Lymphocyte reconstitution following autologous stem cell transplantation for progressive MS.

BACKGROUND: Autologous stem cell transplantation (ASCT) for progressive multiple sclerosis (MS) may reset the immune repertoire. OBJECTIVE: The objective of this paper is to analyse lymphocyte recovery in patients with progressive MS treated with ASCT. METHODS: Patients with progressive MS not responding to conventional treatment underwent ASCT following conditioning with high-dose cyclophosphamide and antithymocyte globulin. Lymphocyte subset analysis was performed before ASCT and for two years following ASCT. Neurological function was assessed by the EDSS before ASCT and for three years post-ASCT. RESULTS: CD4+ T-cells fell significantly post-transplant and did not return to baseline levels. Recent thymic emigrants and naïve T-cells fell sharply post-transplant but returned to baseline by nine months and twelve months, respectively. T-regulatory cells declined post-transplant and did not return to baseline levels. Th1 and Th2 cells did not change significantly while Th17 cells fell post-transplant but recovered to baseline by six months. Neurological function remained stable in the majority of patients. Progression-free survival was 69% at three years. CONCLUSION: This study demonstrates major changes in the composition of lymphocyte subsets following ASCT for progressive MS. In particular, ablation and subsequent recovery of thymic output is consistent with the concept that ASCT can reset the immune repertoire in MS patients.

Treatment of patients with multiple myeloma who are not eligible for stem cell transplantation: position statement of the myeloma foundation of Australia Medical and Scientific Advisory Group.

Options for treatment of elderly patients with multiple myeloma have expanded substantially following the development of immunomodulatory drugs (IMiD), proteasome inhibitors and with enhancement in safety of high-dose therapy and autologous stem cell transplant (HDT + ASCT). The recognition of biological heterogeneity among elderly patients has made delivery of therapy more challenging. An individualised approach to treatment selection is recommended in an era in which highly efficacious treatment options are available for transplant-ineligible patients. Here, we summarise recommendations for patients who are considered unsuitable for HDT + ASCT, including pretreatment considerations, and induction, maintenance and supportive care therapies.

Treatment of patients with multiple myeloma who are eligible for stem cell transplantation: position statement of the Myeloma Foundation of Australia Medical and Scientific Advisory Group.

The survival of patients with multiple myeloma (MM) has improved substantially since the introduction in the late 1980s of high-dose chemotherapy (HDT) supported by autologous stem cell transplantation (ASCT). Further improvements have been observed following the availability of immunomodulatory drugs (IMiD) such as thalidomide and lenalidomide, and the proteasome inhibitor, bortezomib. Here, we summarise the recommendations of the Medical Scientific Advisory Group to the Myeloma Foundation of Australia for patients considered suitable for HDT + ASCT as part of initial therapy. These recommendations incorporate the various phases of treatment: induction, HDT conditioning and maintenance therapy.

Management of systemic AL amyloidosis: recommendations of the Myeloma Foundation of Australia Medical and Scientific Advisory Group.

Systemic AL amyloidosis is a plasma cell dyscrasia with a characteristic clinical phenotype caused by multi-organ deposition of an amyloidogenic monoclonal protein. This condition poses a unique management challenge due to the complexity of the clinical presentation and the narrow therapeutic window of available therapies. Improved appreciation of the need for risk stratification, standardised use of sensitive laboratory testing for monitoring disease response, vigilant supportive care and the availability of newer agents with more favourable toxicity profiles have contributed to the improvement in treatment-related mortality and overall survival seen over the past decade. Nonetheless, with respect to the optimal management approach, there is a paucity of high-level clinical evidence due to the rarity of the disease, and enrollment in clinical trials is still the preferred approach where available. This review will summarise the Clinical Practice Guidelines on the Management of Systemic Light Chain (AL) Amyloidosis recently prepared by the Medical Scientific Advisory Group of the Myeloma Foundation of Australia. It is hoped that these guidelines will assist clinicians in better understanding and optimising the management of this difficult disease.

Prognostic nomogram for diffuse large B-cell lymphoma incorporating the International Prognostic Index with interim-positron emission tomography findings.

BACKGROUND/AIMS: Results from interim-positron emission tomography (PET) studies in diffuse large B-cell lymphoma (DLBCL) patients are varied. We evaluated the prognostic value of interim-PET in our centre. To improve concordance, interim-PET was combined with the International Prognostic Index (IPI). METHODS: We retrospectively reviewed 100 new consecutive DLBCL patients treated with immunochemotherapy from 2005 to 2010. Twenty-four patients did not receive interim-PET and were excluded. Interim-PET images were re-examined using a qualitative assessment technique. Progression-free survival (PFS) and overall survival (OS) were analysed by the Cox proportional hazards model and prognostic accuracy was assessed using Harrell's C statistics (C). RESULTS: Eleven patients were positive, and 65 were negative at interim-PET. The 2-year OS and PFS were 70.8% and 60.0%, respectively, in the PET-negative group, 36.4% and 36.4% for the PET-positive group (log-rank P-value 0.0008 for PFS, 0.0001 for OS). The IPI and interim-PET were minimally correlated. On Cox regression analysis, both were significant indicators of PFS (P < 0.001 and P = 0.002 respectively). The prognostic accuracy for PFS of a negative PET result was limited (C = 0.63), as it was for IPI (C = 0.75), but with the two indicators combined, the predictive accuracy was improved (C = 0.81). A nomogram, predictive for relapse-free survival at 2 years, was constructed. CONCLUSION: In DLBCL patients treated with immunochemotherapy, the IPI and interim-PET provide independent prognostic information. In combination, a more powerful predictive model may be created as a nomogram. This can be refined in prospective trials and may help clinical decision making.

Tacrolimus-induced thrombotic microangiopathy in orthotopic liver transplant patients: case series of four patients.

Thrombotic microangiopathy (TMA) is a potentially fatal complication in solid organ and bone marrow transplant patients, with reported incidence of 0.5-3% and mortality of about 75%. To emphasise the importance of early diagnosis and prompt commencement of therapy results in improved clinical outcomes. A retrospective study of all patients who underwent orthotopic liver transplantation (OLTX) at the Western Australian Liver Transplantation Service from May 1994 to December 2010 was conducted to identify patients who developed tacrolimus-induced TMA. We identified four patients with tacrolimus-induced TMA post-OLTX, derived from a cohort of 104 patients treated with tacrolimus in our institution. The mean age at diagnosis was 40 years, and the mean time of onset was 63 ± 7.5 weeks after OLTX. The indications for OLTX in the four patients were fulminant hepatic failure in three (Wilson disease, paracetamol overdose and post-partum thrombotic thrombocytopenic purpura) and hepatitis C virus-related cirrhosis. All patients had tacrolimus post-OLTX. At diagnosis, tacrolimus was discontinued in all patients, and three of the four patients underwent plasma exchange and all patients improved clinically. Mean duration of follow up was 15 ± 7.5 months. There was no mortality 6 months post-TMA. Early diagnosis with immediate discontinuation or conversion of calcineurin inhibitors and plasma exchange should be offered to OLTX patients with TMA as it results in good outcomes.

When the safety net of treatment has been removed: patients' unmet needs at the completion of treatment for haematological malignancies.

OBJECTIVE: To determine patients' information, emotional and support needs at the completion of treatment for a haematological malignancy. METHODS: A self-report questionnaire was mailed to 113 adult patients. RESULTS: Sixty-six questionnaires were returned. The most frequently endorsed patient needs related to care co-ordination and help to manage the fear of recurrence. The most frequently endorsed unmet needs included managing the fear of recurrence, the need for a case-manager and the need for communication between treating doctors. Predictors of unmet needs included younger patients (p=0.01), marital status (p=0.03) and employment (p=0.03). Almost two-thirds of patients (59%) reported they would have found it helpful to talk with a health care professional about their experience of diagnosis and treatment at the completion of treatment and endorsed significantly more need in the arenas of Quality of Life (p=0.03) and Emotional and Relationships (p=0.04). CONCLUSION: This study provides valuable data on haematological cancer patients' needs in the first 12 months of finishing treatment. It appears that many needs emerge or remain unresolved at this time. PRACTICE IMPLICATIONS: An opportunity for patients to talk with a health professional about making the transition from active treatment to extended survivorship may be helpful.

Unsuspected colchicine overdose in a female patient presenting as an acute abdomen.

We report a case of multi-system organ failure as a result of unsuspected colchicine overdose in a patient with known gout and bulimia nervosa. The patient had initially presented with mild gastrointestinal symptoms with rapid progression to fulminant hepatic failure and multiple organ dysfunction before the causative agent was identified. The patient survived with aggressive intensive care support and ongoing medical treatment. Physicians should be aware of the risk assessment based on the ingested dose, that the clinical presentation of colchicine in toxic doses may be nonspecific with high potential for severe morbidity or death and that survival may occur despite multiple organ failure requinng aggressive support.

Urgent liver transplantation for acute liver failure due to parvovirus B19 infection complicated by primary Epstein-Barr virus and cytomegalovirus infections and aplastic anaemia.

An 11-year-old boy presented with hepatic failure secondary to parvovirus B19 infection, requiring urgent liver transplantation. His recovery was complicated by primary Epstein-Barr virus and cytomegalovirus infections. He subsequently developed aplastic anaemia that has been refractory to antithymocyte globulin and cyclosporine therapy and may now require bone marrow transplantation. We present this case to emphasize parvovirus as a rare cause of hepatic failure and of aplastic anaemia as a complication of the virus.

The utility of an automated electronic system to monitor and audit transfusion practice.

BACKGROUND AND OBJECTIVES: Transfusion laboratories with transfusion committees have a responsibility to monitor transfusion practice and generate improvements in clinical decision-making and red cell usage. However, this can be problematic and expensive because data cannot be readily extracted from most laboratory information systems. To overcome this problem, we developed and introduced a system to electronically extract and collate extensive amounts of data from two laboratory information systems and to link it with ICD10 clinical codes in a new database using standard information technology. MATERIALS AND METHODS: Three data files were generated from two laboratory information systems, ULTRA (version 3.2) and TM, using standard information technology scripts. These were patient pre- and post-transfusion haemoglobin, blood group and antibody screen, and cross match and transfusion data. These data together with ICD10 codes for surgical cases were imported into an MS ACCESS database and linked by means of a unique laboratory number. Queries were then run to extract the relevant information and processed in Microsoft Excel for graphical presentation. We assessed the utility of this data extraction system to audit transfusion practice in a 600-bed adult tertiary hospital over an 18-month period. RESULTS: A total of 52 MB of data were extracted from the two laboratory information systems for the 18-month period and together with 2.0 MB theatre ICD10 data enabled case-specific transfusion information to be generated. The audit evaluated 15,992 blood group and antibody screens, 25,344 cross-matched red cell units and 15,455 transfused red cell units. Data evaluated included cross-matched to transfusion ratios and pre- and post-transfusion haemoglobin levels for a range of clinical diagnoses. Data showed significant differences between clinical units and by ICD10 code. CONCLUSION: This method to electronically extract large amounts of data and linkage with clinical databases has provided a powerful and sustainable tool for monitoring transfusion practice. It has been successfully used to identify areas requiring education, training and clinical guidance and allows for comparison with national haemoglobin-based transfusion guidelines.

Rituximab is effective in the management of refractory autoimmune cytopenias occurring after allogeneic stem cell transplantation.

Autoimmune haemolytic anaemia (AIHA), immune thrombocytopenia (ITP) and autoimmune neutropenia (AIN) are well-recognised complications of allogeneic stem cell transplantation (SCT), but have previously only been reported in the context of myeloablative conditioning regimens. Management of AIHA, ITP or AIN occurring after allogeneic SCT is unsatisfactory since they frequently prove refractory to conventional therapies including splenectomy. As a consequence, autoimmune cytopenias occurring after allogeneic SCT are associated with substantial morbidity and mortality. We report four patients who developed AIHA or ITP after allogeneic transplantation -- three of which occurred after a reduced-intensity conditioning (RIC) regimen. All patients demonstrated a complete response to Rituximab, having failed to respond to conventional treatment including high-dose prednisolone and intravenous immunoglobulin (IVIg). We conclude that Rituximab can be a valuable agent in the management of autoimmune cytopenias occurring after allogeneic SCT and that autoimmune cytopenias may be a hitherto unrecognised complication of RIC regimens.