Early cessation of calcineurin inhibitors is feasible post haploidentical blood stem cell transplant-the ANZHIT-1 study.

Haploidentical haematopoietic stem cell transplant (Haplo HSCT) using post -transplant cyclophosphamide (PTCy) is appropriate for those who lack matched donors. Most studies using PTCy have been retrospective with multiple conditioning regimens making conclusions difficult. ANZHIT-1 was a phase II study conducted at six Australian allogeneic HSCT centres. The primary endpoints were disease free and overall survival at 2 years post HSCT. The reduced intensity regimen (RIC) was fludarabine, cyclophosphamide, 200cGy TBI and the myeloablative regimen (MAC) was IV fludarabine, busulfan. PTCy, MMF (to D35) and a calcineurin inhibitor (CNI) were used as GVHD prophylaxis. CNIs were weaned and ceased by D+120 in eligible patients at D60. Patients (n=78, 52M:26F) with various haematological malignancies were included in the study with a median follow up of 732 days (28-1728). HSCT was RIC in 46 patients and MAC in 32 patients. Disease free survival probability at two years was 67.5% (95% CI: 53.2-85.6) for MAC recipients and 68.3% (95% CI: 56.3-83.01) for RIC recipients. Transplant related mortality (TRM) at D100 and 1 year were 4.9% (95% CI: 1.6-15.3) and 17.9% (95% CI: 8.8-36.5) in the MAC group compared to 3.1% (95% CI: 0.8.1-12) and 11.6% (95% CI: 6-22.4) respectively in the RIC group. The median time for elective cessation of CNI was D142.5 (47-1255) with no excess cGVHD or mortality. Of the evaluable patients, 71.6% were off immunosuppression at 12 months post-transplant. This prospective Haplo HSCT trial utilising PTCY demonstrates encouraging survival rates whilst demonstrating that early CNI withdrawal is feasible and safe. Clinical Trial # ACTRN 12617000151336.