Alemtuzumab for Treatment of Acute Gvhd In Steroid-Refractory Patients.
Authors: Sucupira Alexandre , Ostronoff Mauricio , Ostronoff Fabiana , Maior ANA Patricia Souto , Freitas Jose Carlos , Florencio Rodrigo , Botelho Luis Fabio , Martins Monique , Calixto Rodolfo 
Published: October 2019

Abstract
Abstract 4545
Acute GVHD is associated with high-mortality. Alemtuzumab is a humanized monoclonal antibody against CD52 and although alemtuzumab has been used in the treatment of steroid-refractory acute GVHD, there is limited data. The severe immunosuppresion caused by alemtuzumab nonetheless is worrisome. We used lower dose of alemtuzumab subcutaneously to reduce the degree of immunosuppresion.
Between August 2008 and April 2010, ten patients underwent allo-BMT from matched related donors (7) and unrelated donors (3) developed grade ≥ III, steroid-refractory acute GVHD. Their underlying diagnoses were SAA (3), Hodgkin's lymphoma (3), CML (1), AML (2) and non-Hodgkin's lymphoma (1). Median age was 30 years (range 6 to 45 years), 8 were males and 2 females. Four patients received myeloablative conditioning regimen with busulfan (Bu) and cyclophosphamde and 6 patients received reduced intensity conditioning with Bu and fludarabine/GVHD prophylaxis consisted of cyclosporine A and mycofenolate mofetil. Five patients received bone marrow harvest stem cells from either related donor (4) or unrelated donor (1), 4 received PBSC (3 related and one unrelated) and one received umbilical cord stem cells.
All patients developed grade ≥ III acute GVHD. They were initially treated with 2mg of methylprednisolone daily for 5 consecutive days without response. They were then treated with alemtuzumab 10mg/day SQ for 5 consecutive days. The methylprednisolone was reduced to 1mg/kg/day in alternating days.
Complete response was considered complete resolution of all manifestation by day 28; partial response if at least one organ target resolved and non response if no regression was seen till D+14.
All patients received antibiotics, antifungal treatment and PCP prophylaxis with sulfamethoxazole and anti-CMV/HSV prophylaxis with gancyclovir and acyclovir.
The treatment with alemtuzumab SQ was well tolerated. Five patients developed significant hematological toxicities: 4 developed neutropenia (ANC <500/mm3), median duration 6 days (3 to 11 days) and thrombocytopenia (PLT < 20,000) median duration 8 days (5 to 12 days). They recovered their cell count without any specific intervention. They all had complete chimerism by VNTR.
Nine patients (90%) responded to treatment. Seven patients (70%) had complete resolution of GVHD. One patient did not respond and died of GVHD and Pseudomonas aeruginosa infection. One CR case had recurrence of GVHD 9 months later and died from sepsis and four others responsive patients died from infectious complications. Four patients remain free of GVHD for 4, 9, 15 and 16 months, their underlying diseases were AML (1), CML (1), SAA (2). One of these patients developed chronic GVHD six months later involving the lungs and responded to budesonide and systemic steroids. Three patients remain well and two with moderated thrombocytopenia.
Viral infectious reactivations were frequent, nonetheless, they were non-fatal: 2 cases of BK-virus associated hemorrhagic cystitis treated with leflunomide and 3 cases with CMV positive antigenemia treated with gancyclovir.PTSAge/SexDiagnosisaGVHD (Day post-BMT)Level of aGVHD GUT–SKIN-LIVERAlemtuzumab Start (Day post-BMT)ResponsePROGRESS (Day post BMT)IAMP15/MHD983-0-0115CRD, sepsis (198)SAF41/MCML543-0-059CRChronic GVHD (466)GJS35/MNHL953-0-2101PRD, Fusarium (113)MMS27/MSAA334-2-038NRD, P.aeruginosa (101)MRS33/FHD274-2-031PRD, P.aeruginosa (62)RCPA45/MSAA213-0-027CRD, Aspergillus (194)WMA26/MSAA213-0-036CRNo GVHD (274)VGA30/MHD323-0-049CRD, K. pneumoniae (243)VAS6/MAML483-2-053CRNo GVHD (483)JTS30/FAML493-0-055CRNo GVHD (121)Low dose of alemtuzumab SQ can be useful in patients with severe acute GVHD. It requires diligent infectious surveillance and treatment.

Disclosures:
No relevant conflicts of interest to declare.