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1.
Leukemia ; 21(12): 2428-32, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17914408

ABSTRACT

We have investigated the hypothesis that constitutional genetic variation in IL-5 signalling may be associated with the development or severity of FIP1L1-PDGFRA-positive chronic eosinophilic leukaemia (CEL) in humans. We genotyped six single-nucleotide polymorphisms (SNP) within or close to the IL5RA or IL5 genes in 82 patients with FIP1L1-PDGFRA-positive CEL plus, as controls, healthy individuals (n=100), patients with FIP1L1-PDGFRA-negative eosinophilia (n=100) or patients with chronic myeloid leukaemia (CML) (n=100). We found no association between SNP allele frequency between FIP1L1-PDGFRA-positive and control cases. However, for FIP1L1-PDGFRA cases, we found an association between the genotype at rs4054760, an SNP in the 5'-UTR of IL5RA and peripheral blood eosinophil count (P=0.026) as well as the presence or absence of tissue infiltration (P=0.032). Although these associations fell below the level of significance once corrected for multiple testing, no such association was seen in FIP1L1-PDGFRA-negative cases and no difference in allele frequencies for rs4054760 was seen in control populations across Europe. Furthermore, in an analysis of 112 patients with CML, IL5RA expression was strongly related to rs4054760 genotype (P<0.001). These data suggest that the variations in IL5RA expression are linked to constitutional IL5RA genotype and severity of FIP1L1-PDGFRA disease.


Subject(s)
5' Untranslated Regions/genetics , Hypereosinophilic Syndrome/genetics , Interleukin-5 Receptor alpha Subunit/genetics , Neoplasm Proteins/genetics , Oncogene Proteins, Fusion/analysis , Polymorphism, Single Nucleotide , Receptor, Platelet-Derived Growth Factor alpha/analysis , mRNA Cleavage and Polyadenylation Factors/analysis , Chronic Disease , Eosinophils , Europe/epidemiology , Gene Expression Regulation, Leukemic , Genotype , Humans , Hypereosinophilic Syndrome/blood , Hypereosinophilic Syndrome/epidemiology , Interleukin-5/genetics , Interleukin-5 Receptor alpha Subunit/biosynthesis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Leukocyte Count , Neoplasm Proteins/biosynthesis , Oncogene Proteins, Fusion/genetics , Phenotype , Receptor, Platelet-Derived Growth Factor alpha/genetics , mRNA Cleavage and Polyadenylation Factors/genetics
2.
Clin Lab Haematol ; 26(2): 87-93, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15053801

ABSTRACT

Seven patients who had a diagnostic problem were presented at the British Society for Haematology, Annual Scientific Meeting in 2003. The likely diagnosis was discussed on the basis of a synopsis of the history and blood film and trephine biopsy features and forms the basis of this report. Diagnostic problems dealt with included lymphoproliferative and myeloproliferative disorders and haemolytic anaemia.


Subject(s)
Hematologic Diseases/diagnosis , Hematology , Societies, Medical , Adult , Aged , Aged, 80 and over , Blood Cells/pathology , Child , Congresses as Topic , Female , Hematologic Diseases/genetics , Hematologic Diseases/pathology , Humans , Male , Middle Aged , United Kingdom
3.
Leuk Res ; 28 Suppl 1: S75-7, 2004 May.
Article in English | MEDLINE | ID: mdl-15036946

ABSTRACT

We describe here a patient with Philadelphia (Ph) chromosome-positive chronic myeloid leukemia who achieved a complete cytogenetic response following treatment with imatinib and then progressed abruptly to lymphoid blastic transformation. The sequence of events suggests that at least in some cases patients who respond well to imatinib may still harbor residual leukemia progenitor or 'stem' cells that are susceptible to acquisition of molecular events that underlie progression to advanced phase disease. The case highlights the need for molecular monitoring of responders and the need to develop strategies for reducing to a minimum or totally eradicating leukemia cells.


Subject(s)
Cell Transformation, Neoplastic , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Piperazines/therapeutic use , Pyrimidines/therapeutic use , Aged , Benzamides , Blast Crisis/etiology , Blast Crisis/pathology , Cytogenetic Analysis , Female , Humans , Imatinib Mesylate , Neoplastic Stem Cells/pathology , Remission Induction
6.
Eur J Neurol ; 7(4): 443-7, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10971606

ABSTRACT

A 57-year-old female in complete remission of grade IV non-Hodgkin lymphoma whilst on intensive chemotherapy, suddenly developed unilateral hemispheric stroke with a fatal outcome in 3 days. She was apyrexial and had received antifungal prophylaxis during her treatment. Post-mortem examination showed complete thrombosis of the internal carotid artery leading to infarction in the territory of the middle and anterior cerebral arteries. Microscopic examination of the brain showed involvement of intra-cranial vessel walls and brain parenchyma by mucormyces, with no evidence of systemic mucormycosis. Isolated cerebral mucormycosis is a rare occurrence, more commonly found in intravenous drug abusers, but can occur in patients with haematological malignancy.


Subject(s)
Central Nervous System Fungal Infections/complications , Central Nervous System Fungal Infections/etiology , Cerebral Infarction/microbiology , Lymphoma, Non-Hodgkin/complications , Mucormycosis/complications , Mucormycosis/etiology , Central Nervous System Fungal Infections/pathology , Cerebral Arteries/microbiology , Cerebral Arteries/pathology , Cerebral Arteries/physiopathology , Cerebral Infarction/pathology , Cerebral Infarction/physiopathology , Female , Humans , Middle Aged , Mucormycosis/pathology , Thrombosis/microbiology , Thrombosis/pathology , Thrombosis/physiopathology
7.
Clin Lab Haematol ; 21(4): 277-80, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10583331

ABSTRACT

Apoptosis as introduced by Kerr and colleagues describes a distinct set of morphological features that represent programmed cell death. Apoptosis frequently arises owing to genetic programming, cytotoxic drugs and physical stimuli. In order to ascertain whether all of the natural triggers of apoptosis have been identified, we looked for the presence of apoptotic cells in all routine blood films throughout a 5-month period. Patients with known malignant disease or on chemotherapy were excluded from the study. Forty-nine blood films, from 10,000 examined in this period, showed apoptosis. The number of apoptotic cells ranged from the occasional cell to 20%. Apoptotic cells were either mainly lymphoid (34 of 49) or mainly myeloid (15 of 49). All 34 cases with lymphoid apoptotic cells were seen in patients with suspected infectious mononucleosis (IM). In patients with IM, the presence of large numbers of apoptotic cells was associated with a prolonged, severe clinical course. Myeloid apoptotic cells were found in a variety of conditions, including one patient who had persistent apoptosis and was found to have myelodysplasia. Unexplained persistent apoptosis in blood films requires further investigation.


Subject(s)
Apoptosis , Blood Cells/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Blood Physiological Phenomena , Child , Child, Preschool , Female , Humans , Infant , Infectious Mononucleosis/blood , Lymphocytes/pathology , Lymphocytes/physiology , Male , Mass Screening , Middle Aged
8.
Blood Rev ; 11(3): 129-45, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9370044

ABSTRACT

An increase in the blood eosinophil count may occur in a number of disease states including allergies, parasitic infections, vascular disease and as a reaction to the presence of malignant tumours. This article defines those disorders that are not purely reactive, and describes in detail the diagnosis and features of clonal eosinophilic disorders and the hypereosinophilic syndrome. The clonal disorders that are associated with eosinophilia are discussed, in particular the acute and chronic eosinophilic leukaemias and clonal eosinophilias in association with acute myeloid leukaemia, myeloproliferative disorders and myelodysplastic syndromes. Whether eosinophilia is produced by a clonal or reactive disorder, the end result can often be the same, i.e. end organ damage produced by sustained hypereosinophilia in the presence of eosinophil activation. When no cause for the eosinophilia leading to the end organ damage is found, this disease is termed 'idiopathic hypereosinophilic syndrome'. Its pathogenesis, clinical features and management are discussed with particular reference to the possibility of it being a T-cell-associated disorder.


Subject(s)
Hypereosinophilic Syndrome , Animals , Clone Cells , Humans , Hypereosinophilic Syndrome/diagnosis , Hypereosinophilic Syndrome/etiology , Hypereosinophilic Syndrome/pathology , Leukemia, Myeloid, Acute/complications , Myelodysplastic Syndromes/complications , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications
10.
J Infect ; 32(1): 27-32, 1996 Jan.
Article in English | MEDLINE | ID: mdl-8852548

ABSTRACT

The treatment of salmonella osteomyelitis in sickle cell disease (SCD) is difficult and the emergence of antibiotic resistance in Salmonella spp presents further problems for clinicians treating SCD. Three patients presented with salmonella bacteraemia. Treatment with several intravenous antibiotics did not prevent the subsequent development of osteomyelitis. Emergence of resistance to multiple antibiotics, including ciprofloxacin, during the treatment of salmonella osteomyelitis in SCD patients is reported here for the first time. Ceftriaxone 2 g once daily given for 3 months to 3 years was an effective and convenient treatment for osteomyelitis caused by multiply-resistant salmonella. Two of these patients gave a definite history of diarrhoea, and stool cultures confirmed the presence of Salmonella spp in one. Our experience shows that salmonella osteomyelitis may not be prevented by early treatment of bacteraemia in SCD patients. Other measures to reduce the risk of salmonella infection are therefore necessary.


Subject(s)
Anemia, Sickle Cell/complications , Anti-Infective Agents/therapeutic use , Ciprofloxacin/therapeutic use , Osteomyelitis/drug therapy , Salmonella Infections/drug therapy , Salmonella/drug effects , Adult , Drug Resistance, Microbial , Female , Humans , Male , Osteomyelitis/etiology , Salmonella Infections/etiology
12.
Br J Haematol ; 76(2): 210-4, 1990 Oct.
Article in English | MEDLINE | ID: mdl-2094323

ABSTRACT

Over a 4 1/2-year period, 141 patients with acute leukaemia had morphologic, immunophenotypic and cytochemical studies performed at King's College Hospital. Seven cases were noted to have blast cells which did not express myeloid or lymphoid antigens or cytochemical staining indicative of differentiation but were HLA DR and CD 34 positive. Based on these criteria we have used the term stem cell acute leukaemia to denote these patients. There were five women and two men with a median age of 61 years (16-86). Presentation marrows were heavily infiltrated with blasts (greater than 95% in 6/7) which were usually pleomorphic. Type 2 blasts. Auer rods and dysplastic features were absent. Two of six cases studied showed clonal karyotypic abnormalities. Four patients were treated with high dose chemotherapy. Three of these achieved a complete remission but relapsed at 3, 6 and 7 months respectively. The median survival of the group was 7 months (2-12). We conclude that the stem cell acute leukaemias are a distinct clinicomorphological group which appear to have a poor prognosis with conventional chemotherapy.


Subject(s)
Antigens, Surface/analysis , Leukemia/physiopathology , Acute Disease , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal , Antigens, CD/analysis , Bone Marrow/pathology , Female , Hematopoietic Stem Cells/pathology , Humans , Karyotyping , Leukemia/immunology , Leukemia/pathology , Male , Middle Aged , Phenotype , Retrospective Studies
14.
Br J Haematol ; 73(1): 76-81, 1989 Sep.
Article in English | MEDLINE | ID: mdl-2572271

ABSTRACT

We treated 14 patients with Ph-chromosome-positive chronic myeloid leukaemia still in chronic phase by autografting with blood-derived haemopoietic stem cells. Eleven patients were autografted electively after cytoreductive treatment with busulphan (16 mg/kg) and melphalan (60 mg/m2) and three were autografted after marrow cells from HLA-identical sibling donors had failed to engraft. In 13 patients haemopoiesis recovered; one failed to engraft and died 114 d after autografting. Two other patients became pancytopenic and received further stem cell transfusions at 3 and 40 months respectively after first autografting. One patient entered lymphoid transformation and died 14 months after autografting. Twelve patients survive at a median of 41 months (range 24-53) after autografting. Nine of the survivors have required further chemotherapy after autografting and four of the nine were electively autografted on a second occasion. Three patients surviving after autografting for 28, 43 and 53 months respectively have not required further chemotherapy. In two of these patients haemopoiesis is now predominantly Ph-negative. We conclude that autografting in chronic phase might prolong survival in some cases by reducing the size of the leukaemic stem cell population. The fact that initially successful grafts failed in two patients suggests that blood-derived stem cells may have a finite potential for self-replication.


Subject(s)
Hematopoiesis , Hematopoietic Stem Cell Transplantation , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Busulfan/adverse effects , Chronic Disease , Combined Modality Therapy , Female , Follow-Up Studies , Graft Rejection , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Male , Middle Aged
15.
Leuk Res ; 13(7): 605-7, 1989.
Article in English | MEDLINE | ID: mdl-2668647

ABSTRACT

A 55-yr old woman with refractory anaemia with excess of blasts in transformation developed prolonged bone marrow hypoplasia following two courses of mitozantrone and cytosine arabinoside. The administration of granulocyte-monocyte colony stimulating factor after two months of pancytopenia led to recovery of normal bone-marrow function, without any morphological evidence of myelodysplasia, which has persisted until the last blood count (6 months +).


Subject(s)
Anemia, Refractory, with Excess of Blasts/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cell Transformation, Neoplastic/drug effects , Colony-Stimulating Factors/administration & dosage , Growth Substances/administration & dosage , Anemia, Refractory, with Excess of Blasts/blood , Anemia, Refractory, with Excess of Blasts/therapy , Bone Marrow/drug effects , Bone Marrow/pathology , Cell Transformation, Neoplastic/pathology , Cytarabine/administration & dosage , Female , Granulocyte-Macrophage Colony-Stimulating Factor , Humans , Middle Aged , Mitoxantrone/administration & dosage
17.
Br J Haematol ; 68(4): 411-5, 1988 Apr.
Article in English | MEDLINE | ID: mdl-3163932

ABSTRACT

We describe the occurrence of an unusual mode of relapse in six of 24 patients who presented with de novo acute myeloid leukaemia (AML) associated with trilineage myelodysplasia (TMDS). After the induction of complete remission (CR) by intensive chemotherapy in five patients and following bone marrow transplantation (BMT) in one, the myelodysplastic state, but not overt AML, recurred. Relapse of myelodysplasia occurred at a median of 147 weeks (50-520) from presentation and in two instances was followed a year later by AML. In five cases, myelodysplastic relapse was treated with low-dose cytosine arabinoside given alone or with other chemotherapeutic agents. Three patients remain in CR after 1, 2 and 5 years. The reappearance of myelodysplastic features in these six patients was strongly correlated with the presence of TMDS at presentation of the AML. It was not observed once in the 136 AML patients, treated similarly, who did not have associated TMDS at presentation (P less than 0.001). Thus, relapse with myelodysplasia is not an effect of chemotherapy as has been previously postulated.


Subject(s)
Leukemia, Myeloid, Acute/pathology , Myelodysplastic Syndromes/pathology , Adolescent , Adult , Female , Humans , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/therapy , Male , Middle Aged , Myelodysplastic Syndromes/complications , Myelodysplastic Syndromes/therapy , Time Factors
18.
Eur J Haematol ; 40(2): 185-7, 1988 Feb.
Article in English | MEDLINE | ID: mdl-3257929

ABSTRACT

A case of T-prolymphocytic leukaemia (T-PLL) presenting with deafness and confusion is reported. Computerised tomography (CT) of the head showed several well-defined, rounded, high attenuation areas in the temporal, parietal and occipital regions of the brain substance that were suggestive of metastases. Treatment with weekly intravenous deoxycoformycin produced complete resolution of the CT abnormalities together with haematological evidence of disease regression 6 weeks after treatment was started.


Subject(s)
Brain/diagnostic imaging , Coformycin/therapeutic use , Leukemia, Lymphoid/drug therapy , Ribonucleosides/therapeutic use , Antineoplastic Agents/therapeutic use , Coformycin/analogs & derivatives , Humans , Injections, Intravenous , Leukemia, Lymphoid/diagnostic imaging , Male , Middle Aged , Pentostatin , Tomography, X-Ray Computed
20.
Br J Haematol ; 66(4): 445-50, 1987 Aug.
Article in English | MEDLINE | ID: mdl-3478074

ABSTRACT

Primary myelodysplastic syndromes progress to acute myeloid leukaemia (AML) in about 30% of cases. We have sought evidence of pre-existing trilineage myelodysplasia (TMDS) using the FAB criteria (1982) in 160 consecutive cases of primary de novo AML. TMDS was found in 24 cases (15%) including two of 33 cases of M1 (6%), four of 40 cases of M2 (10%), none of 18 cases of M3, five of 31 cases of M4 (15%), six of 30 cases of M5 (20%), all of six cases of M6 and one of two cases of M7. The median presentation bone-marrow blast-cell count in the 24 AML/TMDS cases was 53% (30-90%) and 82% (45-100%) in the 136 cases of AML without TMDS. 60% of the AML/TMDS bone-marrow aspirates contained fewer than 60% of blasts compared with only 11% of those from AML without TMDS (P less than 0.001). In AML the occurrence of symptomatic cytopenias when the marrow blast-cell count is below 60% and the peripheral blood blast-cell count is below 20% is highly correlated with dysplastic haemopoiesis (P less than 0.001).


Subject(s)
Leukemia, Myeloid, Acute/etiology , Myelodysplastic Syndromes/complications , Adolescent , Adult , Aged , Bone Marrow/pathology , Female , Humans , Leukemia, Myeloid, Acute/blood , Leukemia, Myeloid, Acute/pathology , Male , Middle Aged
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