A noninvasive diagnostic approach using per-rectal portal scintigraphy for sinusoidal obstruction syndrome after allogeneic hematopoietic cell transplantation

Abstract The Endothelial Activation and Stress Index (EASIX) is a laboratory-based prognosis index defined as creatinine × lactate dehydrogenase/platelets. When measured at pretransplantation evaluation (EASIX-PRE), it predicts allogeneic hematopoietic cell transplantation (alloHCT) mortality. This study explores its ability to predict intensive care unit (ICU) admission and validates EASIX-PRE predictive power for overall survival (OS) and nonrelapse mortality (NRM) in 167 consecutive patients undergoing alloHCT. EASIX-PRE was calculated retrospectively in all patients and transformed into log2 values (log2-EASIX-PRE). Log2-EASIX-PRE predicted ICU admission (hazard ratio [HR], 1.41; P < .001), OS (HR, 1.19; P = .011), and NRM (HR, 1.28; P = .004). The most discriminating EASIX-PRE cutoff value for risk of ICU admission was the 75th percentile (2.795); for OS and NRM, it was the median value (1.703). Patients with EASIX-PRE >2.795 had higher incidence of ICU admission in comparison with patients with lower EASIX-PRE values (day +180, 35.8% vs 12.8%; HR, 2.28; P = .010). Additionally, patients with EASIX-PRE >1.073 had lower OS (2 years, 57.7% vs 68.7%; HR, 1.98; P = .006) and higher NRM (2 years, 38.7% vs 18.5%; HR, 2.92; P = .001) than patients with lower EASIX-PRE results. Log2-EASIX-PRE was not associated with incidence of transplantation-associated microangiopathy, sinusoidal obstruction syndrome, or acute graft-versus-host disease. This study proposes EASIX-PRE as a prognostic tool to identify patients undergoing alloHCT at increased risk of severe organ dysfunction and who would therefore require ICU admission. Early identification of patients at high risk of severe events could contribute to personalized intervention design. Additionally, it validates the association between EASIX-PRE and OS and NRM in those undergoing alloHCT.

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A Prospective Randomized Comparison of Cyclophosphamide Versus Fludarabine in Addition of Antithymocyte Globuline for Allogeneic Hematopoietic Cell Transplantation in Patients with Adult Severe Aplastic Anemia; Interim Analysis

Blood ◽

10.1182/blood.v124.21.3890.3890 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3890-3890

Author(s):

Hawk Kim ◽

Won-Sik Lee ◽

Yeo-Kyeoung Kim ◽

Young-Don Joo ◽

Jinny Park ◽

...

Keyword(s):

Aplastic Anemia ◽

Cell Transplantation ◽

Hematopoietic Cell Transplantation ◽

Hematopoietic Cell ◽

Allogeneic Hematopoietic Cell Transplantation ◽

Phase Iii ◽

Severe Aplastic Anemia ◽

Sinusoidal Obstruction Syndrome ◽

Phase Iii Trial ◽

Engraftment Failure

Abstract Our previous study showed that a less toxic regimen comprising reduced cyclophosphamide (Cy), fludarabine and anti-thymocyte globulin (ATG) (Cy-Flu-ATG), was less toxic for allogeneic hematopoietic cell transplantation (alloHCT) compared with standard Cy-ATG in patients with adult severe aplastic anemia (AA). We postulated that replacing Cy with Flu (Flu-ATG) would be more beneficial. Therefore we performed a randomized phase III study to compare the regimen-related toxicities (RRTs) of two different conditioning regimens: Cy-ATG vs. Flu-ATG. We present the interim alaysis. Patients in the Cy-ATG arm received Cy at 200 mg/kg. Those in the Flu-ATG arm received fludarabine (Flu) at 180 mg/m2. A total of 36 patients (21 in the Cy-ATG and 15 in the Flu-ATG) were enrolled. The basic patientsÕ characteristics were similar between both arms except for donor type and HLA-matching. There were more unrelated donor (38.1% vs. 73.3%; p=0.037) and HLA mis-matching (0% vs. 40%; p=0.001) in Flu-ATG arm. All predefined RRTs were similar between Cy-ATG and Flu-ATG (33.3% vs. 33.3%; p=1.000). There was no primary engraftment failure in both arms and only one patients in Cy-ATG died of treatment-related hepatic toxicity before engraftment. Also there were no differences between Cy-ATG and Flu-ATG arms in terms of secondary engraftment failure (20% vs. 20%; p=1.000), hepatic sinusoidal obstruction syndrome (0% vs. 0%; p=1.000), hemorrhagic cystitis (4.8% vs. 0%; p=1.000), pulmonary complications (12.5% vs. 16.7%; p=1.000). The incidence of acute graft-versus-host disease (GvHD) (14.3% vs. 20.0%; p=0.677) and chronic GvHD (11.8% vs. 7.7% ; p=1.000) were also similar. The 3-year survival rate did not differ (77.3% vs. 77.0%; p=0.995; Figure 1). Flu-ATG can be Figure 1 promising in terms of RRT without increasing engraftment failure in Flu-ATG arm when considering more unrelated and HLA-mismaching patients were enrolled. We will continue this phase III trial. Figure 1. promising in terms of RRT without increasing engraftment failure in Flu-ATG arm when considering more unrelated and HLA-mismaching patients were enrolled. We will continue this phase III trial. Disclosures No relevant conflicts of interest to declare.

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