Extracorporeal Photophoresis in Reduced Intensity Conditioning: 14 Year Follow-up of 206 Patients Reveals an Efficacious Regimen with Low Rates of Gvhd

Background:  Extracorporeal photopheresis (ECP) modulates host antigen presenting cells implicated in graft versus host disease (GVHD) development. Incorporation of ECP into a reduced intensity conditioning (RIC) regimen may prevent acute (a) and chronic (c) GVHD.  

Methods: Data were collected from Tufts Medical Center BMT and Center for International Bone Marrow Transplantation Registry (CIBMTR) databases. All patients who received PPT conditioning (ECP on days -6 and -5, Pentostatin on days -4 and -3, 600 cGy TBI on days -2 and -1) at Tufts between 10/1999 – 12/2013 were included. Cyclosporine and methotrexate were used for GVHD prophylaxis.

Results: 206 pts (56% male) received PPT. Median age was 53 (19-70) with 45% > 55. Median time from diagnosis to transplant was 17 months (1-180). 59% had matched related donors.  Marrow was the stem cell source in 72%. 8% of transplants were mismatched at 1 antigen. Most common indications were Acute Myeloid Leukemia (AML) (35%), Myelodysplastic Syndrome (16%) and Non-Hodgkin Lymphoma (12%). Of the 73 pts with AML, 33% were in first complete remission (CR1), 18% were in a second or greater complete remission (CR ≥2) and 49% had active disease.  

Median times to neutrophil and platelet engraftment were 17 and 19 days, respectively.  Grade 3-4 aGVHD occurred in 20% and 14% in the total cohort and AML subset respectively. cGVHD developed in 54% (17% extensive stage) and 35% (8% extensive stage) of pts in the total cohort and AML subset respectively.

The 5 year OS for the entire cohort was 29% [95% CI (23%-36%)], and varied by diagnosis (Fig 1). NRM at 100 days was 17% [95% CI (13%-23%)].

On univariate analysis of the entire cohort, only 1-antigen mismatch [HR 1.96, p-value=0.01] and KPS <80 [HR 10.66, p-value <0.001] were associated with worse OS.  In the AML cohort, active disease at HSCT (HR 2.43 p=0.001), failure to engraft (HR 4.84 p<0.001), and grade 3-4 aGVHD (4.08 p<0.001) were associated with worse OS. In multivariate analysis after stepwise selection, advanced age (aHR 1.36, p=0.04), active disease (aHR 2.46, p-value=0.003) (Fig 2), engraftment syndrome (aHR 43, p=0.001) and grade 3-4 aGVHD (aHR 5.23 p<0.001) were associated with worse OS.

Conclusions: We report over a decade of experience with the PPT regimen. OS and low NRM are similar to other reported RIC regimens despite high rates of active disease at HSCT. Rates of severe acute and extensive chronic GVHD were low. PPT remains a viable regimen for pts not eligible for myeloablative conditioning.

Figure 1. Overall Survival of Patients Receiving PPT Conditioning by Diagnosis

Figure 2. Overall Survival  of AML Patients by Remission Status.