Survival benefit of high-dose therapy in poor-risk aggressive non-Hodgkin's lymphoma: concerns about omissions in the data presented.
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Publications and source records attributed to T C Morris.
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Breast lymphoma accounts for less than 1% of all non-Hodgkin's lymphomas (NHLs) and approximately 0.1% of all breast neoplasms. Most breast lymphomas are classified as diffuse large B cell or mucosa associated lymphoid tissue (MALT) lymphomas. The case of a 53 year old woman presenting with a breast mass and found to have mantle cell lymphoma is described. Core biopsy of the breast lesion showed a B cell NHL, probably of large cell type and of high grade. Morphological and immunophenotypic analysis of peripheral blood and bone marrow samples suggested a mantle cell lymphoma (MCL). This was confirmed by the detection of a t(11;14) in the bone marrow aspirate and breast tissue by polymerase chain reaction analysis. There have been no previous reports of an MCL presenting as a breast lump. Because a diagnosis of MCL has prognostic and therapeutic implications, this case highlights the need for an awareness of MCL presenting in this way, and the requirement for specialised investigations in its detection.
A phase II study to further evaluate any possible antimyeloma activity of clarithromycin was conducted following a report of possible clinical efficacy. Twenty patients, 11 male and 9 female with a median age of 73 yr, received clarithromycin 500 mg twice daily with monthly intravenous infusions of disodium pamidronate. None of the study patients received concomitant cytotoxic or steroid therapy. Ten patients had relapsed disease, five had refractory disease, four were previously untreated, and one patient was unsuitable for cytotoxic therapy. The median number of previous treatment modalities was 1.5. Serum M protein levels and urinary M protein excretion were monitored along with other parameters to assess response. Median duration of therapy was 16 wk and six patients had dose escalation. A significant decrease in M protein production occurred in one patient at wk 12 of therapy, which maximized following dose escalation to a 47% decrease from baseline. Two patients had incremental but unsustained M protein reductions. Serum/urine M protein levels remained static in six patients and rose in the remaining six evaluable patients. The M protein response rates in this study are much lower than those previously reported and do not confirm efficacy. In addition, the recently postulated antimyeloma activity of pamidronate may explain some of the M protein decreases.
We report two cases of acute myeloid leukaemia FAB classification M4Eo with high white cell counts at presentation, who developed acute respiratory failure with pulmonary infiltrates on chest radiograph soon after commencing conventional cytotoxic chemotherapy plus all-trans retinoic acid (ATRA). We suggest that in patients with M4Eo ATRA should be used with caution, perhaps delaying its commencement until the white cell count is < 10 x 109/l.
Cytochemical staining of monocyte-specific esterase (MSE) is widely used for identification of the monocytic lineage in leukaemias. Deficiency of this enzymatic activity occurs as a familial trait and the deficiency has been shown to occur with greater frequency in patients with lymphoproliferative or gastrointestinal malignant neoplastic diseases than in normal blood donors. Reverse transcriptase polymerase chain reaction (RT-PCR), sequencing and quantification by Northern blot analysis was conducted on the MSE mRNA of 12 subjects with monocyte esterase deficiency (MED) and seven MSE-positive subjects to examine whether mutations were present or whether the defect was quantitative. Mutations were not found in the mRNA sequences. However, MED subjects had significantly less MSE mRNA than MSE-positive subjects (P = 0.001). These findings show that deficiency of monocyte esterase activity in MED is not as a result of the presence of inactive isoenzymes and may be owing to an abnormality in the regulation of mRNA production.
A 58 year old man presented in 1995 with a swollen testicle. After orchidectomy, a diagnosis of poorly differentiated lymphoma was made. Lymphoid, epithelial, and seminoma markers were all negative. Six months later he developed a buccal lesion, which was biopsied and reported as a high grade non-Hodgkin's lymphoma. It responded completely to chemotherapy but within a year he developed a forearm swelling, which was biopsied and imprints made before fixation of the material. Immunocytochemistry on the imprints showed positivity with antibodies to CD4, CD68, and muramidase, and the non-specific esterase cytochemical stain was strongly positive, leading to a diagnosis of true histiocytic lymphoma. Despite further treatment, the patient entered a terminal acute leukaemic phase, the blasts marking as monoblasts. Review of all the biopsies, including molecular investigations and further immunohistochemistry studies performed retrospectively on the original biopsy, demonstrated that this was the same malignant cell line throughout, and we conclude that this is a case of histiocytic lymphoma, initially presenting as a testicular tumour and terminating in acute monoblastic leukaemia. A diagnosis of histiocytic lymphoma should be considered when lymphoid markers are negative in an apparent lymphoma, but should not be made without recourse to appropriate immunophenotypic and molecular studies.
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Aging has been shown to be accompanied by various changes in the lymphocyte subset distribution in the elderly. We have investigated more fully, and in a large number of subjects, age-related changes within several subpopulations bearing natural killer (NK) cell-associated surface antigens and changes in several cytokines involved in NK cell expansion. A total of 229 healthy subjects from all decades of life from 20 to 98 years of age was included in this cross-sectional study. A significant increase with age was found in both the absolute counts and the proportions of CD3-CD(16+56)+, CD3+CD(16+56)+, CD57+CD8+, CD57+CD8(low)+, and CD57+CD8- cells, whereas the CD57+CD8(high)+ subset, which may represent the cytolytic T cell population more precisely, showed less change with age. Some evidence is also provided to suggest that these expanded NK cell populations are in an activated state. Soluble IL-2 receptor levels were also found to increase significantly with age and correlated with certain NK cell subsets. Although the functions of some of these subsets remain to be elucidated, their expansion in the elderly may represent a remodeling of the immune system with increasing age, with an increase in non-MHC-restricted cells perhaps compensating for the previously reported decline in T and B cells in the elderly. Alternatively, increased numbers of these cells may be a direct result of cytokine dysregulation or increased antigenic or neoplastic cell challenge.
We describe a patient with M4 AML treated with standard chemotherapy followed by G-CSF who developed marked monocytosis on day 8 of G-CSF therapy. Fourteen days after discontinuation of G-CSF therapy his monocyte counts returned to normal levels and a marrow aspirate showed a reduction in blast cells. He received further chemotherapy without G-CSF and without any recurrence of the raised leucocyte count but failed to achieve full remission. Although this G-CSF-driven leucocytosis was alarming it did not appear to have adversely affected the patient's prognosis.
The purpose of this study was to determine whether or not peripheral blood monocyte esterase deficiency occurring in patients on CAPD was a familial characteristic. The peripheral blood monocyte esterase status of 74 patients on CAPD was determined by a naphthyl acetate esterase staining of cytospin preparations of their mononuclear cells following separation over ficoll. The peripheral blood of first degree relatives and spouses of monocyte esterase deficiency patients was similarly investigated for the deficiency. Three patients bad monocyte esterase deficiency and familiality of the defect was demonstrated in two of their families. The third family was incompletely investigated because of lack of consent. The monocyte esterase deficiency demonstrated in this cohort of patients did not result from their renal failure but was a familial characteristic.
We reviewed the long-term survival, treatment-related mortality and morbidity of a continuous cohort of patients with Hodgkin's disease diagnosed and staged at the Haematology unit of the Belfast City Hospital between January 1973 and October 1992. The analysis included a comparison of the survival of those patients who were entered into BNLI (British National Lymphoma Investigation) trials compared to those not entered during this 20 year period. In addition univariate and multivariate analysis of prognostic factors was performed. The complete remission rate (CR) was 79.6% with a 15 year survival of 55.3%. On multivariate analysis in which deaths due to active Hodgkin's disease only were considered age > 50 emerged as the most significant prognostic factor (P < 0.0007), the presence of B symptoms also having independent significance (P = 0.008). Trial status did not have any independent prognostic significance. Eighty one deaths occurred: active Hodgkin's disease (50), second malignancy (9), treatment-related (10), unrelated (9), unknown (3). This long-term follow up study provides useful information additional to the data produced by clinical trials which are biased by selection criteria. The occurrence of Haemophilus Influenzae meningitis in a patient 17 years following splenectomy highlights the need for appropriate vaccination of patients splenectomised for Hodgkin's disease.
A quantitative analysis of peripheral blood stem cell (PBSC) yield, measuring absolute numbers of CD34+ cells x 10(6)/kg and CFU-C x 10(4)/kg was performed in 74 consecutive patients. The interval or 'gap' from the end of previous chemotherapy to the date of priming was recorded in weeks. Geometric mean CD34 and CFU-C values were significantly higher in patients with a score of < or = 60 compared to those with score > 60 (P = 0.003 and 0.02, respectively) and a significant difference in CD34 values was also found when scores of < or = 38 were compared with scores > 38 (P = 0.003), with the difference in CFU-C values approaching significance (P = 0.08). Patients exposed to toxicity factor 4 drugs had significant lowering of both CD34 and CFU-C values (P < 0.001 and P = 0.038) and this emerged as the only independent factor when analysed using linear regression. No significant difference in the geometric mean CD34 or CFU-C values of patients was found in any of the gap categories analysed. Prior exposure to toxicity factor 4 drugs had a significant adverse effect on stem cell yield and should be avoided or minimized prior to stem cell harvesting.
AIMS: To compare the polymerase chain reaction (PCR) assay with standard Southern blot (SB) hybridisation for the detection of clonal T cell receptor (TCR) gene rearrangements in large granular lymphocyte (LGL) proliferations; to evaluate the reliability and practicality of the methods for routine diagnostic use; and to determine the sensitivity of the PCR method. METHODS: Blood lymphocytes were isolated from 12 patients with persistent CD3+CD8+ lymphocytosis with LGL morphology. Clonal rearrangements of the TCR gene were demonstrated by SB hybridisation with a TCR beta constant probe, and by PCR amplification of portions of the TCR beta and TCR gamma genes. RESULTS: Monoclonal TCR beta gene rearrangements were detected in eight patients (67%) by PCR analysis and five patients (42%) by SB hybridisation. PCR analysis also showed that seven patients (58%) had monoclonal TCR gamma gene rearrangements. All cases which had TCR beta clonal rearrangements shown by SB hybridisation were similarly identified by PCR. Sensitivity tests suggested that the TCR beta PCR technique was capable of detecting clonality in as little as 50 pg of DNA. The TCR beta primers could detect one clonal cell in approximately 200 or more normal cells (< 0.5%), a sensitivity level that at least doubles that of the SB hybridisation technique. CONCLUSIONS: The use of PCR technology proved to be superior to SB hybridisation for the routine investigation of suspected cases of LGL leukaemia. Nine patients (75%) in this study were found to have TCR beta and/or TCR gamma monoclonal gene rearrangements. This approach is ideal for distinguishing between reactive and clonal LGL proliferation in a routine diagnostic laboratory.
Monocyte esterase deficiency (MED) has been found to be linked with autoimmune (1,2) and lymphoproliferative (2,3) disease. The incidence of MED where > 85% of peripheral blood monocytes are consistently negative in the cytochemical stain for monocyte esterase activity, was shown to be significantly raised in patients with renal failure (3.8%) as compared to the incidence in normal blood donors (0.8%) in a survey performed at the Belfast City Hospital in 1987 (2). The overall occurrence of any proportion of esterase-negative monocytes (ENMs) in patients with renal disease has not been previously studied. The aims of this study were to document this occurrence, and by examining the clinical and biochemical parameters associated with ENMs to identify possible reasons for their occurrence. The original survey data were reexamined and further information previously unreported regarding the occurrence of ENMs was extracted from the renal patient cohort data. Clinical and biochemical data were obtained from the hospital notes of the renal patients and associations sought between these parameters and the occurrence of ENMs. ENMs occurred in a significantly higher proportion (31%) of the renal patients than in the normal population (8%; p < 0.001 chi-sq.) or any other hospital population. A highly significant association between rising serum phosphate levels and increasing proportions of ENMs was identified (p < .001) and this association proved to be independent of serum creatinine levels and renal dialysis status. There is a marked increase in occurrence of esterase-negative monocytes in patients with renal failure. This increase was not caused by the degree of renal failure as reflected by serum creatinine levels, nor by renal transplantation or immunosuppressive therapy. A significant association between rising serum phosphate and increasing proportion of esterase-negative monocytes was identified. This new information, when considered with the previously described experimental and epidemiology evidence for malfunction of esterase negative monocytes, identifies a phenomenon which may contribute to the immunological difficulties of patients with chronic renal failure.
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