aGvHD,   cGvHD

Post-transplant cyclophosphamide use in matched HLA donors

Studies in the haploidentical transplantation setting have demonstrated that post-transplant cyclophosphamide (PTCy) works by eliminating alloreactive T cells, while preserving the memory and regulatory T cells, resulting in less GvHD, better immune tolerance and less graft rejection.

While (PTCy) is widely and successfully used for the prevention of GvHD after haploidentical stem cell transplants (HSCT),1 only a few studies have looked at the use of PTCy for patients undergoing HLA-matched related (MRD) and matched unrelated (MUD) transplants.

Riad El Fakih, from the Department of Adult Hematology & Stem Cell Transplant, King Faisal Hospital & Research Center, Riyadh, SA and colleagues conducted a literature review2 from the PubMed and Cochrane databases, using the search terms, ‘post-transplant cyclophosphamide’ and ‘matched donors’. The team selected English language and peer-reviewed journals.

Use of PTCy after intensive conditioning transplants

The team reviewed a number of studies of intensive pre-transplant conditioning.

Study

N

Conditioning

Donor type

Graft

aGvHD

cGvHD

Luznik et al3

117

BU/CY

MRD

MUD

BM

II: 43%

III: 10%

-

Carnevale-Schianca et al4

35

Intensive

MRD: 10

MUD: 25

PB

II: 12%

Two year: 7%

Greco et al5

28

Diverse

MRD: 15

MUD: 13

PB

II: 23%

III: 4%

One year: 13%

Mielcarek et al6

43

BU/FLU

MRD: 12

MUD: 31

PB

II: 77%

One year: 16%

Acute leukemia working party EBMT7

423

Myeloablative/RIC

MRD: 241

MUD: 182

BM: 108

PB: 315

No significant difference

-

Table 1: Comparison of studies using PTCy after intensive conditioning

Use of PTCyafter reduced intensity conditioning (RIC)

Study

N

Conditioning

Donor type

Graft

aGvHD

cGvHD

NCT 02208037

92

RIC

MRD

MUD

PB

 

 

Solomon et al8

26

RIC: BU/FLU/CY

MRD: 17

MUD: 9

PB

II—IV: 46%

III—IV: 15%

 

Alousi et al9

49

BU/CY

MRD: 15

MUD: 34

PB: 11

BM: 38

II: 26

III: 11

N = 9

Moiseev et al10

86

RIC: 76%

MAC: 24%

MUD

PB

II—IV: 19%

III—IV: 4%

16%

Ruggari et al11

423

RIC: 42%

MAC: 54%

MRD: 241

MUD: 182

PB: 271

BM: 108

II—IV: 27.9%

One year: 33%

Table 2: Comparison of studies using PTCy after RIC

Discussion

The analysed literature suggests that PTCy reduces the incidence of both aGvHD, cGvHD, and GRFS compared with standard GvHD prophylaxis, without significantly increasing the risk of relapse. Adding calcineurin inhibitors may further reduce GvHD incidences after blood cell grafts.

The team elaborated on the limitations of their review; detailing how there are very few studies with high quality data, with most studies being uncontrolled, having few patients that have a variety of disease diagnoses and states. Often, the studies use differing donor types, graft types and conditioning regimens, and combine the use of cyclophosphamide with other immunosuppressant drugs. This makes it difficult to define the contribution of each drug to the observed outcomes.

Understanding with certainty whether PTCy is actually effective in the prevention or reduction of cGvHD or aGvHD, would require testing the hypothesis in randomized, double-blind clinical studies with large numbers of patients.

References
  1. Bashey, Asad, et al. T-cell–replete HLA-haploidentical hematopoietic transplantation for hematologic malignancies using post-transplantation cyclophosphamide results in outcomes equivalent to those of contemporaneous HLA-matched related and unrelated donor transplantation. Journal of Clinical Oncology. 2013 Apr 1. 31(10):1310-1316. DOI: 10.1200/JCO.2012.44.3523
  2. El Fakih R. et al. Post-transplant cyclophosphamide use in matched HLA donors: a review of literature and future application. Bone Marrow Transplantation. 2019 May 14:1. DOI: 1038/s41409-019-0547-8
  3. Luznik L, et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008 Jun 1. 14(6):641-50. DOI: 1016/j.bbmt.2008.03.005
  4. Carnevale-Schianca F. et al. Post-Transplant Cyclophosphamide and Tacrolimus–Mycophenolate Mofetil Combination Prevents Graft-versus-Host Disease in Allogeneic Peripheral Blood Hematopoietic Cell Transplantation from HLA-Matched Donors. Biol Blood Marrow Transplant. 2017 Mar 1. 23(3):459-66. DOI: 1016/j.bbmt.2016.12.636
  5. Greco R. et al. Posttransplantation cyclophosphamide and sirolimus for prevention of GVHD after HLA-matched PBSC transplantation. Blood. 2016 Sep 15. 128(11):1528-31. DOI: 10.1182/blood-2016-02-699439
  6. Mielcarek M, et al. Posttransplantation cyclophosphamide for prevention of graft-versus-host disease after HLA-matched mobilized blood cell transplantation. Blood. 2016 Mar 17. 127(11):1502-8.
  7. Ruggeri A, Labopin M, Bacigalupo A, Afanasyev B, Cornelissen JJ, Elmaagacli A, et al. Post-transplant cyclophosphamide for graft-versus-host disease prophylaxis in HLA matched sibling or matched unrelated donor transplant for patients with acute leukemia, on behalf of ALWP-EBMT. J Hematol Oncol. 2018. 11:40.
  8. Solomon S.R. et al. Calcineurin inhibitor–free graft-versus-host disease prophylaxis with post-transplantation cyclophosphamide and brief-course sirolimus following reduced-intensity peripheral blood stem cell transplantation. Biol Blood Marrow Transplant. 2014 Nov 1. 20(11):1828-34. DOI: 1016/j.bbmt.2014.07.020
  9. Alousi A.M. et al. Phase II trial of graft-versus-host disease prophylaxis with post-transplantation cyclophosphamide after reduced-intensity busulfan/fludarabine conditioning for hematological malignancies. Biology of Blood and Marrow Transplantation. 2015 May 1. 21(5):906-12.
  10. Moiseev I.S. et al. Graft-versus-host disease prophylaxis in unrelated peripheral blood stem cell transplantation with post-transplantation cyclophosphamide, tacrolimus, and mycophenolate mofetil. Biology of Blood and Marrow Transplantation. 2016 Jun 1. 22(6):1037-42.
  11. Ruggeri A. et al. Post-transplant cyclophosphamide for graft-versus-host disease prophylaxis in HLA matched sibling or matched unrelated donor transplant for patients with acute leukemia, on behalf of ALWP-EBMT. Journal of hematology & oncology. 2018 Dec. 11(1):40.
Download this article:

You can now download this article in Adobe PDF® format.

Download as PDF
Was this article informative? Thank you for your feedback!