J A Barnes

Massachusetts General Hospital, Boston, MA, United States

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Publications (3)17.37 Total impact

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    ABSTRACT: ABSTRACT We conducted a phase 1 trial evaluating the oral nucleoside analogue clofarabine in patients with relapsed/refractory non-Hodgkin lymphoma. Patients were treated once daily on days 1 through 21 of a 28 day cycle for a maximum of 6 cycles. The study was conducted with a 3+3 design with ten additional patients treated at the recommended phase 2 dose. Thirty patients were enrolled including indolent B-cell lymphomas (21), mantle cell (6), and diffuse large B-cell lymphoma (3). The primary toxicities were hematologic including grade 3-4 neutropenia (53%) and thrombocytopenia (27%). Three mg was determined to be the recommended phase 2 dose. Tumor volume was reduced in 70% of patients, and the overall response rate was 47% including 27% complete remissions. Responses were seen in indolent B-cell lymphomas and mantle cell lymphoma. At a median follow-up of 17 months, 68% of responding patients remain in ongoing remission. Oral clofarabine was well tolerated with encouraging efficacy in indolent B-cell lymphomas and mantle cell lymphomas, warranting further investigation.
    Leukemia & lymphoma 01/2013; · 2.61 Impact Factor
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    ABSTRACT: Burkitt's lymphoma (BL) is a highly aggressive B-cell non-Hodgkin's lymphoma (NHL) that may be cured with intensive chemotherapy. The addition of the CD20-directed monoclonal antibody rituximab to CODOX-M/IVAC (cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate, alternating with ifosfamide, etoposide, and cytarabine) has not been studied despite efficacy in other aggressive CD20-positive NHLs. Eighty adult BL patients treated with or without rituximab were identified at our institutions. Response rate, overall survival (OS), and progression-free survival (PFS) are calculated. There were fewer relapses in rituximab-treated patients (3 of 40 versus 13 of 40, P = 0.01). There was a trend for improvement in outcome favoring rituximab-containing therapy, with 3-year PFS (74% versus 61%) and 3-year OS (77% versus 66%), although these did not reach statistical significance. Advanced age and central nervous system involvement were associated with poorer OS on multivariable Cox regression analysis, adjusting for treatment, human immunodeficiency virus (HIV) involvement, and risk group. CODOX-M/IVAC, with or without rituximab, is a highly effective regimen for the treatment of adult BL. Rituximab decreased the recurrence rate and showed a trend in favor of improvement in PFS and OS. HIV-infected patients achieved outcomes comparable with those of their non-HIV-infected counterparts.
    Annals of Oncology 02/2011; 22(8):1859-64. · 7.38 Impact Factor
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    ABSTRACT: Early interim positron emission tomography (PET) scans appear powerfully predictive of outcome in Hodgkin's lymphoma (HL), particularly in advanced-stage disease where it has been predominantly studied. The prognostic value of interim PET in limited-stage patients with nonbulky disease has not been well established. Ninety-six patients with nonbulky limited-stage HL were identified who had interim and end-of-treatment PET scans. Response rate, overall survival (OS), and progression-free survival (PFS) were calculated. Four-year PFS and OS for the entire cohort were 88% and 97%, respectively. Interim PET did not predict outcome, with PFS in positive and negative patients 87% versus 91% (P=0.57), respectively. End-of-treatment PET result was predictive of outcome, with PFS of 94% in end PET-negative patients versus 54% in end PET-positive patients (P<0.0001). Four-year OS was 100% in end PET-negative patients and 84% in end PET-positive patients (P<0.0001). Interim PET scans were not predictive of outcome, compared with scans carried out at completion of therapy. End-of-treatment PET was highly predictive of PFS and OS, regardless of interim PET result. In this low-risk patient population, even patients with interim positive PET scans show a favorable prognosis.
    Annals of Oncology 10/2010; 22(4):910-5. · 7.38 Impact Factor