Papers by Dorothy Barnard
Hämatologie und Bluttransfusion, 2001
The primary objective of Children’s Cancer Group (CCG) study 2891 is to improve the event-free su... more The primary objective of Children’s Cancer Group (CCG) study 2891 is to improve the event-free survival (EFS), disease-free survival (DFS) and survival of children with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). The secondary objective to identify prognostically discrete subsets of patients. To achieve these objectives CCG-2891 uses randomized comparisons of 2 induction strategies and 3 post-remission strategies and prospectively examines several patient subsets.
Journal of Pediatric Hematology Oncology, Feb 1, 2007
ABSTRACT Immune thrombocytopenic purpura (ITP) in children is a common pediatric bleeding disorde... more ABSTRACT Immune thrombocytopenic purpura (ITP) in children is a common pediatric bleeding disorder with heterogeneous manifestations and a natural history that is not fully understood. To better understand the natural history of chronic ITP and detect response trends and outcomes of therapy, we conducted a 10-year retrospective survey of children from age 1 to 18 years with a diagnosis of chronic ITP. Data on 198 patients from 8 Canadian Pediatric Hematology/Oncology centers were analyzed. The majority of patients were female (58%), and were previously diagnosed with acute (primary) ITP (85%). The age at diagnosis of chronic ITP ranged from 1.1 to 17.2 years with a mean of 8.2+/-4.4 years. Ninety percent of patients received some form of treatment. Untreated patients had a higher mean platelet count at diagnosis of chronic ITP (P=0.009) despite similarities in mean age at first presentation and mean duration of follow-up. Thirty-four (17%) patients underwent splenectomy. Splenectomized patients tended to be significantly older, had a lower mean platelet count at diagnosis of chronic ITP, and had a longer duration of follow-up. The results from this study are consistent with published reports.
The Journal of Pediatrics, Mar 1, 1983
Pediatric Blood & Cancer, Oct 1, 2009
Pediatric Research, Dec 1, 1979
Blood prematurity coagulation studies prothrombin cydrenogen thrombin newborn
Cancer, Mar 5, 2012
BACKGROUND-Children who are treated for myeloid leukemia associated with Down syndrome (DS) exper... more BACKGROUND-Children who are treated for myeloid leukemia associated with Down syndrome (DS) experience superior survival compared with children who have myeloid leukemia without DS. To maintain excellent outcomes while avoiding toxicity, the Children's Oncology Group (COG) conducted the phase 3 trial COG A2971, the first trial solely designed to provide uniform treatment of myeloid leukemia in North American children with DS. A2971 eliminated 2 induction drugs and 3 months of maintenance therapy from the standard-timing regimen of dexamethasone, cytarabine, 6-thioguanine, etoposide, and rubidomycin/daunomycin (DCTER) used in the previous study (Children's Cancer Group [CCG] 2891). METHODS-COG A2971 was a multi-institutional, nonrandomized, clinical trial that enrolled 132 patients who had DS with either acute myeloid leukemia (n = 91) or myelodysplastic syndrome (n = 41).
Journal of Clinical Oncology, Aug 1, 1993
Childrens Cancer Group (CCG) protocol 2861 was designed to test the feasibility of aggressively t... more Childrens Cancer Group (CCG) protocol 2861 was designed to test the feasibility of aggressively timed induction therapy followed by autologous or allogeneic bone marrow transplantation (BMT) as the sole postremission therapy for newly diagnosed children with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Between April 1988 and October 1989, 142 patients were eligible for study. All patients entered received a timing-intensive five-drug induction of dexamethasone, cytarabine (Ara-C), thioguanine, etoposide, and daunorubicin (DCTER) over 4 days with a second cycle administered after 6 days of rest, irrespective of hematologic status at that time. Most patients subsequently received a second two-cycle induction course. Those who achieved remission were eligible for bone marrow ablative therapy with busulfan and cyclophosphamide, followed by 4-hydroperoxy-cyclophosphamide (4-HC)-purged autologous or allogeneic BMT rescue. One hundred eight (76%) patients achieved remission: 19 (13%) died of complications of the leukemia and/or chemotherapy, and 15 (11%) failed to achieve remission. Seventy-four patients subsequently underwent BMT with either autologous (n = 58) or allogeneic (n = 16) rescue. For patients who received autologous rescue with 4-HC-purged grafts, the actuarial disease-free survival (DFS) rate at 3 years from the day of transplant is 51%, compared with 55% for patients who received allogeneic grafts (P = .92). At 3 years, the overall actuarial survival rate for all 142 patients entered on this study is 45%, with an event-free survival (EFS) rate of 37%. Adverse prognostic factors for outcome included an elevated WBC count or the presence of CNS leukemia at the time of AML diagnosis. Results suggest that aggressively timed induction therapy followed by marrow ablation and BMT rescue with either autologous or allogeneic grafts for children with newly diagnosed AML or MDS is both feasible and effective.
Journal of Clinical Oncology, Sep 15, 2003
To determine the outcome of children with Down syndrome (DS) and acute myeloid leukemia (AML) rec... more To determine the outcome of children with Down syndrome (DS) and acute myeloid leukemia (AML) receiving standard timing chemotherapy without bone marrow transplantation (BMT), with determination of prognostic factors. Patients and Methods: Children with DS and newly diagnosed AML or myelodysplasia were prospectively enrolled on Children's Cancer Group study 2891 (N ؍ 161) and treated uniformly with four standard timing induction courses of dexamethasone, cytarabine arabinoside, 6-thioguanine, etoposide, daunorubicin (DCTER) followed by intensively timed high-dose cytarabine. Results: Children with DS were significantly younger at diagnosis than those without (median age, 1.8 v 7.5 years, respectively; P < .001), with more megakaryocytic leukemia (70% v 6%; P < .001). Higher complete remission rates (91%) were achieved in children with DS than among those without DS (75%; P < .001). Equivalent grade 3 to 4 toxicity (29% v 30%; P ؍ .84) was seen, though children with DS had greater pulmonary toxicity (P < .01) during induction and mucositis during intensification (P ؍ .12). Children with DS had significantly better 8-year event-free survival (EFS; 77% v 21% standard and 40% intensive induction; P < .0001). Multivariate analysis in children with DS revealed that only age at diagnosis of 2 years or older was a risk factor for greater relapse risk (odds ratio, 4.9; P ؍ .006) and worse survival. Children between ages 0 to 2 years (n ؍ 94) had a 6-year EFS of 86%; those from 2 to 4 years (n ؍ 58), 70%; and those older than 4 years (n ؍ 9), 28%. Remission failures were the primary reason for worse 6-year EFSs (1% in those 0 to 2 years v 14% if >2 years; P ؍ .002). Conclusion: Outcome for children with DS and AML is excellent with standard induction therapy, but declines with increasing age.
The Journal of Pediatrics, Dec 1, 1993
Fifty-three children, aged 7 months to 14.4 years and with typical acute immune thrombocytopenic ... more Fifty-three children, aged 7 months to 14.4 years and with typical acute immune thrombocytopenic purpura and platelet counts &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; or = 20 10(9)/L, were randomly assigned to receive intravenously administered immune globulin G (IVIG), 1 gm/kg per day for 2 consecutive days (n = 19); orally administered prednisone, starting at a dose of 4 mg/kg per day, with tapering and discontinuation of corticosteroids by day 21 (n = 18); or no therapy (n = 16). Both IVIG and prednisone resulted in significantly fewer days with platelet counts &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; or = 20 x 10(9)/L in comparison with no therapy (median, 1 and 2 days vs 4 days; corresponding ranges, 1 to 20 and 1 to 11 days vs 1 to 132 days; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01). Reversal of clinically important thrombocytopenia assessed by the number of days taken to achieve a platelet count of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or = 50 x 10(9)/L was significantly faster in children randomly assigned to receive IVIG (median, 2 days; range, 1 to 34 days) than in those receiving prednisone (median, 4 days; range, 2 to 13 days; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) or no therapy (median, 16 days; range, 2 to 132 days; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Because the risk of intracranial hemorrhage in children with acute immune thrombocytopenic purpura is highest in the group with severe thrombocytopenia, and appears to be restricted to children with platelet counts &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; or = 20 x 10(9)/L, these results support the use of IVIG or high doses of prednisone as initial therapy in children with acute immune thrombocytopenic purpura and severe thrombocytopenia (platelet counts &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; or = 20 x 10(9)/L).
Blood, May 15, 2004
In Children's Cancer Group (CCG) study 2891, patients who were recently diagnosed with acute myel... more In Children's Cancer Group (CCG) study 2891, patients who were recently diagnosed with acute myelocytic leukemia (AML) were assigned randomly to standard-or intensive-timing induction chemotherapy. Patients in first complete remission (CR1) and who had a human leukocyte antigen (HLA)-identical, related donor or a donor disparate at a single class I or II locus were nonrandomly assigned to receive a bone marrow transplant (BMT) by using oral busulfan (16 mg/kg) and cyclophosphamide (200 mg/kg). Methotrexate only was given for graft-versus-host disease (GVHD) prophylaxis. One hundred fifty patients received transplants. Grade 3 or 4 acute GVHD occurred in 9% of patients. Patients younger than 10 years had a lower incidence of grade 3 or 4 GVHD (4.6%) compared with patients 10 years or older (17.4%) (P ؍ .044). Disease-free survival (DFS) at 6 years was 67% and 42% for recipients of intensive-and standardtiming induction therapies, respectively. Multivariate analysis showed that receiving intensive-timing induction therapy (P ؍ .027) and having no hepatomegaly at diagnosis (P ؍ .009) was associated with favorable DFS, and grades 3 and 4 acute GVHD were associated with inferior DFS. Multivariate analysis showed that grades 1 or 2 GVHD (P ؍ .008) and no hepatomegaly at diagnosis (P ؍ .014) were associated with improved relapse-free survival (RFS). Our results show that children older than 10 years are at higher risk for developing severe GVHD; acute GVHD is associated with favorable RFS. (Blood.
Haemophilia, Mar 1, 2004
Summary. The demonstrated benefits of home care for haemophilia include improved quality of life... more Summary. The demonstrated benefits of home care for haemophilia include improved quality of life, less pain and disability, fewer hospitalizations, and less time lost from work or school. Although reduced mortality has not been demonstrated, the substantial increase in longevity since the early 1980s correlates with the introduction of home treatment and prophylaxis programmes. These programmes must be designed and monitored by haemophilia treatment centres (HTC), which are staffed with professionals with broad and complementary expertise in the disease and its complications. In return, patients and their families must be willing to accept the reciprocal responsibilities that come from administering blood products or their recombinant equivalents at home. Patients with inhibitors to factors VIII or IX pose special challenges, but these complications do not obviate participation in home care programmes. Home care was an essential prerequisite to the introduction of effective prophylactic factor replacement therapy. Prophylaxis offers significant improvements in quality of life, but requires a substantial commitment. The use of implantable venous access devices can eliminate some of the difficulty and discomfort of peripheral venous access in small children, but brings additional risks. The future holds the promise of factor concentrates for home use that have longer half‐lives, or can be administered by alternate routes. Knowledge of patient genotypes may allow treatments tailored to avoid complications such as inhibitor development. Gene therapy trials, which are currently ongoing, will ultimately lead to gene‐based treatments as a complement to traditional protein‐based therapy.
Haemophilia, Mar 1, 2004
Summary. Several measures of quality of life (QoL) are available for children with haemophilia. ... more Summary. Several measures of quality of life (QoL) are available for children with haemophilia. However, most are not disease‐specific and few focus on children's perspectives. The purpose of this study was to develop a psychometrically sound measure of QoL that included the perspectives of boys with haemophilia. A list of potential items was developed from the literature, other measures, and input from five discussion sessions with adults with haemophilia, children with haemophilia and their parents and haemophilia nurses. The list was augmented with items generated by three focus groups with children and three focus groups with parents. These groups also prioritized items and recommended a domain structure. Supplemental information was gathered by surveying haematologists. Data from all sources were analysed to reduce the number of items using a two‐step approach, based on rules that weighted the children's priorities most heavily. The remaining items were compiled into a questionnaire that was pilot tested with 10 children and their parents. The total item pool contained 228 potential items. Of these, 33 were removed based on three focus groups and survey responses, 72 were removed after the completion of all focus groups and 46 were removed due to redundancy. This resulted in a 77‐item version of the CHO‐KLAT. Pilot testing identified the need to subdivide two items, resulting in a 79‐item CHO‐KLAT. The CHO‐KLAT is a promising disease‐specific measure of QoL that reflects children's unique perspectives. This child‐centric focus distinguishes the CHO‐KLAT from alternative measures of QoL. Further research will assess the measurement properties of the CHO‐KLAT.
Pediatric Research, Apr 1, 1977
In the newborn ET has been utilized both therapeutically and prophylactically. In spite of freque... more In the newborn ET has been utilized both therapeutically and prophylactically. In spite of frequent ETs done, no studies of platelet-white cell microaggregates (MA) which cause RDS in massively transfused adults have been examined in blood to be used for neonatal ET. The presence of MA in blood used for prophylactic ET may explain some of the discordant results of clinical trials. This study examined coagulation and MA by the Swank filtration pressure method (SFP) in fresh blood (FB), blood stored 96 hours, and buffy coat poor (BCP) reconstituted blood (RBI from 4-day-old packed cells and fresh frozen plasma. Mean results from the 15 units were: YO go K PTT V VIII Plt. Ct. x 103 FB 3T6 4 7. 2 103 84 15 200 96 hr.
Blood, Dec 7, 2006
To assess the impact of minimally differentiated acute myeloid leukemia (AML-M0) morphology in ch... more To assess the impact of minimally differentiated acute myeloid leukemia (AML-M0) morphology in children, we analyzed 2 sequential Children's Cancer Group AML clinical trials. We compared presenting characteristics and outcomes of 82 CCG-2891 and CCG-2961 patients with de novo, non-Down syndrome (DS) AML-M0 with those of 1620 patients with non-M0 AML, and of 10 CCG-2891 patients with DSassociated AML-M0 with those of 179 with DS-associated non-M0 AML. Morphology and cytogenetics were centrally reviewed. The non-DS AML-M0 children had a lower white blood cell (WBC) count (P ؍ .001) than their non-M0 counterparts and a higher incidence of chromosome 5 deletions (P ؍ .002), nonconstitutional trisomy 21 (P ؍ .027), and hypodiploidy (P ؍ .002). Outcome analyses considering all children with non-DS AML demonstrated no significant differences between M0 and non-M0 patients. Analyses restricted to intensive-timing CCG-2891 and CCG-2961 demonstrated comparable complete response (CR) rates (79% and 78%) between non-DS M0 and non-M0 patients. Overall survival (OS) from diagnosis (38% ؎ 14% versus 51% ؎ 3%; P ؍ .160) was not significantly different between the 2 groups. OS from end of induction (45% ؎ 17% versus 63% ؎ 3%; P ؍ .038), event-free survival (EFS; 23% ؎ 11% versus 41% ؎ 3%; P ؍ .018), and disease-free survival (DFS; 31% ؎ 14% versus 52% ؎ 3%; P ؍ .009) were inferior in the M0 group. There was no significant outcome difference between DS-associated AML-M0 and non-M0 children. This study suggests that intensively treated non-DSassociated AML-M0 children have an inferior outcome compared with children with non-M0 AML.
Pediatric Blood & Cancer, 2006
BackgroundIt is important to measure the quality of life (QoL) of boys with haemophilia, because ... more BackgroundIt is important to measure the quality of life (QoL) of boys with haemophilia, because the diagnosis has a significant impact on their lives and this impact fluctuates over time. A disease‐specific measure of QoL is required because the aspects of life that are affected by haemophilia may differ from those assessed by generic QoL measures. This paper describes the final phase of development of a disease‐specific measure of QoL for boys with haemophilia: the Canadian Haemophilia Outcomes‐Kids Life Assessment Tool (CHO‐KLAT).ProcedureA 79‐item version of the CHO‐KLAT was administered to 52 children. A detailed item analysis was conducted to shorten the CHO‐KLAT. The reliability of the revised version was assessed using intraclass correlation coefficients. Validity was assessed by comparing it to the PedsQL and the HaemoQoL.ResultsThe item analysis resulted in the retention of 35 strongly performing items (CHO‐KLAT35). These items were aggregated into the CHO‐KLAT35 summary score. Repeated measures reliability of the CHO‐KLAT35 was 0.74 for children and 0.83 for parents, and the child–parent concordance was 0.75. The validity of the CHO‐KLAT35 was confirmed by a correlation of 0.78 with the Haemo‐QoL and of 0.59 with the PedsQL.ConclusionsThe CHO‐KLAT35 is a reliable and valid measure of QoL for boys with haemophilia. Pediatr Blood Cancer 2006;47:305–311. © 2005 Wiley‐Liss, Inc.
Journal of Pediatric Hematology Oncology, 2003
ABSTRACT
The Journal of Pediatrics, Apr 1, 1992
The Journal of Pediatrics, May 1, 2007
To refine the disease-specific health-related quality of life measure in immune (idiopathic) thro... more To refine the disease-specific health-related quality of life measure in immune (idiopathic) thrombocytopenic purpura (ITP) and to determine its validity, reliability, and responsiveness to change. The initial phase involved cognitive debriefing of 12 families, on the basis of which the measure was modified and then named Kids&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; ITP Tools (KIT). The measure was administered on 2 occasions with the Pediatric Quality of Life Inventory (PedsQL) to 41 patients with acute ITP and 49 patients with chronic ITP, 2 to 18 years old, and their parents (proxy-respondents) at 6 North American centers. Patients with acute ITP had lower scores when compared with patients with chronic ITP (child 64 versus 76, proxy 69 versus 77). The KIT moderately correlated with the PedsQL. Child versus proxy KIT scores showed moderate correlation, and the KIT was superior to the PedsQL. Test-retest reliability was substantial in the child report, but only moderate for the proxy report, similar to the PedsQL. The KIT showed a mean score change of 13 in the child and 15 in the proxy, which was greater than the PedsQL child&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s change of 7 and proxy change of 5. The KIT is valid, with good distinction between acute and chronic ITP and a moderate correlation with the PedsQL. The KIT demonstrated reliability comparable with that of the PedsQL, yet it was more responsive to change. Therefore the KIT can be used as an outcome measure in future clinical trials of childhood ITP.
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Papers by Dorothy Barnard