Graft-versus-leukaemia effect post fludarabine, melphalan and alemtuzumab reduced intensity allogeneic stem cell transplantat in HIV-infected patient with acute myeloid leukaemia.

Allogeneic stem cell transplantation (Allo-HSCT) is sine qua non to cure high-risk acute myeloid leukaemia (AML). In spite the advent of highly active antiretroviral treatment, HIV-infected patients display a remarkable risk for haematological neoplasms such as non-Hodgkin lymphomas, Hodgkin lymphoma and acute leukaemia. Several case series have confirmed the efficacy of the autologous stem cell transplantation for the treatment of non-Hodgkin lymphomas in the HIV setting. Nonetheless, there is a paucity of data for the role of the Allo-HSCT in HIV-infected individuals with haematological malignancies. Herein, we presented the successful long-term outcome of a HIV-infected patient who received reduced intensity conditioned, matched unrelated donor transplant with alemtuzumab as graft-versus-host disease prophylaxis for therapy-related acute myeloid leukaemia. We propose that Allo-HSCT in HIV patients is safe and that alemtuzumab-based conditioning could further work to eradicate HIV in those whose donor is not CCR5 homozygous.

Impact of pre-transplant co-morbidities on outcome after alemtuzumab-based reduced intensity conditioning allo-SCT in elderly patients: a British Society of Blood and Marrow Transplantation study.

The advent of reduced intensity conditioning (RIC) regimens has permitted the extension of allo-SCT to selected patients into their eighth decade but GVHD remains a major cause of morbidity and mortality. Alemtuzumab is increasingly used to reduce the risk of severe GVHD, but there are concerns that T-cell depletion may compromise outcome particularly in older patients. We therefore studied the impact of pre-transplant factors on the outcome of 187 patients with a haematological malignancy over the age of 60 transplanted using an alemtuzumab-based RIC regimen of whom co-morbidity scoring was possible in 169. Of the patients, 120 had a haematopoietic cell transplantation co-morbidity index (HCT-CI) of 0 or 1 and 49 had a score of 2 or more. The 5-year OS was 33%. In multivariable analysis, OS was determined by co-morbidity score (P=0.001) and disease status at transplant (P=0.004) but not by patient age. Non-relapse mortality was determined by co-morbidity score (P=0.001). Two-year OS for patients with a HCT-CI of 0-1 was 59 versus 6% for patients with a higher score. Alemtuzumab-based RIC allografts can be delivered safely in patients aged over 60 but co-morbidity scoring is mandatory to identify patients who will benefit.

Intestinal lymphoma--a review of the management of emergency presentations to the general surgeon.

INTRODUCTION: Intestinal non-Hodgkin's lymphoma (NHL) is uncommon but not rare. This paper aims to review the recent evidence for the management of perforated NHL of the intestine, consider when chemotherapy should be commenced and examine the likely outcomes and prognosis for patients presenting as surgical emergencies with this condition. METHODS: MEDLINE and Cochrane databases were searched using intestinal lymphoma, clinical presentation, perforation, management and prognosis. The full text of relevant articles was retrieved and reference lists checked for additional articles. FINDINGS: Emergency surgery was required at disease presentation for between 11 and 64% of intestinal NHL cases. Perforation occurs in 1-25% of cases, and also occurs whilst on chemotherapy for NHL. Intestinal bleeding occurs in 2-22% of cases. Obstruction occurs more commonly in small bowel (5-39%) than large bowel NHL and intussusceptions occur in up to 46%. Prognosis is generally poor, especially for T cell lymphomas. CONCLUSIONS: There is a lack of quality evidence for the elective and emergency treatment of NHL involving the small and large intestine. There is a lack of information regarding the impact an emergency presentation has on the timing of postoperative chemotherapy and overall prognosis. It is proposed that in order to develop evidence-based treatment protocols, there should be an intestinal NHL registry.

Post-transplant T cell chimerism predicts graft versus host disease but not disease relapse in patients undergoing an alemtuzumab based reduced intensity conditioned allogeneic transplant.

In this multicentre retrospective study we have studied the impact of T cell chimerism on the outcome of 133 patients undergoing an alemtuzumab based reduced intensity conditioning allograft (RIC). The median age of the patients was 50 years (range 42-55 years). 77 patients were transplanted using an HLA identical sibling donor while 56 patients received a fully matched volunteer unrelated donor graft. 64 patients had a lymphoid malignancy and 69 were transplanted for a myeloid malignancy. 38 patients (29%) relapsed with no significant difference in risk of relapse between patients developing full donor and mixed donor chimerism in the T-cell compartment on D+90 and D+180 post transplant. Day 90 full donor T cell chimerism correlated with an increased incidence of acute GVHD according to NIH criteria (p=0.0004) and the subsequent development of chronic GVHD. Consistent with previous observations, our results confirmed a correlation between the establishment of T cell full donor chimerism and acute GVHD in T deplete RIC allografts. However our study failed to identify any correlation between T cell chimerism and relapse risk and challenge the use of pre-emptive donor lymphocyte infusions (DLI) in patients with mixed T cell chimerism transplanted using an alemtuzumab based RIC regimen.

Midazolam in conjunction with local anaesthesia is superior to Entonox in providing pain relief during bone marrow aspirate and trephine biopsy.

AIM: To compare intravenous titrated midazolam 5-10 mg and inhaled Entonox in addition to local anaesthesia in order to identify which agent provides optimum pain relief. METHODS: Randomised, controlled trial. 49 patients were recruited, of which 46 were evaluable. 24 and 22 patients were recruited into the Entonox and midazolam arms, respectively. Patient experiences as well as staff observations were recorded with questionnaires after recovery from the procedure and 24 hours later. RESULTS: 45% and 59% of the patients in the midazolam arm could recollect the procedure after 15 minutes and 24 hours, respectively, compared to 96% and 88% who received Entonox. Midazolam provided a more comfortable experience (p<0.01) and improved pain relief (p = 0.01) compared to Entonox immediately after the procedure; this further improved when recalled 24 hours later. Nausea, dizziness and hallucinations were observed with both treatments, but dizziness was significantly more frequent with Entonox (p = 0.048). Clinically relevant respiratory depression (O(2) saturation <90%) occurred in 19% of patients in the midazolam arm; sedation was reversed with flumazenil. CONCLUSION: Midazolam in conjunction with local anaesthesia provides rapid and reversible sedation as well as effective pain relief during bone marrow biopsy, and is superior to Entonox; however, care must be taken to monitor respiratory function.