Normative values for esophageal functional lumen imaging probe measurements: A meta-analysis.

BACKGROUND: The functional lumen imaging probe (Endoflip™) is increasingly used for evaluation of patients with esophageal symptoms. To improve the interpretation of Endoflip™ in clinical practice, normative values with appropriate cut-off values are required. METHODS: Original clinical studies describing Endoflip™ use for measurements of esophageal motility in healthy adults were considered. Meta-analysis was performed based on published values. RESULTS: A total of 17 articles were included in the systematic review, 15 of which were included in the meta-analysis, representing 154 unique subjects. At 40 ml distention, the 5th-95th and 10th-90th percentiles for esophagogastric junction distensibility index (EGJ-DI) were 1.96-10.95 mm2 /mmHg and 2.36-8.95 mm2 /mmHg, respectively. An EGJ-DI below 2 mm2 /mmHg was found in 5.4%, and below 3 mm2 /mmHg in 20.1% of healthy subjects. At 50 ml distention, the 5th-95th and 10th-90th percentiles for EGJ-DI are 2.86-10.66 mm2 /mmHg and 3.28-9.12 mm2 /mmHg, respectively (below 2 mm2 /mmHg: 0.6%, 3 mm2 /mmHg: 6.3%). The 5th-95th and 10th-90th percentiles for EGJ-DI at 60 ml distention were 3.06-8.14 mm2 /mmHg and 3.33-7.18 mm2 /mmHg, respectively (below 2 mm2 /mmHg: 0.0%, 3 mm2 /mmHg: 7%). A clear cut-off for lower values was identified while a large spread in values was observed for upper limits of normal for EGJ-DI for all filling volumes. CONCLUSIONS: Given these observations, we recommend using a cut-off of 2 mm2 /mmHg for clinical practice, values below can be considered abnormal. Given that 5.4% of the healthy subjects will have an EGJ-DI below 2 mm2 /mmHg at 40 ml, we recommend using the 50 and 60 ml distention volumes. The clinical use of an upper limit for normality of EGJ-DI seems questionable.

High-dose imatinib improves cytogenetic and molecular remissions in patients with pretreated Philadelphia-positive, BCR-ABL-positive chronic phase chronic myeloid leukemia: first results from the randomized CELSG phase III CML 11 "ISTAHIT" study.

BACKGROUND: Imatinib 400 mg/day is the standard treatment for patients with chronic phase chronic myeloid leukemia. Recent reports suggested higher and more rapid cytogenetic and molecular responses with higher doses of imatinib. DESIGN AND METHODS: In this prospective international, multicenter phase III study, 227 patients with pre-treated Philadelphia chromosome-positive, BCR-ABL-positive chronic myeloid leukemia were randomized to a standard-dose imatinib arm (400 mg/day) or a high-dose imatinib arm (800 mg/day for 6 months followed by 400 mg/day as maintenance therapy). In this planned interim analysis hematologic, cytogenetic and molecular responses as well as toxicity were evaluated. RESULTS: Compared to the standard-dose, high-dose imatinib led to higher rates of major and complete cytogenetic responses at both 3 months (major: 21% versus 37%, P=0.01; complete: 6% versus 25%, P<0.001) and 6 months (major: 34% versus 54%, P=0.009; complete: 20% versus 44%, P<0.001). This was paralleled by a significantly higher major molecular response rate at 6 months in the high-dose imatinib arm (11.8% versus 30.4%; P=0.003). At 12 months, the rates of major cytogenetic response (the primary end-point) were comparable between the two arms (57% versus 59%). In contrast to non-hematologic toxicities, grade 3/4 hematologic toxicities were more common in the high-dose arm. Cumulative complete cytogenetic response rates were higher in patients without dose reduction in the high-dose arm (61%) than in the patients with no dose reduction in the standard-dose arm (36%) (P=0.014). CONCLUSIONS: This is the first randomized phase III trial in patients with pre-treated chronic phase chronic myeloid leukemia demonstrating improvements in major cytogenetic response, complete cytogenetic response and major molecular response rates with high-dose imatinib therapy (ClinicalTrials.gov Identifier: NCT00327262).

Imatinib mesylate in the treatment of newly diagnosed or refractory/resistant c-KIT positive acute myeloid leukemia. Results of an Italian Multicentric Phase II Study.

We evaluated safety and efficacy of imatinib (600 mg) in 36 c-KIT+ acute myeloid leukemia patients not amenable to receive conventional chemotherapy. No patient achieved complete remission. One patient obtained a hematologic improvement (platelet increase with transfusion independence). Median overall survival was 3 months (0.5-44+). Non-hematologic toxicity was overall mild.

The efficacy of imatinib mesylate in patients with FIP1L1-PDGFRalpha-positive hypereosinophilic syndrome. Results of a multicenter prospective study.

BACKGROUND AND OBJECTIVES: The hypereosinophilic syndrome (HES) may be associated with the fusion of the platelet derived growth factor receptor a (PDGFRalpha) gene with the FIP1L1 gene in chromosome 4 coding for a constitutively activated PDGFRalpha tyrosine kinase. These cases with FIP1L1-PDGFRalpha rearrangement have been reported to be very sensitive to the tyrosine kinase inhibitor imatinib mesylate. DESIGN AND METHODS: A prospective multicenter study of idiopathic or primary HES was established in 2001 (Study Protocol Registration no. NCT 0027 6929). One hundred and ninety-six patients were screened, of whom 72 where identified as having idiopathic or primary HES and 63 were treated with imatinib 100 to 400 mg daily. RESULTS: Twenty-seven male patients carried the FIP1L1-PDGFRalpha rearrangement. All 27 achieved a complete hematologic remission (CHR) and became negative for the fusion transcripts according to reverse transcriptase polymerase chain reaction (RT-PCR) analysis. With a median follow-up of 25 months (15-60 months) all 27 patients remain in CHR and RT-PCR negative, and continue treatment at a dose of 100 to 400 mg daily. In three patients imatinib treatment was discontinued for few months, the fusion transcript became rapidly detectable, and then again undetectable upon treatment reassumption. Thirty-six patients did not carry the rearrangement; of these, five (14%) achieved a CHR, which was lost in all cases after 1 to 15 months. INTERPRETATION AND CONCLUSIONS: All patients meeting the criteria for idiopathic or primary HES should be screened for the FIP1L1-PDGFRalpha rearrangement. For all patients with this rearrangement, chronic imatinib treatment at doses as low as 100 mg daily ensures complete and durable responses.