BEAM-alemtuzumab reduced-intensity allogeneic stem cell transplantation for lymphoproliferative diseases: GVHD, toxicity, and survival in 65 patients

Abstract

We report the outcomes of reduced-intensity allogeneic stem cell transplantation using BEAM-alemtuzumab conditioning (carmustine, etoposide, cytosine arabinoside, melphalan, and alemtuzumab 10 mg/d on days ؊5 to ؊1) in 6 United Kingdom transplant centers. Sixty-five patients with lymphoproliferative diseases underwent sibling (n ‫؍‬ 57) or matched unrelated donor (n ‫؍‬ 8) transplantation. Sustained donor engraftment occurred in 60 (97%) of 62 patients. Of the 56 patients undergoing chimerism studies, 35 (63%) had full donor chimerism. Overall, 73% were in complete remission (CR) after transplantation. At a median follow-up of 1.4 years (range, 0.1-5.6 years), 37 remain alive and in CR. Acute graft-versus-host disease (GVHD) occurred in 11 (17%) of 64, grades I-II only. Estimated 1-year transplantation-related mortality (TRM) was 8% for patients undergoing first transplantation but was significantly worse for those who had previously undergone autologous transplantation. Six patients relapsed (estimated 2-year relapse risk, 20%). Histologic diagnosis (mantle cell lymphoma and high-grade non-Hodgkin lymphoma) and age at transplantation (> 46 years) were significantly associated with higher relapse risk and worse event-free survival. Relapse did not occur in any patient who developed acute or chronic GVHD. This study demonstrates that reduced-intensity allogeneic stem cell transplantation for lymphoproliferative diseases using a BEAM-alemtuzumab preparative regimen is associated with sustained donor engraftment, a high response rate, minimal toxicity, and a low incidence of GVHD. (Blood. 2004;103: 428-434)

Current role of allogeneic stem cell transplantation in follicular lymphoma

“…14 Subsequent studies showed that FL has the most favorable outcome among lymphoprolyferative disorders. [15][16][17] In a cohort of patients enrolled in a multicenter Italian trial, the 3-year overall survival of patients with FL was 69%, similar to the survival rate reported by Vigouroux et al in this issue of the journal. 18 The optimal conditioning regimen has not been defined yet: fludarabine-based chemotherapy seems suitable because it combines both immunosuppression and anti-tumor activity.…”

“…Alemtuzumab has been used as an in vivo T-cell depleting agent in several conditioning regimens. 16,17 So far, published data have shown that patients with similarly treated low-grade non-Hodgkin's lymphoma undergoing T-cell depleted transplants have (compared to similarly treated patients with aggressive non-Hodgkin's lymphoma) a superior event-free survival and a lower relapse rate compared to patients with aggressive histologies. 15 16 This observation is in contrast with the data published in this issue showing that patients in CR and PR had similar outcomes.…”

“…Second, TRM has been shown to be related to patients' age and previously failed autologous SCT. 17,23 Third, although data from prospective phase III trials are lacking, the outcome of allografted patients compared favorably with that of patients undergoing autologous SCT with PCR-positive grafts, suggesting that at least in these patients RIC allogeneic SCT may be considered a valuable option. 24 Finally, another question arises in the era of RIC: what is the current role of conventional allogeneic SCT in FL?…”

Cellular and complement-dependent cytotoxicity of Ep-CAM-specific monoclonal antibody MT201 against breast cancer cell lines

“…Recently, several mAbs that predominantly act by ADCC and CDC have been approved for the treatment of cancer patients. These include chimaeric IgG1 mAb rituximab (Rituxan s ) binding to the B-cell differentiation antigen CD20 for the treatment of Bcell lymphomas (Grillo-Lopez et al, 1999;Smith, 2003), humanised IgG1 mAb trastuzumab (Herceptin s ) targeting HER-2 (human epithelial growth factor receptor type 2) overexpressed in a subgroup of breast cancers (Vogel et al, 2001), humanised IgG1 alemtuzumab (Campath s ) targeting the differentiation antigen CD52 for the treatment of B-cell chronic lymphocytic leukaemia (Hale et al, 1998;Kottaridis et al, 2000;Faulkner et al, 2004) and edrecolomab (Panorex s ), a murine IgG2a mAb targeting Ep-CAM (epithelial cell adhesion molecule), which gained temporary approval in Germany for the treatment of colorectal carcinoma (Riethmuller et al, 1994;Gruber et al, 1996;Schwartzberg, 2001;White et al, 2001). Several other mAbs are currently at advanced stages of clinical development.…”

Impact of pre-transplant co-morbidities on outcome after alemtuzumab-based reduced intensity conditioning allo-SCT in elderly patients: A British Society of Blood and Marrow Transplantation study

“…Patients over the age of 60 who were transplanted in transplant centres, which routinely utilised alemtuzumab-based RIC regimens including combinations of fludarabine and melphalan (Flu/Mel), 15 fludarabine and Bu (Flu/Bu), 16 BCNU, BEAM 17 and fludarabine and Cy (Flu/Cy) ( Table 1) 18 were studied. GVHD prophylaxis consisted of CYA (5 mg/kg) commenced pre-transplant and subsequently dose-adjusted to achieve therapeutic levels.…”