"Physician, heal thyself": how teaching holistic medicine differs from teaching CAM.

The term complementary and alternative medicine (CAM) has been adopted to describe a system of health care not generally recognized as part of mainstream medical practice. It is often conflated with an older term, holistic medicine, which can briefly be defined as the art and science of healing the whole person-body, mind, and spirit-in relation to that person's community and environment. Coursework in CAM is now offered in at least two thirds of U.S. medical schools. There is also a growing number of courses in the medical humanities and in spirituality and health. However, courses explicitly designed to introduce students to the principles and practices of holistic medicine are unusual. The author describes the fundamental differences between CAM and holistic medicine, highlighting holistic medicine's emphasis on the promotion of healthy lifestyles for practitioners and patients alike. He argues that offering physicians-to-be more coursework in holistic medicine could lay the groundwork for future physicians' adopting and modeling healthy lifestyles.

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.

Treatment of post-transplant lymphoproliferative disease with induction chemotherapy followed by haploidentical peripheral blood stem cell transplantation and Rituximab.

Management of monoclonal lymphoproliferative disease following stem cell transplantation is difficult and previous attempts to eradicate tumor using chemotherapy or radiation therapy alone have not been successful. We report successful early eradication of an EBV negative, B cell non-Hodgkin's lymphoma in a child who received a T cell-depleted, maternal haploidentical bone marrow transplant for severe combined immunodeficiency disease. Our treatment strategy involved combining conventional induction chemotherapy with re-transplantation using the paternal donor as a source of peripheral blood stem cells, followed by treatment with anti-CD 20 monoclonal antibody (Rituximab). This strategy exploits the potential graft-versus-tumor activity of the mature T cells in the graft, while providing a source of stem cells to confer long-term immune function. The administration of Rituximab in the early post-transplant course may provide additional anti-tumor activity without affecting the new stem cell compartment.

Brief report: parents of children undergoing bone marrow transplantation: documenting stress and piloting a psychological intervention program.

OBJECTIVE: To document levels of stress in parents of children undergoing bone marrow transplantation (BMT) over the course of hospitalization and to pilot a psychological intervention program designed to teach parents techniques for managing stress associated with their child's illness and hospitalization. METHODS: Twenty-two mothers of children (ages 2-16) undergoing BMT were followed prospectively from preadmission to three weeks posttransplant. Eleven mothers, randomly assigned to participate in a pilot intervention program, were compared with 11 control mothers receiving standard care preparation of their child's BMT. RESULTS: Repeated measures ANOVAs detected significant changes in stress over time, with most stress reported preadmission. Mothers in the intervention condition reported using more stress management techniques than mothers in the standard care condition, though the majority of analyses revealed no significant differences in stress between groups. CONCLUSIONS: Increased levels of parenting distress may occur pretransplant, suggesting the need for additional psychological intervention at that time.

Comparison of two doses of intravenous immunoglobulin after allogeneic bone marrow transplants.

Intravenous immunoglobulin has been used after bone marrow transplants to prevent infections and acute graft-versus-host disease. However, the minimum dose required for protection is unknown. This may have significant economic implications. A multicenter randomized clinical trial compared the impact of two intravenous immunoglobulin doses on systemic infections and acute graft-versus-host disease in transplant recipients. Either 250 mg/kg or 500 mg/kg was given weekly from day -8 to day +111. Multivariate analysis was used to assess the effect of dose and other risk factors on event-free survival, systemic infection, and acute graft-versus-host disease. The two-dose cohorts had similar event-free survival and infection frequencies. The higher dose was associated with less acute graft-versus-host disease (P = 0.03).

Thalidomide in children undergoing bone marrow transplantation: series at a single institution and review of the literature.

Thalidomide has one of the most notorious drug histories because of its teratogenicity. Its widespread use in the 1960s led to a worldwide epidemic of phocomelia in inborns; this in turn led to its complete ban in most of the world. However, it has now been licensed for selected indications including graft-versus-host-disease (GVHD) after bone marrow transplantation, wasting associated with tuberculosis and human immunodeficiency virus infection, and leprosy. Little is known, however, about its use in children in these settings. Therefore, we report our experience and review the literature on thalidomide in children for GVHD after bone marrow transplantation. We studied 6 patients, 2 with chronic GVHD, 2 with acute GVHD, and 2 with acute GVHD progressing into chronic disease. One patient with chronic GVHD had a complete response, whereas the other had a partial response. Side effects consisted primarily of sedation and constipation, which are reported previously and well known side effects. None had neuropathy. One patient had rash, eosinophilia, and early pancreatitis that began shortly after initiation of thalidomide, persisted, and resolved only after discontinuation of thalidomide. Eosinophilia and pancreatitis are both previously unreported side effects or associated findings of thalidomide treatment. Review of the literature reveals three major studies of thalidomide in GVHD; of these two included children and adults together, and one in which age range of patients was not mentioned. In addition, four series of children receiving only thalidomide are reported. These series contained 1 to 14 patients each. Results show efficacy in at least 50% of children with chronic GVHD and little or no efficacy in children with exclusively acute GVHD. Side effects are similar to those reported in adults and consisted mostly of sedation and constipation, both of which subsided over time and resolved after discontinuing the drug. We speculate on the reasons for which thalidomide is more effective in chronic, compared with acute, GVHD in children, and make recommendations for future study.

Increased clearance of tacrolimus in children: need for higher doses and earlier initiation prior to bone marrow transplantation.

The pharmacokinetics of tacrolimus have been studied in healthy volunteers and in adults undergoing bone marrow transplantation. However, there is little information on the pharmacokinetics of tacrolimus in children undergoing BMT. We studied pharmacokinetics of tacrolimus in seven patients (age 8-17 years) undergoing allogeneic stem cell transplantation. Four patients received matched unrelated donor (MUD) transplants, two underwent HLA-matched related donor transplants, and one underwent an umbilical cord blood donor transplant. All patients received tacrolimus by continuous infusion at 0.03-0.04 mg/kg/day beginning on the day prior to transplant. Tacrolimus whole blood concentrations were monitored by microparticle enzyme immunoassay. Our goal was to maintain a blood tacrolimus level of 10-20 microg/ml. Once patients were tolerating oral medications, tacrolimus infusion was converted to oral dosing using a 4:1 conversion. Dose of tacrolimus and resulting tacrolimus concentrations were recorded and the total body clearance of tacrolimus was calculated retrospectively. The mean clearance, based on first steady-state tacrolimus concentrations necessary for achieving a therapeutic level (10-20 microg/ml), was 108.1 ml/h/kg (range 79.7-142.0 ml/h/kg), greater than that reported in adult BMT patients (71 +/- 34 ml/h/kg). The average dose required to achieve that therapeutic range was 0.0354 mg/kg/day as an intravenous continuous infusion. Over the entire course of intravenous tacrolimus, mean clearance was 97.0 ml/h/kg (range 33.4-153.3 ml/h/kg). In six of the seven patients, clearance values dropped after 2-4 weeks of therapy by an average of 32.5 ml/h/kg. In two patients, sharp drops in clearance were temporally related to changes in liver function tests. Three of the seven patients died of severe acute GVHD; all these had undergone matched unrelated donor transplantation, and two of these three had initial clearance levels over 120 ml/h/kg. Thus, children appear to have more rapid tacrolimus clearance than adults and may need to begin therapy earlier in order to obtain stable and optimal levels. More studies are needed to confirm these preliminary results.

Transplantation in children. A longitudinal assessment of mothers' stress, coping, and perceptions of family functioning.

This study examined the parenting stress, coping resources, and family functioning among 27 mothers of children undergoing bone marrow, liver, kidney, and heart transplantation. The mothers completed a comprehensive battery of psychological instruments at the pretransplant stage and at 1- and 6-month posttransplant stages. Increased parenting stress, financial strain, caregiver burden, and family stress were reported following transplantation and persisted for several months. The mothers reported using coping strategies characterized by attempts to maintain family integration and to understand the child's medical situation. Development and evaluation of intervention programs to enhance parents' ability to cope with stress and maintain family stability are warranted.

Toxicity associated with high-dose cytosine arabinoside and total body irradiation as conditioning for allogeneic bone marrow transplantation.

Seventy-three patients with hematological cancers undergoing allogeneic bone marrow transplantation (BMT) were evaluated for event-free survival (EFS) and toxicity. All received 36 g/m2 cytosine arabinoside (HDA) and 1200 cGy fractionated total body irradiation (TBI). We assessed the association of EFS and toxicities with the following risk factors; age, gender, diagnosis, initial relapse risk and patient-donor histocompatibility. The EFS probability is 33% at 800 days post-BMT. Twenty-six patients (36%) died of toxicity within 100 days and 14 (19%) have relapsed. EFS was inversely associated with age (P < 0.0001) and initial relapse risk (P = 0.007). The risk of pulmonary (P = 0.023) and hepatic toxicity (P = 0.011) increased with age. Diagnosis other than acute lymphoblastic leukemia (ALL) was a risk factor (P = 0.015) for graft-versus-host disease (GVHD); and fewer ALL patients died from toxicity (P = 0.014). The probability of sepsis within 100 days post-BMT correlated (P = 0.007) with initial relapse risk. We conclude: (1) the lower EFS and greater pulmonary and hepatic toxicity associated with increasing age indicate a need for less toxic regimens that maintain high antileukemic efficacy for older patients; (2) the high GVHD and sepsis rates seen in certain categories of patients indicate a need for careful definition of eligibility criteria for this still highly toxic treatment.

Use of alternative therapies for children with cancer.

OBJECTIVE: To compare the use of alternative therapy (AT) in families of children with cancer with its use in those with routine pediatric conditions. BACKGROUND AND RATIONALE: AT refers to healing practices such as therapeutic massage, acupuncture, and use of medicinal herbs that have become increasingly popular with the general public, but are not widely accepted by the medical profession. Although studies have investigated the use of AT in the families of both healthy children and children with cancer, no comparison of the incidence of its use between these two populations has been published. We hypothesized that AT was used more frequently among the families of children with cancer. METHODS: Using a prevalence survey design, we interviewed 81 parents of children with cancer attending a pediatric hematology/oncology clinic and 80 parents of children attending a continuity care clinic for routine check-ups and acute care. We explored the types of AT being used, the reasons for its use, and the frequency with which it was discussed with the patient's physician. RESULTS: 1) Overall, 65% of the cancer group were using AT, compared with 51% of the control group. This was not statistically significant. 2) Prayer, exercise, and spiritual healing were three AT practices most often used by the cancer group, and prayer, massage, and spiritual healing by the control group. 3) Discussion of AT with the physician varied according to group, with 53% of the cancer patients discussing its use; income level, with 59% of parents in the higher income group discussing its use; and ethnicity, with 47% of whites discussing its use. CONCLUSION: Use of AT is not limited to the families of children with life-challenging illnesses, but is commonly used by those of children with routine pediatric problems. Pediatricians need to be aware that their patients may not tell them about AT practices they are using in addition to prescribed treatment.

Perceptions of parenting stress and family relations by fathers of children evaluated for organ transplantation.

18 fathers of children evaluated for solid organ or bone marrow transplantation completed measures of parenting stress and family functioning. Comparisons with normative data indicated that these fathers reported less parenting stress, less family conflict, more concern about family finances, and more limitations in family activities. These data highlight the need for family-based assessments in pediatric transplantation.

Mothers of children evaluated for transplantation: stress, coping resources, and perceptions of family functioning.

The stress, coping resources, and family functioning of 36 mothers of children awaiting transplantation were evaluated. Using standardized assessment techniques, we found that, overall, 20% of mothers reported clinically elevated stress responses and that parenting stress was higher for mothers of children evaluated for solid organ transplantation (vs. bone marrow transplantation). Coping strategies characterized by maintenance of personal and family stability were strongly associated with lower levels of parenting stress. Findings also showed significant disruption in family planning and activities, as well as a strong association between lower socioeconomic status and higher parenting stress. There is a need for the longitudinal assessment of parental and family functioning throughout the transplantation process as well as for interventions designed to reduce parenting distress.

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 Ewing's 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 Ewing's 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 Ewing's 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.

Autologous bone marrow transplantation versus intensive consolidation chemotherapy for acute myeloid leukemia in childhood. Pediatric Oncology Group.

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 Down's syndrome, were nonrandomly assigned to receive intensive chemotherapy. RESULTS: The rates of event-free survival and overall survival for the entire group at three years were 34 +/- 2.5 percent and 42 +/- 2.6 percent, respectively. For patients who were randomly assigned to one of the two treatment groups, the mean (+/- SE) rates of event-free survival three years after randomization were not significantly different in the two groups when examined by intention-to-treat analysis: 36 +/- 5.8 percent for the intensive-chemotherapy group as compared with 38 +/- 6.4 percent for the autologous-transplantation group; and the relative risk of treatment failure for the chemotherapy group as compared with the autologous-transplantation group was 0.81 (P = 0.20 by the log rank test; 95 percent confidence interval, 0.58 to 1.12). Overall survival at three years followed a similar pattern. There was a lower relapse rate (31 percent vs. 58 percent, P < 0.001) but a higher rate of treatment-related mortality (15 percent vs. 2.7 percent, P = 0.005) in the group treated with autologous transplantation than in the intensive-chemotherapy group. The event-free survival at three years for the nonrandomized intensive-chemotherapy group was 39 +/- 5.1 percent, and for a contemporaneous group of patients each of whom received a histocompatible bone marrow transplant from a sibling, it was 52 +/- 8.0 percent. CONCLUSIONS: Treatment of children with AML in first remission with either autologous bone marrow transplantation or intensive chemotherapy prolongs event-free survival equally.

Behavioral distress, fear, and pain among children hospitalized for bone marrow transplantation.

This study assessed the extent of behavioral distress, fear, and pain of 10 children hospitalized for bone marrow transplantation. Parents and nurses completed bi-daily ratings of the child's level of behavioral distress, fear, and pain, while children completed bi-daily ratings of their fear and pain. Analyses showed high parent-nurse agreement on ratings of children's behavioral distress, but generally low interrespondent agreement on ratings of children's fear and pain. Results also indicated significant changes over time for ratings of children's fear and pain, but not for ratings of behavioral distress.

Children awaiting invasive medical procedures: do children and their mothers agree on child's level of anxiety?

Examined correspondence between mother and child reports of child anxiety immediately preceding a scheduled invasive medical procedure. The State-Trait Anxiety Inventory for Children (STAIC) was administered to 101 children ages 10-18 years. Mothers completed the STAIC and the State-Trait Anxiety Inventory to assess their perceptions of the child's anxiety and their own level of anxiety, respectively. Children were reported to have significantly more state anxiety as perceived by themselves and their mothers relative to the normative sample. Results also revealed low overall mother-child correspondence on child anxiety, particularly for mothers reporting more anxiety in themselves. Additionally, while age, gender, and socioeconomic status were not associated with mother-child correspondence, an unexpected relationship between race and correspondence emerged. Overall, our findings indicate that reliance on parents' perceptions of child anxiety prior to an invasive medical procedure is not sufficient.

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 of an art program on a bone marrow transplant unit.

This article describes a project created as part of the Arts in Medicine program at Shands Hospital at the University of Florida. The overall mission is to identify and develop connections between the creative arts and the healing arts that will improve the physical, mental, emotional, and spiritual health of our community. The immediate aim of this project is to facilitate the development of similar programs on other clinical units and in other hospitals. The key component is the inclusion of professional artists as artists in residence in an intensive care unit setting. Their primary function is to conduct creative arts workshops and to work one on one to facilitate the use of art as a therapeutic intervention with patients, families, and health caregivers. This pilot program is being conducted on the Bone Marrow Transplant Unit and is exploring the links between nurses, physicians, artists, patients, and families in the creative process. The nurse's role has proved to be that of facilitator and advocate, directly incorporating the artist's interactive process into the daily activities of patients and families. The artists have designed and implemented each creative project and acted as consultants in how to incorporate it. The basic assumption is that every individual is a natural artist. We believe that creating opportunities for everyone to explore the possibilities of artistic expression without judgment or criticism can lead to greater self-awareness and self-esteem and can release our innate creative energy. We hypothesize that this energy can be directed as a potent force into our physical, mental, and spiritual healing.