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W P Bowman

Publications and source records attributed to W P Bowman.

At least 19 recordsLinked to original sources
PubMed2000

Description of a multihospital process to develop a care path for the child with acute lymphoblastic leukemia.

This article describes the National Association of Children's Hospitals and Related Institutions (NACHRI) collaborative group process used to create a multihospital care path for the child with acute lymphoblastic leukemia (ALL), and presents strategies for implementation and future direction. Although most children in the United States with cancer are treated according to National Cancer Institute-sponsored comprehensive protocols, there is a wide variation in the implementation of protocols by physicians and hospitals. The development of this care path was based on evidence from the literature, review of practice patterns, expert opinion, and group participant consensus building. The resulting 4-day care path was organized into six categories of care (e.g., assessment practices, diagnostic tests, teaching, and discharge planning). Discharge criteria are stated at the beginning of the care path to emphasize the planning process immediately on admission. Clinical outcomes, skill and knowledge outcomes for the parent and child, and home assessment considerations are also included. Strategies to create change and gain support of various stakeholders toward implementation of the care path are presented. The strength of the resulting care path is possible in large part because the multihospital group process brought professionals from around the country together to discuss, analyze, and reach consensus on the practices related to the child with ALL. The group process enabled the development of a care path that goes beyond a traditional care path developed by a single institution.

Child↗
PubMed2000

Universal inactivation of both p16 and p15 but not downstream components is an essential event in the pathogenesis of T-cell acute lymphoblastic leukemia.

p16/p15 regulate the cell cycle pathway by inhibiting the cyclin Ds-CDK4/6 mediated phosphorylation of pRb. We reported previously that in T-cell acute lymphoblastic leukemia (T-ALL), p16 and p15 were frequently (approximately 70%) inactivated at the DNA level by deletion, mutation, or hypermethylation. Therefore, we hypothesize that inactivation of the cell cycle regulatory pathway may be essential in the pathogenesis of T-ALL, and that the remaining T-ALL with a wild-type p16/p15 gene likely harbor inactivation of these genes at RNA or protein levels. Alternatively, the downstream components of the pathway including CDK4/6, cyclin Ds, and pRb may be deregulated. In 124 primary T-ALLs, we found inactivation of the p16 and p15 genes at the DNA level in 79 (64%) and 64 (52%) samples, respectively. Only 9 of the 45 samples with wild-type p16 expressed p16 protein, whereas the remaining 36 lacked p16 expression at the RNA or protein level. In the 60 samples with an intact p15 gene, only 2 expressed p15 mRNA, and the only one analyzed lacked p15 protein. Overall, the abrogation rates for p16 and p15 at DNA/RNA/protein levels were 93% (115 of 124) and 99% (123 of 124), respectively. Although no alterations were evident in cyclin Ds or CDK4/6, pRb was hyperphosphorylated in the majority of samples investigated. These findings strongly support that both p16 and p15 are specific targets in the deregulation of the cell cycle pathway in T-ALL and that the inactivation of these genes is most likely essential in the pathogenesis of this disease.

Blotting, Western↗
PubMed1997

Treatment of children with epipodophyllotoxin-induced secondary acute myeloid leukemia.

BACKGROUND: Secondary acute myeloid leukemia (AML) after treatment with epipodophyllotoxins is being observed with increased frequency. Therapeutic options are limited for patients with secondary AML and the role of bone marrow transplantation is unclear. METHODS: The authors report the treatment outcome of a cohort of 17 children who developed epipodophyllotoxin-induced secondary AML after therapy for childhood acute lymphoblastic leukemia (ALL) that included etoposide but no irradiation or alkylating agents. Thirteen patients (76%) had 11q23 chromosomal abnormalities that were not present at the initial diagnosis of ALL. RESULTS: Remission induction was attempted in 16 children, with 13 (81%) achieving a complete remission. After consolidation, 9 of these 13 patients received a bone marrow transplant (BMT): 2 with 4-hydroperoxycyclophosphamide-purged autologous marrow, 4 from a human leukocyte antigen (HLA)-identical sibling, 1 from a mismatched parental donor, and 2 from a matched unrelated donor. One additional child underwent allogeneic BMT without an attempt at reinduction. Of the 10 patients who received transplants, 2 were alive and well 27+ and 36+ months, respectively, after BMT. Of the 7 patients who did not receive a transplant, at last follow-up 1 had survived off therapy for 8 months for recurrent ALL whereas 6 died of AML. CONCLUSIONS: These data confirm the poor prognosis of secondary AML after epipodophyllotoxin treatment for childhood ALL. Although patients with secondary AML can achieve a remission, it is usually of brief duration. Allogeneic BMT may offer the possibility of long term remission in some of these patients. More information is needed to better define the risks and benefits of epipodophyllotoxin therapy for childhood ALL.

Acute Disease↗
PubMed1997

Fractionated cylophosphamide and back to back high dose methotrexate and cytosine arabinoside improves outcome in patients with stage III high grade small non-cleaved cell lymphomas (SNCCL): a randomized trial of the Pediatric Oncology Group.

BACKGROUND: The Pediatric Oncology Group (POG) conducted a two-arm, randomized study for the treatment of children and adolescents with stage III small, non-cleaved cell lymphoma (SNCCL). Regimen A, based on the group's previous best treatment for this group of patients, included cyclophosphamide (CTX) and high-dose methotrexate (MTX), as well as vincristine (VCR), prednisone (PRED), and intrathecal (IT) chemoprophylaxis. Regimen B, based on a single institution pilot study (Total B therapy), consisted of two rapidly alternating chemotherapy combinations (CTX, VCR, doxorubicin; MTX, and cytarabine (Ara-C) plus coordinated IT chemotherapy. PROCEDURE: One hundred thirty-four consecutive patients were entered on this study. Seventy patients were randomized to Regimen A, and 64 patients to Regimen B. One hundred and twenty-two patients are eligible for response. RESULTS: Complete remission (CR) was achieved by 81% (52/64) of patients on Regimen A, and 95% (55/58) of patients on Regimen B (p=0.014 one-sided). The two-year event-free survival (EFS) is 64% (SE=6%) on Regimen A, and 79% (SE=6%) on Regimen B (p=0.027 by one-sided logrank test). No patient has relapsed on either regimen after a year from diagnosis, although one patient had a second malignancy at day 371. Severe, but manageable, hematologic toxicity was seen in the majority of patients on both regimens, but was more frequent on Regimen B. CONCLUSIONS: We conclude that the cure rate in stage III SNCCL is significantly improved with the use of a short, six-month chemotherapy regimen of fractionated CTX alternated with coordinated MTX and Ara-C. Results suggest that drug schedule, not simple drug selection, influences outcome.

Adolescent↗
PubMed1997

Serum aminotransferase elevation during and following treatment of childhood acute lymphoblastic leukemia.

PURPOSE: The clinical significance of methotrexate (MTX)-induced hepatic toxicity in children with acute lymphoblastic leukemia (ALL) is poorly defined. Therefore, we conducted a study to determine whether intensive MTX therapy could be safely delivered despite isolated serum ALT elevations in children with ALL. PATIENTS AND METHODS: A total of 243 children with B-precursor ALL were treated with extended pulses of oral divided-dose MTX (dMTX). Serum ALT levels were measured approximately every 7 weeks during therapy, as well as after its cessation. By protocol design, treatment was continued without modification in the presence of ALT elevations if there was no other evidence of liver dysfunction. RESULTS: Of 239 assessable patients, 159 (66.5%) had an ALT level > or = 180 IU/L during therapy and 28 patients (17.6%) had one or more values > or = 720 IU/L. After the completion of therapy, only 17 of 104 assessable patients have had one or more elevated ALT value. Eight of these 17 patients (47%) are hepatitis C virus (HCV)-seropositive. The remaining nine children had subsequent normal or near normal ALT values, and none have clinical evidence of liver disease. CONCLUSION: Our data show that MTX can be safely delivered without dose modification in patients with isolated ALT elevations and that continued therapy does not lead to clinically apparent liver disease. ALT elevations are not a reliable predictor of the presence or extent of hepatic injury, and persistently increased ALT values following the completion of ALL therapy are rare in the absence of HCV infection. Continued MTX therapy allows for increased dose-intensity and may improve outcome in children with ALL.

Adolescent↗
PubMed1996

Intensive oral methotrexate protects against lymphoid marrow relapse in childhood B-precursor acute lymphoblastic leukemia.

PURPOSE: To describe the use of combination chemotherapy, including divided-dose oral methotrexate (dMTX), for children with B-precursor acute lymphoblastic leukemia (ALL). dMTX produced prolonged MTX exposure on an outpatient basis. PATIENTS AND METHODS: Two hundred forty-three patients were treated from January 1986 to May 1992. dMTX was given weekly during consolidation and biweekly for the first 16 months of continuation therapy with mercaptopurine (6-MP) and asparaginase (L-ASP). Initially, etoposide (VP-16) and cytarabine (Ara-C) pulses were included. Treatment continued for 30 months with single-dose weekly MTX replacing dMTX during continuation, part 2. Unexpected acute neurotoxicity was eliminated by the addition of leucovorin. VP-16 and Ara-C were omitted in the face of acute myelogenous leukemia (AML). RESULTS: Two hundred thirty-nine patients entered remission: 16 had a lymphoid marrow relapse, two each with testicular or CNS relapse; 19 a CNS relapse; 16 secondary AML; three other second malignancies; two withdrew for transplant; three died in remission; 16 withdrew because of noncompliance, and nine withdrew with toxicity. Event-free survival (EFS) at 4 years was 73 +/- 4%; 81 +/- 4% for 150 patients with better risk features and 60 +/- 7% for 93 with high-risk features. Lymphoid marrow relapse-free survival in the standard- and high-risk patients was 94 +/- 3% and 86% +/- 6%, respectively. The most common adverse event was secondary AML in the standard-risk group and isolated CNS relapse in the high-risk group. CONCLUSION: This therapy produced an overall EFS similar to other published regimens, but the pattern of failures is very different, with few patients having a lymphoid marrow relapse. These data suggest that highly effective therapy for children with ALL can be delivered on an outpatient basis using a regimen featuring repetitive dMTX.

Administration, Oral↗
PubMed1996

Improved survival for children with B-cell acute lymphoblastic leukemia and stage IV small noncleaved-cell lymphoma: a pediatric oncology group study.

PURPOSE: In an effort to improve outcome for children with advanced B-cell malignancies, a treatment plan based on a published regimen that consists of four courses of fractionated cyclophosphamide (cyclo) given with doxorubicin (doxo) and vincristine (VCR) was intensified by alternating with sequential high-dose methotrexate (MTX) and cytarabine (Ara-C), given in conjunction with intrathecal (IT) MTX and Ara-C. PATIENTS AND METHODS: From October 1986 to October 1992, 133 eligible patients were enrolled: 74 with B-cell (surface immunoglobulin-positive [Slg+] acute lymphoblastic leukemia (B-ALL) and 59 with stage IV small noncleaved-cell lymphoma (SNCCL). The median age was 8 years; there were 103 males and 30 females. Abdominal tumor masses were prominent in 63 cases (33 B-ALL and 30 stage IV SNCCL). RESULTS: Complete remission (CR) was achieved in 66 B-ALL and 57 stage IV patients (93% overall). At 4 years, the estimated event-free survival (EFS) rate is 65% +/- 8% for patients with B-ALL and 79% +/- 9% for those with stage IV SNCCL. Among patients with CNS involvement, 23 of 36 remain in CR (4-year EFS rate, 64% +/- 13%). Relapses occurred early; only 3 patients relapsed after completion of therapy. Thirteen relapses occurred in the marrow, three in the CNS, and six in other sites. Of 11 CNS-positive patients who relapsed, only two recurred primarily in the CNS. CONCLUSION: The results of this study indicate that with intensified chemotherapy an increasing potential for cure exists for patients with B-ALL and stage IV SNCCL.

Adolescent↗
PubMed1994

Treatment of advanced stage diffuse, small non-cleaved cell lymphoma in childhood: further experience with total therapy B.

Prior to the development of intensive treatments for patients with advanced stage B-cell non-Hodgkin's lymphoma (B-NHL), the prognosis for such patients was dismal. A minority of patients attained long-term, disease-free survival. Since 1981, we have treated 28 children with advanced stage B-NHL with an intensive chemotherapeutic protocol, Total Therapy B. This regimen employs cycles of fractionated high-dose cyclophosphamide, doxorubicin, and vincristine alternating with sequential infusions of high-dose methotrexate and escalating doses of cytarabine, in addition to intensive intrathecal therapy. The planned duration of therapy is approximately 6 months. Two patients had B-cell acute lymphoblastic leukemia and 26 had stage III B-NHL; none had CNS involvement. The median age was 7 years. All 28 patients achieved complete remission (CR). Both patients with B-ALL and 21 of 26 with stage III B-NHL remain in CR, with a median follow-up of 51 months. Treatment failures included 3 patients with recurrent or progressive disease, 1 toxic death in CR, and 1 patient who developed a secondary mediastinal T-cell lymphoblastic lymphoma 4 1/2 years after the diagnosis of B-NHL. The 2- and 5-year event-free survival rates were 85.7 +/- 6.6% (SE) and 79.6 +/- 8.5%, respectively. Total Therapy B is a highly effective therapy for children with advanced stage B-NHL without CNS involvement.

Adolescent↗
PubMed1994

Phase I trial of continuous infusion carboplatin and etoposide in children with refractory acute leukemia: a Pediatric Oncology Group study.

PURPOSE: The purpose of this phase I study was to determine the toxicities and response to continuous infusion carboplatin in combination with a fixed dose of etoposide (VP-16) in children with refractory acute leukemia. PATIENTS AND METHODS: From January 1989 to February 1992, 20 patients received 28 courses of treatment. Each course of treatment consisted of a 1-hour intravenous (IV) infusion of VP-16 100 mg/m2/d for 5 days, followed by a 23-hour IV infusion of carboplatin each day. The initial, total 5-day dose of carboplatin (1,000 mg/m2) was escalated by 250- to 375-mg increments to a final, total dose of 1,875 mg/m2 over 5 days. RESULTS: Significant marrow suppression was observed in all patients, with prolonged marrow aplasia at the 1,875-mg/m2 dose level. Grade III diarrhea occurred in three patients; 10 patients experienced life-threatening infection and three had severe thrombocytopenic bleeding. Major marrow responses (two complete remissions and two partial remissions) occurred in four patients (20%). CONCLUSION: In view of the apparent antileukemic efficacy and minimal extramedullary toxicity, carboplatin deserves further study in a phase II trial.

Acute Disease↗
PubMed1993

Common region of ALL-1 gene disrupted in epipodophyllotoxin-related secondary acute myeloid leukemia.

Translocations at chromosomal band 11q23 characterize most de novo acute lymphoblastic leukemias (ALL) of infants, acute myeloid leukemias (AML) of infants and young children, and secondary AMLs following epipodophyllotoxin exposure. The chromosomal breakpoints at 11q23 have been cloned from isolated cases of de novo ALL and AML. Using an 859-base pair BamHI fragment of human ALL-1 complementary DNA that recognizes the genomic breakpoint region for de novo ALL and AML, we investigated two cases of secondary AML that followed etoposide-treated primary B-lineage ALL. In the first case, the translocation occurred between chromosomes 9 and 11 and the breakpoint at 11q23 localized to the same 9-kilobase region of the ALL-1 gene that is disrupted in most of the de novo leukemias. In the second case the translocation was between chromosomes 11 and 19. The breakpoint occurred outside of the ALL-1 breakpoint cluster region.

Child, Preschool↗
PubMed1993

Secondary acute myeloid leukemia in children with acute lymphoblastic leukemia treated with etoposide.

PURPOSE: To describe the occurrence of secondary acute myeloid leukemia (AML) in children with acute lymphoblastic leukemia (ALL) treated with etoposide (VP-16). PATIENTS AND METHODS: Two hundred five consecutive children with early B-lineage ALL were treated according to the Dallas/Fort Worth (DFW) protocol between January 1986 and July 1, 1991. Therapy included a four-drug induction followed by consolidation and continuation phases of nightly oral mercaptopurine (6-MP) and repetitive courses of divided-dose oral methotrexate (dMTX) and asparaginase (L-asp). Three doses of VP-16 and cytarabine (Ara-C) were given during consolidation and later, during continuation, two doses were given 3 to 4 days apart, every 9 weeks. Intrathecal (IT) chemotherapy was given throughout the treatment period. RESULTS: Two hundred three of the 205 patients entered remission. Only eight of these 203 children have had a bone marrow relapse (ALL). However, 10 other children have developed secondary AML 23 to 68 months following the diagnosis of ALL. Overall event-free survival (EFS) at 4 years is 79.3% +/- 5.1%, with a risk of secondary AML at 4 years of 5.9% +/- 3.2%. CONCLUSION: This experience provides strong evidence for a link between epipodophyllotoxin therapy and secondary AML since none of these children received alkylating agent therapy or irradiation. This serious complication raises concern as to the appropriate use of epipodophyllotoxins in the treatment of childhood ALL.

Acute Disease↗
PubMed1992

Unexpected acute neurologic toxicity in the treatment of children with acute lymphoblastic leukemia.

BACKGROUND: Our current protocol for treatment of childhood acute lymphoblastic leukemia (ALL) was designed to assess the efficacy of methotrexate (MTX) plus L-asparaginase and of etopisode (VP-16) plus cytarabine (ARA-C) during intensive consolidation and continuation therapies and to determine the feasibility of intensifying MTX therapy by the use of divided oral doses of MTX. The protocol was associated with unexpected acute neurotoxicity. There are few reports of such toxic effects during therapy for ALL. PURPOSE: This report describes these toxic effects and outlines our successful approach to the problem. METHODS: The standard four-drug induction regimen consisted of vincristine, L-asparaginase, daunorubicin, and prednisone. In consolidation therapy, oral MTX was given in divided doses (dMTX) of 25 mg/m2 every 6 hours four times daily in four weekly courses concomitant with weekly triple intrathecal therapy--MTX, ARA-C, and hydrocortisone--plus one dose of leucovorin 24 hours after triple intrathecal therapy. Consolidation treatment ended with three daily doses of intravenous VP-16 and ARA-C. The first 16 months of continuation therapy included 6-week cycles of dMTX and L-asparaginase, both given every other week for 5 weeks, with 6-mercaptopurine nightly, and then two doses of VP-16 plus ARA-C and one dose of triple intrathecal therapy. RESULTS: Twenty-five of the 138 patients evaluated had acute neurotoxicity. Ten of the first 72 experienced a seizure or episode of transient neurological deficit 9-11 days following the administration of intravenous ARA-C, VP-16, and triple intrathecal therapy. Despite discontinuation of intrathecal ARA-C, which eliminated simultaneous intravenous and intrathecal treatment with ARA-C, acute neurotoxicity was observed in six previously unaffected patients and six of 42 patients treated after the elimination of intrathecal ARA-C. Therefore, as a second amendment, oral leucovorin was given 24 and 36 hours after dMTX and intrathecal MTX in continuation therapy. No acute neurotoxicity has been seen in 24 patients subsequently entered in the study. CONCLUSION: These findings suggest that folate replacement due to administration of leucovorin modulated MTX toxicity and/or modified an interaction among VP-16, ARA-C, intrathecal therapy, and the central nervous system.

Adolescent↗
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

Variant translocations of chromosome 13 in alveolar rhabdomyosarcoma.

In three cases of alveolar rhabdomyosarcoma with variant translocations, two tumors contained an identical translocation, t(1;13)(p36.1;q14); the third tumor contained a t(8;13)(p21;q14). All three patients were 2 years old, markedly younger than the median age for patients with t(2;13)-positive alveolar rhabdomyosarcoma. The alteration of genetic material on chromosome 13 may be of primary importance in the development of alveolar rhabdomyosarcoma.

Child, Preschool↗
PubMed1991

Translocation (3;21)(q26;q22) in secondary leukemia. Report of two cases and literature review.

The authors report two cases of secondary myelodysplasia and acute myeloid leukemia with t(3;21)(q26.3;q22) as the only cytogenetic abnormality in neoplastic bone marrow. This translocation was identified as a rare, recurring, non-random aberration in chronic myeloid leukemia less than five years ago and in secondary acute myeloid leukemia and myelodysplasia in 1990. The known and suspected cases in the literature are reviewed.

Acute Disease↗
PubMed1989

Lipoperoxidation and T-cell leukemia of childhood. Effects of indomethacin.

Serum thiobarbituric acid (TBA) reactivity for lipoperoxidation products was assessed at diagnosis in children with T-cell and common acute lymphocytic leukemia (ALL) and T-lymphoblastic lymphoma. Comparisons were made among these groups and with healthy controls. Mean TBA reactivity (mumol malondialdehyde/L serum) was increased (P less than 0.01) in the T-cell leukemia group versus common ALL and T-lymphoblastic lymphoma patients and controls, respectively. The increase in lipoperoxidation products in T-cell ALL appeared to bear a positive relation to peripheral leukocyte counts, and was accompanied by increased serum prostaglandin E2 (PGE2) levels in most representative cases. Indomethacin added to a childhood T-cell ALL line (SUP-T3), at a concentration known to inhibit prostaglandin synthesis in vitro (i.e., 3 micrograms/mL), effected significant increases in the numbers of natural killer (NK; Leu-11+ and Leu-19+) cells (P less than 0.01) and B-lymphocytes (P less than 0.05), and significant decreases in cell viability (P less than 0.01). Indomethacin may be a useful agent for enhancing the antileukemic immune response in T-cell ALL.

Child↗