Acute leukemia, although rare after liver transplantation, should be considered in the differential diagnosis of hematological complications.

Venous thromboembolism (VTE) is a frequent complication following major abdominal surgery. The use of low-molecular-weight heparins (LMWH) to prevent thrombotic events in these patients is a common and well documented practice. However, there is some controversy surrounding the duration of the prophylaxis, as it has been suggested that the risk persists for several weeks after surgery. The objective of this meta-analysis is to systematically review the clinical studies that compared safety and efficacy of extended use of LMWH (for three to four weeks after surgery) versus conventional in-hospital prophylaxis. An electronic data base search was performed. Only randomized, controlled studies were eligible. Data on the incidence of deep vein thrombosis (DVT), VTE and bleeding were extracted. Only three studies fulfilled the inclusion criteria. The indication for surgery was neoplastic disease in 70.6% (780/1104) of patients. The administration of extended LMWH prophylaxis significantly reduced the incidence of VTE, 5.93% (23/388) versus 13.6% (55/405), RR 0.44 (CI 95% 0.28 - 0.7); DVT 5.93% (23/388) versus 12.9% (52/402), RR 0.46 (CI 95% 0.29 - 0.74); proximal DVT 1% (4/388) versus 4.72% (19/402), RR 0.24 (CI 95% 0.09 - 0.67). We found no significant difference in major or minor bleeding between the two groups: 3.85% (21/545) in the extended thrombo-prophylaxis (ETP) group versus 3.48% (19/559) in the conventional prophylaxis group; RR 1.12 (CI 95% 0.61 - 2.06). There was no heterogeneity between the studies. We conclude that ETP with LMWH should be considered as a safe and useful strategy to prevent VTE in high-risk major abdominal surgery.

Mild chronic neutrofilia is a frequent reason for hematologic consultation and in 70% of the cases there is no identifiable cause. Objective: to determine if smoking habit could be the etiology for leucocytosis with neutrophilia in smokers with no other pulmonary associated disease. Materials and Methods: We questioned 300 consecutive blood donors from our institution, elaborating a complete record of smoking habit. Immediately before blood donation an automated complete blood count was performed. Leucocytosis was defined as a white cell count above 11 x 109/L, and neutrophilia as a neutrophil count over 7.7 x 109/L. All data is stated as mean value ± 1 SD. Results: we studied 195 (65%) men and 105 (35%) women (n=300). Mean age was 36.5 y.o. (18–69). Fifty-five percent (165/300) smoke or were previous smokers; 8.4% (14/165) of these, did not smoke at the time of this investigation, and only two have quit smoking a year prior to questioning. Mean time of duration of smoking habit was 16.4 years ± 10.6 and the average amount of cigarettes smoked through life (estimated from data referred along different phases of each subject’s history) was 1.26 x 105 ± 1.21 x 105. In the following table results from smokers (previous or actual) vs. non-smokers are compared. Leucocytosis was present in 37/165 (22.4%) of smokers and in 3/135 (2.2%) of non-smokers (p<0.001) and neutrophilia was noted in 19/165 (11.5%) of smokers and in 2/135 (1.5%) of non-smokers (p<0.001). None of the volunteers had a WBC count over 20 x 109/L. A direct association was established for the number of cigarettes smoked and the WBC count and neutrophil count. Discussion: smoking habit affects ciliar movement, inhibits alveolar macrophage function and produces hyperplasia on mucous glands within bronquial walls. These alterations result in entrapment of mucous secretions that will ultimately lead to bacterial colonization. The neutrophilia observed in smokers would be the result of a normal physiologic response to a potential infectious focus. In conclusion, is our understanding that the smoking habit should be considered as a common etiology for mild leucocytosis and neutrophilia. Smokers (n:165) Non-smokers (n:135) p (t-test) WBC x 109/L 9.6 ± 2.1 6.8 ± 1.3 < 0.001 Neutrophils x 109/L 5.7 ± 1.6 3.9 ± 1.0 < 0.001 Hct % 45.9 ± 3.7 45.2 ± 3.6 NS Platelets 207 ± 48.7 206.4 ± 45.8 NS

Introduction: The treatment of chronic myeloid leukemia (CML) suffered a dramatic change with the introduction of Imatinib mesylate. This drug has become the choice for first line treatment of CML. However, it has been shown that the effectiveness of the treatment requires a high compliance with the prescribed dose for a long period of time, and sub-dosing has been associated with a delay in achieving cytogenetic response and development of resistance. We conducted a prospective case-control study, in order to analyze how a better compliance affects the cytogenetic response to Imatinib. Materials and Methods: Between January and June 2006, 24 patients with newly diagnosed Phi (+) chronic phase CML were recruited and followed for the next 12 months. Patients were put on 400mg of Imatinib and were asked to note down all taken doses, and reasons for non-compliance. During each of the monthly visits, the dosing schedules were revised, non-adherence reasons were discussed and the medication was counted. All adverse events were noted and graded according to the NCI CTCAE (VERSION 3.0) code. Reductions or interruptions in the schedule were only allowed for related adverse events with a CTC score ≥3. All other events were treated accordingly, without modifications in the Imatinib dosing. As a control group, we matched each case with a chronic phase Phi (+) CML patient from our data base (controls were matched for sex, age, and hematological response). Only patients who received treatment with Imatinib and with complete information about dosing and adverse events were acceptable as controls. Compliance was measured as: mg taken /mg prescribed x 100 during the study period. Cytogenetic response was reported as the percentage of t(9;22) negative metaphases. Results: Twenty-four patients, 14 males with median age 55 yo (range: 23–82) were included in the study; three were lost to follow up, leaving only twenty-one for analysis of compliance. At the end of the year of follow up, all patients have achieved a complete hematological response. Compliance during the 12 months was 96.1 ± 9% 1SD for the cases group, which is clearly superior to the 80% reported in the setting of clinical trials. As for one year cytogenetic response, 60 ± 25% of the control group achieved a mayor response (Phi < 35%), while 89.9 ± 20% of the cases achieved that same response. This difference is statistically significant with a p=0.027. The incidence of adverse events was similar for both groups, being nausea, vomiting, peripheral edema and skin rash the most common ones. As for hematological toxicity, CTC grade 1–2 leucopenia (11%) and thrombocytopenia (17%) were the more frequent. However, although moderate, these were the main reasons for interruption or reduction of Imatinib dosage in the control group. Conclusions: This study shows that improving compliance is associated with a better cytogenetic response. As this response is the ultimate goal in the treatment of CML patients, physicians should make an effort to assure the best adherence to the treatment and avoid sub-dosing. Doing this will help patients obtain a better cytogenetic response which has already proved to be essential for long term survival in CML.

Background: Since the introduction of Imatinib (IM), the treatment of chronic myeloid leukemia (CML) experienced its most important change. As this drug became the first line for the treatment of CML, we learned that under-dosing was associated with a delay in achieving cytogenetic response and the development of acquired resistance. Last year we presented a case-control study that analyzed how compliance affects the cytogenetic response to Imatinib. This is an update of that data. Materials and Methods: Twenty-four patients with newly diagnosed Ph (+) chronic phase CML (CP-CML) were included and followed for 24 months. Patients received 400mg of IM and were asked to note down all taken doses, and reasons for non-compliance. Follow up visits were scheduled every 28–30 days and prescriptions were filled in order to last for only 30 days. During each visit, the medication was counted and non-adherence reasons were determined. Adverse events were graded according to the CTC and modifications in the Imatinib dose were only allowed with related adverse events with a CTC score ≥3. As a control group, we matched each case with a Phi + CP-CML patient from our data base of the same sex and similar age as the case patient. All control patients had to have complete information about dosing and response. They all received initial treatment with IM 400mg; thereafter, dose was adjusted according to each physician’s criteria. Compliance was measured as: mg prescribed/mg taken during the study period. Results: Twenty-four patients, 14 males median age 56 yo (range: 24–83), were included in the study. Three were lost to follow up, leaving only twenty-one for analysis of compliance. At the end of the first year, all patients had complete hematological response. Compliance during these 12 months was 96.1, which is clearly superior to the 80% reported in the setting of clinical trials. All patients had a complete hematological response, 89.9 achieved a major cytogenetic response (MCyR) and 87.4 a complete cytogenetic response (CCyR), compared to 60 of the control group with a MCyR (p=0.027) and 57.8 a CCyR (p=0.025). During the second year, four patients lost CCyR, three responded to an increase in IM dose and one progressed to an accelerated phase and died. Compliance fell slightly during this period to 90.86% which was reflected in 81.66% CCyR, which was still statistically higher than the 54% of major responses in the control group (p=0.033). In both groups, none of the patients not achieving MCyR at 12 months achieved MCyR at 24 months. Hematological toxicity was more frequently observed within the first 6 months of treatment and after the increase in dosage. Severity and incidence of adverse events were similar in both groups, and were the main reasons for interruption or reduction of IM dose in the control group. The only additional difference besides compliance between the two groups was the average IM dose prescribed during the duration of the study (cases group: 430mg – control group: 330mg). Conclusions: Adherence to Imatinib is associated with an improvement in cytogenetic response that can be seen even at two years after the start of therapy. Since outcome and development of resistance seem to be associated with compliance to therapy, emphasis should be put on maintaining treatment at an adequate dose for as long as possible.

Until the 1990 s, the treatment of chronic myeloid leukemia (CML) recognized hematopoietic stem cell transplantation as the best treatment for those patients with an available donor. With the advent of imatinib in 2001, this paradigm changed dramatically as this drug provided outstanding and durable rates of hematologic, cytogenetic, and molecular responses. As a consequence it became the gold standard first-line treatment for most patients. However, after almost a decade of its use, it is clear that although very effective, imatinib cannot cure CML as transplantation has already proven so. Furthermore, the new non-myeloablative regimens and the improvements in survival after allogeneic transplant, especially in the field of unrelated transplants, offer this option to a broader population of patients with CML. This adds to the old question of whom to transplant, when and how to proceed with the allograft. This article reviews the current role of transplantation in the era of tyrosine kinase inhibitors and will try to elucidate its role in the frontline setting as well as after first- and second-line kinase inhibitors failure.

The FLIPI prognosis score for follicular lymphoma (FL) was developed based on cases diagnosed between 1985 and 1992, and treated with different schemes that did not include rituximab (R). In the present study, we report the evolution of all FL treated in a single institution through the last decade and analize whether FLIPI mantains its effectiveness to identify different risk groups within patients treated with the new therapeutic alternatives available. Material and Methods: We identified sixty two patients with diagnosis of grade I-II-IIIa FL. Patients characteristics: median age 57.5 yr (r, 30–80); 36 males; 63% stages III–IV, and 37% with bone marrow infiltration at the time of diagnosis. Thirty eight percent had a low risk by FLIPI, 34% had an intermediate risk and 27.4% had a high risk. In 19 pts (30.6%) the initial decision was “watch and wait” but 82% received a form of treatment at some point. R was used in 36 pts (58%) with some of the following regimes: chemotherapy (chemo) + R and/or R as consolidation therapy and/or R as monotherapy and/or R as maintenance therapy. Of all prescribed treatments (excluding R as monotherapy and/or maintenance treatment), 52.8% were chemo alone, 20.2% chemo + R, 21.3% radiotherapy and 5.6% received a bone marrow transplant. Results: we considered the analysis of overall survival (OS) the most appropiate approach, since most treatments were seeking the control of the FL, and not the complete remission or cure. The follow up median time was 53.2 months ± 34.8 1SD. The 5-yr OS for the 62 pts was 81.8% ± 11.3 CI 95%. The 5-yr OS for those with a low, intermediate and high risk FLIPI was 100% −5, 84.2% ± 21 and 52% ±26.2, respectively. The difference in 5-yr OS was statistically significant between low and high risk, intermediate and high risk, but failed to prove a significant difference between low and intermediate risk. Among the different risk factors tested in a univariate analysis only age ≥ < 60 yr old demonstrated a significant difference, 60.7% vs 90%, respectively. Conclusions: The 5-yr OS in our series is higher than the one described in the original FLIPI study (Blood2004; 104:1258–65) which was 81.8% vs 71% for the whole group; 90% vs 78.1% for pts <60 yr old; 60.7% vs 57.7% for ≥ 60 yr old; 100% vs 90.6% for low FLIPI and 84.2% vs 77.6% for intermediate FLIPI. The only group that failed to prove an improvement was the high risk FLIPI with 52% vs 52.5%. The impact of novel therapies was more evident in patients with a low or intermediate FLIPI and was even more evident in patients younger than 60 yr old. According to our results, FLIPI maintains its effectiveness in differentiating two risk groups, i.e., low-intermediate vs high. We believe that the OS curves will probably continue to improve as the treatments that are considered today as the most effective ones, were just included in our series in the last three years.