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

•Haplo-HSCT results in encouraging disease-free survival despite significant hemorrhagic cystitis in the MAC arm.•Early cessation of CNI is feasible in haplo-HSCT, with most patients discontinuing immunosuppression at 12 months. [Display omitted] Haploidentical hematopoietic stem cell transplant (ha...

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Published in:	Blood advances Vol. 7; no. 18; pp. 5554 - 5565
Main Authors:	Moore, John, Hamad, Nada, Gottlieb, David, Bajel, Ashish, Ritchie, David, Yeung, David, Greenwood, Matthew, Purtill, Duncan, Tran, Steven, Solterbeck, Annie, Aarons, Donna, Kwan, John
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 26-09-2023 The American Society of Hematology
Subjects:	Clinical Trials and Observations
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Summary:	•Haplo-HSCT results in encouraging disease-free survival despite significant hemorrhagic cystitis in the MAC arm.•Early cessation of CNI is feasible in haplo-HSCT, with most patients discontinuing immunosuppression at 12 months. [Display omitted] Haploidentical hematopoietic stem cell transplant (haplo-HSCT) using posttransplant cyclophosphamide (PTCy) is appropriate for those who lack matched donors. Most studies using PTCy have been retrospective making conclusions difficult. ANZHIT-1 was a phase 2 study conducted at 6 Australian allogeneic HSCT centers. The primary end points were disease-free and overall survival at 2 years after HSCT. The reduced-intensity conditioning (RIC) included fludarabine, cyclophosphamide, and 200 cGy total body irradiation, and the myeloablative conditioning (MAC) was IV fludarabine and busulfan. PTCy, MMF and a calcineurin inhibitor (CNI) were used for graft-versus-host disease (GVHD) prophylaxis. CNIs were weaned and ceased by day +120 in eligible patients on day 60. Patients (n = 78) with hematological malignancies were included in the study, with a median follow-up of 732 days (range, 28-1728). HSCT was RIC in 46 patients and MAC in 32 patients. Disease-free survival probability at 2 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) on day 100 and year 1 was 4.9% (95% CI, 1.6-15.3) and 17.9% (95% CI, 8.8-36.5), respectively, in the MAC group compared with 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 day 142.5 days, with no excess chronic GVHD (cGVHD) or mortality. Of the evaluable patients, 71.6% discontinued immunosuppression 12 months after transplant. This prospective haplo-HSCT trial using PTCY demonstrated encouraging survival rates, indicating that early CNI withdrawal is feasible and safe.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	2473-9529 2473-9537
DOI:	10.1182/bloodadvances.2023009840