Dataset Information

Fragmented Red Cell as a Possible Favorable Prognostic Marker of Hematopoietic Stem Cell Transplantation Associated Thrombotic Microangiopathy.

ABSTRACT:

Background

Fragmented red cell (FRC) by automated hematologic analyzer is known to detect schistocyte. In this study, it is noted that FRC might be a favorable prognostic marker of hematopoietic stem cell transplantation associated thrombotic microangiopathy (TA-TMA).

Methods

The peripheral blood samples and clinical data of 89 patients were collected. The diagnosis of TA-TMA was defined by the Blood and Marrow Transplant Clinical Trials Network's criteria and schistocyte or both schistocyte- and FRC-positive cases and other parameters fulfilled are regarded as TA-TMA.

Results

Schistocyte and FRC displayed a correlation coefficient of 0.461 (P < 0.001) by Spearman's method. The diagnostic concordance of TA-TMA using schistocyte and FRC was 92.1% with kappa index of 0.531 (P < 0.001). The number of diagnosed patients and mean survival month were as follows: TA-TMA by schistocyte, 8 (8.9%), 13.5 month; TA-TMA by schistocyte and FRC, 7 (7.8%), 40.4 month; No TMA, 74 (83.1%), 38.3 month, respectively. Kaplan-Meier survival analysis by log-rank method of the patient with TA-TMA by schistocyte and rest of the group showed statistical significance (P < 0.01).

Conclusion

As evidenced by the data, FRC might be a favorable prognostic marker for TA-TMA, but additional studies with larger patients groups are required for validation of clinical applications.

SUBMITTER: Jekarl DW

PROVIDER: S-EPMC6807144 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Fragmented Red Cell as a Possible Favorable Prognostic Marker of Hematopoietic Stem Cell Transplantation Associated Thrombotic Microangiopathy.

Jekarl Dong Wook DW Kim Yonggoo Y Lim Jihyang J Kim Myungshin M Han Kyungja K Cho Bin B Kim Hak-Ki HK Min Woo-Sung WS Min Chang-Ki CK

Journal of clinical laboratory analysis 20141110 6

<h4>Background</h4>Fragmented red cell (FRC) by automated hematologic analyzer is known to detect schistocyte. In this study, it is noted that FRC might be a favorable prognostic marker of hematopoietic stem cell transplantation associated thrombotic microangiopathy (TA-TMA).<h4>Methods</h4>The peripheral blood samples and clinical data of 89 patients were collected. The diagnosis of TA-TMA was defined by the Blood and Marrow Transplant Clinical Trials Network's criteria and schistocyte or both ...[more]

PMID: 25385174

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Project description:Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA) is a severe and potentially life-threatening complication. HSCT-TMA is often underdiagnosed due to multifactorial pathophysiology and a historic lack of standard diagnostic criteria. Identification of the multi-hit hypothesis and the key role of the complement system, particularly the lectin pathway of complement, has led to development of treatments targeting the underlying pathogenesis of HSCT-TMA. Additional research is ongoing to investigate the efficacy and safety of these targeted therapies in patients with HSCT-TMA. Advanced practice providers (APPs; nurse practitioners and physician assistants) and pharmacists are critical members of the multidisciplinary HSCT team and ensure management of patients throughout the continuum of care. Additionally, pharmacists and APPs can improve patient care through medication management of complex regimens; transplant education for patients, staff, and trainees; evidence-based protocol and clinical guideline development; assessment and reporting of transplant-related outcomes; and quality improvement initiatives to improve outcomes. Understanding the presentation, prognosis, pathophysiology, and treatment options for HSCT-TMA can improve each of these efforts. Collaborative practice model for monitoring and care of HSCT-TMA. Advanced practice providers and pharmacists contribute to many aspects of patient care in transplant centers, including medication management for complex regimens; transplant education for patients, staff, and trainees; evidence-based protocol and clinical guideline development; assessment and reporting of transplant-related outcomes; and quality improvement initiatives. HSCT-TMA is a severe and potentially life-threatening complication that is often underdiagnosed. The collaboration of a multidisciplinary team of advanced practice providers, pharmacists, and physicians can optimize recognition, diagnosis, management, and monitoring of patients with HSCT-TMA, thereby improving outcomes for these patients.

Project description:Thrombotic microangiopathy (TMA) after hematopoietic stem cell transplantation (HSCT) associated with terminal complement activation, as measured by elevated plasma terminal complement (sC5b-9) concentrations, has a very high mortality. The complement inhibitor eculizumab may be a therapeutic option for HSCT-associated TMA. We examined the pharmacokinetics and pharmacodynamics (PK/PD) of eculizumab in children and young adult HSCT recipients with TMA and activated complement to determine drug dosing requirements for future efficacy trials. We analyzed prospectively collected laboratory samples and clinical data from 18 HSCT recipients with high-risk TMA presenting with complement activation who were treated with eculizumab. We measured eculizumab serum concentrations, total hemolytic complement activity, and plasma sC5b-9 concentrations. Population PK/PD analyses correlated eculizumab concentrations with complement blockade and clinical response and determined interindividual differences in PK parameters. We also compared transplant survival in patients treated with eculizumab (n = 18) with patients with the same high-risk TMA features who did not receive any targeted therapy during a separate prospective observational study (n = 11). In the PK analysis, we found significant interpatient variability in eculizumab clearance, ranging from 16 to 237 mL/hr/70 kg in the induction phase. The degree of complement activation measured by sC5b-9 concentrations at the start of therapy, in addition to actual body weight, was a significant determinant of eculizumab clearance and disease response. Sixty-one percent of treated patients had complete resolution of TMA and were able to safely discontinue eculizumab without disease recurrence. Overall survival was significantly higher in treated subjects compared with untreated patients (56% versus 9%, P = .003). Complement blocking therapy is associated with improved survival in HSCT patients with high-risk TMA who historically have dismal outcomes, but eculizumab pharmacokinetics in HSCT recipients differ significantly from reports in other diseases like atypical hemolytic uremic syndrome and paroxysmal nocturnal hemoglobinuria. Our eculizumab dosing algorithm, including pr-treatment plasma sC5b-9 concentrations, patient's actual body weight, and the first eculizumab dose (mg), accurately determined eculizumab concentration-time profiles for HSCT recipients with high-risk TMA. This algorithm may guide eculizumab treatment and ensure that future efficacy studies use the most clinically appropriate and cost-efficient dosing schedules.

Dataset Information

Fragmented Red Cell as a Possible Favorable Prognostic Marker of Hematopoietic Stem Cell Transplantation Associated Thrombotic Microangiopathy.

Background

Methods

Results

Conclusion

Publications

Fragmented Red Cell as a Possible Favorable Prognostic Marker of Hematopoietic Stem Cell Transplantation Associated Thrombotic Microangiopathy.

Similar Datasets

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