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Biomedical subjects

G R Buchanan

Publications and source records attributed to G R Buchanan.

At least 37 records · Page 2Linked to original sources
PubMed2000

Alternating drug pairs with or without periodic reinduction in children with acute lymphoblastic leukemia in second bone marrow remission: a Pediatric Oncology Group Study.

BACKGROUND: Children with acute lymphoblastic leukemia (ALL) who experience hematologic recurrence while receiving chemotherapy or within 6 months after its cessation have a low cure rate. In this study (Pediatric Oncology Group Protocol 8303) two methods were examined for improving the outcome in these children. METHODS: After remission induction with prednisone, vincristine, daunorubicin, and asparaginase (PVDA) and consolidation chemotherapy with teniposide and cytarabine, patients received weekly continuation chemotherapy with rotating pairs of drugs, comprised of teniposide and cytarabine and vincristine and cyclophosphamide. In addition, they were randomized to receive or not receive repeated reinduction with PVDA. Patients with matched sibling donors were allowed to receive allogeneic bone marrow transplantation (BMT) instead of continued chemotherapy. RESULTS: Of 297 evaluable patients 258 (87%) achieved second complete hematologic remission. However, only 23 of these patients remained continuously free of leukemia > or =7 years after chemotherapy or BMT. Neither PVDA pulses nor BMT appeared to influence outcome at a statistically significant level. CONCLUSIONS: The results of the current study confirm prior reports of the low cure rate of children with ALL who experience hematologic recurrence during initial therapy or shortly after its cessation. New approaches are needed to prevent and retreat hematologic recurrence in pediatric ALL patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Outpatient penile aspiration and epinephrine irrigation for young patients with sickle cell anemia and prolonged priapism.

The optimal management of prolonged priapism for patients with sickle cell anemia (SCA) has not been established. We prospectively studied in an outpatient setting the efficacy and safety of a procedure that employs aspiration of blood from the corpora cavernosa and irrigation with a dilute epinephrine solution under local anesthesia to relieve priapism in young patients with SCA. If hydration and analgesics failed to produce detumescence or if priapism had lasted >4 hours, the protocol was activated in the emergency room or clinic. Fifteen patients with homozygous SCA (Hb SS) were treated on 39 occasions; 10 patients were treated once, 1 patient twice, 2 patients 3 times, 1 patient 6 times, and 1 patient 15 times. Median age of patients at first treatment was 14.3 years (range, 3.9-18.3 years). The procedure was successful in producing immediate detumescence on 37 of 39 occasions (95% efficacy, 95% confidence intervals (CI): 81%-99%). No serious immediate or long-term side effects were observed. None of the patients who demonstrated detumescence required hospitalization. The 2 patients whose priapism persisted after aspiration and irrigation presented with episodes lasting >24 hours. All evaluable patients whose priapism resolved after aspiration and irrigation self-reported normal erectile function at a median of 40 months (range, 3-58 months) after the last procedure. Thus, aspiration of the corpora cavernosa followed by irrigation with dilute epinephrine is effective in producing immediate and sustained detumescence and should be the initial therapy employed for patients with SCA and prolonged priapism. (Blood, 2000; 95:78-82)

Adolescent↗
PubMed2000

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↗
PubMed2000

Immunotoxins against CD19 and CD22 are effective in killing precursor-B acute lymphoblastic leukemia cells in vitro.

Monoclonal antibodies (Mabs) conjugated to toxins or their subunits (immunotoxins or ITs) are undergoing clinical testing in adults with a variety of malignancies. The potential impact of this form of therapy in pediatric precursor B-lineage acute lymphoblastic leukemia (pre-B ALL) has yet to be determined. Mabs directed against the cell surface antigens, CD19 and CD22 conjugated to deglycosylated ricin A chain (dgRTA) have been tested in patients with non-Hodgkin's lymphoma (NHL), but not in patients with pre-B ALL. Because of the encouraging performance of these ITs in phase I trials, we evaluated the specific cytotoxicity of anti-CD19 (HD37-dgRTA) and anti-CD22 (RFB4-dgRTA) ITs or their combination (Combotox) on patient-derived pre-B ALL cells maintained in vitro on a stromal feeder layer. After 48 h in culture, cytotoxicity to tumor cells was determined by flow cytometry using propidium iodide (PI) and fluorescein isothiocyanate (FITC)-conjugated anti-CD10, 19, and 22. Both RFB4-dgRTA and HD37-dgRTA induced a statistically significant reduction in the number of viable leukemic cells, and Combotox was even more effective. Our results demonstrate that these ITs are specifically cytotoxic to primary pre-B ALL cells and that they should be further evaluated for the therapy of B-lineage ALL.

Adult↗
PubMed2000

Idiopathic thrombocytopenic purpura: beyond consensus.

Idiopathic thrombocytopenic purpura (ITP) is the most common acquired bleeding disorder encountered by pediatricians. Most children with ITP have minimal bleeding and complete platelet count recovery within weeks to months. Therapy for ITP has ranged from close observation without medical intervention to aggressive management with corticosteroids, intravenous immunoglobulin G, or anti-D immune globulin. The topic of ITP has incited great debate among practitioners, and this debate prompted the development of ITP practice guidelines by the British Paediatric Haematology Group in 1992 and by the American Society of Hematology in 1996. A better understanding of the clinical course of, risk for significant bleeding in, and optimal evaluation and therapy of childhood ITP will require carefully designed, multicenter, clinical trials.

Child↗
PubMed1999

Correlation of serum cholylglycine level with hepatic dysfunction in children with sickle cell anemia.

Hepatic dysfunction occurs commonly in children with sickle cell disease (SCD). Although the etiology is multifactorial, cholestasis is a prominent feature. Serum cholylglycine (CG) has been found to be a very sensitive indicator of cholestasis. Our objective was to determine whether CG levels are elevated in children with SCD and whether they are predictive of hepatic dysfunction. Blood samples were obtained from 97 children with SCD. Liver function tests were done and serum CG concentrations were measured. Patients were followed up for 2 years. Thirty-eight percent of the patients had an elevated CG level. During the 2 years of follow-up, 16% of the children with a previously elevated CG level developed abnormal liver function test results or required a cholecystectomy as compared with 13% with a previously normal CG level (p = 0.92). We conclude that although CG level was elevated in 38% of the patients with SCD, it did not appear to predict liver dysfunction during the ensuring 2 years.

Anemia, Sickle Cell↗
PubMed1999

The effect of devices used to reduce the risk of blood spillage or needlestick injury on the flow of intravenous infusion systems.

We evaluated the effect of two devices used to reduce needlestick injury and blood spillage on the flow of saline, polygeline and blood through intravenous infusion equipment and their effects on methods of increasing flow. The devices studied all reduced flow compared with control. The reductions were less for the reflux valve (< or = 9%) and greater for the anaesthesia extension set (< or = 59%), with little further reduction in flow when both were used in series (< or = 60%). Reductions in flow increased with increasing viscosity of the fluid infused, being greatest with blood. The flow reduction produced by the reflux valve was more than compensated by increasing pressure or increasing to the next larger cannula size. The flow reduction produced by the anaesthesia extension was compensated by increasing pressure but not by increasing cannula size.

Blood↗
PubMed1999

Improved survival of children with isolated CNS relapse of acute lymphoblastic leukemia: a pediatric oncology group study .

PURPOSE: Isolated meningeal relapse in children with acute lymphoblastic leukemia (ALL) usually has been followed by bone marrow relapse and limited survival. The purpose of this study was to prevent marrow relapse by administering intensive therapy before delayed craniospinal radiation. PATIENTS AND METHODS: Eighty-three patients with ALL in first bone marrow remission with an isolated CNS relapse were treated with systemic chemotherapy known to enter into the CSF and intrathecal chemotherapy for 6 months. Craniospinal irradiation (24 Gy cranial/15 Gy spinal) was then administered, followed by 1.5 years of maintenance chemotherapy. RESULTS: All 83 patients achieved a second remission. The 4-year event-free survival (EFS) rate was 71.1% +/- 5.3%. There was a fourfold increased risk of relapse for children whose initial remission was less than 18 months. The 4-year EFS rate for patients with a first complete remission >/= 18 months was 83.3% +/- 5.3%, and for those with a first complete remission less than 18 months, it was 46.2% +/- 10.2% (P =.0002.) There was a low incidence of neurologic toxicity and an unexpectedly high rate of allergic reactions to L-asparaginase. Five patients developed secondary malignancies: two with acute nonlymphoblastic leukemia during therapy, one with myelodysplasia after therapy, and two with brain tumors 1.5 to 2 years after cessation of therapy. CONCLUSION: For children with ALL and an isolated CNS relapse, treatment that delays definitive craniospinal irradiation by 6 months to allow for more intensive systemic and intrathecal chemotherapy results in better EFS than has been previously reported. Using this approach, the long-term prognosis for children with first complete remission >/= 18 months is comparable to that at the time of original diagnosis of ALL.

Adolescent↗
PubMed1999

Quantitative and qualitative platelet disorders.

Platelet disorders are common during childhood. Those conditions that are clinically significant are generally diagnosed with ease. Qualitative platelet disorders rarely cause clinical problems. The armamentarium of diagnostic tests, although limited, is usually satisfactory to allow for accurate diagnosis and effective treatment of those children with platelet disorders who are at risk of hemorrhage.

Blood Platelet Disorders↗
PubMed1998

Beneficial effect of intravenous dexamethasone in children with mild to moderately severe acute chest syndrome complicating sickle cell disease.

Acute chest syndrome (ACS) in patients with sickle cell disease (SCD) has historically been managed with oxygen, antibiotics, and blood transfusions. Recently high-dose corticosteroid therapy was shown to reduce the duration of hospitalization in children with SCD and vaso-occlusive crisis. Therefore, we chose to assess the use of glucocorticoids in ACS. We conducted a randomized, double-blind placebo-controlled trial to evaluate the efficacy and toxicity of intravenous dexamethasone (0.3 mg/kg every 12 hours x 4 doses) in children with SCD hospitalized with mild to moderately severe ACS. Forty-three evaluable episodes of ACS occurred in 38 children (median age, 6.7 years). Twenty-two patients received dexamethasone and 21 patients received placebo. There were no statistically significant differences in demographic, clinical, or laboratory characteristics between the two groups. Mean hospital stay was shorter in the dexamethasone-treated group (47 hours v 80 hours; P = .005). Dexamethasone therapy prevented clinical deterioration and reduced the need for blood transfusions (P < .001 and = .013, respectively). Mean duration of oxygen and analgesic therapy, number of opioid doses, and the duration of fever was also significantly reduced in the dexamethasone-treated patients. Of seven patients readmitted within 72 hours after discharge (six after dexamethasone; P = .095), only one had respiratory complications (P = 1.00). No side effects clearly related to dexamethasone were observed. In a stepwise multiple linear regression analysis, gender and previous episodes of ACS were the only variables that appeared to predict response to dexamethasone, as measured by lengh of hospital stay. Intravenous dexamethasone has a beneficial effect in children with SCD hospitalized with mild to moderately severe acute chest syndrome. Further study of this therapeutic modality is indicated.

Acute Disease↗
PubMed1998

Major hemorrhage in children with idiopathic thrombocytopenic purpura: immediate response to therapy and long-term outcome.

OBJECTIVES: We retrospectively characterized children with idiopathic thrombocytopenic purpura (ITP) who had major hemorrhage to determine response to therapy and long-term outcome. STUDY DESIGN: We reviewed the medical records of 332 children with ITP diagnosed at our center during the last 10 years for occurrence of major hemorrhage, defined as (1) intracranial hemorrhage, (2) epistaxis requiring cautery or nasal packing, (3) gross hematuria, or (4) other bleeding causing a decline in hemoglobin concentration. RESULTS: Of 332 patients with ITP, 58 (17%) had 68 episodes of major hemorrhage; 56 of these episodes were treated with corticosteroids, intravenous immunoglobulin, or both. The platelet count rose to > or =20,000/mm3 within 24 hours after presentation after only 18% of evaluated events, and 28% of patients with major hemorrhage still had a platelet count <20,000/mm3 after 7 days. Twenty-seven of 49 patients available for evaluation had resolution of ITP within 6 months, 21 had chronic ITP, and 1 died of sepsis. CONCLUSIONS: We observed that 17% of children with ITP had major hemorrhage. Only a minority of these patients had an immediate rise in platelet count after receiving intravenous immunoglobulin, corticosteroid treatment, or both. Prospective studies of childhood ITP focusing on short-term outcome variables in addition to platelet count should be performed to better define optimal treatment for each affected child.

Adolescent↗
PubMed1998

Implantable venous access devices in children with hemophilia: a report of low infection rates.

OBJECTIVE: The objective of this study was to define the efficacy and complications of implantable venous access devices (IVADs) in children with hemophilia. STUDY DESIGN: Records were reviewed on all patients with congenital blood coagulation disorders monitored at two children's hospitals in whom one or more central venous catheters had been placed. RESULTS: Since 1989 external and implantable central venous catheters have been inserted to enhance venous access for regular factor concentrate infusion in 45 patients with hemophilia ranging in age from 8 months to 19.5 years (median 7.4 years); 37 patients had factor VIII deficiency and 8 factor IX deficiency. Hemorrhagic complications of catheter placement were infrequent and minor. In the 41 patients having one or more IVADs in place for a median of 31 months, only six episodes of bacteremia occurred in 5 patients during 44,070 days of follow-up. The overall rate of bacteremia complicating IVADs in these patients was 0.14 episodes per 1000 catheter days. Other catheter-related complications were uncommon. Catheters are still in place in 33 patients for a median of 32 months. CONCLUSION: The low risk of infection and other complications associated with the use of IVADs makes the use of these devices attractive in the treatment of patients with hemophilia who require frequent venous access for factor concentrate infusions.

Anti-Bacterial Agents↗
PubMed1998

Contrast venography in young haemophiliacs with implantable central venous access devices.

To assess the risk of deep vein thrombosis in haemophiliacs with long-term central venous catheters, we studied haemophiliacs followed at our centre with implantable venous access devices (ports) in place for > 6 months. Medical records were reviewed for a history of catheter-related complications. Each patient was examined for physical stigmata of thrombosis. Patency of the vessels was evaluated by contrast venography. Of 21 males with ports, 19 had factor VIII deficiency and two factor IX deficiency. Nineteen ports were evaluable (i.e. were in place for > 6 months). Seventeen patients have their original ports in place; two ports were replaced for mechanical dysfunction (1) and recurrent infection (1). Difficulty withdrawing or infusing occurred with three ports, two of which were cleared with urokinase. Physical examination was normal on all 19 patients. Venograms were performed in 13 of 19 patients. Parents of the remaining six patients refused venography because of the need for peripheral venipuncture. One patient had a small nonocclusive thrombus on the same side as his functioning catheter, and another had minimal narrowing of the subclavian vein at the site of a prior catheter. The overall prevalence of clinically relevant upper venous system thrombosis identifiable by contrast venography was zero (95% CI, 0-23%). We conclude that haemophiliacs do not have as high a risk of thrombosis as other populations of patients with central venous catheters. The theoretical risk of thrombosis should not preclude use of central venous catheters in patients with haemophilia.

Adolescent↗
PubMed1998

Programs for adult survivors of childhood cancer.

PURPOSE: The potential for late effects of treatment necessitates long-term monitoring of adult survivors of childhood cancer. The purpose of this study was to determine how institutions follow up young adult survivors of pediatric malignancy. Specifically, we were interested in the types of health care providers who follow up these patients, how the follow-up is administered, and what barriers to follow-up have been encountered. METHODS: A 16-item questionnaire was mailed to the 219 members of the Children's Cancer Group (CCG) and the Pediatric Oncology Group (POG). The survey consisted of four categories of questions that asked for information regarding the existence of a program to follow up young adults, the setting of the program, routine activities of the program, and commonly encountered barriers to care. RESULTS: One hundred eighty-two members returned the survey (83% response rate). Fifty-three percent of the respondents have a long-term follow-up clinic at their institution. Whereas 44% have a mechanism for following up adult survivors, only 15% of the programs have established a formal database for adults. Nearly all the programs (93%) use a pediatric oncologist. Although an adult oncologist assists in 13% of the programs, primary care physicians are uncommonly (8%) involved. CONCLUSION: Few programs focus on the long-term health care needs of adult survivors of childhood cancer. The majority of existing programs are in pediatric institutions, without significant input from adult-oriented, generalist health care providers.

Adult↗
PubMed1997

Treatment of children with epipodophyllotoxin-induced secondary acute myeloid leukemia.

BACKGROUND: Secondary acute myeloid leukemia (AML) after treatment with epipodophyllotoxins is being observed with increased frequency. Therapeutic options are limited for patients with secondary AML and the role of bone marrow transplantation is unclear. METHODS: The authors report the treatment outcome of a cohort of 17 children who developed epipodophyllotoxin-induced secondary AML after therapy for childhood acute lymphoblastic leukemia (ALL) that included etoposide but no irradiation or alkylating agents. Thirteen patients (76%) had 11q23 chromosomal abnormalities that were not present at the initial diagnosis of ALL. RESULTS: Remission induction was attempted in 16 children, with 13 (81%) achieving a complete remission. After consolidation, 9 of these 13 patients received a bone marrow transplant (BMT): 2 with 4-hydroperoxycyclophosphamide-purged autologous marrow, 4 from a human leukocyte antigen (HLA)-identical sibling, 1 from a mismatched parental donor, and 2 from a matched unrelated donor. One additional child underwent allogeneic BMT without an attempt at reinduction. Of the 10 patients who received transplants, 2 were alive and well 27+ and 36+ months, respectively, after BMT. Of the 7 patients who did not receive a transplant, at last follow-up 1 had survived off therapy for 8 months for recurrent ALL whereas 6 died of AML. CONCLUSIONS: These data confirm the poor prognosis of secondary AML after epipodophyllotoxin treatment for childhood ALL. Although patients with secondary AML can achieve a remission, it is usually of brief duration. Allogeneic BMT may offer the possibility of long term remission in some of these patients. More information is needed to better define the risks and benefits of epipodophyllotoxin therapy for childhood ALL.

Acute Disease↗