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1.
BMJ Case Rep ; 12(8)2019 Aug 13.
Article in English | MEDLINE | ID: mdl-31413062

ABSTRACT

Peritoneal lymphomatosis represents a rare presentation of any type of non-Hodgkin's lymphoma, with relatively few cases reported in the literature. We present here the case of a 61-year-old man who originally presented with increased abdominal distention associated with shortness of breath and diaphoresis who was found to have evidence of peritoneal carcinomatosis on CT scan. Biopsy confirmed diffuse large B-cell lymphoma, and the working diagnosis was subsequently modified to peritoneal lymphomatosis. The patient was treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab (DA-EPOCH-R) therapy with initially good response. His course was complicated by tumour lysis syndrome. We review the limited literature discussing peritoneal lymphomatosis and discuss the importance of facilitating rapid and efficacious treatment.


Subject(s)
Lymphoma, Large B-Cell, Diffuse/diagnosis , Antineoplastic Combined Chemotherapy Protocols , Diabetes Mellitus, Type 2 , Diagnosis, Differential , Fatal Outcome , Humans , Hypertension , Lymphoma, Large B-Cell, Diffuse/diagnostic imaging , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Middle Aged , Peritoneal Neoplasms/diagnosis , Peritoneal Neoplasms/diagnostic imaging , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/pathology , Tomography, X-Ray Computed
2.
Lancet Haematol ; 2(10): e417-26, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26686043

ABSTRACT

BACKGROUND: Patients with myelodysplastic syndrome or acute myeloid leukaemia who are thrombocytopenic and unable to receive disease-modifying therapy have few treatment options. Platelet transfusions provide transient benefit and are limited by alloimmunisation. Eltrombopag, an oral thrombopoietin receptor agonist, increases platelet counts and has preclinical antileukaemic activity. We aimed to assess the safety and tolerability of eltrombopag for the treatment of thrombocytopenia in adult patients with advanced myelodysplastic syndrome, secondary acute myeloid leukaemia after myelodysplastic syndrome, or de-novo acute myeloid leukaemia. METHODS: We did this multicentre, randomised, placebo-controlled, double-blind, phase 1/2 trial at 37 centres in ten countries in Europe, east Asia, and the Americas. Patients aged 18 years or older who had relapsed or refractory disease or were ineligible for standard treatments; had platelet counts of less than 30 × 10(9) platelets per L; had 10-50% bone-marrow blasts; or were platelet transfusion dependent were randomly assigned (2:1), via a telephone-based interactive voice-response system (GlaxoSmithKline Registration and Medication Ordering System) with a permuted-block randomisation schedule (block size of three), to receive once-daily eltrombopag or matching placebo dose adjusted from 50 mg to a maximum dose of 300 mg. Randomisation was stratified by presence of poor-prognosis (complex) karyotype (presence of at least three abnormalities, or chromosome 7 abnormalities, vs absence) and bone-marrow blast count (<20% vs ≥20%). Patients and study personnel were masked to treatment allocation. The primary endpoint was safety and tolerability, including adverse events, non-haematological laboratory grade 3-4 toxic effects, and changes in bone-marrow blast counts from baseline. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT00903422. FINDINGS: Between May 14, 2009, and May 9, 2013, we randomly assigned 98 patients to receive either eltrombopag (n=64) or placebo (n=34). 63 (98%) patients in the eltrombopag group and 32 (94%) patients in the placebo group had adverse events. The most common adverse events were pyrexia (27 [42%] vs 11 [32%]), nausea (20 [31%] vs 7 [21%]), diarrhoea (19 [30%] vs 6 [18%]), fatigue (16 [25%] vs 6 [18%]), decreased appetite (15 [23%] vs 5 [15%]), and pneumonia (14 [22%] vs 8 [24%]). Drug-related adverse events of grade 3 or higher were reported in six (9%) patients in the eltrombopag group and four (12%) patients in the placebo group. Increases in the proportion of peripheral blasts did not differ significantly between groups. Haemorrhage of grade 3 or higher was reported in ten (16%) patients given eltrombopag and nine (26%) patients given placebo. 21 (33%) patients receiving eltrombopag and 16 (47%) patients receiving placebo died while on treatment. No deaths in patients receiving eltrombopag and two deaths in patients receiving placebo were regarded as treatment related. Post-baseline bone-marrow examinations were done in 40 (63%) patients in the eltrombopag group and 17 (50%) patients in the placebo group. The most common reason for no examination was death before the scheduled 3 month assessment. There were no differences between median bone-marrow blast counts or proportions of peripheral blasts between groups. INTERPRETATION: Eltrombopag doses up to 300 mg daily had an acceptable safety profile in patients with advanced myelodysplastic syndrome or acute myeloid leukaemia. The role of eltrombopag in these patients warrants further investigation. FUNDING: GlaxoSmithKline.


Subject(s)
Benzoates/therapeutic use , Hydrazines/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Myelodysplastic Syndromes/drug therapy , Pyrazoles/therapeutic use , Thrombocytopenia/drug therapy , Adult , Aged , Aged, 80 and over , Double-Blind Method , Female , Humans , Leukemia, Myeloid, Acute/complications , Male , Middle Aged , Myelodysplastic Syndromes/complications , Receptors, Thrombopoietin/agonists , Thrombocytopenia/complications , Treatment Outcome
3.
J Clin Oncol ; 30(17): 2134-9, 2012 Jun 10.
Article in English | MEDLINE | ID: mdl-22547607

ABSTRACT

PURPOSE: This 3-year, prospective, multicenter trial assessed the safety and efficacy of deferasirox in low- or intermediate-1-risk myelodysplastic syndrome (MDS). PATIENTS AND METHODS: Eligible patients had serum ferritin ≥ 1,000 µg/L and had received ≥ 20 units of RBCs with ongoing transfusion requirements. The starting dose of deferasirox was 20 mg/kg/d, with dose escalation up to 40 mg/kg/d permitted. RESULTS: A total of 176 patients were enrolled, and 173 patients received therapy. Median serum ferritin decreased 23% in the 53% of patients who completed 12 months of treatment (n = 91), 36.7% in patients who completed 2 years (n = 49), and 36.5% in patients who completed 3 years (n = 33) despite continued transfusion requirement. Reduction in serum ferritin significantly correlated with ALT improvement (P < .001). Labile plasma iron (LPI) was measured quarterly during the first year of the study. Sixty-eight patients (39.3%) had elevated LPI at baseline. By week 13, LPI levels normalized in all patients with abnormal baseline level. Fifty-one (28%) of 173 patients experienced hematologic improvement by International Working Group 2006 criteria; of these, only seven patients received growth factors or MDS therapy. Over the 3-year study, 138 (79.8%) of 173 patients discontinued therapy, 43 patients (24.8%) because of adverse events or disease progression and 23 patients (13.2%) because of abnormal laboratory values. The most common drug-related adverse events were gastrointestinal disturbances and increased serum creatinine. There were 28 deaths, none of which were considered related to deferasirox. CONCLUSION: Deferasirox reduces serum ferritin and LPI in transfusion-dependent patients with MDS. A subset of patients had an improvement in hematologic and hepatic parameters.


Subject(s)
Benzoates/pharmacology , Erythrocyte Transfusion/methods , Ferritins/blood , Iron Chelating Agents/pharmacology , Iron/blood , Myelodysplastic Syndromes/blood , Myelodysplastic Syndromes/drug therapy , Triazoles/pharmacology , Adult , Aged , Aged, 80 and over , Deferasirox , Female , Hemochromatosis Protein , Histocompatibility Antigens Class I/genetics , Humans , Male , Membrane Proteins/genetics , Middle Aged , Mutation , Prospective Studies , Time Factors , Treatment Outcome
4.
J Oncol Pract ; 6(2): 56-9, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20592775

ABSTRACT

A report on how accurately physicians used methodology in a nationwide demonstration by the Centers for Medicare & Medicaid Services to enhance quality of cancer treatment and care and promote evidence-based practices.

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