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Clinical Trial
. 2023 Sep 26;7(18):5554-5565.
doi: 10.1182/bloodadvances.2023009840.

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

John Moore  1 , Nada Hamad  1 , David Gottlieb  2 , Ashish Bajel  3 , David Ritchie  3 , David Yeung  4 , Matthew Greenwood  5 , Duncan Purtill  6 , Steven Tran  7 , Annie Solterbeck  8 , Donna Aarons  7 , John Kwan  2
Affiliations
Clinical Trial

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

John Moore et al. Blood Adv. .

Abstract

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.

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Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Survival outcomes. (A) Probability of DFS in MAC (red) and RIC (blue) recipients. (B) Probability of OS.
Figure 2.
Figure 2.
Relapse and transplant mortality outcomes. Cumulative incidence of (A) TRM and (B) relapse in MAC (red) and RIC (blue) recipients.
Figure 3.
Figure 3.
Infectious morbidity. Cumulative incidence of (A) Hemorrhagic cystitis (P = .007), (B) BK viremia (P = .013), (C) CMV viremia (P = .604), and (D) Epstein-Barr viremia in MAC (red) and RIC (blue) recipients.
Figure 4.
Figure 4.
GVHD outcomes. Cumulative incidence of (A) aGVHD (2-4) and (B) probability of GRFS in MAC (red) and RIC (blue) recipients.
See this image and copyright information in PMC

References

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