Patricia Sheehy

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BACKGROUND Waldenström's macroglobulinemia is an incurable, IgM-secreting lymphoplasmacytic lymphoma (LPL). The underlying mutation in this disorder has not been delineated. METHODS We performed whole-genome sequencing of bone marrow LPL cells in 30 patients with Waldenström's macroglobulinemia, with paired normal-tissue and tumor-tissue sequencing in 10(More)
PURPOSE We examined the activity of bortezomib, dexamethasone, and rituximab (BDR) in patients with symptomatic, untreated Waldenström macroglobulinemia (WM). PATIENTS AND METHODS A cycle of therapy consisted of bortezomib 1.3 mg/m(2) intravenously; dexamethasone 40 mg on days 1, 4, 8, and 11; and rituximab 375 mg/m(2) on day 11. Patients received four(More)
Bortezomib frequently produces severe treatment-related peripheral neuropathy (PN) in Waldenström's macroglobulinemia (WM). Carfilzomib is a neuropathy-sparing proteasome inhibitor. We examined carfilzomib, rituximab, and dexamethasone (CaRD) in symptomatic WM patients naïve to bortezomib and rituximab. Protocol therapy consisted of intravenous carfilzomib,(More)
We report the treatment outcome for 30 relapsed/refractory Waldenström's macroglobulinemia (WM) patients following bendamustine-containing therapy. Treatment consisted of bendamustine (90 mg/m2 I.V. on days 1, 2) and rituximab (375 mg/m2 I.V. on either day 1 or 2) for 24 patients. Six rituximab-intolerant patients received bendamustine alone (n=4) or with(More)
The incorporation of rituximab into various regimens has improved depth of response in Waldenstrom macroglobulinaemia (WM), though the impact of achieving better responses remains to be determined. We examined response depth on progression-free survival (PFS) in 159 rituximab-naïve WM patients who received rituximab-based therapy. The median follow-up was(More)
This study examined the outcome of 248 Waldenstrom macroglobulinaemia (WM) rituximab-naïve patients who responded to a rituximab-containing regimen. Eighty-six patients (35%) subsequently received maintenance rituximab (M-Rituximab). No differences in baseline characteristics, and post-induction categorical responses between cohorts were observed. The(More)
Since the adoption of rituximab, the importance of doxorubicin and vincristine as treatment components remains to be clarified in Waldenström's macroglobulinemia (WM). We therefore examined the outcomes of symptomatic patients with WM who received CHOP-R (cyclophosphamide/doxorubicin/vincristine/prednisone plus rituximab; n = 23), CVP-R(More)
We studied the role of histone deacetylase inhibitors in Waldenstrom's macroglobulinemia (WM). Gene expression profiling of bone marrow CD19+ cells from 30 patients and 10 healthy donors showed overexpression of HDAC4, HDAC9, and Sirt5, with validation of HDAC9 overexpression by q-PCR in primary and BCWM.1 cells. Suberoylanilide hydroxamic acid,(More)
The genetic basis for Waldenström macroglobulinemia (WM) remains to be clarified. Although 6q losses are commonly present, recurring gene losses in this region remain to be defined. We therefore performed whole genome sequencing (WGS) in 30 WM patients, which included germline/tumor sequencing for 10 patients. Validated somatic mutations occurring in >10%(More)
BACKGROUND Hypogammaglobulinemia is common in Waldenström's macroglobulinemia. The etiology of this finding remains unclear, but it has been speculated to be based on tumor-induced suppression of the 'uninvolved' immunoglobulin production DESIGN AND METHODS We evaluated the incidence of IgA and IgG hypogammaglobulinemia in 207 untreated patients with(More)