Janine Campbell

The prognostic impact of bone marrow involvement in patients with diffuse large cell lymphoma varies according to the degree of infiltration and presence of discordant marrow involvement.

Abstract:  Background: The prognostic significance of marrow involvement in diffuse large cell lymphoma (DLCL) is controversial. Factors that that have been reported to influence prognosis include the pattern and extent of marrow infiltration and histological discordance between the primary site and the bone marrow. Methods: Bone marrow biopsies from 172 patients with newly diagnosed DLCL entered in two consecutive trials of the Australasian Leukaemia and Lymphoma Group were analyzed. Progression‐free (PFS) and overall survival (OS) were calculated according to the absence or presence of bone marrow involvement (BMI), the extent of lymphomatous infiltration and the presence of histological discordance between the primary site and the bone marrow. Results: Of 172 patients with DLCL accrued between 1982 and 1990, who were treated with CHOP or CHOP‐like regimens, 47 (27%) demonstrated marrow involvement on examination of multiple levels. Seventy two percent (34/47) of patients had discordant marrow involvement (<50% large cells) and 28 had minimal (<10%) involvement; these latter patients with minimal marrow involvement (<10%) had similar PFS & OS to the 113 patients without involvement. Within the group of 47 patients with marrow involvement, an increasing percentage of BM involvement was significantly associated with an increasing percentage of concordant histology and a decreasing PFS & OS. Conclusions: Minimal BMI, seen in the majority of patients with DLCL with marrow infiltration, appears not to influence the PFS & OS. However, an increasing degree of marrow involvement is associated with an increasing component of large cells and a poorer prognosis in DLCL patients, independent of other risk factors.

Bleeding disorders in teenagers presenting with menorrhagia

Objective:  To assess the prevalence of bleeding disorders and establish the clinical variables that are predictive of a bleeding disorder in adolescent women.

Venous thromboembolic disease: a single-centre case series study.

Aim:  The epidemiology of venous thromboembolism in children has likely changed since first being described a decade ago because of evolving management strategies and a greater awareness of predisposing factors for thrombosis in children. The Royal Childrens Hospital commenced a 4‐year prospective registry of venous thrombosis in 1999 to determine the current Australian epidemiology of venous thrombosis in infants and children.

Arterial thromboembolic disease: A single-centre case series study

Aim:  Paediatric venous thromboembolic disease has been reported with increased frequency during the last decade. In contrast, the pathophysiology of arterial thromboembolic disease in infants and children has not been adequately explored. The aim of this study was to determine the prevalence, aetiology, diagnostic criteria, management and outcome of arterial thromboembolism (TE) in a tertiary paediatric centre.

Anticoagulation in neonates and children: Pitfalls and dilemmas

Anticoagulation in children is problematic for many reasons, related to the patient population as well as the anticoagulant drugs themselves. This paper describes the multitude of reasons why providing anticoagulation therapy in children is different from anticoagulation therapy in adults, and hence why dedicated paediatric anticoagulant services are the ideal structure to provide this service. The paper then describes the three most common anticoagulants used in children, and details specifically what is and is not known about them in the paediatric population. Finally the paper addresses the issue of how best to introduce newer anticoagulant drugs into the paediatric population. There remains much research to be done in this field, in the meantime clinicians need to carefully consider the evidence available to them and manage each individual patient accordingly.

Assessing the outcome of systemic tissue plasminogen activator for the management of venous and arterial thrombosis in pediatrics.

This study sought to ascertain the outcomes of systemic thrombolytic therapy used in a cohort of infants and children. Complete thrombus resolution was achieved in 81% of patients with arterial thromboses (n=16) compared to 0% of children with venous thromboses (n=10). A major bleeding rate of 11.5% occurred across the entire cohort (n=3, all arterial). In our cohort, no patient with venous thromboembolism achieved complete resolution of their thrombosis after thrombolytic therapy. More cohort studies reporting the outcome of uniform protocols of thrombolytic therapy in children are required.

Evaluation of a post-operative thrombin inhibitor replacement protocol to reduce haemorrhagic and thrombotic complications after paediatric liver transplantation.

INTRODUCTION Bleeding and thrombotic complications contribute to morbidity and mortality following paediatric orthotopic liver transplantation (OLT). However, the pathophysiology of haemostasis during paediatric OLT is not well understood. This report consists of two complimentary studies examining the frequency of haemostatic complications before and after the introduction of a post-operative thrombin inhibitor replacement therapy protocol at a single institution. MATERIALS AND METHODS A retrospective study of 40 patients who underwent 43 liver transplants between July 1992 and July 2002, identified bleeding to be the most frequent complication associated with OLT (30%), however thrombotic complications were also common (12.5%). In 2003, following a detailed analysis of haemostatic profiles of children undergoing OLT, a thrombin inhibitor replacement protocol was introduced. A prospective clinical outcome audit was undertaken from April 2003 to September 2008 to determine the effect of the new protocol on haemostasis. RESULTS Commencement of the thrombin inhibitor replacement protocol significantly reduced the incidence of thrombosis (from 5 to 1, p<0.05), graft loss (from 4 to none, p<0.05), mortality due to thrombosis or bleeding (from 3 to none, p<0.05) and was associated with a 50% reduction in frequency of major bleeding. CONCLUSION In conclusion, the introduction of a post-operative thrombin inhibitor replacement therapy protocol following paediatric OLT significantly improved haemostasis-related morbidity and mortality outcomes in children.

Diffuse Large Cell Lymphoma and t(8;22) (q24;q11) in a Patient with Idiopathic CD4+ T-Lymphopenia

We describe a unique case of a patient with a three-year history of idiopathic CD4+T cell lymphopenia (HIV negative) who presented with stage IV diffuse large cell non Hodgkins lymphoma with t(8;22). Despite the severe lymphopenia, the patient tolerated intensive chemotherapy well and at 18 months, remains in complete remission.

The prevalence of inherited thrombophilic polymorphisms in an asymptomatic Australian antenatal population.

Aim: Inherited thrombophilic polymorphisms have been linked to pregnancy‐related thromboembolism and other adverse pregnancy outcomes. As there are limited data on the prevalence of these polymorphisms in Australian populations, we aimed to assess this in an antenatal population.

Autoimmune thrombocytopenia versus idiopathic thrombocytopenic purpura

To the Editor: I have read Drs Campbell and Mitchell’s letter entitled “Immune thrombocytopenia in association with acute lymphoblastic leukemia and a hemophagocytic syndrome” in the October issue of the Journal (1993: 51: 259-261). I would like to indicate that every idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder since antiplatelet antibodies could be shown in each case even after remission (1). However, not every autoimmune thrombocytopenia (AITP) is ITP by definition, despite demonstration of antiplatelet antibodies, which may also be shown in septicemia (2, 3). Therefore, the diagnosis of ITP mainly depends on exclusion of some autoimmune disorders such as systemic lupus erythematosus, Coombs and antinuclear antibodies, throat culture, quantitative gammaglobulin determination and bone marrow studies for the exclusion of bone marrow hypoplasia, infiltration with tumoral and storage cells (etc), in addition to history of drug ingestion, including aspirin. The authors’ patient had bone marrow infiltration with hemophagocytosis, both of which could cause thrombocytopenia. However, if the authors’ patient had had ITP, it could be proven by the demonstration of antiplatelet antibodies in remission also, as was shown by us (1,4), up to 6 years after remission. We have also shown that these antibodies are not present in secondary thrombocytopenia cases, including leukemias (1). The authors have the chance to show antiplatelet antibodies in their patient as in Rao and Pang’s patient (5-7). If the authors could also give proof of such association they could treat their patient’s ITP and ALL by using megadose methylprednisolone (810) orally, which is as effective as the intravenous route (1 1). Instead of “reduced hemopoiesis and granulopoiesis in the bone marrow” as stated by the authors, “erythropoiesis and granulopoiesis” would be more appropriate for the description of bone marrow findings. References