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2018-02-19T10:40:34.000Z

Modified post-transplant cyclophosphamide (PT-CY) regimen provides protection against GvHD with low toxicity in AML

Feb 19, 2018
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The original Baltimore non-myeloablative regimen using high-dose Post-Transplant Cyclophosphamide (PT-CY) is considered a standard of care for unmanipulated HLA Haploidentical (haplo) Bone Marrow Transplant (BMT). However, it is associated with high incidence of relapse in patients with Acute Myeloid Leukemia (AML). The original Baltimore regimen was modified using a myeloabalative (MA) regimen followed by HAPLO BMT with PT-CY. This led, albeit in a single center setting, to reduced toxicity and encouraging survival in AML patients.1 It is not known whether this effect would be reproduced in a multicenter setting.

In a recent edition of Biology of Blood and Marrow Transplantation, Patrizia Chiusolo from the Universita Cattolica, Roma, IT, and colleagues, reported data from a multicenter retrospective study, which included 150 AML patients (median age = 51 years) who were treated at multiple institutions and received umanipulated HAPLO BMT between 2010 and 2016 with standard prophylaxis for Graft versus Host Disease (GvHD). All patients in this study received a modified PT-CY protocol with cyclosporine (CsA) on day 0, mycophenolate on Day +1, and PT-CY (50 mg/kg on days +3 and +5) following a myeloablative regimen.  At the time of transplant, patients were either in First Complete Remission (CR1, n = 68), Second CR (CR2, n = 31) or had Active disease (AD, n = 51). The median follow-up time for surviving patients was 903 days.

Key findings:

  • 100-day Cumulative Incidence (CI) of engraftment = 92% (95% CI, 88% – 98%)
  • GvHD
    • 100-day CI of Acute GvHD grade II-IV = 17% (95% CI, 12% – 24%)
    • 100-day CI of Acute GvHD grade III-IV = 5% (95% CI, 2% – 10%)
    • 4-year CI of Chronic GvHD moderate/severe = 15% (95% CI, 10% – 22%)
  • 4-year CI of Transplant Related Mortality (TRM) = 20% (95% CI, 14% – 28%)
    • 4-year CI of TRM in patients in CR1, CR2 and with AD were 14%, 18% and 30% respectively
  • 4-year CI of relapse = 24% (95% CI, 18% – 33%)
    • 4-year CI of relapse in patients in CR1, CR2 and with AD were 14%, 10% and 47% respectively
  • 4-year Overall Survival (OS) = 57%
    • 4-year OS in patients in CR1, CR2 and with AD were 74%, 70% and 26% respectively
  • AD at transplant was a negative predictor of survival, TRM and relapse
  • Deaths occurred due to relapse (n = 32), infections (n = 14), graft failure (n = 5), multiorgan failure (n=2), acute GvHD (n = 1), chronic GvHD (n=2), second malignancy (n = 1), and interstitial pneumonia (n = 4)

In conclusion, the authors stated that the original Baltimore PT-CY protocol can be modified with CsA administered on Day 0 before PT-CY in AML patients undergoing an unmanipulated HAPLO BMT and this can be successfully applied in a multicenter setting. Additionally, the use of modified PT-CY regimen led to high rate of engraftment, low incidence of GvHD and TRM, very low relapse in remission patients, and promising survival rates.

  1. Raiola A. M. et al. Unmanipulated haploidentical bone marrow transplant and posttransplantation cyclophosphamide for hematologic malignancies after myeloablative conditioning. Biol Blood Marrow Transplant. 2013; 19: 117–122. DOI: 10.1016/j.bbmt.2012.08.014
  2. Chiusolo P. et al. A Modified Post-Transplant Cyclophosphamide (PT-CY) Regimen, for Unmanipulated Haploidentical Marrow Transplantation, in Acute Myeloid Leukemia: a Multicenter Study. Biol of Blood and Marrow Transplantation. DOI: 10.1016/j.bbmt.2018.01.031. [Epub ahead of print].

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