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Biomedical subjects

G D Hammond

Publications and source records attributed to G D Hammond.

At least 73 records · Page 4Linked to original sources
PubMed1990

Open-wedge testicular biopsy in childhood acute lymphoblastic leukemia after two years of maintenance therapy: diagnostic accuracy and influence on outcome--a report from Children's Cancer Study Group.

Bilateral testicular biopsies were performed on 708 males with acute lymphoblastic leukemia completing 24 to 30 months of maintenance chemotherapy in continuous remission. The 73 patients (10.3%) with occult testicular leukemia (TL) had a significantly increased risk of subsequent relapse (P = .0001) and death (P less than .0001) when compared with patients with negative biopsies. Protocol-specified therapy for occult TL included reinduction therapy with concurrent bilateral testicular radiation, and 2 years of maintenance therapy. Four-year event-free survival for patients with negative biopsies was 78.2% +/- 4% versus 65% +/- 14% for patients with occult TL who received protocol-specified therapy (P = .05). This study suggests that (1) occult TL occurs in 10% of males completing 2 years of maintenance therapy; (2) occult TL significantly increases risk for subsequent relapse and death; (3) treatment results for occult TL and isolated overt off therapy TL (no previous biopsy) are similar; and (4) given current therapy, documentation of occult TL after 2 years of therapy does not improve disease-free survival.

Antineoplastic Agents↗
PubMed1990

Day 7 marrow response and outcome for children with acute lymphoblastic leukemia and unfavorable presenting features.

The percent of marrow blasts on day 7 of therapy was determined for 128 children with previously untreated acute lymphoblastic leukemia and white blood count (WBC) greater than or equal to 50,000/microliters and/or lymphomatous features enrolled in the Childrens Cancer Study Group trial of the Berlin Frankfurt Munster 76/79 regimen (CCG-193P). Patients received four-drug induction therapy including vincristine, prednisone, l-asparaginase, and daunomycin. Ninety-seven patients had fewer than 25% marrow blasts on day 7. Of these, 94 survived and maintained remission through day 28 and were designated early responders. Thirty-one patients had greater than 25% marrow blasts on day 7. Of these, 28 survived and achieved remission on day 28 and were designated late responders. The outcome of patients who underwent a day 7 marrow aspiration was similar to those who did not. Early responders had a 77.4% +/- 4.5% (standard deviation) 3-year estimated disease free survival, while late responders had 47.3% +/- 9.8% (P less than 0.001). Early responders had a superior outcome both in the subset with an initial WBC less than 50,000/microliters (P = 0.025) and in the subset with a WBC greater than or equal to 50,000/microliters (P = 0.01). The day 7 marrow response had prognostic value in this population of children with unfavorable presenting features who received four-drug remission induction therapy.

Adolescent↗
PubMed1990

A phase II study of diaziquone in children with recurrent or progressive primary brain tumors: a report from the Childrens Cancer Study Group.

Seventy-five children with recurrent, progressive or metastatic primary brain tumors were treated with aziridinylbenzoquinone (AZQ; Diaziquone) at 9 mg/m2/day by 30-minute intravenous infusion for five days every three weeks. Sixty-six patients were evaluable for response by imaging studies. There were five partial responses and one complete response for a combined response rate of 9%. A complete response lasting for 35+ months occurred in one of twelve patients with metastatic or locally recurrent ependymoma. Objective responses were also seen in patients with primitive neuroectodermal tumors (PNET) (1/8), low-grade glioma (1/6), and primary central nervous system lymphoma (1/1). Stable disease of greater than six months duration was seen in patients with ependymoma, PNET and medulloblastoma. Profound and prolonged myelo-suppression was the significant toxicity observed. As administered in this study, AZQ has marginal activity and severe toxicity.

Adolescent↗
PubMed1990

Acute monoblastic leukemia: a unique subtype--a review from the Childrens Cancer Study Group.

The acute non-lymphocytic leukemias (ANLL) are generally treated as a homogeneous group. However, the literature is replete with articles alluding to distinctive features of acute monoblastic leukemia (AMoL). This review addresses the unique clinical, laboratory, epidemiological, and therapeutic features of AMoL. Leukemic monoblasts are distinguished from other cells in the myelocytic series by physical properties such as greater adhesiveness, deformability, and motility. Patients with AMoL often exhibit hyperleukocytosis, disseminated intravascular coagulation, and extramedullary involvement, particularly in the skin, gingiva, and central nervous system (CNS). AMoL occurs predominantly in adults over 40 and children under 10, fifty percent of whom are under 2 years of age at diagnosis. Its relatively common occurrence in infants parallels the high rate of proliferation of monocytes in that age group. Additionally, its occurrence in young children appears to be associated with in utero exposure to marijuana and parental exposure to pesticides and solvents. Therapeutic results are generally poor due to high rates of fatal complications during induction, induction failures, and frequent extramedullary and medullary relapses. This poor outcome is particularly noted in infants. Higher remission induction rates attained with epipodophyllotoxins and incorporation of bone marrow transplantation have not yet resulted in substantial improvement of long-term outcome. Recurrence of disease in the CNS is minimized by the use of intensive CNS presymptomatic treatment, usually incorporating irradiation. Our review suggests that unique and innovative treatment strategies are needed to improve outcome for patients with AMoL.

Adult↗
PubMed1990

A phase II study of diaziquone in children with recurrent or progressive solid tumors. Report from the Childrens Cancer Study Group.

Seventy-two children with recurrent, progressive, or metastatic lymphomas and other solid tumors, exclusive of primary central nervous system (CNS) tumors, were treated with aziridinylbenzoquinone (AZQ, diaziquone) at 9 mg/m2/day by 30-min intravenous infusion for 5 days every 3 weeks. Fifty-four patients were evaluable for response. Three partial responses occurred, two in patients with recurrent Hodgkin's disease and one in a patient with intraocular retinoblastoma. Sufficient numbers of patients with osteosarcoma, neuroblastoma, and Wilms' tumor were evaluable to demonstrate inactivity of this dosing regimen in these tumor types. Numbers of evaluable patients for other tumor types were insufficient to conclusively demonstrate inactivity. Myelosuppression, which was profound and prolonged, was observed. As administered in this study, AZQ has marginal activity and severe myelotoxicity in children with solid tumors.

Adolescent↗
PubMed1990

The prognostic value of testicular biopsy in childhood acute lymphoblastic leukemia: a report from the Childrens Cancer Study Group.

One of the objectives of Childrens Cancer Study Group (CCSG) study 141 (CCG-141) was to determine the frequency of occult testicular leukemia (TL) after 3 years of disease-free survival (DFS) and to retreat boys with occult TL to prolong their subsequent DFS. Of the 494 boys entered on study, 255 (51.6%) were in complete continuous remission (CCR) 3 years after entering remission and an additional eight were in CCR 3 years after localized extramedullary relapse and retreatment; 263 boys were eligible for testicular biopsy. Elective testicular biopsy was performed on 235 (89.4%) boys. Of the 204 (86.8%) boys with negative biopsies, 175 (85.8%) remained in CCR 10 to 12 years after diagnosis and 25 (12.3%) relapsed, 11 (44%) of whom died. Isolated overt TL occurred in four (2.0%) and all remained in CCR 22+ to 60+ months after re-treatment. Of the 26 boys with occult TL, 16 (62%) remained in CCR. Ten (38%) relapsed despite local testicular irradiation and systemic re-treatment; six of the 10 died. Of the 26 boys who did not undergo biopsy, 21 (80.8%) remained in CCR; two (7.7%) developed isolated overt TL. DFS after testicular biopsy was significantly better in boys without occult TL (P = .001). Occult TL after 3 years of CCR represents aggressive minimal-residual disease and carries a worse prognosis than absence of TL. Initial treatment should be directed at obviating occult and overt testicular relapse. Conventional therapy as used in this study was suboptimal in preventing subsequent bone marrow (BM) relapse and death. If occult TR is identified during or at the end of planned therapy, a higher salvage rate may require intensified alternate therapy. As such, testicular biopsies may be clinically useful. Further investigation is limited by the relative rarity of, and the lack of identifying features in boys with occult TL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

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

Testicular function was evaluated in 60 long-term survivors of childhood acute lymphoblastic leukemia (ALL). All the patients were treated on two consecutive Children Cancer Study Group protocols and received identical chemotherapy and either 18 or 24 Gy radiation therapy (RT) to one of the following fields: craniospinal plus 12 Gy abdominal RT including the gonads (group 1); craniospinal (group 2); or cranial (group 3). The median age at the time of their last evaluation was 14.5 years (range, 10.5 to 25.7), which took place a median of 5.0 years (range, 1 to 10.3) after discontinuing therapy. The incidence of primary germ cell dysfunction as judged by raised levels of follicle-stimulating hormone (FSH) and/or reduced testicular volume was significantly associated with field of RT; 55% of group 1, 17% of group 2, and 0% of group 3 were abnormal (P = .002). Leydig cell function, as assessed by plasma concentrations of luteinizing hormone (LH) and testosterone, and pubertal development, was unaffected in the majority of subjects regardless of RT field. These data indicate that in boys undergoing therapy for ALL, germ cell dysfunction is common following testicular irradiation and can occur following exposure to scattered irradiation from craniospinal RT. In contrast, Leydig cell function appears resistant to direct irradiation with doses as high as 12 Gy.

Adolescent↗
PubMed1990

A comparison of four staging systems for localized and regional neuroblastoma: a report from the Childrens Cancer Study Group.

Four major staging systems have been used to estimate the prognosis for children with local and regional neuroblastoma (NBL). Data obtained at diagnosis for 251 neuroblastoma patients from two Childrens Cancer Study Group (CCSG) studies were analyzed according to staging systems of the CCSG, St Jude Children's Research Hospital, the Pediatric Oncology Group (POG), and the Union Internationale Contre le Cancer (UICC) tumor-nodes-metastasis (TNM) system. The most significant variables were found to be age, tumor stage, extent of tumor removal, transgression of the midline by tumor infiltration, and site of primary tumor. Involvement of lymph nodes per se was not a bad prognostic sign unless associated with extension beyond the midline, the latter being the single most important prognostic variable. All four staging systems had value for prognostication and all identified with accuracy the low stage patient (stage I, stage A) who fares well (greater than or equal to 87% survival). The CCSG definition of stages II and III disease discriminated prognostic groups best among the remaining patients, and was able to identify the child with local-regional NBL with poor survival. The estimated 5-year survival rates for children with regional tumor (stage III, IIIA[N]), according to the four systems were 44%, 74%, 74%, and 74% for the CCSG, St Jude, POG, and UICC methods, respectively. We conclude that all four staging systems effectively define good-prognosis patients with localized disease but that the CCSG staging system most accurately identifies patients with regional tumor who have a poor outcome.

Child↗
PubMed1989

Pre- and postconception factors associated with sporadic heritable and nonheritable retinoblastoma.

A matched case-control study of retinoblastoma was conducted by the Children's Cancer Study Group (CCSG) to investigate the hypotheses that postconception exposures affect the risk of the nonheritable (post-zygotic origin) form of this disease and that preconception exposures affect the risk of the sporadic heritable (prezygotic origin) form. Eligible cases were those patients with retinoblastoma diagnosed in 1982-1985 at any of the CCSG member hospitals. Cases were classified as familial heritable, sporadic heritable, or nonheritable based on family history, tumor laterality, and cytogenetic analysis. Telephone interviews of parents of 201 cases and their pair-matched controls selected by random digit dialing were completed. Analysis of possible risk factors for the 67 sporadic heritable cases and the 115 nonheritable cases was performed. (The 19 familial cases were excluded). For the nonheritable group, gestational exposure to X-ray [odds ratio (OR) = 2.3, P = 0.08] and morning sickness medication (OR = 2.8, P = 0.02) and low maternal educational level (OR = 5.5, P = 0.03) were associated with increased risk; anemia (OR = 0.3, P = 0.02) and multivitamin use (OR = 0.4, P = 0.03) during pregnancy and periconceptional use of barrier contraceptive (OR = 0.1, P = 0.02) or spermicide (OR = 0.2, P = 0.02) were associated with decreased risk. In the sporadic heritable group, observations included a negative association with multivitamins during pregnancy (OR = 0.2, P = 0.02) and nonsignificant positive associations with preconception gonadal X-ray (maternal, OR = 2.0, P = 0.30; paternal, OR = 1.8, P = 0.42) and older parental age (case-control difference 1.0-1.2 years, P = 0.24-0.27). Many of the associations support study hypotheses, although the possibility of recall bias and chance findings suggest cautious interpretation.

Case-Control Studies↗
PubMed1989

Histopathology and prognosis in childhood hepatoblastoma and hepatocarcinoma.

To determine the relationship between outcome and histologic type, the authors examined data from 168 cases of hepatoblastoma (HB) and 28 cases of hepatocarcinoma (HC) accrued from children over a 14-year period. After adjustment for stage of disease, there was no significant difference in median survival between HB and HC. Mitotic activity was associated with poor prognosis. Necrosis or vascular invasion did not influence prognosis. In 55 cases of completely resected HB, pure fetal histologic type (PFH) was associated with improved survival when compared with all other histologic patterns of HB (92% versus 57% 24 months' survival; P = 0.02). A prognostic effect of PFH was not demonstrable in incompletely resected HB, but the absence of mitoses and the presence of differentiated mesenchymal elements improved survival. The fibrolamellar pattern of HC demonstrated survival similar to that of the typical pattern of HC. The authors conclude that features consistent with differentiation in HB convey improved prognosis for survival. These observations may be important in designing future therapy for children with hepatic tumors.

Carcinoma, Hepatocellular↗
PubMed1989

A case-control study of risk factors for hepatoblastoma. A report from the Childrens Cancer Study Group.

Parents of 75 children with hepatoblastoma, registered with the Childrens Cancer Study Group, and 75 age-matched controls, who had been identified through random digit dialing were interviewed. No evidence was found to support the primary study hypotheses relating to hepatitis infection, maternal estrogen exposure, alcohol consumption, smoking, or potential sources of nitrosamines. Case mothers were more likely to report occupational exposure to metals (odds ratio [OR] = 8.0, P = 0.01), petroleum products (OR = 3.7, P = 0.03), and paints or pigments (OR = 3.7, P = 0.05). Metal exposures were commonly to welding or soldering fumes, and most occurred daily, before and during the index pregnancy. Petroleum product exposures were predominantly to lubricating oils or protective greases. The only significant paternal exposure was to metals (OR = 3.0, P = 0.01) and the risk with exposure to petroleum products was marginally significant (OR = 1.9, P = 0.06). These findings provide further evidence that occupational exposures may increase the risk of cancer in offspring.

Adult↗
PubMed1989

Maternal drug use and risk of childhood nonlymphoblastic leukemia among offspring. An epidemiologic investigation implicating marijuana (a report from the Childrens Cancer Study Group).

The Childrens Cancer Study Group conducted a case-control study designed to assess in utero and postnatal exposures in children with acute nonlymphoblastic leukemia (ANLL). Analyses were performed for reported maternal use of medications and drugs in the year preceding and during the index pregnancy of the 204 case-control pairs. An 11-fold risk (P = 0.003) was found for maternal use of mind-altering drugs just prior to or during the index pregnancy. Compared with ANLL cases not exposed to marijuana, exposed cases were significantly younger at diagnosis of ANLL (P less than 0.01) and were more often of the myelomonocytic and monocytic subtypes (P less than 0.01). Use of antinausea medication for more than 11 weeks was also associated with a significantly elevated relative risk of 2.81 and a dose-response relationship was noted (P = 0.05 for trend). These results suggest that maternal drug use of marijuana may have an etiologic role in childhood ANLL and may be specific for morphologically defined subgroups.

Adolescent↗
PubMed1989

Improvement in outcome for children with acute nonlymphocytic leukemia. A report from the Childrens Cancer Study Group.

The Childrens Cancer Study Group conducted four therapeutic studies on a total of 1006 children with acute nonlymphocytic leukemia from 1972 to 1983. This report describes the therapeutic strategies of these studies and examines trends in induction rates and long-term outcome over this period. The remission induction rate has changed from 58% in 1972 to 1975 to 80% for the period 1980 to 1983, and the induction mortality dropped from 20% to 6%. Four-year survival probabilities from time of diagnosis have almost doubled from 19% to 36%. Few deaths occurred more than 5 years after diagnosis: children surviving in first remission beyond 5 years had a 92% survival rate and an 86% relapse-free survival rate over the next 5 years. In contrast, median survival after a marrow relapse was less than 6 months and the 6-year survival probability was 4%. The leukocyte count was a significant prognostic factor, and although the mortality for infants was high initially, long-term survival was not decreased.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Frequency of 13q abnormalities among 203 patients with retinoblastoma.

We studied peripheral blood lymphocyte karyotypes of 203 patients with retinoblastoma. Twelve (5.9%) had a constitutional chromosomal abnormality involving 13q, of whom six had unilateral and six had bilateral disease. Two patients had mosaic deletions, eight had nonmosaic deletions, one had a de novo translocation, and one had a 13q14 deletion and a de novo direct insertion (10;6). Of the total, 4.9% of unilateral and 7.5% of bilateral patients had 13q abnormalities. None of 19 familial retinoblastoma patients had a visible cytogenetic abnormality. The unilateral patients with 13q abnormalities represent prezygotically determined (potentially heritable) cases which would have been classified as postzygotic (sporadic) without cytogenetic analysis. The observed 1% frequency of mosaic deletions is lower than that previously reported.

Child↗
PubMed1989

Remission induction in children with acute non-lymphocytic leukemia using cytosine arabinoside and doxorubicin or daunorubicin: a report from the Childrens Cancer Study Group.

Four hundred ninety evaluable patients were treated on an induction regimen consisting of two to four courses of cytosine arabinoside plus an anthracycline. Overall, 78% of patients went into remission, 10% died during induction, and 12% were induction failures. For the first 152 patients, courses consisted of 7 days continuous infusion with cytosine arabinoside (Ara-C, 100 mg/m2) and 3 days of doxorubicin (30 mg/m2). Because of unacceptable toxicity, particularly for children less than 3 years of age, the anthracycline was changed to daunorubicin, and the doses of both induction drugs for children under 3 was reduced. For children aged 3 years and older the change in anthracycline was associated with a significant increase in induction failures (7% to 16%, P = .04) and a decrease in deaths (15% to 8%, P = .09). For younger children, for whom doses were also changed, the effect was greater; Mortality decreased from 29% to 1% (P less than .0001), and the remission induction rate increased from 66% to 88% (P = .005). The therapy modifications also influenced survival following remission induction: Daunorubicin-treated patients, aged 3 years and over, did significantly better than those given doxorubicin (P = .03), but the opposite was seen in younger children (P = .06). Gastrointestinal and skin toxicities and septicemia were significantly more common when doxorubicin was being used, but the extent of myelosuppression was similar for the two anthracyclines.

Age Factors↗
PubMed1989

A phase II study of cisplatin therapy in recurrent childhood brain tumors. A report from the Childrens Cancer Study Group.

Thirty-six children with brain tumors were treated with surgery, radiation and/or adjuvant chemotherapy. After tumor recurrence, cisplatin (60 mg/m2/day IV X 2) was given every three to four weeks. CT scans were used to measure drug response prior to the first, third and fifth courses. Complete and partial responses were demonstrated in nine of 31 evaluable patients. Dose limiting toxicities were renal and auditory. Seven patients developed the syndrome of inappropriate antidiuretic hormone secretion. This study confirms that cisplatin is active in a spectrum of brain tumors.

Adolescent↗
PubMed1989

Tracing expert thinking in clinical trial design.

This paper describes a method for the analysis of the clinical trial design process used by experts. With this procedure, the scientific ideas and their sources can be identified and related to the clinical trial protocol actually prepared by the experts. An example is given using the work of the Intergroup Rhabdomyosarcoma Study Committee (IRS). That committee has been the primary contributor of information dealing with the treatment of rhabdomyosarcoma in children. The IRS-III protocol was used in this analysis of expert behavior because the protocol was adopted by the leading pediatric oncology clinical trial groups in North America and Europe. The analysis showed that the experts rely heavily, for much of the design, on ideas presented in numerical displays in published documents. Further, those aspects of the design which are innovative can be traced and better understood by applying the new procedure.

Clinical Trials as Topic↗