Long-Term Remission Achieved by Ponatinib and Donor Lymphocytes Infusion in a Ph+ Acute Lymphoblastic Leukemia Patient in Molecular Relapse After Allogenic Stem Cell Transplant and Dasatinib: A Case Report

Currently, the prognosis of Ph+ acute lymphoblastic leukemia (Ph+ ALL) patients relapsing after an allogenic hematopoietic stem cell transplantation (allo-SCT) remains poor, with few therapeutic options available. Here we present the case of a 32 years old patient with dasatinib-resistant post-transplant molecular relapse of ALL, who received, as second-line therapy, the combination of ponatinib and donor lymphocyte infusion (DLI). The therapy was safe and the patient achieved a sustained minimal residual disease negative disease, still ongoing after 22 months, which was accompanied by several changes in the immune populations distribution within the bone marrow (i.e., the increase in the CD8/CD4 lymphocytes ratio). Our report provides evidence of the efficacy of the third generation TKI inhibitor ponatinib in combination with DLI as second line therapy for Ph+ ALL relapsing after an allo-SCT

The high frequency of spontaneous micronuclei observed in lymphocytes of systemic sclerosis patients: preliminary results.

OBJECTIVE: Aim of the study is to assess the presence of spontaneous chromosome damage in patients affected by limited (lSSc) or diffuse (dSSc) Systemic Slerosis, using the micronucleus (MN) assay.METHODS: We evaluated MN frequency in cultured peripheral lymphocytes of 18 SSc and in a group of 20 healthy controls. Patients were also classified as ACA+, Scl70+, FAN+ according to the presence of the specific anti-nuclear antibodies. We also explored the hypothesis that the extent of cytogenetic alteration might be related to the severity of the pathological condition and/or to the immunological profile.RESULTS: Compared to controls, the patient group as a whole showed significantly higher MN frequencies (10.8+/-4.5 vs. 27.8+/-13.7, p<0.001). No correlation was found between spontaneous chromosome damage and severity of the disease, being MN frequency 33.1+/-17.0 and 19.8+/-2.7 in lSSc and dSSc, respectively. Interestingly, ACA+ subjects displayed the highest MN frequency (36.9+/-15.0), as compared to patients with different antibody pattern (Scl70+, FAN+; 19.7+/-8.2).CONCLUSIONS: Our results confirm the presence of chromosomal damage in circulating lymphocytes of SSc patients and would suggest a key role of antibodies to the centromere in determining the observed cytogenetic anomalies

The high frequency of spontaneous micronuclei observed in lymphocytes of systemic sclerosis patients: preliminary results

Objective: aim of the study is to assess the presence of spontaneous chromosome damage in patients affected by limited (lSSc) or diffuse (dSSc) Systemic Slerosis, using the micronucleus (MN) assay. Methods: we evaluated MN frequency in cultured peripheral lymphocytes of 18 SSc and in a group of 20 healthy controls. Patients were also classified as ACA+, Scl70+, FAN+ according to the presence of the specific anti-nuclear antibodies. We also explored the hypothesis that the extent of cytogenetic alteration might be related to the severity of the pathological condition and/or to the immunological profile. Results: compared to controls, the patient group as a whole showed significantly higher MN frequencies (10.8±4.5 vs. 27.8±13.7, p<0.001). No correlation was found between spontaneous chromosome damage and severity of the disease, being MN frequency 33.1±17.0 and 19.8±2.7 in lSSc and dSSc, respectively. Interestingly, ACA+ subjects displayed the highest MN frequency (36.9±15.0), as compared to patients with different antibody pattern (Scl70+, FAN+; 19.7±8.2). Conclusions: our results confirm the presence of chromosomal damage in circulating lymphocytes of SSc patients and would suggest a key role of antibodies to the centromere in determining the observed cytogenetic anomalies

Serological survey of bovine viral diarrhea (BVDV-1), brucellosis, and leptospirosis in captive white-lipped peccaries (Tayassu pecari) from the Midwest region in Brazil

The present study was conducted to assess the occurrence of anti-Brucella sp., anti-BVDV-1, and anti-Leptospira spp. antibodies from captive white-lipped peccary (Tayassu pecari). A cross-sectional survey was performed testing 100 serum samples collected in a commercial breeding herd. All samples were submitted to the acidified antigen test (AAT), virus neutralization test (VNT) and microscopic agglutination test (MAT) with live antigens. None of the samples tested agglutinated in the AAT screening test. In the VNT, 28 samples presented a cytotoxic effect and were excluded from the evaluation. For BVDV-1, only one sample (1/72; 1.38%) was positive, with antibody titers of 40. For leptospirosis, 9% (9/100) of the samples reacted to at least one of the 24 serovars tested, with 8% (8/100) positive for serovar Patoc and 1% (1/100) for serovar Grippotyphosa. The maximum titer observed was 100. The identification of antibodies against the serovars Patoc and Grippotyphosa suggests that the sampled individuals have been exposed to the pathogen at some point during their lifetime. Regarding BVDV-1, this may be the first serological survey to describe seropositive samples in tayassuids

Anomalie cromosomiche, valutate come frequenza di micronuclei spontanei, in soggetti con fenomeno di Raynaud sospetto presclerodermico [Chromosome aberrations, valued as frequency of spontaneous micronuclei, in subjects with suspected presclerodermic Raynaud's phenomenon]

Objective: To evaluate the prevalence of spontaneous chromosome damage in cultured peripheral lymphocytes of subjects with suspected presclerodermic Raynaud’s phenomenon (RP), by means of molecular cytogenetic analysis. Methods: We studied 20 suspected presclerodermic RP, 20 idiopathic RP and 25 healthy subjects. As marker of chromosome alteration we used the micronucleus assay. All subjects were also classified as ANA-, ACA+ or Scl70+. To identify the mechanism of MN formation, a MN fluorescence in situ hybridisation (FISH) analysis using a pancentromeric DNA probe was also performed. Results: Suspected presclerodermic RP subjects, showed significantly higher MN frequencies than idiopathic RP and controls (39±15.2 vs 10±2.1 and 9.8±3.5 respectively p<0.0001). Interestingly, subjects with idiopathic RP displayed MN frequency comparable to that of controls. Furthermore, ACA+ subjects showed the highest MN frequencies (44±8.1) as compared to subjects with different antibody pattern (26±7.1). Conclusions: Our results show the presence of higher levels of chromosomal damage in circulating lymphocytes of suspected presclerodermic RP. They also would suggest a key role of anti-centromere antibody in determining the observed cytogenetic anomalies. FISH analysis indicated that both aneuploidogenic and clastogenic events contribute to the formation of MN observed in suspected presclerodermic RP

Chromosome aberrations, valued as frequency of spontaneous micronuclei, in subjects with suspected presclerodermic Raynaud's phenomenon

OBJECTIVE: To evaluate the prevalence of spontaneous chromosome damage in cultured peripheral lymphocytes of subjects with suspected presclerodermic Raynaud's phenomenon (RP), by means of molecular cytogenetic analysis.METHODS: We studied 20 suspected presclerodermic RP, 20 idiopathic RP and 25 healthy subjects. As marker of chromosome alteration we used the micronucleus assay. All subjects were also classified as ANA-, ACA+ or Scl70+. To identify the mechanism of MN formation, a MN fluorescence in situ hybridisation (FISH) analysis using a pancentromeric DNA probe was also performed.RESULTS: Suspected presclerodermic RP subjects, showed significantly higher MN frequencies than idiopathic RP and controls (39+/-15.2 vs 10+/-2.1 and 9.8+/-3.5 respectively p&lt;0.0001). Interestingly, subjects with idiopathic RP displayed MN frequency comparable to that of controls. Furthermore, ACA+ subjects showed the highest MN frequencies (44+/-8.1) as compared to subjects with different antibody pattern (26+/-7.1).CONCLUSIONS: Our results show the presence of higher levels of chromosomal damage in circulating lymphocytes of suspected presclerodermic RP. They also would suggest a key role of anti-centromere antibody in determining the observed cytogenetic anomalies. FISH analysis indicated that both aneuploidogenic and clastogenic events contribute to the formation of MN observed in suspected presclerodermic RP