Update on the use of defibrotide

INTRODUCTION: Defibrotide is a polydisperse oligonucleotide obtained from porcine intestinal mucosa and prepared by controlled depolymerization of DNA. It is a nucleic acid polymer, predominantly single-stranded, which has anti-ischemic and anti-thrombotic properties. AREAS COVERED: The efficacy and safety of defibrotide in the treatment of veno-occlusive disease (VOD) occurring after high-dose chemotherapy and hematopoietic stem-cell transplantation is now well established in Phase II - III trials. A recent randomized, Phase III trial in pediatric patients has also demonstrated its role in the prevention of VOD. Preclinical studies reported the inhibitory effects of defibrotide on myeloma cells' growth through an antiangiogenic action and a regulation of the tumor-microenvironment interactions. A recent Phase II trial underlines the efficacy and safety of defibrotide-thalidomide-melphalan combination in the treatment of relapsed/refractory multiple myeloma. EXPERT OPINION: Defibrotide may be effective in the prophylaxis and the treatment of veno-occlusive disease. Recent experimental results suggest that defibrotide may belong to the new generation of anti-cancer drugs that can prevent tumor angiogenesis. In multiple myeloma, defibrotide may overcome the prothrombotic effect of thalidomide on endothelial cells. Further preclinical and clinical investigations are needed to assess the precise role of defibrotide in the treatment of patients with multiple myeloma.     

Allogeneic hematopoietic stem cell transplantation for solid tumors in the United States: a review

The field of bone marrow transplantation has undergone dramatic changes over the past few decades. Not only has the terminology changed (e.g., hematopoietic stem-cell transplantation), but the role of allogeneic transplantation has been modified from supportive to immunotherapeutic and the applications have expanded from hematologic malignancies to solid tumors. The development of nonmyeloablative conditioning regimen has greatly increased the number of patients eligible for this kind of treatment. Use of hematopoietic stem-cell transplantation as a form of adoptive immunotherapy in the treatment of cancer depends on advances in tumor immunology, particularly the identification of tumor antigens and mechanisms of immunotherapy. The earliest use of allogeneic transplantation of immunogenic cells for the treatment of solid tumors in the late 1960s and early 1970s produced no definite graft-versus-tumor effects. However, as conventional allogeneic hematopoietic stem-cell transplantation methods for the treatment of hematologic malignancies have matured, these methods have reestablished the foundation for expanding their application to solid tumors. From the first case reports on medulloblastoma and breast cancer to subsequent case series reports on breast cancer and renal cell carcinoma, allogeneic hematopoietic stem-cell transplants have demonstrated graft-versus-tumor effect. At present, the most common solid tumor for which this treatment is used is advanced renal cell carcinoma, but allogeneic hematopoietic stem-cell transplants have proven feasible for other solid tumors as well. Directions for future study include the identification of the definitive tumor antigens involved in the graft-versus-tumor effect and means of selecting those patients who will benefit the most from this form of treatment. This review summarizes the peer-reviewed literature on the use of allogeneic transplantation for solid tumors based on US studies.     

Prevention and treatment of veno-occlusive disease

OBJECTIVE: To review the current options for prevention and treatment of veno-occlusive disease in bone marrow transplant patients. DATA SOURCES: Articles were selected from a MEDLINE search (1966-October 1999) using the key terms veno-occlusive disease and bone marrow transplantation. In addition, references of all articles were examined for articles not found in the computer-based search. DATA EXTRACTION: All clinical trials, case-control studies, and case reports were evaluated. RESULTS: Heparin, low-molecular-weight heparin, prostaglandin E1, ursodiol, and glutamine have been studied for prevention of veno-occlusive disease. Heparin has been studied most extensively; however, no preventive regimen has a defined role in therapy. For treatment, tissue plasminogen activator has been evaluated most thoroughly, yet its safety and efficacy have not been clearly established in patients with veno-occlusive disease. Other possible treatment options include antithrombin-III, defibrotide, glutamine plus vitamin E, and surgery. CONCLUSIONS: Based on the available data, the most promising agents are ursodiol for prevention and defibrotide or glutamineplus vitamin E for treatment of veno-occlusive disease. Further clinical trials are needed to establish the appropriate preventive and treatment options available for bone marrow transplant patients suffering from veno-occlusive disease. To date, such decisions depend largely on poorly designed trials, case reports, and clinical experience.     

Gemtuzumab ozogamicin-induced sinusoidal obstructive syndrome treated with defibrotide: a case report

New treatments for relapse of acute myeloid leukaemia (AML), include gemtuzumab ozogamicin (GO), an anti-CD33 monoclonal antibody. We describe a second case of GO-induced sinusoidal obstructive syndrome (SOS) effectively treated with defibrotide (DF). No stem-cell transplantation was involved. On day 23 after the first GO dose, a patient presented with ascites, weight gain, liver enlargement and pain in the right upper quadrant. Sudden hepatic cytolysis (transaminases at six times the normal range: grade 3) and cholestasis [alkaline phosphatase ALP and gamma-glutamyltransferase (GGT) respectively at four and eight times the normal range: grade 2] were observed but there was no evidence of increase serum bilirubin. Treatment with DF (Prociclide), Crinos; 10 mg/kg/day, or 200 mg, q.i.d.) improved the hepatic abnormality within a few days (serum transaminases decreased from 312 to 103 IU/L for aspartate aminotransferase (AST) and from 141 to 80 IU/L for alanine aminotransferase (ALT) within 3 days ALP increased from 253 to 383 IU/L and gamma-GT from 238 to 417 IU/L 4 days after administration of DF. The clinical and biological features of our case suggest a direct involvement of GO in causing SOS, even when used as monotherapy, without allogenic stem-cell transplantation. Low dose DF (10 mg/kg/day) given early during the development of SOS associated with GO was effective. Unfortunately, in our case the patient eventually died of multi-organ failure probably because of failure of GO.     

Micafungin

OBJECTIVE: To review the pharmacology, mycology, chemistry, in vitro susceptibility, pharmacokinetics, clinical efficacy, safety, tolerability, dosage, and administration of micafungin, an echinocandin antifungal agent. DATA SOURCES: A MEDLINE search, restricted to English language, was conducted from 1978 to November 2003. Supplementary sources included program abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy and the Infectious Diseases Society of America from 1996 to 2003 and information available through the manufacturer's Web site. STUDY SELECTION AND DATA EXTRACTION: In vitro and preclinical studies, as well as Phase II and III clinical trials, were evaluated to summarize the clinical efficacy and safety of micafungin. All published and unpublished trials and abstracts citing micafungin were selected. DATA SYNTHESIS: Micafungin has shown in vitro activity against many yeasts and a variety of molds. Micafungin can be administered only parenterally. Efficacy has been illustrated in open noncomparative studies of esophageal candidiasis in HIV-infected patients and in comparative trials as antifungal prophylaxis in patients undergoing hematopoietic stem-cell transplantation. Adverse events appear mild and limited; the most commonly reported adverse events include hyperbilirubinemia, nausea, and diarrhea. CONCLUSIONS: Micafungin has activity against Aspergillus spp. and a variety of Candida spp., including azole-resistant strains. Micafungin demonstrates efficacy in the treatment of esophageal candidiasis in HIV-infected patients and appears superior to fluconazole as antifungal prophylaxis in patients undergoing hematopoietic stem-cell transplantation. Based on case reports and in vitro efficacy, micafungin may prove to be a clinically useful agent in the treatment of other fungal diseases; however, these indications await the results of clinical trials.     

干细胞移植治疗糖尿病

背景：干细胞移植可以从细胞和基因水平治疗糖尿病,从而达到临床治愈。目的：综述近年来国内外干细胞移植治疗糖尿病的相关研究进展。方法：应用计算机检索2000-01/2010-06PubMed数据库、中国期刊全文数据库相关文章,检索词为＂stemcells,diabetesmellitus,transplantation,insulin-secretingcell,treatment;干细胞,糖尿病,移植,胰岛素分泌细胞,治疗＂,共纳入27篇文章进行综述。结果与结论：糖尿病是一组由于胰岛素绝对或相对不足所引起的以慢性高血糖为特征的代谢性疾病,目前尚无根治的方法。干细胞具有极强的自我更新和多向分化潜能,可诱导分化为胰岛素分泌细胞,在体内和体外发挥调节血糖的作用,成为胰岛β细胞替代物的新资源。目前干细胞移植治疗糖尿病已在动物实验和小规模临床研究中取得了一定成果。     

Advances in stem-cell–generated transplantation therapy for Parkinson's disease

Introduction: Human pluripotent stem cells have the potential to differentiate into different cell lineages of the human body, including dopaminergic (DA) neurons. Previous studies have shown that stem-cell–derived DA neurons can improve the motor deficits of Parkinson's disease (PD) animal models. That is why current research interests focus on the development of stem-cell–derived neural cells for transplantation therapies for PD patients.

Areas covered: This review article emphasizes the safety and efficacy requirements of human pluripotent stem-cell–derived neural cells and usage of reliable preclinical animal models prior to clinical trials. The current advances and hurdles related to cell production, differentiation and transplantation are also summarized.

Expert opinion: Before entering the clinic, transplantable cell populations must be differentiated and characterized according to good manufacturing practice (GMP) regulations both in vitro and in vivo. Taking into account the rapid development of the stem-cell field and technological improvements in cell preparations and GMP facilities, we think that pluripotent stem-cell–derived DA neurons will offer a relevant cell therapy option for treatment of PD in the near future.     

Targeting the proteasome with bortezomib in multiple myeloma: update on therapeutic benefit as an upfront single agent, induction regimen for stem-cell transplantation and as maintenance therapy

Bortezomib is the first therapeutic inhibitor of the proteasome that has demonstrated a significant clinical response in patients with otherwise refractory or rapidly advancing disease. Bortezomib has received US Federal Drug Administration approval for the treatment of the hematologic malignancies such as multiple myeloma and mantle cell lymphoma. Herein, the use of bortezomib as an upfront therapy, as an induction regimen before stem-cell transplantation and as maintenance therapy in the treatment of multiple myeloma is discussed.     

Incidence and risk factors for hepatic sinusoidal obstruction syndrome after allogeneic hematopoietic stem cell transplantation: A retrospective multicenter study of Turkish hematology research and education group (ThREG)

Hepatic sinusoidal obstruction syndrome (HSOS) is a potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively evaluated the incidence, risk factors, treatment and survival for HSOS after allo-HSCT in Turkey. We also reported our experience of defibrotide (DF) for HSOS prophylaxis in high-risk (HR) patients. Across Turkey, 1153 patients from 10 centers were enrolled in the study. We evaluated the medical records of patients who were treated with allo-SCT between January 2012 and December 2015. The study included 1153 patients (687 males/466 females) with median age of 38 (15−71) years. The incidence of HSOS was 7.5 % (n = 86). The incidences of HSOS in the HR/DF+, HR/DF- and standard risk (SR) group were 8%, 66.7 % and 6.2 %, respectively. The rate of HSOS development was not statistically different between HR/DF + and SR group (p = 0.237). HSOS prophylaxis (defibrotide) was significantly decreased HSOS-related mortality (p = 0.004). The incidence of HSOS was found similar to literature in this large Turkish cohort. Defibrotide prophylaxis appears to be associated with low incidence of HSOS development and reduced HSOS-related mortality. Although these results are promising, future studies are needed to support the efficacy of defibrotide prophylaxis in patients with risk of HSOS.     

干细胞移植治疗糖尿病下肢血管病变：细胞因子与血管新生

背景：干细胞在一定诱导条件下可分化成为血管性内皮细胞,可促进局部血管再生,生成新的毛细血管网,建立丰富的侧支循环,以达到改善和治疗下肢缺血的目的。目的：概述糖尿病下肢血管病变的发病机制,以及自体外周血干细胞移植、脐血干细胞移植、干细胞联合细胞因子移植治疗糖尿病下肢血管病变的基础研究和临床研究现状。方法：检索1983至2014年PubMed数据库、维普中文科技数据库及万方数据相关文献。英文检索词为＂stem cells;stem cell transplantation;cord blood stem cell transplantation;diabetic angiopathies＂;中文检索词为＂干细胞;干细胞移植;脐血干细胞移植;糖尿病血管病变＂。结果与结论：糖尿病下肢血管病变的发病机制可能与免疫异常诱发炎症反应有关,目前还缺乏有效的治疗方法。干细胞移植治疗糖尿病并发症在动物模型及临床上均取得了一定的成果,其中应用较多的有胚胎干细胞、间充质干细胞和内皮祖细胞,其治疗糖尿病下肢血管病变的机制主要与其参与新生血管形成、启动和分泌相关因子、免疫调节以及干细胞的增殖和分化能力等有关。目前的基础研究主要限于单纯的干细胞移植和联合基因治疗的干细胞移植。与外周血干细胞移植相比,自体骨髓干细胞移植所采细胞更原始,操作更简单,费用更低。证实干细胞分泌的细胞因子不足以促进血管新生,而是刺激骨骼肌细胞分泌足够的细胞因子促进血管新生。目前干细胞的临床应用有很多的问题有待解决。     

造血干细胞移植治疗1型糖尿病机制的研究现状

造血干细胞移植逐渐用于治疗多种自身免疫性疾病,如系统性红斑狼疮、多发性硬化等,同时也为1型糖尿病的治愈带来了希望。1型糖尿病的发生主要与细胞免疫有关,体液免疫也参与其发病。本文综述了造血干细胞移植治疗1型糖尿病动物实验和临床实践的研究近况,探讨造血干细胞移植治疗1型糖尿病的可能机制。     

干细胞移植在心血管疾病应用中急待解决的问题

背景：干细胞作为细胞移植的种子细胞治疗心血管疾病已成为近年来研究的热点,许多动物实验及临床研究均表明干细胞移植是提高心功能新的治疗措施。目的：针对干细胞在心血管疾病应用中的移植种类选择、移植途径、移植时机及其安全性问题进行综述。方法：由第一作者应用计算机检索2000/2010 PubMed数据库及中国期刊全文数据库中有关干细胞移植在心血管疾病中应用的文章,英文检索词为＂stem cell transplantion,cardiovascular disease＂,中文检索词为＂干细胞移植,心血管疾病＂。排除重复性研究及无关研究,共保留25篇文章进行综述。结果与结论：干细胞移植可以改善缺血心肌的灌注,减少心肌细胞死亡,限制左室重构,从而从根本上改善患者的心功能,降低死亡率。但干细胞移植治疗心血管疾病的研究目前还处于初级阶段,尚有许多问题急待解决。     

急性GVHD的治疗研究新进展

急性移植物抗宿主病(aGVHD)是异基因造血干细胞移植后常见并发症。尽管对于移植免疫的认识在不断进步,但aGVHD仍然是异基因造血干细胞移植后病人死亡的主要原因之一。以前认为全身应用激素是治疗aGVHD的标准首要治疗方法,但一旦出现激素耐药,就没有标准的治疗方案了。在过去的10多年中,单克隆抗体、生物工程制品及免疫制剂的化学疗法成为了治疗这种疾病的新方法。许多药物如麦考酚酸乙酯、抗肿瘤坏死因子抗体、人源化抗CD25(白介素2受体α链)对治疗激素耐药性aGVHD显示出了较好的疗效,但因为感染率高,aGVHD患者的长期生存率仍然较低。提高aGVHD的治愈率关键在于成功的初始治疗以及适时的减低激素用量以促进免疫重建。临床上已经出现治疗药物与全身性激素应用相结合的尝试。在本文中,对于aGVHD的治疗方法,诸如aGVHD的首选治疗,aGVHD的二线治疗进行了综述。     

Hepatic veno-occlusive disease (sinusoidal obstruction syndrome) after hematopoietic stem cell transplantation in adult patients: Diagnosis,incidence, prophylaxis,and treatment

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) affecting the liver is a rare, possibly life-threatening complication of hematopoietic stem cell transplantation (HSCT). Sinusoidal endothelial cell (SEC) damage triggered by various factors (especially conditioning regimen) results in post sinusoidal portal hypertension due to obstruction of the hepatic vein. Diagnosis is guided by traditional clinical diagnostic criteria; the modified Seattle criteria, the Baltimore and revised European Group for Blood and Marrow Transplantation (EBMT), specifically. While there are promising results of imaging techniques studies in the diagnosis of VOD/SOS, none of those imaging techniques are routinely utilized in diagnosis yet. However, risk stratification is essential; conflicting results have been shown in studies aiming to define risk factors for development of VOD/SOS conducted to date. The only approved drug for the treatment of VOD/SOS yet is defibrotide, with early treatment offering higher chances of survival. In this review, we will focus on pathogenesis, clinical presentation and diagnostic criteria, risk factors, prophylaxis, and treatment of the VOD/SOS occurring post-HSCT.     

干细胞移植治疗脊髓损伤的研究进展

背景：干细胞移植作为治疗脊髓损伤最具前景的方法,已经在大量的动物实验和临床试验中得到证实。目的：综述干细胞移植治疗脊髓损伤的相关研究进展。方法：应用计算机检索2006-01/2010-12中国知网、Medline数据库相关文章,中文检索词＂干细胞,脊髓损伤,细胞移植＂,英文检索词＂stem cells,spinal cord injury,cell stransplantation＂,共检索到文献494篇,最终纳入符合标准的文献24篇。结果与结论：研究发现,移植的干细胞可以在脊髓内迁移、分化为神经元并分泌神经营养物质,促进神经组织的修复,改善神经功能。胚胎干细胞最早用于治疗脊髓损伤,但潜在的致瘤性等成为其临床应用的障碍;神经干细胞理论上是治疗脊髓损伤的首选干细胞,由于分离纯化技术要求严格,费用昂贵等使其在研究中进展缓慢;骨髓间充质干细胞来源丰富、取材方便,可行自体移植,避开了伦理学和移植后排斥等问题,目前被认为是一种理想的自体干细胞移植来源。随着细胞联合移植、基因修饰及组织工程支架移植治疗脊髓损伤的研究不断取得进展,许旺细胞、嗅鞘细胞的应用范围和治疗效果也得到提升。     

Aprepitant: a novel antiemetic for chemotherapy-induced nausea and vomiting

OBJECTIVE: To evaluate the safety and efficacy of aprepitant in the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV). DATA SOURCES: MEDLINE and PubMed database searches were conducted from 1966 to May 2004 using the following search terms: aprepitant, Emend, substance P, neurokinin-1, chemotherapy, nausea, vomiting, L-754,030, and MK-869. STUDY SELECTION AND DATA EXTRACTION: Large, randomized Phase II and III clinical trials examining the use of aprepitant for CINV, as well as all published drug interaction studies with aprepitant, were included and reviewed. Data lacking in published trials were supplemented with the manufacturer product information. DATA SYNTHESIS: The pharmacokinetics of aprepitant are favorable for once-daily oral dosing. Based on the results of published clinical trials, aprepitant appears to augment the effects of corticosteroids and 5-HT3 antagonists when given prior to highly emetogenic chemotherapy, including cisplatin. Aprepitant appears to have the most benefit in the prevention of delayed CINV and in preventing emesis rather than nausea. Data in pediatric patients, patients undergoing stem-cell transplantation, and those receiving multiple-day or moderately emetogenic chemotherapy are lacking. Common adverse effects are limited to hiccups, asthenia, and diarrhea. More serious but rare adverse effects include neutropenia. Because aprepitant is a CYP3A4 substrate, a 3A4 inhibitor and inducer, and a 2C9 inducer, close monitoring for drug interactions is warranted. CONCLUSIONS: Triple antiemetic therapy with aprepitant, a corticosteroid, and a 5-HT3 antagonist appears to provide improved efficacy in the prevention of emesis in patients receiving highly emetogenic chemotherapy. Due to its novel mechanism of action and demonstrated efficacy in this combination, aprepitant should be considered for formulary addition.     

What is the role of apheresis technology in stem cell transplantation?

Since the demonstration that hematopoietic cells are present in circulating blood, peripheral blood stem cell transplantation (PBSCT) has become an area of interest. The invention of growth factors such as the granulocyte colony-stimulating factor (G-CSF) and the availability of apheresis techniques allowed the wide application of peripheral blood stem cells (PBSC) in both autologous and allogeneic hematopoietic stem cell transplantation settings. It has been since 1986 that clinically introduced, peripheral blood stem cells replaced bone marrow as a stem-cell source to nearly 100% in the autologous and to approximately 75% in the allogeneic transplantation setting. During this period of time, remarkable development occurred in both stem cell mobilizing agents (i.e. CXCR4 antagonists) and apheresis techniques. Currently, apheresis technology is being increasingly used in not only for collection of PBSC or blood product support, but also for treatment and/or prevention of several transplantations related complications. Apheresis technology also allows to manipulate stem cells and thus provides opportunity to curative treatment of certain diseases.     

嗅鞘细胞移植治疗脊髓损伤：问题与瞻望

背景：嗅鞘细胞兼具有许旺细胞和星形胶质细胞的特性,能分泌多种神经生长因子和营养因子,改善脊髓损伤局部的微环境、诱导轴突的再生及髓鞘化、促进脊髓损伤后的功能恢复。目的：总结当前嗅鞘细胞移植治疗脊髓损伤的最新研究成果,将研究思路和最新研究进展相结合进行综述。方法：以＂olfactory ensheathing cell,transplantation,spinal cord injury＂为检索词,检索PubMed数据库（1990-01/2012-01）,以＂嗅鞘细胞,移植,脊髓损伤＂为检索词,检索CNKI数据库（2000-01/2012-01）,文献检索语种为英文和中文。纳入与嗅鞘细胞移植治疗脊髓损伤相关的文献,排除重复文献。结果与结论：计算机初检得到372篇文献,根据纳入排除标准,对其中23篇文献进行分析。大量动物及临床实验研究表明,嗅鞘细胞移植能有效促进脊髓损伤局部形态及功能的恢复,为临床治疗脊髓损伤患者提供了新途径。但是如何解决嗅鞘细胞的来源问题、如何避免异体移植免疫排斥反应的发生、以及异种移植中的生物安全问题是限制嗅鞘细胞移植治疗脊髓损伤临床应用的重要因素。因此,自体嗅鞘细胞移植治疗脊髓损伤能够较好地解决上述问题,将有可能成为后续研究的热点。     

嗅鞘细胞移植治疗慢性脊髓损伤的临床研究进展

背景：虽然迄今为止大量的体外和动物实验都证实了嗅鞘细胞对脊髓损伤的修复作用,但是利用嗅鞘细胞移植治疗脊髓损伤的临床试验尚处于起步阶段.目的：观察嗅鞘细胞移植治疗慢性脊髓损伤的临床安全性、有效性及实用性.方法：由第一作者检索至2012年5月为止 PubMed数据及CNKI中国期刊全文数据库有关嗅鞘细胞移植治疗慢性脊髓损伤的临床试验研究及安全性、疗效方面相关的报道,以“olfactory ensheathing cel s, spinal cord injury, clinical research”为英文检索词,“嗅鞘细胞移植,脊髓损伤”为中文检索词.结果与结论：计算机初检得到133篇文献,阅读标题和进行初筛,排除重复性研究,共34篇文献符合纳入标准.结果显示,利用嗅鞘细胞移植治疗脊髓损伤,在体外试验和动物模型中获得了良好的效果.在临床试验方面,到目前为止,嗅鞘细胞病灶直接移植治疗慢性脊髓损伤按嗅鞘细胞来源分主要集中在以下几个方面：①胚胎嗅鞘细胞移植.②嗅黏膜移植.③嗅黏膜源性嗅鞘细胞移植.3种嗅鞘细胞移植方法的总体安全性（96.4%）和有效性（23.4%）较高,但是其移植方法均存在明显的不足.提示嗅鞘细胞移植治疗慢性脊髓损伤的安全性和有效性还需要进一步验证,转化为临床应用还有很长的路要走.     

Autoimmune hemolytic anemia in pediatric liver or combined liver and small bowel transplant patients: a case series and review of the literature

BACKGROUND: Autoimmune hemolytic anemia (AIHA) occurring after solid organ transplantation is an infrequently reported entity. We describe in this report six cases of AIHA in pediatric liver or combined liver and small bowel transplant patients. STUDY DESIGN AND METHODS: We retrospectively identified and reviewed the records of pediatric liver or combined liver and small bowel transplant patients with both serologic and clinical evidence of AIHA. We also performed an English language literature review for prior publications of AIHA occurring after solid organ transplantation. RESULTS: We identified six patients presenting with severe hemolysis 9 months to 14 years after transplantation. All six developed warm AIHA, and two had concomitant cold agglutinins. All except one patient received various therapeutic combinations including steroids, intravenous immune globulin, rituximab, plasmapheresis, splenectomy, and vincristine. Five patients achieved remission 2 weeks to 3 months after presentation. Although tacrolimus has been speculated to play a causative role in the development of AIHA after organ transplantation, our case series demonstrated slightly better outcomes despite continuing tacrolimus compared to published cases where most patients either received significantly reduced doses of tacrolimus or were switched to a different immunosuppressant (83% vs. 76% cumulative literature remission rate). CONCLUSION: AIHA may occur in solid organ transplant patients at a much higher frequency than previously believed. Hemolysis is often severe and resistant to steroid treatment alone. Thus early diagnosis and institution of aggressive multimodality treatment, including the use of rituximab, may be needed to achieve remission.