Hypoalbuminemia (&lt; 3.0 g/dl) and Poor Karnofsky Performance Score (&lt;80) at Day 90 Following Allogeneic Hematopoietic Stem Cell Transplantation (allo-HCT) Are Independent Predictors of Worse Non-Relapse Survival (NRS) and Overall Survival (OS): A Multivariable Analysis Approach of Various Clinical, Laboratory and Pharmacologic Parameters
Authors: Kharfan-Dabaja Mohamed A , Chavez Julio C. , Fernandez-Vertiz Eduardo Ivan , Yu Daohai , Zhu Weiwei , Perkins Janelle , Field Teresa , Ayala Ernesto , Fernandez Hugo F. , Alsina Melissa , Perez Lia , Raychaudhuri Jyotishankar , Ochoa-Bayona J. Leonel , Brand Linda , Sullivan Dan , Anasetti Claudio 
Published: April 2020

Abstract
Models using acute GVHD (aGVHD) to predict post allo-HCT survival rely on criteria with considerable inter-observer subjectivity. We study the impact of clinical, laboratory and pharmacologic parameters, during the immediate post-transplant phase [from hematologic engraftment till day 90 (±7)] on NRS and OS. In this analysis, 326 consecutive pts underwent allo-HCT between 09/2000 until 03/2007; 26 pts who died within 90 days from stem cell infusion and 3 recipients of syngeneic allo-HCT were excluded. A total of 297 (M/F=170/127) pts, median age 46 (range: 17–69) yrs received an allo-HCT [MRD=154 (52%), MUD=109 (37%), MMRD=3 (1%), MMUD=31 (10%)] using PBSC=261 (88%) or BM=36 (12%) following myeloablative=99 (33%), RIC=174 (59%), or NMT=24 (8%) for various hematologic malignancies stratified by CIBMTR risk [low=87 (30%); int=85 (29%); high=125 (42%)] using various GVHD prophylaxis regimens [MTX-based=244(82%); MMF-based=53 (18%)]. Pre-transplant variables [significant (p&lt;0.05) or not-significant (NS) (p≥0.05) in multivariable Cox proportional hazards regression analysis] included: age (≥55 vs. &lt; 55 yrs) [OS: p=0.035, HR=1.6 (95% CI: 1.0–2.4); NRS: p=0.03, HR=2.0 (95% CI: 1.1–3.6)], donor-gender [OS: NS; NRS: NS], cell source (BM vs. PB) [OS: NS; NRS: NS], baseline Karnofsky score (KPS) (≤80 vs. &gt;80) [OS: NS; NRS: NS], CIBMTR risk (low vs. int. vs. high) [OS: NS; NRS: NS], regimen (myeloablative vs. RIC/NMT) [OS: NS; NRS: NS], donor/recipient matching-status (MRD, MUD, mismatched (ref)) [OS: p=0.03, MRD vs. ref: HR=2.7 (95% CI: 1.2–6.1), MUD vs. ref: HR=2.7 (95% CI: 1.2–6.1); NRS: NS], CD34+ dose (&lt; 3×106/kg, 3–7.9 ×106/kg, ≥8×106/kg) [OS: NS; NRS: NS], GVHD prophylaxis (MTX-based vs. MMF-based) [OS: NS; NRS: NS], recipient/donor CMV status [OS: NS; NRS: NS]. Multivariable regression analysis of post-transplant variables (table 1) at day 90 show that a KPS&lt;80 and hypoalbuminemia &lt;3.0 g/dl are independent predictors of worse NRS and OS. A worsening serum creatinine (≥30%) and additional antimicrobials apart from standard prophylaxis are independent predictors of worse OS; whereas pneumonia (&gt;0 episode by day 90) and cumulative dose of prednisone exceeding &gt;2,650 mg are independent predictors of worse NRS. A KPS &lt;80 and hypoalbuminemia (&lt;3.0 g/dl), at day 90, are stronger predictors of survival than aGVHD, and should be considered when prognosticating outcome after allo-HCT. Multivariable Regression Analysis for OS and NRS† Post-transplant variables at day 90 (±7) post-allo HCT§
OS NRS †Table entry: 1st line=p-value (p) for the covariate effect, 2nd line=Hazard ratio (HR) (95% CI). §The effects of post-transplant variables were adjusted for baseline variables such as age, KPS and patient/donor CMV statuses in this regression, whenever appropriate/necessary. Statistical significance defined as &lt;0.05; NS: not significant (p≥0.05). TPN: total parenteral nutrition; *from hematopoietic engraftment until day 90 (±7). **from initiation of conditioning chemotherapy (baseline) until day 90 (±7). ^ additional anti-GVHD therapy(ies) apart from standard GVHD prophylaxis and glucocorticoids until day 90 (±7). ^^ additional antimicrobials apart from acyclovir, fluconazole or voriconazole (whenever used for primary prohylaxis) and trimethoprin-sulfamethoxazole (or equivalents). ¥ development of infiltrates requiring additional/alternative antimicrobials. Hospital stay ( 5 vs. &gt;5 days)* NS NS Days of TPN (&gt;0 vs. 0)* NS NS PRBC transfusion (&gt;0 vs. 0)* NS NS Platelets transfusion (&gt;0 vs. 0)* NS NS Pneumonia episodes (&gt;0 vs. 0)*¥ NS p=0.0008 2.8 (1.5, 5.1) Episodes of CMV reactivation (&gt;0 vs. 0)* NS NS Cumulative dose of steroids (&lt;2,650mg vs. 2,650mg)* NS p=0.001 0.4 (0.2, 0.7) Total days of steroids (&lt;60 vs.≥60)* NS NS Dose of steroid at day 90 (±7) (&lt;20 vs. ≥20mg/day) NS NS % weight loss (≤10% vs. &gt;10%)** NS NS Acute GVHD (max grade) 0–I vs. II vs. III–IV NS NS KPS at day 90 (±7) (&lt;80 vs.≥ 80) p&lt;0.0001 4.7 (3.0, 7.4) p&lt;0.0001 3.9 (2.0, 7.5) Total bilirubin at day 90 (±7) (&lt;1.1 vs. ≥1.1mg/dl) NS NS % Creatinine change (≥30 vs. &lt;30)* p=0.0002 2.2 (1.5, 3.3) NS Albumin at day 90 (±7) &lt; 3.0 g/dl vs. &gt; 3.5 g/dl 3.0–3.5 g/dl vs. &gt; 3.5 g/dl p=0.006 2.5 (1.4, 4.5) 1.5 (0.9, 2.3) p=0.01 3.2 (1.4, 7.1) 1.2 (0.6, 2.3) Additional immunosuppressive therapy (ies) (&gt;0 vs. 0)^ NS NS Additional anti-microbial(s) (&gt;0 vs. 0)^^ p=0.002 2.8 (1.5, 5.3) NS