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D A Galton

Publications and source records attributed to D A Galton.

At least 19 recordsLinked to original sources
PubMed1992

Haematological differences between chronic granulocytic leukaemia, atypical chronic myeloid leukaemia, and chronic myelomonocytic leukaemia.

Chronic myeloid leukaemia (CML) is a generic term that include five apparently distinct entities. The best known form, the classical Ph-positive subtype, accounts for about 90% of all cases of CML. The morphology of its presentation blood film is highly characteristic but is also seen in about half of the remaining 10% of cases, which are Ph-negative. This classical morphological subtype, whether Ph-positive or Ph-negative I describe as 'chronic granulocytic leukaemia' to refer to the exuberant granulocytic proliferation which is its hallmark. This term is often used indiscriminately and interchangeably with 'chronic myeloid leukaemia' and similar terms, just as 'chronic lymphocytic leukaemia' was, until recently, used to cover the chronic lymphoid leukaemias in general, but is now used in a specific sense. Chronic granulocytic leukaemia (CGL), whether Ph-positive or Ph-negative, is almost always BCR-rearranged and associated with the production of a unique 210-kd protein with enhanced tyrosine kinase activity. Most of the remaining cases of Ph-negative CML are examples of either chronic myelomonocytic leukaemia (CMML), a subtype almost as homogeneous as CGL, and characterized in its presentation blood film by the presence of monocytes and neutrophils but few immature granulocytes, or atypical CML (aCML), distinct from and less homogeneous than either CGL or CMML, in which some cases also share features with CGL while others share some with CMML. CMML and aCML do not show BCR rearrangement and are not associated with the production of p210kd. CGL, CMML, and aCML, though characterized on morphological features differ in their clinical features and behaviour, response to treatment and survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1991

Proposal for the recognition of minimally differentiated acute myeloid leukaemia (AML-MO)

We describe a form of acute myeloid leukaemia (AML), designated AML-MO, with minimal myeloid differentiation, not included previously in the FAB classification. AML-MO cannot be diagnosed on morphological grounds alone as the blast cells are large and agranular, sometimes resembling L2 or, rarely, L1 lymphoblasts, and should be identified by the following features: negative myeloperoxidase (MPO) and Sudan Black B reaction (or positive in less than 3% of blasts), negative B and T lineage markers and expression of myeloid antigens recognized by at least one monoclonal antibody, CD13 or CD33. Other myeloid markers are also often positive and these include CD11b and the enzyme MPO demonstrated by immunocytochemistry and/or electron microscopy analysis. The findings in a group of 10 cases satisfying the criteria for AML-MO are described. AML-MO represents 2-3% of all cases of AML and 1-1.5% of all acute leukaemias. Its clinical and biological significance is not yet apparent but its identification in a larger number of cases may achieve this aim.

Acute Disease↗
PubMed1989

Autografting for patients with chronic myeloid leukaemia in chronic phase: peripheral blood stem cells may have a finite capacity for maintaining haemopoiesis.

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.

Adult↗
PubMed1989

Marrow aplasia developing 3 years after treatment with busulphan for chronic myeloid leukaemia.

A 31-year-old woman with Philadelphia chromosome-positive chronic myeloid leukaemia (CML) was treated intermittently with high-dose busulphan over a 6-yr period (total dose 1320 mg). 3 yr later (after receiving no further cytotoxic drugs) she developed pancytopenia and marrow aplasia of relatively abrupt onset. Transfusion of reconstituted blood-derived stem cells (collected 7 yr previously) re-established chronic phase CML. These events are more consistent with 'stem cell exhaustion' than with an acquired marrow microenvironmental defect occurring in the course of CML. The contribution of busulphan is uncertain.

Adult↗
PubMed1989

Proposals for the classification of chronic (mature) B and T lymphoid leukaemias. French-American-British (FAB) Cooperative Group.

Peripheral blood, bone marrow films, and bone marrow biopsy specimens from 110 patients, well characterised by clinical and laboratory studies, including electron microscopy, were reviewed, to determine proposals for the classification of chronic (mature) B and T cell leukaemias. On the basis of cytology and membrane phenotype the following disorders were defined: (i) B cell type: chronic lymphocytic leukaemia (CLL); CLL of mixed cell type, which includes cases with more than 10% and less than 55% prolymphocytes (CLL/PL), and a less well defined form with pleomorphic lymphocytes but less than 10% prolymphocytes; prolymphocytic leukaemia (PLL); hairy cell leukaemia (HCL); HCL variant; splenic lymphoma with circulating villous lymphocytes; leukaemic phase of non-Hodgkin's lymphoma (follicular lymphoma, intermediate, or mantle zone lymphoma and others); lymphoplasmacytic lymphoma with peripheral blood disease (mostly Waldenström's macroglobulinaemia); and plasma cell leukaemia. (ii) T cell type: T/CLL, which was differentiated from reactive T/lymphocytosis; T/PLL; adult T cell leukaemia/lymphoma; and Sézary's syndrome. The recognition of distinct entities within the B and T cell leukaemias seems to have clinical and epidemiological connotations. It is hoped that these proposals may serve as the basis for further work, discussion, and improved management of patients.

Adult↗
PubMed1989

Terminal transformation in B-cell chronic lymphocytic leukaemia.

Terminal transformation of chronic lymphocytic leukaemia (CLL) comparable to the blast-cell transformation which is responsible for almost all deaths in the chronic myeloid leukaemias is a rare event because the majority of CLL patients die without a major or easily recognised morphological transformation of the leukaemia cells having occurred. However, a substantial proportion of these patients die with progressive treatment-resistant disease or from intractable infections resulting from CLL-related immunodeficiency. In many of these patients biological transformation of the leukaemia cells can be associated with the appearance of complex chromosomal changes not present earlier or additional to the commonly present trisomy 12(1). In a broad sense, therefore, all of these patients may be said to undergo lethal transformation of their disease in contrast to the, admittedly substantial numbers, especially of elderly males who die from causes totally unrelated to their CLL, especially cardiovascular and cerebrovascular diseases, and other malignant diseases. In the narrow sense the term 'terminal transformation' is usually restricted to those conditions in which the terminal event is the proliferation of a new population of lymphoid cells of enhanced malignancy. There are three well-known types of transformation. One, 'prolymphrocytoid' transformation is relatively low-grade, while the other two, 'Richter's syndrome' and 'immunoblastic transformation' are rapidly progressive conditions. The last two account for about 5% of all deaths in CLL, but the slowly progressive prolymphocytoid transformation has been described too recently to permit reliable estimates of its frequency in unselected series to CLL. It may be of the order of 10%.

Blast Crisis↗
PubMed1988

Myelodysplastic relapse of de novo acute myeloid leukaemia with trilineage myelodysplasia: a previously unrecognized correlation.

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.

Adolescent↗
PubMed1988

Morphology and immunology of circulating cells in leukaemic phase of follicular lymphoma.

Ten patients with follicular lymphoma presented with a high white cell count (45-220 x 10(9)/l) which resembled chronic lymphocytic leukaemia (CCL): all had pronounced splenomegaly and, except one, generalised lymphadenopathy. The blood lymphocytes were small with scanty cytoplasm, densely condensed nuclear chromatin, and deep clefts originating in sharp angles from the nuclear surface. CLL cells are larger, have more cytoplasm, a different pattern of chromatin condensation, and may have shallow nuclear indentations or foldings rather than clefts. The circulating follicular lymphoma cells had moderate to strong membrane immunoglobulins (SmIg), low mouse (M)-rosettes, strong reactivity with the monoclonal antibody FMC7, and occasional expression of the CD5-antigen; at least one third of cells in each case were positive with anti-cALLa (J5,CD10). Half the cases were referred as B-CLL but none had the typical B-CLL immunophenotype: weak SmIg, M-rosettes of greater than 50%, CD5 positive, FMC7 and J5 negative. The diagnosis of follicular lymphoma was confirmed by lymph node biopsy in seven of the 10 cases. The overall response to treatment was poor and five patients died within three years of diagnosis. This aggressive form of follicular lymphoma needs to be distinguished from B-CLL as different management is required.

Adult↗
PubMed1988

The correlation of breakpoint cluster region rearrangement and p210 phl/abl expression with morphological analysis of Ph-negative chronic myeloid leukemia and other myeloproliferative diseases.

The chromosome 22 derivative, the Philadelphia (Ph) chromosome, results from a reciprocal translocation t(9;22) (q34;q11) and is associated with chronic myeloid leukemia (CML). The translocation can be identified at the DNA level in Ph-positive CML by using a probe to the breakpoint cluster region (bcr). In addition, as a result of this translocation an abl-related 210-kd protein with protein tyrosine kinase (PTK) activity is produced. We analyzed 28 cases of Ph-negative CML for rearrangement of the chromosome 22 sequences and found that eight of the 28 show rearrangement of the bcr. When 12 of the Ph-negative cases were independently reviewed, five were indistinguishable from Ph-positive CML on the basis of morphology, peripheral blood film and clinical details. These five also showed bcr rearrangement. The other seven were reclassified as six atypical CML (aCML) and one chronic myelomonocytic leukemia (CMML). None of these seven showed bcr rearrangement. In addition 11 cases of bcr- CML were assayed for abl-related PTK, and no detectable activity was present, whereas p210 phl/abl PTK was observed both in Ph-positive (three cases examined) and Ph-negative, bcr + (four cases examined) CML. Therefore, bcr + CML, whether or not the Ph chromosome is cytogenetically apparent, involves a similar molecular alteration and produces the 210-kd protein with enhanced PTK activity. Furthermore, these cases can be distinguished from Ph-negative bcr- CML by careful evaluation of clinical and hematologic data.

Chromosomes, Human, Pair 22↗
PubMed1987

Haematological classification of the chronic myeloid leukaemias.

Chronic myeloid leukaemia (CML) includes five subtypes, and the term should be used in the same way as the term chronic lymphoid leukaemia to refer to a group of related conditions. The subtypes of CML are: 1. Chronic granulocytic leukaemia (CGL) (95% of all CML; 90% are Ph+, BCR+, 5% are Ph-, BCR+); 2. Juvenile CML (extremely rare; Ph-, BCR- in the few so far examined); 3. Chronic neutrophilic leukaemia (CNL) (extremely rare; Ph-, BCR- in the few so far examined); 4. Chronic myelomonocytic leukaemia (CMML). CMML with low or normal leukocyte counts is classified as a myelodysplastic syndrome; CMML with high leukocyte count is both myelodysplastic and myeloproliferative. Ph-, BCR-; 5. Atypical CML (aCML). Intermediate between CGL and CMML but has distinctive features. Ph-, mostly BCR-. Significance of few reported BCR+ uncertain. Markedly worse survival than CGL and probably worse than CMML. Definition needs refining. Types 2, 3, 4 and 5 account for 5% of all CML. CGL, CMML, aCML and CNL can be diagnosed in the great majority of cases from the morphological profile of presentation peripheral blood films, but high-quality Romanowsky staining is essential.

Blood Cell Count↗
PubMed1987

A comparison of the incidence of the myelodysplastic syndrome and acute myeloid leukaemia following melphalan and cyclophosphamide treatment for myelomatosis. A report to the Medical Research Council's working party on leukaemia in adults.

Twelve of 648 patients in the Medical Research Council's first two trials in myelomatosis have developed myelodysplasia or acute leukaemia. This corresponds to a 5-year actuarial prevalence of 3% and an 8-year prevalence of 10%. Patients were randomised to treatment with either melphalan or cyclophosphamide and the relative capabilities of these two drugs to cause these conditions were examined as a function of duration of treatment. A significant relationship with length of melphalan treatment was found but no relationship was observed for cyclophosphamide treatment. The amount of melphalan treatment given in various intervals before diagnosis of myelodysplasia or leukaemia was studied and it was found that the amount of treatment in the most recent 3-year period was the most important determinant of risk (P = 0.0001). It is estimated that the risk of haemopoietic neoplasia after 10 years of follow-up is about 3% for each year of melphalan treatment and that much of this risk will occur within three years of the last treatment.

Aged↗