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V J Land

Publications and source records attributed to V J Land.

At least 37 records · Page 2Linked to original sources
PubMed1991

A pilot study of intermediate-dose methotrexate and cytosine arabinoside, "spread-out" or "up-front," in continuation therapy for childhood non-T, non-B acute lymphoblastic leukemia. A Pediatric Oncology Group study.

One hundred six children with newly diagnosed non-T-, non-B-cell acute lymphoblastic leukemia (ALL) were treated in a Pediatric Oncology Group (POG) pilot study in which six courses of intermediate-dose methotrexate (MTX) and cytosine arabinoside (Ara-C) (1 g/m2 each) were added to a "backbone" of standard continuation therapy. The dose and sequence of MTX/Ara-C administration were based on a preclinical model that demonstrated synergism between MTX and Ara-C. Poor-risk patients (n = 49) were assigned to "up-front" therapy, in which the MTX/Ara-C courses were administered during the initial 15 weeks of remission. Standard-risk patients (n = 57) were assigned to "spread-out" therapy, in which the MTX/Ara-C courses were interspersed at 12-week intervals within continuation treatment. Toxicity after intermediate-dose MTX/Ara-C, principally neutropenia and fever, was judged significant but manageable. Unexpectedly, the incidence of fever and neutropenia less than 500/mm3 was greater after "spread-out" therapy (38%) than after "up-front" therapy (6%). At 4 years, the Kaplan-Meier estimate of event-free survival (EFS) is 71% (+/- 7%) for standard-risk patients and 53% (+/- 8%) for poor-risk patients. The results of this pilot study support the use of intermediate-dose MTX/Ara-C in additional studies.

Adolescent↗
PubMed1991

Clinical characteristics and treatment outcome of childhood acute lymphoblastic leukemia with the t(4;11)(q21;q23): a collaborative study of 40 cases.

The t(4;11)(q21;q23) chromosomal abnormality was identified in 40 (2%) of 1,986 children with newly diagnosed acute lymphoblastic leukemia (ALL). This translocation was associated with female sex (63%), age less than 1 year (60%), hyperleukocytosis (median leukocyte count, 156.5 x 10(9)/L), CD10-/CD19+ B-precursor cell immunophenotype, and myeloid-associated antigen (CD15) expression (63%). Nearly all cases had at least some CD24- blast cells. The CD10-/CD15%/CD19+/CD24/+ phenotype was found in 20 of the 32 t(4;11) cases tested. None of the 40 cases had the cytogenetic finding of hyperdiploidy greater than 50, which is a favorable prognostic feature. For clinical comparison, the t(4;11) cases were divided into three groups according to age at diagnosis: less than 1 year (n = 24), 1 to 9 years (n = 8), and greater than or equal to 10 years (n = 8). Compared with older patients, infants were more likely to have initial central nervous system leukemia (P = .05) and less likely to have pre-B-cell ALL (P = .05). Complete continuous remission has been maintained in only 7 of 24 infants and 2 of 8 patients aged greater than or equal to 10 years, in contrast to 7 of 8 children in the intermediate age group (P = .048). These findings suggest that the t(4;11) is an adverse prognostic feature in these two age groups.

Adolescent↗
PubMed1991

Remission induction and continuation therapy in children with their first relapse of acute lymphoid leukemia. A Pediatric Oncology Group study.

Between January 1979 and April 1983, 113 children undergoing their first relapse of acute lymphoid leukemia (ALL) at any site were registered in Pediatric Oncology Group study 7834; 98 were eligible and evaluable. In addition to radiotherapy administered to sites of local relapse, induction consisted of vincristine, doxorubicin, and prednisone (VAP) chemotherapy. Continuation therapy consisted of triple-drug intrathecal therapy and regimens of 6-thioguanine and cytarabine alternating with vincristine, prednisone, cyclophosphamide, and cytarabine. Randomization in continuation was between VAP pulses or no pulse, regardless of the site of relapse. This report provides long-term follow-up of these patients. Thirty-two of 39 children with bone marrow involvement achieved a complete response (CR). Only one of these is alive in an unmaintained remission, a child who did not have an initial CR. Thirty-four of 36 evaluable children with central nervous system involvement as the site of relapse achieved CR. Of these ten are alive; eight are in continuing CR. Nineteen of 20 boys with testicular relapse achieved CR. Of these, 14 are still alive and not receiving therapy, although only one half received treatment in compliance with the protocol described. These results illustrate the possibility of cure of patients who have relapsed with ALL when it is (1) confined to a meningeal or gonadal site and (2) treated vigorously with radiotherapy and a new regimen of systemic chemotherapy. The results reconfirm the need to prevent an initial relapse at any site.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Toxicity trials of amsacrine (AMSA) and etoposide +/- azacitidine (AZ) in childhood acute non-lymphocytic leukemia (ANLL): a pilot study.

Recurrent or induction therapy-resistant ANLL carries a grave prognosis. The combination of AMSA at 100 mg/M2 daily for 5 days and etoposide at 200 mg/M2 daily for the first 3 days of therapy was given to 40 patients with refractory ANLL. An additional 17 patients received those two agents plus azacitidine at a dosage of 250 mg/M2 on days 4 and 5. All three drugs were given as one-hour infusions. All patients had normal electrolyte determinations daily and were on cardiac monitors during the period of drug administration. No arrhythmias were detected in 522 doses of AMSA. Toxicities observed were primarily related to myelosuppression. Forty-nine of the 57 patients required hospitalization for suspected or proven infection. Nausea/vomiting and mucositis were the next most commonly occurring toxicities. Responses were seen in 22 patients.

Adolescent↗
PubMed1990

Near-triploid and near-tetraploid acute lymphoblastic leukemia of childhood.

Cytogenetic and DNA flow cytometric analyses of leukemic cells from 1,971 children with newly diagnosed acute lymphoblastic leukemia (ALL) identified stem lines with modal chromosome numbers greater than 65 in 26 patients (1.3%). Near-triploidy (66 to 73 chromosomes) was found in six cases and near-tetraploidy (82 to 94 chromosomes) in 20. A striking morphologic finding was the presence of clumped chromatin with grooved nuclei or Rieder cell formation in 20 cases. Other than a slight excess of the pre-B immunophenotype, the near-triploid cases did not appear to differ substantially from the general ALL population in clinical features. In contrast, near-tetraploid cases were more often associated with a T-cell immunophenotype (47% v 14%, P less than .001) and L2 morphology (30% v 22%, P less than .01), and were older at diagnosis (median age, 8.6 v 4.8 years, P = .01) than cases with other ploidies. Moreover, an unusually high proportion of near-tetraploid cases tested (6 of 15) expressed one or more of the myeloid-associated antigens CD13, CD15, and CD33. Despite the use of contemporary intensive chemotherapy and short follow-up for most patients, 6 of the 20 near-tetraploid cases have relapsed or died. This study suggests that the near-tetraploid subtype differs from other cases of hyperdiploid greater than 50 ALL, which have been associated with a favorable prognosis.

Adolescent↗
PubMed1990

Clinical presentation, karyotypic characterization, and treatment outcome of childhood acute lymphoblastic leukemia with a near-haploid or hypodiploid less than 45 line.

Cytogenetic and DNA flow cytometric analyses of leukemic cells from 2,184 children with newly diagnosed acute lymphoblastic leukemia (ALL) identified 27 cases (1.2%) that had a hypodiploid line with fewer than 45 chromosomes per cell. Had cytogenetic techniques been used alone, seven cases would have been missed, compared with five if only flow cytometry had been used. For comparative purposes, the 27 cases were divided into three groups: near-haploid (n = 10), hypodiploid 30-40 (n = 9), and hypodiploid 41-44 (n = 8). Blast cells from patients with near-haploid ALL lacked structural chromosomal abnormalities; showed nonrandom retention of two copies of chromosomes 8, 10, 14, 18, 21, and the sex chromosomes; and had a second leukemic line with exactly twice the number of chromosomes or DNA content. Karyotypic analysis of the hypodiploid 30-40 and hypodiploid 41-44 groups disclosed structural abnormalities in the stemline or sideline of most of the well-banded cases; those in the latter group were similar to findings in cases with 45 chromosomes. As in the near-haploid group, chromosome 21 and the sex chromosomes were preferentially retained in the hypodiploid 30-40 and 41-44 cases. Except for a slight excess of female patients in the near-haploid group and an older age at diagnosis in the hypodiploid 30-40 cases, there were no initial clinical features that distinguished these patients from the general ALL population. Despite intensive treatment and short follow-up, 17 of the 27 patients have relapsed. This study suggests that the poor treatment responsiveness of hypodiploid ALL is not limited to the more than 80% of the patients who have 45 chromosomes per leukemic cell and demonstrates that cytogenetic and flow cytometric analyses are complementary in the evaluation of children with ALL.

Aneuploidy↗
PubMed1990

Prognostic significance of CD34 expression in childhood B-precursor acute lymphocytic leukemia: a Pediatric Oncology Group study.

We studied the blasts from 795 children greater than 1 year of age with newly diagnosed, untreated B-precursor acute lymphoblastic leukemia (ALL) for expression of the hematopoietic stem cell-associated antigen CD34. All cases were confirmed as B-lineage lymphoblastic leukemia by virtue of expression of CD19 and/or CD22, lack of T-cell antigens, and lack of surface-membrane immunoglobulin (Ig). The CD34 antigen was present in at least 10% of blast cells in 587 (73.8%) of the patients. There was no significant difference in presenting clinical characteristics between CD34+ and CD34- patients save for an increased incidence of CNS involvement at diagnosis in the latter. Patients with CD34+ leukemia were more likely to have blasts expressing CD22, CD9, and CD13 antigens but were less likely to coexpress CD20. Patients with pre-B (cytoplasmic mu) ALL were significantly more likely to lack CD34 on their blasts, while children with hyperdiploid ALL were more likely to be CD34+. Although remission induction rates were not significantly different between patients with CD34+ and CD34-ALL (P = .23), event-free survival was shorter for patients with CD34- leukemia (P = .0014). Even though CD34 expression was associated with certain other known prognostically favorable variables including hyperdiploidy and lack of cytoplasmic Ig, it had an independent favorable effect on treatment outcome, even after adjusting for competing prognostic factors.

Antigens, CD↗
PubMed1989

Multiple plasma exchanges successfully maintain a young adult patient with Crigler-Najjar syndrome type I.

Plasmapheresis has been shown to reduce total and free bilirubin levels in acute exacerbations of Crigler-Najjar syndrome, type I (CNS-TI), but its effectiveness in long-term management has not been reported. An 18-year-old (yo) male with CNS-TI, who required prolonged daily high-intensity phototherapy to prevent cerebral nervous system symptoms, developed increasingly frequent bouts of confusion, nausea, and vomiting associated with free bilirubin concentrations (fbcs) greater than 10-15 nmol/L. Pending consideration of orthotopic liver transplantation, plasma exchange (approximately 3 liters per procedure) was begun in 12/84 using the IBM/COBE 2997 with 5% albumin as replacement fluid. Frequency of treatments was guided by twice weekly fbcs, with plasma exchange for fbc greater than 10-15 nmol/L. Pre-exchange and postexchange fbcs ranged from 27.5 to 11 nmol/L and 9.2 to 2 nmol/L, respectively. Seventy-two exchanges were performed over a 28 month period. Irreversible CNS damage did not occur, and the patient underwent successful liver transplantation in April of 1987, with complete correction of his metabolic disorder. He remains well 18 months following transplantation.

Adolescent↗
PubMed1989

Long-term results in the treatment of acute nonlymphocytic leukemia: a Pediatric Oncology Group Study.

Complete remission (CR), 5-year remission duration (RD), and overall 5-year survival rates are 74%, 28% and 25%, respectively, for previously untreated children with acute nonlymphocytic leukemia diagnosed between 1977 and 1981, following induction therapy with vincristine, doxorubicin and prednisone (VAP), consolidation therapy with 6-thioguanine, cytosine arabinoside (TA) and cyclophosphamide/vincristine/cytosine arabinoside/prednisone (COAP), and maintenance therapy of alternating TA and COAP with or without VAP pulses. Approximately 20% are free of their disease for more than 5 years. High white blood cell counts (WBC) at diagnosis and M3 and M6 morphology were associated with lower CR rates, while M5 morphology was associated with higher CR rates. Patients with M1 morphology had shorter remission duration as compared to those with M4 or M5 morphology. Low WBC and age between 2 and 10 years at diagnosis were associated with longer remission durations and survival. Patients with M4 morphology also survived longer. The observed CR rates are comparable to other studies initiated at the same time as this study but survival is less than those reported more recently. Low WBC at diagnosis and M4/M5 morphology may identify relatively favorable prognostic groups.

Adolescent↗
PubMed1989

Isolated thrombocytopenia in children with acute lymphoblastic leukemia: a rare event in a Pediatric Oncology Group Study.

To determine how many children with acute lymphoblastic leukemia were initially referred to a pediatric hematologist because of isolated significant thrombocytopenia ([platelet count less than 50,000/mm3] and an otherwise normal complete blood cell count and physical findings), a retrospective review of the Pediatric Oncology Group's charts was undertaken. Review of the records of 2239 children enrolled in the past two acute lymphoblastic leukemia protocols showed that none of these children had significant thrombocytopenia with no other hematologic or physical manifestations of acute lymphoblastic leukemia when they were first seen by the hematologist. The results suggest that routine bone marrow aspiration in the child with isolated thrombocytopenia may be unnecessary to rule out acute lymphocytic leukemia.

Child↗
PubMed1987

Toxicity evaluation of dihydroxyanthracenedione (DHAD) in combination with cytosine arabinoside (Ara-C).

To determine optimal dosage, Dihydroxyanthracenedione (DHAD) was given once daily for 3 days at dosage levels of 6, 7, 8, and 10 mg/m2 in combination with a 7-day continuous infusion of cytosine arabinoside (Ara-C). Nineteen of 20 children with leukemia who received these agents developed fever requiring hospitalization. There were 4 deaths-2 due to proven infection. One patient developed nonfatal cardiotoxicity. No other significant toxicity was noted. Responses were seen in 7 of 20 patients. The recommended DHAD dosage was 8 mg/m2/day when given in combination with Ara-C.

Adolescent↗
PubMed1986

Second or subsequent remission with a disease-free survival of 5 years or longer in acute lymphocytic leukemia of childhood: results of a national survey.

A national survey was conducted to determine the number of children with acute lymphocytic leukemia who have survived 5 years or longer in their second or subsequent remission. Seventy-two such patients were identified. The clinical and laboratory characteristics of these patients as well as their therapy are described. It is concluded that long-term second or subsequent remission may occur more frequently than previously appreciated.

Child↗
PubMed1985

Comparison of maintenance treatment regimens for first central nervous system relapse in children with acute lymphocytic leukemia. A Pediatric Oncology Group study.

Eighty-seven children with central nervous system (CNS) leukemia were randomized to receive either induction intrathecal chemotherapy (ITC) and cranial irradiation (CRT) plus maintenance ITC, or induction ITC and craniospinal irradiation (CSpRT) with no maintenance ITC. ITC consisted of six weekly injections of methotrexate, hydrocortisone, and arabinosylcytosine. Also, intensification of systemic induction and maintenance chemotherapy was given. CRT + ITC was given as CRT, 2400 rad in 12 fractions followed by ITC maintenance bimonthly for 2 years. Craniospinal irradiation consisted of CRT + 1400 rad in ten fractions to the spine. Randomization was stratified according to whether CNS leukemia occurred at initial diagnosis of acute lymphocytic leukemia (ALL) (Stratum I, 15 patients), during first bone marrow (BM) remission (Stratum II, 49 patients), simultaneous with first BM relapse (Stratum III, 12 patients), or during second BM remission (Stratum IV, 11 patients). The median follow-up for patients who remain at risk is 15 + months. Eight children (seven on CRT + ITC, one on CSpRT) developed presumed therapy related encephalopathy. In Stratum II, 16 of 29 (55%) patients receiving CRT + ITC experienced adverse events: 3 deaths during continuous complete remission (CCR) and 13 relapses (2 CNS, 1 CNS + BM, 1 BM + testes, and 2 testes) as compared with only 5 relapses in 20 (25%) patients on CSpRT (1 CNS, 1 CNS + BM, 1 BM, and 2 testes). The children on both regimens were comparable for sex, race, age at initial ALL diagnosis, time from ALL diagnosis to first episode of CNS leukemia, systemic therapy both before and after CNS relapse, and number of blasts in the spinal fluid at diagnosis of CNS leukemia. The conclusion is that children with isolated CNS leukemia can achieve prolonged survival with aggressive therapy, and that CSpRT is possibly less toxic and more likely than is CRT + ITC to prevent subsequent BM and testicular relapse (P less than 0.02), but not subsequent CNS relapse (P = 0.7). A possible systemic therapy effect of spinal irradiation is postulated to explain the superiority of CSpRT.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Metastatic chondroblastoma. Report of a fatal case with a review of the literature on atypical, aggressive, and malignant chondroblastoma.

A boy with metastatic and fatal chondroblastoma is presented. Unlike previously published examples of metastatic chondroblastoma, these metastases developed before any operative manipulation of the primary tumor. The histologic characteristics of the primary, metastatic, and locally recurrent tumors were those of a conventional chondroblastoma. A review of published cases of atypical, aggressive, and malignant chondroblastoma is presented with current follow-up information. Although some metastatic chondroblastomas may result from operative manipulation of the primary tumor and are clinically benign, other histologically benign chondroblastomas exist that are capable of pursuing a malignant course. The authors designate these as malignant chondroblastomas. No histologic criteria exist for the separation of these tumors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Evaluation of AMSA in children with acute leukemia. A Pediatric Oncology Group study.

One hundred four children with advanced leukemia in relapse (74 with acute lymphocytic leukemia [ALL] and 30 with acute nonlymphocytic leukemia [ANLL]) received AMSA (4'-(9-Acridinylamino) methanesulfon -m-anisidide) at a dose of 120 mg/m2/day for 5 days (Regimen I) or 60 mg/m2/day for 10 days (Regimen II). Children with ALL were randomized between Regimens I and II (31 and 36 evaluable patients, respectively). All 29 evaluable patients with ANLL were treated on Regimen I. Eighty-eight percent of evaluable patients experienced severe or life-threatening toxicity, with no statistical differences between Regimens I and II. Bacterial or fungal infections (considered life-threatening or fatal) occurred in 17 children with ALL and in 7 with ANLL. Fatal cardiac toxicity occurred in one patient. Complete or partial response occurred in 25.0% (SE = 8.8%), 28.1% (SE = 8.0%), and 25.9% (SE = 8.4%) of evaluable patients on ALL Regimen I, ALL Regimen II, and ANLL, respectively. However, responses were of short duration (16-91 days). There was no significant difference in the duration of survival from treatment start for the two ALL regimens (P = 0.46). The median duration of survival for ANLL patients was significantly longer (P = 0.004) than that of ALL patients treated on Regimens I and II combined. Eighty-two percent of the complete or partial responses (18 of 22) occurred after the first course of AMSA. At the dose schedules investigated, and in a heavily pretreated patient population, AMSA had activity in childhood leukemia. However, the high incidence of severe, life-threatening, or fatal infections meant that the quality and quantity of responses and survival was not commensurate with the toxicity, and that it would be difficult to incorporate this drug into combination chemotherapy with other myelosuppressive agents.

Acute Disease↗
PubMed1984

An analysis of neuroblastoma at a single institution.

Between 1949 and 1978, 119 children with the diagnosis of neuroblastoma or ganglioneuroblastoma were treated at the Washington University Medical Center. Of these, 50 (41%) were alive and disease-free 3 or more years after diagnosis. Important prognostic variables included stage of tumor (Evans staging), histology, age at diagnosis, and site of primary tumor. A stepwise logistic regression analysis of these data has shown that, in order of significance, stage, histology and age at diagnosis are independent prognostic variables. Sex of the patient and nodal status at diagnosis (where known) were not significant prognostic variables. No effects of individual treatment modalities could be detected. This study confirms the overwhelming influence of factors unrelated to treatment in determining the prognosis of neuroblastoma.

Adolescent↗
PubMed1984

Combination chemotherapy with vincristine (NSC-67574), procarbazine (NSC-77213), prednisone (NSC-10023) with or without nitrogen mustard (NSC-762)(MOPP vs OPP) in children with recurrent brain tumors.

Seventy-three patients under 18 years of age with a recurrent central nervous system tumor were randomized to receive combination chemotherapy with MOPP or OPP. Patients were stratified according to the tumor type into four major disease categories: (1) medulloblastoma, (2) astrocytoma and other glioma, (3) ependymoma, and (4) miscellaneous tumors to provide equal distribution of patients for each treatment within each disease category. Evaluation of response was based on computerized brain scan findings. Thirty-five patients received MOPP and 38 received OPP treatment. There were three complete and six partial remissions among patients receiving MOPP and one complete and five partial remissions among patients receiving OPP. In addition, six patients on MOPP had stable disease for seven to 21 months. Only two patients on OPP had stable disease(6 and 36 months). Most of responses in both treatment regimens occurred in patients with medulloblastoma and astrocytoma. Median duration of remission was nine months for the MOPP and 11 months for the OPP. Two patients on MOPP regimen had fatal myelosuppression. Although the more toxic MOPP regimen produced more responses than OPP in children, differences in the duration of response or survival were not statistically significant (P = .79 and P = .84, respectively).

Adolescent↗