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Biomedical subjects

D Wurster-Hill

Publications and source records attributed to D Wurster-Hill.

13 recordsLinked to original sources
PubMed1996

Acute myeloid leukemia-type chemotherapy for newly diagnosed patients without antecedent cytopenias having myelodysplastic syndrome as defined by French-American-British criteria: a Cancer and Leukemia Group B Study.

PURPOSE: To determine the treatment outcome of standard acute myeloid leukemia (AML)-type chemotherapy in a subset of patients with newly diagnosed myelodysplastic syndromes (MDS) compared with that of patients with de novo AML as defined using French-American-British (FAB) criteria. In addition, to determine the pretreatment variables having prognostic significance for treatment outcome in patients with MDS. PATIENTS AND METHODS: Nine hundred seven newly diagnosed patients with no history of cytopenias having a local institutional de novo AML successfully karyotyped and treated on Cancer and Leukemia Group B (CALGB) protocols for AML from 1984 to 1992. Thirty-three of the 907 patients were reclassified as having MDS on central pathology review using FAB criteria and form the basis of this analysis. RESULTS: The treatment outcomes for patients with MDS and AML were similar; the complete remission (CR) rate was 79% and 68%, respectively (P = .37); median CR duration was 11 and 15 months, respectively (P = .28); and median survival was 13 and 16 months, respectively (P = .72). For the MDS patients, there were no prognostic variables for CR rate identified. For CR duration, only the Sanz classification had prognostic value. The prognostic factors for survival in a univariate analysis included age, WBC count, Sanz classification, and percent blood blasts. In a proportional hazards analysis of survival, age greater than 60 years and WBC less than 2.6 x 10(9)/L were adverse prognostic factors. CONCLUSION: In patients with no known history of cytopenias who are treated intensively at diagnosis, the FAB distinctions between MDS (refractory anemia with excess blasts and refractory anemia with excess blasts in transformation) and AML appear to have little therapeutic relevance.

Acute Disease↗
PubMed1995

Morphologic characteristics of erythroleukemia (acute myeloid leukemia; FAB-M6): a CALGB study.

We have reviewed the clinical, morphologic, immunophenotypic, and cytogenetic features of 52 patients with erythroleukemia (FAB Cooperative Group; AML-M6) studied by the Cancer and Leukemia Group B (CALGB). The purpose of this study was to correlate morphology with the clinical features, immunophenotypes, and karyotypes of neoplastic cells, and with the response to therapy of patients with AML-M6. Thirty-three patients (63%) were male, median age 59 (range 16-81) years, 47 patients (90%) were white, and 42 patients (81%) had a performance status of < 2. Myelodysplastic changes were observed in at least 1 cell lineage in all cases, and in 2 cell lineages in 45 of 52 (86%) cases. Fifty percent or more of cases studied were positive for CD11b, CD13, CD15, CD33, glycophorin-A, and HLA-DR markers. Fourteen of 27 cases (52%) in whom karyotypic analyses were conducted had cytogenetic abnormalities. Five (19%) were simple (< 3 karyotypic abnormalities), while 9 (33%) were complex (> or = 3 abnormalities). We observed either a complete or partial loss of chromosomes 5, 7, or 12p, or the presence of trisomy 8, in 11 of 27 (41%) patients. Cases of AML-M6 were divided into group 1 (14 patients with bone marrow proerythroblasts and basophilic erythroblasts > 25% of all erythroblasts) and group 2 (38 patients with proerythroblasts and basophilic erythroblasts < or = 25% of all erythroblasts). We observed no significant differences between groups 1 and 2 in regard to sex, age, race, performance status, percentage of blood erythroblasts or myeloblasts, percentage of bone marrow erythroblasts, and periodic acid-Schiff (PAS) or myelodysplasia scores. Six of 6 (100%) patients of group 1, and 7 of 21 (33%) patients of group 2, had normal karyotypes (P = .006). Nine of 13 (69%) patients of group 1 and 15 of 33 (45%) patients of group 2 had a complete remission (CR) (P = .2). Eight of 11 (73%) cytogenetically normal patients achieved CR: 5 of 6 (83%) in group 1, and 3 of 5 (60%) in group 2. Five of 12 (42%) cytogenetically abnormal patients achieved CR. No difference in duration of survival (group 1, median = 4.6 months vs. group 2, median = 10.2 months; P = .93) was observed between the 2 groups. We conclude that AML-M6 is typified by multilineage involvement of hematopoietic cells. The morphology of erythroblasts in patients with AML-M6 may correlate with cytogenetic abnormalities and rate of CR.

Adolescent↗
PubMed1995

Low incidence of TAL1 gene rearrangements in adult acute lymphoblastic leukemia: A cancer and leukemia group B study (8762)

TAL1 gene rearrangements have been described in approximately 25% of children with T cell acute lymphoblastic leukemia (ALL). Three percent of these rearrangements are the result of a reciprocal translocation, t(1;14)(p34;q11). The remainder of these rearrangements are submicroscopic and involve a nearly precise 90-kilobase pair deletion of the TAL1 gene. Detection of these submicroscopic rearrangements can be accomplished easily using Southern blot and PCR technology and may have potential value for monitoring disease during and following treatment. The incidence of TAL1 gene rearrangements in adults with ALL is unknown. In this pilot study, we performed Southern blot and PCR analysis in a group of newly diagnosed adult ALL patients to determine the incidence of TAL1 rearrangements. Thirty-three adults with T cell ALL were studied; of these, one patient had a t(1;14)(p34;q11) and molecular rearrangement of TAL1. No submicroscopic deletions of TAL1 were detected (95% confidence intervals, 0.000 and 0.106). Unlike pediatric T cell ALL, the incidence of TAL1 rearrangements in adult ALL appears to be very low.

Journal Article↗
PubMed1994

Prognostic importance of mutations in the ras proto-oncogenes in de novo acute myeloid leukemia.

Mutations of the N- and K-ras genes are the most frequent genetic aberrations in acute myeloid leukemia (AML) and their detection in preleukemic conditions such as the myelodysplastic syndrome (MDS) suggests a role in the earliest phases of leukemogenesis. Despite these observations, little is known about the clinical importance of ras mutations in AML. We studied the clinical impact of ras mutations in 99 patients with de novo AML. All patients were treated in two prospective multicenter trials. The polymerase chain reaction was used to amplify areas surrounding the codons 12, 13, and 61 of the three ras genes N-, K-, and H-ras from DNA from bone marrow cells, ras mutations were detected by an algorithm based on allele-specific oligonucleotide hybridization. Eighteen of 99 (18%) patients harbored mutations in either N- or K-ras. All of the observed mutations occurred in N-ras (N = 10) and K-ras (N = 5) or concurrently in both N- and K-ras (N = 3). There were no significant differences between ras-negative and ras-positive patients according to age, sex, blood counts, cytogenetic abnormalities, or French-American-British classification. However, univariate analysis suggested a longer survival in ras-positive patients (P = .11). When adjusted for age, which was the most important factor affecting outcome, the presence of a ras mutation emerged as a significant predictor for improved survival (P = .03) and along with lower bone marrow blast counts (P = .02) and better cytogenetic category (P = .01). However, the presence of an aberrant ras allele was strongly correlated with lower bone marrow blast counts (P = .007). Thus, whether a mutation in the N-ras or K-ras proto-oncogenes directly affects treatment outcome or indirectly through an association with lower leukemic burden remains to be determined. Nevertheless, these findings counter the prevailing bias that oncogene mutations lead to more aggressive behavior in human malignancies.

Adult↗
PubMed1994

Detection of MLL gene rearrangements in adult acute lymphoblastic leukemia. A Cancer and Leukemia Group B study.

Specific structural rearrangements involving chromosome band 11q23 occur in a variety of hematologic malignancies, including an estimated 2-7% of patients with acute lymphoblastic leukemia (ALL). Translocations involving chromosome band 11q23 have been associated with a poor prognosis in patients with ALL. Recently, a gene known as MLL has been identified which is involved in acute lymphoid and myeloid leukemias with rearrangements at 11q23. A 0.74-kilobase (kb) cDNA probe from the MLL gene can detect both common and uncommon rearrangements involving MLL on conventional Southern blots. We studied 86 newly diagnosed adults entered on an ALL clinical trial to investigate the incidence of MLL gene rearrangements and to determine clinical, morphologic, immunologic and cytogenetic characteristics of such patients. Two of 86 patients had MLL gene rearrangements detected by Southern blot analysis. One of these 86 patients had an 11q23 translocation by cytogenetic analysis whereas the second patient was unevaluable by standard cytogenetic analysis. Southern blot identification of rearrangements involving MLL, especially in patients with limited material for cytogenetic analysis, can provide critical diagnostic and prognostic information which may be useful in the clinical management of patients with these abnormalities.

Adolescent↗
PubMed1992

Morphologic characteristics of acute lymphoblastic leukemia (ALL) with abnormalities of chromosome 8, band q24.

The CALGB prospectively studied 140 adult acute lymphoblastic leukemia (ALL) patients for cytogenetic abnormalities. Seven (5%) patients with adequate cytogenetic preparations had t(8;14)(q24;q32) or t(8;22)(q24;q11). Patients were compared with non-8q24 patients for clinical and laboratory characteristics, response to therapy, and survival. The median age of patients with translocations involving 8q24 (71% males) was 40 years. Forty-three percent had lymphadenopathy, 29% splenomegaly, and 29% hepatomegaly. None exhibited central nervous system (CNS), skin, or gum involvement. These features did not differ significantly from non-8q24 ALLs. Patients with 8q24 translocations had higher hemoglobins (11.5 vs. 9.8 g/dl; P = 0.04) and lower percentage of blasts in the peripheral blood (8.5% vs. 69%; P = 0.007). Although all seven were finally categorized as ALL-L3, a marked variation in the proportion of typical L3 blasts was observed that initially resulted in the diagnoses of ALL-L2 in three cases and prolymphocytic leukemia in one. In five of five patients, the blasts typed as B cells (SIg+ and CD19+). Complete remission rates for patients with 8q24 translocations were 43%, whereas they were 68% for non-8q24 ALLS (P = 0.22). Furthermore, patients with 8q24 abnormalities exhibited significantly shorter survival (4.8 vs. 18.4 mo; P less than 0.001). We conclude that ALL with translocations of 8q24 in adults shows a mature B-cell immunophenotype (SIg+), poor prognosis and morphology ranging from classical ALL-L3 to ALL with a subpopulation of L3 cells. Thus, the diagnosis of ALL-L3 should be made when blastic cells possess a mature B-cell immunophenotype (SIg+) and an 8q24 translocation, even though the number of L3 cells is low.

Adult↗
PubMed1991

Prognostic value of lymphocyte surface markers in acute myeloid leukemia.

We studied the expression of cell surface antigens associated with myeloid and lymphoid leukemias on bone marrow-derived blast cells from 339 patients with newly diagnosed de novo acute myeloid leukemia (AML) enrolled on Cancer and Leukemia Group B (CALGB) chemotherapy protocols. Surprisingly, of 211 cases studied for the expression of CD2 (T-cell marker, sheep erythrocyte binding receptor for T lymphocytes) 45 were positive (21%). In addition, of 298 patients studied for CD19 (B-lymphocyte marker), 41 were positive (14%). Overall, of 170 patients studied for both CD2 and CD19, 56 (33%) were positive. Interestingly, central review of the French-American-British (FAB) morphology of the CD2- and CD19-positive cases showed that FAB M3 was twice as frequent, and M4E eight times as frequent compared with the CD2- and CD19-negative cases. Of 22 lymphocyte antigen-positive cases in which cells were available for studies of Ig or T-cell antigen receptor (TCR) gene rearrangement, 20 were germline, one had a rearranged Ig heavy chain gene, and one had rearranged TCR beta and Ig heavy chain genes. The presence of messenger RNA for CD2 was demonstrated in four CD2 surface antigen-positive cases, thus validating the cell surface data. Lymphocyte antigen-positive cases had karyotypes commonly seen in AML; 71% of cases with an abnormal clone had t(8;21)(q22;q22), inversion 16(p13q22), t(15;17)(q22;q12), or t(9;11)(p22;q23). The patients with lymphocyte markers had a significantly higher incidence of these karyotypic abnormalities compared with patients with lymphocyte antigen-negative AML (34% v 15%, P less than .02). When the outcome to therapy of the lymphocyte antigen-positive cases was compared with that for the CD2, CD19-negative cases, we found that the CD2, CD19-positive cases actually had higher complete remission rates (75% v 59%, P = .04), and significantly longer time to failure (P = .02; 32.4% +/- 6.0% v 18.0% +/- 4.1% at 2 years) and overall survival (P = .02; 43.5% +/- 6.3% v 26.0% +/- 4.5% at 2 years). CD2 antigen-positive cases also had a significantly superior survival (P = .02; 43.8% +/- 7.9% v 29.8% +/- 3.8% at 2 years). There were no significant differences (P less than or equal to .05) between the two groups in age, leukocyte count at diagnosis, incidence of extramedullary disease, or FAB classification.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1989

Restriction fragment length polymorphisms within proximal 15q and their use in molecular cytogenetics and the Prader-Willi syndrome.

Restriction fragment length polymorphisms (RFLPs) are described in detail for 6 DNA probes (D15S9-13, D15S18) that localize to the proximal long arm of human chromosome 15 (15q11-15q13: this report and Tantravahi et al., Am. J. Med. Genet. 33:78-87. Multiple RFLPs are detected by the probe that identifies locus D15S13, and these RFLPs are shown by genomic mapping to result from a nearby insertion or deletion of 1.8 kilobases (kb) of DNA. This set of RFLPs detected by proximal 15q probes can be used for studies on the Prader-Willi syndrome (PWS) and on mentally retarded individuals with a supernumerary inv dup(15) chromosome. Five of the polymorphic loci (D15S9-13) map to the region implicated in the cause of the PWS (15q11.2-15q12). Each of 4 families tested with these probes, as well as an additional "PWS-like" patient, was informative by RFLP analysis. The two PWS deletions studied, which occurred de novo, were inherited from the chromosome 15 provided by the father. By contrast, the 2 inv dup(15) chromosomes analyzed were of maternal origin. The use of RFLPs can also simplify the molecular determination of copy number in chromosomal aneuploidy, as exemplified by analysis of individuals with the PWS and a deletion, patients with an inv dup(15), and one patient with a more complex rearrangement involving chromosome 15. Our studies demonstrate the application of DNA probes for both molecular cytogenetic studies on this chromosome region and the development of diagnostic molecular markers to aid early clinical diagnosis of the PWS.

Chromosome Deletion↗
PubMed1989

Quantitative calibration and use of DNA probes for investigating chromosome abnormalities in the Prader-Willi syndrome.

Ten genomic DNA probes, subcloned from inserts derived from a phage library constructed from the DNA of flow-sorted chromosomes, have now been mapped to locations within 15q11-15q13. By dosage blotting and densitometry, 5 of these probes map to the 15q11.2-15q12 segment missing in one 15 chromosome of a Prader-Willi syndrome (PWS) patient with a prominent cytological deletion. A sixth probe most likely maps to the same region. The other 4 probes map outside of this segment but within 15q11-15q13. Several of the 15q11.2-15q12 probes, and a cDNA probe homologous to one, have been used to test the DNA from 8 patients exhibiting a wide range of the clinical manifestations expected for PWS patients. DNA deletion was observed in all 3 patients with cytological 15q1 deletions as well as in a patient with an unbalanced (Y;15) translocation. DNA from 1 PWS patient with an unbalanced (5;15) translocation and an inverted duplication of the short arm and proximal long arm of 15 showed at least 1 and possibly 2 extra copies of each genomic probe tested. In the other 3 patients with no cytological deletions, no DNA deletions were found. Thus, the molecular probes described can be used in most PWS patients to analyze the region of proximal 15q implicated in this syndrome.

Adolescent↗
PubMed1989

A genetic linkage map of 32 loci on human chromosome 10.

We have constructed a genetic linkage map of human chromosome 10 based on DNA probes that detect 47 restriction fragment length polymorphisms (RFLPs) at 32 different loci. Segregation data were collected on a set of multigenerational families provided by the Centre d'Etude du Polymorphisme Humain and maps were constructed using recently developed multipoint analysis techniques. The length of the sex-averaged map is 178 cM and the sex-specific map lengths are 131 cM in males and 255 cM in females. Recombination is significantly higher in female meioses. The mean distance between loci is 5.6 cM for the sex-averaged map. The genetic map spans the length of the chromosome as judged by physical localization of probes by in situ hybridization techniques and mapping of the probes on human-hamster hybrid cell lines containing all or part of chromosome 10. The informativeness of two loci near the locus responsible for multiple endocrine neoplasia type 2A (MEN-2A) has been increased by isolation of cosmids that reveal additional RFLPs at these loci.

Animals↗