Preliminary experience of allogeneic stem cell transplantation for lymphoproliferative disorders using BEAM–CAMPATH conditioning: an effective regimen with low procedure‐related toxicity

Abstract

Summary. Autologous transplantation has an established role in the treatment of lymphoproliferative disorders, but allogeneic transplantation remains controversial. In an attempt to reduce the high procedure-related mortality reported with allografting in lymphoma, we have used BEAM (BCNU, etoposide, cytarabine and melphalan), a standard conditioning regimen for autologous transplantation. As BEAM may be insuf®ciently immunosuppressive to permit durable engraftment in the allogeneic setting, patients received additional pretransplant immunosuppression with the anti-CD52 antibody CAMPATH-1G from day À5 to day À1.Twelve patients (median age 46 years) underwent allogeneic transplantation for lymphoma (n 11) or chronic lymphocytic leukaemia (n 1) from HLA-identical (n 9) or mismatched (n 3) sibling donors. Cyclosporin A and methotrexate were used as graft-versus-host disease (GVHD) prophylaxis. One patient died of progressive lymphoma at day 12, the remaining 11 patients engrafted rapidly, with eight demonstrating full donor chimerism. One patient had an episode of rejection and received a further stem cell infusion with sustained recovery. Only one patient developed GVHD (grade I). The low incidence of acute GVHD may be in part related to persisting levels of in vivo CAMPATH-IG at the time of transplantation. Of 11 evaluable patients, nine achieved complete remission (CR), and a further patient achieved CR after donor lymphocyte infusion at 5 months.Our preliminary experience is that this regimen was well tolerated with a low risk of GVHD and appears no more toxic than a BEAM autograft. Further follow-up is required to see whether the low incidence of GVHD impacts upon relapse risk.

A novel reduced intensity regimen for allogeneic hematopoietic stem cell transplantation associated with a reduced incidence of graft-versus-host disease

“…In contrast to other RIT cytoreductive regimens, no patient in our study developed VOD, mucositis, or serious gastrointestinal side effects. 5,10,21,36 Our regimen was associated with a lower than expected incidence of serious aGVHD and cGVHD. In other RIT regimens using purine analogs and low doses of TBI or melphalan, the incidence of aGVHD ranged from 25 to 50%, compared to the 9% incidence of grade III-IV aGVHD in our study.…”

“…( Figure 5) Discussion RIT preparative regimens differ greatly in the intensity of the preparative regimen, the types of the immune suppression utilized to prevent graft rejection, and the intensity and duration of the prophylaxis used to prevent serious aGVHD. 3,5,7,13,35,36 Many regimens result in mixed hematopoietic chimerism, requiring subsequent DLIs to establish full donor chimerism, maintain engraftment, and augment the GVM effect. 7,[37][38][39][40] Despite decreased regimen-related toxicities and NRM with these regimens, the incidence of serious grade II-IV aGVHD, in non-T-cell-depleted HSCTs, remains at 25-50%.…”

“…The 100-day NRM of 11% reported here compares favorably with other reduced intensity regimens. 5,[9][10][11]36 Moreover, the fractionated 600 cGy TBI and pentostatin were effective in the establishment of early full donor chimerism and controlled active disease in the majority of patients. All evaluable patients demonstrated full donor chimerism and none required the subsequent infusion of donor lymphocytes to maintain engraftment or augment the GVM response.…”

Alemtuzumab (Campath-1H) for treatment of lymphoid malignancies in the age of nonmyeloablative conditioning?

“…The addition of alemtuzumab to minimally immunosuppressive conditioning regimens may improve this aspect of transplant-related morbidity and mortality, as suggested in preliminary studies. In one, Campath-1G was added to the conditioning regimen, BEAM, 55 a protocol more commonly used to precede autologous transplantation. In these 12 patients, 10 with NHL and two with CLL, the combination of alemtuzumab and BEAM produced high remission rates (75%) and a notably low incidence of GVHD.…”

“…However, high-dose regimens are now being replaced by well-tolerated procedures which are immunosuppressive rather than totally myeloablative, and are usually based on fludarabine, often in combination with cyclophosphamide, busulphan or other alkylating agents or low-dose radiation (nonmyeloablative stem cell transplants, NST). [48][49][50][51][52][53][54][55] Conveniently, there is substantial overlap between these new preparative regimens and the drug schedules most effective in reducing tumour burden in B-CLL. Alemtuzumab is a prime example, because it is an effective antitumour agent for B cell malignancies and facilitates engraftment of allogeneic stem cells, particularly in the context of NST.…”