205 - Immune Reconstitution and Outcomes after Peripheral Blood Haploidentical Transplantation with Novel Conditioning and Post-Transplant Cyclophosphomide (PTCY)

Abstract

The outcomes after Haploidentical HCT with Flu-CY-TBI and PTCY using BM as a graft source have been associated with high relapse and delayed immune recovery. Additionally, there is limited knowledge regarding immune reconstitution post haploidentical HCT with the use of mobilized peripheral blood. We hypothesized that the immunogenic properties of pre-transplant low dose Cyclophosphamide along with immunomodulatory effects of Melphalan would enhance early post-transplant engraftment and early peripheral T cell recovery through enhanced cytokine release and antigen alloreactivity. We examined the clinical outcomes and immune reconstitution recovery of 12 consecutive haploidentical HCT patients with high-risk hematological malignancies. Patients and Graft characteristics is as shown in Table 1. Conditioning regimen was low dose Cy 14.5 mg/m2 on day -6 & day −5, Flu 30 mg/m2 day −6 to Day −2 and Mel 70 mg/m2 on day −3 & −2. Graft versus host disease prophylaxis (GVHD) was PTCY 50 mg/Kg on day +3 and day +4 along with Tacrolimus and Mycophenolate starting at day +5. Immune reconstitution performed on days +60, +120 and +180 post HCT. All the patients treated according to an institutional protocol and records reviewed retrospectively after IRB approval.Table 1 All patients engrafted with median time to engraftment of 17 days (range 12-23). Chimerism studies revealed enhanced engraftment with 100% donor in bone marrow and peripheral blood at day 30 in all 12 patients. Post HCT immune recovery shown in Table 2. There was significant early recovery at day 60 of all T cell subsets, most pronounced in activated T cells. While we have observed a progressive reduction in the median number of early-activated T cells at day 120 & 180, the number CD4 and NK cells has improved (Figure 1).Table 2Table 2 With median duration of follow up of 323 days, range (123-451), the overall survival at day 100 and projected one year is 92% and 81% respectively. Only 2/12 had relapsed at 95 and 321 days post- transplant. Treatment related mortality (TRM) was limited to 1/12 patients. Acute GVHD grade 2-4 developed in six of 12 patients, two of whom were grade 3-4. Chronic GVHD has developed in four patients (1 serositis, 1 pericardial effusion and 2 nephrotic range proteinuria). CMV reactivation occurred in 9/12 patient with no CMV disease. Aspergillus antigen positivity in serum occurred in 4 /12 but only two of them developed clinical fungal infection. Conclusion: In this limited series of patients with high- risk hematological malignancies who underwent haploidentical HCT with Cy/Flu and Melphalan with PTCY, the regimen was well tolerated and resulted in effective disease control. The regimen has also demonstrated enhanced early engraftment and robust immune recovery in comparison to other studies, Table 3. The study provide unavailable knowledge about immune reconstitution post Haplo-identical HCT with PTCY with the use of mobilized peripheral blood.Table 3