Biomedical subjects
J R Graham-Pole
Publications and source records attributed to J R Graham-Pole.
Late follow-up of a short-term intensive regimen for Ewing's sarcoma.
Twenty-two patients received a short-term intensive regimen for Ewing's sarcoma between November 1977 and December 1981. The regimen consisted of vincristine (1.5 mg/m2) on day 1, and doxorubicin HCl (75 mg/m2) plus cyclophosphamide (1,000 mg/m2) on day 2. Six cycles were given at 28-day intervals. Local irradiation was started shortly after cycle 2. Eight patients with lesions of expendable bones also underwent surgery as part of the treatment to the primary site, 4 at the end of chemotherapy and 4 at diagnosis. The 5-year event-free survival rate was 45% for all patients and 48% for those with localized disease at diagnosis. Two patients died of treatment-related toxicity. The most common form of failure was distant metastases, indicating that finding a better systemic treatment remains the problem in eradicating Ewing's sarcoma.
Immunomagnetic microsphere mediated purging of cALLa positive leukemic cells from bone marrow for autologous reinfusion.
Bone marrow from sixteen patients with cALLa positive ALL have been treated with a monoclonal antibody (MoAb) cocktail which includes DuALL-1 (CD9), WCMH15.14 (CD10) and HD-37 (CD19). Following antibody treatment, marrows were incubated (30 minutes) with anti-murine-IgG1 (Fc) coated magnetic microbeads and passed through a graded magnetic field chamber. Two problems have had to be addressed: (1) More marrow cells must be processed than in marrows from patients with neuroblastoma, for which the separation chamber was originally developed, requiring the use of more beads, causing occlusion of the chamber's collection surface. This has been corrected by using a large surface area pre-magnet for the elimination of excess microbeads prior to processing in the main chamber; (2) Up-modulation (up to 40% positive cells) of the CD9 associated antigen has been detected. To avoid difficulty, marrows are being routinely screened prior to harvest for purging, and purging is delayed for patients with elevated CD9 levels. Eight patients have been reinfused, with no morbidity or mortality associated with the purging or other ex vivo handling of the marrow.
Transporting bone marrow for in vitro purging before autologous reinfusion.
We describe the procedures employed for transporting bone marrow to and from a central facility. Marrow has been harvested from 80 patients with neuroblastoma, at 16 centers which are geographically dispersed throughout North America. Marrow from the outside transplant centers was packed on wet ice or cold packs in insulated containers, and transported by commercial carriers or chartered aircraft to the central processing laboratory. Post processed marrows were frozen in liquid nitrogen and returned by commercial carrier to the referring institution. In comparing transported with non-transported but similarly treated marrows, no differences were found in any of the following parameters: (1) CFU-GM recovery, (2) fraction viable cells at thawing, or (3) time to engraftment in patients. We conclude the transportation of harvested marrows to a central purging facility is safe. Based on this experience, we propose a set of standards, which, if adhered to, will insure the continued safe processing, shipping, and storage of bone marrow in all centers so engaged.
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.
Vasoocclusion with homozygous hemoglobin-C disease.
Hemoglobin-CC is a relatively uncommon hemoglobinopathy, seen primarily in the black population. These patients usually have a mild clinical course, without significant risk of vasoocclusive crises. There are no routine recommendations for preparation prior to surgery. We present a patient who developed a clinical picture suggestive of major vasoocclusion after cardiac by-pass surgery. In retrospect, these signs appear to be the result of hemodynamic instability and cardiogenic shock instead of vasoocclusion.
In vitro studies with melphalan and pediatric neoplastic and normal bone marrow cells.
Chemotherapeutic agents are used in increasingly high dosages to treat patients with refractory cancers. An in vitro clonogenic assay was used to investigate the effects of melphalan on cultures of human neuroblastoma, Ewing's sarcoma, and osteosarcoma cells, as well as on normal bone marrow cells. A 1-hr incubation with 10(-5) M melphalan significantly inhibited tumor colony growth of both fresh neuroblastoma and osteosarcoma cells (p less than 0.01) while Ewing's sarcoma cells and normal bone marrow appeared resistant to melphalan even at a 100-fold higher concentration. Incubation with melphalan for 8 hr did not significantly increase the sensitivity of neuroblastoma and osteosarcoma or the relative resistance of Ewing's sarcoma cells; however, normal bone marrow which had remained resistant to melphalan after 1 hr of incubation, showed significant inhibition of colony growth after an 8-hr incubation with the agent. Repeated exposure to melphalan increased the degree of inhibition of both tumor and normal marrow colonies. Fresh neuroblastoma cells were significantly more sensitive than long-term cultured neuroblastoma cells at all drug doses tested. HPLC studies demonstrated that the loss of melphalan followed first-order kinetics with a half-life of 69 min, and that in addition to the 2 known breakdown products, mono- and dihydroxy-melphalan, several other peaks were present which were not attributable to the tissue culture medium or the buffer solutions.
Pediatric neuroblastoma: postoperative radiation therapy using less than 2000 rad.
There is considerable controversy regarding the role of radiation therapy in the treatment of neuroblastoma. Postoperative irradiation in the range of 2500-4000 rad is commonly used in the treatment of Evans Stage II or III disease, but there are no data in the literature to suggest the optimum dose of radiation that is necessary. Because much lower doses have been used at the University of Florida, a retrospective study was undertaken in an attempt to determine the optimum dose necessary in conjunction with surgery. From March 1964 through July 1979, 21 children with Stage II or III neuroblastoma were seen at the University of Florida. One patient died postoperatively. The remainder received postoperative irradiation with doses ranging from 900 to 4500 rad. The lower dose of radiation used did not adversely influence survival, particularly for patients less than two years of age at diagnosis. In this group, no patient had a local recurrence or died of disease, even though nine of 15 available patients received doses of 900-1500 rad.
The use of four-drug combination chemotherapy (D.A.V.E.) in the treatment of advanced Wilms' tumour.
A study was begun in 1971 at St. Bartholomew's Hospital with a combination of 4 drugs, dactinomycin (actinomycin D), adriamycin, vincristine and Endoxan (cyclophosphamide) (D.A.V.E.), together with surgery and radiation, in the treatment of stage III and stage IV Wilms' tumour. Seventy-one percent of the children treated achieved complete response. The median survival from diagnosis was 19 months, and in those children achieving complete response the median disease-free survival has not yet been reached. Toxicity was not a serious problem. The study group is compared with a group of children treated at this hospital before 1971. There is an improved survival in the children treated with D.A.V.E. Children who have relapsed with stage I or stage II disease may also respond. This four-drug combination was well tolerated and effective, and confirms recent experience suggesting that intensive multiple-drug regimens may be curative even in advanced disease.
Letter: Survival in acute myeloid leukaemia.
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The marriage of art and science in health care.
This paper invites the reader to consider the marriage of art and science as antidote to much epidemic disease, for our greater personal and societal health. The history of arts medicine is reviewed, identifying its persisting although often tenuous link with health care from pre-history to the present. The author describes his personal encounter with art at the bedside, and how it led to his establishing a comprehensive artist-in-residence program at his university hospital. The scientific evidence underscoring the efficacy of art-making for physical and psychological health are outlined, together with the physiological and biochemical data. The author describes his own program, and offers examples of healing art in action.