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Biomedical subjects

Peter Jacobs

Publications and source records attributed to Peter Jacobs.

24 records · Page 2Linked to original sources
PubMed2002

Myelodysplasia and the acute myeloid leukaemias.

The myelodysplastic syndromes are increasingly recognised clinical entities reflecting a stem cell defect that gives rise to ineffective clonal haematopoiesis. The spectrum extends from relatively indolent refractory anaemia through varying combinations of leucopoenia and thrombocytopenia to acute leukaemia. Diagnosis rests on marrow hypercellularity with dysplastic morphology, apoptosis and, often distinctive cytogenetic defects. Stratification to risk-related protocols range from occasional blood transfusions or erythropoietin through innovative options including thalidomide or amifostine to haematopoietic stem cell transplantation in selected individuals. Acute myeloid leukaemia, conceptually segregated from preleukaemia, is treated differently although accumulating cellular and molecular data favour a more integrated approach. Morphology and immunophenotyping are complemented by molecular genetics. On this basis chemotherapy alone is sufficient in defined sub-groups whereas others benefit by autologous or allogeneic grafting. Attention to demonstrating minimal residual disease is the basis for more specific intervention exemplified by monoclonal antibodies or maturation-inducing agents as with retinoic acid in acute progranulocytic leukaemia

Acute Disease↗
PubMed2002

Chronic lymphocytic leukaemia--the haematologic basis for diagnosis and treatment.

Clinically diagnosis may be incidental when absolute lymphocytosis is uncovered at routine medical examination. More usually there is a recurrent sinopulmonary infection reflecting a varying degree of humoral and cellular immune deficiency. Autoimmune phenomena may result in haemolytic anaemia or thrombocytopenia. Expanding tumour bulk underlies the lymphadenopathy which may be prominent. Diagnosis is confirmed on morphology of the smear where atypical variants need to be distinguished from other indolent lymphoproliferative disorders. Immunophenotyping is indispensable in classification. Prognosis is predicated by cytogenetics and markers of tumour biology that include beta-2 microglobulin and peripheral blood lymphocyte doubling time. Management is dictated by symptoms and signs of progression superimposed upon performance status that includes age. Disease that is asymptomatic and truly indolent, particularly in the elderly, qualifies for a careful watch-and-wait policy. In other circumstances stratification to therapy requires entry into peer-reviewed protocols if optimal outcome is to be achieved. Established regimens, of demonstrably equal efficacy, are pulsed single-agents exemplified by chlorambucil or combinations of cyclophosphamide with vincristine and prednisone. The purine analogues, particularly when administered with an alkylating agent and mitoxantrone, are emerging as superior options. In selected patients any properly accredited program will make provision for escalation in chemotherapy requiring haematopoietic stem cell transplantation on the one hand or use of serotherapy with CD52 antibodies on the other. Less commonly, but in a defined subgroup, immunoglobulins directed against membrane CD20 may be effective. Perspective for the generalist is anchored in recognising that the previous cavalier approach to drug medication, with or without radiotherapy, is unwise whereas integrated management is now the international standard of practice. The previous anachronism of dabbling by occasional therapists is to be deprecated since this will generally deny patients access to proper diagnosis and risk-adjusted multi-disciplinary treatment.

Antineoplastic Agents↗