Rejection after bone marrow transplantation for aplastic anemia using an identical twin, followed by permanent success utilizing immunosuppression.
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Biomedical subjects
Publications and source records attributed to M E Nesbit.
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Lymphoblasts from 61 untreated patients with acute lymphoblastic leukemia (ALL), classified according to the French-American-British (FAB) morphologic classification, were studied for cytochemical characteristics and membrane surface markers. Seventy-three % (eight of 11) of patients with E-rosette positive lymphoblasts (T ALL) had strong focal paranuclear acid phosphatase (AcP) activity in more than 75% of their lymphoblasts; lymphoblasts from only 6% (three of 48) (p = 0.005) of patients with E-rosette negative, surface immunoglobulin negative lymphoblasts (non-T, non-B ALL) exhibited this characteristic AcP activity. The non-T, non-B ALL cases that manifested focal paranuclear AcP activity had clinical features more characteristic of the T ALL cases. The distribution of beta-glucuronidase activity in the lymphoblast cytoplasm was similar to that of AcP for T ALL and non-T, non-B ALL but the stain was generally more difficult to interpret THan the AcP and was a less reliable indicator of immunologic type of ALL. The periodic acid-Schiff (PAS) and nonspecific esterase stains were not useful in distinguishing between T ALL and non-T, non-B ALL but PAS negativity was associated with certain clinical features within the non-T, non-B ALL group. Cytochemical evaluation of the lymphoblasts at diagnosis in patients with ALL may be useful in identifying subsets of ALL that have distinct immunologic and clinical characteristics and important therapeutic and prognostic implications.
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Results are reported on 724 children and adolescents with acute leukemia-lymphoma. One hundred patients had immunologic marker analysis that defined the major phenotypic groups, i.e., T-cell, B-cell (Burkitt), myeloid, and the most frequent form, non-T, non-T "common" or "undifferentiated" acute leukemia. Pre-T, pre-B, and "null" leukemias are included in the latter group. Response to therapy and survival was best in non-T, non-B acute lymphocytic leukemia, intermediate in T-cell disease, and worst in B-cell (Burkitt) disease. Additional factors resulting in decreased survival include elevated peripheral leukocyte count, presence of enlarged nodes, less depression of hemoglobin and platelets, and age greater than 7 years (all associated with 'lymphomatous" disease). Other factors resulting in decreased survival include age under 3 years and depression of serum immunoglobulins. Definition of the heterogeneity of childhood leukemia-lymphoma dictates differing forms of therapy for the various types of these diseases.
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L-Asparaginase, in the dose of greater than or equal to 6000 IU/sq m three times weekly, was demonstrated to be an effective agent in reinduction of remissions in childhood leukemia. Four hundred thirteen children with acute lymphocytic leukemia were treated with L-asparaginase. Doses i.m. ranged from 300 to 12,000 IU/sq m. None of the patients had received prior asparaginase therapy. 6-Mercaptopurine was given p.o. concurrently. All of the patients had experienced several previous relapses, and their disease was not responsive to 6-mercaptopurine. L-Asparaginase was found to be effective in reinducing remissions at the following rates: 9.5% for 300 IU/sq m; 35.1% for 3,000 IU/sq m; 53.5% for 6,000 IU/sq m; and 62.5% for 12,000 IU/sq m. The drug was given three times weekly for four weeks. Hypersensitivity reactions occurred in 6.5% of patients.
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A newborn infant presented with hepatosplenomegaly, rash, anemia, and leukocytosis at one day of age and manifested characteristic myeloid metaplasia by one mouth of life. Vitamin B12 and leukocyte alkaline phosphatase were elevated and platelet aggregation was impaired. Myelofibrosis was not present and neutrophil function was preserved. An unidentified high isoelectric point hemoglobin with unusual chromatographic and electrophoretic behaviors was found to comprise 12% of the total hemoglobin. The myeloid metaplasia and mutant hemoglobin disappeared over the subsequent months without biochemical or clinical residual. The available evidence was consistent with the mutant hemoglobin representing either a gamma chain or clonal embryonic chain variant. The inability to clarify prognostic factors in these unusual myeloproliferative syndromes suggests caution in the initiation of cytotoxic therapy.
A female patient with severe idiopathic aplastic anaemia received a successful bone-marrow transplant from her HLA-identical, mixed-lymphocyte-culture-compatible, brother. 8 months after transplantation she had localised cutaneous measles. Chronic sclerodermatous changes developed which were indistinguishable from chronic graft-versus-host disease and were limited to the areas of the original exanthem. Interaction between viral infection and minor histocompatibility differences probably resulted in graft-versus-host disease in this patient.
A carcinoid tumor was discovered by chance in a 25-year-old woman with the dominant type of retinitis pigmentosa. Although a coincidental association cannot be ruled out, there is at least a possibility that the two diseases have a common embryologic origin.
Platelet function was evaluated in eight patients with chronic granulocytic leukaemia (CGL), seven Ph1 positive and one Ph1 negative. Seven of the eight patients' platelets had an absence of the second wave of adrenaline induced aggregation on at least one occasion, while five had impaired collagen aggregation. The platelets of all seven patients with abnormal responses to adrenaline, aggregated with arachidonic acid, thus ruling out a cyclo-oxygenase deficiency. A marked decrease in the ADP, serotonin, and dense body content of platelets was found in all five patients evaluated. Mixtures of CGL patient platelets with platelets from normal donors who had ingested aspirin gave a normal biphasic response to adrenaline. Normal release of the storage pool contents from aspirin treated platelets was shown by stirring a mixture of CGL platelets and 14C-serotonin labelled aspirin treated platelets with adrenaline. The CGL platelets alone or in the mixture produced malondialdehyde in response to adrenaline. These experimental results suggest that CGL platelets have a storage pool deficiency but can synthesize prostaglandins and thromboxanes in response to arachidonic acid and adrenaline.
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One hundred consecutive newly diagnosed cases of leukemia and lymphoma in children from 0 to 16 years of age presenting at the University of Minnesota from 1973 to 1977 were studied. Clinical features were correlated with phenotypic features of blast cells, including surface markers and cytomorphology. Four groups with distinct clinical and pathologic features emerged from the study: a) The acute leukemias of the "null" or "undifferentiated" group were those in which the malignant cells carried distinctive null leukemia surface antigen and lacked features of either T cells (E-rosette positivity) or B cells (surface immunoglobulin positivity). These cases occurred most frequently in the series (56% of total cases), peaked in incidence at 6 years, were associated with extensive bone marrow involvement, lacked distinguishing cytomorphologic features, and had the best response to therapy of all groups. b) The acute myelogenous leukemias, including those with myeloid, monocytoid, or erythroid features or a combination of the above, had extensive bone marrow involvement and the characteristic morphology. This group was seen with intermediate frequency and showed an intermediate response to therapy. c) Leukemia-lymphomas of the T-cell group were frequently associated with mediastinal masses and other masses, a cytomorphology which was different from the B-cell group but similar to the null group, and high white cell counts. These cases occurred with intermediate frequency (14%) and had a worse prognosis than the null group. d) Leukemia-lymphomas of the B-cell group had monoclonal surface immunoglobulin with mu-heavy and either kappa or lambda light chain. These patients were least frequent in the series, frequently presented with abdominal masses, and had a characteristic Burkitt cell morphology. Prognosis was the worst of all patients in our series. These data suggest that the major phenotypic groups of childhood leukemia and lymphoma have differing prognoses and should receive differing forms of therapy. Clinical and pathologic features of each group are sufficiently distinctive to suggest that they may have different causes.
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This communication contributes a family with 12 cases of cancer and two cases of leukemia. Chromosomal analysis was performed on three occasions, 9 months apart. In unaffected first-degree relatives, we have demonstrated high frequency of tetraradial figures: in parents, 1:243 mitoses, and in all first degree relatives, 1:328 mitoses. The rate of chromosomal breakage was moderately elevated in comparison with carefully matched controls, mainly in father (6.17), mother (4.01) and one sister (4.07). G-banded and C-banded karyotypes revealed no structural chromosomal abnormality in relatives of leukemic children. This family is one of five leukemic families investigated. Analogous methods of chromosomal analysis have been employed in all, but chromatid exchange figures and elevated chromosomal breakage were detected only in the presently reported pedigree. It has been postulated that in this family there exists a possible relation between increased incidence of chromatid exchange figures and increased tendency to leukemia.
Zoster immune plasma (ZIP) was given to 31 susceptible immunocompromised children one to seven days (median, two days) following household, playmate, or hospital exposures to varicella. The average amount of ZIP transfused was 7 ml/kg. Twenty-one children did not develop varicella or persistent antibodies to varicella-zoster virus (VZV). Eight (26%) of the 31 contracted clinical varicella. Seven cases were mild, but in one child, who was given ZIP seven days after exposure, visceral disease developed and the child died. Two children had subclinical varicella that was documented by persistence of VZV antibodies for at least ten months after passive immunization. Because none of the 30 children given ZIP one to six days following exposure had severe varicella, we conclude that ZIP is effective in preventing or modifying varicella in immunocompromised patients if given shortly after exposure.
Serial coagulation studies were performed in 26 pediatric patients with acute lymphoblastic leukemia during initial induction therapy with vincristine, prednisone, and L-asparaginase. Prolongation of screening coagulation tests was frequent: prothrombin time (in 16 of 26 patients), partial thromboplastin time (23/26) and thrombin time (21/26). In all 26 patients fibrinogen levels fell below .20 g/100 ml and 16 had levels below .10 g/100 ml. Sixteen patients had plasma coagulation factor assays performed. In these 16 patients, Factor XI was less than 40% in 14 and Factor XI was less than 70% in 9, with only a few scattered low levels of other factors. There were no clinical bleeding episodes. Coagulation abnormalities returned to normal at the completion of L-asparaginase therapy while the patients remained on vincristine and prednisone.