Elsa Nucifora

Partial and total monosomal karyotypes in myelodysplastic syndromes: comparative prognostic relevance among 421 patients.

Myelodysplastic syndromes (MDS) include a group of heterogeneous hematological disorders with a variable risk of leukemic evolution and short survival. Around 40–50% of patients show abnormal karyotypes that are mostly characterized by monosomies or deletions. Cytogenetic findings are an independent prognostic factor and the International prognostic scoring system (IPSS) differentiates three cytogenetic categories, despite the Intermediate one being heterogeneous. The aim of this study, including 421 Argentinean patients with primary MDS, is to characterize the cytogenetic profile, to test its prognostic value and to compare partial and monosomal karyotypes against other cytogenetic findings. An abnormal karyotype (median survival: 26 months) was observed in 176 patients. The presence of complex karyotypes, number of alterations, and the IPSS cytogenetic groups showed significant differences for predicting outcome. Behavior of patients with isolated deletions (median survival: 49 months) did not differ from those with normal karyotype (56 months, P = 0.654) or Good prognostic findings (43 months, P = 0.371). However, a worse prognosis was observed when another alteration was added (31 months, P = 0.043). Karyotypes with autosomal monosomies (median survival: 16 months) had a prognostic impact similar to other Poor cytogenetic findings (17 months, P = 0.626). In our population classified according to French‐American‐British (FAB) or World Health Organization (WHO), this new categorization of cytogenetic abnormalities, recognizing three different risk groups, showed an independent prognostic impact and a better discriminating power than the IPSS categories. It can be concluded that all isolate deletions (excluding 7q‐) are good prognostic findings and all monosomies (excluding Y chromosome loss) are bad indicators. Am. J. Hematol., 2011.

Decitabine in myelodysplastic syndromes and chronic myelomonocytic leukemia: Argentinian/South Korean multi-institutional clinical experience

This multicenter, open-label study evaluated the efficacy and safety of decitabine in patients from Argentina and South Korea with myelodysplastic syndromes or chronic myelomonocytic leukemia. Of 106 patients who received decitabine 20 mg/m2 intravenously over 1 h once daily for 5 days in 4-week cycles, 99 patients were evaluable after receiving at least two cycles. The overall improvement rate was 35% (19% complete response +4% marrow complete response +4% partial response +8% hematologic improvement). Overall survival at 2 years was 71%. Treatment-related adverse events included febrile neutropenia, thrombocytopenia and bleeding, asthenia, fatigue, and eosinophilia. After complete response (CR), three patients received an allogeneic stem cell transplant. Four patients who relapsed after CR responded to decitabine retreatment. Acute myelogenous leukemia developed during follow-up in 21% of patients. Decitabine in a 5-day outpatient administration schedule was effective and well tolerated in typical clinical practice settings in South America and Asia.

COMBINATION SALVAGE CHEMOTHERAPY WITH MIZE (IFOSFAMIDE-MESNA, IDARUBICIN AND ETOPOSIDE) FOR RELAPSING OR REFRACTORY LYMPHOMA

In this study, 54 patients with relapsed or refractory non-Hodgkins lymphoma (NHL) were treated in a phase II, multicentric trial with ifosfamide-mesna 1500 mg/m2 IV days 1-3, idarubicin 12 mg/m2 IV day 1 and etoposide 100 mg/m2 IV day 1-3 (MIZE). Overall response was 72%; complete response (CR) and partial response (PR) were 46% and 26% respectively. In Stage I-II pts CR was 59% and in Stage III-IV pts CR was 40.5%. Patients who relapsed from an initial CR had a 64% CR rate when treated with MIZE, in contrast to refractory diseases patients who only had 19% CR (p = 0.004). The group of pts that had an objective response (CR + PR) to front line therapy had a 2 year survival rate of 55% compared with none for refractory disease (p = 0.029) after salvage therapy. Median survival for the entire group was 17.5 months. Better survival was seen in pts who were asymptomatic with low levels of LDH, previous CR, non high-grade histology, and limited disease stage at relapse. Toxicity was mainly hematologic: 91.5% had neutropenia, (56.5% grade III-IV), and 9.5% died from infectious complications. Other clinical toxicities including cardiac toxicity were negligible. MIZE chemotherapy was effective in patients with relapsed and refractory lymphoma and showed limited clinical and cardiac toxicity. Myelosupression was the most frequent single toxicity.

Incidence rate of amyloidosis in patients from a medical care program in Buenos Aires, Argentina: a prospective cohort

Abstract Background: There are limited data concerning the incidence density (ID) of ATTRwt, AL and AA amyloidosis in the Argentinean population. Our aim was to estimate the ID of ATTRwt, AL and AA amyloidosis at the Hospital Italiano Medical Care Program in Buenos Aires, Argentina. Methods: Population was all members of a hospital-based health maintenance organization who were affiliated since January 2006 to December 2014. Each person was followed contributing time at risk since January 2006 or enrollment date to the final date. Incident cases of amyloidosis were captured from the institutional registry of amyloidosis. Incidence rate was calculated with 95% confidence intervals. Results: During the nine-year study period, there were 15 patients with ATTRwt, 12 with AL and 2 with AA amyloidosis for 1 105 152 person-years of follow-up. The crude ID of ATTRwt amyloidosis was 13.5 (95%CI 8.1–22.4), that of AL amyloidosis 11 (95%CI: 6–19) and that of AA amyloidosis 1.8 (95%CI: 0.5–7.2) per 1 000 000 person-years. The highest ID was found in men (31.7 for ATTRwt, 15.9 for AL and 2.27 for AA amyloidosis per 1 000 000 person-years). The ID adjusted to the population of the city of Buenos Aires was 6.46 (95%CI: 3.17–9.74) for ATTRwt, 6.13 (95%CI: 2.57–9.7) for AL and 1.21 (95%CI: 0.56 to 2.99) for AA amyloidosis. Conclusions: This is the first paper to report the incidence density of ATTRwt, AL and AA amyloidosis in Latin America. Our results are consistent with other studies from other regions. Although systemic amyloidosis is a rare disease, it is a major health problem because of its morbi-mortality.

Transthyretin-related hereditary amyloidosis in an Argentinian family with TTR Tyr114Cys mutation

Transthyretin-related hereditary amyloidosis is an autosomal dominant inherited disease caused for mutations in the transthyretin (TTR) gene. Corresponding to the various transthyretin gene mutations and a wide range of geographical distribution, this disorder presents diverse characteristics in genotype-phenotype correlation. Familial amyloid polyneuropathy (FAP) is the more common clinical presentation and the Val30Met is its more frequent mutation described [1].