Extracorporeal Photopheresis, Pentostatin, and TBI for Reduced-Intensity Preparation: Adaptation of the Tufts Experience at a Single Transplant Center.

Abstract Conditioning regimens utilized in reduced intensity transplants are designed to optimize immune suppression to allow a graft vs. tumor effect. One reduced intestiy regimen reported to result in a reduced incidence of GVHD while demonstrating disease response consists of extracorporeal photopheresis, pentostatin, 4 mg/m2/day X 2, and reduced dose total body irradiation(TBI; 600 cGy given in 3 fractions) (Miller KB et al; BMT 2004; 34:881–9). This regimen has been utilized in our center in 45 patients who have at least 6 months of follow up. All were ineligible for a conventional conditioning regimen, and from 3/03, this regimen was utilized for all reduced intensity transplants with exception of those wherein prior radiation precluded this dose of TBI. The median age of the patients was 55 years with age range 27 through 67 years. Thirty-three of the patients were 50 years of age or older. Twenty-five patients received sibling and 20 an unrelated donor (UD) transplant. All but one sibling transplant was a 6/6 match, whereas 8/20 of the UD transplants involved mismatched loci. GVHD prophylaxis consisted of tacrolimus and short course methotrexate in 43, tacrolimus/MMF in 1, and tacrolimus/sirolimus in 1. Seventeen patients had AML, 3 MDS, 2 ALL, 2 CML, 11 CLL, and 8 NHL. One had HD, and one had Waldenstrom's. Eight of the 45 had prior stem cell transplantation. The median number of CD34+ cells infused was 4.54 X 106/kg recipient weight. Nine patients were transplanted in CR or early disease phase. The remainder had more advanced stages of disease. Five patients died before anticipated neutrophil recovery. Two others had no neutrophil nadir, and median time to neutrophil engraftment in the remainder was 14.5 days. In those evaluable for platelet engraftment, the median time to engraftment was 18.7 days. For those surviving to approximately Day+30, the median donor chimerism as assessed by VNTRs was 94% (range 34%–100%). The overall Day 100 survival was 69% (31/45), with 80%(20/25) of sibling graft recipients alive and 55% (11/20) of UD recipients still living. Twelve patients developed regimen related toxicity. In five, this manifested as ARDS or multi-organ failure with a capillary leak syndrome, and 2 had renal failure. Ten patients had disease resistance or relapse after transplant, and all of those have died. The overall survival to date is 42%; 48% for sibling transplant recipients and 35% for UD recipients with range of follow up in survivors from 283 to 1366 days (median 535 days). Acute GVHD of grade III or IV was seen in only 3 patients. For those surviving past 100 days, 27% had extensive GVHD. No patients transplanted with this regimen for AML not in remission survived. Only one patient with NHL not in CR or a chemotherapy sensitive relapse state survived. This conditioning regimen of extracorporeal photopheresis, pentostatin, and TBI therefore appears most effective for patients with AML in first or greater remission or for CLL patients in early relapse with responsive disease. The regimen was associated with a capillary leak/organ failure syndrome in seven patients but was otherwise well-tolerated. Its long-term effects on GVHD incidence and coincident graft vs. malignancy benefit remain to be better understood as compared to other reduced intensity regimens which do not contain extracorporeal photopheresis.