Addition of Tocilizumab to Cyclosporine-a/ Mycophenolate Mofetil (CSA/ MMF) Graft-Vs-Host Disease (GVHD) Prophylaxis Significantly Abrogates Pre-Engraftment Syndrome (PES) & Severe Acute Gvhd after Adult Double Unit Cord Blood Transplantation (dCBT)

• Published in: Biology of blood and marrow transplantation 2020-03, Vol.26 (3), p.S30-S30
• Main Authors: Politikos, Ioannis, Maloy, Molly A., Devlin, Sean M., Naputo, Kristine, Bhatt, Valkal, Skinner, Kelcey, Cho, Christina, Dahi, Parastoo B., Giralt, Sergio A., Gyurkocza, Boglarka, Hanash, Alan M., Jakubowski, Ann A., Papadopoulos, Esperanza B., Perales, Miguel, Peled, Jonathan U., Sauter, Craig S., Scordo, Michael, Shah, Gunjan L., Tamari, Roni, Ponce, Doris M., Barker, Juliet N.
• Format: Article
• Language: English
• ISSN: 1083-8791; 1523-6536
• DOI: 10.1016/j.bbmt.2019.12.100

Anti-thymocyte globulin-free dCBT is associated with high rates of acute GVHD (aGVHD) especially involving the GI tract. Investigation of augmented aGVHD prophylaxis is indicated. We are investigating the addition of a single dose of tocilizumab 8 mg/kg (day -1) to CSA/ MMF (starting day -3) aGVHD prophylaxis in adult patients (pts) with hematologic malignancies undergoing dCBT with intermediate intensity Cy 50/ Flu 150/ Thio 10/ TBI 400 conditioning (NCT03434730). Outcomes of the first 26 patients (with survivor follow-up of at least 100 days) were analyzed & compared to 54 dCBT historic controls transplanted with identical conditioning & only CSA/ MMF. All patients received letermovir if CMV seropositive. 26 pts [median age 47 years (range 26-60), median weight 82 kg (range 59-125), 11 AML, 8 ALL, 2 MPAL, 3 MDS/ CML, 2 NHL, median age-adjusted HCT-CI 2.5 (range 0-6)] received dCB grafts with a median CD34+ cell dose of 1.5 × 105/kg/unit  (range 0.23-5.94) & median unit-recipient 8-allele HLA-match of 5/8 (range 3-6). One patient had graft failure in the setting of low graft viability/ disseminated adenovirus & a second pt had early transplant-related mortality (TRM) with incomplete count recovery. The remaining 24 patients engrafted at a median of 24 days (range 18-40) for a cumulative incidence of 92% (95%CI:67-98). 88% (95%CI:59-97) of pts engrafted platelets at a median of 43 days (range 32-78). Of evaluable pts, 68% & 83% had 100% single-unit donor chimerism in the blood at days 30 & 100, respectively; single-unit dominance was observed in the remaining cases. Six of 26 pts (23%) developed pre-engraftment syndrome (PES) at a median of 12.5 days, & only 3 of these (12%) required systemic corticosteroids. Additionally, 16 pts (62%) had no neutropenic fever prior to engraftment. The day 100 cumulative incidence of grade II-III & grade III aGVHD was 62% (95%CI:39-78) & 4% (95%CI: