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Biomedical subjects

Cindy L Schwartz

Publications and source records attributed to Cindy L Schwartz.

11 recordsLinked to original sources
PubMed2006

Chronic health conditions in adult survivors of childhood cancer.

BACKGROUND: Only a few small studies have assessed the long-term morbidity that follows the treatment of childhood cancer. We determined the incidence and severity of chronic health conditions in adult survivors. METHODS: The Childhood Cancer Survivor Study is a retrospective cohort study that tracks the health status of adults who received a diagnosis of childhood cancer between 1970 and 1986 and compares the results with those of siblings. We calculated the frequencies of chronic conditions in 10,397 survivors and 3034 siblings. A severity score (grades 1 through 4, ranging from mild to life-threatening or disabling) was assigned to each condition. Cox proportional-hazards models were used to estimate hazard ratios, reported as relative risks and 95% confidence intervals (CIs), for a chronic condition. RESULTS: Survivors and siblings had mean ages of 26.6 years (range, 18.0 to 48.0) and 29.2 years (range, 18.0 to 56.0), respectively, at the time of the study. Among 10,397 survivors, 62.3% had at least one chronic condition; 27.5% had a severe or life-threatening condition (grade 3 or 4). The adjusted relative risk of a chronic condition in a survivor, as compared with siblings, was 3.3 (95% CI, 3.0 to 3.5); for a severe or life-threatening condition, the risk was 8.2 (95% CI, 6.9 to 9.7). Among survivors, the cumulative incidence of a chronic health condition reached 73.4% (95% CI, 69.0 to 77.9) 30 years after the cancer diagnosis, with a cumulative incidence of 42.4% (95% CI, 33.7 to 51.2) for severe, disabling, or life-threatening conditions or death due to a chronic condition. CONCLUSIONS: Survivors of childhood cancer have a high rate of illness owing to chronic health conditions.

Adolescent↗
PubMed2006

APE chemotherapy for children with relapsed Hodgkin disease: a Pediatric Oncology Group trial.

BACKGROUND: MOPP (mechlorethamine, vincristine, procarbazine, prednisone) and ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) are effective therapies for Hodgkin disease (HD) that may cause long-term toxicities in children. APE (cytosine arabinoside, cisplatin, etoposide) is a non-cross-resistant regimen with limited toxicities. We evaluated this regimen for patients with recurrent or refractory disease. METHODS: Patients with recurrent Hodgkin disease who were <or=21 years of age and had previously received standard alkylating agent and doxorubicin-based therapy, were treated with APE chemotherapy (cytosine arabinoside 750 mg/m(2), cisplatin 15 mg/m(2), etoposide 20 mg/m(2)) every 12 hr, administered three or four times per cycle. Response, Event-free survival (EFS), and overall survival (OS) were assessed. RESULTS: Thirty-one patients in first (n = 25) or second (n = 6) relapse of Hodgkin disease were eligible and evaluable. APE chemotherapy was well-tolerated, with the major toxicity consisting of short duration, grade 3/4 hematopoietic toxicity. The CR/PR response rate was 68% (42% CR, 26% PR). Allowing subsequent stem cell transplantation in some patients, 4-year EFS and OS were 27% +/- 8% and 49% +/- 9%, with 8-year EFS and OS of 23% +/- 9% and 34% +/- 10%. DISCUSSION: APE is an efficacious regimen with minimal toxicity. Novel regimens are necessary to: (1) re-induce remission, (2) treat newly diagnosed patients, and (3) augment therapy in patients with slow response to standard regimens. This regimen had minimal toxicity and an excellent response rate that facilitated long term survival, often in conjunction with transplantation. The Children's Oncology Group is using a similar regimen to augment therapy for slow responders on a current Hodgkin disease trial.

Adolescent↗
PubMed2006

POG 8625: a randomized trial comparing chemotherapy with chemoradiotherapy for children and adolescents with Stages I, IIA, IIIA1 Hodgkin Disease: a report from the Children's Oncology Group.

To determine if 6 courses of chemotherapy alone could achieve the same or better outcome than 4 courses of chemotherapy followed by radiation therapy (chemoradiotherapy) in pediatric and adolescent patients with Hodgkin disease. Children < or =21 years old with biopsy-proven, pathologically staged I, IIA, or IIIA1 Hodgkin disease were randomly assigned 6 courses of alternating nitrogen mustard, oncovin, prednisone, and procarbazine/doxorubicin, bleomycin, vinblastine, and dacarbazine (treatment 1) or 4 courses of alternating nitrogen mustard, oncovin, prednisone, and procarbazine/doxorubicin, bleomycin, vinblastine, and dacarbazine +2550 cGy involved-field radiotherapy (treatment 2). The complete response rate was 89%, with a complete response and partial response rate of 99.4%. There was no statistically significant difference in event-free survival (EFS) or overall survival between arms. The EFS for those who achieved an early complete response was significantly higher than for those who did not. For pediatric patients with asymptomatic low-stage and intermediate-stage Hodgkin disease, chemotherapy and chemoradiotherapy both resulted in 3-year EFS of approximately 90% and statistically indistinguishable 8-year EFS and overall survival, without significant long-term toxicity. Early response to therapy was associated with higher EFS, a concept that has led to the Children's Oncology Group paradigm of response-based risk-adapted therapy for pediatric Hodgkin disease.

Adolescent↗
PubMed2005

Osteosarcoma: a randomized, prospective trial of the addition of ifosfamide and/or muramyl tripeptide to cisplatin, doxorubicin, and high-dose methotrexate.

PURPOSE: To determine whether the addition of ifosfamide and/or muramyl tripeptide (MTP) encapsulated in liposomes to cisplatin, doxorubicin, and high-dose methotrexate (HDMTX) could improve the probability for event-free survival (EFS) in newly diagnosed patients with osteosarcoma (OS). PATIENTS AND METHODS: Six hundred seventy-seven patients with OS without clinically detectable metastatic disease were treated with one of four prospectively randomized treatments. All patients received identical cumulative doses of cisplatin, doxorubicin, and HDMTX and underwent definitive surgical resection of the primary tumor. Patients were randomly assigned to receive or not to receive ifosfamide and/or MTP in a 2 double dagger 2 factorial design. The primary end point for analysis was EFS. RESULTS: Patients treated with the standard arm of therapy had a 3-year EFS of 71%. We could not analyze the results by factorial design because we observed an interaction between the addition of ifosfamide and the addition of MTP. The addition of MTP to standard chemotherapy achieved a 3-year EFS rate of 68%. The addition of ifosfamide to standard chemotherapy achieved a 3-year EFS rate of 61%. The addition of both ifosfamide and MTP resulted in a 3-year EFS rate of 78%. CONCLUSION: The addition of ifosfamide in this dose schedule to standard chemotherapy did not enhance EFS. The addition of MTP to chemotherapy might improve EFS, but additional clinical and laboratory investigation will be necessary to explain the interaction between ifosfamide and MTP.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed2005

Special issues in pediatric Hodgkin's disease.

Childhood Hodgkin's disease (HD) is not a biologically unique disease; it differs from adult HD primarily in the relative incidence of disease histology. Preadolescent children are more likely to have Mixed Cellularity and nodular lymphocyte predominant HD. Adolescent and young adult HD is indistinguishable, with a predominance of nodular sclerosing (NS) HD. Nonetheless, treatment paradigms have diverged over the years as pediatric oncologists responded first to developmental issues in the young child, and later to the long-term treatment consequences in all young survivors. The latter concerns are of equal relevance to the young adult with HD. The increasing convergence of treatment approaches in the past decade is therefore most appropriate. Reproductive potential, risk of secondary malignancy and cardiopulmonary consequences of therapy have driven the pediatric treatment paradigm of care. Chemotherapy with low dose, limited field radiation is standard, with low-stage patients often treated by chemotherapy alone. Algorithms tailor therapy to response. The prognostic importance of very early chemotherapy response rather than end-of-chemotherapy response has led the Children's Oncology Group to use early response (after 6 wk) to titrate individual therapy and dense regimens to maximize the early response rates. Although the dose dense regimens of adult groups are similar, the pediatric algorithms emphasize using the enhanced efficacy to limit cumulative therapy. This review intends to address the special issues of childhood HD, with the intent of further encouraging understanding that will foster convergence of pediatric and adult treatment paradigms.

Adolescent↗
PubMed2003

Prognostic factors in pediatric Hodgkin disease.

The sensitivity of pediatric Hodgkin disease to radiation and chemotherapy has resulted in cure for most children and adolescents who have been diagnosed in the past three decades. Identification of prognostic factors in clinical trials has allowed for tailoring of therapeutic approaches to improve outcome in sequential trials. Tumor burden, symptoms, clinical features, pathology, response to therapy, biology, and host factors are reviewed in this context. New developments should be directed toward identification of factors associated with biologic mechanisms of disease to facilitate the development of biologically targeted therapies that will be more efficacious and less toxic.

Hodgkin Disease↗
PubMed2003

The management of Hodgkin disease in the young child.

Although childhood Hodgkin disease is sensitive to the treatment regimens devised for Hodgkin disease in adults, long-term toxicity is enhanced in the developing individual. As a result, there have been dual goals in the design of clinical trials for pediatric Hodgkin disease: 1) to reduce long-term organ injury; and 2) to increase efficacy. Radiation dose and field has been reduced by enhanced reliance on chemotherapy, thus limiting the risks of hypoplasia, hypothyroidism, secondary cancers, and valvular and atherosclerotic heart disease. Multiagent, chemotherapeutic regimens for children have been developed to avoid the risks of sterility, leukemia, and cardiopulmonary toxicity. Newer approaches advocate for early dose intensity to limit cumulative therapy using response-based paradigms. Targeting molecular mechanisms specific for the Reed-Sternberg cell may allow for less toxic and more efficacious treatments in the future.

Adolescent↗
PubMed2002

Phase II/III trial of etoposide and high-dose ifosfamide in newly diagnosed metastatic osteosarcoma: a pediatric oncology group trial.

PURPOSE: The objectives of this trial were to estimate the response rate, progression-free survival, and overall survival of patients who received therapy with etoposide and high-dose ifosfamide, and to define the toxicity of this combination when provided with standard chemotherapy in patients with newly diagnosed metastatic osteosarcoma. PATIENTS AND METHODS: Eligible patients received infusions of 100 mg/m(2) per day of etoposide and 3.5 g/m(2) per day of ifosfamide for 5 days. Therapy with granulocyte colony-stimulating factor was begun on day 6. This was repeated 3 weeks after therapy was begun. Response was determined at week 6 by both standard World Health Organization response criteria and by pathologic determination of tumor necrosis of the primary tumor. RESULTS: Forty-three patients were registered; 39 were assessable for response and 41 for toxicity and survival. Twenty-eight (68%) of 41 had metastatic sites only in the lung; 12 (29%) had metastatic sites in other bones with or without lung involvement. Four patients (10%) experienced complete response, and 19 patients (49%) experienced partial response, for an overall response rate of 59% +/- 8%. The projected 2-year progression-free survival (PFS) for the 28 patients with metastases to lungs was 39% +/- 11%. The projected 2-year PFS for the 12 patients with metastases to other bones (with or without pulmonary metastases) was 58% +/- 17%. Two patients died as a result of therapy toxicity. Eighty-three percent of patients had grade 4 neutropenia, and 29% had grade 4 thrombocytopenia. Ten patients (24%) had sepsis. Fanconi's syndrome was observed in five patients. CONCLUSION: The combination of etoposide and high-dose ifosfamide is effective induction chemotherapy for patients with metastatic osteosarcoma, despite significant associated myelosuppression sometimes complicated by infection and renal toxicity.

Adolescent↗