CTLA4Ig-primed donor lymphocyte infusions following haploidentical transplantation improve outcome with a distinct pattern of early immune reconstitution as compared to conventional donor lymphocyte infusions in advanced hematological malignancies.

CTLA4Ig has a unique property to spare or even potentiate natural killer (NK) cell-mediated cytotoxicity, whilst inhibiting T cell activation. We explored the efficacy of prophylactic DLI following CTLA4Ig (CTLA4Ig-DLI group, n = 75), compared to conventional DLI (DLI group, n = 50), in patients with advanced hematological malignancies receiving PTCy-based haploidentical transplantation. Acute and chronic GVHD in the CTLA4Ig-DLI group were 9.6% and 15.3% compared to 18.8% [p = 0.09] and 36.5% [p = 0.01] in the DLI group. Both non-relapse mortality (4% vs 14.4%) and disease progression (DP) (15.7% vs 31.1%) were lower in CTLA4Ig-DLI group (p = 0.04). GVHD and progression-free survival was significantly improved in the CTLA4Ig-DLI group (p = 0.001). The recovery of CD56dimNK cells, NKG2A-KIR + NK subsets and Tregs was significantly better in the CTLA4Ig-DLI group at all time points and memory T cells at day +90. Immune recovery in relation to DP showed distinct patterns, with T cell subsets in the DLI group and NKG2A-KIR+NK cells in CTLA4Ig-DLI group having favorable impact. CTLA4Ig-DLI was thus associated with an improved outcome, possibly on account of the distinct pattern of immune recovery shown with this novel approach.

Total Hip Arthroplasty in 52 Active Advanced Tubercular Arthritic Hips.

BACKGROUND: The role of total hip arthroplasty (THA) in healed tuberculosis (TB) of the hip has been reported with success in the past. However, the role and success of THA in active TB of the hip has remained controversial. METHODS: We retrospectively evaluated a prospective study of 52 THAs done for active TB of the hip in 51 patients. The protocol includes 3-6 months of effective preoperative and 9-18 months postoperative anti-TB therapy. All THAs were performed by the same surgeon (author 1). The selection criteria excluded patients with poor immunity, HIV +ve patient, and presence of discharging sinus. The type of THA implant includes 12 cemented, 38 uncemented, and 2 hybrid fixations. RESULTS: The mean follow-up was 10.5 years (2-29). Six patients were (6 THAs) lost to follow up after 4 years, including 2 deaths unrelated to TB or THA. There was no reactivation of TB. Mean Harris Hip Score improved from preop 31.77 (20-51) to postop 88 (72-100) in the last follow-up. Two patients had delayed wound healing up to 21 days postop with no evidence of subsequent episode till last follow-up. There was no case of dislocation, neurological complication in any patient. Seven THAs underwent revision for aseptic loosening unrelated to TB. CONCLUSION: Single-stage THA is safe in active advanced tubercular arthritic hips with good immunity status under cover of effective anti-TB therapy using strict preop selection protocol.