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D Swirsky

Publications and source records attributed to D Swirsky.

At least 19 recordsLinked to original sources
PubMed2001

Cytogenetic and morphological abnormalities in paroxysmal nocturnal haemoglobinuria.

Paroxysmal nocturnal haemoglobinuria (PNH) is characterized by the expansion of a haematopoietic stem cell clone with a PIG-A mutation (the PNH clone) in an environment in which normal stem cells are lost or failing: it has been hypothesized that this abnormal marrow environment provides a relative advantage to the PNH clone. In patients with PNH, generally, the karyotype of bone marrow cells has been reported to be normal, unlike in myelodysplastic syndrome (MDS), another clonal condition in which cytogenetic abnormalities are regarded as diagnostic. In a retrospective review of 46 patients with a PNH clone, we found a karyotypic abnormality in 11 (24%). Upon follow-up, the proportion of cells with abnormal karyotype decreased significantly in seven of these 11 patients. Abnormal morphological bone marrow features reminiscent of MDS were common in PNH, regardless of the karyotype. However, none of our patients developed excess blasts or leukaemia. We conclude that in patients with PNH cytogenetically abnormal clones are not necessarily malignant and may not be predictive of evolution to leukaemia.

Adolescent↗
PubMed1999

Quinine-induced immune thrombocytopenic purpura followed by hemolytic uremic syndrome.

Immune thrombocytopenic purpura (ITP) mediated by quinine-dependent platelet reactive antibodies is well recognized. More recently there have been a number of reports of quinine-induced hemolytic-uremic syndrome (HUS). We describe a patient with quinine-induced immune thrombocytopenia who subsequently developed HUS after re-exposure to a single dose of this drug. To our knowledge, this is the first such case reported. Multiple quinine-dependent antibodies have been characterized in the patient's serum. Initially, quinine-dependent antibodies were directed solely against the platelet glycoprotein complex GPIb/IX. After rechallenge with quinine, there was broadening of quinine-dependent antibody specificities, which were now also directed against the platelet glycoprotein complexes GPIb/IX and GPIIb/IIIa, endothelial cells, and leukocytes. We have shown quinine-dependent antibody-mediated endothelial cell activation, which supports an immunopathogenic role for quinine-dependent antibodies in the causation of this disease.

Antibodies↗
PubMed1997

Oral squamous cell carcinoma after allogeneic bone marrow transplantation for Fanconi anaemia.

We report a case of oral squamous cell carcinoma (SCC) originating in the buccal mucosa of an 18-year-old female patient with chronic graft-versus-host disease (GVHD) 9 years after HLA-identical sibling bone marrow transplantation (BMT) for Fanconi anaemia (FA). The case highlights the problems of malignant change in FA and also the increased risk of second malignancy after BMT. The literature is reviewed with regard to previous cases and the possible aetiology of tumour formation. A high index of suspicion to any epithelial lesion in FA is appropriate so that early diagnosis may lead to improved prognosis.

Adolescent↗
PubMed1997

Incidence of AML1/ETO fusion transcripts in patients entered into the MRC AML trials. MRC Adult Leukaemia Working Party.

Acute myeloid leukaemia (AML) with the t(8;21)(q22;q22) is deemed to be a 'good-risk' disease. 396 patients with AML at diagnosis were screened for the presence of t(8;21) and AML1/ETO fusion transcripts by cytogenetic and RT-PCR techniques respectively. 32 cases of t(8;21) were detected, all of which were also PCR positive. A further 19 cases were detected at the molecular level, predominantly but not exclusively in M1 and M2 FAB types. Approximately 12% of all new cases of AML are estimated to have AML1/ETO fusion transcripts and it is suggested that molecular screening should be performed in all cases with the possible exception of the M3 FAB type.

Acute Disease↗
PubMed1996

Leukemia-associated changes identified by quantitative flow cytometry. IV. CD34 overexpression in acute myelogenous leukemia M2 with t(8;21).

During the immunodiagnosis of 517 cases of acute myelogenous leukemia (AML) entered into the Medical Research Council (MRC) AML 10 trials, we have observed the CD34 precursor cell antigen more frequently in AML of M2 morphology, especially in the 84% of cases with the t(8;21) chromosomal translocation, than in any other French-American-British classification group. CD34 expression was then quantified (using QIFI and Quantum Simply Cellular beads [Flow Cytometry Standards, Research Triangle Park, NC] and CD34+ standard cells). When CD34 antibody-binding capacity (ABC) of normal bone marrow (BM) precursors and leukemic blasts was compared, it was shown that AML M2 cases with t(8;21) not only had the highest percentages of CD34+ blasts, but in > 80% of CD34+ cases the individual blasts expressed higher than normal levels of CD34 antigen (> 60 x 10(3) ABC per cell). In addition, in 73% of this group CD34 antigen was overexpressed in an asynchronous combination with cytoplasmic myeloperoxidase (MPO). Other signs of asynchrony included high CD34 expression with CD15 and/or CD56, as well as aberrant combinations of CD13 with terminal deoxynucleotidyl transferase (TdT) and CD19. These findings demonstrate that asynchrony is identifiable in virtually every case of AML with t(8;21), although it does not always involve the same antigens. M2 cases with t(8;21), mostly CD34+, had a 100% remission rate and 71% 5-year survival rate; other patients with CD34+ or CD34- AML showed 69% and 84% remission rates and 31% and 36% 5-year survival rates, respectively. Consequently, individual markers such as CD34 should be interpreted in relation to other features such as chromosomal changes. These simple methods, which are well suited to quantify the expression of ligands, are a useful contribution to diagnosis: 60% to 65% of M2 cases with t(8;21) are rapidly identified by CD34 overexpression alone. This aberration, together with the other signs of asynchrony seen at presentation, can be used to search for residual leukemia after therapy.

Adolescent↗
PubMed1996

Establishing the presence of the t(15;17) in suspected acute promyelocytic leukaemia: cytogenetic, molecular and PML immunofluorescence assessment of patients entered into the M.R.C. ATRA trial. M.R.C. Adult Leukaemia Working Party.

Detection of the t(15;17) or its molecular consequence, the PML-RAR alpha rearrangement, is critical for meaningful analysis of clinical trials involving patients with suspected acute promyelocytic leukaemia (APL). Its presence remains the best predictor of a favourable response to retinoids, such as ATRA, which in combination with chemotherapy confer significant improvements in disease-free survival. We have evaluated the relative efficacy of RT-PCR, cytogenetics and PML immunofluorescence staining to identify the existence of the translocation in 100 patients entered into the Medical Research Council (M.R.C.) ATRA trial. RT-PCR successfully identified PML-RAR alpha rearrangements in 93/100 patients, including 65 where only peripheral blood or post-induction marrow samples were available for analysis and in 12 patients in whom cytogenetic assessment failed to demonstrate t(15;17) due to poor-quality metaphases (10/12) or as a reflection of cryptic PML-RAR alpha rearrangements (2/12). Parallel employment of the RAR alpha-PML assay confirmed expression of del(17q)-derived transcripts in 81% and permitted determination of the PML breakpoint (a potential independent prognostic variable) in all 93 cases. Sequencing of RT-PCR products derived from 50 patients with 3' PML breakpoints revealed five bcr 2 cases, including a novel exon 5 breakpoint. 35/81 (43%) patients with cytogenetic evidence of t(15;17) possessed additional karyotypic abnormalities. In four patients with available buffy coat smears, lack of cytogenetic or molecular evidence of the t(15;17) was confirmed by a wild-type PML immunofluorescence nuclear staining pattern, in contrast to the characteristic microparticulate distribution detected in 14 patients with RT-PCR evidence of the rearrangement. However, although PML immunofluorescence staining is suitable for rapid determination of patients likely to benefit from ATRA, this approach does not obviate the need for cytogenetic and RT-PCR analysis of all patients entered into APL clinical trials, because both techniques provide additional information which may prove to be of independent prognostic significance.

Adolescent↗
PubMed1996

DNA haplotypes in Africans and West Indians with sickle cell anaemia or SC disease.

Considering that genetic variation linked to the beta S mutation may influence the clinical manifestations of sickle cell disease, we have analyzed the beta globin cluster haplotypes in 47 patients with this condition (33 SS homozygotes, one S/beta thal (0), and 13 SC) living in London (30 West Indian, 17 West African). Of the 80 chromosomes tested, 82.5% had the Benin haplotype and of the 13 C chromosomes tested, 85% had the Bantu-A4 haplotype. A minority of patients had Bantu or Senegal haplotypes, and in 5 patients we found new haplotypes called E, H and O which may have arisen through mutation or recombination. Because of the predominance of a single haplotype (Benin) nearly all our homozygous S patients were either homozygous or heterozygous for this haplotype. We concluded that the beta globin haplotype is unlikely to be an important determinant of the clinical severity in this patient population.

Africa, Western↗
PubMed1995

Recommended procedures for the classification of acute leukaemias.

The classification of acute leukaemias is now widely based on a combined morphological, cytochemical and immunophenotyping approach. Difficulties are frequently encountered however in reaching an acceptable degree of diagnostic concordance between different laboratories because of variations in the techniques used (in terms of methodologies, reagents and equipment) and diagnostic interpretation. The International Council for Standardization in Haematology (ICSH) convened an expert panel to consider currently available diagnostic techniques with the aim of defining a minimum cytochemical and immunological diagnostic panel that could be used as core components for the classification of acute leukaemia. The proposed ICSH scheme, which attempts to balance the basic requirement for providing precise and informative diagnostic information without limiting its use to only those laboratories with sophisticated facilities, is based on three sequential levels of investigation; primary cytochemistry, intracellular phenotyping and membrane immunophenotyping. The minimum ICSH recommended cytochemistries comprise myeloperoxidase (MPO), chloroacetate esterase (ChlorE) and alpha-naphthyl acetate esterase (ANAE), and standardised methods for these cytochemistries are detailed in this communication. For cases of acute leukaemia that remain unclassified by primary cytochemistry, subsequent immunological analyses for cytoplasmic CD3, CD22, MPO and nuclear TdT are recommended. The ICSH panel considers that the use of these minimum primary cytochemical and intracellular phenotyping procedures will lead to the consistent classification of most acute leukaemias, and that the third level of investigation (membrane immunophenotyping) should be used for the purposes of confirmation, diagnostic clarification of atypical leukaemias, and the subtyping of acute lymphoblastic leukaemias (ALL). The ICSH panel also recognised that there are a number of additional technologies which can provide definitive diagnostic information, such as cytogenetics and DNA genotyping, but these were excluded from the minimum panel because of their restricted availability. While many specialised laboratories, particularly in the areas of diagnostic research, will continue to use individual investigatory protocols, it is considered that the inclusion of the ICSH scheme as core components would lead to greater consistency when comparing independent studies of acute leukaemia.

Acute Disease↗
PubMed1994

Myelodysplasia in a patient with pre-existing paroxysmal nocturnal haemoglobinuria: a clonal disease originating from within a clonal disease.

Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired haemolytic anaemia, clonal in nature, due to somatic mutation. PNH may evolve to aplastic anaemia; more rarely to a myelodysplastic syndrome (MDS) or to acute myeloid leukaemia (AML). We have studied a patient who suffered from PNH and later developed refractory anaemia with ringed sideroblasts (RARS) associated with trisomy 8. By testing peripheral blood cells with appropriate antibodies we have shown that all of the red cells, neutrophils and monocytes, as well as 20% of the lymphocytes, belonged to the PNH clone; in contrast, only 43% of neutrophils and 22% of monocytes belonged to the MDS clone. We infer that the MDS must have arisen from within the PNS clone.

Adult↗
PubMed1993

Chronic liver disease due to hepatitis C.

The low concentration of hepatitis C virus in the blood of infected patients has made it difficult to detect. Infected patients can now be identified by using more sensitive immunoassays and amplification of viral RNA by the polymerase chain reaction. Nevertheless, the virus remains difficult to eliminate. We present the case of a woman with a history of autoimmune haemolytic anaemia, thrombocytopenia, and common variable immunodeficiency who developed chronic hepatitis.

Adult↗
PubMed1993

Recommended procedures for the classification of acute leukaemias. International Council for Standardization in Haematology (ICSH).

The classification of acute leukaemias is now widely based on a combined morphological, cytochemical and immunophenotyping approach. Difficulties are frequently encountered however in reaching an acceptable degree of diagnostic concordance between different laboratories because of variations in the techniques used (in terms of methodologies, reagents and equipment) and diagnostic interpretation. The International Council for Standardization in Haematology (ICSH) convened an expert panel to consider currently available diagnostic techniques with the aim of defining a minimum cytochemical and immunological diagnostic panel that could be used as core components for the classification of acute leukemia. The proposed ICSH scheme, which attempts to balance the basic requirement for providing precise and informative diagnostic information without limiting its use to only those laboratories with sophisticated facilities, is based on three sequential levels of investigation; primary cytochemistry, intracellular phenotyping and membrane immunophenotyping. The minimum ICSH recommended cytochemistries comprise myeloperoxidase (MPO), chloroacetate esterase (ChlorE) and alpha-naphthyl acetate esterase (ANAE), and standardised methods for these cytochemistries are detailed in this communication. For cases of acute leukaemia that remain unclassified by primary cytochemistry, subsequent immunological analyses for cytoplasmic CD3, CD22, MPO and nuclear TdT are recommended. The ICSH panel considers that the use of these minimum primary cytochemical and intracellular phenotyping procedures will lead to the consistent classification of most acute leukaemias, and that the third level of investigation (membrane immunophenotyping) should be used for the purposes of confirmation, diagnostic clarification of atypical leukaemias, and the subtyping of acute lymphoblastic leukaemias (ALL). The ICSH panel also recognised that there are a number of additional technologies which can provide definitive diagnostic information, such as cytogenetics and DNA genotyping, but these were excluded from the minimum panel because of their restricted availability. While many specialised laboratories, particularly in the areas of diagnostic research, will continue to use individual investigatory protocols, it is considered that the inclusion of the ICSH scheme as core components would lead to greater consistency when comparing independent studies of acute leukemia.

Acute Disease↗
PubMed1992

Diagnosis of acute promyelocytic leukaemia by RT-PCR: detection of PML-RARA and RARA-PML fusion transcripts.

Acute promyelocytic leukaemia (APL; AML M3) is identified by a unique t(15;17) translocation which fuses the PML gene to the retinoic acid receptor alpha gene (RARA). Reverse transcription coupled with the polymerase chain reaction (RT-PCR) has been used to develop a diagnostic test for APL based on the PML-RARA fusion message. Separate PCR assays were designed to amplify either PML-RARA (15q+ derived) or RARA-PML (17q- derived) chimaeric transcripts. PML-RARA transcripts were detected in every case from a series of 18 APL patients with cytogenetically confirmed t(15;17) translocations, whereas RARA-PML messages were detected in only 67% (12/18) of these patients. This suggests that it is the 15q+ derivative which mediates leukaemogenesis. Furthermore the PCR approach (or Southern analysis) may be used to identify in which of the alternative PML introns the breakpoint occurs; 52% of cases (15/29 patients) utilize a 5' PML intron and 48% the 3' intron (14/29 cases). Neither the choice of PML intron nor the expression of the 17q- derivative could be correlated with the microgranular variant of APL (M3V), overall survival rate, age, sex or presence of coagulopathy. Finally, the fusion message is undetectable in five remission samples. This indicates a possible use for RT-PCR in monitoring remission patients for evidence of relapse.

Adolescent↗