Survival After Allogeneic Transplant for Relapsed Leukemia Following Cyclophosphamide, Etoposide, and Total Body Radiation (TBI) with Lung Shielding: Influence of cGVHD on Relapse and Lung Shielding on Pulmonary Complications

High dose chemotherapy and allogenic stem cell transplant is used to consolidate relapsed leukemia. GVT is an important component of curing leukemia in this setting and GVHD and TBI are important causes of toxicity, most notably late lung complications. We have employed lung shielding to reduce pulmonary complications in long term survivors of SCT. We report the impact of cGVHD on relapse and the incidence of late lung complications in these patients. Thirty-three patients with ALL (24), AML (8), and NHL (1) in CR2 (28), and > or equal to CR3 (5) received allogeneic PBSCT. Graft source was unrelated (20), HLA mismatched related (1), or HLA identical sibling donor (12). All received 1200 cGy TBI, etoposide 1500mg/m2, and cyclophosphamide 120mg/kg. Unrelated or mismatched related stem cell recipients also received ATG (90mg/kg over 3 days). TBI was delivered in 200cGy fractions twice daily for 3 days with double lung blocks to reduce lung dose to 300cGy. The chest wall was boosted with electrons to 1200cGy. GVHD prophylaxis was cyclosporin for matched siblings or tacrolimus (all others) and short course methotrexate (10mg/M2 days 1, 3, 6, and 11 except 1 recipient of cord blood who received steroids). OS and DFS were 19/33 (actuarial 53%) and 17/33 with median time from transplant of 41 and 47 months. For patients >1 and >4 years from transplant, TRM was 4/28 at 1 year and 4/15 at year 4. Relapse for patients >1 year from transplant was 7/28 (6/11 matched sibling, 1/16 unrelated, 0/1 mismatched related donor). All relapses occurred <1 year after transplant except 1 (21 month). The relapse rate for sibling transplants complicated by cGVHD was 0/4 (all survived at least 1 year) and was 6/7 for sibling transplants with no cGVHD. The relapse rate for recipients of unrelated PBSC grafts was 1/12 with 10/12 complicated by cGVHD. Of the 14 patients with cGVHD it has resolved in 4, requires continued treatment in 5, 2 died of complications from cGVHD, and 1 relapse. There was one case of idiopathic pneumonitis in a sibling donor transplant occurring within 50 days of transplant. Among 20 patients surviving at >1 year after transplant there is 1 case of severe restrictive lung disease due to chest wall contractures from cGVHD. 1. The best predictor of DFS in this series was presence of cGVHD. 2. GVHD was the strongest predictor of TRM. 3. Late pulmonary complications were rare.