Impact of treatment and outcomes for patients with posttransplant drug‐associated thrombotic microangiopathy

Abstract

BACKGROUND: Drug-induced transplant-associated thrombotic microangiopathy (DTA-TMA) is a rare but serious complication that can occur after hematopoietic cell transplantation (HCT) or solid organ transplantation (SOT) without guidelines for optimal management of this condition. STUDY DESIGN AND METHODS:Given the ambiguity surrounding the treatment for DTA-TMA, we conducted a retrospective review to evaluate the impact of different treatment strategies in DTA-TMA patients. Our primary endpoint was to determine the overall response rate (ORR) for DTA-TMA based on the type of treatment modality chosen while secondary endpoints included the time to response, relapse rates, and overall survival for DTA-TMA cases.RESULTS: There were a total of 14 DTA-TMA patients of whom nine were post-HCT and five were post-SOT. Most of the DTA-TMA cases were due to tacrolimus (n 5 11) with a minority related to sirolimus (n 5 3). A total of nine of 14 patients demonstrated response and five had no response to therapy. The ORR among the DTA-TMA patients after HCT and SOT who received plasma exchange (PLEX) were 25 and 100%, respectively. The ORRs among the patients (includes HCT and SOT) who received rituximab (n 5 3) and eculizumab (n 5 5) were 67 and 60%, respectively. There were two relapses noted in our study and both were in the HCT group.CONCLUSION: While discontinuation of the offending agent may be sufficient for treatment of DTA-TMA after HCT, PLEX may be a reasonable option for DTA-TMA after SOT. Although the results are encouraging with rituximab and eculizumab in the treatment of DTA-TMA, larger prospective studies are needed to validate our findings.T hrombotic microangiopathy (TMA) is a multifactorial disease where generalized endothelial dysfunction leads to microangiopathic hemolytic anemia, intravascular platelet (PLT) activation, and formation of PLT-rich thrombi within the microcirculation.1,2 TMAs, though uncommon, are of considerable clinical importance because of their abrupt onset and high mortality when left untreated. The two major classes of drugs associated with druginduced transplant-associated TMA (DTA-TMA) after allogeneic hematopoietic cell transplantation (HCT) or solid organ transplantation (SOT) include calcineurin inhibitors (CNIs; cyclosporine A and tacrolimus) and mammalian target of rapamycin inhibitors (mTORi; sirolimus, temsirolimus, and everolimus). Given the rarity of the disease, there are no evidenced-based treatment guidelines for management of DTA-TMA. Due to this ambiguity surrounding the optimal treatment for DTA-TMA, we conducted a retrospective review to evaluate the impact of different treatment strategies on outcomes in patients with DTA-TMA. MATERIALS AND METHODS Study designWe retrospectively reviewed patients treated at Medical College of Wisconsin Cancer Center between January 1, 2008, and December 31, 2014. The Medical College of Wisconsin Scientific Review Committee and Institutional Review Board approved this study. Patients with TMA after HCT and SOT were identified from the...

Differences and similarities between disseminated intravascular coagulation and thrombotic microangiopathy

“…Disseminated intravascular coagulation (DIC) [ 1 , 2 ] is a serious disease that causes microvascular thrombosis associated with thrombocytopenia, a bleeding tendency and organ failure. These symptoms and laboratory data are similar to those of thrombotic microangiopathy (TMA) [ 3 ] which includes thrombotic thrombocytopenic purpura (TTP) [ 4 , 5 ], Shiga-toxin-producing Escherichia coli (STEC) - hemolytic uremic syndrome (HUS) [ 6 , 7 ], complement-mediated TMA (also called atypical HUS; aHUS) [ 7 , 8 ] and secondary TMA [ 3 , 9 ]. DIC also has several clinical subtypes, including asymptomatic type, marked bleeding type, organ failure type and complication types such as TTP or heparin-induced thrombocytopenia [ 10 ].…”

When to Stop Eculizumab in Complement-Mediated Thrombotic Microangiopathies

“…No comment on recurrent TMA was made. This study did, however, report a significantly reduced median cost of inpatient care and DOI: 10.1159/000492033 TA-TMA following solid-organ transplant has been reported in a wide spectrum of donor organ types including renal, small bowel, lung, liver, heart, and pancreas [12,14,40]. In existing case series, better outcomes have been observed in TA-TMA associated with solid organs.…”

“…The follow-up duration varied for each patient, though no recurrences of TMA were reported after a maximum of 17.5 months follow-up [12]. Similarly, in a recent smaller case series, responses were observed in 100% of those with solid-organ transplants [40].…”

Thrombotic microangiopathy after renal transplantation: Current insights inde novoand recurrent disease

“…Institution of therapeutic options is highly dependent on diagnosis as well as the patient’s response. The following approaches have been suggested: (1) Immunosuppressive medication management: the role of immunosuppressive medications ( e.g ., CNI or mTORi) has been reported in the literature, with a documented better response after switching from one CNI member to another or to an mTORi)[ 5 , 129 - 134 ]. However, this was not agreed by Satoskar et al[ 6 ], who denied any difference in outcomes between temporary discontinuation, dose modulation, withdrawal or continuation of CyA in management of de novo TMA.…”