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Biomedical subjects

M P Link

Publications and source records attributed to M P Link.

At least 91 records · Page 5Linked to original sources
PubMed1987

Prognostic factors in childhood acute myelogenous leukemia.

The prognostic significance of initial clinical and laboratory parameters was evaluated in 125 children with acute myelogenous leukemia (AML) treated on two consecutive protocols (VAPA and 80-035). Both protocols used an anthracycline with cytosine arabinoside (ara-C) for induction therapy followed by 12 to 14 months of intensive sequential postremission chemotherapy. Results are similar for the two treatment regimens. Seventy-two percent of patients achieved a complete remission, with 42% projected 5-year disease-free survival for the complete responders. Monocytic or myelomonocytic leukemic subtype (French-American-British [FAB] types M4 and M5), WBC count less than 100,000/microL, and age less than 2 years at diagnosis all predicted increased risk of relapse and decreased overall survival in univariate analyses. FAB subtype and high white count continued to predict for an increased risk of relapse in multivariate analyses and only M5 leukemic subtype independently predicted for poor survival. Patients with M4 or M5 leukemic subtype had a higher incidence of initial relapses in the CNS. The addition of intrathecal cytosine arabinoside in the second protocol, 80-035, decreased the percentage of patients with initial failure in the CNS, but did not improve overall survival. Improved CNS prophylaxis, better systemic therapy, and/or different treatment strategies are needed to improve therapy in these high-risk patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Giant cell pneumonia caused by parainfluenza type 3 in a patient with acute myelomonocytic leukemia.

A 4 1/2-year-old boy with acute myelomonocytic leukemia developed fever, neutropenia, and a prolonged respiratory illness while receiving maintenance chemotherapy. An open lung biopsy specimen demonstrated a giant cell pneumonia with intracytoplasmic and probable intranuclear viral inclusions of the paramyxovirus type. Serologic studies demonstrated convincing evidence of a parainfluenza type 3 infection. Although parainfluenza type 3-induced giant cell pneumonia has been reported in infants with the severe combined immunodeficiency syndrome, to our knowledge, this is the first reported case of this complication in a patient with leukemia.

Child, Preschool↗
PubMed1987

Improved results of treatment of adult acute lymphoblastic leukemia.

We designed a treatment program to improve the outcome for adults with acute lymphoblastic leukemia (ALL). Treatment included a remission-induction phase followed by intensive alternating cycles of non-cross-resistant chemotherapy and prolonged oral maintenance therapy. Eighty-one consecutive previously untreated patients were entered on this study. Ninety-four percent of patients entered complete remission. A Kaplan-Meier analysis predicts that 53% +/- 9% (SEM) of patients in remission will remain free of disease at 3 years. Neither age, sex, WBC count, nor immunophenotype had a significant effect on remission duration. This program of intensive cyclical chemotherapy has improved the disease-free survival of patients with adult ALL.

Adolescent↗
PubMed1986

A unique antigen on mature B cells defined by a monoclonal antibody.

A novel 42,000 dalton antigen (MB-1) expressed by mature human B cells in blood and tonsil was identified and characterized by utilizing a hybridoma monoclonal antibody. A comparison of MB-1 with other known B cell antigens suggests that the MB-1 antigen has not been previously identified. From one-and two-color immunofluorescence studies, it appears that the MB-1 antigen is found on all normal immunoglobulin (Ig)-expressing cells, but not on T cells, thymocytes, granulocytes, or platelets. Studies of malignant B cell tumors reveal that the antigen is expressed by virtually all Ig-expressing B cell tumors but only 10% of SIg- B-lineage leukemias. Data from these studies suggest that the MB-1 antigen is expressed late in B cell ontogeny before the expression of SIg.

Antibodies, Monoclonal↗
PubMed1986

Common mechanism of chromosome inversion in B- and T-cell tumors: relevance to lymphoid development.

An inversion of chromosome 14 present in the tumor cells of a patient with childhood acute lymphoblastic leukemia of B-cell lineage was shown to be the result of a site-specific recombination event between an immunoglobulin heavy-chain variable gene and the joining segment of a T-cell receptor alpha chain. This rearrangement resulted in the formation of a hybrid gene, part immunoglobulin and part T-cell receptor. Furthermore, this hybrid gene was transcribed into messenger RNA with a completely open reading frame. Thus, two loci felt to be normally activated at distinct and disparate points in lymphocyte development were unified and expressed in this tumor.

B-Lymphocytes↗
PubMed1986

The effect of adjuvant chemotherapy on relapse-free survival in patients with osteosarcoma of the extremity.

We conducted a randomized controlled trial to determine whether intensive multi-agent adjuvant chemotherapy improves the chances of relapse-free survival in patients with nonmetastatic high-grade osteosarcoma of the extremity, as compared with concurrent controls. After undergoing definitive surgery, 36 patients were randomly assigned to adjuvant chemotherapy or to observation without adjuvant treatment. At two years the actuarial relapse-free survival was 17 percent in the control group, similar to that found in studies before 1970, and 66 percent in the adjuvant-chemotherapy group (P less than 0.001). Similar results were observed among 77 additional patients who declined to undergo randomization but who elected observation or chemotherapy. We conclude that the natural history of osteosarcoma of the extremity has remained stable over the past two decades, that adjuvant chemotherapy increases the chances of relapse-free survival of patients with high-grade osteosarcoma, and that it should be given to all such patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Chromosome clues to acute leukemia in Down's syndrome.

Surprisingly few cases of Down's syndrome with acute leukemia have been documented by chromosome banding studies of the leukemia cells. We studied a Down's syndrome child with acute myelomonocytic leukemia and found that, including this case, only 24 cases of Down's syndrome and acute leukemia have been reported with chromosome banding analysis. Twenty-three of the patients had a trisomy 21 chromosome complement, whereas, one had a translocation. The types of acute leukemia included acute myeloblastic leukemia, acute myelomonocytic leukemia, acute monoblastic leukemia, acute lymphoblastic leukemia, and erythroleukemia. Only three cases had chromosomes missing from the leukemic cells. Sixteen of the 24 patients had extra chromosomes in their malignant cells. Chromosomes #8 and #21 were extra in six cases each and chromosomes #19 and #22 were extra in four cases each. Chromosome rearrangements were observed in nine cases. Three of the nine cases had partial deletion of the long arm of chromosome #6. Cases of Down's syndrome with acute leukemia need to be reported with high-resolution chromosome banding of the leukemia cells. There is as yet no clear chromosome clue as to the precise basis of the etiologic association between Down's syndrome and acute leukemia.

Acute Disease↗
PubMed1986

Cytogenetic and immunophenotypic analysis of cell lines established from patients with T cell leukemia/lymphoma.

Cell lines were established from five patients with T cell malignancies. Two patients had T cell lymphoblastic lymphoma (T-LL), whereas three patients had T cell acute lymphoblastic leukemia (T-ALL). Both T-LL cell lines expressed cell surface antigens characteristic of midthymocytes (Leu 2, 3, 6+). One T-ALL cell line also expressed this immunophenotype, one expressed suppressor/cytotoxic antigens (Leu 2+; Leu 3, 6-), and one expressed antigens of a mature but uncommitted T cell (Leu 4+; Leu 2, 3, 6-). Cytogenetic analysis showed that each cell line had 46 chromosomes with pseudodiploidy. The three T-ALL cell lines had only a few chromosome changes; one cell line had one deletion, another had two deletions, and the third had a translocation and two deletions (including loss of part of 9p). In comparison, both T-LL cell lines had complex chromosome changes, including most notably a rearrangement of band 14q11.2. The immunophenotypes and chromosome breakpoints showed patterns of interlock between the T-LL and T-ALL cell lines because common abnormalities occurred at six distinct chromosome sites. Cell lines with limited and specific chromosomal abnormalities are important because they can provide the basic material for molecular genetic studies that could elucidate the genetic mechanisms involved in neoplasia.

Adolescent↗
PubMed1986

Lymphoblastic lymphoma: an immunophenotype study of 26 cases with comparison to T cell acute lymphoblastic leukemia.

A series of 26 lymphoblastic lymphomas (LLs) and 13 T cell acute lymphoblastic leukemias (ALLs) were investigated using a battery of monoclonal antibodies applied to tissue frozen sections. Twenty-one of the LLs were of T lineage. All but one of the T cell LLs were of immature thymic phenotype, mostly corresponding to stage II cortical thymocyte development. The T cell LLs expressed Leu-1 in 100%, Leu-4 and Leu-9 in 95%, and Leu-5 in 85% of the cases. The high percentage of Leu-4 expression in this series is probably due to detection of cytoplasmic antigen with our methods. One LL was of pre-B or B cell and two cases were of common ALL phenotype. Two cases were of undefined phenotype, expressing markers of both B and T cell differentiation. Pediatric cases showed a greater tendency toward T cell phenotype than did adult cases. The cases of T cell ALL were immunophenotypically similar to the cases of T cell LL but showed a tendency toward a more immature phenotype.

Adolescent↗
PubMed1985

Conservative management of testicular endodermal sinus tumor in childhood.

Endodermal sinus tumor is the most common testicular neoplasm in childhood. The management of children with this neoplasm remains controversial. We have treated prospectively 5 children with stage I endodermal sinus tumor with limited surgery and no adjuvant therapy. The median patient age at diagnosis was 21 months (range 5 to 24 months). All children underwent an inguinal orchiectomy with high ligation of the spermatic cord. Retroperitoneal node dissection was not performed in any case and no child received adjuvant chemotherapy or radiation therapy. All patients were well without evidence of recurrent disease at a median followup of 46 months (range 19 to 72 months). Because these tumors usually are localized at the time of diagnosis, rarely spread to the retroperitoneal nodes and have a biological marker in most cases, and because good salvage chemotherapy is available for patients with relapse, we believe that nonmetastatic testicular endodermal sinus tumors in children can be managed with radical orchiectomy alone. Retroperitoneal node dissection is not necessary and adjuvant therapy is not indicated if markers return to normal. Further treatment should be reserved for the rare child with relapse.

Castration↗
PubMed1985

Discordance between surface and cytoplasmic expression of the Leu-4 (T3) antigen in thymocytes and in blast cells from childhood T lymphoblastic malignancies.

We have examined the expression of the Leu-4 (T3) antigen on the cell surface and in the cytoplasm of blast cells from 23 patients with T cell acute lymphoblastic leukemia and T cell lymphoblastic lymphoma. In the majority of cases (17), the Leu-4 antigen was absent from the cell surface; however, in 16 of these 17 cases, blast cells demonstrated cytoplasmic expression of Leu-4. This discordance between surface and cytoplasmic expression of Leu-4 was also found in thymocytes and appeared to be restricted to Leu-4, in that tests of other T cell antigens rarely revealed discordance between surface and cytoplasmic expression. To study further the cytoplasmic determinant identified by anti-Leu-4 in malignant T lymphoblasts, immunoprecipitation studies were performed that utilized biosynthetic labeling of established T cell lines derived from T lymphoblastic malignancies. By one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis, identical Leu-4 polypeptide families were immunoprecipitated from surface Leu-4+ and surface Leu-4-/cytoplasmic Leu-4+ cell lines. Because T lymphoblastic malignancies represent proliferations of immature T cells, and because the cases studied demonstrated surface phenotypes corresponding to all of the proposed stages of T cell ontogeny, it appears that cytoplasmic expression of Leu-4 occurs early in T cell development. The reason for the failure of these immature T cells to transport the Leu-4 molecule to their surface remains to be elucidated.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1985

Leukemia with Down's syndrome: translocation between chromosomes 1 and 19 in acute myelomonocytic leukemia following transient congenital myeloproliferative syndrome.

A girl with Down's syndrome was born with a myeloproliferative disorder. The child had spontaneous regression of the myeloproliferation, with acute leukemia developing at a later date. Morphologic, cytochemical, immunologic, and immunoglobulin gene configuration studies all supported the diagnosis of acute nonlymphocytic leukemia. High-resolution chromosome studies revealed that the leukemic cells consistently contained a translocation between chromosomes 1 and 19: der(19)t(1;19)(q25;p13). Spontaneous regression of the transient myeloproliferative syndrome of the newborn with Down's syndrome may not always be permanent, and the transient myeloproliferative syndrome may sometimes represent an early sign of acute nonlymphocytic leukemia.

Antibodies, Monoclonal↗
PubMed1985

Acute leukemias associated with the 4;11 chromosome translocation have rearranged immunoglobulin heavy chain genes.

Studies of acute leukemia with the 4;11 translocation have yielded conflicting results regarding the lineage of the cell of origin in this disease. To investigate this issue further, we have examined the state of immunoglobulin genes in tumor cells from two affected patients, immunophenotyped their leukemic cells using a number of monoclonal antibody reagents with specificities for lymphoid or myelomonocytic antigens, and examined the malignant cells by electron microscopy. DNA was extracted from leukemic bone marrow cells and hybridized with radiolabeled DNA fragment probes specific for the constant region of immunoglobulin heavy chain and kappa and lambda light chain genes. Autoradiographs revealed rearrangement of both allelic heavy chain genes, but a germline configuration of light chain genes in both cases. Surface marker analysis showed that blasts from both patients expressed HLA-DR and the myeloid antigens Leu-M1, 1C2, 2D1, and 4B3, but lacked common acute lymphocytic leukemia antigen or T antigens. Furthermore, they did not have sheep erythrocyte receptors nor did they express surface or cytoplasmic immunoglobulin or B cell precursor determinants. Electron microscopy analysis showed that blast cells from patient 1 exhibited numerous monoribosomes, polyribosomes, and isolated strands of rough endoplasmic reticulum in their cytoplasm. These ultrastructural features are characteristic for both common acute lymphocytic leukemia and pre-B-ALL cells, but not for T-ALL or acute myelogenous leukemia cells. Peroxidase was undetectable in cells from both patients. Our study suggests that this disorder represents a unique subtype of leukemia. The cell of origin may be an early B cell progenitor that shares certain surface antigens with myeloid cells or a stem cell with the potential for both lymphoid and myelomonocytic differentiation.

Antigens, Neoplasm↗
PubMed1985

Non-Hodgkin's lymphoma in children.

The childhood non-Hodgkin's lymphomas (NHL) are histologically, immunologically, and clinically a heterogeneous group of diseases. Recent advances in our understanding of NHL have demonstrated the similarities between childhood NHL and childhood acute lymphoblastic leukemia (ALL). Treatment strategies utilizing systemic chemotherapy and modeled after successful treatment programs for ALL have resulted in a dramatic improvement in prognosis for children with NHL, and the majority of affected children are now curable.

Abdomen↗
PubMed1984

Thyroid dysfunction after radiotherapy in children with Hodgkin's disease.

Thyroid function was measured in 119 children, 16 years of age or less, after radiotherapy (XRT) for Hodgkin's disease. Thyroid abnormalities developed in 4 of 24 children (17%) who received 2600 rad or less, and in 74 of 95 children (78%) who received greater than 2600 rad to the cervical area, including the thyroid. The abnormality in all but three (one with hyperthyroidism and two with thyroid nodules) included the development of elevated levels of thyroid stimulating hormone (TSH). Age, sex, and administration of chemotherapy were not significant factors in the development of thyroid dysfunction. All children had lymphangiograms (LAG) and no time relationship was noted between thyroid dysfunction and LAG-XRT interval. The mean interval from radiotherapy to documented thyroid dysfunction was 18 months in the low-dose group and 31 months in the high-dose group, with most patients becoming abnormal within 3 to 5 years. Of interest was a spontaneous return of TSH to within normal limits in 20 children and substantial improvement in another 7. This study confirms the occurrence of dose-related occult hypothyroidism in children following external irradiation of the neck.

Adolescent↗