John Graham-Pole

Autologous bone marrow transplantation versus intensive consolidation chemotherapy for acute myeloid leukemia in childhood

Background The value of autologous bone marrow transplantation in the treatment of children with acute myeloid leukemia (AML) is unknown. We compared autologous bone marrow transplantation with intensive consolidation chemotherapy as treatments for children with AML in first remission. Methods We induced remission with one course of daunorubicin, cytarabine, and thioguanine, followed by one course of high-dose cytarabine (3 g per square meter of body-surface area for six doses). Patients in remission after the second course of induction therapy were eligible for randomization. Between June 1988 and March 1993, 552 of 649 enrolled patients who could be evaluated (85 percent) entered remission. A total of 209 patients were not eligible for randomization; of the remaining 343 patients, 232 were randomly assigned to receive six courses of intensive chemotherapy (117 patients) or autologous transplantation (115 patients). Of the original 649 patients, 189, including 21 with Downs syndrome, were nonrandomly as...

Bone marrow transplants from HLA-identical siblings as compared with chemotherapy for children with acute lymphoblastic leukemia in a second remission

BACKGROUND It is unclear how best to treat children with acute lymphoblastic leukemia who are in a second remission after a bone marrow relapse. For those with HLA-identical siblings, the question of whether to perform a bone marrow transplantation or to continue chemotherapy has not been answered. METHODS We compared the results of treatment with marrow transplants from HLA-identical siblings in 376 children, as reported to the International Bone Marrow Transplant Registry, with the results of chemotherapy in 540 children treated by the Pediatric Oncology Group. A preliminary analysis identified variables associated with treatment failure in both groups. We selected cohorts by matching these variables. A possible bias associated with differences in the interval between remission and treatment was controlled for by choosing matched pairs in which the duration of the second remission in the chemotherapy recipient was at least as long as the time between the second remission and transplantation in the transplant recipient. A total of 255 matched pairs were studied. RESULTS The mean (+/- SE) probability of a relapse at five years was significantly lower among the transplant recipients than among the chemotherapy recipients (45 +/- 4 percent vs. 80 +/- 3 percent, P < 0.001). At five years the probability of leukemia-free survival was higher after transplantation than after chemotherapy (40 +/- 3 percent vs. 17 +/- 3 percent, P < 0.001). The relative benefit of transplantation as compared with chemotherapy was similar in children with prognostic factors indicating a high or low risk of relapse (the duration of the first remission, age, leukocyte count at the time of the diagnosis, and phenotype of the leukemic cells). CONCLUSIONS For children with acute lymphoblastic leukemia in a second remission, bone marrow transplants from HLA-identical siblings result in fewer relapses and longer leukemia-free survival than does chemotherapy.

Development and Validation of the Pediatric Oncology Quality of Life Scale.

This study describes the development of a 21-item, parent report measure for assessing the quality of life (QOL) of children with cancer. The Pediatric Oncology Quality of Life Scale (POQOLS) provides a total score and three factor scores that assess physical function and role restriction, emotional distress, and reaction to current medical treatment. Internal consistency reliabilities of the total scale and the three factors were high, as was interparent agreement. In addition, POQOLS scores demonstrated good concurrent and discriminant relationships with scores on measures of adjustment hypothesized to covary with the dimensions of QOL assessed.

The effect of varied physician affect on recall, anxiety, and perceptions in women at risk for breast cancer: an analogue study.

Evaluated the effect of varied physician affect on subject recall, anxiety, and perceptions in a simulated tense and ambiguous medical situation. Forty women at risk for breast cancer viewed videotapes of an oncologist presenting--with either worried or nonworried affect--mammogram results. Although the mammogram results and the oncologist were the same in both presentation, analyses indicated that, compared to the women receiving the results from a nonworried physician, the women receiving the results from a worried physician recalled significantly less information, perceived the clinical situation as significantly more severe, reported significantly higher levels of state anxiety, and had significantly higher pulse rates. These results suggest that physician affect plays a critical role in patient reaction to medical information. Implications for compliance research, patient satisfaction, and physician training are discussed.

Surgical treatment for osteosarcoma.

Fifty-three patients who had a high-grade osteosarcoma had either a limb-salvage resection or an amputation. They all received adjuvant therapy that consisted of administration of Adriamycin (doxorubicin) and whole-lung irradiation. At the time of follow-up, the surgical margin was assessed by examination of the surgical specimen. Each patient was followed for at least three years or until death. The data suggested that a wide surgical margin is adequate to control a primary osteosarcoma. When a wide surgical margin can be used and a functional limb can be salvaged, an amputation probably is not required.

High-risk ewing's sarcoma: end-intensification using autologous bone marrow transplantation

Because of retrospective analysis showing survival to be related to primary tumor size, in February 1982 a study to test this hypothesis prospectively was begun at the University of Florida. Patients with primary tumors 8 cm or less in maximum diameter and no metastases received adjuvant chemotherapy consisting of vincristine, cyclophosphamide, doxorubicin, and dactinomycin plus radiotherapy or surgery (standard-risk protocol). All others received a similar regimen followed by end-intensification with high-dose melphalan and autologous bone marrow transplantation (Protocol HR-2). Because of poor results of HR-2, another high-risk protocol (HR-3) was initiated in January 1985. Patients on HR-3 received 2 cycles of chemotherapy containing vincristine, cyclophosphamide, and doxorubicin followed by local radiation therapy and maintenance chemotherapy. At the end of this therapy, autologous bone marrow transplantation (ABMT) was performed, using a preparatory regimen of total body irradiation and intensive chemotherapy. The 2-year disease-free survival rate was 70% for the standard-risk protocol, 20% for HR-2, and 80% for HR-3. The follow-up on HR-3 is still short, but the results are promising enough to warrant further clinical trials.

Local control and function after twice-a-day radiotherapy for Ewing's sarcoma of bone

Between February 1982 and December 1987, 39 patients with Ewings sarcoma of bone have been treated at the University of Florida with a twice-a-day radiotherapy regimen to their primary lesion, 35 with radiation alone and 4 with a combination of radiation and surgery. Although three separate systemic regimens were used (standard risk, 1982-1987 [SR-1]; high-risk, 1982-1984 [HR-2]; and high-risk, 1985-1987 [HR-3]), the radiotherapy regimen remained constant through the years of the study. Those patients whose soft-tissue mass completely regressed after induction chemotherapy received 5040 cGy (as did patients with no soft-tissue mass at diagnosis), those who had 50% or greater resolution of the soft-tissue mass received 5520 cGy, and those who had less than 50% regression of the soft-tissue mass or progressive disease during induction chemotherapy received 6000 cGy. All patients were treated with 120 cGy twice a day and a 6-hr separation between fractions. Thirteen patients also received 800 cGy of total body radiotherapy (TBI) 1 to 3 months after local radiotherapy as part of their systemic treatment. In the 33 patients treated with radiotherapy alone who were eligible for local control analysis, there have been three local failures to date, all within the first 21 months after diagnosis. The 5-year local control rate was 88% for SR-1, 80% for HR-2, and 92% for HR-3. Local control was not related to total dose, but by design, the patients with the largest lesions and the poorest response to chemotherapy had the highest doses. In the 20 patients presenting with extremity primary lesions, there have been no pathologic fractures. In patients evaluated for limb function, the late effects have been minimal. The twice-a-day regimen used appears to produce good local control rates with improved long-term function as compared with once-a-day regimens.

Local control and functional results after twice-daily radiotherapy for ewing's sarcoma of the extremities

PURPOSE Radiotherapy (RT) has been the predominant local treatment for Ewings sarcoma of bone at the University of Florida. Twice-daily hyperfractionated RT was initiated in 1982 to improve local control and functional outcome. This retrospective review compares the results of once-daily vs. twice-daily RT in patients with primary Ewings sarcoma of an extremity, with emphasis on functional outcome. METHODS AND MATERIALS Between June 1971 and January 1990, 37 patients were treated at the University of Florida for nonmetastatic Ewings sarcoma of bone with a primary lesion in an extremity. Three patients underwent amputation. Of 34 patients treated with RT, 31 had RT alone and 3 had a combination of RT and local excision. Before 1982, 14 patients received once-daily RT; since 1982, 17 patients have received twice-daily RT. Doses of once-daily RT varied from 47 to 61 Gy at 1.8-2 Gy per fraction. Doses of twice-daily RT varied, depending on the response of the soft-tissue component of the tumor to chemotherapy, and ranged from 50.4 to 60 Gy at 1.2 Gy per fraction. Some patients in the twice-daily RT group also received total body irradiation 1-3 months after local RT as part of a conditioning regimen before marrow-ablative therapy with stem cell rescue. They received either 8 Gy in two once-daily fractions or 12 Gy in six twice-daily fractions. The six patients who received surgery were excluded from local control analysis. Local control rates were calculated using the Kaplan-Meier (actuarial) method. Fifteen patients had a formal functional evaluation. RESULTS In the 31 patients treated with RT alone, the actuarial local control rate at 5 years was 81% for patients treated twice daily and 77% for those treated once daily (p = NS). No posttreatment pathologic fractures occurred in patients treated twice daily, whereas five fractures occurred in those treated once daily (p = 0.01). On functional evaluation, less loss in range of motion (15 degrees vs. 28 degrees of loss, p = 0.02) and a lesser degree of muscle atrophy (8% vs. 21% loss in muscle circumference, p = 0.0004) occurred with twice-daily than with once-daily RT. A trend toward less fibrosis and less local alopecia was seen in patients treated twice daily. Patients treated twice daily received a higher Musculoskeletal Tumor Society functional rating (determined by the Department of Orthopaedics) than those treated once daily (29.4 vs. 26.0, p = 0.15). CONCLUSIONS Local control rates were similar in the two groups (77% vs. 81%), but functional results were superior in the group treated twice daily.

The state of the arts in healthcare in the United States

The arts in healthcare in the United States is a field emerged from grassroots beginnings in the mid-twentieth century. Through an overview of the fields development as well as consideration of practice, research, and educational structures, this paper summarizes the current state of the field in the United States. Practice is explored in the context of types of programs, recent field assessments, geographic prevalence of programs, funding mechanisms, and organization of the field. Research is considered in the context of evaluation, traditional research, economic studies, theoretical frameworks, and academic centers, as well as non-academic centers that support field research. The final section explores education and training standards and programs conducted by universities and non-academic organizations, and the roles of the arts and humanities in the education of health professionals.

Improved response of patients refractory to random-donor platelet transfusions by intravenous gamma globulin.

Because of frequent unavailability of HLA-compatible platelets or their inefficiency in increasing platelet counts in patients requiring platelet transfusions, platelet refractoriness remains a major problem. Since human gamma globulin has been shown to interfere with the binding of platelet-reactive immunoglobulin G (IgG) to platelets in vitro, and since gamma globulin has proved effective in reversing destruction of platelets in idiopathic thrombocytopenic purpura, we decided to investigate intravenous gamma globulin as an adjunct to random-donor platelet transfusions. We studied three patients, one with acute T-cell leukemia, and two with aplastic anemia. When a total dose of 2 g/kg of body weight of intravenous gamma globulin was infused over five to six days in these patients, two of them showed a remarkable increment in platelet counts and improved hemostasis with random-donor platelet transfusions. We conclude that intravenous gamma globulin may be used in critical situations to improve the response of patients refractory to random-donor platelet transfusions.