Gary V. Dahl

Stanford University

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Norman J. Lacayo

Lucile Packard Children's Hospital

Catherine Metayer

University of California, Berkeley

Joseph L. Wiemels

University of Southern California

Adam J. de Smith

University of Southern California

Kyle M. Walsh

Duke University

David K. Kalwinsky

University of Tennessee Health Science Center

Luoping Zhang

University of California, Berkeley

Helen M. Hansen

University of California, San Francisco

Steve Selvin

University of California, Berkeley

Xiaorong Shao

University of California, Berkeley

Cooperative Institutions

Stanford University

171

St. Jude Children's Research Hospital

154

University of California, San Francisco

Stanford Medicine

University of Tennessee Health Science Center

Palo Alto University

Children's Oncology Group

University of Tennessee at Knoxville

Lucile Packard Children's Hospital

Dana-Farber Cancer Institute

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Gene Expression Profiling Predicts Outcome in De Novo Acute Myeloid Leukemia (AML) with Normal Karyotype: Results of Children’s Oncology Group (COG) Study POG #9421.

Blood (2006)

Norman J. Lacayo Maureen M. O’Brien Shweta Jain Soheil Meshinchi R. James Yu

Cog

10.1182/blood.v108.11.1915.1915

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Citations (2)

Anaphylactoid reactions to escherichia coli and erwinia asparaginase in children with leukemia and lymphoma

Cancer (1982)

William E. Evans Anastasios A. Tsiatis Gaston K. Rivera Sharon B. Murphy Gary V. Dahl

The incidence and clinical characteristics of anaphylactoid reactions to intravenous asparaginase were assessed in 196 patients given E. coli asparaginase and 49 patients given Erwinia asparaginase. All patients were given a 50 IU intravenous test dose followed in 30 min by the full dosage (10,000 IU/m2), if no reaction occurred to the test dose. Twenty-nine of 196 patients (14.8%) given E. coli asparaginase had an anaphylactoid reaction, occurring after their first through 12th doses. The probability of an anaphylactoid reaction was significantly greater in those patients not receiving concomitant prednisonevincristine and patients with a hiatus between courses of asparaginase therapy. By logistic regression analysis, other variables such as age, sex, race, diagnosis, total number of doses and concurrent methotrexate or arabinosylcytosine did not contribute significantly to the probability of a reaction. Twentythree of the patients who had reacted to E. coli asparaginase and 26 patients who had not reacted to E. coli asparaginase were subsequently given Erwinia asparaginase. Seven of these 49 patients (14%) had an anaphylactoid reaction. The probability of a reaction to Erwinia asparaginase was significantly related to a prior reaction to E. coli asparaginase, concomitant prednisone-vincristine therapy, total number of asparaginase doses, number of prior E. coli asparaginase doses, and diagnosis, when assessed by a logistic regression model. However, after adjusting for prior reaction to E. coli asparaginase and the total number of asparaginase doses given, the other variables did not contribute significantly to the probability of a reaction. Only 5/29 patients reacting to E. coli asparaginase and 1/7 reacting to Erwinia asparaginase had a reaction to the test dose. None of the reactions were fatal.

Asparaginase

Concomitant

10.1002/1097-0142(19820401)49:7<1378::aid-cncr2820490713>3.0.co;2-z

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Citations (112)

Teniposide plus cytarabine improves outcome in childhood acute lymphoblastic leukemia presenting with a leukocyte count greater than or equal to 100 x 10(9)/L.

Journal of Clinical Oncology (1987)

Gary V. Dahl Gaston K. Rivera A. Thomas Look H. Omar Hustu David K. Kalwinsky

Childhood acute lymphoblastic leukemia with an initial leukocyte count greater than or equal to 100 X 10(9)/L responds poorly to conventional chemotherapy. To extend event-free survival (EFS) in this disease, we devised a protocol that specifies intensive 2-week courses of teniposide (VM-26, 165 mg/m2) plus cytarabine (ara-C, 300 mg/m2), before and immediately after standard 4-week remission induction therapy with prednisone, vincristine, and L-asparaginase. The VM-26 and ara-C combination was also administered intermittently for the first year of continuation treatment with oral 6-mercaptopurine and methotrexate. CNS prophylaxis consisted of periodic intrathecal (IT) injections of methotrexate and delayed cranial irradiation. At a median follow-up of 4 years, the estimated EFS rate for 57 consecutive patients with leukocyte counts of 100 to 1,000 X 10(9)/L was 44%, compared with 10% for matched controls (P less than .001). Remission induction rates in the two groups were similar (82% v 72%, P = .16). Twenty-five patients in the VM-26/ara-C group have survived without adverse events for 2.7 to 6.8 years, whereas only nine of the controls achieved more than a year of EFS. The most common complications during early treatment were acute hyperkalemia from rapid tumor cell lysis and infections due to prolonged marrow aplasia. Continuation chemotherapy was well tolerated. We conclude that VM-26 plus ara-C, added to each phase of an otherwise basic regimen of chemotherapy, will substantially improve prognosis in this high-risk form of childhood leukemia.

Teniposide

Acute lymphocytic leukemia

Mercaptopurine

Regimen

Induction chemotherapy

Chemotherapy regimen

10.1200/jco.1987.5.7.1015

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Citations (45)

Variation by race in presenting clinical and biologic features of childhood acute lymphoblastic leukaemia: Implications for treatment outcome

Leukemia Research (1985)

David K. Kalwinsky Gaston K. Rivera Gary V. Dahl Paula K. Roberson Stephen L. George

10.1016/0145-2126(85)90300-5

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Citations (40)

High‐dose methotrexate improves clinical outcome in children with acute lymphoblastic leukemia: St. Jude total therapy study X

Medical and Pediatric Oncology (1988)

Minnie Abromowitch Judith Ochs Ching‐Hon Pui David K. Kalwinsky Gaston K. Rivera

Abstract High‐dose methotrexate (HDMTX, 1,000 mg/m 2 ) and cranial irradiation/sequential chemotherapy (RTSC) were compared for ability to extend complete remission durations in children with acute lymphoblastic leukemia (ALL). Three hundred thirty patients were enrolled in the study, according to our criteria for standard‐risk ALL: a leukocyte count < 100 × 10 9 /L, no mediastinal mass, no leukemic involvement of the central nervous system (CNS), and blast cells lacking sheep erythrocyte receptors and surface immunoglobulin. Prednisone‐vin‐cristine‐asparaginase induced complete remissions in 95% of the patients, who were then randomized to receive either HDMTX (n = 154) or RTSC (n = 155). HDMTX was administered with intrathecal MTX for the first 3 weeks following remission induction, and then every 6 weeks with daily mercaptopurine (MP) and weekly oral MTX for a total of 18 months. The RTSC regimen consisted of 1,800 cGy cranial irradiation and intrathecal MTX for 3 weeks, followed by MP/MTX, cyclophosphamide/doxorubicin, and teniposide/cytarabine administered sequentially over 18 months. The final 12 months of treatment for both groups was MP and oral MTX; all patients received intrathecal MTX every 12 weeks. With a median follow‐up of 5 years, complete remission durations have been significantly longer among children treated with HDMTX, compared with RTSC ( P = .049) or historical institutional control regimens ( P = .002). Approximately 67% of the patients receiving HDMTX and 56% of those receiving RTSC are expected to be in continuous complete remission at 4 years. Overall, isolated CNS relapse rates were similar ( P = .17) in the two treatment groups, although by newer risk criteria cranial irradiation could be expected to provide better protection in patients with an unfavorable prognosis. These findings indicate that addition of intermittent HDMTX infusions to conventional chemotherapy is an effective method for extending complete remissions in children with ALL.

Teniposide

Acute lymphocytic leukemia

Mercaptopurine

Regimen

10.1002/mpo.2950160502

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Citations (68)

What causes leukemia?

Pediatric Blood & Cancer (2015)

Gary V. Dahl Joseph L. Wiemels

Biostatistics

Associate editor

10.1002/pbc.25526

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Citations (2)

Clinical utility of initial terminal deoxynucleotidyl transferase determinations in childhood acute leukemias.

PubMed (1981)

David K. Kalwinsky William H. Weatherred Gary V. Dahl W. Paul Bowman Susan L. Melvin

Terminal deoxynucleotidyl transferase (TDT) activity was measured in bone marrow lymphoblasts obtained at diagnosis from 168 consecutive patients with childhood acute leukemia. Absolute concentrations of TDT were increased (greater than or equal to 20 units/10(8) blasts) in samples from 98 of 112 assessable patients with acute lymphocyte leukemia (ALL). The values ranged from less than 1 to 1502 units/10(8) blasts with a median of 90 units contrasted with less than 1 to 219 units (median, 2.6 units) in studies of children without leukemia. Results of an immunofluorescence assay were in good agreement with enzymatic detection of the polymerase. Among 115 patients with adequate marrow smears, 105 had TDT-positive blasts. By contrast, in most children with acute myelogenous leukemia, TDT activity was either undetectable or less than 10 units/10(8) blasts. Although the highest levels of TDT were found in blasts with the common ALL phenotype, quantitative determinations were not significantly related to the major immunological subtypes of ALL or to morphological features or periodic acid-Schiff reactivity of the lymphoblasts. The probability that a newly diagnosed case of leukemia would be ALL was 90% if TDT levels were greater than 20 units/10(8) blasts. We conclude that absolute concentrations of TDT, as determined in this study, are of little value in identifying subclasses of ALL. The immunofluorescence assay, which is much less expensive and easier to perform than the enzyme assay, should prove useful for confirming the diagnosis of ALL and for detecting extramedullary sites of leukemic infiltration.

Terminal deoxynucleotidyl transferase

Lymphoblast

Immunofluorescence

Acute lymphocytic leukemia

Source

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Citations (24)

Hematopoietic Stem Cell Transplant for Pediatric Acute Promyelocytic Leukemia

Biology of Blood and Marrow Transplantation (2008)

Christopher C. Dvorak Rajni Agarwal Gary V. Dahl John Gregory James H. Feusner

The optimal form of treatment for children with relapsed or refractory acute promyelocytic leukemia (APL) is unclear. We retrospectively analyzed the results of 32 (11 autologous, 21 allogeneic) hematopoietic stem cell transplants (HSCT) performed for children originally treated on either the Eastern Cooperative Group E2491 Trial or the Cancer and Leukemia Group B C9710 Trial and subsequently diagnosed with relapsed or refractory APL. For autologous HSCT, the incidence of treatment-related mortality (TRM) and relapse was 0% (95% confidence interval [CI], 0%-30%) and 27% (95% CI, 9%-57%), respectively. The 5-year event-free survival (EFS) and overall survival (OS) following autologous HSCT was 73% (95% CI, 43%-91%) and 82% (95% CI, 51%-96%), respectively. For allogeneic HSCT, the incidence of TRM and relapse was 19% (95% CI, 7%-41%) and 10% (95% CI, 2%-30%), respectively. The 5-year EFS and OS following allogeneic HSCT was 71% (95% CI, 50%-86%) and 76% (95% CI, 55%-90%), respectively. There was no significant difference in EFS or OS between autologous and allogeneic HSCT. This data demonstrates that autologous and allogeneic HSCT are both effective therapies for treatment of children with relapsed or refractory APL. Autologous HSCT is associated with a low incidence of TRM, whereas allogeneic HSCT is associated with a low incidence of relapse, suggesting a strong GVL effect against residual APL.

Cumulative incidence

Refractory (planetary science)

10.1016/j.bbmt.2008.04.015

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Citations (39)

Prognostic features in acute megakaryoblastic leukemia in children without Down syndrome: a report from the AML02 multicenter trial and the Children’s Oncology Group Study POG 9421

Leukemia (2012)

Maureen M. O’Brien Xueyuan Cao Stanley Pounds Gary V. Dahl Susana C. Raimondi

Acute megakaryoblastic leukemia

Pediatric Oncology

Multicenter trial

10.1038/leu.2012.223

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Citations (47)

WT1 expression at diagnosis does not predict survival in pediatric aml: A report from the Children's Oncology Group

Pediatric Blood & Cancer (2009)

Suzie A. Noronha Jason E. Farrar Todd A. Alonzo Robert B. Gerbing Norman J. Lacayo

Abstract WT1 is a transcription factor that is aberrantly overexpressed in acute and chronic leukemias. Overexpression of WT1 in pediatric acute myeloid leukemia has been reported, but the prognostic significance is unclear because sample sizes in these studies have been relatively small. WT1 expression was measured by quantitative RT‐PCR in samples obtained at diagnosis from 155 pediatric AML patients treated on a cooperative group protocol. Neither overall survival nor event‐free survival was correlated with WT1 expression. Pediatr Blood Cancer 2009;53:1136–1139. © 2009 Wiley‐Liss, Inc.

Pediatric Oncology

10.1002/pbc.22142

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Citations (31)