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Biomedical subjects

W M Crist

Publications and source records attributed to W M Crist.

At least 37 records · Page 2Linked to original sources
PubMed1999

Progress in the surgical management of vaginal rhabdomyosarcoma: a 25-year review from the Intergroup Rhabdomyosarcoma Study Group.

BACKGROUND/PURPOSE: During its 25 years of experience, the Intergroup Rhabdomyosarcoma Study Group (IRSG) has completed four sequential prospective clinical trials to improve survival and decrease morbidity rates in childhood rhabdomyosarcoma (RMS). Surgical management of vaginal RMS has changed dramatically. METHODS: The records of 72 patients with localized vaginal RMS were reviewed to assess surgical therapy, chemotherapy, and radiotherapy and their relation to outcome. RESULTS: Each successive IRSG trial resulted in decreased need for surgical resection (IRS-I, 100%; IRS-II, 70%; IRS-III, 30%; IRS-IV, 13%) and excellent disease-free survival using increasingly effective multiagent chemotherapy. CONCLUSIONS: Primary chemotherapy after initial biopsy provides excellent tumor control. Local resection may be appropriate, but removal of organs (ie, complete vaginectomy/hysterectomy) has no role except in persistent or recurrent disease. Mature, residual rhabdomyoblasts may be evidence of a chemotherapy response, and further surveillance and biopsy without surgical resection is adequate treatment.

Algorithms↗
PubMed1999

Does debulking improve survival rate in advanced-stage retroperitoneal embryonal rhabdomyosarcoma?

UNLABELLED: BACKGROUND, METHODS, AND PURPOSE: The authors examined demographic and clinical features, therapy, and outcome of patients with advanced (group III or IV) rhabdomyosarcoma (RMS) of the retroperitoneum and nongenitourinary pelvis treated in the Intergroup Rhabdomyosarcoma Study Group (IRSG) III (1984 to 1991, n = 41) or IV pilot (1987 to 1991, n = 53) studies to assess the role of initial debulking surgery. RESULTS: Ninety-four patients with retroperitoneal primary tumors and gross locoregional residual tumor (group III, n = 53) or metastatic disease (group IV tumors, n = 41) were treated with combination chemotherapy (ie, vincristine, dactinomycin, and cyclophosphamide with or without other agents plus radiation therapy, RT) after biopsy only or subtotal resection. These retroperitoneal tumors usually were invasive (T2, 76%). Most patients were younger than 10 years of age (n = 69, 73%), the male to female ratio was 1.4, and tumors usually were embryonal (n = 64, 68%). Overall 4-year failure-free survival (FFS) was 50%; survival was 60%. Survival rate was better for girls (4-year survival rate, 75% v49% for boys; P = .05) and was not significantly different for patients treated in IRS-III (66%) or IRS-IV pilot (52%). However, it was better for patients with embryonal versus alveolar or undifferentiated tumors (4-year survival rate, 70% v 42%; P = .002). In adolescents, RMS is different from that seen in children less than 10 years old; most cases are alveolar or undifferentiated (16 of 29, 55%). Surgery for most (21 of 24) patients with alveolar tumors comprised biopsy only. By contrast, of 64 patients with embryonal tumors, 39 (61%) underwent biopsy only, whereas 25 (39%) had debulking surgery. Patients whose tumors were debulked fared better than those whose tumors underwent biopsy only (4-year FFS rate, 72% v48%; P = 0.03). Patients with group IV embryonal tumors fared unexpectedly better than those with group IV alveolar or undifferentiated tumors (70% versus 42% 4-year survival rate, P < .05), and patients less than 10 years of age with group IV embryonal tumors had 4-year survival rate of 77%, indicating the importance of the biology of these tumors. CONCLUSIONS: Multimodal therapy, including multiagent chemotherapy plus RT, appears to improve survival rate in patients with advanced embryonal RMS arising in the retroperitoneum. These data suggest that debulking tumors of embryonal histology improves outcome further. This approach will be assessed in IRSG V.

Adolescent↗
PubMed1999

Large proportion of Epstein-Barr virus-associated small noncleaved cell lymphomas among children with non-Hodgkin's lymphoma at a single institution in Moscow, Russia.

To evaluate clinical and biologic features of children with non-Hodgkin's lymphoma (NHL) treated in Moscow, Russia, we studied 53 cases treated in the Republican Children's Hospital from 1990 to 1994. Histologic examination disclosed a predominance of the small noncleaved cell subtype (32 cases, 60%); a smaller percentage of the lymphoblastic and large-cell subtypes (14 cases, 26% and 7 cases, 13%, respectively) were identified. The frequencies of primary sites of involvement in descending order included 60% in abdomen, 19% in mediastinum, 15% in head/neck, and 4% in peripheral nodes. The majority of children presented with advanced stage disease (St. Jude stage III/IV/B-ALL, 92.5%). Of interest, 8 of 15 (53%) small noncleaved cell NHL cases examined contained Epstein-Barr virus (EBV). The high frequency of EBV association in this study suggests that this virus may play a more global role in NHL pathogenesis than previously recognized.

Adolescent↗
PubMed1999

Indications for radiotherapy and chemotherapy after complete resection in rhabdomyosarcoma: A report from the Intergroup Rhabdomyosarcoma Studies I to III.

PURPOSE: To evaluate the outcome of patients with rhabdomyosarcoma (RMS) treated with complete surgical resection and multiagent chemotherapy, with or without local radiotherapy (RT). PATIENTS AND METHODS: Four hundred thirty-nine patients with completely resected (ie, group I) RMS were further treated with chemotherapy (vincristine and actinomycin D +/- cyclophosphamide, doxorubicin, and cisplatin) on Intergroup Rhabdomyosarcoma Studies (IRS) I to III between 1972 and 1991. Eighty-three patients (19%) also received local RT as a component of initial treatment. RESULTS: Eighty-six patients relapsed (10-year failure-free survival [FFS] 79%, overall survival 89%). Six percent of failure sites were local, 6% were regional, and 7% were distant. Poor prognostic factors were tumor size greater than 5 cm, alveolar or undifferentiated histology, primary tumor sites other than genitourinary, and treatment on IRS-I or II. For patients with embryonal RMS who were treated with RT, there was a trend for improved FFS but no difference in overall survival. On IRS-I and II, patients with alveolar or undifferentiated sarcoma who received RT compared with those who did not receive RT had greater 10-year FFS rates (73% v 44%, respectively; P =.03) and overall survival rates (82% v 52%, respectively; (P =.02). Such patients who received RT on IRS III also benefited more than those who did not receive RT (10-year FFS, 95% v 69%; P =.01; overall survival, 95% v 86%; P =.23). CONCLUSION: Patients with group I embryonal RMS have an excellent prognosis when treated with adjuvant multiagent chemotherapy without RT. Patients with alveolar RMS or undifferentiated sarcoma fare worse; however, FFS and overall survival are substantially improved when RT is added to multiagent chemotherapy (IRS-I and II). The best outcome occurred in IRS-III, when RT was used in conjunction with intensified chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Survival after relapse in children and adolescents with rhabdomyosarcoma: A report from the Intergroup Rhabdomyosarcoma Study Group.

BACKGROUND: Despite advances in therapy, nearly 30% of children with rhabdomyosarcoma experience progressive or relapsed disease, which is often fatal. PATIENTS AND METHODS: To facilitate the development of a retrieval therapy protocol, we studied potential risk factors that were predictive of survival after first relapse in 605 children who were enrolled onto three consecutive Intergroup Rhabdomyosarcoma Study Group protocols. RESULTS: The median survival time from first recurrence was 0.8 years; the estimated percentage of patients who survived 5 years from first recurrence was 17% +/- 2% (mean +/- SD). Univariate analysis showed that tumor histology was an important predictor of 5-year survival (P <.001): the 5-year survival rate was 64% for patients with botryoid tumors (n = 19), 26% for patients with embryonal tumors (n = 313), and 5% for patients with alveolar or undifferentiated sarcoma (n = 273). Further analysis identified prognostic factors within histologic subtypes (P <.001). For patients with embryonal tumors, the estimated 5-year survival rate was 52% for patients who initially presented with stage 1 or group I disease, 20% for those with stage 2/3 or group II/III disease, and 12% for those with group IV disease. For patients with stage 1/group I disease, estimated 5-year survival rates were higher for patients with local (72%) or regional (50%) recurrence than for those with distant (30%) recurrence. Among patients with alveolar or undifferentiated sarcoma, only the disease group predicted outcome: the 5-year survival estimate was 40% for group I versus 3% for groups II through IV. We identified a "favorable risk" group (approximately 20% of patients) whose 5-year estimated survival rate was near 50%; for all other patients, the estimated survival was near 10%. CONCLUSION: This analysis demonstrates that the probability of 5-year survival after relapse for rhabdomyosarcoma is dependent on several factors at the time of initial diagnosis, including histologic subtype, disease group, and stage. These findings will form the basis of a multi-institutional risk-adapted relapse protocol for childhood rhabdomyosarcoma.

Adolescent↗
PubMed1998

Increased mortality after successful treatment for Hodgkin's disease.

PURPOSE: To determine the impact of treatment toxicity on long-term survival in pediatric Hodgkin's disease. PATIENTS AND METHODS: We studied late events in 387 patients treated for pediatric Hodgkin's disease on four consecutive clinical trials at St Jude Children's Research Hospital from 1968 to 1990. Relative risks, actuarial risks, and absolute excess risks for cause-specific deaths were calculated. RESULTS: As of April 1997, 316 (82%) of patients were alive, with a median follow-up of 15.1 (range, 2.9 to 28.6) years. In this cohort, which represented 5,623 person-years of follow-up, 71 fatal events resulted from Hodgkin's disease (n=36), second malignancies (n=14), infections (n=7), accidents (n=7), cardiac disease (n=6), and asphyxiation (n=1). The 5-year estimated event-free survival (EFS) for the entire cohort was 79.6%+/-2.1 %, which declined to 63.1%+/-4.4% by 20 years. Cumulative incidences of cause-specific deaths at 25 years were 9.8%+/-1.6% for Hodgkin's disease, 8.1%+/-2.6% for second malignancy, 4.0%+/-1.8% for cardiac disease, 3.9%+/-1.5% for infection, and 2.1%+/-0.8% for accidents. Standardized incidence ratios showed excess risk for all second malignancies (12; 95% confidence interval [CI], 8 to 17), acute myeloid leukemia (81; 95% CI, 16 to 237), solid tumors (11; 95% CI, 7 to 16), and breast cancer (33; 95% CI, 12 to 72). Standardized mortality ratios also showed excess mortality from cardiac disease (22; 95% CI, 8 to 48) and infection (18; 95% CI, 7 to 38). CONCLUSION: Compared with age- and sex-matched control populations, survivors of pediatric Hodgkin's disease who were treated before 1990 face an increased risk of early mortality related to second cancers, cardiac disease, and infection.

Adolescent↗
PubMed1997

Human granulocyte colony-stimulating factor after induction chemotherapy in children with acute lymphoblastic leukemia.

BACKGROUND: Recombinant human granulocyte colony-stimulating factor PO1 CA-20180ilgrastim) hastens the recovery from neutropenia after P30 CA-21765emotherapy, but its role in the management of childhood leukemia is unclear. METHODS: We randomly assigned 164 patients with acute lymphoblastic leukemia (age range, 2 months to 17 years) to receive placebo or G-CSF (10 microg per kilogram of body weight per day subcutaneously), beginning one day after the completion of remission-induction therapy and continuing until the neutrophil count was greater than or equal to 1000 per cubic millimeter for two days. The clinical and laboratory effects of this therapy were documented for 21 days. The area under the plasma G-CSF concentration-time curve was measured on days 1 and 7 in both groups. RESULTS: Responses to the growth factor could be assessed in 148 patients (73 in the G-CSF group and 75 in the placebo group). G-CSF treatment did not significantly lower the rate of hospitalization for febrile neutropenia (58 percent in the G-CSF group vs. 68 percent in the placebo group; relative risk, 0.85; 95 percent confidence interval, 0.59 to 1.16), increase the likelihood of event-free survival at three years (83 percent in both groups), or decrease the number of severe infections (five in the G-CSF group vs. six in the placebo group). Patients treated with G-CSF had shorter median hospital stays (6 days vs. 10 days, P=0.011) and fewer documented infections (12 vs. 27, P=0.009). The median total costs of supportive care were similar in the G-CSF and placebo groups ($8,768 and $8,616, respectively). Among patients who did not have febrile neutropenia during the first week of G-CSF or placebo injections, higher systemic exposure to the growth factor on day 7 was significantly related to a lower probability of subsequent hospitalization (P=0.049). CONCLUSIONS: G-CSF treatment had some clinical benefit in children who received induction chemotherapy for acute lymphoblastic leukemia, but it did not reduce the rate of hospitalization for febrile neutropenia, prolong survival, or reduce the cost of supportive care.

Adolescent↗
PubMed1997

XYY syndrome in children with acute lymphoblastic leukemia.

Certain constitutional chromosomal abnormalities increase the risk of malignancy and/or decrease treatment tolerance. We identified two patients with the XYY syndrome among a total of 444 male children with acute lymphoblastic leukemia who had complete cytogenetics studies. In both cases, the leukemic cell karyotype suggested a constitutional XYY abnormality that was confirmed in studies of lymphocytes obtained during remission. The incidence rate in our series is higher than that of the XYY syndrome in the general population (0.0045 vs. 0.001), but not significantly so. This finding and a literature review failed to confirm an increased frequency of the XYY syndrome among children with acute lymphoblastic leukemia. Both of our patients remain in remission 24 and 28 months, respectively, postdiagnosis. Their tolerance of intensive treatment, including high-dose methotrexate, suggests that the untoward treatment toxicity seen in patients with chromosomal abnormalities such as trisomy 21 does not extend to the XYY syndrome.

Adolescent↗
PubMed1997

Systemic hemophagocytosis masking the diagnosis of large cell non-Hodgkin lymphoma.

An 11-year-old female presented with clinical features suggestive of malignant histiocytosis: fever, weight loss, subcutaneous nodules, pulmonary infiltrates, adenopathy, and hepato-splenomegaly. On biopsy, lymph node and bone marrow demonstrated necrosis and extensive hemophagocytosis with no definitive evidence of malignancy: the subcutaneous nodules, however, demonstrated large-cell non-Hodgkin lymphoma. This clinicopathologic picture has been reported in adults, but not in children. Although serum G-CSF, M-CSF, and TNF levels were not elevated in this child, it is possible that other cytokines induced either directly or indirectly by the subcutaneous lymphoma resulted in hemophagocytosis.

Bone Marrow↗
PubMed1997

Primary and metastatic rhabdomyosarcoma in the breast: neoplasms of adolescent females, a report from the Intergroup Rhabdomyosarcoma Study.

UNLABELLED: The occurrence of rhabdomyosarcoma (RMS) primary in or metastatic to breast has been regarded as an uncommon event, associated with an unfavorable outcome. Records of 26 patients with diagnoses of breast RMS, either primary or secondary, entered in the Intergroup Rhabdomyosarcoma Study (IRS) (1972-1992) were reviewed and compared with data regarding 47 similar patients in published reports. Of the 26 IRS cases, the histologic subtype was alveolar in 24, embryonal in 1, and not determined in 1. All were female with ages ranging from 11.5 to 20.2 years (median, 15.2 years; mode, 14-16 years). This compact age distribution of both primary (n = 7) and metastatic (n = 19) breast RMS was seen in previously reported series. Among the 19 cases of RMS with initial dissemination to breast, primary tumor sites, were extremity (n = 8), nasopharynx/paranasal sinuses (n = 7), and trunk (n = 4). IRS treatment was risk-based according to site and extent of disease. Four of 7 patients with primary RMS remain disease free 2.9 to 7 years post diagnosis. Among 19 patients with RMS initially metastatic to breast, including 7 in IRS clinical group IV at original diagnosis, three are disease free at 7.6, 15.7 and 17.0 years. CONCLUSIONS: primary or metastatic RMS in breast is almost confined to adolescent females having tumors with alveolar histology. Approximately one-half of the patients with primary breast disease and 15% of those with metastatic breast disease as an initial recurrence are long-term survivors.

Adolescent↗
PubMed1997

Rhabdomyosarcoma. Biology and treatment.

Rhabdomyosarcoma is the most common soft-tissue sarcoma of childhood. Recognition of specific genetic changes in the two most common subtypes of rhabdomyosarcoma has allowed better understanding of the pathogenesis of this disease. In addition, identification of prognostic factors and the use of risk-directed multimodal therapy have improved the outcome for these patients significantly, with cure rates approaching 70%.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Predominance and characteristics of Burkitt lymphoma among children with non-Hodgkin lymphoma in northeastern Brazil.

The purpose of this paper was to define the histologic distribution, clinical features, and treatment response of childhood non-Hodgkin lymphoma (NHL) in northeastern Brazil. We reviewed medical records and histopathologic studies of 98 children treated for NHL from 1980 to 1987 at a major pediatric cancer center in Recife, Brazil. Treatment outcome was evaluated in relation to tumor burden (stage and serum LDH) and type of therapy (LSA2L2 vs other multiagent chemotherapy). There was a striking predominance of the small noncleaved cell (Burkitt) subtype, which occurred in 92 of the 98 children and adolescents diagnosed with NHL. Subsequent analyses focused on these patients. The majority (n = 84) had advanced (stage III/IV) disease at diagnosis. The abdomen was the most common site of disease (84 cases); jaw involvement was rare (three cases). Five-year event-free survival (excluding treatment refusals) was significantly better for patients with limited vs advanced stage disease (75 +/- 14% vs 42 +/- 6%; P < 0.04). Elevated serum LDH (>500 U/l) was associated with a poorer outcome (P = 0.008). The type of chemotherapy did not affect EFS (P = 0.95). Only 39% of patients are long-term survivors, reflecting the high rate of septic deaths (25% of patients) and parental refusal/abandonment of therapy (10%). Epstein-Barr virus (EBV) was detected in tumor cells from eight of the 11 cases studied. In clinical presentation, these cases resemble sporadic Burkitt lymphoma, yet in their apparent responsiveness to LSA2L2 therapy and association with EBV, they do not. Childhood NHL in northeastern Brazil is predominantly of the Burkitt subtype, and is associated with clinical features that appear to distinguish it from the endemic and sporadic forms of this tumor. These cases may represent a third or intermediate subtype of Burkitt lymphoma.

Adolescent↗
PubMed1997

TEL gene rearrangement in acute lymphoblastic leukemia: a new genetic marker with prognostic significance.

PURPOSE: TEL gene rearrangements due to the 12;21 chromosomal translocation are the most common molecular genetic abnormality in childhood acute lymphoblastic leukemia (ALL), occurring in approximately 25% of cases with a B-precursor immunophenotype. The limited number of clinically useful genetic markers in this leukemia subtype prompted us to assess TEL status as a predictor of treatment outcome. PATIENTS AND METHODS: We determined the status of the TEL gene (rearranged or germline) in 188 cases of B-precursor acute leukemia using Southern blot analysis and related the findings to event-free survival. All comparisons of outcome were stratified by treatment regimen, risk classification, age, and leukocyte count. RESULTS: Forty-eight patients (26%) had a rearranged TEL gene. At 5 years of follow-up, an estimated 91% +/- 5% (SE) of this group were event-free survivors, compared with only 65% +/- 5% of the group with germline TEL (stratified log-rank P = .011). For nonhyperdiploid patients, the odds ratio of an adverse event in the germline TEL group to that for the rearranged TEL group was 4.06 (95% confidence interval, 1.86 to 8.84). The relationship of TEL rearrangement to a favorable prognosis was independent of recognized good-risk features in B-precursor leukemia, including age, initial leukocyte count, and hyperdiploidy. CONCLUSION: Rearrangement of the TEL gene distinguishes a large subset of children with favorable-prognosis B-precursor leukemia who cannot be identified by standard prognostic features. It may be possible to treat these patients less aggressively without loss of therapeutic efficacy.

Child↗
PubMed1996

Overt testicular disease at diagnosis is associated with high risk features and a poor prognosis in patients with childhood acute lymphoblastic leukemia.

BACKGROUND: The impact of overt testicular disease on survival was assessed among patients treated at the study institution for childhood acute lymphoblastic leukemia (ALL) over a 15-year period. To the authors' knowledge, the frequency of overt testicular involvement at diagnosis of ALL and its impact on treatment outcome have not been reported previously. METHODS: The medical records of all 651 boys with ALL enrolled on St. Jude Total Therapy Studies X-XIIIA (May 1979 to December 1993) were reviewed to determine the frequency of overt testicular involvement at diagnosis. The log rank test and sequential Cox regression analyses, adjusted for known adverse features, were used to compare event free and overall survival for patients with and without testicular leukemia. A matched-pairs analysis was then conducted for both outcome measures. RESULTS: Thirteen of the 651 male patients (1.9%) presented with overt testicular leukemia. Compared with the other patients, these 13 boys had a significantly higher frequency of infant or adolescent age at diagnosis, hyperleukocytosis, splenomegaly, and mediastinal mass; a poorer 5-year event free survival (38% [95% confidence interval (CI), 15.4-61.4%] vs. 58% [95% CI, 53.6-61.7%], P = 0.06, log rank test); and a significantly poorer 5-year overall survival (37% [95% CI, 14-60.4%] vs. 75% [95% CI, 71.3-78.4%], P = 0.002). The difference in overall, but not event free, survival was supported by sequential Cox regression analyses and by the matched-pairs analysis (P = 0.04). CONCLUSIONS: Overt testicular involvement with leukemia at diagnosis was associated with an adverse survival in boys with ALL. Testicular irradiation may not be necessary in those patients who present with overt testicular involvement. This finding merits prospective evaluation in a larger sample of similarly treated patients.

Adolescent↗
PubMed1996

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↗