Kristine Ward

High‐Dose Cyclophosphamide in the Treatment of Multiple Sclerosis

High dose cyclophosphamide (HDC) has been successfully used for the treatment of a variety of autoimmune diseases. In this study, we sought to determine whether the use of high dose cyclophosphamide provided stabilization of relapsing remitting MS (RRMS), secondary progressive MS (SPMS), or primary progressive MS (PPMS). The parameters evaluated were EDSS scores, lesion load and brain volumes by MRI and frequency of relapses. Twenty‐three patients underwent immunoablative therapy with HDC and were followed for 3.5 years. Nine were relapsing remitting (RRMS), 11 secondary progressive (SPMS), and 3 primary progressive (PPMS). Four of 9 RRMS have had no clinical progression up to 3.5 years following treatment. Three of 9 patients maintained a normal neurologic examination with improved EDSS scores. Seven of the nine RRMS patients had reduction in flare frequency which was maintained for 3.5 years following treatment or no immunomodulating agents. Subgroup analysis in the RRMS patients of lesion load and brain parenchymal volume revealed a favorable trend in these parameters which did not reach statistical significance. The treatment was generally ineffective for SPMS and failed in the 2 PPMS patients. HDC was well tolerated, demonstrated a good safety profile and had minimal adverse effects. These results along with previous reports suggest that early use of HDC therapy in RRMS is promising.

Evaluation of a Pretest Scoring System (4Ts) for the Diagnosis of Heparin-Induced Thrombocytopenia in a University Hospital Setting

Abstract The initial diagnosis of heparin–induced thrombocytopenia (HIT) is made on clinical grounds because the assays with the highest sensitivity (eg, heparin–platelet factor 4 antibody enzyme–linked immunosorbent assay [ELISA]) and specificity (eg, serotonin release assay) may not be readily available. The clinical utility of the pretest scoring system, the 4Ts, was developed and validated by Lo et al in the Journal of Thrombosis and Haemostasis in 2006. The pretest scoring system looks at the degree and timing of thrombocytopenia, thrombosis, and the possibility of other etiologies. Based on the 4T score, patients can be categorized as having a high, intermediate, or low probability of having HIT We conducted a retrospective study of 100 consecutive patients who were tested for HIT during their hospitalization at Hahnemann University Hospital (Philadelphia, PA) in 2009. Of the 100 patients analyzed, 72, 23, and 5 patients had 4T pretest probability scores of low, intermediate, and high, respectively. A positive HIT ELISA (optical density > 1.0 unit) was detected in 0 of 72 patients (0%) in the low probability group, in 5 of 23 patients (22%) in the intermediate probability group, and in 2 of 5 patients (40%) in the high probability group. The average turnaround time for the HIT ELISA was 4 to 5 days. Fourteen (19%) of the 72 patients with a low pretest probability of HIT were treated with a direct thrombin inhibitor. Ten (71 %) of the 14 patients in the low probability group treated with a direct thrombin inhibitor had a major complication of bleeding requiring blood transfusion support. In this retrospective study, a low 4T score showed 100% correlation with a negative HIT antibody assay. We recommend incorporating the 4T scoring system into institutional core measures when assessing a patient with suspected HIT, selecting only patients with intermediate to high probability for therapeutic intervention, which may translate into reduced morbidity and lower health care costs.

Intracerebral progression of Hodgkin lymphoma in a man with HIV.

Abstract Intracerebral relapse of Hodgkin lymphoma is a rare occurrence, with a reported incidence of < 0.5%. To the best of our knowledge, only 4 cases have been reported in the literature. We report the case of a human immunodeficiency virus (HIV)-seropositive man with disseminated Hodgkin lymphoma who presented with left facial weakness and sensory abnormalities as the only symptoms of disease progression 3 months after chemotherapy-induced disease remission. Because of the relative rarity of the condition, there are no randomized controlled trials or evidence-based strategies for managing patients with HIV and intracerebral Hodgkin lymphoma. The diagnostic difficulty of this case emphasizes the necessity for a high index of suspicion for the diagnosis of HIV-associated intracerebral lymphoma in the appropriate clinical setting. In the post-genomic era, the development of sophisticated clinical and/or molecular biomarkers could contribute to earlier diagnosis and potentially improve disease prognosis.

Intracranial tumor lysis and cerebral edema after administration of intrathecal methotrexate: a case report and discussion

Methotrexate is a common agent used in the management of hematological malignancies, but is often associated with the development of diverse central nervous system adverse events, such as seizures. We present a case of seizures after intrathecal administration of methotrexate, during the management of diffuse large B-cell lymphoma. There was complete resolution of the CNS lesions after chemotherapy along with the interval development of diffuse cerebral edema. We hypothesize that tumor lysis is the underlying mechanism of this untoward event, resulting in the corresponding clinical presentation.