Thrombotic complications associated with stem cell transplantation

Nadir, Yona; Brenner, Benjamin

doi:10.1016/j.blre.2012.05.001

Cited by 23 publications

(19 citation statements)

References 83 publications

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“…59 Thrombotic Microangiopathy Associated with Bone Marrow or Stem Cell Transplantation TMA following allogeneic and autologous transplantation is estimated to occur in 0.5 to 15% and 0.1 to 0.25% of cases, respectively. 203 Diagnosing TMA in the setting of BMT/SCT is challenging because thrombocytopenia, renal insufficiency, and the presence of schistocytes may also represent other complications, such as graft versus host disease (GvHD) and systemic infections. 141,204 Endothelial cell injury, induced by chemotherapy 205 and cyclosporine, 184 a prothrombotic state 206 and additional risk factors such as intravenous catheters, infections, and GvHD may well contribute to TMA pathogenesis.…”

Section: Thrombotic Microangiopathy Associated With Antibody-mediatedmentioning

confidence: 99%

“…141,204 Endothelial cell injury, induced by chemotherapy 205 and cyclosporine, 184 a prothrombotic state 206 and additional risk factors such as intravenous catheters, infections, and GvHD may well contribute to TMA pathogenesis. 203 In addition, endothelial cell regeneration is limited, as bone marrow endothelial progenitor cell populations, the source for endothelial cell repair, are depleted by the conditioning treatments. 203 We have recently detected CFH antibodies in 3 of 12 patients undergoing allogeneic SCT, on the background of a heterozygous CFHR3-CFHR1 deletion in two patients.…”

Section: Thrombotic Microangiopathy Associated With Antibody-mediatedmentioning

confidence: 99%

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Spectrum of Complement-Mediated Thrombotic Microangiopathies: Pathogenetic Insights Identifying Novel Treatment Approaches

Riedl

Fakhouri

Quintrec

et al. 2014

Semin Thromb Hemost

125

116

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Thrombotic microangiopathy (TMA) is a rare but severe disorder characterized by endothelial cell activation and thrombus formation. It manifests with the triad of hemolytic anemia, thrombocytopenia, and organ failure. Prompt diagnosis and treatment initiation are crucial for long-term outcome. TMA often manifests subsequent to infectious events, of which (enterohemorrhagic) Escherichia coli is the most frequently reported. TMA also occurs on the background of genetic/autoimmune defects in the complement system (atypical hemolytic uremic syndrome [aHUS]) and underlying conditions, such as pregnancy, transplantation, drugs, other glomerulopathies, vasculitides, or metabolic defects. Complement activation or defects in its regulation have now been described in an increasing number of acquired diseases with TMA. Coinciding with this expanding spectrum of complement-mediated diseases, the question arises which patients might benefit from a complement-targeted therapy. Success of therapy depends on the individual contribution of complement activation in disease pathogenesis. The advent of eculizumab, a monoclonal antibody that blocks terminal complement activation, has markedly improved outcome and quality of life in patients with aHUS. This review discusses the contribution of complement and highlights its complex interaction with inflammation, coagulation, and the endothelium. Treatment experiences focusing on eculizumab therapy are discussed in detail across the emerging spectrum of complement-mediated thrombotic microangiopathies.

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Section: Thrombotic Microangiopathy Associated With Antibody-mediatedmentioning

confidence: 99%

Section: Thrombotic Microangiopathy Associated With Antibody-mediatedmentioning

confidence: 99%

Spectrum of Complement-Mediated Thrombotic Microangiopathies: Pathogenetic Insights Identifying Novel Treatment Approaches

Riedl

Fakhouri

Quintrec

et al. 2014

Semin Thromb Hemost

125

116

View full text Add to dashboard Cite

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“…Consistent with this, all six cases of TMA in our cohort were likely secondary to either CLL treatment (allogeneic stem cell transplantation in 1 case, pentostatin in 4 cases) or potential CLL complications (metastatic cancer in 1 case). Although the association between TMA and metastatic cancer or stem cell transplantation is well recognized, 37,38 chemotherapyinduced TMA can be underappreciated, particularly for less frequently used drugs such as pentostatin. Pentostatin is a specific inhibitor of adenosine deaminase providing response frequencies comparable to those of fludarabine but with apparently lower toxicity and greater ease of administration.…”

Section: © F E R R a T A S T O R T I F O U N D A T I O Nmentioning

confidence: 99%

Renal complications in chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis: the Mayo Clinic experience

et al. 2015

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© F e r r a t a S t o r t i F o u n d a t i o ntent interstitial lymphocytic infiltration was observed. Standard processing of kidney biopsies evaluated at the Mayo Clinic included light microscopy, immunofluorescence, and electron microscopy. For light microscopy, biopsy specimens were stained with hematoxylin-eosin, periodic acid Schiff, Masson trichrome, and Jones methenamine silver. For immunofluorescence, 3-micron cryostat sections were stained with polyclonal fluorescein isothiocyanate-conjugated antibodies to IgG, IgM, IgA, C3, C1q, kappa and lambda light chains, fibrinogen, and albumin (Dako), as per routine clinical testing. Electron microscopy was performed as per clinical routine.Immunohistochemical stains for CD3, CD5, CD20, and CD23 were done in cases of interstitial lymphocytic infiltration (and for PAX5 and CD19 in selected cases) to help assess CLL/SLL involvement. Renal biopsy findings were further classified according to a potential causal relationship with CLL. Cases of membranoproliferative glomerulonephritis (MPGN), CLL infiltrate as primary etiology, minimal change disease (MCD), acute interstitial nephritis, amyloidosis, light chain cast nephropathy, membranous glomerulonephritis, and unclassified mesangial proliferative glomerulonephritis were considered directly related to CLL. Cases secondary to CLL-associated conditions, such as infections, autoimmune disease, and other cancers, or CLL treatment were considered potentially indirectly related to CLL. Cases secondary to non-CLL associated comorbidities or non-CLL treatment, such as diabetes, hypertension or obesity, were considered unrelated to CLL. Statistical analysisDescriptive statistics of baseline characteristics were calculated. The Mann-Whitney test was used for comparisons of medians. Overall survival was defined as time from diagnosis to death or last follow up. Survival curves were calculated using the Kaplan-Meier method, and comparisons were made using the log-rank test. All P-values were two-sided and considered statistically significant if ≤0.05. Statistical analyses were completed using SPSS 21. Results Baseline characteristicsBetween January 1 st , 1995 and June 30 th , 2014, 4,024 patients with CLL, SLL or MBL were followed at our institution. Of these patients, 49 (1.2%) had an ultrasound-guided kidney biopsy during follow-up to evaluate renal failure and/or nephrotic syndrome. Of these biopsies, 10% were performed before 2005, 49% between 2005 and 2010, and 41% after 2010. The indication for renal biopsy was renal insufficiency (without evidence of post-renal compression or tumor lysis) in 34 patients (69%; median creatinine 3.2 mg/dL, range 1.7-15) and nephrotic syndrome in 15 (31%; median proteinuria 11.3 g/24 hours, range 4-54.9). The pertinent baseline characteristics of these 49 patients at the time of CLL diagnosis are shown in Table 1.Kidney biopsy results are shown in Table 2. The distribution of renal pathology based on the indication for biopsy is shown in Figure 1. Of interest, among the five patie...

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“…Thrombotic events are well‐known complications associated with the acute or late phase of HSCT . Because DMSO can cause a direct damage to cell membranes, including endothelial cells, it is possible that DMSO activates the coagulation processes after infusion.…”

Section: Discussionmentioning

confidence: 99%

“…The relatively small number of patients is a clear limitation of our study, and additional experiments addressing the influence of DMSO on direct endothelial toxicity are needed. Direct endothelial damage has been previously postulated …”

Section: Discussionmentioning

confidence: 99%

Cryopreserved stem cell products containing dimethyl sulfoxide lead to activation of the coagulation system without any impact on engraftment

et al. 2013

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Thrombotic complications associated with stem cell transplantation

Cited by 23 publications

References 83 publications

Spectrum of Complement-Mediated Thrombotic Microangiopathies: Pathogenetic Insights Identifying Novel Treatment Approaches

Spectrum of Complement-Mediated Thrombotic Microangiopathies: Pathogenetic Insights Identifying Novel Treatment Approaches

Renal complications in chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis: the Mayo Clinic experience

Cryopreserved stem cell products containing dimethyl sulfoxide lead to activation of the coagulation system without any impact on engraftment

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