CD38 on B-cell chronic lymphocytic leukemia cells has higher expression in lymph nodes than in peripheral blood or bone marrow

To the editor:Prophylaxis with defibrotide prevents veno-occlusive disease in stem cell transplantation after gemtuzumab ozogamicin exposure Gemtuzumab ozogamicin (GO; Mylotarg; Wyeth, PA) is a humanized anti-CD33 antibody conjugated to the cytotoxic agent calicheamicin.Although the efficacy of this agent is now being explored in phase 3 trials, there is significant concern about the risk of hepatic injury consequent on exposure to GO, particularly in relation to the incidence of veno-occlusive disease (VOD) after allogeneic stem cell transplantation (SCT).In a recent article in this journal, Wadleigh et al described 14 adults with AML who had received GO therapy prior to allogeneic SCT, of whom 9 (64%) developed VOD compared with only 4 (8%) of 48 who had not received GO. 1 Regression analysis highlighted a short interval (Ͻ 3 months) between GO exposure and conditioning as conveying the greatest risk for the development of VOD after SCT.In an accompanying editorial it was suggested that, based on these data, allogeneic SCT should not take place within 3.5 months of GO therapy. 2 In light of the above information, we wish to draw attention to our experience with 7 children who received GO within 2 months of transplantation, with emphasis on the occurrence and management of VOD.Between July 2001 and July 2003, 4 boys and 3 girls with a median age of 6 years (range, 1-12 years) with more than 30% CD33 ϩ myeloid blasts in the marrow were treated with GO as a single agent as cytoreduction prior to SCT.Of these children, 2 (unique patient number [UPN] 2 and UPN 5) had primary refractory AML, having failed 2 courses of therapy as per AML XII 3 and subsequent exposure to at least one course of FLAG 4 ; 5 children with refractory relapse (all had a first complete remission [CR1] of Ͻ 12 months following therapy with AML XII) had failed 2 courses of fludarabine, Ara-C, G-CSF (FLAG) with or without Daunoxome (Gilead, Foster City, CA).Between 1 and 4 doses of GO were given in a dose of 9 mg/m 2 per dose.SCT from the best available donor was then undertaken with conditioning planned to commence 14 to 21 days after exposure to the final dose of GO.The median interval between GO exposure and day 0 of SCT was 32 days (range, 27-60 days).All patients except UPN 6 received full-intensity conditioning busulphan (20 mg/kg)/cyclophosphamide (120 mg/kg) (2 cases); cyclophosphamide (120 mg/kg) total body irradiation (TBI; 14.4 Gy) (3 cases); and TBI (13.2 Gy) melphalan (100 mg/m 2 ) (1 case).UPN 6 received a reduced intensity conditioning (fludarabine 125 mg/m 2 and melphalan 100 mg/m 2 ) due to concerns over anthracycline-induced cardiomyopathy.UPN 1 underwent SCT 27 days after a single dose of GO due to concerns over the risk of VOD.Ursodeoxycholic acid was given as VOD prophylaxis.No hepatic problems occurred.