Exchange transfusion for hyperleukocytosis, anemia, and metabolic abnormalities in leukemia.
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Biomedical subjects
Publications and source records attributed to Y Ravindranath.
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A 7-week-old infant with methylmalonic acidemia had pancytopenia and hypoplastic bone marrow. The patient responded to large doses of vitamin B12 treatment, and within 3 wk, the blood counts and bone marrow cellularity returned to normal. To understand the mechanism of marrow depression in this infant, we examined the effect of the patient's plasma and methylmalonic acid itself on the in vitro growth of bone marrow-committed stem cells. The patient's plasma obtained before B12 treatment completely inhibited the marrow cell growth, whereas the posttreatment plasma showed no inhibition. Methylmalonic acid when added to the culture dishes in concentrations comparable to those reported in plasma of methylmalonic acidemia patients, inhibited growth of marrow stem cells in a concentration-dependent fashion. On the other hand, 16 to 18 hr incubation of cells in the same concentration of methylmalonic acid did not affect the recovery of viability of the cells. The observations suggest that methylmalonic acid is inhibitory to the proliferation of marrow stem cells. The mechanism of inhibition is yet to be elucidated.
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A 28-month prospective study of 54 leukemic children was carried out to determine the incidence and type of infection associated with febrile episodes. Fever was caused by infections in 84 of 199 episodes (71%). Two-thirds of the febrile episodes and 57% of the documented infections occurred when leukemic activity was demonstrable. However, only nine of 29 febrile episodes which occurred at the time of initial diagnosis of acute leukemia were due to infection. All serious bacterial infections occurred in children with absolute granulocyte counts less than 500/mm3. Septicemia was responsible for seven of the 17 deaths which occurred during the period of observation. The five children with Pseudomonas infections were colonized 10 to 30 days before they developed their infection. The majority of viral infections occurred in patients in remission, and were principally caused by cytomegalovirus, varicella-zoster virus, or Epstein-Barr virus. With the exception of one patient who died with a complex infection (CMV and Pneumocystis carinii), the children in this study responded well to viral infections.
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Recurrences of CNS infarction often lead to progressive neurologic disability in sickle cell anemia. To prevent such reccurrence, a periodic blood transfusion program was begun in 1969. Currently, 27 patients are on this regimen. Before inclusion in the program, 12 patients had had one to nine CNS recurrences each. Since the program was started, two patients have had transient CNS ischemia. There were no other recurrences and none of the patients have shown progression of neurologic abnormalities. In addition, there was a striking decrease in bacterial infection and pain. We conclude that periodic transfusions are effective in preventing recurrent CNS infarction in sickle cell anemia. The benefits must be weighed against the potentially serious problem of iron overload, as evidenced by moderately elevated serum ferritin values.
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A 6-month-old infant with primary malignant cutaneous lymphoma is presented. The histologic differentiation between benign cutaneous lymphoid hyperplasia and cutaneous malignant lymphoma is discussed. Intensive therapy is warranted at the onset because of early dissemination and poor response to treatment after dissemination.
We have recently observed the development of second leukemia of a morphologically different type in three patients with acute lymphoblastic leukemia (ALL) while on therapy. The "second" leukemia occurred while on therapy at 23, 27, and 32 months of initial remission. All three were receiving systemic chemotherapy (CT) and prophylactic fractional irradiation to the central nervous system (CNS). The second leukemias in these three cases were one case of juvenile chronic myelogenous leukemia (JCML) and two cases of acute leukemia of the myeloblastic type by the usual morphologic criteria including the presence of Auer rods in one. In two cases a cytogenetically new clone was detected in the remission marrow 10 and 12 months preceding the overt change in clinical status. These three cases demonstrate that second leukemia occurs in patients with ALL and that some late "relapses" fall into this categpry. The possible etiologic role of modern intensive treatment regimens in the development of second leukemia is discussed.
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Cytogenetic examination of bone marrow cells from three patients with juvenile chronic granulocytic leukemia (CGL) showed 46,XX,3p-,11p+ ,t(11p:3p) in one case, 45XY,-E in another, and 45X(X),-C/47,XX,+G in the third. The case with the translocated chromosome originally presented like an acute lymphocytic leukemia (ALL). TAn overt clinical picture of juvenile CGL emerged two and a half years later. Serial study of this case revealed no cytogenetic abnormalities until two years after the diagnosis of ALL, when the translocated chromosome was first observed. Unlike the Ph1 chromosome in adult type CGL, chromosomal abnormalities in juvenile CGL lack specificity, resembling ALL in this respect.
To clarify the nature of null cell acute lymphoblastic leukemia (ALL) we tested null lymphoblasts and other leukemic cells for human T and B lymphocyte antigens detected by reciprocally absorbed rabbit antisera prepared against autologous T and B lymphoblast cell lines HSB-2 and SB. Blasts from 4 of 4 patients with T cell leukemia and from 2 of 10 patients with null cell leukemia expressed T cell but not B cell antigens. Blasts from 8 of 10 patients with null cell leukemia, one patient with B cell leukemia, and 3 of 3 patients with acute myelogenous leukemia expressed B cell but not T cell antigens. T lymphocyte antigen-positive null cell ALL appear to be a form of T cell ALL. B antigen-positive null cell leukemia could arise from either immature B cell precursors or from multipotential stem cells.
A protocol for the prophylaxis of CNS leukemia was devised involving intermittent low-dosage radiation of the craniospinal axis combined with single intrathecal injections of MTX. The retionale for this protocol was the timing of first CNS relapses in patients not receiving prophylaxis which suggests that leukemic colonization of the CNS is not restricted to the initial stage of the disease and that periodic measures might be advantageous. The low dosage of radiation was chosen because it is well tolerated and has been found temporaily effective in overt CNS relapse. The two series of patients were comparable as to various parameters. Results after three years of observation were comparable to those obtained by other with a single initial course of high-dose radiation, with an expected 50% uninterrupted complete 5-year remission. On the basis of 30 months follow up in 26 patients, the therapy is well tolerated. An increase in morbidity due to infections in remission was not associated with a higher mortality.
Of 148 children with acute lymphoblastic leukemia (ALL) 34 had bilateral interstitial pneumonia (BIP). Their records were reviewed retrospectively to evaluate the incidence of this pneumonia and delineate the various etiologic factors involved. All but 1 were in remission; 82% of the episodes occurred within the first 6 months, the majority of these occurring during the first 3 months of diagnosis of ALL; 16 were receiving methotrexate (MTX), and 14 were receiving combination chemotherapy with vincristine, prednisone and 6-mercaptopurine (6-Mp) and 4 were on no systemic therapy. Thirty patients with 35 episodes recovered within an average period of 18 days, including clearance of radiologic findings; 4 died. Four had open lung biopsies without complications. There was a single case of pneumocystis carinii infection diagnosed postmortem. Laboratory data and histopathologic findings (of 4 biopsies and 3 remaining autopsies) were suggestive of a viral etiology. The incidence of BIP in ALL at Children's Hospital of Michigan is 22.9% with a mortality rate of 10.3%. The incidence of pneumocystis carinii infection appeared to be low. Hypersensitivity to MTX was not substantiated.
Serial cytogenetic and cytological studies in 2 cases of erythroleukaemia in children indicated that erythropoiesis is not involved in the malignant process itself, but represents a response caused by unknown stimuli. A good correlation was observed between the percentage of aneuploid cells and blasts in mitosis, thus during the erythroid phase aneuploidy was minimal or absent, while during the myeloblastic phase a high percentage of members of the aneuploid clone was present. An inverse correlation between peripheral normoblast count and haemoglobin level indicated that erythropoiesis was under physiological control. Taken together these observations constitute evidence that, in the cases of erythroleukaemia studied, erythroid cells do not have inherent malignant properties. Cytogenetic analysis offers a tool for differentiating this type of erythroleukaemia from other forms of DiGuglielmo's syndrome.
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