Palumbo et al. Clinical and Laboratory Features of TA-TMA. Morgan GJ, Gregory WM, Davies FE, Bell SE, Szubert AJ, Brown JM, et al. Consolidation therapy with low-dose thalidomide and prednisolone prolongs the survival of multiple myeloma patients undergoing a single autologous stem-cell transplantation procedure. Overview of TA-TMA TA-TMA is triggered by injury to endothelial cells, such as from radiation, use of calcineurin or mTOR inhibitors, infections, or chemotherapy. Gruppo Italiano Trapianto Midollo Osseo (GITMO). Blood and marrow transplant clinical trials network toxicity committee consensus summary: thrombotic microangiopathy after hematopoietic stem cell transplantation. Differential impact of complement mutations on clinical characteristics in atypical hemolytic uremic syndrome. Bone Marrow Transplant. Shirley MH, Sayeed S, Barnes I, Finlayson A, Ali R. Incidence of haematological malignancies by ethnic group in England, 20017. De novo TMA, on the other hand, represents an overwhelming majority of the cases of post-transplant TMA and is a substantially more heterogeneous entity than recurrent aHUS. Moreover, finding complement gene mutations may identify patients at risk, but whether such patients benefit from prophylactic anti-complement therapies before BMT remains to be studied. The authors concluded that thalidomide might still be an option as post-ASCT maintenance in developing countries where access to IMiDs and proteasome inhibitors is limited [37]. Chua JS, Baelde HJ, Zandbergen M, Wilhelmus S, van Es LA, de Fijter JW The etiology of post-BMT TMA is thought to be multifactorial, including the effects of immunosuppressive agents, viral infections, TBI and GvHD. Different phase III trials have examined the relative role of these two approaches post-ASCT. Furthermore, as conditioning regimens have evolved over time, they have had an effect on the incidence of post-BMT TMA. In a recent study, Magro et al.26 used skin biopsies to diagnose aHUS, and they found extensive microvascular depositions of C5b-9, which supported the diagnosis. Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome. Lenalidomide maintenance versus observation for patients with newly diagnosed multiple myeloma (Myeloma XI): a multicentre, open-label, randomised, phase 3 trial. Chronic health conditions in adult survivors of childhood cancer. Akari Therapeutics Receives Positive Opinion on Orphan - TradingView In total, 62% of these patients had systemic TMA with hemolysis and thrombocytopenia, whereas 38% had TMA localized only to the graft. 2Division of Community Internal Medicine, Mayo Clinic Health System, Austin, USA, 3Mayo Clinic Health System, Albert Lea, MN USA, 1Division of Hematology, Mayo Clinic, Rochester, MN USA. Updated analysis of CALGB (Alliance) 100104 assessing lenalidomide versus placebo maintenance after single autologous stem-cell transplantation for multiple myeloma: a randomised, double-blind, phase 3 trial. et al. They also found that factor H did not bind to the surface of these microparticles released from cyclosporine-treated endothelial cells, demonstrating a decreased factor H activity. HSCT-TMA is often underdiagnosed due to. Even though it represents a potentially curative treatment, creating a sense of urgency to initiate the treatment, PE carries a high risk of serious complications.90 PE had been used as a main treatment for years because of its ability to remove mutated complement, antibodies against complement and other triggering factors for endothelial dysfunction, until a new therapeutic agent was found. A double-blind RCT confirmed prolonged PFS in lymphoma patients who received the patient-specific Id vaccine [60]. Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. Complete response improved by 21% with the combination therapy, compared to 11% with thalidomide and 17% with interferon alone. Received 2020 Apr 22; Accepted 2021 Feb 3. Ongoing clinical trials were also reviewed. Meehan SM, Kremer J, Ali FN, Curley J, Marino S, Chang A They found that C4d deposits were present in 88.1% of these tissues. In 1988, a randomized trial compared maintenance melphalan and prednisone to no maintenance therapy in patients with MM who responded to primary therapy. 1-4 Awareness of TA-TMA has increased in recent years, resulting in more centers implementing prospective screening for this condition. Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA) is a severe and potentially life-threatening complication. Caprioli J, Castelletti F, Bucchioni S, Bettinaglio P, Bresin E, Pianetti G The https:// ensures that you are connecting to the Early studies have highlighted the importance of anticomplement therapies in treating post-BMT TMA. The incidence of post-BMT TMA is affected by evolving therapies such as conditioning regimens. Waxman AJ, Mink PJ, Devesa SS, Anderson WF, Weiss BM, Kristinsson SY, et al. The authors reported no acute vaccine-related reactions. Another phase I/II trial using carfilzomib-melphalan conditioning followed by ASCT and carfilzomib maintenance in patients with relapsed myeloma demonstrated good PFS and OS. However, recently Chua et al.54 examined 42 renal sections with histologically confirmed TMA. HHS Vulnerability Disclosure, Help Treatment of de novo PT-TMA should be based on correcting the potential cause of the disease and varies depending on the time of onset. Patients received thalidomide, doxorubicin and dexamethasone or vincristine, doxorubicin and dexamethasone induction, followed by high-dose melphalan conditioning and stem cell transplant prior to receiving maintenance therapy. Thrombotic Microangiopathy - Johns Hopkins Medicine Glezerman IG, Jhaveri KD, Watson TH, Edwards AM, Papadopoulos EB, Young JW et al. Sonneveld P, Schmidt-Wolf IG, van der Holt B, el Jarari L, Bertsch U, Salwender H, et al. Ludwig H, Adam Z, Tthov E, Hajek R, Labar B, Egyed M, et al. Robson M, Cte I, Abbs I, Koffman G, Goldsmith D. Thrombotic micro-angiopathy with sirolimus-based immunosuppression: potentiation of calcineurin-inhibitor-induced endothelial damage? It can occur as a de novo disease or as a recurrence of a previous aHUS (sometimes undiagnosed before kidney transplantation). The wide range of reported incidence rates for post-BMT TMA is related to the inability to obtain a tissue biopsy and therefore a reliance on clinical parameters. Le Quintrec M, Zuber J, Moulin B, Kamar N, Jablonski M, Lionet A FDA approval summary: lenalidomide as maintenance therapy after autologous stem cell transplant in newly diagnosed multiple myeloma. This review focuses on diagnostic criteria, pathophysiology, treatment and renal outcomes of post-BMT TMA. Impact of FDA approval of lenalidomide maintenance therapy in the first-line treatment of multiple myeloma after autologous stem cell transplant on total healthcare costs. Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (TA-TMA) is a fatal post-transplant complication. Autologous transplantation and maintenance therapy in multiple myeloma. et al. Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome. Twenty-two patients (5%) were diagnosed with TMA by Fuge et al.19 among 436 patients who underwent allogeneic BMT. Treatment duration ranges from 4 weeks to 107 weeks. This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. 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Bone marrow transplant-associated thrombotic microangiopathy (TA-TMA) is a relatively frequent but under-recognized and under-treated hematopoietic stem cell transplant (HSCT) complication that leads to significant post-transplant morbidity and mortality. They are among the most serious and potentially fatal complications of transplantation. Post-bone marrow transplant TMA (post-BMT TMA) is a life-threatening condition that has been reported to afflict between 0.5 and 63.6% of BMT patients. and transmitted securely. Abstract. Validation of recently proposed consensus criteria for thrombotic microangiopathy after allogeneic hematopoietic stem-cell transplantation. Oxygen radicals mediate endothelial cell damage by complement-stimulated granulocytes. (Table (Table2).2). A retrospective chart review of 245 patients with MM treated at the Princess Margaret Cancer Centre confirmed prolonged PFS in patients who were on maintenance therapy after ASCT [44]. Thrombotic microangiopathy (TMA) is a systemic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia and organ failure. The Japan Study Group for Cell Therapy and Transplantation JSCT-MM12 trial included 64 patients with symptomatic myeloma. Goldberg RJ, Nakagawa T, Johnson RJ, Thurman JM. Higher expression of immune regulatory CD4+ and CD8+ T cells was noted in the treatment arm, translating to an enhanced clinical response [62]. government site. Siami K, Kojouri K, Swisher KK, Selby GB, George JN, Laszik ZG. All the trials also demonstrated significant toxicity associated with thalidomide use, especially peripheral neuropathy [25, 2737]. Major studies utilizing thalidomide as maintenance therapy, 2Thalidomide, doxorubicin, dexamethasone, Intensive groupCTD/CVAD, followed by HDM, VAD vincristine, doxorubicin and dexamethasone, TD thalidomide and dexamethasone, MP melphalan and prednisolone, CTD cyclophosphamide, thalidomide and dexamethasone, CVAD cyclophosphamide, vincristine, doxorubicin and dexamethasone, HDM high-dose melphalan, RCT randomized controlled trial, PFS progression-free survival, OS overall survival, DVT deep vein thrombosis. The ideal duration of maintenance therapy remains unknown, and the current recommendation is to continue maintenance until disease progression, particularly in patients with high-risk disease. PE may confer some benefit in patients with secretory antibodies.