Nephrotic Syndrome After Allogeneic Hematopoietic Cell Transplantation: Incidence and Outcomes.
Authors: Khaled Yasser , Choi Sung , Hanauer David A , Reddy Pavan 
Published: October 2019

Abstract
Abstract 3324
Poster Board III-212
The NIH Consensus recognizes nephrotic syndrome (NS) as part of the chronic GVHD symptomatology, but this manifestation is rare and the incidence and outcomes have not been well-defined. To characterize this complication, we conducted an IRB-approved retrospective review of 626 consecutive patients (age > 16 yrs: related donor [RD], n=352; unrelated donor [URD], n=274) who underwent allogeneic hematopoietic cell transplantation (HCT) between October 2000 and December 2007 at the University of Michigan. Data abstraction was facilitated by the use of an electronic medical record search engine (EMERSE) that allowed for efficient identification of key concepts based on a specified set of key words and phrases (e.g. “GVHD,” “proteinuria,” and “nephrotic syndrome”). Conditioning regimens included full intensity (FIC) in 470 patients and reduced intensity (RIC) in 156 patients. Nephrotic range proteinuria was identified in 17 of the patients, which is the largest cohort reported to date following allogeneic HCT. Renal biopsy confirmed the diagnosis in seven of these patients. The median time to onset of NS was 7.3 months (range 1.4 – 40.6 months) following allogeneic HCT. Clinical manifestations included hypoalbuminemia (100%), hypercholesterolemia (82%), edema (76%), renal impairment (65%), and thrombosis (29%). The overall cumulative incidence of NS was 2.9%: 2.4% in FIC and 4.6% in RIC HCT recipients; and 2.3% in RD and 3.7% URD HCT recipients. Of note, in patients who received irradiation-based conditioning regimens, there was an increased cumulative incidence of NS compared to those who did not, 4.8% versus 2.1%, respectively.
Diagnostic symptoms of chronic GVHD based upon the NIH Consensus was seen in 65% (n=11) of the patients, all of whom were on immunosuppressive therapy at the time of diagnosis of NS. Prior history of acute GVHD was seen in 65% (n=11) of the patients. Interestingly, history of symptomatic cystitis was seen in 53% (n=9) of the patients, eight of whom had BK virus detected in the urine. The management and treatment for NS was variable. All of the patients received systemic steroids (0.25 mg/kg – 2 mg/kg), with or without mycophenolate mofetil and a calcineurin inhibitor. Additional therapy with rituximab was administered in nine patients. Durable remission with no further recurrence of proteinuria was observed in 47% of the patients (n=8). The median time to response was 4.8 months (range 0.3 – 13.5 months). Recurrence of proteinuria was seen in 29% of the patients (n=5), and primary refractory proteinuria was observed in 23% of the patients (n=4). Overall survival for the cohort was 49.5% at 4 years (confidence interval 24% - 75%) with median follow up of 5.1 years. The median survival from diagnosis of NS was 2.5 years. As of May 2009, eight patients are alive and nine have died. The causes of death include GVHD (n=6), relapse (n=2) and unknown (n=1). NS is a rare but important complication following allogeneic HCT. Early recognition of the clinical presentations and identification of high-risk groups may limit the potential morbidity and mortality associated with NS.
Patient MUD/MRD PB vs BM Age at TP Conditioning Regimen DX Proteinuria estimate (g/24h) Gender GVHD Regimen Kidney Biopsy 1 MUD PB 53 FluBuTLI MPD 5.5 F Tacro/MTX Minimal change GN 2 MUD PB 56 FluBuTLI MM 14 M Tacro/MTX Membranous GN 3 MRD PB 57 BuCy MDS 14 M Tacro/MTX Membranous GN 4 MUD PB 55 BAC AML 3.4 M Tacro/MTX N/A 5 MRD PB 30 CVB NHL 3.74 M Tacro/MTX Membranous GN 6 MRD PB 47 BAC AML 10 M Tacro/MTX Membranous GN 7 MUD PB 49 FluBuTLI NHL 6.9 M Tacro/MMF N/A 8 MUD PB 38 BuCy AML 8.7 F Tacro/MMF N/A 9 MUD BM 18 CyATG Aplastic Anemia 4.22 F Tacro/MTX N/A 10 MRD PB 34 BAC AML 5.96 F Tacro/MTX N/A 11 MUD PB 61 FluBuTLI MDS 13.27 M Tacro/MTX N/A 12 MRD PB 26 BuCy CMML 3.58 F Tacro/MMF N/A 13 MRD PB 63 FluBuTLI NHL 4.54 F Tacro/MMF/MTX N/A 14 MUD PB 55 BuCy AML 22.57 M Tacro/MTX/Etanercept Minimal change GN 15 MRD PB 59 CVB-R NHL 3.37 M Tacro/MMF N/A 16 MRD PB 62 FluBuTLI AML 5.47 F Tacro/MMF/MTX Membranous GN 17 MUD PB 46 CyTBI AML 7.96 F Tacro/MTX/Etanercept N/A MUD = matched unrelated donor; MRD = matched related donor; PB = peripheral blood; BM = bone marrow; GN = glomerulonephritis; N/A = non applicable; MTX = methotrexate; MMF = mycophenolate mofetil; FluBuTLI = Fludarabine, Busulfan, Total Lymphoid Irradiation; BuCy = Busulfan, Cytoxan; BAC = Busulfan, Ara-C, Cytoxan; CVB = Cytoxan, Etoposide, BCNU; CyATG = Cytoxan, ATG

Disclosures
Hanauer: UMERSE, LLC: Consultancy, Patents & Royalties.