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3383 Largest Reported Series of Adults Who Received Treatment with Eculizumab (ECU) for Hematopoietic Cell Transplantation-Associated Thrombotic Microangiopathy (TA-TMA). a Single Center Experience

Program: Oral and Poster Abstracts
Session: 721. Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities: Poster II
Hematology Disease Topics & Pathways:
Diseases, Biological, antibodies, Therapies, Clinically relevant
Sunday, December 2, 2018, 6:00 PM-8:00 PM
Hall GH (San Diego Convention Center)

Alan P Skarbnik, MD1, Mary E Dilorenzo, APN2*, Michele Simone, APN3*, Scott D. Rowley, MD3, David H. Vesole, MD, PhD4, Maribel Pereiras, Pharm D5*, Tracy Andrews, MSc6*, Andrew L. Pecora, MD7* and Michele L. Donato, MD4

1John Theurer Cancer Center, Myeloma and Lymphoma Divisions, Hackensack University Medical Center, Closter, NJ
2John Theurer Cancer Center, Hackensack, NJ
3John Theurer Cancer Center, Hackensack
4John Theurer Cancer Center, Myeloma and Lymphoma Divisions, Hackensack University Medical Center, Hackensack, NJ
5John Theurer Cancer, Hackensack Meridian Health, Hackensack
6Department of Biostatistics, John Theurer Cancer Center at Hackensack Meridian Health, Hackensack, NJ
7John Theurer Cancer Center at Hackensack Meridian Health, Hackensack, NJ


TA-TMA is a life-threatening complication of hematopoietic cell transplantation (HCT), usually manifested as a combination of non-immune mediated hemolytic anemia, thrombocytopenia and end-organ dysfunction (renal, neurologic and/or hypertension). Reported mortality rates following TA-TMA are high (50-75%; Gavriilaki et al, Bone Marrow Transplantation 2017). It is more commonly associated with allogeneic HCT, however, may infrequently occur with autologous HCT. Traditionally, treatment for TA-TMA consisted in removing possible offending agents (calcineurin inhibitors, sirolimus) and/or instituting total plasma exchange (PLEX). These approaches have not resulted in significant improvement in the natural history of TA-TMA, with complete resolution in 12-20% of pts (Mulay et al, J Clin Apher 2015).

Recent evidence of alternate complement pathway activation has been implicated in the pathophysiology of TA-TMA (Jodele et al, Blood 2013). Eculizumab (ECU) is an anti-C5 monoclonal antibody, approved for treatment of PNH and aHUS, which has been used anecdotally as treatment for TA-TMA. Most reports consist of pediatric patients. In this analysis, we evaluated consecutive cases of adult recipients of HCT who developed TA-TMA and have received ECU therapy at our institution.


We reviewed electronic records of consecutive patients who presented with a diagnosis of TA-TMA (non-immune hemolytic anemia plus worsening thrombocytopenia and end-organ dysfunction) and were treated with ECU between 2015 and 2017 at our institution. Univariate and bivariate statistics were calculated for the sample; Fisher’s exact tests and Wilcoxon rank sum tests were utilized to test for differences across groups.


Table 1 shows the baseline characteristics of these pts. A total of 15 pts were included in the analysis; 2/3 were female and the median age was 62. ECU was given according to the usual schedule for aHUS (900 mg IV weekly x 4, 1200 mg every other week starting on week 5). Median time from TA-TMA diagnosis to initiation of ECU was 2 days. All patients received prophylaxis for Neisseria meningitides with ciprofloxacin and antifungal prophylaxis at initiation of ECU. Three (20%) pts received PLEX prior to ECU. Seven (47%) patients were receiving tacrolimus at diagnosis, however, levels were not within toxic range (3.7-7.9 ng/mL). Median time post-HCT for development of TA-TMA was 135 days. Median LDH, hemoglobin, platelet count and creatinine at TA-TMA diagnosis were 1724 U/L, 7.3 g/dL, 33,000/mcL and 1.7 mg/dL, respectively. Ten (66.6%) patients had acute kidney injury and 7 (46.6%) pts had neurologic manifestations. Eight (53.3%) pts had evidence of GVHD concurrent with TA-TMA diagnosis. Ten (63.3%) pts developed systemic infections during their TA-TMA treatment. No pts developed meningitis or fungal infections.

Median follow-up was 4.5 months after initiation of ECU. Eight (53.3%) patients had complete resolution of TA-TMA (i.e. resolution of hemolytic anemia, thrombocytopenia and end-organ damage), 4 of these 8 pts were recipients of autologous HCT. Median time to resolution was 98 days and median cumulative ECU dose was 10,200 mg (range 4800-36400mg). An additional 2 pts (13%) presented clinical improvement without complete resolution of TA-TMA.

Mortality secondary to TA-TMA or its complications was 33%. Median time to death was 31 days. The most common cause of mortality were infectious complications. Median survival for the entire cohort was 130 days (range 6-833 days, Figure).

LDH >1300 U/L; more than one organ involvement, allogeneic HCT, use of tacrolimus and early (<100 days) onset of TA-TMA post-HCT were associated with lower rates of TA-TMA resolution and higher mortality. PLEX prior to ECU did not correlate with improved outcomes.


To our knowledge, this is the largest reported series of adult pts with TA-TMA who were treated with ECU. Treatment with ECU for TA-TMA is associated with higher rates of resolution and lower rates of cause-specific mortality than what has been previously reported with other approaches. We hypothesize that higher cumulative doses of ECU are warranted to achieve resolution of TA-TMA. A prospective study utilizing a more intensive schedule of ECU infusions is required to confirm such hypothesis. Based on our analysis, we conclude that ECU is an appropriate - and potentially better - option in the treatment of TA-TMA.

Disclosures: Skarbnik: Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz Pharmaceuticals: Honoraria, Speakers Bureau; Genentech: Honoraria, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Gilead Sciences: Honoraria, Speakers Bureau.

*signifies non-member of ASH