High-dose chemotherapy using BEAM without autologous rescue followed by reduced-intensity conditioning allogeneic stem-cell transplantation for refractory or relapsing lymphomas: a comparison of delayed versus immediate transplantation

Abstract

Patients with refractory/relapsing lymphoma are rarely cured by chemotherapy. High-dose chemotherapy (HDC) for tumor debulking followed by reduced-intensity conditioning (RIC) hematopoietic stem-cell transplantation (HSCT) has been advocated as a concept. We previously treated 10 patients (group A) with BEAM chemotherapy followed by delayed RIC HSCT at day 28. We now report on the subsequent 11 patients receiving BEAM followed immediately by fludarabine/total body irradiation and allogeneic HSCT (group B), and compare the outcome to group A patients. Non-hematological toxicity before engraftment was comparable, only gut toxicity was higher in group B. Days in aplasia, days on antibiotics and length of hospital stay were significantly longer in group A. Cumulative incidence of acute (GvHD) >or=grade II and incidence of chronic GvHD were lower in group B. At last follow-up, seven patients in group A were alive, with six of them in complete remission. In group B, nine patients were alive, seven of them in complete remission. No significant difference in estimated 3-year overall survival was seen. These data challenge the initial concept of debulking first and delaying allogeneic RIC HSCT. Allogeneic HSCT with standard BEAM conditioning is a valid alternative for patients with resistant/relapsed lymphoma, which might be considered earlier in the disease course.

Tandem autologous-allo-SCT is feasible in patients with high-risk relapsed non-Hodgkin’s lymphoma

“…Toxicity observed was acceptable, with 0 and 6% of early and 2-year TRM respectively. These results compared favorably with previous reported experiences using fludarabine/ CY 20 and fludarabine/TBI [21][22][23] as conditioning regimens for allo-SCT. In the study by Gutman et al, 21 overall TRM was 43% and chronic GVHD were 69% and 61% for sibling and unrelated donors, respectively.…”

Sclerotic-type chronic GVHD of the skin: clinical risk factors, laboratory markers, and burden of disease

“…Reducedintensity conditioning is frequently used to avoid the toxicity associated with myeloablation 20 and may also result in less acute GVHD than traditional myeloablation. 21 Unfortunately, the use of reduced-intensity regimens has not led to a reduced incidence of cGVHD, 22 possibly because of survival of recipient antigenpresenting cells.…”

Evidence of a clinical response at one yr after reduced-intensity allogeneic hematopoietic stem cell transplantation in heavily pretreated adolescents with aggressive refractory Hodgkin’s lymphoma

“…To improve outcome, the option of allografting should be considered when the tumor burden is lower. For truly primary refractory patients or for patients in chemo‐refractory relapse, autologous HSCT might be considered as an initial debulking therapy in the context of tandem procedures followed by an allogeneic transplant as consolidation therapy (21). In these patients, RIC‐AHSCT can produce durable disease‐free survival.…”