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Biomedical subjects

M M Hudson

Publications and source records attributed to M M Hudson.

At least 55 records · Page 3Linked to original sources

Tobacco use among pediatric cancer patients: recommendations for developing clinical smoking interventions.

PURPOSE AND METHODS: The current status of tobacco use among young cancer patients and the acute and chronic complications associated with tobacco use in these patients is reviewed. RESULTS AND CONCLUSION: Studies report that adolescent cancer survivors use tobacco as much as their peers who have never been treated for cancer, despite the adverse consequences of engaging in this unhealthy habit. Health care professionals have the opportunity and responsibility to incorporate tobacco counseling as a routine component of medical care delivery. Nurse/physician-delivered smoking interventions have been found to promote smoking cessation in adults, although little effort has been devoted to the development of similarly effective smoking interventions for pediatric cancer patients who smoke. Components of existing smoking prevention/cessation curricula from successful school-based interventions and physician-delivered smoking interventions can be adapted and tailored to pediatric cancer patients in medical settings. Smoking interventions that educate patients about their increased vulnerability to tobacco-related consequences, relative to their healthy peers, may have an enhanced impact. Guidelines for conducting a comprehensive assessment of tobacco use and implementing smoking interventions with pediatric cancer patients is provided. Strategies for modifying the cancer patient's perceived vulnerability to tobacco-related consequences is also discussed.

Adolescent↗

Late mortality of long-term survivors of childhood cancer.

PURPOSE: To determine the frequency and patterns of late mortality among long-term survivors of childhood cancer. MATERIALS AND METHODS: Medical records of patients who survived at least 5 years after the diagnosis of childhood cancer were reviewed to determine the causes of subsequent deaths. Estimated 15-year survival and standardized mortality ratios for deaths from nonneoplastic treatment complications were compared with adjusted United States population estimates. The study included 2,053 patients who had survived > or = 5 years, grouped by treatment eras that reflected increased intensity of therapy and significantly improved survival (early era, 1962 to 1970; recent era, 1971 to 1983). RESULTS: There have been 258 subsequent deaths in the 2,053 childhood cancer survivors; 169 occurred 5 to 10 years postdiagnosis and 89 > or = 10 years post diagnosis. For the study period as a whole, deaths were attributed to recurrent primary malignancy in 61% of cases, second malignancy in 20%, nonneoplastic treatment complication in 10%, and unintentional injury/suicide in 8%. Late death from recurrent disease decreased significantly for survivors treated in the recent era (P < .0001), while the risk of death from second malignancies increased, although not statistically significantly (P = .10). Projected 15-year survival estimates for all > or = 5-year survivors in both treatment eras was greater than 90%, but differed from expected rates. CONCLUSION: Late mortality from recurrence after treatment for childhood cancer decreases with more effective initial therapy. Prolonged disease-free status is associated with an expected survival that approaches that of the general population for patients treated from 1971 through 1983. The impact of more recent intensified and novel therapies for high-risk patients remains to be determined.

Adolescent↗

Effectiveness of intensified rotational combination chemotherapy for late hematologic relapse of childhood acute lymphoblastic leukemia.

Relapsed acute lymphoblastic leukemia (ALL) usually carries a dire prognosis. We evaluated the effectiveness and long-term complications of intensive rotational combination chemotherapy for late hematologic relapse (median, 16 months after elective cessation of therapy) among 34 children and young adults (ages 4 to 23 years). Concurrent central nervous system (CNS) relapse was present in 3 cases and testicular relapse in 4. Secondary therapy comprised an intensive five-drug reinduction (6 weeks) followed by continuation treatment with four drug pairs, rotated weekly in 4-week cycles over 120 weeks. Intrathecal chemotherapy (methotrexate, hydrocortisone, cytarabine) was given three times during reinduction and every 8 weeks during continuation. Treatment was electively discontinued at week 120 in the absence of detectable disease. Thirty-three patients (97%) attained a second complete remission. At a median follow-up of 9.3 years (range, 4.5 to 11.4), estimates of 5-year second event-free and overall survival (+/- SE) are 65% +/- 8% and 79% +/- 7%, respectively. Eleven patients had a second relapse (9 marrow, 2 testicular) and one developed secondary myeloid leukemia. There have been no CNS relapses or deaths in remission. Treatment was well-tolerated and was given largely on an outpatient basis. Late effects are primarily endocrinologic; one child had a second malignant solid tumor (presumed related to initial radiation therapy) that was treated successfully. Intensive treatment with alternating non-cross-resistant drug pairs for late hematologic relapses of ALL is effective and well-tolerated, and produces results similar to those achieved in patients with newly diagnosed ALL. Event-free survival compares favorably with reports of other relapse regimens, including those incorporating bone marrow transplantation.

Adolescent↗

Serial pulmonary function studies in children treated for newly diagnosed Hodgkin's disease with mantle radiotherapy plus cycles of cyclophosphamide, vincristine, and procarbazine alternating with cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine.

BACKGROUND: The pulmonary toxicity of bleomycin-containing chemotherapy combined with mantle radiotherapy in children treated for Hodgkin's disease was longitudinally assessed. METHODS: The results of serial pulmonary function studies in 37 children, newly diagnosed and treated at St. Jude Children's Research Hospital between September 23, 1983, and June 30, 1988, with cyclophosphamide, vincristine, and procarbazine (COP) alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) plus low dose mantle radiotherapy are analyzed. All patients had pulmonary function studies at least before the first bleomycin dose, after completion of radiotherapy, and serially upon discontinuation of therapy. Bleomycin therapy was withheld whenever measured carbon monoxide diffusing capacity was less than 50% of the predicted value. RESULTS: Vital capacity, diffusing capacity, and diffusing capacity per unit of alveolar volume declined during the first 6 months of therapy but improved there after. At 2 years postdiagnosis, diffusing capacity per unit of alveolar volume remained significantly reduced. Only one patient was symptomatic at the 2-year point. The survival rate of these patients was 95% at a median follow up of 93 months. CONCLUSION: If bleomycin is with held when diffusing capacity is diminished to 50% predicted, clinical compromise of pulmonary function appears to be minimal in pediatric patients receiving alternating cycles of COP/ ABVD in combination with low-dose mantle radiotherapy. Survival was excellent, even with reduction of the total bleomycin dose.

Adolescent↗

Subsequent malignancies in children and adolescents after treatment for Hodgkin's disease.

PURPOSE: We assessed the cumulative risk of malignancies following treatment for Hodgkin's disease in childhood and adolescence and investigated related patient and treatment characteristics. PATIENTS AND METHODS: Medical records of 499 Hodgkin's disease patients treated between 1962 and 1993 were reviewed. There were 385 adolescents (> or = 10 years of age at diagnosis) and 114 preadolescents (< 10 years). Most patients (n = 346) were treated with radiation plus multiagent chemotherapy, while 30 received only chemotherapy and 123 only radiation therapy. Radiation doses ranged from 20 to 42 Gy. RESULTS: At a median follow-up duration of 9 years (range, 0.1 to 27.4), 25 patients have had second malignancies: 19 solid tumors, four acute nonlymphoblastic leukemias (ANLLs), 1 non-Hodgkin's lymphoma (NHL), and one chronic myeloid leukemia (CML). Three patients have had a third malignancy. The estimated cumulative risk of second malignancies increased from 1.5% at 5 years to 7.7% at 15 years. All but two of the patients with second malignancies were > or = 10 years of age at initial diagnosis, which reflects the higher risk among patients treated for Hodgkin's disease as adolescents (P = .01). Second malignancies were more common among female patients (P = .0002), even when those breast cancer were excluded (P = .007), and in those treated for recurrent Hodgkin's disease (P = .02). Patients with ANLL/NHL were older at diagnosis of Hodgkin's disease than those with solid tumors, (median age, 18.3 v 13.8 years; P = .04). There was no difference between groups treated with radiation therapy alone, chemotherapy alone, or radiation plus multiagent chemotherapy. CONCLUSION: Adolescents treated for Hodgkin's disease are at greater at risk of second malignancies than younger patients. Overall, adolescent females treated for recurrent Hodgkin's disease appear to be at greatest risk, while preadolescents appear to be protected from this late complication.

Adolescent↗

Efficacy and toxicity of multiagent chemotherapy and low-dose involved-field radiotherapy in children and adolescents with Hodgkin's disease.

PURPOSE: Between May 1980 and September 1990, 85 patients with Hodgkin's disease were treated with a regimen designed to increase cure rates while reducing late toxicity. PATIENTS AND METHODS: Therapy consisted of five cycles of cyclophosphamide, Oncovin (vincristine; Eli Lilly and Co, Indianapolis, IN), and procarbazine (COP), alternated with four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and low-dose (20 Gy) regional radiotherapy. Vincristine and cyclophosphamide were administered as tolerated during irradiation and during the 2- to 4-week rest period between radiation volumes. The need for staging laparotomy was defined by clinical presentation. RESULTS: The median age at diagnosis was 14 years (range, 4 to 20), and 56% of patients were male. The majority (67%) had stage III or IV disease and 68% (19 of 28) of stage II patients had bulky mediastinal disease. Nodular sclerosing histology predominated (67%). Ninety-three percent of patients were alive without disease with a median follow-up of 4.1 years. Abnormalities were detected on chest roentgenograms and/or pulmonary function tests in 58% and 25% of clinically asymptomatic patients who were tested at least 1 year after completion of therapy. The only symptomatic patient had pulmonary fibrosis after treatment with bleomycin (20 U/m2) and mantle (20 Gy)/lung (13 Gy) irradiation, and developed multiple spontaneous pneumothoraces that required cortical stripping. One patient had congestive heart failure 19 months post-treatment, and two had abnormalities on echocardiograms. Thyroid abnormalities occurred in 21 (27%) patients who were assessable for late toxicity. The majority of female patients have had regular menstrual cycles. Six developed ovarian failure, and 10 have had a total of 17 pregnancies. Other than one documented case of oligospermia, information was not available on male fertility. CONCLUSION: The results demonstrate excellent disease control for the COP/ABVD regimen, with acceptable toxicity.

Adolescent↗

Acute hypersensitivity reactions to etoposide in a VEPA regimen for Hodgkin's disease.

PURPOSE: We report an unexpectedly high incidence of hypersensitivity to etoposide among 45 patients with newly diagnosed Hodgkin's disease treated with vinblastine, etoposide, prednisone, and doxorubicin (VEPA) plus radiation. PATIENTS AND METHODS: Twenty-three of 45 patients (51%) had one or more acute hypersensitivity reactions to etoposide administration. The 23 patients were 8 to 18 years of age (median, 15 years); 12 were males. Four patients had experienced prior allergic reactions to antibiotics or intravenous contrast media. RESULTS: Hypersensitivity reactions followed the first or second dose of VEPA in most cases. The reactions occurred at a median time of 5 minutes (range, 3 to 120) from the start of the etoposide infusion. Fifteen patients reacted early (within 10 minutes), four midway through the infusion, and four after completion of the infusion. Signs and symptoms included flushing, respiratory problems, changes in blood pressure, and abdominal pain with or without nausea and vomiting. Respiratory problems included dyspnea, chest pain/tightness, bronchospasm, and cyanosis. Symptoms were alleviated by discontinuing the etoposide infusions and administering diphenhydramine and/or hydrocortisone; epinephrine was required to reverse bronchospasm in three cases. All 23 patients recovered without adverse sequelae and were rechallenged with etoposide. Fifteen patients tolerated subsequent etoposide infused at a slower rate, with antihistamine and/or corticosteroid premedication; five had recurrent hypersensitivity despite these measures. Three of these five developed similar symptoms when teniposide was substituted for etoposide. Three patients who had isolated episodes of hypotension on completion of the etoposide infusion successfully received subsequent infusions without premedication or change in infusion rate or concentration. CONCLUSION: Despite this unexpectedly high incidence of hypersensitivity among Hodgkin's disease patients treated with etoposide, rechallenge with the drug was successful in 78% of cases.

Acute Disease↗

Childhood acute leukemia with t(11;19) (q23;p13).

From 583 cases of acute lymphoblastic leukemia (ALL) and 181 cases of acute myeloid leukemia (AML) in childhood, seven patients were identified to have t(11;19) (q23;p13) by sequential cytogenetic analyses. The t(11;19) was associated with B-precursor ALL at diagnosis in three patients and at relapse in one patient. All four tested patients with B-precursor failed to express the CD10 antigen when the t(11;19) was detected, and one of three patients tested expressed myeloid-associated markers. In three other patients the translocation was detected either at lineage conversion from ALL to M5 AML (n = 2) or from AML to CD10- B-precursor ALL (n = 1). Leukemic blasts of four patients had an entirely different karyotype at the time of lineage conversion or loss of CD10 expression, suggesting an induction of a second neoplasm. Thus the t(11;19) can be found in de novo or secondary acute leukemia with lymphoid (CD10-) or myeloid (monoblastic) phenotype. Further investigation of the gene(s) involved in the 11q23 chromosomal region and the breakpoints in the 19p13 region is needed to understand the leukemogenesis of this apparently heterogeneous group of disorders.

Adolescent↗

Methotrexate plus L-asparaginase. An active combination for children with acute nonlymphocytic leukemia.

Forty-one children with refractory acute nonlymphocytic leukemia (ANLL) were treated from March 1975 to February 1979 with a schedule-dependent combination of methotrexate (MTX) and L-asparaginase. Intravenous (IV) MTX was followed 24 hours later by IV L-asparaginase (10,000 units [U]/m2). The MTX dose was started at 60 to 100 mg/m2 and was escalated by 20 to 40 mg/m2 as tolerated. This sequence was repeated every 7 to 10 days. Eight patients (20%) achieved a complete remission (CR) and six others had a partial response (PR), with clearance of blasts from the peripheral blood and reduction of bone marrow blasts to less than 25% of nucleated marrow cells. Responding patients received a median maximum MTX dose of 120 mg/m2 (range, 60 to 220 mg/m2). The median number of courses required to achieve a CR was 6 (range, 2 to 13 courses). Toxicity consisted of allergic reactions to L-asparaginase (n = 12), stomatitis (n = 6), minimal elevation of hepatic enzymes (n = 2), and hyperglycemia (n = 1). Treatment was given on an outpatient basis in 95% of all courses. The data indicate that this combination therapy has antileukemic activity and is relatively nontoxic in childhood ANLL.

Adolescent↗

Effect of recombinant human interleukin 4 on human monocyte activity.

Recombinant human interleukin 4 (rhuIL-4), a lymphokine that reportedly stimulates tumoricidal activity in mouse macrophages, is currently undergoing clinical studies to determine its efficacy in the treatment of cancer. IL-4 is known to participate with other cytokines to regulate growth and differentiation of various hematopoietic cells as well as modulate the immune response. Little is known about the effect of rhuIL-4 on human monocyte tumoricidal activity. The purpose of these studies was to examine the effect of rhuIL-4 on human peripheral blood monocytes. Peripheral blood monocytes isolated from normal donors failed to demonstrate tumoricidal activity or interleukin 1 secretion after treatment with rhuIL-4 in vitro. Furthermore, monocyte-mediated cytotoxicity induced by recombinant human gamma-interferon plus muramyl dipeptide was suppressed in a dose-dependent manner by rhuIL-4. This reduction in cytotoxicity corresponded to a reduction in IL-1 production and secretion. Further investigation of rhuIL-4 and its role in the cytokine network is necessary for the development of effective immunotherapy in cancer patients.

Acetylmuramyl-Alanyl-Isoglutamine↗

In vitro and in vivo effect of adriamycin therapy on monocyte activation by liposome-encapsulated immunomodulators.

The purpose of these studies was to determine the effect of Adriamycin (ADR) on the ability of liposome-encapsulated immunomodulators to activate human blood monocytes to the tumoricidal state. We undertook these experiments because we envisioned using encapsulated activators in addition to chemotherapy to destroy pulmonary micrometastases in patients with osteosarcoma (OS). Prior to the initiation of such therapy, it was important to determine whether chemotherapy interferes with monocyte function. First, human peripheral blood monocytes were isolated from normal donors and preincubated with ADR (0.5-500 ng/ml) for 1 h and then washed prior to the addition of free or liposome-encapsulated activators. After 18-24 h incubation, the activating agents were washed off and [125I]IdUrd-labeled A375 melanoma cells were added. Lysis of radiolabeled tumor cells was quantified 72 h later. Monocytes were also incubated with ADR for 24 h in the presence of free or liposome-encapsulated activators and their cytotoxicity quantified. ADR had no effect on the ability of either free or liposome-encapsulated agents to activate monocyte tumoricidal function. We also studied the in vivo effect of ADR therapy on monocyte function in nine patients with OS. At the time of diagnosis and 1 month after ADR therapy (75 mg/m2) patient monocytes could be activated to the tumoricidal state by liposome-encapsulated agents at levels equal to or greater than pretherapy levels. Monocytes isolated from four patients with OS 1 day after ADR therapy and then activated by liposome-encapsulated agents also demonstrated tumoricidal activity. These studies indicated that the monocytes isolated from osteosarcoma patients treated with ADR can be activated in vitro to kill tumor cells and that additional therapy with liposome-encapsulated immunomodulators may be combined with ADR in the treatment of metastatic pulmonary OS.

Adjuvants, Immunologic↗

Diagnostic value of surgical testicular biopsy after therapy for acute lymphocytic leukemia.

Inasmuch as several cooperative research groups currently require routine testicular biopsy in boys with acute lymphocytic leukemia before cessation of therapy, we performed bilateral open wedge biopsies in 38 boys aged 4 1/2 to 18 years, all of whom were completing 3 years of therapy, were apparently in complete remission, and had palpably normal testes. Biopsy specimens from two other patients were examined during therapy for specific clinical indications. Among the 40 patients, one biopsy revealed leukemia bilaterally; 39 patients had negative biopsy results, three of whom had overt, biopsy-proved testicular relapse 6 weeks to 17 months after normal biopsy. All four patients with testicular relapse are in complete remission six to 50 months after testicular irradiation. We conclude that random sampling during routine testicular biopsies may fail to demonstrate occult leukemia, and that the high rate of complete remissions following retrieval therapy after overt testicular relapse makes routine biopsies before cessation of therapy unnecessary.

Adolescent↗