Ana Lisa Basquiera

Clinical significance of V617F mutation of the JAK2 gene in patients with chronic myeloproliferative disorders.

Abstract Objective: To determine the prevalence of JAK2 V617F mutation and its clinical correlation in patients with chronic myeloproliferative disorders (CMD): polycythemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF). Materials and methods: Detection of JAK2 V617F mutation by allele specific-PCR. Results: One hundred and three patients with CMD were included in the study. JAK2 V617F distribution was PV 40/45 (89%), ET 30/43 (69%), and IMF 7/15 (47%). In PV and ET patients only, 18 had thrombosis at diagnosis and 12 during follow-up (these were microvascular: 11, venous: 7 and arterial: 12); of these 28/70 (40%) were JAK2pos versus 2/18 (11%) JAK2neg; P=0·02. In a median of 4 years, two patients with PV JAK2pos evolved to myelofibrosis and one patient with PV presented in leukemic transformation (JAK2pos before and after transformation); six patients died: four patients with IMF and two patients with PV. Conclusions: We found an association between JAK2 V617F and thrombotic events in patients with PV and ET.

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.

Long-term remission in a patient with refractory thrombotic thrombocytopenic purpura treated with rituximab and plasma exchange

Dear Editor, We describe the case of a patient with thrombotic thrombocytopenic purpura (TTP) who received prolonged therapeutic plasma exchange (TPE) therapy; this treatment could only be discontinued when rituximab was added. A 16-year-old female was admitted at our Institution in January 2005; she presented thrombocytopenia, anemia and neurological symptoms. The patient had history of hypothyroidism with positive antibodies and atopic eczema. Three days before, she had developed paresthesias of the right hemibody. Two days later, she was hospitalized in other institution because of confusional syndrome and dysarthria. She had a platelet count of 11×10/l (reference interval: 150–300×10/l) and the Hb level was 6.9 gr/dl (females: 12.3–13.7 gr/dl). The brain CT-scan and magnetic imaging resonance were normal. She received dexametasone with transient clinical improvement. At admission, upon clinical examination she was lucid and oriented, and no neurological focus were noticed. She presented jaundice, petechiae in the oral mucosa, bilateral subconjunctival haemorrhages and ecchymosis in abdomen and legs. Her white blood cell count and differential count were normal. Her Hb level was 8.5 gr/dl and her platelet count was 12× 10/l. The peripheral blood smear showed red-cell fragmentation (schistocytes). A direct Coombs’ test had negative results. The serum creatinine level was 1.25 mg/dl, total bilirubin level 1.8 mg/dl, and lactate dehydrogenase 1,670 U/l (LDH; normal < 460 U/l). The diagnosis of TTP was stated and she immediately underwent daily TPE, exchanging 1.0 to 1.5 times the predicted plasma volume of the patient. The procedure was performed on a Haemonetics MCS and isovolemic exchanges were done using fresh frozen plasma. Informed consent for the procedure was obtained. Also TPE, prednisone 2 mg/kg/day was started. On day 7 after admission, a favorable clinical response was evidenced with a platelet count increasing to 66×10/l and LDH level falling to 533 U/l. The following day, thrombocytopenia and LDH levels worsened and intravenous vincristine was started. Prednisone was tapered and TPE continued. On day 9, ADAMTS13 activity and inhibitor serum activity were evaluated in a reference laboratory. Protease activity was 30% (reference value: 46 to 114%) and the inhibition of protease was 54% (reference value: 0%). She completed four doses of weekly vincristine and 28 TPE, obtaining a platelet count of 147×10/l, Hb level of 7.7 gr/dl and LDH 463 U/l. She was discharged under daily TPE; maintaining a platelet count above 150× 10/l while undergoing TPE. However, every attempt to stop TPE was followed by a rapid decrease of the platelet count (Fig. 1). On day 51, and after undergoing 46 TPE, rituximab therapy was started at a 375 mg/m weekly dose for a total of four intravenous doses. After the second dose of rituximab, TPE was tapered and stopped on day 65, after Ann Hematol (2008) 87:321–323 DOI 10.1007/s00277-007-0384-5

Allogeneic hematopoietic stem cell transplantation in pediatric myelodysplastic syndromes: a multicenter experience from Argentina.

Allogeneic hematopoietic stem cell transplantation (AHSCT) represents the only curative treatment for the majority of pediatric patients with Myelodysplastic Syndrome (MDS). We aimed to evaluate overall survival (OS), disease‐free survival (DFS), non‐relapse mortality (NRM) and relapse incidence in children who underwent AHSCT for MDS in six institutions from Argentina.

Hematopoietic Cell Transplantation–Specific Comorbidity Index Predicts Morbidity and Mortality in Autologous Stem Cell Transplantation

The hematopoietic cell transplantation-specific comorbidity index (HCT-CI) score is a useful tool to assess the risk for nonrelapse mortality (NRM) after allogeneic hematopoietic stem cell transplantation. Although the HCT-CI has been investigated in autologous stem cell transplantation (ASCT), its use is limited. To improve on the current use of the HCT-CI score on the morbidity and mortality after ASCT, we assessed the 100-day morbidity defined as orotracheal intubation (OTI), dialysis or shock (vasopressors need), 100-day NRM, early composite morbidity-mortality (combined endpoint that included any previous endpoints), and long-term NRM. We retrospectively reviewed a cohort of 1730 records of adult patients who received an ASCT in Argentinean centers between October 2002 and August 2016. Median follow-up was 1.15 years, and median age was 53 years. Diseases were multiple myeloma (48%), non-Hodgkin lymphoma (27%), and Hodgkin lymphoma (17%); 51% were in complete or partial remission; and 13% received ≥ 3 chemotherapy lines before transplant (heavily pretreated). Early NRM (100-day) was 2.7%, 5.4% required OTI, 4.5% required vasopressors, and 2.1% dialysis, with an early composite morbidity-mortality of 6.8%. Long-term (1 and 3 years) NRM was 4% and 5.2% and overall survival 89% and 77%, respectively. High-risk HCT-CI patients had a significant increase in 100-day NRM compared with intermediate and low risk (6.1% versus 3.4% versus 1.8%, respectively; P = .002), OTI (11% versus 6% versus 4%, P = .001), shock (8.7% versus 5.8% versus 3%, P = .001), early composite morbidity-mortality (13% versus 9 % versus 4.7%, P < .001), and long-term NRM (1 year, 7.7% versus 4% versus 3.3%; and 3 years, 10.8% versus 4% versus 4.8%, respectively; P = .002). After multivariate analysis these outcomes remained significant: early composite morbidity-mortality (odds ratio [95% confidence interval] compared with low risk: intermediate risk 2.1 [1.3 to 3.5] and high risk 3.3 [1.9 to 5.9]) and NRM (hazard ratio [95% confidence interval] compared with low risk: intermediate risk .97 [.8 to 2.4] and high risk 3.05 [1.3 to 4.5]). No significant impact was observed in overall survival. Other than comorbidities, significant impact was observed for heavily pretreated patients, age ≥ 55 years, non-Hodgkin lymphoma, and bendamustine-etoposide-citarabine-melphalan conditioning. We confirmed that the HCT-CI had a significant impact on NRM after ASCT, and these findings are mainly due to early toxicity express as 100-day NRM and the 3 main morbidity outcomes as well as the composite endpoint.

C-reactive protein, platelets, and patent ductus arteriosus

Abstract The association between inflammation, platelets, and patent ductus arteriosus (PDA) has not been studied so far. The purpose of this study was to evaluate whether C-reactive protein (CRP) is related to low platelet count and PDA. This was a retrospective study of 88 infants with a birth weight ≤1500 g and a gestational age ≤30 weeks. Platelet count, CRP, and an echocardiogram were assessed in all infants. The subjects were matched by sex, gestational age, and birth weight. Differences were compared using the χ2, t-test, or Mann–Whitney U-test, as appropriate. Significant variables were entered into a logistic regression model. The association between CRP and platelets was evaluated by correlation and regression analysis. Platelet count (167 000 vs. 213 000 µl−1, p = 0.015) was lower and the CRP (0.45 vs. 0.20 mg/dl, p = 0.002) was higher, and the platelet count correlated inversely with CRP (r = −0.145, p = 0.049) in the infants with vs. without PDA. Only CRP was independently associated with PDA in a logistic regression model (OR 64.1, 95% confidence interval 1.4–2941, p = 0.033).

A case of chronic myeloid leukemia with the m-bcr (p190) molecular rearrangement identified during treatment

Chronic myeloid leukemia (CML) is a hematological malignancy in which a high percentage of patients cytogenetically express the Philadelphia chromosome. This chromosome results from the reciprocal translocation, t(9;22)(q34;q11.2). During this exchange, the Abelson gene (abl) on chromosome 9 and the breakpoint cluster region gene (bcr) on chromosome 22 generate the breakpoint cluster region-Abelson murine leukemia (BCR-ABL) fusion gene. The most frequent breakpoint on chromosome 22, located between exons 12 and 16, is called the major breakpoint cluster region (M-bcr) and with its counterpart in exon 2 of chromosome 9 results in the b2a2 and b3a2 transcripts that code for a 210 kDa protein. Less frequently, a second rearrangement, minor breakpoint cluster

Application of the revised International Prognostic Scoring System for myelodysplastic syndromes in Argentinean patients

Dear Editor, The International Prognostic Scoring System (IPSS) [1], the gold standard for risk assessment in myelodysplastic syndromes (MDS), has been recently revised (IPSS-R). The authors proposed a new prognostic model including novel components: five cytogenetic prognostic subgroups with specific classification of a number of less common cytogenetic subsets [2, 3]; the 2–<5%; depth of cytopenias at clinically relevant cut-points for haemoglobin level, platelet count, and absolute neutrophil count [2]. As the score [2] was established in MDS patients including all French–American–British classification subtypes [4], the aim of this study was to apply the IPSS-R in Argentinean MDS patients classified according to the World Health Organization (WHO) classification [5]. We retrospectively analysed a cohort of 371 de novo MDS patients [6] diagnosed between 1981 and 2012. According to the WHO classification, 43 patients were classified as refractory cytopenia with unilineage dysplasia/ refractory anaemia with ringed sideroblasts, 17 as del(5q) syndrome, 201 as refractory cytopenia with multilineage dysplasia, 44 as RAEB type 1, and 66 as RAEB type 2. The median age was 70 (17–92) years with 72 % of patients above 60, the gender ratio was 1.4 (M/F: 214/ 157), and 157 (42 %) patients showed an abnormal karyotype. During the follow-up (median 23.3 months), 80 (22 %) showed

Reactivation of Chagas Disease in a Patient With Follicular Lymphoma Diagnosed by Means of Quantitative Real-Time Polymerase Chain Reaction

We report a case of Chagas disease reactivation in a patient with stage IIb follicular lymphoma in the cecum. He was admitted to the hospital with neutropenia and fever. He had a history of right hemicolectomy 6 months earlier and had received the sixth cycle of chemotherapy with cyclophosphamide/doxorubicin/vincristine/prednisone/rituximab. Blood and urine cultures were negative, but the fever persisted. Reactivation of Chagas disease was confirmed by means of quantitative real-time polymerase chain reaction (qRT-PCR). Parasitic load was 577 950 parasite equivalents/mL. The patient began treatment with benznidazole 5 mg/k per day every 12 hours. After 1 month, the qRT-PCR control was undetectable. The patient completed 60 days of treatment and is currently asymptomatic. Trypanosoma cruzi qRT-PCR may become a useful diagnostic method for reactivation of Chagas disease.

Prognostic relevance of cytogenetic systems in myelodysplastic syndromes

* On behalf of the Argentine MDS Study Group, Argentine Society of Hematology, Argentina. Correspondence: Dr. Carolina B. Belli, PhD, Laboratorio de Gen é tica en Hematolog í a, Instituto de Medicina Experimental – Consejo Nacional de Investigaciones Cient í fi cas y T é cnicas (IMEX – CONICET)/Academia Nacional de Medicina (ANM), Pacheco de Melo 3081, 1425, Buenos Aires, Argentina. Tel: 54-11-48058803. Fax: 54-11-4803-9475. E-mail: cbelli@hematologia.anm.edu.ar