Yan Beauverd

A body-packer with a cocaine bag stuck in the stomach

Management of patients carrying packets of drugs in the digestive tract is a frequent medical problem. We report on a patient who was referred by the police after ingestion of packets of cocaine. After spontaneous elimination of 81 drug packets, the patient had three unremarkable stools. A plain abdominal X-ray disclosed no residual packet but computed tomography (CT) scan showed one in the stomach. As this was not eliminated during the 10 d following ingestion, it was removed through gastrotomy. This case stresses the usefulness of the CT scan to ensure that no residual packet is present before hospital discharge.

Pegylated interferon alpha-2a for essential thrombocythemia during pregnancy: outcome and safety. A case series

Pregnant woman with essential thrombocythemia (ET) are at higher than normal risk of pregnancy complications. Current recommendations suggest that aspirin and cytoreductive therapy should be offered for high-risk pregnancies but Pegylated interferon alpha-2a (PEG-IFN) has never been investigated in

Hematologic modifications in natalizumab-treated multiple sclerosis patients An 18-month longitudinal study

Objective: To monitor the hematologic modifications in the peripheral blood of patients with relapsing-remitting multiple sclerosis treated with natalizumab. Methods: The cohort included 44 patients with relapsing-remitting multiple sclerosis treated monthly with natalizumab for 18 months. Peripheral blood was collected before treatment initiation and on a monthly basis during the treatment course. Complete blood cell count was performed using automated hematology systems. Blood smears were prepared and analyzed when abnormal values were detected. Results: Mean total white blood cell, lymphocyte, and eosinophil counts were significantly higher 1 month after treatment initiation and remained stable during the 18 months of follow-up. Monocyte counts increased progressively during the 18-month treatment with natalizumab. Erythroblasts and neutrophil precursors were absent before treatment initiation but were present in 16% and 6.8% of patients, respectively, 1 month after the first natalizumab infusion. The proportion of patients with erythroblasts and neutrophil precursors remained stable throughout the 18-month follow-up period. On an individual patient basis, a fluctuating level of erythroblasts and neutrophil precursors was observed. No difference in mean erythrocyte, hemoglobin, hematocrit, thrombocyte, and neutrophil levels was observed before and after 18 months of natalizumab treatment. No cases of myelodysplastic syndrome or acute leukemia were observed. Conclusion: Chronic treatment with natalizumab is associated with significant modifications in complete blood cell count, including emergence of hematopoietic precursors that are not present in peripheral blood under normal conditions. None of these modifications were associated with malignancy.

Protein modelling to understand FGB mutations leading to congenital hypofibrinogenaemia

Congenital hypofibrinogenaemia is a quantitative fibrinogen disorder characterized by proportionally decreased levels of functional and antigenic fibrinogen. Mutations accounting for quantitative fibrinogen disorders are relatively frequent in the conserved COOH‐terminal globular domains of the γ and Bβ chains. The latter mutations are of particular interest since the Bβ‐chain is considered the rate‐limiting chain in the hepatic production of the fibrinogen hexamer.

Disease characteristics and outcomes in younger adults with primary and secondary myelofibrosis.

Myelofibrosis (MF) is a rare haematopoietic disorder, commonly diagnosed in the 6th decade: less than 20% are diagnosed before the age of 50 years. In this retrospective study we included all patients given a diagnosis of World Health Organization‐defined primary or secondary MF when aged ≤50 years. Forty‐three patients with a median age of 43 years were included. Median follow up was 44 months. Twenty‐two (51%) harboured the JAK2 V617F mutation, 18/43 (42%) CALR, 0/43 (0%) MPL mutations and 3/43 (7%) were ‘Triple Negative’ (TN). At the time of diagnosis, no significant differences existed in haematological and clinical phenotypes between JAK2, CALR and TN patients. The frequency of splenomegaly was greater (P = 0·047) in the JAK2‐mutated group compared to CALR‐mutated patients. In the whole cohort, the 5‐year probability of developing anaemia, thrombocytopenia and marked leucocytosis was 24%, 10% and 13% respectively. Finally, the cumulative incidence of thrombotic events and progression to acute myeloid leukaemia was 1% and 0·5% patient‐year respectively. No death was reported during the follow‐up. These findings suggest that MF in younger patients may have a more indolent course when compared to older patients.

Suspicion of heparin-induced thrombocytopenia in internal medicine: How appropriate is the ordering of anti-PF4/heparin antibody testing?

Abstract Thrombocytopenia is frequent in hospitalized patients, and heparin-induced thrombocytopenia (HIT) is often suspected when a decrease in platelet count is concomitant with heparin treatment. ELISA tests used for anti-PF4/heparin antibodies detection usually have high sensitivity but only fair specificity for HIT. Pre-test probability scores (such as 4Ts or HEP scores) have been validated and a low probability score rules out HIT without anti-PF4/heparin testing. The aims of this study are to evaluate the appropriateness of anti-PF4/heparin testing according to pre-test probabilities of HIT and to compare the abilities of the 4Ts and HEP scores to avoid inappropriate anti-PF4/heparin testing. This retrospective observational study included 74 consecutive patients hospitalized in a general internal medicine division who had anti-PF4/heparin testing for suspicion of HIT. 4Ts and HEP scores were computed retrospectively. About 73% of patients who had ordering of an anti-PF4/heparin were at low risk according to the 4Ts score, and 46% according to the HEP score. Heparin was discontinued in 61% and 62% of low-risk patients according to 4Ts and HEP scores and switched to alternative anticoagulant in 31% and 32% of them, respectively. No case of HIT was diagnosed in patients with a low-risk score. One major bleeding and no thrombosis were observed. For the 4Ts score, the sensitivity was 100%, the negative predictive value (NPV) was 100%, the specificity was 77%, and the positive predictive value (PPV) was 20% (95% CI: 7–44). For the HEP score, the sensitivity was 100%, the NPV was 100%, the specificity was 49%, and the PPV was 10%. In conclusion, pre-test probability scores were vastly underused in this internal medicine population despite their ability to rule out HIT without laboratory testing in a large proportion of patients. Appropriate use of those instruments should be actively promoted.

Pacritinib: a new agent for the management of myelofibrosis?

Introduction: Myelofibrosis (MF) is a clonal haematological disease associated with recurrent somatic gene mutations (JAK2V617F, MPL, CALR) and constitutive activation of the Janus kinase (JAK)/Signal Transducer and Activator of Transcription pathway. MF is often characterised by debilitating symptoms and JAK inhibitors (JAKIs) have revolutionised available therapeutic options. Ruxolitinib, a JAK1 and 2 inhibitor, is the only currently approved agent. Several other JAKIs are undergoing evaluation in the clinical trial setting and Pacritinib, a novel JAK2 and FLT3 inhibitor, is at an advanced stage of investigation with recent completion of a Phase III trial and another ongoing. Areas covered: Within this article we focus on pacritinib, summarising the development, preclinical and up-to-date results from the Phase I – III trials. We present the most recent data on efficacy and safety and indirectly compare this novel JAKI with ruxolitinib. Expert opinion: The kinome array data for pacritinib suggests that it has a range of targets differing to those for ruxolitinib. Pacritinib appears to be an effective agent for the control of MF-related symptoms and splenomegaly with potentially fewer haematological side-effects when compared with ruxolitinib and seems a particularly promising agent for anaemic and thrombocytopenic patients. It is also an attractive drug for potential combination studies due to its good tolerability.

Outcome of hematopoietic stem cell transplantation is similar for patients with a partial in vitro T-cell-depleted graft compared with a non-T-cell-depleted graft when stratified by the refined disease risk index.

Comparisons of hematopoietic stem cell transplantation (HSCT) methods in retrospective studies are often hampered by the heterogeneity of comparison groups. The refined disease risk index (DRI) is a potentially interesting tool to compare HSCT protocols as it is based on the disease type and burden at transplant and stratifies patients into four prognostic groups for overall survival (OS). We included 265 patients with partial T-cell-depleted graft (TDEP) and 163 non-TDEP patients in a retrospective study and compared outcomes following stratification using the refined DRI. The 2-year OS rate for TDEP patients was 81.6, 60.9 and 43.3% for the low-, intermediate- and high-risk groups, respectively (P<0.001). For non-TDEP patients, the 2-year OS rate was 62.9, 48.8, 44.2 and 7.6% for the low-, intermediate-, high- and very-high-risk groups, respectively (P<0.001). There was no significant difference when comparing OS between TDEP and non-TDEP for the low-, intermediate- and high-risk groups, but TDEP patients had less acute GvHD grades II–IV. In conclusion, we confirm that the refined DRI is a valuable tool to compare the outcomes of different HSCT protocols. We demonstrate also that TDEP did not impact on the outcome of HSCT, but it did reduce the incidence of acute GvHD.

Ruxolitinib: evolution or revolution in treatment of patients with polycythemia vera?

Current treatments for polycythemia vera have remained unchanged for decades with phlebotomy, hydroxycarbamide (also named hydroxyurea) and to a lesser extent interferon being the cornerstones in our therapeutic armamentarium. However, some patients do not respond to, or indeed experience significant side effects to, these current agents and development of alternative therapeutic options is required. Ruxolitinib, a potent JAK1/2 inhibitor, initially approved for myelofibrosis, was recently approved for patients with polycythemia vera refractory or intolerant to hydroxycarbamide. In this article, we review the currently available efficacy and safety data.

Impact of T-cell depletion on outcome of patients undergoing allogeneic hematopoietic cell transplantation for myelodysplastic syndrome.

Myelodysplastic syndromes (MDS) are clonal stem cell disorders usually characterized by cytopenia and dysplasia. MDS are usually diagnosed during the sixth decade and are associated with reduced life expectancy, mainly related to transformation to acute leukemia, infections, or bleeding. Currently, the only potentially curative treatment for MDS is allogeneic hematopoietic stem cell transplantation (HSCT) [1–3]. However, HSCT is associated with significant morbidity and mortality mainly related to acute or chronic graft-vs.-host disease (aGvHD or cGvHD) [4, 5]. In the Geneva Stem Cell Transplant Center we use partial in vitro T-cell-depleted grafts usually for patients in complete remission at transplant to reduce GvHD incidence [6]. Indeed, partial T-cell depletion decreases the number of alloreactive donor T cells triggering GvHD. However, it is hypothesized that this strategy could increase relapse incidence (RI) and decrease overall survival (OS) due to the loss of the graft-vs.-leukemia effect mediated by donor lymphocytes. Impact of partial T-cell depletion was previously investigated in a cohort of patients, including heterogeneous diseases and results had shown no worsening of outcome for partially T-cell-depleted patients [7]. However, the impact of partial T-cell depletion was never specifically investigated for patients undergoing transplantation for MDS. In this retrospective study, we investigated patients allografted for a diagnosis of MDS over a 19 years’ period (from 01 January 1998 to 31 August 2016). Patients aged ≥18 years old at transplant time, who had a diagnosis of MDS according to the 2008 World Health Organization criteria, and who had a first HSCT were included. Patients with haploidentical transplantation, stem cell from identical twins, umbilical cord blood transplantation, or more than two human leukocyte antigen (HLA) locior allelemismatched unrelated donor (MMUD) transplantation were excluded. This study was approved by an ethics committee. Primary outcomes were comparison of 3-year OS, progression-free survival (PFS), GvHD-free/relapse-free survival (GRFS) [8], RI, and non-relapse mortality (NRM) between partially T-cell-depleted patients and non-T-celldepleted ones. Secondary outcomes were impact of partial T-cell depletion on grade 2–4 acute and chronic GvHD. Sixty-two patients were included. Forty-four percent were female, median age at transplant was 48 years (range: 18–70 years) with myeloablative conditioning for 66% and reduced intensity for 34%. Median time from diagnosis to HSCT was 7.5 months (range: 3–86 months). Peripheral blood stem cell (90%) or bone marrow (BM; 10%) grafts were from HLA-identical siblings (45%), HLA-matched unrelated donor (MUD; 42%), or MMUD (13%). Antithymocyte globulin was used for 56% of patients and partial T-cell depletion was performed for 52% of patients. Median follow-up was 4.6 years (range: 0–15). Patients’ characteristics and data on transplantation are shown in Table 1. Myeloablative conditioning usually consisted of cyclophosphamide (120 mg/kg) with either total body irradiation These authors contributed equally: Maude Raboud, Yan Beauverd.