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Biomedical subjects

T C Griffin

Publications and source records attributed to T C Griffin.

12 recordsLinked to original sources

Slow disappearance of peripheral blood blasts is an adverse prognostic factor in childhood T cell acute lymphoblastic leukemia: a Pediatric Oncology Group study.

The rapidity of response to induction therapy is emerging as an important prognostic factor in children and adolescents with acute lymphoblastic leukemia (ALL). We studied the relationship between rapidity of reduction in peripheral blood blast count and treatment outcome in children with T cell ALL (T-ALL). Initial systemic chemotherapy included prednisone, vincristine, doxorubicin and cyclophosphamide. A Cox analysis evaluated the correlation between the length of time that the peripheral blood absolute blast count (ABC) remained above 1000/mm3 following the start of treatment and event-free survival (EFS). Data were available for 281 patients. Patients for whom the ABC remained >1000/mm3 for 3 or more days following administration of intensive therapy had an estimated 5-year EFS of 34.2% (s.e. = 7.2) vs 58.3% (3.5) for those whose ABC was <1000/mm3 within 0-2 days, with a hazard ratio (HR) of failure of 2.03 (95% CI = 1.35-3.06, P < 0.001) for the slower responding patients. Pre-treatment of some type (usually with prednisone) occurred in 128 patients (average duration 1.7 days). When this was accounted for, patients with an ABC >1000/mm3 for 5 or more days following the start of treatment of any kind had a HR for failure of 2.27 (95% CI = 1.38-3.72, P < 0.001) compared to those responding within 0-4 days. Inclusion of other clinical and biological factors in a multivariate analysis did not alter the prognostic importance of slower blast clearance. Pediatric patients with T-ALL who have a circulating blast count >1000/mm3 at diagnosis and a relatively slower response to initial treatment are at increased risk of treatment failure. Rapidity of response may therefore be a clinically useful prognostic factor for patients with T-ALL.

Adolescent↗

Hb Cook [beta 132(H10)Lys-->Thr]: a new hemoglobin variant in a southeast Asian family.

Approximately 700 hemoglobin variants have been reported, causing a variety of clinical manifestations, with the majority being clinically silent. We report a new hemoglobin variant, Hb Cook, that was found in combination with Hb E in a child of Thai origin. DNA sequencing of the beta-globin gene showed that the mutation is AAA-->ACA in codon 132, corresponding to beta 132 (H10)Lys-->Thr.

Asia, Southeastern↗

High-dose intravenous methylprednisolone therapy for pain in children and adolescents with sickle cell disease.

BACKGROUND AND METHODS: The management of episodes of severe pain in patients with sickle cell disease is a difficult clinical problem. We studied 36 children and adolescents with sickle cell disease who had 56 acute episodes of severe pain (44 in 27 patients with sickle cell anemia, 8 in 7 patients with sickle cell-hemoglobin C disease, and 4 in 2 patients with sickle cell-beta (+)-thalassemia). The patients were randomly assigned in double-blind fashion to receive an intravenous infusion of either saline placebo or high-dose methylprednisolone (15 mg per kilogram of body weight, to a maximum of 1000 mg) on their admission to the hospital and again 24 hours later. All the patients received intravenous morphine sulfate until severe pain abated and were then given acetaminophen with codeine. RESULTS: For all episodes of pain, the duration of inpatient analgesic therapy (intravenous and oral) was significantly shorter for the patients who received methylprednisolone than for those given placebo (mean, 41.3 vs 71.3 hours; P = 0.030). The difference was still significant (31.0 vs. 62.5 hours; P = 0.010) when we excluded seven episodes that were complicated by the chest syndrome (three in the methylprednisolone group and four in the placebo group). The patients who received methylprednisolone had recurrent episodes of pain shortly after the discontinuation of therapy more often than did the patients receiving placebo. No adverse effects of methylprednisolone were observed. CONCLUSIONS: A short course of high-dose methylprednisolone decreased the duration of severe pain in children and adolescents with sickle cell disease, but patients who received methylprednisolone had more rebound attacks after therapy was discontinued. On balance, corticosteroids are promising as an adjunct to supportive therapy for painful episodes in children and adolescents with sickle cell disease.

Adolescent↗

Treatment of advanced stage diffuse, small non-cleaved cell lymphoma in childhood: further experience with total therapy B.

Prior to the development of intensive treatments for patients with advanced stage B-cell non-Hodgkin's lymphoma (B-NHL), the prognosis for such patients was dismal. A minority of patients attained long-term, disease-free survival. Since 1981, we have treated 28 children with advanced stage B-NHL with an intensive chemotherapeutic protocol, Total Therapy B. This regimen employs cycles of fractionated high-dose cyclophosphamide, doxorubicin, and vincristine alternating with sequential infusions of high-dose methotrexate and escalating doses of cytarabine, in addition to intensive intrathecal therapy. The planned duration of therapy is approximately 6 months. Two patients had B-cell acute lymphoblastic leukemia and 26 had stage III B-NHL; none had CNS involvement. The median age was 7 years. All 28 patients achieved complete remission (CR). Both patients with B-ALL and 21 of 26 with stage III B-NHL remain in CR, with a median follow-up of 51 months. Treatment failures included 3 patients with recurrent or progressive disease, 1 toxic death in CR, and 1 patient who developed a secondary mediastinal T-cell lymphoblastic lymphoma 4 1/2 years after the diagnosis of B-NHL. The 2- and 5-year event-free survival rates were 85.7 +/- 6.6% (SE) and 79.6 +/- 8.5%, respectively. Total Therapy B is a highly effective therapy for children with advanced stage B-NHL without CNS involvement.

Adolescent↗

Elective surgery in children with sickle cell disease without preoperative blood transfusion.

It is generally recommended that patients with sickle cell disease receive red blood cell (RBC) transfusions before undergoing general anesthesia and surgery. Since RBC transfusions are costly, inconvenient, and may cause serious complications, it might be useful to identify groups of patients for whom they are not absolutely necessary. We report our experience with 54 pediatric patients undergoing 66 elective surgical procedures without preoperative transfusion preparation. All patients were felt to be clinically and hematologically stable in the immediate preoperative period. For the majority of procedures (57/66, 86%) no transfusions were administered at any time during the perioperative course. There were no intraoperative complications or postoperative deaths. Overall, some type of postoperative complication was encountered after 17 procedures (26%). Complications were usually minor and were more likely to occur after procedures involving thoracotomy or laparotomy (10/20, 50%) and tonsillectomy/adenoidectomy (T&A) (5/9, 56%) than other procedures (2/37, 5%; P < .001). Pulmonary complications were especially more prevalent in the group undergoing thoracotomy, laparatomy, or T&A (9/29 v 0/37 for all other procedures, P < .001). We conclude that preoperative transfusions might be avoided in children with sickle cell disease who undergo most minor surgical procedures on an elective basis. Patients undergoing thoracotomy, laparotomy, or T&A are at a relatively higher risk of developing postoperative complications and would comprise ideal groups for evaluation of preoperative transfusion regimens in prospective carefully controlled, randomized studies.

Adolescent↗

Hematologic predictors of bone marrow recovery in neutropenic patients hospitalized for fever: implications for discontinuation of antibiotics and early discharge from the hospital.

We evaluated the timing and pattern of changes in the complete blood cell count that preceded marrow recovery during 107 consecutive episodes of fever and neutropenia in 64 children with cancer. Four measures derived from serial daily measurement of the complete blood cell count were evaluated: total leukocyte count, absolute neutrophil count, absolute phagocyte count, and platelet count. During 70 (65%) of these 107 episodes, patients were discharged with an absolute neutrophil count of fewer than 500 cells/mm3; 24 patients were discharged from the hospital despite an absolute neutrophil count of fewer than 100 cells/mm3. During all but one of these 70 episodes, however, signs of early marrow recovery were present before discharge; sustained increases were observed in these patients' leukocyte, absolute neutrophil, absolute phagocyte, and platelet counts 2 or more days before their discharge in 41%, 49%, 50%, and 39% of cases, respectively. Although they were neutropenic at discharge, most patients had signs of multilineage marrow recovery at that time; 59 of 70 had increases in three of four of the measurements that we studied. None of the 69 patients who had evidence of marrow recovery at discharge had recurrence of fever. We conclude that children with cancer who were hospitalized for fever during periods of neutropenia have increases in the peripheral blood cell count that herald imminent bone marrow recovery, often several days before the absolute neutrophil count recovers to 500 cells/mm3. Our success in discharging such patients before resolution of neutropenia suggests that further controlled trials are needed to evaluate the safety and feasibility of cessation of antibiotic therapy and early discharge from the hospital.

Adolescent↗

Childhood acute lymphoblastic leukemia with both t(1;19) and t(9;22).

The chromosomal rearrangements t(1;19)(q23;p13.3) and t(9;22) (q34;q11.2) are independent abnormalities commonly observed in the blast cells of children with acute lymphoblastic leukemia (ALL). We report three children whose leukemic cells contained both translocations at diagnosis. The patients, two males aged 3 and 8 years and a female aged 14 years, all presented with central nervous system involvement. One patient exhibited a pre-B leukemic phenotype (cytoplasmic immunoglobulin, cIg, positive), while two had an early pre-B phenotype (cIg negative). All three patients received radiotherapy and multiagent chemotherapy which included an epipodophyllotoxin in two patients. Two patients suffered relapses of ALL, in both cases with disappearance of t(1;19)-containing clones but persistence of t(9;22). The two patients who received an epipodophyllotoxin as part of their chemotherapeutic regimen both developed secondary myeloid leukemia with entirely new cytogenetic findings, including abnormalities of chromosome band 11q23. These patients are the first to be described with this unusual combination of cytogenetic abnormalities.

Adolescent↗

Family history evaluation as a predictive screen for childhood hypercholesterolemia. Pediatric Practice Research Group.

A study was conducted to evaluate the efficacy of family history factors as screening criteria for childhood hypercholesterolemia. When they were seen for routine care at one of eight office practices, 1005 prepubertal children underwent random serum cholesterol determinations. Parental and grandparental histories of cardiovascular risk factors and atherosclerotic complications prior to 55 years of age were also obtained. Of the initial group, 274 children had total cholesterol levels greater than or equal to 175 mg/dL, and 175 of these children returned for retesting after an overnight fast. A total of 88 children were found to have low-density lipoprotein-cholesterol (LDL-C) values greater than or equal to 90th percentile for age and sex. Maternal and paternal histories of hypercholesterolemia were significantly associated with elevated LDL-C (odds ratio = 7.3 and 2.9, respectively), but had extremely low sensitivities (0.09, 0.15) despite modest positive predictive values (0.42, 0.22). Grandparental histories of sudden death, peripheral vascular disease, and gout were associated with elevated LDL-C, but sensitivities and positive predictive values for all of these factors were less than 0.22. Family history factors most commonly recommended as criteria for cholesterol screening in children did not identify half of all the children with elevated LDL-C and did not selectively identify the most severely affected children. Adding information concerning the presence of childhood obesity did not result in appreciable improvement in LDL-C detection beyond that achieved by family history factors alone. It was concluded that if thorough identification of young children with elevated LDL-C is desired, inclusive population screening rather than a family history-based strategy would be the most effective approach.

Adolescent↗