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Biomedical subjects

G D Hammond

Publications and source records attributed to G D Hammond.

At least 91 records · Page 5Linked to original sources
PubMed1989

Improvement in survival after excision of primary tumor in stage III neuroblastoma.

Fifty-eight patients with stage III neuroblastoma (according to the Childrens Cancer Study Group) underwent 86 operative procedures. Initial diagnostic or therapeutic operations were followed by chemotherapy and radiation therapy, and second- or third-look procedures were performed on patients whose tumors showed evidence of clinical response. Complete resection was obtained during the initial procedure in 12 patients, during the second operation in 12 others, and at the time of the third procedure in two additional children. Twenty of these 26 patients have survived with no evidence of disease for a median duration of greater than 3 years since initiation of therapy. Only nine of the 32 patients in whom complete tumor excision could not be accomplished are still alive. The chemotherapy and radiation therapy employed in this protocol may have enhanced resectability in many patients. The site of the primary tumor does not seem to influence ease of resectability or outcome in this group. The "favorable" prognostic factors of patient age and histopathology of the tumor do not necessarily predict that the tumor will be resectable. While patients with complete resection at the time of the second operation had an outcome superior to those with incomplete resections, the influence of the inherent tumor biology or other selection factors on the eventual tumor resectability in these patients is not known. Extensive operative procedures were required to completely resect stage III tumors, and a moderate complication rate may be anticipated. However, this may be justifiable if complete tumor resection can be achieved and ultimate patient survival possibly enhanced.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Early response to induction therapy as a predictor of disease-free survival and late recurrence of childhood acute lymphoblastic leukemia: a report from the Childrens Cancer Study Group.

The Childrens Cancer Study Group (CCSG) CCG-160 protocol series was designed to evaluate prognostic factors in acute lymphoblastic leukemia (ALL). Patients were assigned to one of three prognostic groups based upon initial WBC count and age. To determine the optimal duration of therapy, CCG-160 patients completing 2 years of treatment in continuous remission were randomized ("late randomization") to discontinue therapy or receive another year of maintenance therapy. The prognostic significance of early response to induction therapy, as measured by the percentage of lymphoblasts in the day-14 bone marrow (d14 BM) aspirate, was evaluated in 2,516 children. For 1,490 patients with complete data, the status of the d 14 BM was a highly significant predictor of disease-free survival (DFS) by univariate and multivariate analysis (P less than .0001). The observed/expected (O/E) failure rate in patients with d14 M1 (less than 5% blasts), M2 (4% to 25% blasts), or M3 (greater than 25% blasts) BM rating who were subsequently M1 on day 28 or day 42, was .87, 1.59, and 2.30, respectively (P less than .0001). Patients with M2 or M3 d14 BM were more likely to have L2 ALL (modified French-American-British [FAB] morphologic classification), P less than .001. The significance of the d14 BM rating persisted after correction was made for WBC count and clinical prognostic groups using current CCSG criteria, except in infants less than 12 months of age. The d14 BM was also the most significant predictor of DFS in 975 patients after late randomization at 2 years following diagnosis. The O/E failure rate in patients with d14 M1, M2, or M3 BM was .88, 1.78, and 2.02, respectively (P = .0002, trend). Other significant predictors of late relapse were prognostic groups (P = .0003, trend) and initial WBC count (P = .004, trend). Predictive for both early and late relapse of ALL, early response should be monitored closely and alternative treatment regimens should be considered for slow responders.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Excellent outcome of stage II neuroblastoma is independent of residual disease and radiation therapy.

The optimal management for patients with stage II neuroblastoma has not yet been established. In order to determine the impact of adding chemotherapy and/or radiation therapy to surgery, we reviewed by questionnaire 156 patients with stage II neuroblastoma treated by 28 Childrens Cancer Study Group (CCSG) institutions from 1978 to 1985. Survival and progression-free survival (PFS) were analyzed by life-table methods with respect to age at diagnosis, site and size of primary tumor, spinal cord involvement, extent of initial resection, and treatment in addition to surgery. The overall 5-year survival was 96%; the PFS was 90%, similar to previous CCSG studies. Age at diagnosis had a small impact on PFS, with 92% PFS for patients less than 2 years of age at diagnosis, and 84% for those greater than 2 (P = .10). The only site with an adverse outcome was the head and neck (n = 11), with a PFS of 68% compared with 93% for the remaining sites (P = .02). Size of primary and intraspinal extension of primary did not affect PFS. The extent of resection and subsequent treatment with radiation therapy and/or chemotherapy did not affect the PFS. The outcome for 75 patients treated with surgery alone (6-year PFS, 89%) was not significantly different from that of 66 patients receiving radiation therapy (6-year PFS, 94%). There was no significant difference between 40 patients with gross or microscopic residual disease treated with surgery alone (PFS, 92%) and 59 patients with residual disease who also received radiation (PFS, 90%). Five of seven patients who progressed after surgery alone have been salvaged with further therapy and are now free of disease. One survives with disease, so that the 6-year survival is 98% for those treated initially with surgery alone, compared with 95% for those receiving radiation therapy and/or chemotherapy. These data suggest that surgery alone, even if complete resection is not achieved, is sufficient initial therapy for stage II neuroblastoma. The data also identify another stage of neuroblastoma, in addition to stage IV-S, for which almost all patients have a favorable prognosis because their tumor may be biologically limited in growth.

Abdominal Neoplasms↗
PubMed1989

Three versus five years of maintenance therapy are equivalent in childhood acute lymphoblastic leukemia: a report from the Childrens Cancer Study Group.

Childrens Cancer Study Group protocol 141 (CCG-141), a randomized trial, was designed in part to compare 3 v 5 years of maintenance therapy, to evaluate the role of late reinduction, and to identify factors that predict relapse after 3 years of continuous complete remission (CCR) in acute lymphoblastic leukemia (ALL). Of 880 patients entered on study, 827 (94%) achieved complete remission and 499 (56.7%) were in CCR after 3 years of maintenance therapy. Boys were required to have negative testicular biopsies before randomization. A total of 481 patients were eligible for the duration of therapy phase of the study. Of the 310 (64.4%) randomly assigned patients, 101 were entered on regimen A: discontinue therapy; 105 on regimen B: reinduction for 4 weeks, then discontinue therapy; and 104 on regimen C: continue maintenance therapy for 2 more years, then discontinue. After a median follow-up of over 72 months, no significant differences in disease-free survival (DFS) or survival were noted in the three regimens. At 6 years from randomization, 93.0%, 89.1%, and 89.1% of patients on regimens A, B, and C, respectively, remained in CCR. Isolated CNS or overt testicular relapses were not significantly different in any of the study regimens. Isolated testicular relapse after a negative biopsy occurred in only two of 137 randomized males (1.5%). DFS (P = .10) and survival (P = .83) were not significantly different for all boys and girls randomized to regimens A, B, or C. The relapse rate was higher in boys than in girls randomized to discontinue therapy (11% v 4%), but the difference was not statistically significant (P = .14). Except for the presence of occult testicular leukemia (TL) in males, no other factors were identified that predicted for adverse events after 3 years of CCR. We conclude that prolongation of maintenance therapy beyond 3 years does not improve survival or decrease the risk of relapse.

Adolescent↗
PubMed1989

Multiple sclerosis in mothers of children with acute lymphoblastic leukemia.

The Childrens Cancer Study Group used data from a self-administered questionnaire to compare the observed and expected frequencies of multiple sclerosis (MS) in the parents of 1,027 children with acute lymphoblastic leukemia (ALL), 2,053 parents of children with other cancers, and in parents of 838 children without cancer. There were significant excesses seen for mothers of children with ALL (relative risk, RR = 4.0, p = 0.02), but no excess was found for acute nonlymphoblastic leukemia or lymphoma. There was no increase risk of MS for the fathers of these children.

Adolescent↗
PubMed1988

Phase I/II study of bisantrene in childhood cancer: a report from the Childrens Cancer Study Group.

A phase I/II study of bisantrene using a 3-week schedule was undertaken in 171 children with refractory leukemias and solid tumors. The doses ranged from 190 to 430 mg/m2. The maximum tolerated dose for children with solid tumors and acute leukemias was 280 mg/m2 and 360 mg/m2 every 3 weeks, respectively. The dose limiting toxicities were hepatic and hematologic. One patient with ALL achieved a complete remission and partial responses were observed in three patients with soft-tissue sarcomas. The data indicate that bisantrene, at the doses and schedule used in this study, has limited antitumor activity in pretreated children with cancer.

Adolescent↗
PubMed1988

The relationship of various aspects of surgical management to outcome in childhood nonmetastatic osteosarcoma: a report from the Childrens Cancer Study Group.

Recently, much attention has been focused on the role of adjuvant chemotherapy in the treatment of osteosarcoma. Surgery, however, remains the primary modality for the ablation of this disease. In this report, we examine the relationship of various aspects of surgical management of osteosarcoma to prognosis for disease-free survival (DFS) in a randomized study of 234 pediatric patients. Attention is restricted to 166 patients with nonmetastatic disease confined to an extremity and who were randomized to receive one of two chemotherapeutic regimens. No advantage with respect to DFS was attributable to the various aspects of surgical management considered: interval from first symptoms to definitive surgery, surgical sequence, and type of surgery. Only two local recurrences were seen. One occurred in an above knee amputation stump and the other occurred in a patient receiving a tibial allograft. One of these patients died of pulmonary metastases within 6 months of recurrence; the other patient is alive without evidence of disease at last contact after resection of the recurrence followed by chemotherapy.

Adolescent↗
PubMed1988

An evaluation of the role of surgery in metastatic neuroblastoma.

The role of surgery was evaluated in 320 patients with metastatic neuroblastoma (Children's Cancer Study Group [CCSG] stage IV, excluding IV-S) enrolled in two CCSG treatment protocols between June 1978 and November 1982. The regimens consisted of combination chemotherapy, radiation therapy, and surgery. Two hundred seventy-seven surgical procedures were performed in 214 of the 320 eligible patients. Surgical intervention at the primary site was performed at initiation of therapy in 86 patients. There was a slight survival advantage when complete resection of the primary tumor was achieved (P = .09). Delayed surgery was performed in 89 patients. Gross complete resection of primary tumor was feasible in 57 of these patients (64.0%). However, survival analysis showed that resolution of metastases had a more important impact on subsequent length of survival than resectability at the delayed procedure (P = .005).

Adolescent↗
PubMed1988

Prognostic value of histopathology in advanced neuroblastoma: a report from the Childrens Cancer Study Group.

We report the histopathologic findings in 420 patients with stage III and IV neuroblastoma enrolled in Childrens Cancer Study Group trials conducted from 1980 to 1983. A prospective study of individual cytohistologic features showed that outcome was related in a statistically significant manner to mitotic rate, multi-nuclearity, foam cells, ganglion cells, necrosis, and calcification, but only the latter was consistent for both stages. A similar test of four selected published classifications indicated the greatest prognostic value for the system developed by Shimada et al to distinguish favorable from unfavorable tumors. This classification proved significant in both stages and on examination of both primary and metastatic sites. Concordance in histologic assignment of prognosis by two observers was 83%. We conclude that the Shimada classification is valid and reproducible, and that it may be useful in planning therapy in advanced neuroblastoma. Selected cytohistologic parameters and the other classifications were less strongly predictive of outcome, but are worthy of continued study.

Adolescent↗
PubMed1988

A phase II study of diaziquone in childhood leukemia: a report from the Children's Cancer Study Group.

Diaziquone (aziridinylbenzoquinone, AZQ) was given by 30-min infusion at 25 mg/m2/day on a daily x 5 schedule to 16 children with acute lymphoblastic leukemia (ALL) in bone marrow relapse, 16 children with acute nonlymphocytic leukemia (ANLL) in bone marrow relapse, and 1 child with chronic myelocytic leukemia in blast crisis. None of the children achieved bone marrow remission. Five children (four with ALL and one with ANLL) were also evaluable for the response of central nervous system leukemia; all had a significant reduction in the cerebrospinal fluid blast count. Mild transient transaminase elevation was commonly seen. Grade 3 and 4 hyperbilirubinemia was seen in association with sepsis. AZQ was ineffective for induction of bone marrow remission as utilized in this study.

Adolescent↗
PubMed1988

Modified BFM therapy for children with previously untreated acute lymphoblastic leukemia and unfavorable prognostic features. Report of Children's Cancer Study Group Study CCG-193P.

The Children's Cancer Study Group's (CCG) clinical trials in acute lymphoblastic leukemia (ALL) prior to 1981 consistently demonstrated that patients presenting with a white blood cell count (WBC) greater than or equal to 50,000/microliter or the "lymphoma syndrome" had a less than 40% 3-year event-free survival (EFS). The Berlin Frankfurt Munster (BFM) 76/79 study suggested that the prognosis of these patients could be improved. Before testing this therapy in a randomized setting, 29 CCG institutions used it for treatment of 209 newly diagnosed children with ALL and an initial WBC greater than or equal to 50,000/microliter or the lymphoma syndrome. In the intensive phases of therapy, 77% of cumulative parenteral doses and 55% of cumulative oral doses were within 10% of protocol requirements or were modified appropriately for reported toxicity. One hundred ninety-five patients achieved remission (93.3%). Eleven patients died in remission (5.6%)--10 during the intensive reinduction/reconsolidation phase. The 4-year EFS (+/- 1 SD) was 62% (+/- 3.7%) with a median follow-up of 40 months. Only one patient has had an isolated CNS relapse. These results appear superior to past CCG studies for high-risk patients and extend observations made from studies of similar therapy.

Adolescent↗
PubMed1988

The effect of initial management of hyperleukocytosis on early complications and outcome of children with acute lymphoblastic leukemia.

Data were collected from 124 patients with newly diagnosed acute lymphoblastic leukemia (ALL) and WBC greater than 200,000/microL seen at institutions affiliated with the Children's Cancer Study Group (CCSG) from April 1981 to May 1983. The presenting characteristics, initial management, early complications, and outcome were reviewed. All the children received vigorous intravenous (IV) hydration, alkalinization of the urine, and allopurinol. Thirty-two patients were started on full therapy with no additional measure. One or more special measures believed to reduce the complications of leukostasis and blast cell lysis were administered to 92 patients as follows: small initial doses of prednisone, 63; emergency cranial irradiation, 26; exchange transfusion, 21; and leukopheresis, 19. The incidence of CNS hemorrhage was only 3% (4/124). Seven patients expired during induction and four failed to achieve a remission by day 28. Nineteen patients (15%) had documented bacterial or fungal sepsis. Mild to moderate electrolyte abnormalities occurred in 29 patients: three patients required renal dialysis. Pretreatment with small doses of prednisone did not decrease the incidence of electrolyte abnormalities in those patients when compared with patients who received full chemotherapy. The event-free survival (EFS) for the 106 patients treated on one of the three intensive pilot studies is 55% at 36 months. On multivariate analysis the two significant adverse prognostic factors were massive splenomegaly (P = .02) and WBC count greater than 600,000/microL (P = .05). In conclusion, in patients with hyperleukocytosis the complications of blast cell lysis and leukostasis were manageable with acceptable morbidity and minimal mortality in a group of patients treated with vigorous hydration, allopurinol, and alkalinization of the urine before beginning chemotherapy. Selected patients with severe hyperuricemia and renal dysfunction may benefit from leukopheresis. No beneficial role was demonstrated for the use of small initial doses of prednisone or emergency cranial irradiation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

A randomized study comparing high-dose methotrexate with moderate-dose methotrexate as components of adjuvant chemotherapy in childhood nonmetastatic osteosarcoma: a report from the Childrens Cancer Study Group.

Methotrexate (MTX) has demonstrated significant activity against relapsed and metastatic osteosarcoma. However, there is little published data to indicate the appropriate dose for MTX when given as a component of a multidrug regimen for the treatment of osteosarcoma. Therefore, the investigators at the Childrens Cancer Study Group undertook a randomized clinical trial that compared Adriamycin and vincristine given with either high-dose methotrexate or moderate-dose methotrexate as postoperation chemotherapy in the treatment of childhood osteosarcoma. We report here the results for 166 patients with completely resected nonmetastatic disease of an extremity. The two therapies demonstrated equivalent disease-free survival (DFS). Further, no therapy prejudices survival after relapse. Approximately 38% of patients remain disease free 4 years after diagnosis. Two relapses occurred in patients free of disease at least 36 months after initiation of treatment. Some factors found by other investigators to be prognostic of poorer DFS, namely, male sex, primary tumor in the humerus or femur, and larger primary tumors, demonstrated similar though not statistically significant trends. The presence of spontaneous necrosis in the tumor sample from the definitive surgery was associated with poor prognosis for DFS. We postulate that this feature represents rapidly growing tumors with increased potential for metastases.

Adolescent↗
PubMed1987

Long-term evaluation of a CNS prophylaxis trial--treatment comparisons and outcome after CNS relapse in childhood ALL: a report from the Childrens Cancer Study Group.

The current status of children with acute lymphoblastic leukemia (ALL) who had developed CNS disease while being treated on protocol CCG-101 was investigated. Seven hundred thirty-six eligible patients were entered into the study between June 1972 and July 1974. All children who were greater than 18 months of age were eligible for randomization to a CNS prophylaxis trial for which one regimen gave only a short course of intrathecal methotrexate (IT MTX) as prophylaxis. All other regimens included radiation therapy as prophylaxis. Current follow-up (median, greater than 10 years) shows no significant difference by standard life-table analysis for ultimate survival, although a substantial excess of CNS episodes occurred on the IT MTX regimen. Of the 675 patients who completed induction therapy and achieved remission in the study, 100 (14.8%) developed CNS disease as the first evidence of relapse. Fifty-five of these 100 had no subsequent CNS episodes. Only 17 of these 55 patients are surviving without further relapses since the CNS episode. The median time to isolated CNS relapse was 457 days. Time to the initial CNS relapse was found to be the most important factor for predicting outcome. Thirty-five of the 55 patients with isolated relapse subsequently relapsed in the bone marrow, and of these, 32 have died. Twenty patients of the 100 with CNS disease as the first evidence of relapse developed two episodes of CNS involvement and 17 of these 20 patients subsequently relapsed in the bone marrow; only one patient survived. Twenty-five patients of the 100 have shown a pattern of chronic CNS disease with multiple CNS relapses. The overall disease-free survival for the 100 patients who developed one or more relapse was only 16%. These data demonstrate that the occurrence of a CNS relapse is an indicator of poor subsequent outcome. Comparison of results of groups receiving different CNS prophylaxis required careful consideration of the entire pattern of relapses and mortality.

Adolescent↗
PubMed1987

Effects of radiation on ovarian function in long-term survivors of childhood acute lymphoblastic leukemia: a report from the Childrens Cancer Study Group.

The Childrens Cancer Study Group has assessed serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and pubertal development in 97 long-term female survivors of childhood acute lymphoblastic leukemia (ALL). All patients received identical induction and maintenance therapy with either 18 or 24 Gy of radiation therapy (RT) to one of the following fields: cranial, craniospinal, or craniospinal plus 12 Gy abdominal RT including the ovaries. Thirty-six percent (35 patients) were found to have above normal levels of FSH and/or LH. The percentages of elevated values for RT fields were 93% for craniospinal plus abdominal RT, 49% for craniospinal RT, and 9% for cranial RT (P less than .001). A dose-response relationship was observed between 18 Gy and 24 Gy in females receiving only craniospinal RT (P = .01). Craniospinal plus abdominal RT and abnormal FSH/LH levels were significantly associated with lack of pubertal development and delayed onset of menses. Duration of maintenance chemotherapy was not associated with abnormal gonadotropin levels or the development of secondary sexual characteristics. Additional follow-up of this cohort is needed to establish the ultimate pubertal development and fertility of these patients.

Adolescent↗
PubMed1987

Improved survival of infants less than 1 year of age with acute lymphoblastic leukemia treated with intensive multiagent chemotherapy.

Infants with acute lymphoblastic leukemia (ALL) have a poor prognosis. Early disease recurrence, rather than excessive toxicity and complications resulting in limitation of therapy is the major factor responsible for this disappointing outcome. The CCG-192P trial was a groupwide pilot study of the Childrens Cancer Study Group for the treatment of ALL in patients at high risk for relapse, which was defined by wbc count greater than 50 X 10(3)/microliters at diagnosis. Because of the recognized poor prognosis, all infants less than 1 year of age were entered in this study regardless of wbc count at diagnosis. Therapy included intensive induction and consolidation followed by a cyclic, sequential maintenance program. The CNS prophylaxis consisted of intrathecal chemotherapy and cranial irradiation, which was deferred until patients were greater than 1 year of age. During the period January 1982 to January 1984, 27 infants ranging in age from 2 days to 11 months who had ALL were entered in this study; 71% had wbc counts greater than 50 X 10(3)/microliters, and 23% presented with CNS leukemia. Complete remission was achieved in 93% of the patients. The median duration of remission is 17 months. With a median follow-up of 43 months, the life-table estimate of event-free survival (EFS) is 36% at 4 years. A recently reported historical control group of infants with ALL who were treated with previous Childrens Cancer Study Group protocols demonstrated a median remission duration of 8 months and an estimated EFS of only 21% at 4 years. Toxicity and therapy-related complications were not observed more frequently in infants than in older patients treated with this protocol. However, EFS of infants was significantly worse than that of patients greater than 1 year of age (P = less than 0.001). All four CNS relapses occurred in patients who had received cranial irradiation. A wbc count less than 50 X 10(3)/microliters at diagnosis demonstrated significance (P = 0.03) as a favorable prognostic indicator in this small patient sample. Although these data are preliminary, they suggest that intensive therapy is reasonably well tolerated by infants and results in prolongation of remission duration and improved EFS.

Age Factors↗