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Biomedical subjects

C P Steuber

Publications and source records attributed to C P Steuber.

At least 55 records · Page 3Linked to original sources
PubMed1988

Human leukocyte alpha interferon-induced transient neurotoxicity in children.

Neuropsychiatric complications with recombinant alpha interferon (rIFN-alpha) have been described in adults. Little documentation of similar toxicity in pediatric phase I and phase II trials exists. Two children, treated with rIFN-alpha, experienced confusion, somnolence and syncope, associated with transient electroencephalographic abnormalities. Symptoms abated and electroencephalographic findings improved with termination of therapy. Readministration at lower dosages has not been associated with recurrence of neurotoxicity.

Adolescent↗
PubMed1987

Malignant rhabdoid tumor of the extremity.

Two cases of malignant rhabdoid tumor (MRT) involving the sciatic nerve are described. Despite the close affiliation of the tumor with neural tissue, staining characteristics in these patients do not suggest a neural origin of MRT. Survival in patients with renal and extrarenal MRT has been poor. Our patients were treated with an aggressive chemotherapy program using cisplatin, Adriamycin (doxorubicin), vincristine, cyclophosphamide, actinomycin D, and DTIC. One child died of progressive disease; the other is well 35 months after diagnosis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Pediatric Oncology Group Study of in vitro clonal growth patterns of leukemic cells in childhood acute nonlymphocytic leukemia as a predictor of induction response.

Previous studies have shown that clonal growth patterns of leukemic cells from adult patients with acute nonlymphocytic leukemia (ANLL) have prognostic significance for achieving complete remission (CR). In order to determine if a similar correlation between clonal growth patterns and response to chemotherapy exists in childhood ANLL, bone marrow cells from 189 children with newly diagnosed ANLL were cultured in agar. After 7 days of incubation, colonies (greater than 50 cells), large clusters (20 to 50 cells), and small clusters (4 to 20 cells) were counted. Cultures were analyzed for frequency of clusters and colonies as well as for size of clusters. Two growth patterns significantly associated with poor prognosis for achieving CR were large-cluster growth and high cluster incidence (defined as greater than 400 clusters/10(5) bone marrow cells). The CR rate for the former was 53% (versus 79% for non-Group 1 patients; P = 0.03); the CR rate for the latter was 46% (versus 81% for non-Group 2 patients; P = 0.004). These findings indicate that clonal growth characteristics of leukemic cells from childhood ANLL patients are significantly correlated with response to induction chemotherapy and are useful in identifying a subset of patients with poor prognosis.

Acute Disease↗
PubMed1987

Toxicity evaluation of dihydroxyanthracenedione (DHAD) in combination with cytosine arabinoside (Ara-C).

To determine optimal dosage, Dihydroxyanthracenedione (DHAD) was given once daily for 3 days at dosage levels of 6, 7, 8, and 10 mg/m2 in combination with a 7-day continuous infusion of cytosine arabinoside (Ara-C). Nineteen of 20 children with leukemia who received these agents developed fever requiring hospitalization. There were 4 deaths-2 due to proven infection. One patient developed nonfatal cardiotoxicity. No other significant toxicity was noted. Responses were seen in 7 of 20 patients. The recommended DHAD dosage was 8 mg/m2/day when given in combination with Ara-C.

Adolescent↗
PubMed1986

Extraneural metastases from medulloblastoma: long-term survival after sequentially scheduled chemotherapy and radiotherapy.

Extraneural relapse of medulloblastoma is an uncommon event which has typically been associated with a fatal outcome. We present a case of a 2 1/2-year-old male who developed extensive bone marrow and bone metastases 19 months after diagnosis and treatment of a medulloblastoma. This patient was successfully treated with a sequentially scheduled combination of vincristine, cyclophosphamide, and doxorubicin and remained free of disease for more than 5 years from the time of relapse.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Effect of retinoic acid on myeloid antigen expression and clonal growth of leukemic cells from children with acute non lymphocytic leukemia--a Pediatric Oncology Group Study.

We have used a panel of 5 monoclonal antibodies against normal myeloid-differentiation antigens to determine retinoic acid-induced changes in cell surface antigens on ANLL bone marrow cells from 24 children at the time of diagnosis. Two of these antibodies (T5A7 and 5F1) detect antigens expressed on normal mature granulocytes and on all monocytes, respectively. The percentage of positive cells for each monoclonal antibody was determined by indirect immunofluorescence. After 5 days incubation with 1 microM RA in liquid culture, cells from 11 of 24 patients showed substantially increased expression of one or both antigens detected by T5A7 and 5F1. Leukemic bone marrow cells from these patients were also cultured in methylcellulose medium with and without 1 microM RA for one week, and cells from 16 of 24 patients showed clonal growth. Cultures from 10 of these 16 patients showed RA-induced inhibition of colony growth; of these 10 patients, cultures from six patients showed RA-induced increases in antigens associated with maturing myeloid cells. This suggests that the RA-induced inhibition of clonal growth observed with leukemic cells from these patients may be accompanied by the increased expression of maturation-associated myeloid antigens by these cells in the presence of RA.

Acute Disease↗
PubMed1985

Pediatric Oncology Group experience with modified LSA2-L2 therapy in 107 children with non-Hodgkin's lymphoma (Burkitt's lymphoma excluded).

From September 1976 to August 1979 the Pediatric Oncology Group accessed 145 children to study the effectiveness of modified LSA2-L2 therapy for the treatment of non-Hodgkin's lymphoma (NHL). Burkitt's lymphoma patients were ineligible; E-rosette-positive patients with greater than or equal to 25% blasts in the marrow entered after February 1977 were reported separately. Radiotherapy could be used to treat patients with compressive mediastinal disease at diagnosis and was prescribed for those with residual abdominal disease as demonstrated by second-look surgery on completion of induction chemotherapy. Confirmation of diagnosis by the Pathology Panel and Repository Center for Lymphoma Clinical Trials was mandatory. Diagnostic tissues of 131 patients were reviewed. Among 107 evaluable patients, 91 (85%) achieved complete remission. Differences in response rates among the three major histologic groups (lymphoblastic, undifferentiated, and large cell) were of statistical significance, with response being poorest for diffuse undifferentiated lymphoma (P = 0.03). Failure-free survival did not differ significantly for the three major histologic diagnoses. While response rate was lowest for Murphy Stage III patients (79%), the differences among the stages were not significant. Stage was not a significant prognostic factor for failure-free survival (P = 0.08). The number of patients still at risk and the Kaplan-Meier estimate of percentage of patients remaining at risk after 3 years is: Stage I, 8 (100%); Stage II, 10 (67%); Stage III, 28 (57%); Stage IV, 6 (39%); and greater than 25% blasts, 1 (13%). Stage III failure curves for lymphoblastic disease show continuing stepwise failure through 3 years. Among patients with diffuse large cell and undifferentiated disease, most failures occurred by 8 months. M1 and M2 levels of marrow involvement were not prognostic among children with lymphoblastic disease. The presence of a mediastinal mass was a significant factor contributing to failure in children with lymphoblastic disease without marrow involvement. Leucocytosis greater than 10,000/1, was a significant (P = less than 0.001) factor predicting failure-free survival for patients with large cell lymphoma. The delivery of radiotherapy was not a significant factor in achieving remission. No consistent benefit resulted from using radiotherapy to treat postinduction residual disease demonstrated on second-look exploration. The LSA2-L2 regimen was associated with considerable toxicity, severe or worse in 77% and life-threatening to 40% of these patients. Four died of toxicity. However, therapy was given more easily and safely as investigator experience increased.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1984

Impact of the timing of triple intrathecal therapy on remission induction in childhood acute lymphoblastic leukemia: a Pediatric Oncology Group study.

Five weekly doses of triple intrathecal (IT) chemotherapy (methotrexate, hydrocortisone, cytosine arabinoside) starting on day 1 of treatment were added to systemic induction therapy in a regimen (Arm 3) that was compared to three other regimens (Arms 1, 2, and 4) in which central nervous system (CNS) prophylaxis was initiated after complete marrow remission (CR) was attained. The CR rate for Arm 3 was only 83% as compared to 91-92% for other Arms. The lower CR rate was the result of a significantly higher death rate during induction for patients receiving early CNS prophylaxis (10.6 vs 0.9-3.5%). These differences were only observed in high risk patients as defined in the study. The early death rate was especially high (30%) in Arm 3 for children who were less than 2 years of age. Infection was the primary cause of morbidity and mortality. Severe infection following the initiation of induction therapy was found in 16.7% of patients on Arm 3 vs 1.8-6% on other regimens. Immediate triple IT chemoprophylaxis during induction therapy of acute lymphoblastic leukemia as used in this study appears to be associated with increased susceptibility to infection and this form of CNS prophylaxis has increased hazards of morbidity and mortality in infants and other high risk patients.

Age Factors↗
PubMed1984

Effect of retinoic acid on the clonal growth of childhood myeloid and lymphoid leukemias: a pediatric oncology group study.

We have studied the effects of retinoic acid (RA) on bone marrow leukemic cells from children with acute nonlymphocytic leukemia (ANLL) at the time of diagnosis, and on cells from four ALL/lymphoma cell lines (common-ALL, pre-B-ALL, T-ALL, and Burkitt's lymphoma) derived from children with these diseases. Cells were cultured in methylcellulose medium with clinically attainable concentrations (0.25-2.0 microM) of RA for two weeks prior to colony and cluster quantitation. Myeloid progenitor cells (CFU-GM) obtained from children with hematologically normal bone marrows were also cultured with RA. Of 19 patients with ANLL whose cells formed colonies, 16 (84%) were inhibited by RA; three patients showed either increased or unchanged colony numbers with RA. RA had a similar effect on both ANLL cluster and colony growth. RA (1-2 microM) also inhibited colony growth of the pre-B-ALL, common-ALL, and Burkitt's lymphoma lines; the T-ALL line and normal bone marrow CFU-GM were not inhibited. The inhibitory effects of RA on pediatric ANLL bone marrow cells and on some ALL/lymphoma cell lines compared with CFU-GM indicate that RA may be of value in the treatment of these malignancies in children.

B-Lymphocytes↗
PubMed1982

Equivalence of intrathecal chemotherapy and radiotherapy as central nervous system prophylaxis in children with acute lymphatic leukemia: a pediatric oncology group study.

The efficacy of intrathecal (i.t.) chemoprophylaxis was compared with cranial radiotherapy plus i.t. methotrexate (MTX) in a Southwest Oncology Group (SWOG) study accessing 408 patients from September 10, 1974, to October 29, 1976. Randomization was stratified by prognostic groups (PGs) based on age and white blood cell count at diagnosis. All received induction therapy with vincristine and prednisone (Pred); maintenance therapy consisted of daily 6-mercaptopurine and weekly MTX. Consolidation for arm 1 employed cyclophosphamide and L-asparaginase followed by biweekly 5-day courses of parenteral MTX. The first dose of each course of MTX was given i.t. in triple chemoprophylaxis (MTX, hydrocortisone, and cytosine arabinoside). During maintenance, i.t. chemoprophylaxis was bimonthly and 28-day Pred "pulses" were given every 3 mo. Arm 2 i.t. chemoprophylaxis was initiated on achievement of remission, and arm 3 i.t. on treatment day 1; both continued 1 yr. Arm 4 induction included two doses of L-asparaginase. On achievement of remission, CNS prophylaxis (radiotherapy, 2400 rad plus i.t. MTX) was given. For all, therapy was discontinued after 3 yr of continuous complete remission. Survival and the incidence of extramedullary relapse were similar for the treatments employing either i.t. chemoprophylaxis or radiotherapy plus i.t. MTX upon achievement of remission. Among poor prognosis patients, the duration of complete remission was significantly better with the regimen using i.t. chemoprophylaxis as a component of consolidation therapy than with the regimen employing i.t. chemoprophylaxis early in induction or with the treatment using radiotherapy plus i.t. MTX for CNS prophylaxis. In poor prognosis patients, the initiation of i.t. chemoprophylaxis during consolidation was also associated with hematologic remissions that were significantly better than those achieved with the treatment employing early CNS chemoprophylaxis or with the regimen using radiotherapy plus i.t. MTX. Among average prognosis patients, therapy with CNS chemoprophylaxis during consolidation, as well as the regimen employing radiotherapy and i.t. MTX for CNS prophylaxis, produced hematologic remissions that were significantly longer than those obtained with the regimen using early CNS chemoprophylaxis. Hematologic remissions of good prognosis patients who received treatment with the regimen employing i.t. chemoprophylaxis during consolidation were statistically superior when compared to the regimen employing CNS radiotherapy plus i.t. MTX. This study indicates that i.t. chemoprophylaxis may be substituted for cranial radiotherapy when utilizing effective systemic regimens. Additionally, chemoprophylaxis may be reduced from 3 to 1 yr in patients with good prognostic factors.

Adolescent↗
PubMed1981

Occult testicular leukemia: testicular biopsy at three years continuous complete remission of childhood leukemia: a Southwest Oncology Group Study.

Between June 1977 and December 1978, occult testicular leukemia (OTL) was discovered at three years of continual complete remission (CCR) from the time of diagnosis of acute lymphoblastic leukemia (ALL) in 5 of 59 (8.5%) of males undergoing bilateral wedge testicular biopsy at 1 of 15 participating Southwest Oncology Group (SWOG) institutions. Forty-six of the 54 males with normal biopsies (78% of the total group of 59) have remained free of recurrent ALL at a median of 18 months (range 13 to 23 months) since the biopsy procedure, whereas eight have relapsed for the first time--five bone marrow (BM), one sclera, one simultaneous BM and testes, and one testes--at a median of 12.5 months (range 4 to 22 months) after the normal testicular biopsy. With aggressive therapy after biopsy in the five boys with OTL, one has died 19 months after biopsy (after two BM relapses), one is alive 21 months after biopsy (after two BM relapses), and three are alive and free of recurrent ALL 13, 16, and 19 months, respectively, since the diagnosis of OTL.

Biopsy↗
PubMed1981

Low response rate to 5 aza-cytidine, vincristine, and prednisone therapy in previously treated childhood acute nonlymphocytic leukemia: a Southwest Oncology Group Study.

A combination therapy with 5 aza-cytidine (5 AZA-C), vincristine (VCR), and prednisone (PRED) was given to 53 children with acute nonlymphocytic leukemia resistant to conventional therapy. Of these, eight children obtained a complete remission and seven a partial remission. Maintenance therapy was initiated in 12 children. The remission duration varied between 19 and 176 days (median 69 days). The main toxicity was vomiting and myelosuppression manifested as severe neutropenia and thrombocytopenia. It is concluded that VCR and PRED do not increase the response rate to that of 5 AZA-C as a single agent.

Antineoplastic Agents↗
PubMed1981

Therapy in childhood acute nonlymphocytic leukemia (ANLL). Evolution of current concepts of chemotherapy.

Chemotherapy remains the major treatment modality in childhood acute nonlymphocytic leukemia (ANLL). Current remission induction rates range from 60% to 80%; but even with the improved rate of response to therapy, the median duration of remission has seldom exceeded 1 year. On the other hand, an increasing number of children with ANLL who were treated with intensive induction and maintenance chemotherapy regimens for a prescribed period followed by discontinuation of therapy are remaining in remission. The evolution of present-day chemotherapy approaches to childhood ANLL are reviewed in this article.

Acute Disease↗
PubMed1980

X-linked lymphoproliferative syndrome registry report.

Immune deficiency, especially to the Epstein-Barr virus, and increased susceptibility to fatal infectious mononucleosis, acquired agammoglobulinemia, and lymphoma are the cardinal features of the X-linked lymphoproliferative syndrome. Since the establishment of the XLP Registry in September, 1978, 59 affected males in seven unrelated kindreds were comprehensively studied. A spectrum of lymphoproliferative phenotypes was observed. Thirty-four patients (57%) died from infectious mononucleosis, eight (14%) had fatal infectious mononucleosis with lymphoma (immunoblastic sarcoma), nine (15%) had depressed immunity following EBV infection, and eight (14%) developed lymphoma. Several patients with XLP lacked EBV antibodies despite infection by EBV. The results of this study suggest that EBV can be an oncogenic agent in patients who are immune deficient with XLP.

Adolescent↗