Real-world Outcomes With Rituximab-based Therapy for Posttransplant Lymphoproliferative Disease Arising After Solid Organ Transplant.

BACKGROUND: Optimal upfront therapy for posttransplant lymphoproliferative disease (PTLD) arising after solid organ transplant remains contentious. Rituximab monotherapy (R-Mono) in unselected patients has shown a lack of durable remissions. Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)-based chemotherapy confers improved response rates, although concerns exist about toxicity. METHODS: This multicenter retrospective study reports outcomes for adults with biopsy-proven B-cell PTLD treated initially with R-Mono or Rituximab plus CHOP (R-CHOP). Selection of therapy was made according to physician preference. RESULTS: Among 101 patients, 41 received R-Mono and 60 had R-CHOP. Most (93%) had undergone renal or liver transplantation. R-CHOP showed a trend toward improved complete (53% versus 71%; P = 0.066) and overall (75% versus 90%; P = 0.054) response rates. In the R-Mono group, 13 of 41 (32%) subsequently received chemotherapy, while 25 of 41 (61%) remained progression-free without further therapy. With median follow-up of 47 months, overall survival (OS) was similar for R-Mono and R-CHOP, with 3-year OS of 71% and 63%, respectively (P = 0.722). Non-PTLD mortality was 3 of 41 (7%) and 4 of 60 (7%) within 12 months of R-Mono or R-CHOP, respectively. The International Prognostic Index was statistically significant, with low- (0-2 points) and high-risk (≥3 points) groups exhibiting 3-year OS of 78% and 54%, respectively (P = 0.0003). In low-risk PTLD, outcomes were similar between therapies. However, in high-risk disease R-Mono conferred an inferior complete response rate (21% versus 68%; P = 0.006), albeit with no impact on survival. CONCLUSIONS: Our data support R-Mono as initial therapy for PTLD arising after renal or liver transplantation. However, upfront R-CHOP may benefit selected high-risk cases in whom rapid attainment of response is desirable.

Routine monitoring for heparin-induced thrombocytopenia following lower limb arthroplasty: Is it necessary? A prospective study in a UK district general hospital.

INTRODUCTION: Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening condition associated with heparin administration. Many orthopaedic units routinely prescribe low-molecular-weight heparins as thromboprophylaxis after hip and knee arthroplasty. HYPOTHESIS: We postulated that routine platelet monitoring following heparin administration is of no clinical benefit. We therefore asked: firstly, what was the rate of thrombocytopenia in a large population of patients undergoing lower limb arthroplasty? Secondly, did this rate justify routine platelet monitoring? MATERIALS AND METHODS: Unless contraindicated, all patients (n=1999, 53.05% female, mean age 69.23 years) at a UK district general hospital undergoing hip and knee arthroplasty were given daily prophylactic enoxaparin. Platelet counts were obtained between the 8th and 10th postoperative days and compared to preoperative baseline. A > 50% fall in platelet count was classified as "possible HIT". The minimal acceptable risk of thrombocytopenia was defined using The American College of Chest Physicians (ACCP) 2012 guidelines, which recommend monitoring platelet counts in patients receiving heparin where the expected risk of HIT is>1% and by descriptive cost-benefit analysis based on the cost of routine platelet monitoring in the clinical setting. RESULTS: Complete results were available for 1361 (68.1%) patients, comprising: 653 primary hips, 22 revision hips, 1 hip resurfacing, 665 primary knees, 19 revision knees and 1 unicompartmental knee replacement. Mean platelet level was 281.9×109/L preoperatively and 527.83×109/L postoperatively. Forty-four patients (3.2%) experienced a postoperative fall in platelet levels. However, no patient experienced a drop in platelets to less than 50% of the preoperative value. DISCUSSION: The incidence of HIT in the elective arthroplasty population is low. Therefore, routine postoperative monitoring of platelets is not necessary in this population of patients. LEVEL OF EVIDENCE: II, prospective study.

Neuromuscular disease presentation with three genetic defects involving two genomes.

An extensive range of molecular defects have been identified in the human mitochondrial genome (mtDNA), many associated with well-characterised, progressive neurological syndromes. We describe a patient who presented to a mitochondrial clinic with progressive bilateral ptosis, external opthalmoplegia and increasing difficulty with walking. He had previously been diagnosed with a dominant, demyelinating polyneuropathy due to PMP22 gene duplication and had also developed gout, presenting in acute renal failure, due to an X-linked recessive HPRT gene mutation. Muscle biopsy revealed many COX-deficient fibres which we show contain high levels of a third genetic defect--a novel, mitochondrial tRNA(Leu(CUN)) (MTTL2) gene mutation.