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share last authorship. Authorship Contribution: C.S., M.H., D.M., A.S.S., and C.C.D. life-threatening and causes significant morbidity and mortality. 3 Incomplete immune recovery may predispose to immune dysregulation following HSCT including autoimmune BRD4 Inhibitor-10 cytopenias. Although prednisolone or additional immunosuppressive providers control most episodes, up to 60% of individuals respond incompletely to 1st- or second-line therapies including rituximab.3 We describe an innovative therapy for AIHA post-HSCT refractory to established 1st- and second-line options. Methods We retrospectively evaluated data from 3 individuals treated with daratumumab (Darzalex) for posttransplant AIHA. Written educated consent of individuals and family members for compassionate use of the medication according to the Declaration of Helsinki and BRD4 Inhibitor-10 regulations of local review boards was obtained. Results and discussion Patient medical features and program post-HSCT A 19-year-old female with preCB-cell acute lymphoblastic leukemia (B ALL) with positive minimal residual disease (MRD) underwent myeloablative HSCT from a matched unrelated donor (MUD). Four weeks after HSCT, and one month following BRD4 Inhibitor-10 a second donor lymphocyte infusion (DLI) because of persistently positive MRD and declining donor chimerism, the patient developed Coombs-positive AIHA (hemoglobin [Hb], 4.7 g/dL). Response was partial following treatment with high-dose methylprednisolone (MPN), rituximab, and bortezomib. Because of prolonged MRD and AIHA, the patient was given a stem cell boost after treatment with high-dose cyclophosphamide and antithymocyte globulin (ATG). MRD became bad; however, during the following 14 weeks, prolonged AIHA prompted therapy with MPN, rituximab, alemtuzumab, bortezomib, mycophenolate mofetil (MMF), sirolimus, and ibrutinib. Her Coombs test remained positive and she required 2 packed reddish blood cell (PRBC) transfusions per week. Daratumumab (16 mg/kg per week IV) was given for 6 weeks during which time she required only 1 1 additional PRBC 5 days following the 1st infusion. Her hemoglobin improved without further transfusions and lactate dehydrogenase (LDH) normalized. At 4 weeks after her BRD4 Inhibitor-10 first dose of daratumumab, antibody titers in her Coombs test decreased, but haptoglobin remained undetectable. She required regular monthly PRBC transfusions over a period of 8 weeks after starting daratumumab before recurrence of AIHA. She died of refractory AIHA 2 weeks later on despite reinitiation of prior immunosuppressants and having been treated with plasmapheresis and splenic irradiation (observe Table 1 for more details). Table 1. Characteristics of individuals, HSCT, and posttransplant AIHA thead valign=”bottom” th rowspan=”1″ colspan=”1″ /th th align=”center” rowspan=”1″ colspan=”1″ Patient 1 /th th align=”center” rowspan=”1″ colspan=”1″ Patient 2 /th th align=”center” rowspan=”1″ colspan=”1″ Patient 3 /th /thead DiagnosisPreCB-ALLXLT/WASDNA-ligase IV deficiencyAge at HSCT19 y25 mo20 moDonorMUD (11/12, HLA-DP locus)MUD (9/10, B locus)MFDConditioning regimenBu (targeted cAUC 90); Flu (40 mg/m2); Clo (120 mg/m2); alemtuzumab (0.6 mg/kg)Treo (36 g/m2); Flu (150 mg/m2); Thio (10 mg/kg); alemtuzumab (0.7 mg/kg)Flu (150 mg/m2); Cy (20 mg/kg); alemtuzumab (1 mg/kg)Blood groups, recipient/donorA+/A+0+/0+0+/0+Onset of post-HSCT AIHA, days post-HSCT116138286Chimerism at analysis, % donor cells9210095Isotype/specific antibodiesIgG/anti Rh-E-antigenIgG/warm autoantibodyIgG/anti-RH5 antibodyActivation of complementYesNoYesImmunological phenotyping at onset of AIHANDCD4+ 48/L, CD19+ 108/L, CD56+/CD16+ 192/LCD4+ 792/L, CD19+ 528/L, CD56+/CD16+ 44/LPRBC transfusions prior to daratumumab200 (total)204Cumulative days of steroid treatment* prior to daratumumab50354379Initial treatmentMPN, rituximabPDN, rituximab, plasmapheresisMPN/PDN, rituximabPlasmapheresis sessionsNo36NoCumulative quantity of rituximab doses, 375 mg/m2, prior to daratumumab1187Cumulative quantity of bortezomib programs, 4 1.3 mg/m2, prior to daratumumab323Ongoing second- or third-line treatments at start of daratumumab treatmentBortezomib, sirolimus, MMF, ibrutinib, Cy, ATGMMF, plasmapheresisMMF, sirolimus, eculizumabDay of start daratumumab after onset of AIHA (post-HSCT day time+)503 (619)265 (403)333 (619)Total doses of daratumumab, 16 mg/kg, given once weekly1147Duration of daratumumab treatment, d491743Response to daratumumabPartial/transient (8 mo)YesYesPRBC following daratumumabUntil deathNone1Outcome (follow-up time in weeks after daratumumab/rituximab)Dieda/w (16/12)a/w (13/19)CD4+ T cells, CD45RA %NA1898/L, 75%1565/L, 44%Time to B-cell recovery, moNA7.56.5CD19+CD20+ B-cell recovery at last follow-upNA164/L656/LIgMNA0.44 g/L0.42 g/LCD19+CD38++ plasmablastsNAPresentPresentOn IVIGUntil deathNoYes Open in a separate window a/w, alive and well; B ALL, B-cell acute lymphocytic leukemia; Bu, busulfan; Clo, clofarabine; cAUC, cumulative area under the curve; Cy, cyclophosphamide; HLA-DP, human being leucocyte antigen DP; Flu, fludarabine; MFD, matched Rabbit Polyclonal to ADCK2 family BRD4 Inhibitor-10 donor; NA, not applicable; ND, not carried out; PDN, prednisolone; Thio, thiotepa; Treo, treosulfan; WAS, Wiskott-Aldrich syndrome; XLT, X-linked thrombocytopenia. *PDN 1 mg/kg. A 25-month-old.