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S D Lawler

Publications and source records attributed to S D Lawler.

At least 19 recordsLinked to original sources
PubMed1994

Long-term survival in acute myelogenous leukemia: a second follow-up of the Fourth International Workshop on Chromosomes in Leukemia.

Patients with acute myeloid leukemia (AML, equivalent to acute non-lymphoblastic leukemia [ANLL]) who were studied at the Fourth and Sixth International Workshops on Chromosomes in Leukemia and who have long survival have been re-assessed to identify factors which may be associated with good prognosis in AML. In a long-term survivor (LTS) group, there were more cases than expected in each age decade below 50, more cases than expected with FAB type M3, and fewer cases than expected of secondary leukemia. Of the distribution of chromosome abnormalities, t(15;17), t(8;21), and inv/del(16) were over-represented, and -5, -7, and rearrangements of 11q were under-represented. Multivariate analysis of all patients showed that age group, cytogenetic classification, FAB type, and sex all had independent, significant effects on survival. A new observation from a very small subgroup of patients was that deletion of 7q without concurrent abnormality of chromosome 5 appeared to be associated with a good prognosis.

Adolescent↗
PubMed1993

ABO genotyping of complete hydatidiform moles.

It has been suggested that the ABO blood group of a patient and her partner influence the clinical outcome for patients having a pregnancy with a complete hydatidiform mole (CHM). Since CHM lack red blood cells, it has not previously been possible to type CHM serologically and investigate the relationship between the blood group of the CHM and that of the patient. In the present study we have demonstrated the feasibility of using molecular genotyping to determine the ABO genotype of CHM, the ABO genotype being consistent with the androgenetic origin of CHM in all cases. In the series of 48 cases of CHM, the requirement for chemotherapy was not significantly different in those patients with a CHM of like blood group compared with those with a CHM of unlike blood group.

ABO Blood-Group System↗
PubMed1991

A prospective genetic study of complete and partial hydatidiform moles.

Two hundred two hydatidiform moles were classified by pathologic features and ploidy into partial or complete moles. Further classification was made by using genetic polymorphism, the diagnosis being refined by deoxyribonucleic acid technology. Among 51 partial hydatidiform moles, 44 triploids, two tetraploids, and one diploid were identified. Informative triploid partial hydatidiform moles had one maternal and two paternal sets of chromosomes, the likely origin being dispermy. Among 149 complete hydatidiform moles, one was haploid, one was triploid, and 105 were shown to be diploid or androgenetic; 39 of these were proved homozygous, indicating duplication of the male genome, whereas heterozygous origin by dispermy was likely in 13. The locus-specific minisatellite deoxyribonucleic acid probes were particularly useful for the identification of heterozygous complete hydatidiform moles. None of the patients with partial hydatidiform moles had development of a gestational trophoblastic tumor. No difference was detected in the frequency of requirement for chemotherapy between patients with homozygous or heterozygous complete hydatidiform moles.

Blotting, Southern↗
PubMed1990

Serial cytogenetic studies showing persistence of original clone in Hodgkin's disease.

A case of Hodgkin's disease is described in which cytogenetic studies were performed at intervals for 5 years. Clonally related chromosomally rearranged cells persisted during that time, with emergence of more complex karyotypes in the terminal phase of the disease. The chromosome findings are discussed in relation to the limited data available on banded karyotypes in Hodgkin's disease.

Bone Marrow Cells↗
PubMed1990

Cytogenetic studies of leukemic recurrence in recipients of bone marrow allografts.

Cytogenetic studies were made in 20 leukemic patients who relapsed after treatment by allogeneic bone marrow transplantation (BMT). Seven of the eight patients in whom no chromosomal abnormalities were detected in leukemic cells before BMT developed clonal abnormalities after BMT, and in two of these patients two independent clones were observed. Most patients in whom clones were detected before BMT showed evidence of clonal evolution after BMT. Nonclonal abnormalities were also observed in clonal cells. These additional abnormalities, both clonal and nonclonal, were attributed to the effects of total body irradiation received by the patient before BMT. There was no evidence of recurrence of leukemia in donor cells among these patients. We concluded that the cells found in leukemic recurrence were derived from the original leukemic clone.

Adolescent↗
PubMed1990

Gestational trophoblastic tumours following initial diagnosis of partial hydatidiform mole.

11 patients registered with an initial diagnosis of partial hydatidiform mole (PHM) subsequently required chemotherapy for a gestational trophoblastic tumour. In a retrospective review by histopathological examination and measurement of DNA ploidy, the diagnosis was confirmed as PHM in 5 cases and revised to complete hydatidiform mole in 4; in 2 cases there was no evidence of a molar pregnancy. 4 of the patients with PHM had no other known pregnancy before the gestational trophoblastic tumour and in 2 of these patients the tumour was diagnosed histologically as choriocarcinoma. Not all patients in whom PHM was diagnosed at referring hospitals proved to have the condition. Although the risk of a patient with PHM requiring chemotherapy for gestational trophoblastic tumour is of the order of 1 in 200, compared with 1 in 12 after a complete mole, there is no justification for excluding a patient from follow-up after the evacuation of a PHM.

Adult↗
PubMed1989

Cytogenetic studies of 21 patients with acute lymphoblastic leukemia in relapse.

Karyotypes of 21 patients, originally entered into the Third International Workshop on Chromosomes in Leukemia (3IWCL), were investigated in first, second and/or subsequent relapses. Karyotypes at diagnosis were related to the relapses in the following ways: normal to normal (N-N) (five cases); abnormal to normal (A-N) (two cases); abnormal to abnormal with no change (A-A) (five cases); abnormal to abnormal with clonal evolution (A-A+) (eight cases); and normal to abnormal (N-A) (one case). The A-A group comprised two each of t(4;11) and t(9;22) cases and one pseudodiploid case; included in this group were the only two patients who did not receive intensive treatment. Both A-N cases had been pseudodiploid at diagnosis. Clonal evolution A-A+ occurred in patients who had had 47-49 chromosomes or pseudodiploidy at diagnosis and was mainly due to the addition of structural change. The additional abnormalities were different in each case. The only de novo appearance of a clone (N-A) was in host cells in relapse following bone marrow transplantation. Clonal evolution occurred in patients who had been intensively treated and who relapsed late; the median time from diagnosis to relapse studied for the A-A group was 6 months and for the A-A+ group was 24 months. Survival following relapse was shorter for patients who had had a clonal abnormality at any time (median 10 months) than for those with no abnormality at diagnosis or in relapse (median 26 months).

Adolescent↗
PubMed1989

Frequency of heterozygous complete hydatidiform moles, estimated by locus-specific minisatellite and Y chromosome-specific probes.

Restriction fragment length polymorphisms identified with three locus-specific minisatellite probes and banding patterns with Y chromosome-specific probes have been examined in 39 cases of complete hydatidiform mole (CHM) and the parents. All 39 cases were shown to be androgenetic. Of the 39 cases, 8 were identified as heterozygous CHM using the minisatellite probes. Estimates for the total number of heterozygous CHM in the series ranged from 23%-29%, higher than previously reported. Of the eight identified heterozygous CHM, six had Y chromosome-specific sequences whereas two were female; this is not significantly different from the 2:1 ratio expected. The low frequency of 46,XX heterozygous CHM in the literature may reflect difficulties in distinguishing them from 46,XX homozygous CHM. Examination of RFLPs with a small panel of locus-specific minisatellite probes provides a powerful method of classifying hydatidiform mole, enabling the rare heterozygous 46,XX CHM to be accurately identified.

DNA Probes↗
PubMed1989

Chromosomes and other prognostic factors in acute lymphoblastic leukaemia: a long-term follow-up.

Cytogenetic, clinical and laboratory features at diagnosis were examined in a group of 80 children with acute lymphoblastic leukaemia (ALL) who had been followed up for a minimum of 5 1/2 years. The 17 (21%) with high hyperdiploidy tended to have low leucocyte counts and common ALL, but their favourable outcome (75% event-free survival) was independent of these factors. No patient with hypodiploidy survives while the pseudodiploid and normal groups have an intermediate prognosis. Cytogenetic analysis showed examples of patients with the well-recognized translocations and a number with apparently unique ones. Among the latter were some long-term survivors. We conclude that cytogenetic analysis identifies a good risk group of patients who remain well on long-term follow-up, but that the presence of a translocation does not necessarily imply a poor outcome.

Child↗
PubMed1989

Simultaneous application of immunolabelling and in situ hybridization to detect the origin of B and T lymphocytes in a case of acute lymphocytic leukaemia after bone marrow transplantation.

Previous cytogenetic studies, using selective mitogens, on a patient with B cell acute lymphocytic leukaemia during the 6 years of remission after bone marrow transplantation from an HLA-identical sister indicated persistence of recipient B lymphocytes in the peripheral blood. Such studies are necessarily limited to dividing cells at metaphase, which represent only a small proportion of the total cell population. We have now combined the techniques of immunolabelling and in situ hybridization on the patient's peripheral blood lymphocytes in order to define accurately their individual lineage and gender. A clear difference in the proportion of the persisting recipient lymphocytes was found between B and T lymphocyte lineages.

Adolescent↗
PubMed1988

Genetically homozygous choriocarcinoma following pregnancy with hydatidiform mole.

Genetic studies have been made in two cases of primary choriocarcinoma from patients in whom the antecedent pregnancy was a hydatidiform mole. Restriction fragment length polymorphisms of the DNA from the tumour, the patient and her partner were examined and in both cases the tumours were shown to be androgenetic in origin, having only paternal polymorphisms. While one tumour was shown to be heterozygous, two different paternal alleles being demonstrated with some probes, the other tumour was shown to be homozygous for all informative polymorphisms examined. Thus choriocarcinoma can follow complete hydatidiform mole which may be either heterozygous or homozygous.

Adult↗
PubMed1988

One haplotype matched bone marrow grafts: an investigation using the HLA system as a marker of cellular origin.

HLA antigens were used as markers to study the lymphocyte population in 31 patients with leukaemia, treated with a one-haplotype matched bone marrow transplant (BMT). In 24 patients substained engraftment was achieved and the recipient was repopulated with B and T lymphocytes of donor HLA type. Repopulation occurred at the same rate for lymphocytes of the B and T cell classes, usually within 2 weeks of grafting. In two additional cases bone marrow engraftment was successful but the lymphocyte population was chimeric and cells of both donor and host HLA type were present in the recipient for many weeks. Three patients relapsed after engraftment and peripheral blood lymphocytes were exclusively of host or donor HLA type, or a chimeric population was present. In one chimeric case, peripheral blood T lymphocytes were of donor origin, and B lymphocytes were of host origin. Mononuclear cells in the bone marrow were of host HLA type. The use of the HLA system as a marker is a useful additional approach to determine engraftment or chimerism following an allogeneic one haplotype matched bone marrow transplant.

Adolescent↗
PubMed1987

Cytogenetic studies using Q-band polymorphisms in patients with AML receiving marrow from like-sex donors.

After bone marrow transplantation (BMT), it is important to monitor the bone marrow and lymphoid cell populations of the recipient to document engraftment. When donor and recipient are of unlike sex, the sex chromosomes serve as a useful marker to determine cellular origin. When donor and recipient are of like sex, autosomal heteromorphisms can be used to identify the origin of cells in metaphase. Using Q-banding, we found that 17 of 20 patient/donor pairs (85%) examined showed at least one chromosome heteromorphism that distinguished between recipient and donor cells with certainty. Five of the patients were followed up after BMT in order to document engraftment. Donor metaphases could be detected in the marrow within two weeks of BMT when the graft was successful. Chimaerism was detected in the lymphocyte population even when the graft persisted. In a case of graft failure, donor cells did not persist in the marrow, and the lymphocyte population did not convert to donor type. These studies demonstrate that autosomal heteromorphisms are useful in the study of myeloid and lymphoid chimaeric states after BMT.

Adolescent↗
PubMed1987

A myeloproliferative disease in two infants associated with eosinophilia and chromosome t(1;5) translocation.

Two children are described who presented at the age of 5 and 7 months with anaemia, a high white cell count with eosinophilia and thrombocytopenia. Both children had an identical balanced translocation t(1;5)(q23;q33) and no evidence of a constitutional abnormality. The response to treatment of one child was poor, the other remains well on therapy. This translocation has not been previously reported and is likely to represent a subclass of myeloproliferative disorder analogous to the monosomy 7 syndrome, although less common. The previous literature of acquired chromosome abnormalities involving chromosomes 1 and 5 is reviewed.

Chromosomes, Human, Pair 1↗
PubMed1987

Cytogenetic follow-up studies of recipients of T-cell depleted allogeneic bone marrow.

Serial cytogenetic studies of bone marrow and blood cells were made in leukaemic patients who had received an allogeneic bone marrow graft from a donor of unlike sex. The donor marrow was treated with the monoclonal antibody Campath-1 before infusion. The persistence of a significant proportion of dividing recipient cells in marrow and blood was observed after grafting. These recipient cells showed evidence of radiation damage of both the stable and unstable types. More than one transient clone of chromosomally abnormal recipient cells was observed in three cases. The differences between the cytogenetic findings in patients receiving donor marrow from which T cells have been removed and those cases previously studied in our Leukaemia Unit who had received untreated donor marrow are discussed.

Adolescent↗
PubMed1987

The human chorionic gonadotrophin alpha subunit gene in gestational trophoblastic disease. 1. Restriction fragment length polymorphisms in hydatidiform moles.

The distribution of EcoR1 and HindIII restriction fragment length polymorphisms in the region of the gene coding for the alpha subunit of human chorionic gonadotrophin have been examined in 71 normal controls, six families, and 65 cases of hydatidiform mole, all of European origin. In control samples the genotypes generated by the presence or absence of the restriction sites, fitted a Hardy Weinberg distribution while in family studies the two polymorphisms showed Mendelian inheritance. The distribution of the genotypes in hydatidiform moles differed from that in control samples. However, the frequency of the alternative alleles R+, R- and H+, H- was not significantly different in the two populations and differences in the distribution of genotypes could be explained in terms of the unique origin of hydatidiform moles. The frequency of the rare homozygous genotype R-R-,H+H+, which has previously been suggested to be associated with the development of choriocarcinoma, was similar in those complete moles which resolved spontaneously (35 per cent) and those which progressed to trophoblastic tumours (27 per cent). No association was found between the genotype of the hydatidiform mole and the subsequent clinical outcome of the patient. Thus the pattern of restriction fragment length polymorphisms associated with the human chorionic gonadotrophin alpha subunit gene would not appear to be an appropriate marker of clinical outcome in patients with hydatidiform moles.

Female↗
PubMed1986

Radiation damage in patients treated by total-body irradiation, bone marrow grafting, and cyclosporin.

The bone marrow (BM) and peripheral blood (PB) from 63 patients were assessed for the presence of chromosomal aberrations after bone marrow transplantation (BMT) following total body irradiation (TBI) for leukemia. Forty-one patients showed no abnormalities in either BM or PB, and 22 had aberrations in either BM or PB or both. Only stable aberrations were found in the BM, but both stable and unstable abnormalities were present in the PB, the majority showing only unstable aberrations. Among the 25 patients who had a leukemic relapse, clonal chromosomal abnormalities were found in the BM of 12 out of the 16 cases for whom marrow was studied at the time of the relapse. A statistically significant negative correlation between leukemic relapse and graft versus host disease (GvHD) was found, but the relationships between chromosome damage and leukemic relapse, GvHD, and the pretransplant radiation dose and between the radiation dose and both leukemic relapse and GvHD were not significant.

Adolescent↗