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.