Survival and relapse in patients with thrombotic thrombocytopenic purpura

Hovinga, Johanna A. Kremer; Vesely, Sara K.; Terrell, Deirdra R.; Lämmle, Bernhard; George, James N.

doi:10.1182/blood-2009-09-243790

Cited by 487 publications

(595 citation statements)

References 48 publications

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“…casians. This agrees with the findings of the Oklahoma TTP Registry (Kremer Hovinga et al, 2010) and suggests that these features of TTP are consistent across geographically disparate patient populations. We also confirmed previous findings showing no association between ABO blood group and TTP (Staropoli et al, 2009).…”

Section: Discussionsupporting

confidence: 88%

Impact of severe ADAMTS13 deficiency on clinical presentation and outcomes in patients with thrombotic microangiopathies: the experience of the Harvard TMA Research Collaborative

Bendapudi

Hamdan

et al. 2015

Br J Haematol

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SummaryThe Harvard TMA Research Collaborative is a multi-institutional registrybased effort to study thrombotic microangiopathies (TMA). Laboratory and clinical parameters were recorded for 254 cases of suspected autoimmune thrombotic thrombocytopenic purpura (TTP). Patients with severe ADAMTS13 deficiency (activity ≤10%, N = 68) were more likely to be young, female and without a history of cancer treatment or transplantation. While all patients with severe deficiency were diagnosed with autoimmune TTP, those without severe deficiency frequently had disseminated intravascular coagulation, drug-associated TMA and transplant-related TMA. Patients with severe ADAMTS13 deficiency had superior overall survival at 360 d compared to those without severe deficiency (93Á0% vs. 47Á5%, P < 0Á0001). Almost all patients with severe deficiency received therapeutic plasma exchange (TPE), but the use of TPE in patients with ADAMTS13 activity >10% varied significantly across the institutions in our consortium (13Á2-63Á8%, P < 0Á0001). Nevertheless, 90-d mortality was not different in patients with ADAMTS13 activity >10% between the three hospitals (P = 0Á98). Our data show that patients with severe ADAMTS13 deficiency represent a clinically distinct cohort that responds well to TPE. In contrast, TMA without severe ADAMTS13 deficiency is associated with increased mortality that may not be influenced by TPE.

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Section: Discussionsupporting

confidence: 88%

Impact of severe ADAMTS13 deficiency on clinical presentation and outcomes in patients with thrombotic microangiopathies: the experience of the Harvard TMA Research Collaborative

Bendapudi

Hamdan

et al. 2015

Br J Haematol

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“…[26][27][28][29][30] In the South East England TTP registry, Ͼ 50% of the recorded episodes were relapses. 14 Relapse in TTP BLOOD, 18 AUGUST 2011 ⅐ VOLUME 118, NUMBER 7 For personal use only.…”

Section: Discussionmentioning

confidence: 99%

A phase 2 study of the safety and efficacy of rituximab with plasma exchange in acute acquired thrombotic thrombocytopenic purpura

Scully

McDonald

Cavenagh

et al. 2011

Blood

375

388

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The safety and efficacy of weekly rituximab 375 mg/m 2 (؋4), given within 3 days of acute TTP admission, with standard therapy (PEX and steroids) was evaluated. Clinical outcomes were compared to historical controls (n ‫؍‬ 40) who had not received rituximab. Within the trial group, 15 of 40 required ICU admission and 15% of all cases with the highest troponin T levels on admission were ventilated. Before the second rituximab infusion, 68% of cases had a platelet count > 50 ؋ 10 9 /L and 38% > 150 ؋ 10 9 /L. Fewer PEX were required in whites compared to nonwhite in the rituximab group (mean 14 vs 21, P ‫؍‬ .0095). Inpatient stay was reduced by 7 days in the non-ICU trial cases compared to historical controls (P ‫؍‬ .04), especially in whites, with a mean reduction of 7 days (P ‫؍‬ .05). Ten percent of trial cases relapsed, median, 27 months (17-31 months), compared to 57% in historical controls, median 18 months (3-60 months; P ‫؍‬ .0011).There were no excess infections or serious adverse events with rituximab. In conclusion, rituximab appears a safe and effective therapy. Inpatient stay and relapse are significantly reduced in the rituximab cohort. Rituximab should be considered in conjunction with standard therapy on acute presentation of TTP. This study was registered at www.clinicaltrials.gov as NCT009-3713. (Blood. 2011;118(7): 1746-1753)

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“…[35][36][37] Relapses result from severe ADAMTS13 deficiency caused by the persistence or recurrence of anti-ADAMTS13 antibodies. 35 Each relapse exposes the patient to a risk of death.…”

Section: How To Prevent Relapses?mentioning

confidence: 99%

Treatment of thrombotic thrombocytopenic purpura beyond therapeutic plasma exchange

Coppo

Froissart

2015

Hematology

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Daily therapeutic plasma exchange (TPE) transformed the historically fatal prognosis of acquired, anti-ADAMTS13 antibody-mediated thrombotic thrombocytopenic purpura (TTP), leading to the current overall survival rates of 80%-85%. However, relapses occur in ϳ40% of patients and refractory disease with fatal outcomes still occurs. In this context, the introduction of rituximab has probably been the second major breakthrough in TTP management. Rituximab is now routinely recommended during the acute phase, typically in patients with a suboptimal response to treatment, or even as frontline therapy, with high response rates. In more severe patients, salvage strategies may include twice-daily TPE, pulses of cyclophosphamide, vincristine, as well as splenectomy in more desperate cases.In this life-threatening disease, relapse prevention represents a major goal. Persistent severe acquired ADAMTS13 deficiency in patients who are otherwise in remission is associated with a high risk of relapse and preemptive treatment with rituximab may be considered in this context.In the coming years, the TTP therapeutic landscape should be enriched by original strategies stemming from clinical experience and new agents that are currently being evaluated in large, ideally international, clinical trials. Promising agents under evaluation include N-acetylcysteine, bortezomib, recombinant ADAMTS13, and inhibitors of the glycoprotein-Ib/IX-von Willebrand factor axis. Learning Objectives• Patients with acquired TTP who experience a suboptimal response (refractoriness or disease exacerbation) with standard management need a more intensive treatment • Salvage therapies typically include rituximab, and in the more severe cases twice daily plasma exchange, boluses of cyclophosphamide, vincristine, and splenectomy • A persistent severe acquired ADAMTS13 deficiency during TTP remission should prompt consideration of preemptive rituximab to prevent relapses

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Survival and relapse in patients with thrombotic thrombocytopenic purpura

Cited by 487 publications

References 48 publications

Impact of severe ADAMTS13 deficiency on clinical presentation and outcomes in patients with thrombotic microangiopathies: the experience of the Harvard TMA Research Collaborative

Impact of severe ADAMTS13 deficiency on clinical presentation and outcomes in patients with thrombotic microangiopathies: the experience of the Harvard TMA Research Collaborative

A phase 2 study of the safety and efficacy of rituximab with plasma exchange in acute acquired thrombotic thrombocytopenic purpura

Treatment of thrombotic thrombocytopenic purpura beyond therapeutic plasma exchange

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