Transfusion-related acute lung injury risk mitigation: an update.

Transfusion-related acute lung injury (TRALI) is a life-threatening complication of transfusion. Greater understanding of the pathophysiology of this syndrome has much improved during the last two decades. Plasma-containing components from female donors with leucocyte antibodies were responsible for the majority of TRALI fatalities before mitigation strategies were implemented. Over the past 15 years, measures to mitigate risk for TRALI have been implemented worldwide and they continued to evolve with time. The AABB requires that all plasma containing components and whole blood for transfusion must be collected from men, women who have not been pregnant, or women who have tested negative for human leucocyte antigen antibodies. Although the incidence of TRALI has decreased following the institution of TRALI mitigation strategies, TRALI is still the most common cause of transfusion-associated death in the United States. In this review, we focus on TRALI risk mitigation strategies. We describe the measures taken by blood collection facilities to reduce the risk of TRALI in the United States, Canada and European countries. We also review the literature for the effectiveness of these measures.

Inhibition of FLT3 in AML: a focus on sorafenib.

FMS-like tyrosine kinase 3 (FLT3) is one of the most commonly mutated genes in AML. FLT3 is mutated in ~30% of patients with AML, either by internal tandem duplications (FLT3-ITD) of the juxta-membrane domain or by a point mutation, usually involving the tyrosine kinase domain. Several FLT3 tyrosine kinase inhibitors are being evaluated in multiple studies aiming at improving outcomes. The most widely used is sorafenib, a potent multikinase inhibitor approved for hepatocellular carcinoma and renal cell carcinoma. Sorafenib monotherapy or in combination with conventional chemotherapy, has been evaluated in various settings in AML, including front-line, relapsed or refractory disease including post-allograft failures and, more recently, as post-transplant maintenance therapy. Encouraging data have emerged with several other agents like lestaurtinib, midostaurin, crenolanib, gilteritinib and quizartinib. Although transient responses to FLT3 inhibitors are often observed in case of disease relapse, the most promising approach is the use of FLT3 inhibitors either in combination with induction chemotherapy or as consolidation/maintenance therapy after allogeneic hematopoietic cell transplantation. In this review, we summarize the clinical data on sorafenib and other FLT3 inhibitors in AML.

Platelet transfusion in thrombotic thrombocytopenic purpura.

BACKGROUND: Platelet (PLT) transfusion has been considered contraindicated in patients with thrombotic thrombocytopenic purpura (TTP). However, adverse clinical outcomes and death in patients with TTP after receiving PLT transfusion were based on case reports prior to routine use of plasma exchange (PEX) therapy. PLT transfusions are often required by the interventional radiologist before the insertion of a central venous catheter. In this study, we evaluate whether PLT transfusions are harmful in patients with TTP undergoing PEX. METHODS: We retrospectively reviewed the records of consecutive patients with the clinical diagnosis of TTP who received PEX at our institution between January 2004 and September 2014. An adverse event was defined as any complication including seizures, cerebrovascular accident, bleeding, thrombosis, myocardial infarction or death for any reason within 30 days from the PLT transfusion. Analyses were performed on only patients with ADAMTS13 activity <10%. RESULTS: Our cohort included 110 patients with the clinical diagnosis of TTP. Fifty-five patients had ADAMTS13-deficient TTP, 23 of whom received PLT at some point during disease course. The patients who received PLT transfusion were not different from those who did not in terms of age, gender, race, haematocrit, PLT count, creatinine, LDH and complications. The three patients who received PLT and died had malignancy and complicated disease course. None of them died from a thrombotic event. CONCLUSION: All deaths in the transfused group happened in very ill patients that had alternative causes of death. PLT transfusions in patients with TTP do not appear harmful in regard to thrombotic complications.

G-CSF plus preemptive plerixafor vs hyperfractionated CY plus G-CSF for autologous stem cell mobilization in multiple myeloma: effectiveness, safety and cost analysis.

The optimal stem cell mobilization regimen for patients with multiple myeloma (MM) remains undefined. We retrospectively compared our experience in hematopoietic cell mobilization in 83 MM patients using fractionated high-dose CY and G-CSF with G-CSF plus preemptive plerixafor. All patients in the CY group (n=56) received fractionated high-dose CY (5 g/m(2) divided into five doses of 1 g/m(2) every 3 h) with G-CSF. All patients in the plerixafor group (n=27) received G-CSF and plerixafor preemptively based on an established algorithm. Compared with plerixafor, CY use was associated with higher total CD34+ cell yield (7.5 × 10(6) vs 15.5 × 10(6) cells/kg, P=0.005). All patients in both groups yielded ⩾4 × 10(6) CD34+ cells/kg. Conversely, CY use was associated with high frequency of febrile neutropenia, blood and platelet transfusions need and hospitalizations. The average total cost of mobilization in Lebanon was slightly higher in the plerixafor group ($7886 vs $7536; P=0.16). Our data indicate robust stem cell mobilization in MM patients with either fractionated high-dose CY and G-CSF or G-CSF alone with preemptive plerixafor. The chemo-mobilization approach was associated with twofold stem cell yield, slightly lower cost but significantly increased toxicity.

PRPF8 defects cause missplicing in myeloid malignancies.

Mutations of spliceosome components are common in myeloid neoplasms. One of the affected genes, PRPF8, encodes the most evolutionarily conserved spliceosomal protein. We identified either recurrent somatic PRPF8 mutations or hemizygous deletions in 15/447 and 24/450 cases, respectively. Fifty percent of PRPF8 mutant and del(17p) cases were found in AML and conveyed poor prognosis. PRPF8 defects correlated with increased myeloblasts and ring sideroblasts in cases without SF3B1 mutations. Knockdown of PRPF8 in K562 and CD34+ primary bone marrow cells increased proliferative capacity. Whole-RNA deep sequencing of primary cells from patients with PRPF8 abnormalities demonstrated consistent missplicing defects. In yeast models, homologous mutations introduced into Prp8 abrogated a block experimentally produced in the second step of the RNA splicing process, suggesting that the mutants have defects in proof-reading functions. In sum, the exploration of clinical and functional consequences suggests that PRPF8 is a novel leukemogenic gene in myeloid neoplasms with a distinct phenotype likely manifested through aberrant splicing.

Laparoscopic splenectomy for isolated parenchymal splenic metastasis of ovarian cancer.

Metastatic carcinoma of the spleen occurs in a setting of widespread malignant disease. Solitary parenchymal splenic metastasis of ovarian carcinoma is rare. We report a case of a 59-year-old woman who presented with an elevated serum CA125 level due to a solitary splenic metastasis after a long disease-free period. She was treated with laparoscopic splenectomy followed by chemotherapy. The literature contains 16 cases of solitary parenchymal splenic metastasis of ovarian carcinoma. Our case is the third case that was treated with laparoscopic splenectomy. We review the literature, and we focus on the laparoscopic approach in managing these cases.

Primary pure squamous cell carcinoma of the breast: a case report and review of the literature.

Pure primary squamous cell carcinoma (SCC) of the breast is a rare condition. The exact histogenesis of this malignancy is unclear. The rarity of the condition makes it difficult to draw firm conclusions on the course of the disease and the overall prognosis. We report a case of pure primary SCC of the breast occurring in a 62-year-old woman and presenting as an enlarged breast lesion with bleeding. We also review the literature for all cases of pure primary SCC.