Allogeneic stem-cell transplantation using a reduced-intensity conditioning regimen has the capacity to produce durable remissions and long-term disease-free survival in patients with high-risk acute myeloid leukemia and myelodysplasia.

PURPOSE: The toxicity of allogeneic stem-cell transplantation can be substantially reduced using a reduced-intensity conditioning (RIC) regimen. This has increased the proportion of patients with myeloid malignancies eligible for allogeneic transplantation. However, the capacity of RIC allografts to produce durable remissions in patients with acute myeloid leukemia (AML) and myelodysplasia (MDS) has not yet been defined, and consequently, the role of RIC allografts in the management of these diseases remains conjectural. PATIENTS AND METHODS: Seventy-six patients with high-risk AML or MDS received an allograft using a fludarabine/melphalan RIC regimen incorporating alemtuzumab. The median age of the cohort was 52 years (range, 18 to 71 years). RESULTS: The 100-day transplantation-related mortality rate was 9%, and no patient developed greater than grade 2 graft-versus-host disease. With a median follow-up of 36 months (range, 13 to 70 months), 27 patients were alive and in remission, with 3-year actuarial overall survival (OS) and disease-free survival (DFS) rates of 41% and 37%, respectively. The 3-year OS and DFS rates of patients with AML in complete remission at the time of transplantation were 48% and 42%, respectively. Disease relapse was the most common cause of treatment failure and occurred at a median time of 6 months after transplantation. All but one patient destined to relapse did so within 24 months of transplantation. CONCLUSION: The extended follow-up in this series identifies a high risk of early disease relapse but provides evidence that RIC allografts can produce sustained DFS in a significant number of patients with AML who would be ineligible for allogeneic transplantation with myeloablative conditioning.     

KDIGO Clinical Practice Guidelines for Acute Kidney Injury

No abstract available.     

Current practice of periprocedural haematological management for patients undergoing image-guided procedures

Objective:

To evaluate current UK practice of periprocedural haematological management for image-guided procedures in relation to Cardiovascular and Interventional Radiological Society guidelines, which provide recommendations according to bleeding risk of procedures from Category 1 (lowest) to 3 (highest).

Methods:

Survey of practice in UK radiology departments conducted over a 1-year period

Results:

48 radiology departments responded. The percentage of departments that stop antithrombotics pre-procedurally are as follows (for Category 1, 2 and 3, respectively): aspirin (31.3%, 43.8%, 54.2%); clopidogrel (54.2%, 68.8%, 72.9%); therapeutic low-molecular-weight heparin (56.3%, 77.1%, 75.0%). The percentage of departments that perform pre-procedural laboratory testing are as follows (for Category 1, 2 and 3, respectively): international normalized ratio (INR; 81.3%, 95.8%, 93.8%); activated partial thrombin time ratio (APTTR; 60.4%, 75.0%, 93.8%); platelet (77.1%, 91.7%, 95.7%); haemoglobin (70.8%, 85.4%, 87.5%). Mean threshold (standard deviation) of laboratory results for conducting procedures (Level 1, 2 and 3, respectively) are as follows: INR [1.53 (0.197), 1.47 (0.186), 1.47 (0.188)]; APTTR [1.50 (0.392), 1.50 (0.339), 1.48 (0.344)]; platelet count (x10³ cells per microlitre) [74.4 (28.7), 79.9 (29.1), 80.5 (29.3)]; haemoglobin (grams per decilitre) [9.05 (1.40), 9.00 (1.33), 8.92 (1.21)]. No department practices conformed to current recommendations for (1) pre-procedural cessation of antithrombotics and (2) pre-procedural laboratory testing. Two (4.2%) department practices conformed to recommendations for thresholds of haematological parameters.

Conclusion:

Current peri-procedural haematological management is variable and often does not conform to existing recommendations. Further research into the impact of this variation in practice on patient outcome is required

Advances in Knowledge:

This study demonstrates wide variation in practice in haematological management for image-guided procedures.Periprocedural haematological management, such as correction of coagulopathy, cessation of antithrombotics and pre-procedural laboratory testing (e.g. for haemoglobin levels and platelet count), is an important consideration for patients undergoing image-guided procedures.¹ The challenges of periprocedural haematological management are multifactorial in aetiology. In addition to the increasing range of complex image-guided procedures being performed, the patient population undergoing such procedures may also be complicated.² Many of these patients have comorbidities requiring antithrombotic therapy, or may have liver and marrow dysfunction, which can affect bleeding risk. Decisions on the optimal periprocedural haematological management are also confounded by the lack of high-level evidence, and existing guidelines within the literature can be variable even for equivalent procedures. For example, in two separate internationally accepted guidelines, the recommended international normalized ratio (INR) for chest drain insertion is <1.5 and <2.0.^3,4 There is also limited scope to transfer existing evidence on haematological management from other domains such as open surgery to image-guided interventions. Unlike conventional open surgical procedures where bleeding may be visualized immediately and controlled by direct pressure or vessel ligation, bleeding from image-guided procedures may be difficult to control owing to issues with access and identification.⁵The lack of high-level evidence is unsurprising, given the potential ethical issues in conducting the necessary studies; it would be difficult to justify the randomization of patients to receiving or not receiving coagulopathy correction prior to undergoing various image-guided procedures for the purpose of research.⁶ As a result, current evidence is often based on retrospective studies. To address this complex issue, the Society of Interventional Radiology in conjunction with the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) has previously produced guidelines based on existing evidence and expert consensus on periprocedural haematological management for image-guided procedures which are stratified into three categories according to the bleeding risk (4 However, despite the existence of such guidelines, from our experience, significant variation in practice exists between clinicians, even within our own institution.

Table 1.

Society of Interventional Radiology/Cardiovascular and Interventional Radiological Society of Europe consensus guidelines on periprocedural haematological management for image-guided procedures according to category of bleeding risk

Isolation and Antibiogram of Clostridium tetani from Clinically Diagnosed Tetanus Patients

Clostridium tetani, the etiologic agent of tetanus, produces a toxin that causes spastic paralysis in humans and other vertebrates. This study was aimed for isolation, identification, and determination of antimicrobial susceptibility of C. tetani from clinically diagnosed tetanus patients. Isolation was done from deep-punctured tissues of the foot and arm injuries of 80 clinically diagnosed tetanus patients from the Pakistan Institute of Medical Sciences hospital. We successfully screened out five C. tetani isolates out of 80 samples based on the strain-specific characteristics confirmed through biochemical testing and toxin production. A disc diffusion method was used for antimicrobial susceptibilities and C. tetani isolates showed susceptibility to cefoperazone, chloramphenicol, metronidazole, penicillin G, and tetracycline, but were found to be resistant to erythromycin and ofloxacin. During animal testing, all the infected mice developed symptoms of tetanus. The results showed that identification of C. tetani is possible using biochemical and molecular tools and that the strains of C. tetani isolated had not developed resistance against the antibiotics most often used for the treatment of tetanus.     

Acute myeloid leukaemia blast cells with a tyrosine kinase domain mutation of FLT3 are less sensitive to lestaurtinib than those with a FLT3 internal tandem duplication

FLT3 tyrosine kinase domain mutations (FLT3/TKDs) are associated with a favourable prognosis in acute myeloid leukaemia (AML), unlike FLT3 internal tandem duplications (FLT3/ITDs) that have a poor prognosis. Whilst FLT3/ITD+ cells are more susceptible to the cytotoxic effects of FLT3 inhibitors than wild type (WT) cells, the sensitivity of FLT3/TKD+ cells to therapeutic agents is unclear, as is the importance of the mutant level. We therefore studied the effect of cytarabine and the FLT3 inhibitor lestaurtinib, either alone or in combination, on in vitro survival of blast cells from 36 cases of AML (14 FLT3/WT, 11 FLT3/ITD+ and 11 FLT3/TKD+). All three groups showed similar sensitivity to the cytotoxic effects of cytarabine but FLT3/ITD mutant level was inversely correlated with cytarabine cytotoxicity (P = 0.04) whereas FLT3/TKD mutant level had no impact. FLT3/TKD+ cells showed a similar response to lestaurtinib as FLT3/WT cells, whereas FLT3/ITD+ cells were more sensitive (P = 0.004). There was no correlation between mutant level and lestaurtinib sensitivity for either FLT3/ITD+ or FLT3/TKD+ cells. Synergistic cytotoxicity of lestaurtinib plus cytarabine was demonstrated in all three groups. These results suggest that FLT3/TKD+ and FLT3/WT cases should not be differentiated when considering patients for treatment with FLT3 inhibitors.     

A case of crossed aphasia with apraxia of speech

Apraxia of speech (AOS) is a rare, but well-defined motor speech disorder. It is characterized by irregular articulatory errors, attempts of self-correction and persistent prosodic abnormalities. Similar to aphasia, AOS is also localized to the dominant cerebral hemisphere. We report a case of Crossed Aphasia with AOS in a 48-year-old right-handed man due to an ischemic infarct in right cerebral hemisphere.