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T Hamblin

Publications and source records attributed to T Hamblin.

At least 19 recordsLinked to original sources
PubMed2000

Editorial.

Explore the source record for details and available documents.

Journal Article↗
PubMed2000

Relapsing polychondritis, smouldering non-secretory myeloma and early myelodysplastic syndrome in the same patient: three difficult diagnoses produce a life threatening illness.

Multiple myeloma, relapsing polychondritis and myelodysplastic syndrome are all serious diseases in which making a clear diagnosis can be difficult. This case of a 72-year-old man found after extensive investigation to have all three of the above, demonstrates how difficult diagnosis and treatment can be, producing in this case a life threatening clinical syndrome. We also postulate that the association of these three diseases may be an immune-derived complication of myelodysplastic syndrome.

Aged↗
PubMed1999

Colony-stimulating factors in the treatment of older patients with acute myelogenous leukaemia.

The treatment of acute myelogenous leukaemia (AML) in the elderly is a difficult and increasing problem. The elderly are generally less able to tolerate the intensive chemotherapy required to achieve a sustained remission, and there is an increased incidence of resistant disease in this age group. Granulocyte- and granulocyte-macrophage colony-stimulating factors have been demonstrated to shorten the duration of severe neutropenia following chemotherapy for solid tumours and after bone marrow/peripheral blood stem cell transplantation, and the effect of these growth factors in the treatment of AML has been investigated in a number of trials using 2 distinct strategies. Growth factors may be administered following chemotherapy in an attempt to accelerate neutrophil recovery, and they may be given before and during chemotherapy with the aim to increase the number of leukaemic blast cells in cell cycle and enhance their responsiveness to chemotherapy. Both of these approaches have proved safe despite initial theoretical concerns regarding the expression of receptors for these growth factors on leukaemic cells. The results of trials using these growth factors in the treatment of AML in the elderly generally show a significant reduction in the duration of neutropenia following induction chemotherapy. However, consistent benefits with respect to morbidity and early mortality together with improvements in long term disease outcome have not been observed. The 'priming' approach using growth factors before and during induction chemotherapy has proved equally disappointing in failing to improve response rates or survival. The routine use of these growth factors in the treatment of AML in the elderly population as a whole would, therefore, not seem to be cost effective.

Aged↗
PubMed1998

Insight into the origin and clonal history of B-cell tumors as revealed by analysis of immunoglobulin variable region genes.

Recombination of VH, DH and JH genes is a unique first step in normal B-cell development. Subsequent differentiation to a mature plasma cell is accompanied by further events in the Ig genes, including VL-JL joining, somatic hypermutation and isotype switching. Chromosomal changes leading to B-cell tumors can occur at many points in this sequence, and may be partly a consequence of the genetic mobility and mutability permitted in order to generate a diverse antibody repertoire. V genes of neoplastic B cells may reflect the point of maturation reached by the B cell of origin, prior to transformation. Analysis of tumors therefore provides useful information on V-gene patterns in normal B cells, and may add another dimension to classification of B-cell tumors. Transformation may also preserve cell populations normally destined to die by apoptosis. Tumor cells arrested in the site where somatic hypermutation and isotype switch are occurring can still be subject to these processes, and could be influenced by persisting antigen. However, mutation is silenced at the point of exit to the periphery, leading to fixed mutational patterns in tumors of mature B cells. V-gene analysis provides an invaluable tool for understanding the genesis of neoplastic change. It also has a clear clinical relevance in tracking tumor cells, measuring residual disease, and finally in offering the opportunity of developing vaccines for treatment.

Amino Acid Sequence↗
PubMed1997

International scoring system for evaluating prognosis in myelodysplastic syndromes.

Despite multiple disparate prognostic risk analysis systems for evaluating clinical outcome for patients with myelodysplastic syndrome (MDS), imprecision persists with such analyses. To attempt to improve on these systems, an International MDS Risk Analysis Workshop combined cytogenetic, morphological, and clinical data from seven large previously reported risk-based studies that had generated prognostic systems. A global analysis was performed on these patients, and critical prognostic variables were re-evaluated to generate a consensus prognostic system, particularly using a more refined bone marrow (BM) cytogenetic classification. Univariate analysis indicated that the major variables having an impact on disease outcome for evolution to acute myeloid leukemia were cytogenetic abnormalities, percentage of BM myeloblasts, and number of cytopenias; for survival, in addition to the above, variables also included age and gender. Cytogenetic subgroups of outcome were as follows: "good" outcomes were normal, -Y alone, del(5q) alone, del(20q) alone; "poor" outcomes were complex (ie, > or = 3 abnormalities) or chromosome 7 anomalies; and "intermediate" outcomes were other abnormalities. Multivariate analysis combined these cytogenetic subgroups with percentage of BM blasts and number of cytopenias to generate a prognostic model. Weighting these variables by their statistical power separated patients into distinctive subgroups of risk for 25% of patients to undergo evolution to acute myeloid leukemia, with: low (31% of patients), 9.4 years; intermediate-1 (INT-1; 39%), 3.3 years; INT-2 (22%), 1.1 years; and high (8%), 0.2 year. These features also separated patients into similar distinctive risk groups for median survival: low, 5.7 years; INT-1, 3.5 years; INT-2, 1.2 years; and high, 0.4 year. Stratification for age further improved analysis of survival. Compared with prior risk-based classifications, this International Prognostic Scoring System provides an improved method for evaluating prognosis in MDS. This classification system should prove useful for more precise design and analysis of therapeutic trials in this disease.

Acute Disease↗
PubMed1997

Cytokines to reduce platelet transfusions: non-TPO cytokines.

Although thrombopoietin (TPO) has now been cloned, many pretenders have auditioned for the role. It is clear that interleukin-3, interleukin-6, interleukin-11, stem cell factor, leukaemia inhibitory factor and oncostatin-M all influence the proliferation and maturation of megakaryocytes. This review details the nature of these non-TPO cytokines, giving their genetic identity, molecular structure, receptor, mode of action and range of activities. Their effect on platelet production in preclinical and clinical studies is reported and their potential as agents for thrombopoietic support is discussed.

Cytokines↗
PubMed1996

Trisomy 12 defines a group of CLL with atypical morphology: correlation between cytogenetic, clinical and laboratory features in 544 patients.

We have analysed the clinical and laboratory features in 544 patients with chronic lymphocytic leukaemia (CLL) with available cytogenetics and fluorescence in-situ hybridization (FISH) analysis for trisomy 12 in half of them, to examine the correlation between chromosome abnormalities and clinical or laboratory parameters. Five chromosome groups were defined: (1) trisomy 12 (18%), detected as the sole abnormality or associated with other changes; (2) del(13)(q12-14) (7%); (3) other abnormal karyotypes (20%); (4) normal karyotype (41%); and (5) no divisions (14%). There were no differences in the age distribution between the five groups. Clinical stages (Binet) were: A (74%), B (12%) and C (14%). Stage A was common in cases with del(13q)(82%), normal (84%) and other abnormal karyotypes (74%), whereas it was less common in trisomy 12 cases (64%) and those with no divisions (48%). Typical CLL morphology was found in 83% of cases; 10% had more than 10% prolymphocytes (CLL/PL) and 7% had other atypical features. CLL with trisomy 12 was the only group with a high frequency of either CLL/PL (31%) or atypical morphology (24%). Atypical morphology and CLL/PL were even more frequent when trisomy 12 was associated with other chromosomal abnormalities (70% v 46%). The incidence of cases with CLL/PL and other atypical morphology was significantly lower in the other chromosome groups (P < 0.001). There were no differences in immunophenotype among the various groups except for a higher frequency of stronger Smlg and FMC7 expression in cases with trisomy 12, particularly those with CLL/PL and other atypical morphology. Our findings confirm that trisomy 12 defines a subgroup of CLL with more frequent atypical morphology, including CLL/PL, stronger SmIg and FMC7 expression, more advanced stages (B and C in 18%) and possibly worse prognosis.

Aged↗
PubMed1994

Long-term survival associated with metastatic small cell carcinoma of the esophagus treated by chemotherapy, autologous bone marrow transplantation, and adjuvant radiation therapy.

A 44-year-old woman had small cell carcinoma of the esophagus complicated by liver and lymph node metastases. She was treated with aggressive combination chemotherapy, followed by autologous bone marrow transplantation and adjuvant radiation therapy. (The authors believe this to be the first use of autologous bone marrow transplantation for treatment of this condition.) This regimen resulted in apparent complete regression of the disease as documented by computed tomography and endoscopic study. Three years later, she again experienced general malaise and was found to have extensive recurrent disease in the lung, bone, and liver. Her condition deteriorated rapidly, and she died within 1 month. A review of the literature reveals that this patient survived longer than any others who have had this rare but aggressive tumor. The authors suggest that this form of therapy should be considered for future patients.

Adult↗
PubMed1994

Assessment of the role of clonogenic B lymphocytes in the pathogenesis of multiple myeloma.

The identifiable neoplastic cell in multiple myeloma is the plasma cell, which usually synthesizes and secretes a monoclonal immunoglobulin. However, there exists the possibility that the neoplastic event has occurred in a less mature clonally-related cell, such as a B lymphocyte, prior to Ig class switching. Since the presence of such a clonogenic cell could influence design of therapy, particularly with monoclonal antibodies, we have used the analysis of tumour-related VH genes to approach this question. Cloning and sequencing of PCR products from VH genes of tumour cells obtained from 4/4 patients with myeloma revealed significant mutation of the genes as compared to germ line sequences. In all cases the mutations were scattered throughout the variable region, with a pattern which did not indicate a role for antigen in selection. Importantly for therapy, multiple VH sequences from all patients were completely homogeneous, with no intraclonal variation. These findings indicate that, although IgM-positive clonogenic cells may exist, it is unlikely that they are involved in continuous maintenance of the malignant isotype-switched cell population. One possibility is that the B-cell progenitor population has to undergo further chromosomal changes to generate the malignant cell, and that this occurs at a more mature stage; in this case, antibody therapy should be aimed primarily at the more differentiated cells.

Amino Acid Sequence↗
PubMed1992

Clinical features of MDS.

MDS is primarily a disease of the elderly. Cases who give a history of exposure to X-rays, cytotoxic drugs or leukaemogenic chemicals may be younger. Many cases of MDS present because of an incidental blood count. The most prominent clinical features are those of anaemia, neutropenia, thrombocytopenia. Because haemopoietic tissue is also dysfunctional the pathological effect is often greater than the figures would suggest, even leading to infection of bleeding with normal neutrophil or platelet counts. Occult abscesses are a particular feature. Despite documented abnormalities of the lymphoid system, neither infections characteristic of T-cell immunodeficiency nor autoimmunity is a problem. The proliferation of monocytes in CMML leads to organomegaly, leukaemia cutis, serous effusions and vasculitic lesions caused by the mishandling of circulating immune complexes. Cancer is no commoner than in age-matched controls, but coincident lymphoid tumours do occur. Many patients require long-term blood transfusion and will run into problems of iron overload unless precautions are taken.

Anemia↗
PubMed1992

The treatment of acute myeloid leukaemia preceded by the myelodysplastic syndrome.

Most cases of acute myeloid leukaemia in the elderly and about 15% of the cases in younger patients follow a myelodysplastic disease. This disease may differ biologically from de novo AML making cure more difficult. Understanding post-MDS AML is difficult because of its preponderance in the elderly and the many complicating factors of treating old people. However, it is likely that post-MDS AML is more resistant to chemotherapy than de novo AML, that periods of pancytopenia last longer following chemotherapy and remissions are shorter. In younger patients high complete remission rates are achievable with aggressive chemotherapy and good supportive care. Such patients are best served by subsequent allogeneic bone marrow transplantation if possible, and if not then bone marrow autograft or a maintained remission should be considered. For older patients cure is unlikely and the choice between low-dose cytarabine and aggressive chemotherapy must be made if treatment is to be contemplated at all. The former leads to less hospitalisation and fewer side effects, but the latter gives a greater chance of a complete remission. This will not be long lasting.

Acute Disease↗