Role of upfront autologous transplant for peripheral T-cell lymphoma patients achieving a complete remission with first-line therapy: a systematic review and meta-analysis.

There is currently no consensus on the role of upfront autologous transplantation (ASCT) for patients with peripheral T-cell lymphomas (PTCL), especially in patients achieving first complete remission (CR1) following chemotherapy, and data in the literature is conflicting. A systematic review and meta-analysis was performed to address this question. We searched key databases from January 2000 to February 2022. Six prospective and eleven retrospective studies were included among 2959 unique records. Median follow up in these studies ranged from 22 to 94 months. There was a trend towards benefit in PFS (HR = 0.80, 95% CI 0.62-1.05, p = 0.11) and OS (HR = 0.79, 95% CI 0.57-1.09, p = 0.15) in the ASCT compared to chemotherapy only group. Importantly, in transplant eligible patients in CR1, a significant benefit was demonstrated in both OS (HR = 0.59, 95% CI 0.36-0.95, p = 0.03) and PFS (HR = 0.61, 95% CI 0.47-0.81, p = 0.0004) in the ASCT group. Amongst the nodal PTCL subgroups, ASCT showed a significant PFS benefit for the AITL subgroup (HR = 0.43, 95% CI 0.20-0.94, p < 0.03) but not PTCL-NOS or ALK-ve ALCL subgroups. Our findings support upfront ASCT for transplant eligible PTCL patients achieving CR1 post chemotherapy. In particular, patients with AITL exhibited a significantly better PFS after upfront ASCT.

Assessment of von Willebrand disease as a risk factor for primary postpartum haemorrhage.

It is not clear whether von Willebrand disease (VWD) is associated with an increased risk of postpartum haemorrhage (PPH). We assessed the effect of VWD on PPH in a case-control study. Logistic regression was used to test for differences in the odds of PPH in deliveries to women with and without VWD, before and after adjustment for known risk factors. A total of 62 deliveries in 33 women with VWD were compared with controls matched for age, year of delivery and parity. Primary PPH was observed in 12/62 (19.4%) deliveries in women with VWD and 16/124 (12.9%) controls. The unadjusted odds ratio (OR) for VWD as a risk factor for PPH was 1.62 (95% CI 0.75-3.49, P = 0.22). After adjustment for other risk factors for PPH, the OR for VWD as a risk factor for PPH was 1.31 (95% CI 0.48-3.60, P = 0.60). PPH was observed in 7/24 (29%) deliveries in women known prepregnancy to have VWD. The unadjusted odds for VWD as a risk factor for PPH in this group was significantly greater than the control group (OR 2.78 (95% CI 1.03-7.49) P = 0.043) and remained significant after adjusting for other significant risk factors (OR 3.41 (95% CI 1.07-10.9) P = 0.038). VWD in itself may not be a significant risk factor for PPH, however, women known to have VWD predelivery may represent an at risk sub-group.

Guidelines on the assessment of bleeding risk prior to surgery or invasive procedures. British Committee for Standards in Haematology.

Unselected coagulation testing is widely practiced in the process of assessing bleeding risk prior to surgery. This may delay surgery inappropriately and cause unnecessary concern in patients who are found to have 'abnormal' tests. In addition it is associated with a significant cost. This systematic review was performed to determine whether patient bleeding history and unselected coagulation testing predict abnormal perioperative bleeding. A literature search of Medline between 1966 and 2005 was performed to identify appropriate studies. Studies that contained enough data to allow the calculation of the predictive value and likelihood ratios of tests for perioperative bleeding were included. Nine observational studies (three prospective) were identified. The positive predictive value (0.03-0.22) and likelihood ratio (0.94-5.1) for coagulation tests indicate that they are poor predictors of bleeding. Patients undergoing surgery should have a bleeding history taken. This should include detail of previous surgery and trauma, a family history, and detail of anti-thrombotic medication. Patients with a negative bleeding history do not require routine coagulation screening prior to surgery.

Rare acquired bleeding disorders.

Accurate diagnosis of the cause of bleeding is a prerequisite for determination of the optimal therapeutic response. Clinicians are generally aware of the more prevalent hemorrhagic syndromes but some rare acquired conditions are also of importance. In many of these, inhibitors of coagulation factors or of platelet adhesion/aggregation cause bleeding. These inhibitors are generally, but not always, immunoglobulins. In this review, the less common inhibitors of coagulation and hemostasis, as well as some important but rare nutritional, iatrogenic and disease associated hemorrhagic disorders, are described.

Coagulation.

The haemostatic system comprises four compartments: the vasculature, platelets, coagulation factors, and the fibrinolytic system. There is presently no laboratory or near-patient test capable of reproducing the complex regulated interaction between these four compartments. The prothrombin time (PT) and activated partial thromboplastin time (APTT) only test the coagulation protein compartment of the system and results have to be carefully interpreted in the context of the clinical presentation and assay limitations. This article will give a general overview of the limitations of PT and APTT and discuss specific issues that need to be considered when the tests are requested, in the context of anticoagulant monitoring, bleeding symptoms, and routine preoperative screening. Of these indications, routine preoperative screening is the most controversial and is generally not warranted in the absence of an abnormal bleeding history.

Air travel and thrombosis.

The current literature suggests a weak association between long-distance travel and the development of asymptomatic venous thromboembolism (VTE). Most of the data available relate to air travel and suggest that the risk is largely confined to asymptomatic calf vein thrombosis in passengers with additional risk factors for VTE, travelling for more than 8 h. The risk of both symptomatic and fatal pulmonary embolism (PE) is very small. The causal role of travel-related factors (e.g. stasis, dehydration, cramped seats and hypobaric hypoxia) is not yet proved but, given the plausible risk-free benefit, all passengers should be advised to maintain adequate hydration and exercise. There is currently no evidence for 'routine' thromboprophylaxis using stockings or drugs. In passengers with additional risk factors for VTE, thromboprophylaxis in the form of below-knee graduated compression stockings (providing 15-30 mmHg at the ankle) and/or prophylactic dose low-molecular-weight heparin may be considered. The evidence does not support the use of aspirin, which is associated with a significant rate of adverse gastrointestinal effects.

Inferior vena cava malformation as a risk factor for deep venous thrombosis in the young.

Conditions which result in hypercoagulable blood or venous stasis may predispose to the development of deep vein thrombosis (DVT). Most of the recently described risk factors for DVT induce a hypercoagulable state. Over a 3-year period we have observed anomaly of the inferior vena cava (IVC) in four young patients presenting with spontaneous unprovoked DVT. This is a greater than expected rate (5% observed versus 0.5% expected). Further, bilateral DVT, which constitutes less than 10% of cases in most series, was present in three of the four cases. Anomaly of the IVC is a rare example of a prevalent congenital condition that predisposes to DVT, presumably by favouring venous stasis. This diagnosis should be considered in young patients with spontaneous and bilateral DVT.

Acute promyelocytic leukaemia with t(11;17)(q23;q12-21) and a good initial response to prolonged ATRA and combination chemotherapy.

Acute myeloid leukaemia (AML) of FAB subtype M3 is associated with t(15;17)(q22;q21) and a relatively good prognosis when treated with all-trans retinoic acid (ATRA) and combination chemotherapy. Rarely, alternative balanced translocations have been described in this subtype of AML. The translocation t(11;17)(q23;q21) leading to a PLZF/RARalpha rearrangement has been described in a very small number of cases and has been associated with a poor response to ATRA and an adverse prognosis. We describe a case of AML FAB type M3 with this translocation who entered morphological and cytogenetic complete remission after concurrent prolonged ATRA and one course of induction chemotherapy and remains in morphological and molecular remission at 10 months after presentation. This diagnosis therefore may not always be associated with a poor initial response to treatment.

Sight-threatening varicella zoster virus infection after fludarabine treatment.

Varicella zoster virus (VZV) infection involving the posterior segment of the eye after fludarabine treatment has not previously been described. Two patients, who had completed fludarabine treatment 3 and 18 months previously, presented with visual loss that had been preceded by a recent history of cutaneous zoster. The use of the polymerase chain reaction (PCR) for VZV DNA from ocular specimens allowed rapid confirmation of clinical diagnosis and treatment with a good outcome in one patient. With the increasing use of fludarabine and other purine analogues, an awareness of such complications is important because of their potentially sight-threatening consequences.