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Biomedical subjects

J V Simone

Publications and source records attributed to J V Simone.

At least 19 recordsLinked to original sources
PubMed1992

Impact of three methods of treatment intensification on acute lymphoblastic leukemia in children: long-term results of St Jude total therapy study X.

Long-term follow-up observations are reported on 427 patients who received one of three different intensified therapies in total therapy study X for acute lymphoblastic leukemia (ALL). In the trial for 'standard-risk' ALL, 154 of 309 patients in complete remission were randomized to receive high-dose methotrexate (HDMTX, 1 g/m2) periodically during the first 72 of 120 weeks of standard continuation therapy with 6-mercaptopurine and oral MTX; the remaining 155 patients received 1800 cGy cranial irradiation and intrathecal MTX, followed by 6-mercaptopurine/MTX therapy interrupted from week 36-71 for substitution of two other pairs of drugs. At 9 years of follow-up, significantly higher proportions of patients in the HDMTX group have maintained complete remissions (64 +/- 7%, SE, vs. 52 +/- 6%, p = 0.03), hematologic remissions (73 +/- 6% vs. 62 +/- 6%, p = 0.03), and testicular remissions (94 +/- 5% vs. 80 +/- 8%, p = 0.03); however, the proportion continuing in central nervous system remission has been lower (84 +/- 5% vs 93 +/- 4%, p = 0.02). In the evaluation of teniposide/cytarabine and delayed cranial irradiation for 'high-risk' ALL, 36 +/- 9% of 101 patients are predicted to be event-free survivors at 9 years. Altogether, 217 (51%) of the 427 patients are event-free survivors after at least 7 years of follow-up (median, 9 years); an additional 75 patients are alive and free of leukemia for a median of 6.4 years after successful remission retrieval therapy, boosting the total number of long-term survivors to 292 (68%). These results establish the efficacy of HDMTX for patients with standard-risk ALL and indicate the potential of teniposide/cytarabine for use in multiagent regimens for patients with high-risk disease. The overall survival figure, 68%, affords a benchmark for other studies assessing long-term outcome in ALL.

Child↗
PubMed1991

The survivors of childhood solid tumors.

With the improvement in cancer therapy in recent years, the number of cancer survivors is rapidly increasing. Potential late medical and psychosocial sequelae of cancer therapy are reviewed. A practical guide for the primary health care giver is provided.

Central Nervous System↗
PubMed1991

Risk of adverse events in children completing treatment for acute lymphoblastic leukemia: St. Jude Total Therapy studies VIII, IX, and X.

We studied the frequency, causes, and predictors of adverse events in 624 patients who had completed treatment for acute lymphoblastic leukemia (ALL) in three consecutive total therapy studies (VII, IX, and X, 1972 to 1983). Event-free survival in study X was significantly better overall than that in studies VIII and IX (P less than .0001 by the log-rank test). In study X, 75% of the patients were electively taken off therapy, compared with 54% in studies VIII and IX. However, the risks of having an adverse event during the first 5 years after completion of therapy were remarkably similar: 22% (95% confidence interval, 17% to 29%) in study X versus 24% (20% to 29%) in studies VIII and IX. Bone marrow, testicular, and CNS relapses accounted for the majority of failures in both groups (85% in study X and 92% in studies VIII and IX). Late adverse events consisted largely of hematologic relapses and the development of solid tumors. Black race (P = .001) and leukemia without an anterior mediastinal mass (P = .05) were associated with an increased risk of failure after completion of treatment in the two earlier clinical trials, whereas a lower leukemic cell DNA content (DNA index less than 1.16) was the only predictor of late treatment failure in the more recent trial (P = .019). None of the other presenting features that were examined (eg, age, leukocyte count, and sex) had value as predictors of late failure. Thus, improved treatment altered the impact of specific prognostic factors and the distribution of sites of relapse, but it did not significantly affect the risk of delayed failure.

Adolescent↗
PubMed1991

Curing leukemia.

Explore the source record for details and available documents.

Acute Disease↗
PubMed1985

Central nervous system morbidity following an initial isolated central nervous system relapse and its subsequent therapy in childhood acute lymphoblastic leukemia.

The frequency and types of major CNS toxicity and morbidity were analyzed in 107 children with acute lymphoblastic leukemia (ALL) following an isolated primary CNS relapse. Seventy-nine (73%) have had multiple subsequent marrow or CNS relapses requiring intensive and prolonged therapy to the CNS. Median survival time is two years. Of these 79 patients, two thirds have had one or more types of major CNS toxicity, including epileptiform seizures (35), moderate to severe structural abnormalities (24 of 27 evaluated), major motor disabilities (9), blindness (2), CNS infection (6), cranial nerve palsies (2), and intracranial lymphoma (2). The remaining 28 patients (26%) have had no or one additional CNS relapse and have received therapy for a median of eight years. One half of this surviving group of patients have had major CNS toxicity, including seizures (9), major motor disability (2), and intracranial calcifications (12/19). When neuropsychologic evaluations were compared between the 28 survivors and 50 of their contemporaries who had been in initial continuous complete remission, the CNS survivors had significantly lower Full Scale IQ scores (83 +/- 16 v 99 +/- 14, P = less than .001) with similarly lower measures of academic performance. The relative contributions of meningeal leukemia itself and intrathecal or radiation therapy to these effects cannot be determined. Since major CNS sequelae occurred in the majority of patients who had a primary isolated CNS relapse, and the frequency of CNS relapse is dependent on the efficacy of the method of CNS prophylaxis, the best method of avoiding major CNS sequelae is the most effective form of CNS prophylaxis.

Acute Disease↗
PubMed1985

The importance of an isolated central nervous system relapse in children with acute lymphoblastic leukemia.

We assessed the influence of an initial isolated meningeal relapse on treatment outcome in 839 children with acute lymphoblastic leukemia (ALL) who were admitted to St Jude Children's Research Hospital (Memphis) from mid-1967 through mid-1979. The patients were entered in a series of five clinical trials (Total Therapy Studies V through IX), each designed to test one or more modifications of treatment for ALL. Two groups were compared: 699 children who received CNS prophylaxis (2,400-rad craniospinal irradiation or 2,400-rad cranial irradiation plus intrathecal methotrexate) v 56 who did not. Our results, obtained with a time-dependent covariate model and a matching technique, indicate a 2 to 3.5-fold increase in the risk of hematologic relapse or death among patients who experienced an isolated CNS relapse compared with similar patients (matched for leukocyte count and length of complete remission) who remained free of CNS involvement. Of the 107 children with an initial isolated CNS relapse, 89 (83%) have died or have had a subsequent relapse. There was no detectable difference in the rate of hematologic relapse or death after a CNS relapse between patients who had received preventive therapy and those who had not. We conclude that CNS prophylaxis is important both for the prevention of initial CNS leukemia and for reducing the risk of hematologic relapse or death subsequent to a CNS relapse.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Central nervous system leukemia in children with acute nonlymphoblastic leukemia.

Factors contributing to the development of central nervous system (CNS) leukemia, and the impact of leukemic involvement of this site on subsequent remission length, were determined in 184 children with acute nonlymphoblastic leukemia who had been treated in two successive clinical trials. Preventive CNS therapy in both studies consisted of intrathecal methotrexate (12 mg/m2) given monthly during the first six months of therapy and then every three months until all treatment was stopped. Children with CNS leukemia at diagnosis or relapse were given intrathecal chemotherapy weekly for four weeks and then monthly throughout the remainder of the treatment course. Those continuing in complete remission received 2,400 rad cranial irradiation plus five doses of intrathecal methotrexate before cessation of therapy. The 38 children (20.7%) with CNS leukemia at diagnosis were more likely to have an initial leukocyte count greater than or equal to 25 X 10(9)/L (P = .01) and age less than 2 years (P = .03). The presence of CNS leukemia at diagnosis did not adversely affect the remission induction rate (P = .13) or the length of complete remissions (P = .73). CNS relapse ended initial remissions in 11 patients only and did not preclude subsequent long-term survival, as four of these children are off therapy and in second complete remission for 33+ to 78+ months. Three features at diagnosis were predictive of CNS relapse: monocytic or myelomonocytic leukemia (P = .002); age less than 2 years (P = .0001); and leukocyte count greater than or equal to 25 X 10(9)/L (P = .012). By stepwise Cox regression analysis, each factor was found to have independent predictive value. Despite the apparent effectiveness of intrathecal methotrexate as preventive CNS treatment, our findings indicate that more effective prophylaxis is needed for patients with features predisposing to CNS relapse.

Acute Disease↗
PubMed1979

A reappraisal of the results of stopping therapy in childhood leukemia.

We examined the results of stopping therapy in children with acute lymphocytic leukemia. Of 639 patients in eight consecutive "total therapy" studies, 278 (44 per cent) had all treatment stopped, usually after 2 1/2 years of complete remission. About one fifth (55 of 278) of this group have relapsed, mainly in the bone marrow. The relapse rate for the first year off therapy was higher than that for the next three years (0.16 vs. 0.04, P less than 0.01). The life-table estimates of the four-year relapse rates were 0.24 for all patients and 0.22 for patients receiving adequate central-nervous system prophylaxis. Boys had a higher relapse rate than girls (0.33 vs. 0.15 P less than 0.01). None of the 79 patients who remained in complete remission for at least four years off therapy have yet relapsed. Acute lymphocytic leukemia appears curable in over one third of all newly diagnosed patients who receive treatment for approximately 2 1/2 years.

Antineoplastic Agents↗
PubMed1979

Childhood leukemia as a model for cancer research: the Richard and Hinda Rosenthal Foundation Award Lecture.

Childhood acute lymphocytic leukemia (ALL) is a model for the study of disseminated cancer. It is always disseminated and relatively uniform, it is accessible to repetitive tissue sampling, and we have highly effective chemotherapy for it. The first systematic, controlled trials of cancer therapy were designed for patients with ALL by physicians with the courage and audacity to aim for cure of a "hopeless" disease. The concept of leukemia cell subpopulations in each patient received major clinical support from ALL. The pharmacological sanctuary, typified by the meninges, was first discovered and specifically attacked in ALL. Combination therapy, aggressive therapy during remission, phase-specific therapy, and the interrelationships of phases of therapy were developed first in ALL. Since leukemia cell features, such as T-cell characteristics, correlate with responsiveness to therapy, powerful new tools may be developed to improve the biological specifically of therapy. In addition to the gratifying results of therapy over the past two decades, childhood ALL continuity offers opportunities for biological research as well as improved therapy for ALL and other forms of disseminated cancer.

Adult↗
PubMed1978

Childhood acute lymphocytic leukemia: study VIII.

This controlled study of children with ALL was designed to test the efficacy and toxicity of one-, two-, three- and four-drug therapy during remission and whether more aggressive therapy in the first eight weeks prolongs remission in patients with features associated with a particularly poor prognosis. After inducing remission with prednisone, vincristine and asparaginase, patients received cranial irradiation and IT methotrexate and were randomized to receive: 1--methotrexate alone; 2--methotrexate plus mercaptopurine; 3--same as in group 2 plus cyclophosphamide; and 4--same as in group 3 plus arabinosyl cytosine. Patients with CNS leukemia at diagnosis received IT methotrexate weekly during the induction period and a higher dose of CNS irradiation. Patients with anterior mediastinal enlargement at diagnosis received radiotherapy to the mass during the induction period. Patients who failed to attain bone marrow remission after four weeks of therapy were given daunorubicin and prednisone for 2--4 additional weeks. Of the 282 patients entering this study between January 1972 and November 1975, 268 (95%) attained complete remission and 228 (85%) were randomized to receive continuation chemotherapy with 1, 2, 3 or 4 drugs. In Group 1 (methotrexate alone), 14 of 20 patients relapsed and 9 developed leukoencephalopathy without antecedent CNS leukemia apparently due to higher doses of intravenous methotrexate; in Groups 2, 3 and 4 the results were equivalent, but without leukoencephalopathy in initial CR. The addition of cyclophosphamide and arabinosyl cytosine increased toxicity and complications without demonstrably increasing the leukemocidal effect. In the 40 patients given additional early therapy, the modalties employed in this study did not prolong remission.

Adolescent↗
PubMed1978

Preventive central nervous system irradiation in children with acute nonlymphocytic leukemia.

In this study of children with acute nonlymphocytic leukemia an attempt was made to prevent central nervous system relapse and to determine whether this therapy, coupled with multiagent chemotherapy, would be successful in prolonging durations of complete remission. Central nervous system relapses were prevented by irradiation, although patients who received this therapy did no better than those who did not receive irradiation. A small group of patients received irradiation to the liver and spleen, but this modality also failed to improve the duration of remission. Control of extramedullary leukemia, in this study, failed to improve remission duration because bone marrow relapse was not prevented or delayed. It is unlikely that focal therapy will have a significant impact in acute nonlymphocytic leukemia until longer marrow remissions are achieved.

Acute Disease↗
PubMed1977

Current progress in the treatment of the child with cancer.

Treatment for the child with cancer has increasingly been on a rational rather than an empiric basis. An understanding has developed of the importance for determining clinical and laboratory features present at diagnosis as an aid not only to establish a prognosis but also to design specific treatment regimens. A system has been developed for bringing new chemotherapeutic agents into clinical trials as effectively as possible. Through both clinical and laboratory studies, an increasing understanding of the biology of cancer is being developed. This understanding will provide the basis for more rational treatment programs in the future. Physicians of different specialty interests have learned to work together to develop coordinated programs of treatment so important to optimal care. By far the most important lesson learned, however, is that cancer in children is not of necessity a fatal disease, even when dissemination has occurred. For the furture, it will be necessary to develop even more effective methods of treatment, and research must provide a better understanding of this disease that may offer the opportunity for prevention, which, after all, is the number one interest of the pediatrician.

Adolescent↗