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Biomedical subjects

R R Chilcote

Publications and source records attributed to R R Chilcote.

At least 19 recordsLinked to original sources
PubMed1993

Long-term follow-up of patients treated with COMP or LSA2L2 therapy for childhood non-Hodgkin's lymphoma: a report of CCG-551 from the Childrens Cancer Group.

PURPOSE: We analyzed the long-term results of a Childrens Cancer Group (CCG) randomized study comparing cyclophosphamide, vincristine, methotrexate, and prednisone (COMP) versus LSA2L2 as treatment for childhood non-Hodgkin's lymphoma. The initial results were previously reported (N Engl J Med 308:559, 1983). PATIENTS AND METHODS: A total of 429 patients are reported here, 68 with localized disease and 361 with disseminated disease. The distribution of disseminated-disease patients by histologic type was 164 lymphoblastic, 60 large-cell, and 137 undifferentiated lymphomas. Median follow-up duration of surviving patients is 8 years. RESULTS: Event-free survival (EFS) of patients with localized disease was 84% at 5 years. No differences were seen between the two treatment regimens. Results for patients with disseminated disease was dependent on histologic subtype: patients with lymphoblastic lymphoma did better when treated with LSA2L2 (5-year EFS of 64% v 35% for COMP); COMP produced better results for patients with undifferentiated lymphoma (5-year EFS of 50% v 29% for LSA2L2). Results for large-cell lymphoma patients were similar (5-year EFS of 52% for COMP v 43% for LSA2L2). Five percent of patients died of treatment-related complications while on therapy (primarily infections). Only four deaths without progression have been observed off-therapy (two from restrictive lung disease, one from an acute asthma attack, one from colon cancer). Patient survival rates after recurrence were poor. CONCLUSION: Treatment success can be expected in 84% of pediatric patients with localized non-Hodgkin's lymphoma. For patients with disseminated disease, treatment success can be expected in 64% of those with lymphoblastic and 50% of those with undifferentiated or large-cell disease. To date, late adverse events are rare.

Adolescent↗
PubMed1990

Hereditary spherocytosis associated with deletion of human erythrocyte ankyrin gene on chromosome 8.

Hereditary spherocytosis (HS) is one of the most common hereditary haemolytic anaemias. HS red cells from both autosound dominant and recessive variants are spectrin-deficient, which correlates with the severity of the disease. Some patients with recessive HS have a mutation in the spectrin alpha-2 domain (S.L.M. et al., unpublished observations), and a few dominant HS patients have an unstable beta-spectrin that is easily oxidized, which damages the protein 4.1 binding site and weakens spectrin-actin interactions. In most patients, however, the cause of spectrin deficiency is unknown. The alpha- and beta-spectrin loci are on chromosomes 1 and 14 respectively. The only other genetic locus for HS is SPH2, on the short arm of chromosome 8 (8p11). This does not correspond to any of the known loci of genes for red cell membrane proteins including protein 4.1 (1p36.2-p34), the anion exchange protein (AE1, band 3; 17q21-qter), glycophorin C (2q14-q21), and beta-actin (7pter-q22). Human erythrocyte ankyrin, which links beta-spectrin to the anion exchange protein, has recently been cloned. We now show that the ankyrin gene maps to chromosome 8p11.2, and that one copy is missing from DNA of two unrelated children with severe HS and heterozygous deletions of chromosome 8 (del(8)(p11-p21.1)). Affected red cells are also ankyrin-deficient. The data suggest that defects or deficiency or ankyrin are responsible for HS at the SPH2 locus.

Ankyrins↗
PubMed1989

Similar efficacy of 6 and 18 months of therapy with four drugs (COMP) for localized non-Hodgkin's lymphoma of children: a report from the Childrens Cancer Study Group.

Successful treatment of localized non-Hodgkin's lymphoma (NHL) in childhood with 18 months of cyclophosphamide, vincristine, methotrexate (MTX), and prednisone (COMP) prompted a randomized clinical trial to determine whether a 6-month course of the same therapy was as effective as an 18-month course when combined with local irradiation. Two successive Childrens Cancer Study Group (CCSG) protocols (CCG 551 and CCG 501) entered 232 eligible patients from October 1979 until April 1986. Initially, all children with localized disease were considered eligible, but by a subsequent amendment, those with lymphoblastic (LB) histology were excluded. Hence, the study population consisted of 211 patients with nonlymphoblastic (NLB) and 21 with LB disease. Early relapses (before 6 months) occurred in 13 patients with NLB histology. Late relapses were seen in seven patients, three with LB histology. Among the 104 randomized patients who followed the prescribed therapy, there were four recurrences and no differences between 6-month and 18-month therapy. The overall survival for NLB disease was 91% on CCG 551 and 98% on CCG 501. We conclude that 6 months of COMP is excellent therapy for children with localized NLB NHL.

Adolescent↗
PubMed1988

Homozygous deletion of the alpha- and beta 1-interferon genes in human leukemia and derived cell lines.

The loss of bands p21-22 from one chromosome 9 homologue as a consequence of a deletion of the short arm [del(9p)], unbalanced translocation, or monosomy 9 is frequently observed in the malignant cells of patients with lymphoid neoplasias, including acute lymphoblastic leukemia and non-Hodgkin lymphoma. The alpha- and beta 1-interferon genes have been assigned to this chromosome region (9p21-22). We now present evidence of the homozygous deletion of the interferon genes in neoplastic hematopoietic cell lines and primary leukemia cells in the presence or absence of chromosomal deletions that are detectable at the level of the light microscope. In these cell lines, the deletion of the interferon genes is accompanied by a deficiency of 5'-methylthioadenosine phosphorylase (EC 2.4.2.28), an enzyme of purine metabolism. These homozygous deletions may be associated with the loss of a tumor-suppressor gene that is involved in the development of these neoplasias. The relevant genes may be either the interferon genes themselves or a gene that has a tumor-suppressor function and is closely linked to them.

Chromosome Deletion↗
PubMed1987

The pathology of non-Hodgkin's lymphoma of childhood: II. Reproducibility and relevance of the histologic classification of "undifferentiated" lymphomas (Burkitt's versus non-Burkitt's).

The Children's Cancer Study Group conducted prospective clinical trials of 608 children with non-Hodgkin's lymphoma from 1977 to 1983. In 1980, significant differences in survival of children with disseminated disease correlated with histologic diagnosis and the randomized treatment employed. A pathology reproducibility review showed the lymphoblastic lymphoma cases to be virtually 100 per cent distinguishable histologically from the nonlymphoblastic lymphomas (Burkitt's, non-Burkitt's, and "histiocytic"). However, diagnostic reproducibility of the pathologist-of-record was 59 per cent in the Burkitt's and non-Burkitt's lymphoma group. Therefore, 159 cases, agreed on by the pathologist-of-record and the "lymphoma panel" as Burkitt's (77 cases) or non-Burkitt's lymphoma (82 cases) and designated as the "reference diagnosis," were blindly reviewed twice each by two hematopathologists to yield the "review diagnoses." Consensus agreement was achieved in 67 per cent of cases overall, 82 per cent of Burkitt's and 54 per cent of non-Burkitt's lymphoma. Using the "reference diagnoses," we found that the relative frequency of Burkitt's and non-Burkitt's lymphoma was associated with the extent of disease at diagnosis (P = 0.06) but not with other prognostic factors. Despite the difficulties in histologic classification, analyses that used either "reference diagnoses" or "consensus review diagnoses" and that were adjusted for extent of disease consistently demonstrated significantly shorter event-free survival for patients having Burkitt's lymphoma; their failure rate was four times that for patient's with non-Burkitt's lymphoma. Newer cell biologic techniques hopefully will enhance histopathologic distinctions that remain the basis for diagnosis.

Burkitt Lymphoma↗
PubMed1987

Association of red cell spherocytosis with deletion of the short arm of chromosome 8.

Congenital spherocytic anemia is a common disorder, but in most cases the nature of the underlying membrane lesion is unknown and the genetic defect has not yet been unequivocally mapped to a chromosome. We studied two dysmorphic siblings with neurologic findings and hemolytic anemia. Clinical and laboratory findings in these two siblings were consistent with the diagnosis of congenital spherocytosis whereas both parents and two unaffected siblings were normal. The two affected children had an abnormal chromosomal complement as a result of a deletion of the short arm of chromosome 8 [(46,XX,del(8)(p11.1p21.1)]. These results suggest that a gene whose deletion results in a congenital spherocytic anemia phenotype resides on this region on the short arm of chromosome 8.

Chromosome Deletion↗
PubMed1985

Lymphoblastic leukemia with lymphomatous features associated with abnormalities of the short arm of chromosome 9.

Patients with acute lymphoblastic leukemia (ALL) who present with bulky disease of the lymph nodes, spleen, or mediastinum--so-called "lymphomatous ALL"--appear to represent a distinct subgroup among patients with ALL of T-cell lineage who have different clinical findings, but the biologic basis for these differences is not known. While studying 65 patients with lymphoblastic leukemia whose karyotype was determined at diagnosis, we compared the findings in 8 patients with lymphomatous ALL and 57 patients whose presentations were more typical of ALL. Six patients with lymphomatous ALL had karyotypic abnormalities leading to loss of bands p21-p22 on the short arm of chromosome 9. The mechanisms varied and included deletions, unbalanced translocations, or loss of the entire chromosome. Only 1 of the 57 patients without lymphomatous ALL had an abnormality of chromosome 9 at diagnosis (P less than 0.001). These findings indicate that loss of chromosomal material in the region of 9p21-p22 is closely associated with lymphomatous ALL; by analogy with retinoblastoma, in which gene deletions are associated with an enzyme deficiency, this disease may be related to the loss of the enzyme methylthioadenosine phosphorylase, previously reported in some of these patients.

Adolescent↗
PubMed1985

Metastatic Wilms' tumor causing acute hepatic-vein occlusion (Budd-Chiari syndrome).

We describe a case of Wilms' tumor in a 6-yr-old girl which extended from the right kidney and completely obstructed the inferior vena cava and hepatic veins to the level of the right atrium, producing an acute Budd-Chiari syndrome. After an initial course of chemotherapy, the primary tumor was excised and, using cardiopulmonary bypass, the tumor thrombus was removed from the inferior vena cava and hepatic veins. The Budd-Chiari syndrome resolved and after triple-drug chemotherapy and radiotherapy under the National Wilms' Tumor Study-2 protocol the child has remained disease-free for 5 yr.

Budd-Chiari Syndrome↗
PubMed1985

Diffuse malignant peritoneal mesothelioma in a 13-year-old girl. Report of a case and review of the literature.

A case of diffuse malignant peritoneal mesothelioma in a 13-year-old girl is described. The patient had a short history of abdominal pain, distention, and tenderness. At laparotomy she was found to have ascites and numerous nodules and plaques affecting the peritoneal cavity and the omentum. A diagnosis of diffuse pseudotumoral deciduosis was made, which on review was revised to malignant peritoneal mesothelioma. The patient's condition gradually deteriorated and she died 8 months after diagnosis in spite of administration of combination chemotherapy.

Adipose Tissue↗
PubMed1984

Studies on the pathology of non-Hodgkin's lymphoma of childhood. I. The role of routine histopathology as a prognostic factor. A report from the Children's Cancer Study Group.

Between April 1977, and August 1980, the Children's Cancer Study Group (CCSG) conducted a clinical trial of childhood non-Hodgkin's lymphoma (NHL), randomizing 256 patients to one of two treatment regimens. A 4-drug regimen (regimen 1, modified cyclophosphamide, Oncorin [vincristine], methotrexate, prednisone [COMP] ) was compared with a 10-drug regimen (regimen 2, modified LSA2-L2). Using the Rappaport classification, the review pathologist diagnosed the 213 evaluable tissue specimens as follows: lymphoblastic (LC), 73; Burkitt's tumor (BT), 40; "undifferentiated" non-Burkitt's type (NB), 67; large cell or "histiocytic" lymphoma (HI), 29; and other types (OT), 4. Concurrence in classification between the review and institutional pathologists was poor when using the above four categories; however, concurrence was 88% between the review pathologist and other hematopathologists, and 99% when classifying the specimens as lymphoblastic or nonlymphoblastic. For patients with nonlocalized disease, this randomized controlled study demonstrated a new important correlation of histopathology with the effectiveness of treatment. When analyzed without stratification into lymphoblastic and nonlymphoblastic types, the two regimens showed identical relapse free survival (RFS) curves for patients with nonlocalized involvement. However, when patients were stratified according to histologic classification, regimen 2 was superior to regimen 1 for patients with lymphoblastic lymphoma, achieving 74% RFS at 30 months compared to 31% for regimen 1 (P = 0.001). Conversely, those with nonlymphoblastic types (BT, NB, HI) treated with regimen 1 had a 58% RFS at 30 months compared to 32% for those treated on regimen 2 (P = 0.01). This study demonstrates that proper, routine histopathologic classification of NHL is the best criterion for choice of therapy in children with nonlocalized involvement. As a result of this study, all patients with nonlocalized disease, diagnosed after August 1980, were no longer randomized but were assigned to the appropriate treatment regimen based on prospective review of histopathology.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Mediastinal mass in acute lymphoblastic leukemia.

Patients with acute lymphoblastic leukemia who have a mediastinal mass at the time of diagnosis are said to have a poor prognosis. However, many factors which may not be independent contribute to the success of treatment. We compared the disease characteristics and results of therapy in children having large mediastinal masses and lymphoblastic leukemia without mediastinal mass. Patients with a mediastinal mass had less evidence of marrow failure but were burdened with considerably more leukemic cells as measured by peripheral blood white count and extent of lymphadenopathy. Since the presence of mediastinal mass was strongly associated with these and other poor prognostic characteristics, we used multivariate techniques to determine which characteristics were independently associated with an increased risk for relapse. White count, extent of lymphadenopathy, age, and sex were significant predictors of early relapse, but when controlled for these variables the presence of a mass did not predict prognosis.

Adolescent↗
PubMed1984

The treatment of localized non-Hodgkin's lymphoma in children: a report from the Children's Cancer Study Group.

Investigators of the Children's Cancer Study Group entered 73 children with previously untreated localized non-Hodgkin's lymphoma on a prospective randomized trial of systemic treatment with either a four-drug program (cyclophosphamide, vincristine, methotrexate, prednisone [COMP]) or a 10-drug (LSA2-L2 modified) program of 18 months duration. All patients received central nervous system prophylaxis with intrathecal methotrexate and most received local or regional radiation treatment. The three-year relapse-free survival rate for all patients (N = 73) was 84%; for COMP (N = 42) was 85%, and for LSA2-L2 (N = 31) was 84%. Of the 12 patients who suffered adverse events eight relapsed and four died of toxicity. Histopathology was reviewed centrally. Of 32 patients with nonlymphoblastic disease treated with COMP only one relapsed. Of 26 patients treated with LSA2-L2, four relapsed. Patients with localized lymphoblastic disease were uncommon. None of three patients treated with LSA2-L2 relapsed compared with three of nine treated with COMP. COMP is an excellent treatment for patients with localized disease of nonlymphoblastic type, but the relative value of the two regimens for patients with localized lymphoblastic disease is uncertain.

Adolescent↗
PubMed1984

Chromosome abnormalities in tumor cells from patients with sporadic Wilms' tumor.

The karyotype of nine of 11 Wilms' tumors was successfully analyzed using chromosome banding techniques. Peripheral lymphocytes had a normal karyotype in all six analyzed cases. Cultured cells from one tumor had a normal karyotype; however, they appeared to be fibroblasts. A chromosome 11 deletion, del(11)(p13p14), similar to that seen in patients with sporadic aniridia, was found as the sole abnormality in cells from one tumor. Abnormalities of chromosome 1 resulting in trisomy for the long arm (q21-q31) were found in five cases. Two of them had a translocation involving 1q and 16q, although the breakpoints in each chromosome appeared to differ in the two cases. Two patients had an isochromosome of the long arm, i(1q), and a fifth case had a duplication of the long arm as a result of karyotypic evolution. Chromosome 16 abnormalities were found in three cases, resulting in the partial monosomy of the long arm, sharing q22 as a common deletion. The same three cases also had trisomy 1q due to an unbalanced translocation of 1q or an i(1q). Trisomy for both chromosomes 9 and 12 were present in three cases. Two patients each had whole or partial trisomy of chromosomes 6, 7, 8, 17, and 18. Our data show that although an 11p deletion can occur as a mutation confined to tumor cells, the most common changes are trisomy for 1q, and less often a deletion of 16q.

Adolescent↗
PubMed1983

Childhood non-Hodgkin's lymphoma. The results of a randomized therapeutic trial comparing a 4-drug regimen (COMP) with a 10-drug regimen (LSA2-L2).

Members of the Childrens Cancer Study Group treated 234 eligible patients in a randomized trial designed to study the relative effectiveness of two therapy programs for the treatment of childhood and adolescent non-Hodgkin's lymphoma. Two chemotherapeutic strategies were compared: a 4-drug regimen (COMP) and a 10-drug regimen (modified LSA2-L2). Failure-free survival for all patients was 60 per cent at 24 months. In patients with disseminated disease treatment success was influenced by both the histologic subtype of disease and the therapeutic regimen followed. The 10-drug program was more effective than the 4-drug program in patients with disseminated lymphoblastic disease (two-year failure-free survival rate, 76 vs. 26 per cent, respectively; P = 0.0002), whereas the 4-drug program was more effective than the 10-drug program in those with nonlymphoblastic disease (57 vs. 28 per cent, respectively, P = 0.008). The less toxic, more easily administered 4-drug regimen was as effective as the 10-drug regimen in patients with localized disease (89 vs. 84 per cent, respectively).

Adolescent↗