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Two Partial T Cell Depletion Strategies for Unrelated Donor Peripheral Stem Cell Transplantation are Associated with Excellent Outcomes for Pediatric Patients with Bone Marrow Failure (BMF)

Year: 2018

Type: article

Abstract: Background: HSCT for patients with BMF lacking a matched related donor (MRD) is limited by increased risk of graft failure and GvHD. Use of matched (MUD) or mismatched unrelated donor (MMUD) peripheral stem cell transplantation (PSCT) with partial T cell depletion (pTCD) for patients with BMF has potential advantages of enabling high donor stem cell doses for efficient engraftment while reducing GvHD. We present outcomes of 12 patients with BMF who received MUD or MMUD PSCT with pTCD performed using CliniMACS and either CD3+/CD19+ depletion with T cell addback or T cell receptor (TCR)αβ+ T cell/CD19+ depletion. Methods: Patients with BMF who lacked a MRD were eligible for inclusion. Donors were identified through the NMDP and high-resolution HLA typing was performed. Conditioning for patients with severe acquired aplastic anemia (SAAA) or paroxysmal nocturnal hemoglobinuria (PNH) included thymoglobulin, low dose TBI, fludarabine and cyclophosphamide. Patients with Diamond Blackfan Anemia (DBA) received thymoglobulin, busulfan, thiotepa and fludarabine. pTCD methods included CD3+/CD19+ depletion, with 1 × 105 CD3+ cells/kg addback per an expanded access study (n = 9) or TCRαβ+ T cell/CD19+ depletion (n = 3) on a current prospective trial. Results: Nine patients with BMF syndromes including SAAA (6), PNH (1), and DBA (2) received CD3+/CD19+ depletion and T cell addback. Donor match was 10/10 (4), 9/10 (4) and 8/10 (1). Patient age was 2.6-22.9 years and median CD34+ cell dose was 7.6 × 106 cells/kg. Median follow-up is 706 days (35-1241). All 9 patients demonstrated rapid, durable trilinear engraftment. Median time to neutrophil and platelet engraftment was 13 and 15 days per CIBMTR criteria. All are currently alive, transfusion independent, and have greater than 95% total peripheral blood donor chimerism, despite initial low T cell chimerism noted in several patients (Figure 1). Mild acute skin GvHD (grade II) occurred in 1 patient and 2 others developed eczema as the only manifestation of limited chronic skin GvHD. No patient is currently receiving systemic GvHD treatment. CMV and EBV reactivations did occur, but no patient developed symptomatic disease. 3 patients with SAAA received TCRαβ+ T cell/CD19+ depletion. HLA match was 10/10 (1) or 9/10 (2). Age range was 2.7-15.7 years, median CD34+ cell dose was 14.6 × 106 cells/kg, and median TCRαβ+ T cell dose was 6.85 × 104 cells/kg. All patients are alive without graft rejection with follow-up range of 123 to 193 days. Each achieved rapid trilinear engraftment with median neutrophil and platelet engraftment on days 15 and 14. They remain transfusion-independent with no GvHD to date and no history of symptomatic CMV or EBV disease. Conclusion: MUD and MMUD PSCT with pTCD performed either by CD3+/CD19+ depletion with CD3+ T cell addback or by TCRαβ+ T cell/CD19 depletion is associated with excellent failure-free survival and minimal GvHD in patients with BMF.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2017.12.524