What are the probable reasons for the high rate of gastrointestinal complications and TRM? In contrast to the cohort of Bunjes the majority of our patients suffered from Philadelphia chromosome–positive ALL. Several studies demonstrated a high TRM in patients with this disease. 2,3 However, this does not explain the high frequency of acute intestinal GvHD. The second obvious difference was the use of unmanipulated grafts or early incremental T-cell add backs. We therefore assume that the combination of anti-CD66 (a, b, c, e) mAb therapy and early exposure to allogeneic T cells might be the reason for intestinal toxicity. Since anti-CD66 (a, b, c, e) antibodies (clone BW250/183) bind intestinal epithelial cells, radioimmunotherapy might cause tissue dam- age in the bowel. 4 This might also trigger intestinal GvHD. Moreover, the antigen CD66a is expressed on the surface of small intestinal intraepithelial lymphocytes (iIEL). 5,6 Via cross fire radiolabeled intraepi- thelial T-cell binding, mAb might cause additional tissue damage. In summary, allografting without T-cell depletion or with early T-cell add backs after conditioning regimens including 188 Re-labeled anti- CD66 (a, b, c, e) mAb is associated with a high risk of severe intestinal acute GvHD and a high TRM. We therefore suggest that efficient T-cell depletion is strongly recommended for allogeneic hematopoietic cell grafts after a radioimmunotherapy conditioning with anti- CD66 (a, b, c, e) mAb. Furthermore, the anticipated benefit of early T-cell add backs should be weighed out carefully with the risk of severe intestinal GvHD. Stefan A. Klein, Stella Hermann, Christoph F. Dietrich, Dieter Hoelzer, and Hans Martin Correspondence: Stefan A. Klein, Johann Wolfgang Goethe-Universita ¨t, Med Klinik III, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany; e-mail: sal.klein@ t-online.de References 1. Bunjes D, Buchmann I, Duncker C, et al. Rhenium 188-labeled anti-CD66 (a, b, c, e) monoclonal antibody to intensify the conditioning regimen prior to stem cell trans- plantation for patients with high-risk acute myeloid leukemia or myelodysplastic syn- drome: results of a phase I-II study. Blood. 2001;98:565-572. 2. Cornelissen JJ, Carston M, Kollman C, et al. Unrelated marrow transplantation for adult patients with poor-risk acute lymphoblastic leukemia: strong graft-versus-leuke- mia effect and risk factors determining outcome. Blood. 2001;97:1572-1577. 3. Snyder DS, Nademanee AP, O’Donnell MR, et al. Long-term follow-up of 23 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with allogeneic bone marrow transplant in first complete remission. Leukemia. 1999;13:2053-2058. 4. Bosslet K, Luben G, Schwarz A, et al. Immunohistochemical localization and molecular characteristics of three monoclonal antibody-defined epitopes de- tectable on carcinoembryonic antigen (CEA). Int J Cancer. 1985;36:75-84. 5. Donda A, Mori L, Shamshiev A, et al. Locally inducible CD66a (CEACAM1) as an amplifier of the human intestinal T cell response. Eur J Immunol. 2000;30: 2593-2603. 6. Morales VM, Christ A, Watt SM, et al. Regulation of human intestinal intraepi- thelial lymphocyte cytolytic function by biliary glycoprotein (CD66a). J Immunol. 1999;163:1363-1370. Response: Factors influencing gut GvHD after intensified conditioning with Rhenium 188–labeled anti-CD66 monoclonal antibody We are grateful to Klein et al for emphasizing one aspect of our study that received comparatively little attention in the original publication, namely the fact that all patients but one received T-cell–depleted grafts. Therefore the conclusions with respect to organ toxicity and the incidence of graft-versus-host disease (GvHD) only apply to T-cell– depleted stem cell transplantations and cannot be transferred to patients receiving conventional GvHD prophylaxis. Klein et al report a high incidence of gut GvHD in a cohort of patients receiving non–T-cell– depleted grafts after intensified conditioning according to our radioim- munotherapy protocol. We cannot entirely exclude the possibility that the specificity of the anti-CD66 antibody used in our study could have contributed to the gut problems observed. However, we have never observed localization of the antibody to the gut in our dosimetry studies, and we have data demonstrating that the labeled antibody per se does not induce a systemic release of cytokines involved in GvHD (interleukin-1, tumor necrosis factor–alpha, gamma-interferon [Buchmann et al, unpub- lished observations, December 2001]). We have only observed localiza- tion of the antibody to the gut in rare patients with significant infectious complications such as severe appendicitis. We therefore feel that this high incidence of intestinal GvHD is due to the use of conventional GvHD prophylaxis, and in particular to the early application of donor lymphocyte transfusions. Donald Bunjes Correspondence: Donald Bunjes, Department of Haematology/Oncology, Ulm University Hospital, Robert-Koch Strasse 8, 89081 Ulm Germany; e-mail: donald.bunjes@medizin.uni-ulm.de To the editor: Discrepancy between antithrombin activity methods revealed in Antithrombin Stockholm: do factor Xa–based methods overestimate antithrombin activity in some patients? Antithrombin is a single-chain glycoprotein of 432 amino acids. It is the most important endogenous coagulation inhibitor and inhibits several coagulation factors: IXa, Xa, XIa, XIIa, and thrombin (of which the inhibition of thrombin probably is the most important). In 1992 Blajchman et al 1 reported the Antithrombin Stockholm point mutation in codon 392 (Gly to Asp) as a reactive site (RS) type of mutation that results in a type II antithrombin deficiency. It was found in a young woman on oral contraceptives who presented with pulmonary embolism. The authors reported low antithrombin activity measured with thrombin inhibition–based (72%-74%) and factor Xa inhibition–based (53%-56%) methods using chromo- genic peptide substrate assays. 1 Several years later, much to our surprise, the proband and her 2 siblings had normal antithrombin activity in a routine factor Xa inhibition–based test. Her 2 siblings had previously presented with low levels but never suffered from any symptoms. CORRESPONDENCE 2271 BLOOD, 15 MARCH 2002  VOLUME 99, NUMBER 6 Downloaded from http://ashpublications.org/blood/article-pdf/99/6/2271/1681982/2271.pdf by guest on 01 July 2022