherapy. Four of the 7 patients are in continuous complete remission. The longest event-free survival time (over 2 1/2 years) was seen in one patient who had also DOWN-syndrome. Including these 7 patients a clinical analysis of 71 patients with t (4; 11) acute leukemia was made, emphasizing the following characteristics at diagnosis: female sex (62%), age under 2 years (49%), leukocyte count over 100 X 10(9)/1 (61%), splenomegaly (80%), CNS-disease (11%). Survival of over 2 years was reported in less than 15% of the patients. It remains to be seen if risk-adapted treatment can alter the course of this early B-precursor acute leukemia with hitherto very bad prognosis.

Acute Disease↗
PubMed1987

Evolution of tumor cytogenetic aberrations and N-myc oncogene amplification in a case of disseminated neuroblastoma.

Chromosome analyses including in situ hybridization with the protooncogene N-myc were carried out at diagnosis and several times at relapse in the bone marrow cells of a girl with disseminated neuroblastoma (stage IV) at ages 9, 23, 24, and 26 months, respectively. The tumor karyotype was pseudodiploid exhibiting partial monosomy for the short arm of chromosome #1, an aberration of the short arm of chromosome #2, and double minutes at diagnosis. Further structural aberrations of chromosomes #4, #6, and #17, and homogeneously staining regions could be demonstrated at relapse. In particular, the following structural aberrations were encountered: t(1;?)(p22;?),t(2;?)(p24;?), t(4;6)(q31;q25), and a der(17q). All tumor metaphases without homogeneously staining regions contained double minutes. N-myc, normally positioned within bands 2p23-24, was found to be amplified in a homogeneously staining region on the short arm of chromosome #15 by in situ hybridization. It is speculated that the translocation t(2;?)(p24;?) might be related to N-myc oncogene activation and subsequent amplification.

Bone Marrow↗
PubMed1987

[Specific chromosome aberrations in leukemias and tumors in childhood].

Non-random, specific chromosome aberrations can be found by direct preparation in the karyotype of the malignant cell populations of the various leukemias and solid tumors in childhood. These chromosomal deletions in neuroblastoma, Wilms-Tumor, reticlassification and prognosis. There are mainly chromosomal deletions in neuroblastoma, Wilms-Tumor, retinoblastoma whereas translocations predominate in leukemias and lymphomas.

Chromosome Aberrations↗
PubMed1986

A complex translocation in a 5-year-old boy with acute myeloblastic leukemia.

A complex translocation [t(2;10;11)(q34;q11;q13)], an extra chromosome #8, and a duplication of 17q were the major findings in blast cells found in the bone marrow of a 5-yr-old boy with AML-M2 both before treatment and during relapse. The child died 8.5 mo after diagnosis, despite intensive combination chemotherapy.

Child, Preschool↗
PubMed1986

(11; 14) translocation in three boys with acute lymphoblastic leukemia of T-cell immunophenotype.

Three boys, 12, 15 and 5 years old are presented with acute lymphoblastic leukemia resp. Non-Hodgkin's lymphoma with leukemic transformation. Blast cells could be characterized as being of T-cell origin. Hand mirror variant was the predominant morphologic feature of the blast cells in two patients. Chromosome analysis of the leukemic blast cells revealed a pseudodiploid (modal chromosome number = 46) karyotype in two patients and a pseudotetraploid (modal chromosome number = 92) in one patient. A chromosome translocation (11; 14) with breakpoints at (p 13; q 13) (within the human T-cell receptor alpha chain locus!) was found in the leukemic cells of all three cases plus an additional t (7; 9) (q 22; p 13) in one patient.

Adolescent↗
PubMed1986

Tumour karyotype may be important in the prognosis of human neuroblastoma.

When comparing clinical and tumour cytogenetic data on 14 neuroblastoma patients in different stages of disease we found a high incidence of 1p abnormalities (12/12), homogeneously staining regions/double minutes (9/12) and 2p abnormalities (4/12) in 12 unresectable and metastatic tumours (clinical stages III and IV). In contrast, these features were absent in clinical stage II tumours (2/2) with good prognosis. The coincidence of 1p aberrations with poor outcome of disease will be discussed.

Child, Preschool↗
PubMed1984

The prognostic meaning of marker chromosomes in human urinary bladder carcinoma.

In summary, only a chromosome analysis of directly extracted tumour tissue seems to be of prognostic value, because this allows one to exclude alterations that are conditioned by cultures. The number of chromosomes does not give an indication of the malignancy and invasiveness of the tumour. The presence of marker chromosomes in superficial bladder carcinoma seems to worsen the prognosis of those patients significantly. Further observation of the previously investigated patients and new studies are aimed at determining whether the reported tendency proves to be valid. If the presence of marker chromosomes really enables us to predict an unfavourable prognosis, a timely cystectomy, i.e. cystectomy in the preinvasive stage, should decisively ameliorate the poor prognosis of these patients.

Carcinoma↗
PubMedDate not supplied

Prognostic impact of age in children and adolescents with acute lymphoblastic leukemia: data from the trials ALL-BFM 86, 90, and 95.

Large progress has been made in the treatment of acute lymphoblastic leukemia (ALL) of childhood and adolescence over the past 30 years. Eighty percent of the patients can be cured, but clinical subgroups with a dismal outcome can still be identified. In this study, we investigated the association of age with prognosis in 5 181 patients with ALL under 18 years (y) of age enrolled in the three consecutive treatment trials ALL-BFM 86, 90 and 95 in more than 80 centers. Event-free survival (pEFS) of the total group was significantly associated with age. The most unfavorable outcome was found in infancy and the best results were achieved at toddler and pre-school age. Beyond 5 y of age, survival probability decreased (pEFS at 8 y: < 1 y = 0.45; 1-5 y = 0.82; 6-9 y = 0.75; 10-14 y = 0.63; > or = 15 y = 0.59). The proportion of T-ALL as compared to precursor B-cell ALL (pB-ALL) was lower in younger children, due to an incidence peak of pB-ALL in toddlers and at pre-school age compared to a constant incidence of T-ALL. Within the T-ALL group, no correlation of age with sex, initial white blood cell count, CNS disease, or early treatment response was found. Children under 10 y of age had a slightly lower relapse rate compared to older patients. Within pB-ALL patients, the proportion as well as the absolute incidence of TEL/AML1 rearrangement and DNA index of > or = 1.16 was higher in the younger children. A lower proportion of BCR/ABL-positive ALL was observed in the age group of < 6 y when compared to patients aged > or = 6 y, but the absolute incidence was constant across the age groups after the first year of life. More than half of the infants had a CD10-negative pB-ALL. The incidence was constant after a peak in the first year of life, yet the percentage of CD10 negativity increased with rising age in this subgroup. Adolescents with pB-ALL had a significantly higher proportion of prednisone poor-responders. Accordingly, outcome was worse in older patients. This pattern was also evident in the biologically heterogeneous group of patients with a DNA index of > or = 1.16. In contrast, no significant age-related outcome differences could be shown within TEL/AML1- or BCR/ABL-positive patients, as well as within CD10-negative pB-ALL beyond infant age. Analysis of the pB-ALL group in a Cox's regression model including age and the above-listed biological factors revealed age < 1 year and > or = 10 years as independent risk factors. This is in line with the poorer prognosis of these age groups in the pB-ALL subgroup without specific biological characteristics. This subgroup also had an incidence peak at toddler age, presumably containing other favorable biological subsets. An independent prognostic impact of age in pediatric ALL cannot be excluded by this study. However, our analyses show that the age-associated different prognosis in childhood ALL is at least partly related to the different distribution of relevant prognostic subgroups between the age groups.

Adolescent↗
PubMedDate not supplied

[Classification of AML by morphologic, immunologic and cytogenetic criteria. Review with reference to subtypes in the AML-BFM-87 study].

The current FAB classification of acute myelogenous leukemia (AML) by morphologic, immunologic and cytogenetic features is described and the incidence of subtypes and variant forms of AML in study AML-BFM-87 is given. In general, lymphoblastic or myeloid blast populations can be identified by morphologic, cytochemical and immunologic parameters, while immunophenotyping facilitates diagnosis in biphenotypic leukemia. Furthermore, the AML subtypes M0 and M7 (defined in 1985 and 1991) can only be ascertained by the presence of lineage-associated markers. Whereas chromosome aberrations provide an insight into the neoplastic process and assure diagnosis. Thus, next to morphologic findings, immunologic and cytogenetic studies are essential for a definite diagnosis of AML.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

[Prognostic significance of eosinophilia in children with acute myeloid leukemia in the studies AML-BFM-78 and -83].

Initial eosinophilia (greater than or equal to 3%) in the bone marrow was found in 73 out of 269 (27%) patients studied in AML studies BFM-78 and -83. It was predominantly seen in children with FAB types M2 (44%) and M4 (41%). Atypical eosinophils were mostly found in FAB type M4 (20/28 = 71%). Cytogenetic studies in eight children with FAB M4 and eosinophilia showed normal karyotypes in four patients, inversion 16 in one and other aberrations in three children. Study AML-BFM-78 did not demonstrate any differences in prognosis between patients with and without eosinophilia (event-free survival = EFS after 5 years 37%, SD 8%, vs. 38%, SD 6%). In study AML-BFM-83, however, a clear increase in EFS was seen in children with eosinophilia (EFS 72%, SD 8%, vs. 43%, SD 5%, p = 0.001). This improvement of prognosis mainly concerns patients with FAB M4 and eosinophilia (EFS 81%, SD 10%, vs. 23%, SD 11%, p = 0.006). None of the 12 children in study AML-BFM-83 with FAB M4 and atypical eosinophils has suffered a relapse, two patients belong to the early death group. Multivariate analysis shows only eosinophilia as a favorable prognostic factor in FAB type M4. According to these results FAB type M 4 with eosinophilia is a favorable prognostic parameter in children treated according to the therapy protocol of study AML-BFM-83.

Adolescent↗
PubMedDate not supplied

[Chromosome aberrations in acute leukemia in childhood: analysis of 1009 patients].

Leukemia karyotypes were analyzed in 792 children with acute lymphoblastic leukemia (ALL) and 217 patients with acute myelocytic leukemia (AML). These patients were registered and uniformly treated in German multicentre trials from 1984-01-01 to 1989-12-31. In distinct leukemia subgroups specific chromosome abnormalities were found: Numerical aberrations such as hyperdiploidy over 50 chromosomes in c-ALL or structural aberrations (translocations) such as t(8;14) in B-ALL, t(11;14) in T-ALL, t(4;11) in ppB-ALL, t(1;19) in pB-ALL, t(15;17) in AML-M3, t(8;21) in AML-M2. Prognostic significance of the leukemia karyotype probably can be changed by intensive cytotoxic chemotherapy. Unfavorable prognosis, however, still persists in t(9;22) and t(4;11); "favorable" prognosis can be seen in t(8;21) and t(15;17). Inherited or induced chromosome instability is discussed as a possible predisposing factor for the origin of chromosome aberrations.

Child↗