N-Acetylcistein for thrombotic thrombocytopenic purpura: an observational case series study.

Acquired thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder. N-Acetylcysteine (NAC) rapidly degrades ultra-large von Willebrand factor multimers by disrupting the disulfide bonds. We report a series of twelve consecutive patients diagnosed with acquired TTP successfully treated with high-dose NAC (150 mg/kg/day) in combination with plasma exchange and steroids. Eight patients also received rituximab. Two patients presented refractory TTP. All patients achieved a quick clinical response in a median time of 5.5 days after starting NAC and are alive after a median follow-up of 29 months. The treatment was feasible and well tolerated. These data provide further evidence of the potential benefit and safety of adding NAC to the standard of care.

Spinal cord infusion of stem cells in amyotrophic lateral sclerosis: Magnetic resonance spectroscopy shows metabolite improvement in the precentral gyrus.

BACKGROUND AIMS: We aimed to investigate whether magnetic resonance spectroscopy (MRS) metabolite ratios change in the precentral gyrus of patients with amyotrophic lateral sclerosis (ALS) after spinal cord surgical injection of bone marrow mononuclear cells, as well as their relationship with disability and survival. METHODS: Stem cells were surgically injected in the spinal cord of 11 spinal-onset amyotrophic lateral sclerosis patients (group 1); 21 matched patients were the control group (group 2), comprising ALS patients with an intrathecal saline infusion. Single-voxel 1.5T MRS was performed in both precentral gyri just after inclusion/baseline (before surgery in group 1) and a year later (7 patients in group 1 and 11 in group 2). The spectroscopy data, time of survival and clinical parameters (ALS Functional Rating Scale, forced vital capacity [FVC], Medical Research Council Score) were longitudinally assessed and correlated in both groups. RESULTS: Only in group 1was there a significant N-acetyl-aspartate/creatine (NAA/Cr) increase with time in the dominant side (P = 0.024). NAA/Cr also correlated with years of survival in the nondominant side (r = 0.808, P = 0.026). Except for FVC, all group 1 clinical parameters at 12 months correlated with baseline NAA/Cr on both sides (P <0.05); this was not the case in group 2. DISCUSSION: In view of these results, we speculate on a distant beneficial effect of bone marrow stem cells injected at the spinal cord over the upper motor neuron at the precentral gyri in the brain. Spinal cord injection of stem cells shows metabolic improvement in the brain that might be related to longer survival and less disability.

An automatic wash method for dimethyl sulfoxide removal in autologous hematopoietic stem cell transplantation decreases the adverse effects related to infusion.

BACKGROUND: Products cryopreserved with dimethyl sulfoxide (DMSO) in stem cell transplant (SCT) often cause many adverse effects during their infusion (major cardiovascular events, dyspnea … even death). These are especially frequent in pediatric patients. We tested if a fully automated and closed wash procedure (Sepax S-100, Biosafe) allowed us to maintain the absolute CD34+ cell number, cell viability, and engraftment potential, decreasing the untoward reactions. STUDY DESIGN AND METHODS: Forty-six washes of DMSO cryopreserved peripheral blood hematopoietic progenitor (HP) apheresis were studied. Blood aliquots were taken both after thawing and after washing to assess the total nucleated and CD34+ cell counts, as well as cell viability. The washed products were infused in 26 autologous SCTs (ASCTs). Results were compared with the 53 previous SCTs performed without DMSO removal. RESULTS: After washing there were no significant differences between the pre- and postwashing CD34+ cell counts (p=0.08) or viability (p=0.68). No significant differences were observed between washed and nonwashed infusions in relation to the day of the neutrophil (p=0.46) and platelet (p=0.26) engraftment. One adverse event, abdominal pain, occurred during the washed cells infusions. When compared with the 14 untoward reactions that took place during the nonwashed HP infusions, significance was reached (p=0.00043). CONCLUSIONS: The automatic method described is effective in terms of CD34+ cell recovery and viability in ASCT. Moreover, Sepax decreased significantly the untoward reactions during the infusion.