To determine the relative importance of clinical factors on the efficacy of platelet transfusions, 941 pooled platelet transfusions from HLA-unmatched donors were studied prospectively in 133 patients with bone marrow failure. Multiple linear regression analyses identified the major factors influencing one-hour-corrected increments (CI) as prior splenectomy, bone marrow transplantation, disseminated intravascular coagulation, concurrent intravenous amphotericin B, splenomegaly, and HLA antibody grade. The relative impact of these factors on CI has been quantitated by using a formula developed from these data. A linear relationship was demonstrated between increasing percentage of HLA antibody grade and decreasing CI. A number of other factors were less important in the linear regression model than the aforementioned major factors. These included platelet-specific antibodies, concurrent antibacterial antibiotics, clinical bleeding grade, and temperature. Factors that did not influence CI included the number of prior platelet transfusions, prior granulocyte transfusions, prior red cell transfusions, infection, age, blood group, diagnosis, sex, pretransfusion platelet count, prior pregnancies, and concurrent antineoplastic drugs. This study identified major clinical factors that significantly influenced CI and were major causes of refractoriness to pooled platelet transfusions.
Glycolysis and oxidative metabolism were assessed in washed human platelets incubated in a Ca++ and Mg++ free Krebs-Ringer bicarbonate buffer, pH 7.4 at 37° C for 1 hour. Glycolytic rate was 45-65 per cent lower under aerobic than anaerobic conditions. Glycolysis was decreased further when albumin was present in the incubation medium and under these conditions glucose uptake, glycogen utilization and lactate production were 21.4, 15.8 and 78 µmoles/hr. per 1011 platelets, respectively. The oxidation of 6-14C glucose was 0.39 µmoles/hr. per 1011 platelets and of U-14C palmitate 0.19 µmoles/hr. per 1011 platelets, and the rate of oxidation of either substrate was increased in the absence of the other. The uncoupling agent, dinitrophenol, stimulated oxidation of glucose to a much larger extent than fatty acid. It is concluded that both glycolysis and oxidative phosphorylation are important to platelet energy metabolism, that either pathway may compensate for decreased activity of the other and that, under conditions of metabolic stress, glucose is preferred to fatty acids as a substrate for oxidative metabolism.
Fifty-nine patients receiving platelet transfusions for bone marrow failure secondary to malignancy were screened at regular intervals for the presence of antibodies to human leucocyte (HLA) and platelet specific antigens. HLA antibodies occurred in 19 patients, 10 of whom also developed platelet specific antibodies. The HLA antibodies disappeared in 10 of 15 patients followed for periods of 2-14 months. In two patients this occurred whilst still receiving platelet transfusions. Antibody reappeared in only two of six patients subsequently transfused. Antibodies to platelet specific antigens were detected in 28 patients. They were transient, often appeared in association with infection, and in 50% of cases tested demonstrated autoantibody activity. There was no association with antibiotic drug therapy, or PFA/EDTA-dependent cryptantigens. Platelet recovery at 1 h or 20 h post transfusion was not significantly reduced in the presence of platelet specific antibodies. These findings have important implications for the selection of platelet donors for alloimmunized recipients.
CHOP chemotherapy produced results equivalent to those of MACOP-B in patients with intermediate-grade NHL and with significantly fewer toxic complications. Despite relatively poor results in some patient subgroups, CHOP remains the standard chemotherapy for this disease, against which all new regimens should be compared.
A prospective cytogenetic study of patients with non-Hodgkin's lymphoma (NHL) presenting to one institution was commenced in 1983 as part of a larger study including histology, immunophenotyping, cytokinetics and survival. 175 patients were studied over 5 years and G-banded karyotypes were successfully obtained in 147. Chromosome abnormalities were detected in 135 cases (92%) with the commonest abnormality being t(14;18)(q32;q21) in 69 cases. Other non-random translocations were much less frequent, i.e. t(11;14) in seven cases and t(8;14) in four cases. Other specific structural changes included partial deletions of 6q (breakpoints ranging within q13-q23), 3q (breakpoints ranging within q21-q27), 1q and 10q22. Chromosome regions highlighted as being frequently involved in structural abnormalities were 11q13-q25, 1p22-p36, 3q21-q27 and 6q13-q23. Several specific recurring breakpoints were identified and these included 14q32, 18q21, 1p36 and 6q21. Frequently occurring numerical abnormalities were gains of chromosomes 3, 7, X and 12. Correlation with histological type showed, as expected, that t(14;18) was present in 89% of follicular lymphoma but also occurred in 30% of diffuse lymphoma. Abnormalities of 11q were correlated with the diffuse histologies as a group, whereas both numerical and structural abnormalities of chromosome 3 correlated with the diffuse large cell lymphoma (DLCL) subtype, and t(11;14) with diffuse small cleaved cell lymphoma (DSCCL). Although not statistically significant, abnormalities of 6q occurred twice as frequently in DLCL than in any other variety. However, several other commonly occurring abnormalities, such as extra copies of chromosomes 7, X, 12 and most of the structural abnormalities of 1p, did not correlate with any histological type. Therefore this large cytogenetic study has confirmed some previously reported correlations between specific chromosome abnormalities and histological subtypes of non-Hodgkin's lymphoma and has also identified some new correlations which may prove useful in the investigation of the biological basis of the disease.
In 44 out of 758 patients (5.8%) with non-Hodgkin's lymphoma presenting between 1971 and 1982, the central nervous system (CNS) was involved. Patients with a diffuse histology had a 7.6% (34/449) incidence of CNS involvement compared to 3.9% (10/257) for patients with nodular lymphoma. In 63% of patients there was evidence of progressive systemic lymphoma at the time of diagnosis of CNS disease and in 23% CNS relapse occurred in clinical remission. Bone marrow was involved in 34% of patients at diagnosis and in 52% at some time prior to the onset of CNS complications. Cerebrospinal fluid cytology was positive in 63% and an elevated protein level was found in 95% of patients. The median length of survival of the 44 patients was only 3.2 months, but patients who responded to treatment of CNS lymphoma survived significantly longer than those who showed no response or progressed on therapy. Complete response to CNS treatment was achieved in five patients, of whom none relapsed in the CNS and two are long-term disease-free survivors. CNS prophylaxis appears justified for patients with lymphoblastic lymphoma, Burkitt's tumour, and diffuse undifferentiated lymphoma, who are at high risk of developing CNS complications. Patients with diffuse histiocytic, and diffuse poorly differentiated lymphocytic, lymphoma who have bone marrow involvement may also benefit from CNS prophylaxis.
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