Papers by Caroline Hastings
Social Science Research Network, 2022
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Journal of Clinical Oncology, May 20, 2014
10014 Background: Relapsed childhood B-ALL has a poor prognosis. Few risk factors beyond immunoph... more 10014 Background: Relapsed childhood B-ALL has a poor prognosis. Few risk factors beyond immunophenotype, timing, and site of relapse are known to affect outcome. MRD is a powerful predictor of outcome in newly diagnosed ALL, but its significance after relapse is less clear. We report an analysis of MRD and outcome from the AALL0433 protocol for childhood B-ALL with intermediate-risk relapse. Methods: AALL0433 is a Phase 3 study of intermediate-risk relapsed childhood B-ALL, defined as CNS/testicular relapse 36 mo. from diagnosis. Therapy is based upon the AALL01P2 / 9412 platforms. BM MRD was measured by flow cytometry at end-induction; results were blinded to investigators. Only matched family donor SCT was allowed on protocol. 271 eligible patients were enrolled. Outcome by treatment received remains blinded at this time. Results: The 3-yr. EFS/OS for the entire cohort of 271 patients were 60.7 ± 4.6% and 71.3 ± 4.3%, respectively. All 29 patients with isol...
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Journal of Pediatric Hematology Oncology, Aug 1, 1995
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Molecular Genetics and Metabolism, Feb 1, 2012
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Pediatric Blood & Cancer, 2007
Cancer patients undergoing chemotherapy often develop anemia, which can increase the risk for tra... more Cancer patients undergoing chemotherapy often develop anemia, which can increase the risk for transfusions and fatigue. The recombinant erythropoiesis-stimulating agent darbepoetin alfa can effectively treat chemotherapy-induced anemia (CIA) in adults, but limited data are available regarding its use in pediatric cancer patients. The goals of this phase 1, open-label, uncontrolled study were to assess the pharmacokinetic profile and safety of darbepoetin alfa in pediatric patients with CIA. Pediatric patients with nonmyeloid malignancies and CIA received up to six doses of darbepoetin alfa 2.25 mcg/kg subcutaneously. After the first dose, the pharmacokinetic properties of darbepoetin alfa were assessed during a 14-day sampling period. All subsequent doses were given weekly with predose blood samples collected before study drug administration. After a single dose of darbepoetin alfa, the mean (SD) peak serum concentration was 10.5 (3) ng/ml, and the median time to peak concentration was 71.4 hr. Darbepoetin alfa exhibited a mean (SD) terminal half-life of 49.4 (32) hr. Upon repeated weekly administration, no evidence of darbepoetin alfa accumulation was observed though there was high intra- and inter-individual variability. In addition, darbepoetin alfa was well tolerated; some study patients experienced increases in hemoglobin. The pharmacokinetic profile of darbepoetin alfa indicated that it was slowly absorbed and exhibited a long terminal half-life in these pediatric study patients with CIA.
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Pediatric Blood & Cancer, Sep 12, 2016
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Journal of Clinical Oncology, Nov 1, 2009
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Current Hematologic Malignancy Reports, Aug 18, 2010
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British Journal of Haematology, Oct 13, 2014
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Annals of Emergency Medicine, Oct 1, 1991
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Medical and Pediatric Oncology, Aug 29, 2002
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Orphanet Journal of Rare Diseases, Oct 21, 2019
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Cancer-and treatment-related anemia affects many children diagnosed with a variety of malignancie... more Cancer-and treatment-related anemia affects many children diagnosed with a variety of malignancies. The incidence of anemia in children with solid tumors or Hodgkin’s disease at the time of diagnosis has been reported to be 51–74% (Hockenberry et al. 2002). Several pediatric studies report a high incidence of anemia (over 50%) requiring intervention with transfusion in children receiving therapy for Wilms’
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Molecular Genetics and Metabolism, Mar 1, 2023
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Journal of Pediatric Hematology Oncology, Nov 1, 1996
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The Lancet, Dec 1, 2021
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Blood, Nov 16, 2007
Down syndrome patients with ALL (ALL-DS) have unique clinical and biologic features which can mak... more Down syndrome patients with ALL (ALL-DS) have unique clinical and biologic features which can make treatment a challenge particularly in regards to toxicity. In order to evaluate the optimal treatment for ALL-DS with higher risk ALL we compared the outcomes of ALL-DS patients (n=51) enrolled on the Children’s Cancer Group (CCG) 1961 protocol for HR-ALL to those of their non-DS counterparts (n=2001). CCG-1961 was open from November 1996 to May 2002 for patients with ALL age 1–9 years and WBC ≥ 50,000 or age ≥ 10 years with any WBC. Rapid early responders (RER ≤ 25% blasts on day 7 bone marrow after 4 drug induction) were randomized in a 2 × 2 design to receive intensive post-induction intensification therapy (IPII) or standard post-induction intensification therapy (SPII) and 1 or 2 delayed intensification phases. Slow early responders (SER > 25% blasts on day 7 bone marrow) were treated with IPII, and randomized to receive idarubicin or doxorubicin. No up-front therapy modifications were prescribed for DS patients (only for toxicity as per protocol). All DS patients were over 2 years of age. DS patients were more likely to have WBC ≥ 50,000 than non-DS (76% vs 53%) and less likely to have T cell immunophenotype (4% vs 23%), lymphoma syndrome (10% vs 23%) or marked splenomegaly (4% vs 12%) at diagnosis. No differences in gender, race, or extramedullary disease were noted in the DS vs non-DS patients. There were 36 RER DS patients (16 randomized to IPII and 20 SPII) and 16 SER patients. There were 6 deaths in the DS patients: 4 early in induction, 1 in consolidation, and 1 in maintenance. All deaths were associated with toxicity and/or infection and 2 patients had progressive disease. DS patients were more likely to have grade 3–4 stomatitis during intensive treatment phases (15.2% vs 1.8% during induction, 23.1% vs 2.9% during delayed intensification #1). The 5-yr event free survival (EFS) was 69.1% (se 8.4%) for DS patients and 70.4% (se 1.5%) for non-DS patients. The 5-yr overall survival (OS) was equivalent for the two groups: 77.9% (se 7.5%) for DS patients compared to 80.9% (se 1.1%) for non-DS patients. The 5 year death as a first event assessment was 88.2% (se 6.6%) (RHR 2.6) vs 95.5% (se 0.7%) for non-DS patients, consistent with an increased incidence of early toxic deaths in the ALL-DS cohort. IPII therapy for RER DS patients resulted in excellent disease control (0 BM relapses vs 5 with SPII). The 4-yr EFS for the IPII DS patients (RER + SER) was 83.7% (se 6.7%) vs 78.8% (se 11.5%) for the RER DS randomized group only. This difference may be explained by the single event in the 16 SER patients; however the small number precludes a definitive conclusion. In conclusion, HR patients with ALL-DS treated with IPII therapy on CCG-1961 have similar OS and EFS to non-DS patients. These results compare favorably with those of other studies. The early mortality due to toxicity in the DS population does not result in decreased EFS or OS as compared to the non-DS population. IPII therapy is well tolerated and effective in HR ALL-DS, as evidenced by excellent outcomes in the RER and SER groups, and should be considered a reasonable standard of care for this patient population.
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Pediatric Blood & Cancer, Jun 1, 2021
BackgroundNutritional deficiencies in children with cancer at time of diagnosis and during treatm... more BackgroundNutritional deficiencies in children with cancer at time of diagnosis and during treatment may negatively affect disease outcome and increase treatment‐related toxicity. Yet zinc, an essential nutrient important for supporting immune function and known for reducing diarrheal episodes, is rarely assessed in these children.ProceduresFifty children (1 month to 18 years) with recently diagnosed cancer were enrolled in this study. An age and gender matched control group (n = 50) was also recruited. Plasma and urinary zinc, plasma copper, and C‐reactive protein (CRP) levels were measured at baseline, 3, and 6 months following diagnosis. A retrospective review of the toxicity profile was performed in the cohort of children with cancer for the first 4 years after initial diagnosis.ResultsCRP and plasma copper (both acute‐phase reactants) were elevated in patients with cancer compared to controls at baseline, bothp < .03. Plasma zinc levels were not significantly different from controls at baseline, but decreased by 11% in the cancer group over 6 months of treatment, 83.2 ± 15.6 to 74.3 ± 14.8 μg/dl,p = .01. Plasma zinc dropped to deficient levels in 35% of cases over the initial 6 months. Zinc deficiency at 6 months was related to an increased incidence of severe diarrhea during 4 years of follow‐up,p < .001.ConclusionsZinc deficiency is an underrecognized problem among patients undergoing treatment for cancer and is associated with severe diarrhea. Further studies are needed to evaluate causes for zinc deficiency, related effects, and a possible role for zinc supplementation.
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Pediatric Blood & Cancer, Jan 31, 2023
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Papers by Caroline Hastings