Minimal residual disease negativity by next-generation flow cytometry is associated with improved organ response in AL amyloidosis.

Light chain (AL) amyloidosis is caused by a small B-cell clone producing light chains that form amyloid deposits and cause organ dysfunction. Chemotherapy aims at suppressing the production of the toxic light chain (LC) and restore organ function. However, even complete hematologic response (CR), defined as negative serum and urine immunofixation and normalized free LC ratio, does not always translate into organ response. Next-generation flow (NGF) cytometry is used to detect minimal residual disease (MRD) in multiple myeloma. We evaluated MRD by NGF in 92 AL amyloidosis patients in CR. Fifty-four percent had persistent MRD (median 0.03% abnormal plasma cells). There were no differences in baseline clinical variables in patients with or without detectable MRD. Undetectable MRD was associated with higher rates of renal (90% vs 62%, p = 0.006) and cardiac response (95% vs 75%, p = 0.023). Hematologic progression was more frequent in MRD positive (0 vs 25% at 1 year, p = 0.001). Altogether, NGF can detect MRD in approximately half the AL amyloidosis patients in CR, and persistent MRD can explain persistent organ dysfunction. Thus, this study supports testing MRD in CR patients, especially if not accompanied by organ response. In case MRD persists, further treatment could be considered, carefully balancing residual organ damage, patient frailty, and possible toxicity.

The role of macrophages polarization in predicting prognosis of radically resected gastric cancer patients.

Tumour-associated Macrophages (TAM) present two different polarizations: classical (M1) characterized by immunostimulation activity and tumour suppression; alternative (M2) characterized by tumour promotion and immune suppression. In this retrospective study, we evaluated the correlation between the two forms of TAM with survival time in radically resected gastric cancer patients. A total of 52 chemo- and radio-naive patients were included. Two slides were prepared for each patient and double-stained for CD68/NOS2 (M1) or CD68/CD163 (M2) and five representative high-power fields per slide were evaluated for TAM count. The median value of the two macrophage populations density and the median value of M1/M2 ratio were used as cut-off. Twenty-seven patients with M1 density above-the-median had a significantly higher survival compared to those below the median. Twenty-six patients with M1/M2 ratio above the median showed median OS of 27.2 months compared to 15.5 months of the patients below the median. No association between M2 macrophage density and patient's outcome was found. In multivariate analysis, M1/M2 was a positive independent predictor of survival. The M1 macrophage density and M1/M2 ratio, as confirmed in multivariate analysis, are factors that can help in predicting patients survival time after radical surgery for gastric cancer.

Aprepitant for management of severe pruritus related to biological cancer treatments: a pilot study.

BACKGROUND: Itch is a common side-effect of treatment with anti-EGFR antibodies and tyrosine-kinase inhibitors. We designed a pilot single-centre study to assess the effects of aprepitant-a neurokinin receptor inhibitor-for management of severe pruritus induced by biological drugs. METHODS: In this single-group, prospective study, we consecutively enrolled 45 outpatients with metastatic solid tumours treated with biological drugs at the Campus Bio-Medico Hospital of Rome, Rome, Italy, between September, 2010, and November, 2011. We classified patients into two groups: a refactory group, for patients with pruritis refractory to standard treatment, or a naive group, for patients who had not been previously treated for pruritis. Aprepitant (125 mg on day 1; 80 mg on day 3; 80 mg on day 5) was given to patients in the refractory group after at least 1 week of standard systemic treatment. In the naive group, aprepitant was given in the same schedule as the refractory group, after first onset of severe pruritus. Intensity of itch was evaluated by Visual Analogue Scale (VAS) score. The primary endpoint was change in median VAS score. This trial is registered with ClinicalTrials.gov, number NCT01683552. FINDINGS: Median VAS in the refractory group was 8·00 (95% CI 7·93-8·57) at baseline and 1·00 (0·00-2·00) after 1 week of treatment with aprepitant (p<0·0001). In the naive group, VAS score was 8·00 (7·43-8·37) at baseline and 0·00 (0·06-1·08) after 1 week of treatment (p<0·0001). 41 (91%) patients responded to aprepitant (ie, had a >50% reduction in intensity of pruritis) and pruritus recurred in only six (13%) patients. No adverse events related to aprepitant occurred. INTERPRETATION: Aprepitant decreases severe pruritus induced by biological treatments; it is an old drug, widely available, and therefore easy to add to the armamentarium of supportive treatment. Although to our knowledge no other studies of the anti-itch activity of aprepitant are planned, the results of our trial warrant confirmation in phase 2 and 3 trials. FUNDING: None.

The role of S-adenosylmethionine in preventing oxaliplatin-induced liver toxicity: a retrospective analysis in metastatic colorectal cancer patients treated with bevacizumab plus oxaliplatin-based regimen.

BACKGROUND: Hepatotoxicity represents a frequent chemotherapy-related side effect, often associated with course delays, discontinuations, and dose reductions. S-adenosylmethionine (AdoMet) administration is effective in the treatment of a variety of liver injuries, but it has never been evaluated in the prevention of chemotherapy-induced damage. PATIENTS AND METHODS: Seventy-eight patients affected by metastatic colorectal cancer were enrolled. Forty-two patients were treated with bevacizumab and XELOX without administering AdoMet, 32 were treated with the same regimen plus supplementation with AdoMet. Liver enzymes levels were assessed before starting the treatment, and then every therapy cycle, liver toxicity, chemotherapy course delays, discontinuations, and dose reductions due to liver toxicity were recorded. RESULTS: Aspartate aminotransferase (P = 0.02), alanine transaminase (P < 0.001), lactate dehydrogenase (P = 0.008), total bilirubin (P = 0.03), and gamma-glutamyltransferase (P < 0.001) were found to be significantly lower in patients treated with AdoMet than in those who were not. Patients supplemented with AdoMet experimented a lower grade of liver toxicity (P = 0.009) and had a reduced need of course delay (P = 0.042) and dose reduction (P = 0.051). CONCLUSIONS: AdoMet supplementation in patients affected by metastatic colorectal cancer treated with oxaliplatin-based regimen seems to be effective in the prevention of chemotherapy-induced liver injury.

The role of S-adenosyl methionine in preventing FOLFOX-induced liver toxicity: a retrospective analysis in patients affected by resected colorectal cancer treated with adjuvant FOLFOX regimen.

BACKGROUND: Hepatic toxicity is often related to chemotherapy agent administration, and it represents one of the principal causes of dose reduction and chemotherapy delays or discontinuation. S-Adenosyl methionine (AdoMet) supplementation is effective in the treatment of a variety of liver injuries, but it has never been evaluated in the prevention of chemotherapy-induced liver damage. PATIENTS AND METHODS: A total of 105 patients affected by resected colorectal cancer (CRC) were enrolled. Forty-five were treated with FOLFOX IV adjuvant regimen without administering AdoMet, 60 were treated with the same regimen plus supplementation with AdoMet. Liver enzyme levels were assessed before starting the treatment and every therapy cycle. Liver toxicity, chemotherapy course delays, discontinuations and dose reductions due to liver toxicity were recorded. RESULTS: Aspartate aminotransferase (AST) (p < 0.001), alanine transaminase (ALT) (p = 0.003), bilirubin (p = 0.04) and gamma-glutamyltransferase (γ-GT) (p = 0.002) median level at the end of adjuvant therapy were significantly lower in patients treated with Adome. Patients supplemented with AdoMet experimented a lower grade of liver toxicity (p = 0.002) and had a reduced need of course delay (p < 0.0001) and dose reduction (p = 0.031). CONCLUSIONS: The results of our study demonstrate a protective effect of AdoMet supplementation in patients affected by resected CRC treated with FOLFOX IV adjuvant regimen.