Tositumomab/iodine-131 tositumomab (Bexxar) is a novel active agent against CD20-positive lymphoma. There is a paucity of data examining the tolerance and outcome of hematopoietic stem cell transplantation (HSCT) for relapse after tositumomab/iodine-131 tositumomab.
From July 1992 to June 2001, 12 patients relapsing after tositumomab/iodine-131 tositumomab underwent HSCT; 2 of these 12 also had a diagnosis of therapy-related myelodysplasia. There were nine men and three women, with a median age of 55 years (range: 47-66 years). Patients received a median of 3 (range: 2-6) prior chemotherapy regimens (exclusive of tositumomab/iodine-131 tositumomab) before or after tositumomab/iodine-131 tositumomab. The median number of chemotherapy regimens was 2 after tositumomab/iodine-131 tositumomab and prior to HSCT (range: 1-4). The median time from tositumomab/iodine-131 tositumomab therapy to HSCT was 554 days (range: 77-2,893 days). Five patients had low-grade, four transformed low-grade, and three intermediate-grade lymphoma.Eight patients received a myeloablative conditioning regimen; four others received a reduced-intensity regimen consisting of fludarabine (Fludara), busulfan(Drug information on busulfan) (Myleran), tacrolimus(Drug information on tacrolimus) (Prograf), mycophenolate mofetil (CellCept), and 4 Gy of total lymphoid radiation. Five patients received autologous HSCT: three marrow and two peripheral blood stem cells. Among seven allogeneic transplants, three received matched related peripheral blood stem cells and four received matched unrelated marrow (n = 3) or peripheral blood (n = 1) stem cells. Allogeneic recipients received tacrolimus and methotrexate(Drug information on methotrexate) for graft-vs-host disease prophylaxis. Clinical outcome is summarized in the table below:
All patients except two who received reduced intensity had severe mucositis. Reversible veno-occlusive disease of the liver also developed in two patients. There was one death from graft-vs-host disease and no regimen-related mortality. Engraftment was prompt, with a median recovery of absolute neutrophil count to ³ 500/µL of 12 days (range: 11-18 days). Six patients relapsed, including all five autologous and one allogeneic recipients. Four patients were alive with no evidence of disease (three matched unrelated donor and one matched related donor). The other three allogeneic recipients died from either graft-vs-host disease, relapse, or acetaminophen-induced hepatic necrosis.
CONCLUSION: These data demonstrate the feasibility of allogeneic or autologous HSCT in heavily pretreated lymphoma patients who also received tositumomab/iodine-131 tositumomab.