Outcome in patients with diffuse large B-cell lymphoma who relapse after autologous stem cell transplantation and receive active therapy. A retrospective analysis of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation (EBMT).

Autologous hematopoietic stem cell transplantation (auto-HSCT) is the standard of care for patients with diffuse large B-cell lymphoma (DLBCL) who relapse/progress after first line chemoimmunotherapy. Long-term outcome of those who relapse after transplant is poor. We present the results of a retrospective study of 256 adult patients reported to the EBMT registry with DLBCL who relapsed after auto-HSCT performed between 2003 and 2013, and who received active salvage strategies. One hundred and fifty-four (60%) were male; median age was 53 years. Median time to relapse was 7 months, 65% relapsed during the first year. Overall response rate after salvage therapy was 46%. Median follow-up after first salvage therapy was 40 months (IQR 23-63 months). Overall survival (OS) at 3 years was 27% (95% CI 22-33). OS at 3 years of patients relapsing longer than 1 year after auto-HSCT was 41% (95% CI 31-53) compared with 20% (95% CI 14-24) in those who relapsed in less than 1 year. Eighty-two patients (32%) had a second HSCT, an allogeneic HSCT (allo-HSCT) in 69 cases, at a median time of 6.5 months after relapse. OS at 3 years after allo-HSCT was 36% (95% CI 25-51). In conclusion, the prognosis of patients with DLBCL that relapse after auto-HSCT is dismal. Patients who relapse in less than 1 year remain an unmet need, and should be considered for CAR T cell therapy or clinical trials. Patients who relapse after 1 year can be rescued with salvage therapies and a second HSCT. These results provide a benchmark to compare data of new prospective studies.

Medical costs of treatment and survival of patients with acute myeloid leukemia in Belgium.

The advent of new cell-based immunotherapies for leukemia offers treatment possibilities for certain leukemia subgroups. The wider acceptability of these new technologies in clinical practice will depend on its impact on survival and costs. Due to the small patient groups who have received it, these aspects have remained understudied. This non-randomized single-center study evaluated medical costs and survival for acute myeloid leukemia between 2005 and 2010 in 50 patients: patients treated with induction and consolidation chemotherapy (ICT) alone; patients treated with ICT plus allogeneic hematopoietic stem cell transplantation (HCT), which is the current preferred post-remission therapy in patients with intermediate- and poor-risk AML with few co-morbidities, and patients treated with ICT plus immunotherapy using autologous dendritic cells (DC) engineered to express the Wilms' tumor protein (WT1). Total costs including post- consolidation costs on medical care at the hematology ward and outpatient clinic, pharmaceutical prescriptions, intensive care ward, laboratory tests and medical imaging were analyzed. Survival was markedly better in HCT and DC. HCT and DC were more costly than ICT. The median total costs for HCT and DC were similar. These results need to be confirmed to enable more thorough cost-effectiveness analyses, based on observations from multicenter, randomized clinical trials and preferably using quality-adjusted life-years as an outcome measure.

Autologous stem cell transplantation for relapsed/refractory diffuse large B-cell lymphoma: efficacy in the rituximab era and comparison to first allogeneic transplants. A report from the EBMT Lymphoma Working Party.

In the era of chemoimmunotherapy, the optimal treatment paradigm for relapsed and refractory diffuse large B-cell lymphoma has been challenged. We reviewed the outcome of standard salvage therapy with an autologous stem cell transplant (autoSCT) over the last two decades and the outcome of allogeneic SCT (alloSCT) in the most recent decade. AutoSCT recipients diagnosed between 1992 and 2002 (n=2737) were compared with those diagnosed between 2002 and 2010 (n=3980). Patients diagnosed after 2002 had a significantly lower non-relapse mortality (NRM) and relapse incidence (RI) and a superior PFS and overall survival (OS). A total of 4210 patients diagnosed between 2002 and 2010 underwent either an autoSCT or an alloSCT as their first transplant procedure. Two-hundred and thirty patients received an alloSCT (myeloablative (MACalloSCT) n=132, reduced intensity (RICalloSCT) n=98). The 4-year NRM rates were 7%, 20% and 27% for autoSCT, RICalloSCT and MACalloSCT, respectively. The 4-year RI was 45%, 40% and 38% for autoSCT, RICalloSCT and MACalloSCT, respectively (NS). The 4-year PFS were 48%, 52% and 35% for autoSCT, RICalloSCT and MACalloSCT, respectively. The 4-year OS was 60%, 52% and 38% for autoSCT, RIC alloSCT and MACalloSCT, respectively. After adjustment for confounding factors NRM was significantly worse for patients undergoing alloSCT whilst there was no difference in the RI.

A novel HLA-C null allele, HLA-C*05:99N.

HLA-C*05:99N results from a single nucleotide loss compared with its closest allele HLA-C*05:01:01:01.

Relationship between clinical and BK virological response in patients with late hemorrhagic cystitis treated with cidofovir: a retrospective study from the European Group for Blood and Marrow Transplantation.

To investigate the relationship between clinical response and modification of BK viremia, we assessed retrospectively 32 cases of hemorrhagic cystitis (HC) after allogeneic hematopoietic SCT that were treated with i.v. cidofovir (CDV). They were 22 men (69%) and 10 women (31%) with a median age of 24 years, range 3-62. The median number of CDV doses was 3, range 1-8, and the treatment lasted for a median of 3 weeks, range 1-10. Clinical improvement of HC was observed in 27 patients (84%). In 12 of 32 episodes (37.5%), BK viremia was determined before every CDV administration and a complete clinical response was observed in 10 of 12 patients (83%), the reduction of BK viremia load being 1 log by 2 weeks after starting CDV. Nephrotoxicity related to CDV was observed in nine patients. Among 26 patients with 100-day follow-up, 4 of 4 patients who had a complete clinical response by 30 days were alive vs 16 of 22 (73%) who did not have the resolution of HC in this time frame. We conclude that in patients with HC, the response to CDV treatment is usually associated with a significant reduction of BK viremia load.

A warning about agranulocytosis with the use of cocaine adulterated with levamisole.

Since 2004, the US Food And Drug Administration and the European Medicine Agency are giving warnings about cocaine adulterated with levamisole. Levamisole is primarily used as an anti-helminthic. One of the side-effects of levamisole is a decreased bone marrow function. Herein we describe the first case of agranulocytosis and neutropenic fever due to cocaine adulterated with levamisole reported in Europe.

Current diagnostic criteria for the chronic myeloproliferative disorders (MPD) essential thrombocythemia (ET), polycythemia vera (PV) and chronic idiopathic myelofibrosis (CIMF).

The clinical criteria for the diagnosis of essential thrombocythemia (ET) according to the polycythemia vera study group (PVSG) do not distinguish between ET and thrombocythemia associated with early stage PV and prefibrotic chronic idiopathic myelofibrosis (CIMF). The clinical criteria of the PVSG for the diagnosis of polycythemia vera (PV) only detects advanced stage of PV with increased red cell mass. The bone marrow criteria of the World Health Organization (WHO) are defined by pathologists to explicitly define the pathological criteria for the diagnostic differentiation of ET, PV, and prefibrotic and fibrotic CIMF. As the clinical PVSG and the pathological WHO criteria show significant shortcomings, an updated set of European Clinical and Pathological (ECP) criteria combined with currently available biological and molecular markers are proposed to much better distinct true ET from early PV mimicking ET, to distinguish ET from thrombocythemia associated with prefibrotic CIMF, and to define the various clinical and pathological stages of PV and CIMF that has important therapeutic and prognostic implications. Comparing the finding of clustered giant abnormal megakaryocytes in a representative bone marrow as a diagnostic clue to MPD, the sensitivity for the diagnosis of MPD associated with splanchnic vein thrombosis was 63% for increased red cell mass, 52% for low serum EPO level, 72% for EEC, and 74% for splenomegaly indicating the superiority of bone marrow histopathology to detect masked early and overt MPD in this setting. The majority of PV and about half of the ET patients have spontaneous EEC, low serum EPO levels and PRV-1 over-expression and are JAK2 V617F positive. The positive predictive value for the diagnosis of PV of spontaneous growth of endogenous erythroid colonies (EEC) of peripheral blood (PB) and bone marrow (BM) cells is about 80-85% when either PB or BM EEC assays, and up to 94% when BM and PB EEC assays were performed. The diagnostic impact of low serum EPO levels (ELISA assay) in a large study of 186 patients below the normal range (<3.3 IU/l) had a sensitivity specificity and positive predictive value of 87%, 97% and 97.8%, respectively, for the diagnosis of PV. There is a significant overlap of serum EPO levels in PV versus control and controls versus SE. The specificity of a JAK2 V617F PCR test for the diagnosis of MPD is high (near 100%), but only half of ET and MF (50%) and the majority of PV (up to 97%) are JAK2 V617F positive. The use of biological markers including JAK2 V617 PCR test, serum EPO, PRV-1, EEC, leukocyte alkaline phosphatase score and peripheral blood parameters combined with bone marrow histopathology has a high sensitivity and specificity (almost 100%) to diagnose the early and overt stages of ET, PV and CIMF in JAK2 V617F positive and negative MPDs.

A critical appraisal of non-invasive diagnosis and exclusion of deep vein thrombosis and pulmonary embolism in outpatients with suspected deep vein thrombosis or pulmonary embolism: how many tests do we need?

The requirement for a safe diagnostic strategy should be based on an overall posttest incidence of venous thromboembolism of less than 1% during 3 month follow-up. Compression ultrasonography (CUS) has a negative predictive value (NPV) of 97% to 98% indicating the need of repeated CUS testing. Serial CUS testing is safe but you have to repeat 100 CUS to find 1 or 2 CUS positive for deep vein thrombosis (DVT), which is not cost-effective indicating the need to improve the diagnostic work-up of DVT by the use of clinical score assessment and D-dimer testing. The combination of a less sensitive D-dimer test (SimpliRed) and low clinical score does not, whereas the combination of a sensitive D-dimer test (ELISA VIDAS or Tinaquant) and low clinical score does safely exclude DVT without the need of CUS. The combination of a first negative CUS and a negative less sensitive D-dimer test (SimpliRed) or a sensitive ELISA D-dimer at a higher cut off level of 1,000 ng/ml safely excludes DVT with a NPV of > 99% without the need to repeated CUS in about 60%. The sequential use of a sensitive D-dimer and clinical score assessment will safely reduce the need for CUS testing by 40% to 60%. Large prospective outcome studies demonstrate that one negative examination with complete duplex color ultrasonography (CCUS) of the proximal and distal veins of the affected leg with suspected DVT is safe to withhold anticoagulant treatment with a NPV of 99.5%. This indicates that CCUS is equal or superior to serial CUS or the combined use of clinical score, D-dimer testing and CUS. Pulmonary angiography is the gold standard for segmental pulmonary embolism (PE) but not for subsegmental PE. A normal perfusion lung scan and a normal rapid ELISA VIDAS D-dimer test safely exclude PE. Helical spiral CT detects all clinically relevant PE and a large number of alternative diagnoses in symptomatic patients with a non-diagnostic ventilation perfusion scan (VP-scan) or a high probability VP-scan. Single-slice helical CT as the primary diagnostic test in patients with suspected PE in 5 retrospective studies and in 3 prospective management studies indicate that the NPV of a normal helical spiral CT, a negative CUS of the legs together with a low or intermediate pretest clinical probability is 99%. Helical spiral CT can replace both the VP-scan and pulmonary angiography to safely rule in and out PE. The combination of clinical assessment, a rapid ELISA VIDAS D-dimer followed by CUS will reduce the need for helical spiral CT by 40% to 50%.

Diagnosis of deep vein thrombosis: how many tests do we need?

The requirement for a safe diagnostic strategy should be based on an overall post-test incidence of venous thromboembolism (VTE) of less than 1% during 3 month follow-up. Compression ultrasonography (CUS) has a negative predictive value (NPV) of 97 to 98% indicating a post-CUS incidence of deep vein thrombosis (DVT) of 2 to 3%. A post-CUS DVT incidence of 3% implicates that 90 to 120 DVTs per 1 million inhabitants will be overlooked each year indicating the need to improve the diagnostic work-up of DVT as much as possible. The qualitative D-dimer test (SimpliRed) has a sensitivity of 82 to 89% and a negative predictive value of 94 to 95% indicating a 5 to 6% post-test incidence of DVT, which is not sensitive enough for venous thrombosis exclusion. The post-test DVT incidence could be reduced from 3.2% to 0.6% in one study and from 11% to 2% in another study by the combination of a normal CUS and low clinical score and from 4.5% to 1.6% by the combination of low clinical score and a negative SimpliRed test in one study. The combination of a negative CUS and a negative SimpliRed test reduced the post-test incidence of DVT from 2.6% to < 1% or even < 1% in two management studies without the need of a repeated CUS on the basis of which anticoagulant therapy can safely be withheld. The rapid quantitative turbidimetric D-dimer assay (Tinaquant) has a sensitivity and a negative predictive value (NPV) of 97.7% with a 2.3% post-test incidence of DVT. The combination of a normal Tinaquant D-Dimer test result plus a low to moderate clinical score reduces the post-test incidence of DVT from 2.3 to 0.6% without the need of CUS testing in 29% of patients with suspected DVT. The rapid ELISA VIDAS D-dimer assay has a sensitivity and NPV of 98.6 and 99.5% in two management studies for the exclusion of DVT irrespective of clinical score. The combination of a normal ELISA VIDAS D-Dimer test with clinical score assessment will reduce the post-test DVT incidence of less than 0.5% and the need for CUS testing by 40 to 50%. It is concluded that the sequential use of a rapid quantitative D-dimer test, clinical score and CUS appears to be safe and the most cost-effective diagnostic work-up of DVT.

Bortezomib-induced Sweet's syndrome.

Sweet's syndrome is an uncommon acute skin disease, associated with a variety of medical problems. The drug-induced variant is even rarer. We describe two cases of this syndrome associated with the administration of the proteasome inhibitor bortezomib. The diagnostic criteria for drug-induced Sweet's syndrome as proposed by Walker and Cohen were fulfilled. Vasculitis and neutrophilic eccrine hidradenitis were excluded.

Non-invasive exclusion and diagnosis of pulmonary embolism by sequential use of the rapid ELISA D-dimer assay, clinical score and spiral CT.

Pulmonary angiography is the gold standard for segmental pulmonary embolism (PE) but no longer for its subsegmental PE, because the inter-observer agreement for angiographically documented subsegmental PE is only 60%. Two non-invasive tools exclude PE with a negative predictive value of > 99%: a normal perfusion lung scan and a normal rapid ELISA VIDAS D-dimer test. The positive predictive value of a high probability ventilation-perfusion lung scan (VP-scan) is only 85% to 87%. The combination of a low clinical score and a non-diagnostic VP-scan safely exclude PE without the need of angiography. The prevalence of PE and that of an alternative diagnosis in symptomatic patients with a non-diagnostic VP-scan are 10% to 20% and 30% to 45%, respectively. Helical spiral computed tomography (CT) detects all clinically relevant PE and a large number of alternative diagnoses in symptomatic patients with a non-diagnostic or high probability VP-scan. The positive predictive value of the spiral CT is > 95%. Single-slice helical CT as the primary diagnostic test in patients with suspected PE in retrospective outcome studies and in prospective multicenter management studies indicate that the negative predictive value of a negative spiral CT preceded or followed by a negative compression ultrasonography (CUS) is > 99%. Therefore, a helical spiral CT can replace both the VP-scan and pulmonary angiography to safely rule in and out PE. A negative rapid ELISA VIDAS D-dimer test result will reduce the need for helical spiral CT by 25% to 35%.

Aspirin-responsive painful red, blue, black toe, or finger syndrome in polycythemia vera associated with thrombocythemia.

Five patients with red, purple blue, or black toes or fingers due to thrombocythemia associated with polycythemia vera (polycythemia and thrombocythemia vera) in four and essential thrombocythemia (thrombocythemia vera) in one are described. The microvascular erythromelalgic syndrome of thrombocythemia was overlooked and progressed to cold blue swollen and painful fingers or black toes in three patients with polycythemia and thrombocythemia vera due to arteriographically documented occlusions of digital or large peripheral arteries with no evidence of preexistent atherosclerotic vascular disease. Concomitant erythromelalgia of the hand palm could be confirmed by the histopathological findings of arteriolar thrombotic lesions in the reticular dermis in two patients with polycythemia and thrombocythemia vera. The increased hematocrit in the presented patients with polycythemia and thrombocythemia vera contributed to the progression of the microvascular syndrome of thrombocythemia to major occlusive ischemic events of the extremities. Standard therapy with oral anticoagulants and reduction of the hematocrit to normal by bloodletting did not affect the platelet-mediated microvascular erythromelalgic, ischemic symptoms in the patients with polycythemia vera because thrombocythemia vera persisted. Complete relief of pain and restoration of the ischemic acral circulation disturbances in patients with thrombocythemia vera or thrombocythemia associated with polycythemia vera in maintained remission by bloodletting could be obtained by long-term treatment with low-dose aspirin.

Bilateral adrenal swelling as a cause of chest, back, and upper abdominal pain in essential thrombocythemia and polycythemia vera is due to microvascular ischemic thrombosis rather than to hemorrhage.

Bilateral massive adrenal swelling (BAS) on computed tomography (CT) scan with no enhancement after injection of intravenous contrast media has been observed in two completely different clinical settings. On the one hand, BAS is the result of ischemic necrosis and subsequent hemorrhagic infarction in patients with sepsis and hypotension in critically ill situations. On the other hand, BAS is the result of microvascular thrombosis, ischemia, and secondary inflammatory swelling in the setting of thrombotic conditions such as antiphospholipid syndrome (APS), heparin-induced thrombocytopenia and thrombosis (HITT), and thrombocythemia. In this study we present evidence that the etiology of unilateral or BAS in reported cases of essential thrombocythemia (ET) and polycythemia vera (PV) is similar to the etiology of microvascular circulation disturbances in thrombocythemia caused by platelet-mediated inflammation and thrombosis in the peripheral, cerebral, and/or coronary endarterial microvascular circulation.

Thalidomide-induced morbilliform rash: diagnosis and continuation of therapy, premedicated with methylprednisolone.

In the past few years, thalidomide is experiencing a revival in many different fields as a last therapeutic option, because of the potential severe adverse drug reactions (ADR) induced by this drug (teratogenicity, peripheral neuropathy and sedation). Taking into consideration the increased use, we should focus on the prevalence of these and other ADR as well on their management. We describe a patient with multiple myeloma who presented with a morbilliform rash induced by thalidomide. Reintroduction of the drug confirmed the diagnosis. Nevertheless we continued the thalidomide treatment, although combined with methylprednisolone 64 mg. There was no recurrence of the cutaneous drug reaction (CDR). To the best of our knowledge, this is the first case showing that systemic steroids can help to 'treat through' a thalidomide CDR.

Distal deep venous thrombosis in a hemophilia A patient with inhibitor and severe infectious disease, 18 days after recombinant activated factor VII transfusion.

We describe a 38 year old hemophilia A patient with a factor VIII inhibitor who was admitted to our Hematology Department in January 2001 with a seriously infected and bleeding perianal ulcer. To treat infection and bleeding the patient received broad spectrum antibiotics and recombinant activated factor VII (rFVIIa) (Novoseven(R)) for about 1 month (see detailed time of administration and dosing schedule of rFVIIa further in text). Eighteen days after his last rVIIa infusion the patient developed an ultrasound proven right calf vein thrombosis. In the whole period of admission, preceding the thrombotic event the patient biologically showed a picture of severe systemic inflammatory disease as indicated by persistent increased levels of D-dimer and fibrinogen (table). It is an interesting point of discussion whether the calf thrombosis was provoked as a consequence of rFVIIa infusion (with symptoms 18 days after the last infusion) or as a consequence of long-standing immobilization and severe inflammatory disease immobilization and severe infection are conditions well known for promoting venous thromboembolic disease.

Exclusion and diagnosis of deep vein thrombosis in outpatients by sequential noninvasive tools.

Phlebography is the reference gold standard for the diagnosis of deep vein thrombosis (DVT), but due to its invasive nature and associated side effects it has been replaced by compression ultrasonography (CUS). Patients suspected of DVT are subjected to leg vein CUS that actually confirms DVT in only 16 to 28% of outpatients in large prospective management studies. CUS has a high positive predictive value of more than 98% for proximal DVT but usually misses calf vein thrombosis. Its negative predictive value for proximal DVT is about 97-98%, on the basis of which repeated scanning at day 7 after a negative first CUS (serial CUS) in outpatients with a first suspicion of DVT is advocated. Serial ultrasonography is costly and can be simplified and improved by the addition of clinical score and D-dimer testing. The safe exclusion of DVT by a rapid sensitive D-dimer test in combination with clinical score and/or CUS requires a negative predictive value of >99%. The negative predictive value for DVT is determined by the sensitivity of the rapid ELISA D-dimer test and the prevalence of DVT in subgroups of outpatients suspected of the condition. The prevalence of DVT in outpatients with a low, moderate and high clinical score varies widely from 3-10%, 15-30% and >70%, respectively. The combination of a low clinical score (prevalence DVT 3-5%) and a negative rapid ELISA D-dimer alone test will have a very high negative predictive value of >99.9% to exclude DVT without the need of CUS testing. The combination of a negative CUS and a negative rapid ELISA D-dimer test safely excludes DVT in patients with suspected DVT irrespective of the clinical score. The combination of a negative CUS, a low clinical score and a positive ELISA D-dimer but <1000 ng/ml excludes DVT with a negative predictive value of >99% without the need to repeat CUS. Patients with a negative CUS, scan but a positive ELISA D-dimer, and a moderate or high clinical score are still at risk with a probability of DVT of 3-5% and 20-30%, respectively and are thus candidates for repeated ultrasound scanning. The rapid ELISA D-dimer first followed by risk-based no, single or repeated CUS will be the most cost-effective strategy.

Folate and Vitamin B(12) deficiency presenting as pancytopenia in pregnancy: a case report and review of the literature.

We present a case of extreme pancytopenia in a 27-year-old pregnant woman. The initial picture was compatible with a severe hematological problem in the category of aplastic anemia, paroxysmal nocturnal hemoglobinuria or even acute leukemia. The further biochemical investigations revealed, however, a folate deficiency. Nowadays this is a very rare cause of pancytopenia. Next to this she also had a Vitamin B(12) deficiency due to intrinsic factor failure. The recent literature is discussed.

Acquired von Willebrand syndromes: clinical features, aetiology, pathophysiology, classification and management.

Acquired von Willebrand syndrome (AVWS) associated with hypothyroidism is of type I, results from a decreased synthesis of factor VIII and von Willebrand factor (VWF), responds to desmopressin with normal half-life times for factor VIII and VWF parameters, and disappears after treatment with I-thyroxine. AVWS type I or III, which occurs in a minority of patients with Wilms' tumour in the complete absence of an inhibitor against VWF and no absorption of factor VIII or VWF onto nephroblastoma cells, responds to chemotherapy and/or tumour resection. Hyaluronic acid produced by nephroblastoma cells may be the causative factor in atypical AVWS in Wilms' tumour. AVWS associated with thrombocythaemia of various myeloproliferative disorders is characterized by normal factor VIII and von Willebrand factor antigen (VWF: Ag) levels and a selective deficiency of functional ristocetin co-factor activity (VWF: RCo) and collagen-binding activity (VWF: CBA). AVWS type II in thrombocythaemia is caused by a platelet-dependent proteolysis of large VWF multimers, given the inverse relationship between platelet count and large VWF multimers in plasma and specific increases in the number of proteolytic VWF fragments in plasma. The laboratory findings of AVWS associated with systemic lupus erythematosus or IgG benign monoclonal gammopathy are characterized by a prolonged bleeding time and activated partial thromboplastin time, decreased or absent ristocetin-induced platelet activity, low to very low levels of factor VIII coagulant activity (mean 15%), VWF: Ag (mean 10.7%) and VWF: RCo (mean 6.2%), and a type II multimeric pattern of VWF. Neutralizing and non-neutralizing anti-VWF autoantibodies, usually IgG, have been detected in patient plasma either free or tightly bound to the intermediate and high molecular weight VWF factor VIII particles. The bound auto antibody-antigen complex is rapidly cleared from the circulation, resulting in low levels of factor VIII, VWF parameters as documented by a poor response to desmopressin and VWF factor VIII concentrate. High-dose intravenous immunoglobulin transiently corrects the factor VIII coagulant and VWF levels, lasting for a few weeks in AVWS type II associated with systemic lupus erythematosus or IgG benign monoclonal gammopathy. Prednisolone is effective in AVWS associated with autoimmune disorder. Prednisolone and chemotherapy will not affect AVWS associated with IgG benign monoclonal gammopathy because the monoclonal IgG protein remains to act as an anti-VWF autoantibody. An absorption of VWF to malignant cells has been documented in a few patients with various lymphoproliferative disorders or adrenal carcinoma and suggested to result in a depletion of VWF. The clinical picture of AVWS associated with early-stage IgG multiple myeloma, chronic lymphocytic leukaemia or non-Hodgkin's lymphoma without a paraprotein or no detectable underlying disorder is similar to that of AVWS type II in IgG benign monoclonal gammopathy but poorly documented with regard to the underlying immune mechanism of AVWS. The mechanical destruction of large VWF multimers may be of relevance in conditions in which the shear rate of flowing blood is increased, as may occur in cases of aortic stenosis, other heart valve defects or stenosed vessels. Drug-induced AVWS has been described in association with the use of pesticides valproic acid, ciprofloxacin, griseofulvin, tetracycline, thrombolytic agents and hydroxyethyl starch.

Intravascular large B-cell lymphoma or intravascular lymphomatosis: report of a case diagnosed by testicle biopsy.

Intravascular large B-cell lymphoma or intravascular lymphomatosis (IVL) is an extremely rare form of non-Hodgkin's lymphoma. The most common clinical sign is fever of unknown origin (FUO). Histologically, there is proliferation of malignant lymphoid cells within vascular lumina. Cytologically, the cells have features similar to those found in classical large cell lymphoma. Examination of pulmonary artery blood showed the presence of this abnormal population in our patient; to the best of our knowledge there are only four other. reports of detection of circulating tumor cells in IVL. The outcome is very poor. The diagnosis is most frequently made after biopsy of skin or brain but is often established post mortem. We present what is--to our knowledge--the first reported case of IVL diagnosed after biopsy of a testicle. In the event of FUO and suspicion of a malignancy, IVL--although very rare--should be one of the differential diagnoses.