Single center experience with total body irradiation and melphalan (TBI-MEL) myeloablative conditioning regimen for allogeneic stem cell transplantation (SCT) in patients with refractory hematologic malignancies.

We retrospectively evaluated the tolerability and efficacy of fractionated total body irradiation (TBI) (1,200 cGy) and melphalan (MEL) (100-110 mg/m(2)) myeloablative conditioning in 48 patients with nonremission AML (n = 14), ALL (n = 10), NHL (n = 18), and other refractory hematologic malignancies (n = 6) who received allogeneic stem cell transplantation (SCT) between 2002 and 2011. Median age was 48 years (22 to 68); 14 out of 26 leukemia patients (54 %) had circulating blasts at transplant, 20 (50 %) evaluable patients had poor-risk cytogenetics, 12 (25 %) had prior SCT, and 10 (21 %) received stem cells from a mismatch donor. All patients received tacrolimus with or without methotrexate for GVHD prophylaxis. At the time of analysis, 13 patients (27 %) were alive and disease free. Engraftment was complete in all patients. The median time to ANC recovery (>500) was 12 days (range, 6-28). The most common grade III and IV toxicities were mucositis and infections. Eighteen patients (43 %) developed grade II-IV acute GVHD, and eight (26 %) had extensive chronic GVHD. Of 44 evaluable patients for response, 28 (64 %) achieved a complete remission (CR), and seven (15 %) had a partial remission after the transplant. With a median follow-up of 30 months (4 to 124 months) for surviving patients, the cumulative incidence of relapse was 45 % at 1 year, and the probability of overall survival (OS) at 5 years was 22.5 %. Multivariate analysis showed that platelet count (<80,000/mL) and lactic dehydrogenase (>500 IU/L) at SCT were associated with relapse. Age less than 53 years and CR after SCT were associated with better OS. Our data suggest that TBI-MEL can result in CR in two thirds, durable remission in one third, and 5-year survival in about one quarter of patients with nonremission hematologic malignancies. Further studies with TBI-MEL in standard risk transplant patients are warranted.

Recombinant factor VIIa for warfarin-associated intracranial bleeding.

STUDY OBJECTIVE: To examine the efficacy of recombinant factor VIIa (rVIIa) in reversing warfarin-induced coagulopathy in trauma patients presenting with intracranial hemorrhage (ICH). DESIGN: Retrospective, cohort-controlled database review. SETTING: Level 1, university-affiliated trauma center. PATIENTS: 54 patients presenting with ICH associated with chronic warfarin therapy, 30 of whom were treated with rVIIa, and the other 24 patients treated conventionally. MEASUREMENTS: We examined initial and subsequent coagulation studies (prothrombin time, international normalized ratio [INR]), blood product requirement, and clinical outcome, including time to reverse anticoagulation, duration of reversal, and subsequent mortality. MAIN RESULTS: Patients treated with rVIIa required significantly less plasma (4 vs 7 units) to correct their INR, and corrected in a much shorter period of time (2.4 vs 10 hrs). The duration of corrected INR after rVIIa was dose-dependent. CONCLUSIONS: Factor rVIIa provides prompt correction of the INR of dose-dependent duration in patients with ICH intracranial hemorrhage associated with warfarin use.